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Sample records for 1ital dsub 2r

  1. UV-dependent production of 25-hydroxyvitamin D{sub 2} in the recombinant yeast cells expressing human CYP2R1

    SciTech Connect

    Yasuda, Kaori; Endo, Mariko; Ikushiro, Shinichi; Kamakura, Masaki; Ohta, Miho; Sakaki, Toshiyuki

    2013-05-03

    Highlights: •We produce 25-hydroxyvitamin D in the recombinant yeast expressing human CYP2R1. •Vitamin D2 is produced in yeast from endogenous ergosterol with UV irradiation. •We produce 25-hydroxyvitamin D2 in the recombinant yeast without added substrate. -- Abstract: CYP2R1 is known to be a physiologically important vitamin D 25-hydroxylase. We have successfully expressed human CYP2R1 in Saccharomyces cerevisiae to reveal its enzymatic properties. In this study, we examined production of 25-hydroxylated vitamin D using whole recombinant yeast cells that expressed CYP2R1. When vitamin D{sub 3} or vitamin D{sub 2} was added to the cell suspension of CYP2R1-expressing yeast cells in a buffer containing glucose and β-cyclodextrin, the vitamins were converted into their 25-hydroxylated products. Next, we irradiated the cell suspension with UVB and incubated at 37 °C. Surprisingly, the 25-hydroxy vitamin D{sub 2} was produced without additional vitamin D{sub 2}. Endogenous ergosterol was likely converted into vitamin D{sub 2} by UV irradiation and thermal isomerization, and then the resulting vitamin D{sub 2} was converted to 25-hydroxyvitamin D{sub 2} by CYP2R1. This novel method for producing 25-hydroxyvitamin D{sub 2} without a substrate could be useful for practical purposes.

  2. Avalanches and 1/[ital f] noise in evolution and growth models

    SciTech Connect

    Maslov, S.; Paczuski, M.; Bak, P. Department of Physics, State University of New York at Stony Brook, Stony Brook, New York 11790 The Isaac Newton Institute for Mathematical Sciences, 20 Clarkson Road, Cambridge CB4 OEH )

    1994-10-17

    We formally establish the relationship between spatial fractal behavior and long-range temporal correlations for a broad range of self-organized (and not self-organized) critical phenomena including directed percolation, interface depinning, and a simple evolution model. The recurrent activity at any particular site forms a fractal in time, with a power spectrum [ital S]([ital f])[similar to]1/[ital f][sup [ital [tilde d

  3. Coulomb three-body effects in low-energy impact ionization of H(1{ital s})

    SciTech Connect

    Roeder, J.; Rasch, J.; Jung, K.; Whelan, C.T.; Ehrhardt, H.; Allan, R.J.; Walters, H.R. |||

    1996-01-01

    The different kinematical and geometrical arrangements that may be used in ({ital e},2{ital e}) studies are briefly reviewed. The ionization of H(1{ital s}) is considered, and within the confines of a relatively simple theoretical model, it is shown how to define experimental setups where one may extract information on the role of Coulomb three-body effects in the incident and final channels. Theoretical and experimental results are presented for coplanar constant geometry where the focus is primarily on incident channel effects. {copyright} {ital 1996 The American Physical Society.}

  4. Systematic 1{ital /N} corrections for bosonic and fermionic vector models without auxiliary fields

    SciTech Connect

    de Mello Koch, R.; Rodrigues, J.P.

    1996-12-01

    In this paper, colorless bilocal fields are employed to study the large {ital N} limit of both fermionic and bosonic vector models. The Jacobian associated with the change of variables from the original fields to the bilocals is computed exactly, thereby providing an exact effective action. This effective action is shown to reproduce the familiar perturbative expansion for the two and four point functions. In particular, in the case of fermionic vector models, the effective action accounts correctly for the Fermi statistics. The theory also is studied nonperturbatively. The stationary points of the effective action are shown to provide the usual large {ital N} gap equations. The homogeneous equation associated with the quadratic (in the bilocals) action is simply the two particle Bethe-Salpeter equation. Finally, the leading correction in 1/{ital N} is shown to be in agreement with the exact {ital S} matrix of the model. {copyright} {ital 1996 The American Physical Society.}

  5. Correlation between latent interface trap buildup and 1/{ital f} noise in metal{endash}oxide{endash}semiconductor transistors

    SciTech Connect

    Johnson, M.J.; Fleetwood, D.M.

    1997-03-01

    A long-term delayed increase in the 1/{ital f} noise of {ital p}-channel metal{endash}oxide{endash}semiconductor (MOS) transistors is observed in devices that show significant latent interface-trap buildup after exposure to ionizing radiation. During positive-bias postirradiation anneal, the noise increases by more than an order of magnitude above the level observed after irradiation. The increase in noise precedes the latent buildup of interface traps by at least 4.5 days during room-temperature annealing, and by {approximately}1 h during 100{degree}C annealing. The time and temperature dependencies of the increases in noise and interface trap buildup are consistent with the thermally activated motion of protons into the near-interfacial region of the oxide, followed by increases in border trap and interface trap densities. These results suggest hydrogen-related species can significantly affect the 1/{ital f} noise of MOS devices.{copyright} {ital 1997 American Institute of Physics.}

  6. Radiative decay of [ital D][sub 2][sup *](2460) and [ital D][sub 1](2420)

    SciTech Connect

    Fayyazuddin; Mobarek, O.H. )

    1994-08-01

    The [ital E]1 transition decay widths for the decays [ital D][sub 2][sup *][r arrow][ital D][sup *]+[gamma], [ital D][sub 1][r arrow][ital D]+[gamma], and [ital D][sub 1][r arrow][ital D][sup *]+[gamma] are calculated in the nonrelativistic quark model with recoil and relativistic corrections.

  7. Differential perturbations and D{sub {infinity}}-differential modules

    SciTech Connect

    Lapin, S V

    2001-12-31

    In the present paper the notions of a D{sub {infinity}}-differential and a D{sub {infinity}}-differential module are introduced, which are, respectively, homotopically invariant analogues of the differential and the chain complex. Basic homotopic properties of D{sub {infinity}}-differentials and D{sub {infinity}}-differential modules are established. The connection between the Gugenheim-Lambe-Stasheff theory of differential perturbations in homological algebra and the construction of a D{sub {infinity}}-differential module is considered.

  8. Crystallization behavior of Li{sub 1{minus}5{ital x}}Ta{sub 1+{ital x}}O{sub 3} glasses synthesized from liquid precursors

    SciTech Connect

    Allemann, J.A.; Xia, Y.; Morriss, R.E.; Wilkinson, A.P.; Eckert, H.; Speck, J.S.; Levi, C.G.; Lange, F.F.; Anderson, S.

    1996-09-01

    The crystallization of amorphous oxides synthesized by pyrolytic decomposition of mixed Li and Ta 2-ethylhexanoates and alkoxides has been investigated. The study was motivated by thermodynamic considerations that, in the light of experience in other systems, suggest the potential for metastable extension of the LiTaO{sub 3} homogeneity range. Materials investigated are described by the general stoichiometry Li{sub 1{minus}5{ital x}}Ta{sub 1+{ital x}}O{sub 3} and include Li{sub 2}O contents from 0 to 70 mol{percent} ({minus}0.18{le}{ital x}{le}0.2). The samples were prepyrolyzed at 400{degree}C and subsequently crystallized by heat treatments in air at 550{endash}700{degree}C for 0.1{endash}100 h. The first product of crystallization for compositions from 30 to 65{percent} Li{sub 2}O is always the LiTaO{sub 3} phase. Extensive characterization by X-ray and neutron diffraction, as well as {sup 7}Li{endash}NMR spectroscopy, revealed that this phase evolves with a structure and stoichiometry close to equilibrium. For Li{sup +}-deficient compositions, excess Ta{sup 5+} is rejected to the amorphous constituent during crystallization and eventually gives rise to the evolution of Ta{sub 2}O{sub 5}, with the LiTa{sub 3}O{sub 8} phase suppressed in all cases. Similar observations were made for the Li{sup +}-rich compositions, but the evolving second phase is the equilibrium Li{sub 3}TaO{sub 4}. The absence of solubility extension in LiTaO{sub 3}, which appears feasible from a thermodynamic viewpoint, is ascribed to the large differences in mobilities of the Li and Ta species in the parent amorphous oxide resulting from pyrolysis. {copyright} {ital 1996 Materials Research Society.}

  9. 24,26-dihydroxyvitamin D/sub 2/: a unique physiological metabolite of vitamin D/sub 2/

    SciTech Connect

    Koszewski, N.J.; Reinhardt, T.A.; Napoli, J.L.; Beitz, D.C.; Horst, R.L.

    1988-07-26

    A new vitamin D/sub 2/ metabolite, 24,26-dihydroxyvitamin D/sub 2/, has been detected in the plasma of rats fed physiologic amounts of vitamin D/sub 2/. The identity of the new metabolite (isolated from cow plasma) was established by ultraviolet absorbance, mass spectroscopy, chemical reactivity, and NMR spectroscopy. Among these, the mass spectrum was unique for the presence of a peak at M - 48 that was attributed to an intramolecular rearrangement involving both the C-24 and C-26 hydroxyl groups. A 300-MHz /sup 1/H NMR spectrum of 40 ..mu..g of metabolite indicated a downfield shift of the C-28 methyl group signal to delta 1.30 and a multiplet at delta 3.66 corresponding to the hydroxylated C-26 methyl group. They determined that the formation of 24,26-dihydroxyvitamin D/sub 2/ represented a major pathway for further metabolism of 24-hydroxyvitamin D/sub 2/ in rats, exceeding the formation of 24,25-dihydroxyvitamin D/sub 2/. Standard bioassays revealed that 24,26-dihydroxyvitamin D/sub 2/ possessed very little biological activity and most likely represents a deactivation pathway for 24-hydroxyvitamin D/sub 2/.

  10. Determination of vitamin D/sub 3/, vitamin D/sub 2/ and their 25-hydroxy metabolites in porcine liver using high performance liquid chromatography

    SciTech Connect

    Travis, B.D.; Holmes, R.P.

    1986-01-01

    A method has been developed for the determination of vitamin D/sub 3/, vitamin D/sub 2/ and their corresponding 25-hydroxy metabolites in porcine liver. The vitamins and metabolites were estimated by extracting the non-saponifiable lipids from the saponifiable lipids from the samples. This was followed by purification and separation of the vitamin D/sub 2/ and vitamin D/sub 3/ from their 25-hydroxy metabolites using a 3 ml Bond Elut SCX column that was impregnated with silver nitrate. The two fractions were further purified on a Resolve cyanopropyl HPLC column. This column does not separate vitamin D/sub 2/ and vitamin D/sub 3/ but will separate 25-hydroxyvitamin D/sub 2/ from 25-hydroxyvitamin D/sub 2/. Quantitation used Nova Pak C-18 and Resolve C-18 HPLC columns in series, measuring the absorbance at 254 nm. This gave baseline separation of vitamin D/sub 2/ and vitamin D/sub 3/. Recoveries were determined by adding /sup 3/H-vitamin D/sub 3/ and /sup 3/H-25-hydroxyvitamin D/sub 3/ before saponification and assuming similar recoveries for the vitamin D/sub 2/ and 25-hydroxyvitamin D/sub 2/. The method was found to be reproducible when a sample was minced and subdivided. The range of vitamin D/sub 3/ in liver was 5.2 to 14.0 ng/g. Vitamin D/sub 2/, 25-hydroxyvitamin D/sub 2/ were not detectable. Preliminary results indicate the method may also be used with muscle, kidney and adipose, with adipose having a much higher level of vitamin D/sub 3/ than liver.

  11. Hadronic decays of the D/sub s/ meson

    SciTech Connect

    Wasserbaech, S.R.

    1989-06-01

    The D/sub s//sup +/ is the lowest-lying pseudoscalar meson containing charm and anti-strange quarks. Evidence for this state was first reported in 1977, although more recent observations disagree with some of the early results. Since 1983 the weakly decaying D/sub s//sup +/ has been observed in many experiments. Relative branching fractions have been measured for many non-leptonic decay modes, including D/sub s//sup +/ /yields/ /phi//pi//sup +/, /phi//pi//sup +//pi//sup +//pi//sup /minus//, /bar K/*/sup 0/K/sup +/, and f/sub 0/(975)/pi//sup +/. The absolute branching fractions are estimated in high energy e/sup +/e/sup /minus// annihilation from the observed numbers of reconstructed D/sub s//sup +/ decays and the expected D/sub s//sup +/ production cross section. The lowest-lying vector c/bar s/ meson, the D/sub s/*/sup +/, has also been seen in its decay to /gamma/D/sub s//sup +/. Weak decays of the heavy quark and lepton flavors are relevant to the development of the Standard Model of both the electroweak and the strong interactions. Measurements of charmed particle weak decay are useful for determining the parameter of the Standard Model and for testing phenomenological models which include strong effects. 83 refs., 56 figs., 12 tabs.

  12. Implication of BABAR's new data on the D{sub s1}(2710) and D{sub sJ}(2860)

    SciTech Connect

    Li Demin; Ma Bing

    2010-01-01

    The strong decays of the D{sub s1}(2710) and D{sub sJ}(2860) are investigated in the framework of the {sup 3}P{sub 0} model. Its decay properties newly reported by the BABAR Collaboration can be reasonably accounted for in the presence of the D{sub s1}(2710) being a mixture of the D{sub s}(2{sup 3}S{sub 1}) and D{sub s}(1{sup 3}D{sub 1}). The orthogonal partner of the D{sub s1}(2710) is expected to have a mass of about 2.66{approx}2.9 GeV in quark models and a width of about 40{approx}60 MeV in the {sup 3}P{sub 0} model. The predicted decay properties turn out to be consistent with BABAR's new data in both the orthogonal partner of the D{sub s1}(2710) and the D{sub s}(1{sup 3}D{sub 3}) interpretations for the D{sub sJ}(2860). The available experimental information is not enough to distinguish these two possibilities. The E1 radiative transitions of the D{sub s1}(2710) and D{sub sJ}(2860) are also studied. We tend to conclude that the D{sub s1}(2710) can be identified as a mixture of the D{sub s}(2{sup 3}S{sub 1}) and D{sub s}(1{sup 3}D{sub 1}), and the D{sub sJ}(2860) could be either the orthogonal partner of the D{sub s1}(2710) or the D{sub s}(1{sup 3}D{sub 3}). Further experimental information on the D{sub sJ}(2860) in the D{sub s{eta}}, D{sub s}*{eta}, and DK* channels is needed.

  13. Crystal growth and roughening of solid D{sub 2}

    SciTech Connect

    Kozioziemski, B.J.; Collins, G.W.; Bernat, T.P.

    1997-03-26

    Near the triple point, growth shapes of vapor deposited hexagonal close packed D{sub 2} crystals reveal two crystal orientations contain facets which persist up to the melt. This observation is in contrast with previous experiments on rare gas solids and H{sub 2} where the highest T{sub r} measured is 0.8 T{sub tp}.

  14. H{sub 2} and D{sub 2} in intense sub-picosecond laser pulses: Photoelectron spectroscopy at 1053 and 527 nm

    SciTech Connect

    Rottke, H.; Ludwig, J.; Sandner, W.

    1996-09-01

    We report multiphoton ionization experiments on H{sub 2} and D{sub 2} molecules at 1053- and 526.5-nm excitation wavelengths in the intensity range 5{times}10{sup 13}{endash}5{times}10{sup 14} W/cm{sup 2}. The intensity dependence of the total ion yield, the dissociation fraction, and the photoelectron spectrum is investigated. At 1053 nm we find a strong isotope effect in the dissociation fraction, whereas at 526.5 nm no such effect is observed. Up to 1{times}10{sup 14} W/cm{sup 2} the photoelectron spectrum at 526.5 nm is dominated by resonant ionization processes via Rydberg states of the molecules. They are shifted into resonance at intensities above {approximately}10{sup 13} W/cm{sup 2}. The spectra show that the potential energy curves of the resonant states must have a shape very similar to the corresponding ionic ones. They are therefore mainly determined by the dipole coupling between the ion core orbitals 1{ital s}{sigma}{sub {ital g}} and 2{ital p}{sigma}{sub {ital u}}. At 1053 nm two photoionization regimes are observed: the multiphoton regime with Keldysh parameter {gamma}{gt}1 showing resonance ionization structures, and the tunnel regime ({gamma}{lt}1) at high intensity. The isotope effect in the dissociation fraction at 1053 nm has no influence on the shape of the corresponding photoelectron spectra at this wavelength. {copyright} {ital 1996 The American Physical Society.}

  15. Hund{close_quote}s-rule effects in the {ital f}{sup 1}-{ital f}{sup 2} Anderson impurity model: Renormalization of Hund{close_quote}s-rule Coulomb interactions down to low energies

    SciTech Connect

    Landgraf, J.M.; Rasul, J.W.

    1996-10-01

    We examine the problem of an Anderson impurity model where the lowest configurations are {ital f}{sup 1} and {ital f}{sup 2}, with a Hund{close_quote}s-rule splitting (corresponding to Hunds first rule) present. We calculate (using the 1/{ital N} expansion) the single-particle spectrum in the limit of large ferromagnetic triplet-singlet splitting, and find the spectrum to be mostly equivalent to that of a zero Hund{close_quote}s-rule splitting model with reduced hybridization. At low energies, however, additional features arise on a scale given by the Kondo temperature. The results illustrate how the effects of a strong Hund{close_quote}s-rule interaction are renormalized down to low energies, and help understand how a heavy fermion band structure can be resilient against Hund{close_quote}s-rule couplings. {copyright} {ital 1996 The American Physical Society.}

  16. Quantum dynamics study for D{sub 2} + OH reaction

    SciTech Connect

    Zhang, Y.; Zhang, D.; Li, W.; Zhang, Q.; Wang, D.; Zhang, D.H.; Zhang, J.Z.H.

    1995-11-16

    A PA5D (potential averaged 5D) TD (time-dependent) quantum wave-packet calculation is reported for the reaction D{sub 2} + OH {yields} D + DOH on the Schatz-Elgersma potential energy surface. The dynamics calculation is carried out on a workstation with a modest memory, which is made possible by using a normalized angular quadrature scheme to minimize the requirement for computer memory during wave-packet propagation. Reaction probabilities, cross sections, and rate constants are presented for the title reaction, and the comparison of the present result with those of the isotopic reactions, H{sub 2} + OH and HD + OH, is given. Consistent with its isotopic reactions, the rotational orientation of D{sub 2} has a stronger effect than that of OH and, in particular, the D{sub 2} (j=1) reactant produces the largest reaction probability, which is attributed to a general steric effect. The comparison of all three isotopic reactions shows that the reactivity (reaction probability and cross section) of the HH(D) + OH system is in the order of P{sub H(2)} > P{sub HD} > P{sub D(2)}. This trend is in good agreement with reduced dimensionality calculations. 27 refs., 8 figs., 4 tabs.

  17. Fate of tritium-labeled vitamin D/sub 3/ and 25-hydroxyvitamin D/sub 3/ in rabbit does and thier pups

    SciTech Connect

    Hidiroglou, H.

    1984-01-01

    Mammary transfer of label from intraperitoneally injected 50 ..mu..Ci (1..cap alpha.., 2..cap alpha..(n)-hydrogen-3) cholecalciferol, and 50 ..mu..Ci (26,27-methyl-hydrogen-3)cholecalciferol was studied in nursing rabbits. Does were injected at 3 days postpartum with one of the two labeled compounds. Pups were killed at either 1, 2, 3, 4, or 5 days after dosing of the does, and does were killed after 5 days. Concentrations of radioactivity were greater in tissues of does dosed with tritiated vitamin D/sub 3/ than in tissues of those dosed with tritiated 25-hydroxyvitamin D/sub 3/. Concentrations of radioactivity were greater in maternal tissues than in tissues of pups. On the 5th day following administration of tritiated vitamin D/sub 3/ or 25-hydroxyvitamin D/sub 3/, the major portion of the radioactivity in does' plasma and liver was associated with tritiated 25-hydroxyvitamin D/sub 3/. In pups from the tritiated vitamin D/sub 3/ group, the concentration of plasma radioactivity associated with 25-hydroxyvitamin D/sub 3/ (isolated by high pressure liquid chromatography) increased significantly with time, reaching 85% of the total vitamin D and metabolite radioactivity in the pups at the 5th day. Over 90% of the total recovered plasma radioactivity of pups of the tritiated 25-hydroxyvitamin D/sub 3/ group was associated with the 25-hydroxyvitamin D/sub 3/. Much more radioactivity was secreted in the milk of tritiated 25-hydroxyvitamin D/sub 3/ dosed does than in milk of does dosed with tritiated vitamin D/sub 3/. 16 references, 3 tables.

  18. 1,25-Dihydroxyvitamin D/sub 3/ target cells in immature pancreatic islets

    SciTech Connect

    Clark, S.A.; Stumpf, W.E.; Sar, M.; DeLuca, H.F.

    1987-07-01

    Target cells of 1,25-dihydroxyvitamin D/sub 3/ were identified by autoradiography in islets from rats of different ages. Nuclei of pancreatic islet cells selectively concentrated 1,25-(/sup 3/H)dihydroxyvitamin D/sub 3/ but not 25-(/sup 3/H)hydroxyvitamin D/sub 3/ or 24,25-(/sup 3/H)dihydroxyvitamin D/sub 3/. Developmental studies of pancreatic islets indicated that target cells, as revealed by significant nuclear concentration of 1,25-(/sup 3/H)dihydroxyvitamin D/sub 3/, are present in islet cells of fetal rats. The percentage of islet cells that concentrated 1,25-(/sup 3/H)dihydroxyvitamin D/sub 3/ increased from 10 to 15% in the fetus to 60% at 1 day of age. Immunocytochemical staining indicated that insulin-containing cells but not glucagon or somatostatin cells concentrated 1,25-(/sup 3/H)dihydroxyvitamin D/sub 3/. Peak uptake of 1,25(/sup 3/H) dihydroxyvitamin D/sub 3/ was calculated to be 400 pmol/mg DNA, with no significant difference in nuclear accumulation between islets cells from neonatal and adult rats or between islets in vivo and isolated islets in vitro. The results of these studies indicate that (1) 1,25-(/sup 3/H)dihydroxyvitamin D/sub 3/ target cells are present in islets before pancreatic ..beta..-cells are morphologically or functionally mature; (2) islet ..beta..-cells concentrate 1,25-dihydroxyvitamin D/sub 3/, but not 25-hydroxyvitamin D/sub 3/ or 24,25-dihydroxyvitamin D/sub 3/. The authors conclude that only the 1,25-dihydroxyvitamin D/sub 3/ metabolite of vitamin D is accumulated by nuclei of developing and mature ..beta..-cells and suggest that 1,25-dihydroxyvitamin D/sub 3/ plays a role in the maturation of islet ..beta..-cells.

  19. Estimation of vitamin D/sub 2/ vitamin D/sub 3/, and their 25-hydroxy metabolites in animal tissues and foods

    SciTech Connect

    Travis, B.D.

    1987-01-01

    A method was developed for the determination of vitamins D/sub 2/ and D/sub 3/ and their 25-hydroxy metabolites that could be applicable to a variety of tissues and foods. Tritiated vitamin D/sub 3/ and 25-hydroxyvitamin D/sub 3/ were used to monitor vitamin losses through the assay procedure. The first step used a saponification and extraction to free the vitamins D from their matrix and reduce the lipids. Most samples were saponified using the AOAC method, while a new procedure was developed for high fat samples. This utilized greater extraction volumes, a more polar extraction solvent, and three salt washes. Three different types of chromatography were then used to enable quantitation. The method was reproducible and accurate for the estimation of vitamin D/sub 3/ and 25-hydroxyvitamin D/sub 3/, but not as accurate for determining vitamin D/sub 2/ and 25-hydroxyvitamin D/sub 2/ due to a lack of radioisotope standards of these compounds.

  20. Isotopic separation of D.sub.2 O from H.sub.2 O using ruthenium adsorbent

    DOEpatents

    Thiel, Patricia A.

    1990-04-10

    A method of enrichment of D.sub.2 O in solutions of D.sub.2 O in H.sub.2 O by contacting said solutions in the steam phase with hexagonal crystalline to produce enriched D.sub.2 O. The passages may be repeated to achieve a desired amount of D.sub.2 O.

  1. Auger resonant Raman spectroscopy used to study the angular distributions of the Xe 4d{sub 5/2} {yields} 6p decay spectrum

    SciTech Connect

    Langer, B.; Berrah, N.; Farhat, A.

    1997-04-01

    Auger resonant Raman spectroscopy is a powerful tool for studying the resonant Auger decay processes with a resolution narrower than the natural lifetime width of the initial inner-shell hole state. This effect has been used to analyze branching ratios of resonantly excited atoms and molecules. In this paper, the authors present results of a study of angular distributions of the spectator decay lines of Xe following 4d{sub 5/2}{r_arrow}6p excitation using the Auger resonant Raman effect and highly resolved photons from the Advanced Light Source (ALS).

  2. Characterization of the hyperline of D{sub 1}/D{sub 0} conical intersections between the maleic acid and fumaric acid anion radicals

    SciTech Connect

    Takahashi, Ohgi; Sumita, Masato

    2004-10-08

    The cation and anion radicals of symmetrical 1,2-disubstituted ethylenes are expected to have a symmetry-allowed conical intersection (CI) between the ground doublet state (D{sub 0}) and the lowest excited doublet state (D{sub 1}) near a 90 deg.-twisted geometry. By the complete active space self-consistent field method, we characterized the hyperline formed by D{sub 1}/D{sub 0} CIs between the anion radicals of maleic acid (cis) and fumaric acid (trans). An implication of the results for the known one-way cis{yields}trans photoisomerization of the maleic acid anion radical and other related ion radicals is presented.

  3. Comparison of the T(sub 1) and D(sub 1) Diagnostics: A New Definition for the Open-Shell D(sub 1) Diagnostic

    NASA Technical Reports Server (NTRS)

    Lee, Timothy J.; Kwak, Dochan (Technical Monitor)

    2002-01-01

    It is shown that the T(sub 1) operator used in a previous study to define the open-shell D(sub 1) diagnostic is invalid, and leads to an arbitrary definition of the open-shell D(sub 1) diagnostic. A new definition is proposed that eliminates this ambiguity and approximately restores the mathematical relationship previously noted between the closed-shell D(sub 1) and T(sub 1) diagnostics. Statistical comparison of the T(sub 1) and D(sub 1) diagnostics shows a very high degree of correlation between them, although it is argued that both diagnostics used together can provide more information than either can separately.

  4. FORMATION OF D{sub 2}-WATER AND D{sub 2}-CARBONIC ACID IN OXYGEN-RICH SOLAR SYSTEM ICES VIA D{sup +}{sub 2} IRRADIATION

    SciTech Connect

    Ennis, Courtney; Bennett, Chris J.; Jones, Brant M.; Kaiser, Ralf I.

    2011-06-01

    Molecular oxygen (O{sub 2}) and carbon dioxide (CO{sub 2}) ices were irradiated with energetic D{sup +}{sub 2} ions to simulate the exposure of oxygen-bearing solar system ices to magnetospheric H{sup +}{sub 2} and H{sup +} ions and energetic protons from the solar wind. The experiments provided evidence on the incorporation of the implanted deuterium and inherent formation of D{sub 2}-water (D{sub 2}O) as well as D{sub 2}-carbonic acid (D{sub 2}CO{sub 3}). In the molecular oxygen ices, the temporal profiles inferred that D{sub 2}-water formation followed successive deuterium atom addition to atomic oxygen via a D-hydroxyl radical intermediate in the matrix. In the carbon dioxide ices, D{sub 2}-carbonic acid was likely formed via successive deuterium atom reaction with cyclic carbon trioxide. These chemical processes have specific relevance to water formation on outer solar system bodies, such as the icy moons of Jupiter and Saturn, as well as possible implications for the formation of water on the lunar surface.

  5. Direct experimental evidence for a metastable state of D/sub 2/F, an analogue of D/sub 3/O

    SciTech Connect

    Raksit, A.B.; Jeon, S.J.; Porter, R.F.

    1986-05-22

    The D/sub 2/F radical has been studied by a combination of neutralized ion beam and charge stripping techniques. Neutrals formed by D/sub 2/SF/sup +//Na charge exchange are observed in metastable and dissociative states. The lifetime of metastable D/sub 2/F is greater than 0.4 ..mu..s. Metastability is not observed for HDF or H/sub 2/F. The dissociative state of D/sub 2/F releases about 1.9 eV of kinetic energy in its fragmentation products (DF + D). The vertical electron affinity of H/sub 2/F/sup +/ is calculated to be 6.6 +- 0.2 eV. The possibility of observing an emission continuum from electronically excited H/sub 2/F formed by H/sub 2/F/sup +//K charge exchange is suggested. Similarities in the mass spectra of D/sub 2/F and the isoelectronic D/sub 3/O radical are indicated.

  6. An experimental review of the decays of the D/sub S/ meson

    SciTech Connect

    Schindler, R.H.

    1989-06-01

    In this paper I review the current experimental knowledge of the decays of the D/sub s/ meson. I compare D/sub s/ properties to those predicted from recent comprehensive D meson decay models that are based on the better measured charmed isodoublet (D/sup 0/,D/sup +/). 12 refs., 5 figs., 2 tabs.

  7. Production of the D/sub s//sup +- / by high-energy neutrons

    SciTech Connect

    Shipbaugh, C.; Wiss, J.; Binkley, M.; Butler, J.; Cumalat, J.P.; Coteus, P.; DiCorato, M.; Diesburg, M.; Enagonio, J.; Filaseta, J.; and others

    1988-05-23

    We have observed the production of the D/sub s//sup +- / by a high-energy neutron beam on nuclear targets. The D/sub s//sup +- / was observed in the decay mode D/sub s//sup +- /..-->..phi..pi../sup +- /, phi..-->..K/sup +/K/sup -/. The average of the inclusive cross sections for D/sub s//sup +/ and D/sub s//sup -/ hadroproduction is measured to be B dsigmadchi/sub F/ = 2.85 +- 0.80 +- 0.86 ..mu..bnucleon at chi/sub F/ = 0.175 on the assumption of a linear A dependence, where BequivalentGAMMA(D/sub s//sup +- /..-->..phi..pi../sup +- /)GAMMA(D/sub s//sup +- /..-->..all). GAMMA(D/sub s//sup +- /..-->..all)

  8. Specific 1,25-dihydroxyvitamin D/sub 3/ binding macromolecule in chicken bone

    SciTech Connect

    Mellon, W.S.; DeLuca, H.F.

    1980-05-10

    Cytosol prepared from homogenates of bone from vitamin D/sub 3/-deficient chicks contains a 3.7 S macromolecule having high affinity and low capacity for 1,25-dihydroxyvitamin D/sub 3/. Employing 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D/sub 3/ (160 Ci/mmol) an apparent K/sub d/ has been calcuated to be 7.6 x 10/sup -11/ M while the association and dissociation rate constants for the binding process at 25/sup 0/C were determined to be 9.5 x 10/sup 8/ M/sup -1/min/sup -1/ and 2.3 x 10/sup -2/ min/sup -1/, respectively. A 5.5 S molecule is also present which binds 1,25-dihydroxyvitamin D/sub 3/ and 25-hydroxyvitamin D/sub 3/ but appears to prefer 25-hydroxyvitamin D/sub 3/ and is increased by the addition of chick serum to cytosol. The 3.7 S material is neither a serum contaminant nor a component of the 5.5 S molecular species and is likely of intracellular origin. Under low salt conditions the 3.7 S macromolecule migrates to 4.3 S and 5.5 S regions on sucrose gradients suggesting aggregation of the protein. Several vitamin D/sub 3/ metabolites are capable of specifically binding to the 3.7 S macromolecule. The relative order of potency for several analogs causing displacement of specifically bound 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D/sub 3/ is: 1,25-dihydroxyvitamin D/sub 3/ > 1 ..cap alpha..-hydroxyvitamin D/sub 3/ greater than or equal to 25-hydroxyvitamin D/sub 3/ > 24(R),25-dihydroxyvitamin D/sub 3/. It is concluded that chick bone cytosol contains a macromolecule of high affinity and low capacity for 1,25-dihydroxyvitamin D/sub 3/ which may function as a receptor for some physiological events in bone.

  9. Non-factorizable contributions to B{sub d}{sup 0} {yields} D{sub s}{sup (*)}D{sub s}{sup (*)} from chiral loops and tree level 1/Nc terms

    SciTech Connect

    Eeg, J. O.; Fajfer, S.; Prapotnik Brdnik, A.

    2006-01-12

    We point out that the amplitudes for the decays B-bar{sup 0} {yields} D{sub s}{sup +}D{sub s}{sup -} and B-bar{sub s}{sup 0} {yields} D{sup +}D{sup -} have no factorizable contributions. If one or two of the D-mesons in the final state are vectors (i.e D* 's) there are relatively small factorizable contributions through the annihilation mechanism. The dominant contributions to the decay amplitudes arise from chiral loop contributions and 1/Nc suppressed tree level. We predict that the branching ratios for the processes B-bar{sub d}{sup 0} {yields} D{sub s}{sup +}D{sub s}{sup -}, B-bar{sub d}{sup 0} {yields} D{sub s}{sup +}*D{sub s}{sup -} and B-bar{sub d}{sup 0} {yields} D{sub s}{sup +}D{sub s}{sup -}* are all of order (2 - 3) x 10-4, while B-bar{sub s}{sup 0} {yields} D{sub d}{sup +}D{sub d}{sup -}, B-bar{sub s}{sup 0} {yields} D{sub d}{sup +}*D{sub d}{sup -} and B-bar{sub s}{sup 0} {yields} D{sub d}{sup +}D{sub d}{sup -}* are of order (4 - 7) x 10-3. If both D-mesons in the final state are D*'s, we obtain branching ratios of order two times bigger.

  10. Nuclear methods for detecting a diversion of D/sub 2/O

    SciTech Connect

    Fainberg, A.; Zucker, M.S.

    1980-01-01

    The possibility of diverting D/sub 2/O for use in clandestine reactors capable of weapons grade nuclear material production has created interest in safeguarding D/sub 2/O. As part of a program to investigate the technological aspects of safeguarding D/sub 2/O, several proposed nuclear based non-destructive measurement methods have been proposed which do not require the D/sub 2/O containers to be opened. These nuclear techniques all proved workable and could lend themselves, in principle, to field application. They are neutron transmission measurements, neutron capture gamma detection, photoneutron production, and measurements of the lifetime of neutrons injected in the barrel. Since much of the instrumentation is common to several methods, more than one technique may be employed to give added assurance. 6 figures, 2 tables.

  11. The D{sub s1} and its D*K decays

    SciTech Connect

    Segovia, J.; Entem, D. R.; Fernandez, F.

    2010-08-05

    Recently the Belle Collaboration has measured a new decay channel for the charmed strange meson D{sub s1}(2536){sup +{yields}}D{sup +{pi}-}K{sup +} together with an angular analysis of the D{sub s1}(2536){sup +{yields}}D*{sup +}K{sub S}{sup 0} decay. We study this reaction in a constituent quark model which has been able to reproduce the hadronic phenomenology and the baryon-baryon interaction. The reported branching fraction can be explained through a virtual D*{sup 0} and the properties of the D{sub s1}(2536){sup +} state are nicely reproduced. The influence of other intermediate states in the reaction D{sub s1}(2536){sup +{yields}}D{sup +{pi}-}K{sup +} has been analyzed giving negligible contributions.

  12. Studies on the metabolism of prostaglandin D/sub 2/ in humans

    SciTech Connect

    Liston, T.E.

    1985-01-01

    Fifty ..mu..Ci of (/sup 3/H)-prostaglandin D/sub 2/ tracer (100 Ci/mMole) was infused intravenously into a normal human male volunteer. Seventy-five percent of the infused radioactivity was excreted into the urine within 5 hours. This urine was added to urine obtained from two mastocytosis patients with marked overproduction of prostaglandin D/sub 2/. Twenty-five radiolabelled prostaglandin D/sub 2/ urinary metabolites were chromatographically isolated and purified and subsequently identified by gas chromatography-mass spectrometry. Twenty-three of these metabolites, comprising 37% of the recovered radioactivity, had prostaglandin F-ring structures, and only 2 metabolites, comprising 2.7% of the recovered radioactivity retained the prostaglandin D-ring structure. The single most abundant metabolite identified was 9,11-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-energy-1,20-dioic acid which was isolated in a tricyclic form. Different isomeric forms of several prostaglandin F-ring metabolites were identified. To further investigate the metabolism of prostaglandin D/sub 2/, in vitro studies examining the metabolic transformation of prostaglandin D/sub 2/ by human liver were conducted. This study documents that prostaglandin D/sub 2/ is metabolized to PGF-ring metabolites in vivo in humans, and is converted to a structurally new prostaglandin, 9/sub ..cap alpha../, 11/sub ..beta../-PGF/sub 2/ in vitro by a cytosolic NADPH-dependent 11-Ketoreductase in the human liver.

  13. Identification of D/sub 1/-like dopamine receptors on human blood platelets

    SciTech Connect

    De Keyser, J.; De Waele, M.; Convents, A.; Ebinger, G.; Vauquelin, G.

    1988-01-01

    Dopamine is able to inhibit the epinephrine-induced aggregation of human blood platelets, but the mechanism of action has not been elucidated. In this study the authors report that membranes from human blood platelets possess high affinity, saturable and stereoselective binding sites for the D/sub 1/ dopamine receptor antagonist (/sup 3/H)SCH 23390. (/sup 3/H)SCH 23390 appeared to label a single class of binding sites with a B/sub max/ of 18.6 +- 1.6 fmolmg protein and a K/sub D/ of 0.8 nM. The potencies of different dopaminergic antagonists and agonists in displacing (/sup 3/H)SCH 23390 from blood platelet membranes were similar to those obtained for striatal membranes. Unlike the classically defined D/sub 1/ receptors, e.g. those in striatum, the D/sub 1/ receptor sites on platelets appeared no to be coupled to the adenylate cyclase system, hence the term D/sub 1/-like. The D/sub 1/ agonist SKF 38393 was more potent than dopamine in inhibiting platelet aggregation induced by epinephrine, and the effects of dopamine and SKF 38393 were prevented by SCH 23390. These results suggest that the inhibitory action of dopamine on the epinephrine-induced platelet aggregation is mediated through these D/sub 1/-like receptors

  14. Molecular dynamics simulations of D{sub 2}O ice photodesorption

    SciTech Connect

    Arasa, C.; Andersson, S.; Cuppen, H. M.; Dishoeck, E. F. van; Kroes, G. J.

    2011-04-28

    Molecular dynamics (MD) calculations have been performed to study the ultraviolet (UV) photodissociation of D{sub 2}O in an amorphous D{sub 2}O ice surface at 10, 20, 60, and 90 K, in order to investigate the influence of isotope effects on the photodesorption processes. As for H{sub 2}O, the main processes after UV photodissociation are trapping and desorption of either fragments or D{sub 2}O molecules. Trapping mainly takes place in the deeper monolayers of the ice, whereas desorption occurs in the uppermost layers. There are three desorption processes: D atom, OD radical, and D{sub 2}O molecule photodesorption. D{sub 2}O desorption takes places either by direct desorption of a recombined D{sub 2}O molecule, or when an energetic D atom produced by photodissociation kicks a surrounding D{sub 2}O molecule out of the surface by transferring part of its momentum. Desorption probabilities are calculated for photoexcitation of D{sub 2}O in the top four monolayers and are compared quantitatively with those for H{sub 2}O obtained from previous MD simulations of UV photodissociation of amorphous water ice at different ice temperatures [Arasa et al., J. Chem. Phys. 132, 184510 (2010)]. The main conclusions are the same, but the average D atom photodesorption probability is smaller than that of the H atom (by about a factor of 0.9) because D has lower kinetic energy than H, whereas the average OD radical photodesorption probability is larger than that of OH (by about a factor of 2.5-2.9 depending on ice temperature) because OD has higher translational energy than OH for every ice temperature studied. The average D{sub 2}O photodesorption probability is larger than that of H{sub 2}O (by about a factor of 1.4-2.3 depending on ice temperature), and this is entirely due to a larger contribution of the D{sub 2}O kick-out mechanism. This is an isotope effect: the kick-out mechanism is more efficient for D{sub 2}O ice, because the D atom formed after D{sub 2}O photodissociation

  15. Insights into cyclostome phylogenomics: pre-2R or post-2R.

    PubMed

    Kuraku, Shigehiro

    2008-10-01

    Interest in understanding the transition from prevertebrates to vertebrates at the molecular level has resulted in accumulating genomic and transcriptomic sequence data for the earliest groups of extant vertebrates, namely, hagfishes (Myxiniformes) and lampreys (Petromyzontiformes). Molecular phylogenetic studies on species phylogeny have revealed the monophyly of cyclostomes and the deep divergence between hagfishes and lampreys (more than 400 million years). In parallel, recent molecular phylogenetic studies have shed light on the complex evolution of the cyclostome genome. This consists of whole genome duplications, shared at least partly with gnathostomes (jawed vertebrates), and cyclostome lineage-specific secondary modifications of the genome, such as gene gains and losses. Therefore, the analysis of cyclostome genomes requires caution in distinguishing between orthology and paralogy in gene molecular phylogeny at the gene family scale, as well as between apomorphic and plesiomorphic genomic traits in larger-scale analyses. In this review, we propose possible ways of improving the resolvability of these evolutionary events, and discuss probable scenarios for cyclostome genome evolution, with special emphasis on the hypothesis that two-round (2R) genome duplication events occurred before the divergence between cyclostomes and gnathostomes, and therefore that a post-2R state is a genomic synapomorphy for all extant vertebrates. PMID:19267631

  16. (2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

    PubMed Central

    Kozhushkov, Sergei I; Yufit, Dmitrii S; Grosse, Christian; Kaiser, Marcel

    2014-01-01

    Summary Efficient and scalable syntheses of enantiomerically pure (2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-mono(di,tri)fluoromethylcyclopropyl]alanines 9a–c, as well as allo-D-threonine (4) and (2S,3R)-β-methylphenylalanine (3), using the Belokon' approach with (S)- and (R)-2-[(N-benzylprolyl)amino]benzophenone [(S)- and (R)-10] as reusable chiral auxiliaries have been developed. Three new fluoromethyl analogues of the naturally occurring octadepsipeptide hormaomycin (1) with (fluoromethylcyclopropyl)alanine moieties have been synthesized and subjected to preliminary tests of their antibiotic activity. PMID:25550751

  17. Characterization of D/sub 1/ dopamine receptors in the central nervous system

    SciTech Connect

    Hess, E.J.

    1987-01-01

    Several lines of evidence suggest an association of central nervous system dopaminergic systems in the etiology of the schizophrenia. Interest in the role of D/sub 1/ dopamine receptors has revived with the advent of selective drugs for this dopamine receptor, particularly the D/sub 1/ dopamine receptor antagonists, SCH23390. (/sup 3/H)SCH23390 represents a superior radioligand for labeling the two-state striatal D/sub 1/ dopamine receptor in that its high percent specific binding makes it especially suitable for detailed mechanistic studies of this receptor. Striatal D/sub 1/ dopamine receptors have been shown to mediate the stimulation of adenylate cyclase activity via a guanine nucleotide regulatory subunit. Forskolin acts in a synergistic manner with dopamine agonists, guanine nucleotides or sodium fluoride to potentiate the stimulation of rat striatal adenylate cyclase activity mediated by these reagents. By using the aforementioned reagents and the irreversible receptor modifying reagent N-ethoxycarbonyl-2-ethoxy-1,2,-dihydroquinoline, we demonstrated that the D/sub 1/ dopamine receptor population in rat striatum is not a stoichiometrically-limiting factor in agonist stimulation of adenylate cyclase activity.

  18. Polaron dynamics with a multitude of Davydov D{sub 2} trial states

    SciTech Connect

    Zhou, Nengji; Huang, Zhongkai; Zhu, Jiangfeng; Zhao, Yang; Chernyak, Vladimir

    2015-07-07

    We propose an extension to the Davydov D{sub 2} Ansatz in the dynamics study of the Holstein molecular crystal model with diagonal and off-diagonal exciton-phonon coupling using the Dirac-Frenkel time-dependent variational principle. The new trial state by the name of the “multi-D{sub 2} Ansatz” is a linear combination of Davydov D{sub 2} trial states, and its validity is carefully examined by quantifying how faithfully it follows the Schrödinger equation. Considerable improvements in accuracy have been demonstrated in comparison with the usual Davydov trial states, i.e., the single D{sub 1} and D{sub 2} Ansätze. With an increase in the number of the Davydov D{sub 2} trial states in the multi-D{sub 2} Ansatz, deviation from the exact Schrödinger dynamics is gradually diminished, leading to a numerically exact solution to the Schrödinger equation.

  19. 1,25-Dihydroxyvitamin D{sub 3} regulates genes responsible for detoxification in intestine

    SciTech Connect

    Kutuzova, Galina D.; DeLuca, Hector F. . E-mail: deluca@biochem.wisc.edu

    2007-01-01

    1{alpha},25-Dihydroxyvitamin D{sub 3} (1,25-(OH){sub 2}D{sub 3}), the biologically active form of vitamin D{sub 3}, not only plays a major role in mammalian calcium and phosphorous homeostasis but also exerts pleiotropic effects on cell proliferation, differentiation and the immune system. Further, vitamin D is believed to play a significant role in the prevention of colon, prostate, and breast cancer and in reducing the risk of autoimmune diseases. To gain insight into the mechanism whereby vitamin D can have such diverse actions, we have employed microarray technology. We studied the effect of a single dose of 1,25-(OH){sub 2}D{sub 3} on gene expression in the intestine of vitamin D-deficient rats. Within 6 h, 1,25-(OH){sub 2}D{sub 3} stimulates the expression of several phase I and phase II biotransformation genes. There is also an increased expression of antioxidant genes. These results support the idea that vitamin D is a significant factor in detoxification and protection against environmental toxins.

  20. Regulation of cholesterol 25-hydroxylase expression by vitamin D{sub 3} metabolites in human prostate stromal cells

    SciTech Connect

    Wang, J.-H. . E-mail: Jinghuan.Wang@uta.fi; Tuohimaa, Pentti

    2006-06-30

    Vitamin D{sub 3} plays an important role in the control of cell proliferation and differentiation. Cholesterol 25-hydroxylase (CH25H) is an enzyme converting cholesterol into 25-hydroxycholesterol. Vitamin D{sub 3} as well as 25-hydroxycholesterol has been shown to inhibit cell growth and induce cell apoptosis. Here we show that 10 nM 1{alpha},25(OH){sub 2}D{sub 3} and 500 nM 25OHD{sub 3} upregulate CH25H mRNA expression in human primary prostate stromal cells (P29SN). Protein synthesis inhibitor cycloheximide does not block 1{alpha},25(OH){sub 2}D{sub 3} mediated upregulation of CH25H mRNA. Transcription inhibitor actinomycin D blocks basal level as well as 1{alpha},25(OH){sub 2}D{sub 3} induced CH25H mRNA expression. 1{alpha},25(OH){sub 2}D{sub 3} has no effect on CH25H mRNA stability. 25-Hydroxycholesterol significantly decreased the P29SN cell number. A CH25H enzyme inhibitor, desmosterol, increases basal cell number but has no significant effect on vitamin D{sub 3} treated cells. Our data suggest that ch25h could be a vitamin D{sub 3} target gene and may partly mediate anti-proliferative action of vitamin D{sub 3} in human primary prostate stromal cells.

  1. Analysis of various types of single-polypeptide-chain (sc) heterodimeric A{sub 2A}R/D{sub 2}R complexes and their allosteric receptor–receptor interactions

    SciTech Connect

    Kamiya, Toshio; Yoshioka, Kazuaki; Nakata, Hiroyasu

    2015-01-09

    Highlights: • Various scA{sub 2A}R/D{sub 2}R constructs, with spacers between the two receptors, were created. • Using whole cell binding assay, constructs were examined for their binding activity. • Although the apparent ratio of A{sub 2A}R to D{sub 2}R binding sites should be 1, neither was 1. • Counter agonist-independent binding cooperativity occurred in context of scA{sub 2A}R/D{sub 2}R. - Abstract: Adenosine A{sub 2A} receptor (A{sub 2A}R) heteromerizes with dopamine D{sub 2} receptor (D{sub 2}R). However, these class A G protein-coupled receptor (GPCR) dimers are not fully formed, but depend on the equilibrium between monomer and dimer. In order to stimulate the heteromerization, we have previously shown a successful design for a fusion receptor, single-polypeptide-chain (sc) heterodimeric A{sub 2A}R/D{sub 2}R complex. Here, using whole cell binding assay, six more different scA{sub 2A}R/D{sub 2}R constructs were examined. Not only in scA{sub 2A}R/D{sub 2}R ‘liberated’ with longer spacers between the two receptors, which confer the same configuration as the prototype, the A{sub 2A}R-odr4TM-D{sub 2L}R, but differ in size (Forms 1–3), but also in scA{sub 2A}R/D{sub 2L}R (Form 6) fused with a transmembrane (TM) of another type II TM protein, instead of odr4TM, neither of their fixed stoichiometry (the apparent ratios of A{sub 2A}R to D{sub 2}R binding sites) was 1, suggesting their compact folding. This suggests that type II TM, either odr4 or another, facilitates the equilibrial process of the dimer formation between A{sub 2A}R and D{sub 2L}R, resulting in the higher-order oligomer formation from monomer of scA{sub 2A}R/D{sub 2L}R itself. Also, in the reverse type scA{sub 2A}R/D{sub 2L}R, i.e., the D{sub 2L}R-odr4TM-A{sub 2A}R, counter agonist-independent binding cooperativity (cooperative folding) was found to occur (Forms 4 and 5). In this way, the scA{sub 2A}R/D{sub 2L}R system has unveiled the cellular phenomenon as a snapshot of the

  2. Coded aperture imaging of fusion source in a plasma focus operated with pure D{sub 2} and a D{sub 2}-Kr gas admixture

    SciTech Connect

    Springham, S. V.; Talebitaher, A.; Shutler, P. M. E.; Rawat, R. S.; Lee, P.; Lee, S.

    2012-09-10

    The coded aperture imaging (CAI) technique has been used to investigate the spatial distribution of DD fusion in a 1.6 kJ plasma focus (PF) device operated in, alternatively, pure deuterium or deuterium-krypton admixture. The coded mask pattern is based on a singer cyclic difference set with 25% open fraction and positioned close to 90 Degree-Sign to the plasma focus axis, with CR-39 detectors used to register tracks of protons from the D(d, p)T reaction. Comparing the coded aperture imaging proton images for pure D{sub 2} and D{sub 2}-Kr admixture operation reveals clear differences in size, density, and shape between the fusion sources for these two cases.

  3. Nonlinear Fourier-transform spectroscopy of D{sub 2} using high-order harmonic radiation

    SciTech Connect

    Furukawa, Yusuke; Nabekawa, Yasuo; Saugout, Sebastien; Midorikawa, Katsumi; Okino, Tomoya; Yamanouchi, Kaoru

    2010-07-15

    We have determined the multiphoton ionization and dissociation pathways of D{sub 2} with the simultaneous irradiation of the high-order harmonic fields and the low-order harmonic fields of Ti:sapphire laser pulses in the visible-vacuum ultraviolet region with the aid of a nonlinear Fourier-transform spectroscopy. By analyzing the interferometric autocorrelation signal of the measured velocity map images of D{sup +}, we were able to decompose the measured momentum distribution into three momentum distribution images representing the three distinct dissociation pathways, which are sequentially two-photon absorption processes of D{sub 2} via the electronic ground state (X {sup 2{Sigma}}{sub g}{sup +}) of D{sub 2}{sup +} to the first excited state (A {sup 2{Sigma}}{sub u}{sup +}), leading to the dissociation into D{sup +} + D.

  4. Matrix isolation ESR spectroscopy and magnetic anisotropy of D{sub 3h} symmetric septet trinitrenes

    SciTech Connect

    Misochko, Eugenii Ya.; Akimov, Alexander V.; Masitov, Artem A.; Korchagin, Denis V.; Aldoshin, Sergei M.; Chapyshev, Sergei V.

    2013-05-28

    The fine-structure (FS) parameters D of a series of D{sub 3h} symmetric septet trinitrenes were analyzed theoretically using density functional theory (DFT) calculations and compared with the experimental D values derived from ESR spectra. ESR studies show that D{sub 3h} symmetric septet 1,3,5-trichloro-2,4,6-trinitrenobenzene with D=-0.0957 cm{sup -1} and E= 0 cm{sup -1} is the major paramagnetic product of the photolysis of 1,3,5-triazido-2,4,6-trichlorobenzene in solid argon matrices at 15 K. Trinitrenes of this type display in the powder X-band ESR spectra intense Z{sub 1}-transition at very low magnetic fields, the position of which allows one to precisely calculate the parameter D of such molecules. Thus, our revision of the FS parameters of well-known 1,3,5-tricyano-2,4,6-trinitrenobenzene [E. Wasserman, K. Schueller, and W. A. Yager, Chem. Phys. Lett. 2, 259 (1968)] shows that this trinitrene has Double-Vertical-Line D Double-Vertical-Line = 0.092 cm{sup -1} and E= 0 cm{sup -1}. DFT calculations reveal that, unlike C{sub 2v} symmetric septet trinitrenes, D{sub 3h} symmetric trinitrenes have the same orientations of the spin-spin coupling tensor D-caret{sub SS} and the spin-orbit coupling tensor D-caret{sub SOC} and, as a result, have negative signs for both the D{sub SS} and D{sub SOC} values. The negative magnetic anisotropy of septet 2,4,6-trinitrenobenzenes is considerably strengthened on introduction of heavy atoms in the molecules, owing to an increase in contributions of various excitation states to the D{sub SOC} term.

  5. Rate constants for the reactions H+O sub 2 r arrow OH+O and D+O sub 2 r arrow OD+O over the temperature range 1085--2278 K by the laser photolysis--shock tube technique

    SciTech Connect

    Shin, K.S.; Michael, J.V. )

    1991-07-01

    Rate constants for the reactions (1) H+O{sub 2}{r arrow}OH+O and (2) D+O{sub 2}{r arrow}OD+O have been measured over the temperature ranges 1103--2055 K and 1085--2278 K, respectively. The experimental method that has been used is the laser-photolysis--shock-tube technique. This technique utilizes atomic resonance absorption spectrophotometry (ARAS) to monitor H- or D-atom depletion in the presence of a large excess of reactant, O{sub 2}. The results can be well represented by the Arrhenius expressions {ital k}{sub 1}({ital T})=(1.15{plus minus}0.16){times}10{sup {minus}10} exp({minus}6917{plus minus}193 K/{ital T}) cm{sup 3} molecule{sup {minus}1} s{sup {minus}1}, and {ital k}{sub 2}({ital T})=(1.09{plus minus}0.20){times}10{sup {minus}10} exp({minus}6937{plus minus}247 K/{ital T}) cm{sup 3} molecule{sup {minus}1} s{sup {minus}1}. Over the experimental temperature range, the present results show that the isotope effect is unity within experimental uncertainty. The Arrhenius equations, {ital k}{sub {minus}1}({ital T})=(8.75{plus minus}1.24) {times}10{sup {minus}12} exp(1121{plus minus}193 K/{ital T}) cm{sup 3} molecule{sup {minus}1} s{sup {minus}1} and {ital k}{sub {minus}2} ({ital T})=(9.73{plus minus}1.79){times}10{sup {minus}12} exp(526{plus minus}247 K/{ital T}) cm{sup 3} molecule{sup {minus}1} s{sup {minus}1}, for the rate constants of the reverse reactions were calculated from the experimentally measured forward rate constants and expressions for the equilibrium constants that have been derived from the JANAF thermochemical database. The theoretical implications of the present results are also discussed.

  6. Erosion of a-C:D Thin Films by Low Energy D+, D>2+, and D>3+ Ion Beam Irradiation

    SciTech Connect

    Meyer, Fred W; Harris, Peter R; Zhang, Hengda; Jacob, W.; Schwarz-Selinger, T.; Von Toussaint, U.

    2011-01-01

    We report measurements of total C sputtering yields for room temperature a-C:D thin films irrradiated by equal velocity D{sup +}, D{sub 2}{sup +}, and D{sub 3}{sup +} beams in the energy range 30-200 eV/D. The C sputtering yields were deduced from crater volumes determined from 2-D ellipsometry scans, the known thin film C density, and the measured total number of incident D particles during the beam exposures. While our results for incident D{sub 3}{sup +} ions are in good agreement with mass loss measurements for D{sub 3}{sup +}, our results for D{sub 2}{sup +} and D{sup +} incident ions fall systematically below the D{sub 3}{sup +} results, indicating a significant molecular size effect. A molecular size effect has been previously found for CD{sub 4} production during low energy impact of same velocity D{sup +}, D{sub 2}{sup +}, and D{sub 3}{sup +} ions incident on ATJ graphite, which, however, was smaller in magnitude. The ellipsometry-based total C sputtering yields are compared with recently deduced total C production yields based on a mass spectroscopy approach.

  7. Effect of gonadectomy of biochemical indices of striatal dopamine D/sub 1/ and D/sub 2/ receptors, their activity and adaptive response to antipsychotic drug treatment in rat

    SciTech Connect

    Jastrow, T.L.R.

    1987-01-01

    Endogenous gonadal steroids in male and female rats were removed by gonadectomy (Gnx). Striatal D/sub 1/ receptors and their activity were characterized by (/sup 3/H)SCH23390 binding parameters and D/sub 1/ receptor-stimulated adenylate cyclase activity in striatal membranes. Striatal D/sub 2/ receptors and their activity were characterized by (/sup 3/H)sulpiride binding parameters in striatal slices and D/sub 2/ receptor-mediated inhibition of forskolin-activated adenylate cyclase activity in striatal membranes. Sub-chronic D/sub 2/ receptor blockade consisted of the administration of the D/sub 2/ specific antagonist sulpiride (20 mg/kg) or vehicle i.p., 2x daily for 21 days followed by a 3 day drug withdrawal period. Gnx of female rats had no affect on striatal D/sub 1/-stimulated adenylate cyclase activity nor on the striatal D/sub 2/ receptor-mediated inhibition of forskolin-activated adenylate cyclase activity. Sub-chronic sulpiride treatment produced no adaptive changes in D/sub 1/-stimulated adenylate cyclase activity in sham-operated or Gnx female rats. Gnx of male rats produced a statistically significant 10% decrease in striatal (/sup 3/H)SCH23390 binding sites with no change in D/sub 1/-stimulated adenylate cyclase activity and no change in striatal(/sup 3/H)sulpiride binding parameters. Sub-chronic sulpiride treatment of sham-operated male rats produced a desensitization of the striatal D/sub 1/-stimulated adenylate cyclase activity with no change in the number of (/sup 3/H)SCH23390 binding sites and no change in (/sup 3/H)sulpiride binding parameters. Gnx of male rats blocked the development of the striatal D/sub 1/ receptor desensitization response elicited by sub-chronic sulpiride treatment, without affecting striatal (/sup 3/H)SCH23390 or (/sup 3/H)sulpiride binding parameters. We have demonstrated that sub-chronic D/sub 2/ receptor blockade in sham-operated male rats results in the desensitization of striatal D/sub 1/ receptor activity.

  8. No association detected between a D{sub 3} receptor gene-expressed variant and schizophrenia

    SciTech Connect

    Rothschild, L.G.; Badner, J.; Cravchik, A.; Gershon, E.S.; Gejman, P.V.

    1996-04-09

    A missense polymorphism (glycine to serine) in the first exon of the dopamine D{sub 3} (DRD3) gene was examined in a sib-pairs schizophrenia collection by the transmission test for linkage disequilibrium (TDT). No association due to linkage disequilibrium was detected using TDT. Additionally, no evidence for excess homozygosity was found. 26 refs., 3 tabs.

  9. Uncatalyzed reaction of selected unsaturated compounds with D{sub 2}

    SciTech Connect

    Rajagopal, V.K.; Guthrie, R.D.; Shi, B.; Davis, B.H.

    1994-12-31

    In our previous study of the reaction of 1,2-diphenylethane (bibenzyl), DPE, and other compounds with D{sub 2} at temperatures to 450{degrees}C and pressures of 2000 psi in isolation from metal surfaces, we were able to provide strong evidence for a mechanistic scheme wherein radicals formed by the homolysis of weak bonds, react with D{sub 2} to give D atoms. These participate in short radical-chain processes responsible for hydrocracking and exchange of H for D at unsubstituted aromatic positions. In contrast to the simple thermolysis of DPE wherein stilbene (PhCH=CHPh), STH, is formed as a major product, the reaction of DPE with D{sub 2} produces relatively small amounts of this compound. Moreover, the mole % of STB among the products decreases as conversion increases, indicating that initially produced STB is consumed. It, therefore, seemed important to examine the reaction of STB with D{sub 2}. This study has subsequently been extended to other unsaturated compounds and the results are reported below.

  10. A search for the decay B {yields} D{sub s}Xl{bar v}

    SciTech Connect

    Cho, A.; Kim, P.

    1995-04-01

    Using {approximately} 3 fb{sup {minus}1} of data collected on and just below the {Upsilon}(4S) resonance with the CLEO II detector at the Cornell Electron Storage Ring (CESR), the authors have searched for the semileptonic B decay B {yields} D{sub s}X{ell}{bar {nu}}.

  11. Noncommutative D{sub 3}-brane, black holes, and attractor mechanism

    SciTech Connect

    Kar, Supriya; Majumdar, Sumit

    2006-09-15

    We revisit the 4D generalized black hole geometries, obtained by us 14, with a renewed interest, to unfold some aspects of effective gravity in a noncommutative D{sub 3}-brane formalism. In particular, we argue for the existence of extra dimensions in the gravity decoupling limit in the theory. We show that the theory is rather described by an ordinary geometry and is governed by an effective string theory in 5D. The extremal black hole geometry AdS{sub 5} obtained in effective string theory is shown to be in precise agreement with the gravity dual proposed for D{sub 3}-brane in a constant magnetic field. Kaluza-Klein compactification is performed to obtain the corresponding charged black hole geometries in 4D. Interestingly, they are shown to be governed by the extremal black hole geometries known in string theory. The attractor mechanism is exploited in effective string theory underlying a noncommutative D{sub 3}-brane and the macroscopic entropy of a charged black hole is computed. We show that the generalized black hole geometries in a noncommutative D{sub 3}-brane theory are precisely identical to the extremal black holes known in 4D effective string theory.

  12. Endogenous leukotriene D/sub 4/ formation during anaphylactic shock in the guinea pig

    SciTech Connect

    Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

    1987-08-01

    Experiments on the metabolism and excretion of i.v. administered selectively labeled (/sup 3/H/sub 8/)leukotriene C/sub 4/ in bile duct-cannulated guinea pigs indicated predominantly biliary excretion of tritium. The major leukotriene metabolite in bile was identified as leukotriene D/sub 4/. By monitoring leukotriene excretion radioimmunochromatographically, it was shown that guinea pigs suffering from anaphylactic shock produce leukotriene D/sub 4/ endogenously. Immunological challenge of animals sensitized to ovalbumin was accompanied by an increase of biliary leukotriene D/sub 4/ concentrations from 10 +/- 1 to 86 +/- 10 nM. When considering that bile flow was decreased to about half after challenge, the excretion rate of leukotriene D/sub 4/ in bile increased from 0.88 +/- 0.16 before 3.18 +/- 0.38 pmol x min/sup -1/ x kg/sup -1/ after challenge. It is concluded that systemic anaphylaxis in the guinea pig is associated with endogenous generation of leukotriene C/sub 4/.

  13. Interaction of D{sub 2}O with model oxide single crystal surfaces: Clean and oxidized W(110)

    SciTech Connect

    Herman, G.S.; Gallagher, M.C.; Joyce, S.

    1995-12-31

    It has been suggested that the interaction of D{sub 2}O with single crystal oxide surfaces are dominated by defects. To investigate this we have prepared and then characterized oxidized W(110) surfaces with Auger electron spectroscopy, low-energy electron diffraction, and scanning tunneling microscopy. We have also used temperature programmed desorption (TPD) to investigate the interaction of D{sub 2}O with these surfaces. Results indicate that desorption of D{sub 2}O occurs from two states for both the clean and fully oxidized surface. The decomposition of D{sub 2}O was found to occur on the clean surface but not for the fully oxidized surface. This is evident from the observation of residual oxygen remaining on the clean surface after a TPD cycle as well as the observation of two different D{sub 2} desorption features for the clean surface. On the fully oxidized surface neither occur.

  14. Quantitative and high spatial resolution d{sub 33} measurement of piezoelectric bulk and thin films

    SciTech Connect

    Shetty, Smitha Yang, Jung In; Trolier-McKinstry, Susan; Stitt, Joe

    2015-11-07

    A single beam laser interferometer based on a modified Mirau detection scheme with a vertical resolution of ∼5 pm was developed for localized d{sub 33} measurements on patterned piezoelectric films. The tool provides high spatial resolution (∼2 μm), essential for understanding scaling and processing effects in piezoelectric materials. This approach enables quantitative information on d{sub 33}, currently difficult in local measurement techniques such as piezoresponse force microscopy. The interferometer is built in a custom microscope and employs a phase lock-in technique in order to detect sub-Angstrom displacements. d{sub 33} measurements on single crystal 0.67PbMg{sub 0.33}Nb{sub 0.67}O{sub 3}-0.33PbTiO{sub 3} and bulk PbZrTiO{sub 3}-5A ceramics demonstrated agreement within <3% with measurements using a double beam laser interferometer. Substrate bending contributions to out-of-plane strain, observed in thin continuous PbZr{sub 0.52}Ti{sub 0.48}O{sub 3} films grown on Si substrates is reduced for electrode diameters smaller than 100 μm. Direct scanning across room temperature and 150 °C poled 5 μm and 10 μm features etched in 0.5 μm thick PbZr{sub 0.52}Ti{sub 0.48}O{sub 3} films doped with 1% Nb confirmed minimal substrate contributions to the effective d{sub 33,f}. Furthermore, enhanced d{sub 33,f} values were observed along the feature edges due to partial declamping from the substrate, thus validating the application of single beam interferometry on finely patterned electrodes.

  15. Operational guidance for using DOT-6M/2R packaging

    SciTech Connect

    Kelly, D.L.; Hummer, J.H.

    1994-03-01

    The purpose of this paper is to describe a new US Department of Energy (DOE), Transportation Management Division task to create a US Department of Transportation (DOT) Specification 6M/2R packaging configuration user`s guide. The need for a user`s guide was identified because the DOT-6M/2R packaging configuration is widely used by DOE site contractors, and DOE receives many questions about the approved packaging configurations. Currently, two DOE organizations have the authority to approve new DOT-6M/2R configurations. For Defense Programs, the Transportation and Packaging Safety Division (EH-332) administers the program. For Environmental Restoration and Waste Management, the Transportation Management Division (EM-261) administers the program.

  16. Extending the R-2R lens to 360 deg

    NASA Astrophysics Data System (ADS)

    Clapp, R. E.

    1984-07-01

    The R-2R lens is a remarkable microwave device that provides perfect focusing, giving multiple simultaneous antenna beams from a circular or cylindrical array. However, the perfect focusing of the R-2R brings with it a serious limitation on angular coverage as a result of the angular doubling that enters when the array elements in the antenna are connected to the launcher elements on the lens periphery. A way has now been found to modify the R-2R concept so that a full circle of array elements can be mapped onto a full circle of beam ports. The new mapping makes use of hybrid junctions and either four or six physical lenses. The interconnections result in 360 deg of simultaneous antenna beams, each of which can be used both for transmission and for reception.

  17. X(3872) as the {sup 1}D{sub 2} charmonium

    SciTech Connect

    Kalashnikova, Yu. S.; Nefediev, A. V.

    2013-12-15

    The {sup 1}D{sub 2} charmonium assignment for the X(3872) is considered, which is compatible with the 2{sup −+} quantum numbers, as favoured by the BABAR Collaboration analysis presented recently for the π{sup +}π{sup −}π{sup 0}J/ψ decay mode. It is demonstrated that established properties of the X(3872) are in a drastic conflict with the {sup 1}D{sub 2}c c-bar assignment. Furthermore, it is argued that a combined analysis of the data for different decay channels of the X, with the help of theoretical formulae which meet a number of constraints imposed by phenomenology, results in a suitable description of the experimental data for the X compatible with its quantum numbers 1{sup ++}.

  18. Absolute Measurement of Hadronic Branching Fractions of the D{sub s}{sup +} Meson

    SciTech Connect

    Alexander, J. P.; Berkelman, K.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krueger, H.; Mohapatra, D.; Onyisi, P. U. E.; Patterson, J. R.

    2008-04-25

    The branching fractions of D{sub s}{sup {+-}} meson decays serve to normalize many measurements of processes involving charm quarks. Using 298 pb{sup -1} of e{sup +}e{sup -} collisions recorded at a center of mass energy of 4.17 GeV, we determine absolute branching fractions for eight D{sub s}{sup {+-}} decays with a double tag technique. In particular we determine the branching fraction B(D{sub s}{sup +}{yields}K{sup -}K{sup +}{pi}{sup +})=(5.50{+-}0.23{+-}0.16)%, where the uncertainties are statistical and systematic, respectively. We also provide partial branching fractions for kinematic subsets of the K{sup -}K{sup +}{pi}{sup +} decay mode.

  19. Concise Synthesis of (2R,4R)-Monatin.

    PubMed

    Amino, Yusuke

    2016-01-01

    Monatin, 4-hydroxy-4-(3-indolylmethyl)-glutamic acid, is a naturally occurring sweet amino acid. The (2R,4R)-monatin isomer has been found to be the sweetest among its four stereoisomers. A concise and efficient synthesis of (2R,4R)-monatin was accomplished by the alkylation of (4R)-N-tert-butoxycarbonyl (tBoc)-4-tert-butyldimethylsilyoxy-D-pyroglutamic acid methyl ester with tert-butyl 3-(bromomethyl)-1H-indole-1-carboxylate to give (4R)-N-tBoc-4-tert-butyldimethylsilyloxy-4-(N-tBoc-3-indolylmethyl)-D-pyroglutamic acid methyl ester, i.e., the lactam form of (2R,4R)-monatin with protecting groups. This was followed by the hydrolysis of the lactam ring and deprotection. The 4-hydroxyl D-pyroglutamic acid derivative was demonstrated to be a suitable precursor for the efficient preparation of (2R,4R)-monatin in high optical purity because the alkylation proceeded in regioselective and stereoselective manners at C4 to form appropriate asymmetric tetra-substituted carbon center; the resulting alkylated pyroglutamic acid derivative was then easily converted into the linear form of monatin. PMID:27477667

  20. Spectroscopy of B{sub s} and D{sub s} mesons

    SciTech Connect

    MacKenzie, P.B.; Ryan, S.M.; Simone, J.N.

    1998-01-01

    We study B{sub s} and D{sub s} spectroscopy in quenched lattice QCD using the Fermilab approach to heavy quarks. We obtain results at four lattice spacings, a, using O(a)-improved Wilson quarks. We compare and contrast the various methods for heavy quarks on the lattice, discussing which methods work best for different physical systems and the ease with which calculations may be performed.

  1. Guanine nucleotide regulatory protein co-purifies with the D/sub 2/-dopamine receptor

    SciTech Connect

    Senogles, S.E.; Caron, M.G.

    1986-05-01

    The D/sub 2/-dopamine receptor from bovine anterior pituitary was purified approx.1000 fold by affinity chromatography on CMOS-Sepharose. Reconstitution of the affinity-purified receptor into phospholipid vesicles revealed the presence of high and low affinity agonist sites as detected by N-n-propylnorapomorphine (NPA) competition experiments with /sup 3/H-spiperone. High affinity agonist binding could be converted to the low affinity form by guanine nucleotides, indicating the presence of an endogenous guanine nucleotide binding protein (N protein) in the affinity-purified D/sub 2/ receptor preparations. Furthermore, this preparation contained an agonist-sensitive GTPase activity which was stimulated 2-3 fold over basal by 10 ..mu..M NPA. /sup 35/S-GTP..gamma..S binding to these preparations revealed a stoichiometry of 0.4-0.7 mole N protein/mole receptor, suggesting the N protein may be specifically coupled with the purified D/sub 2/-dopamine receptor and not present as a contaminant. Pertussis toxin treatment of the affinity purified receptor preparations prevented high affinity agonist binding, as well as agonist stimulation of the GTPase activity, presumably by inactivating the associated N protein. Pertussis toxin lead to the ADP-ribosylation of a protein of 39-40K on SDS-PAGE. These findings indicate that an endogenous N protein, N/sub i/ or N/sub o/, co-purifies with the D/sub 2/-dopamine receptor which may reflect a precoupling of this receptor with an N protein within the membranes.

  2. Phthalocyanines of a novel structure: Dinaphthotetraazaporphyrins with D[sub 2h] symmetry

    SciTech Connect

    Kobayashi, Nagao; Ashida, Tohru; Osa, Tetsuo Tohoku Univ., Kathahira, Sendai ); Konami, Hideo

    1994-04-27

    Phthalocyanines (Pcs) are compounds in which a benzene ring is fused to each of the four pyrrole rings of tetraazaporphyrins (TAPs). In addition to traditional uses as dyes and in xerography, they are now rapidly increasing in importance in many fields such as batteries, photodynamic cancer therapy, chemical sensors, molecular metals, and liquid crystals. Two naphthalene molecule-fused tetraazaporphyrins (TAPs) with D[sub 2h] symmetry have been synthesized, and some of their spectroscopic and electrochemical properties are reported. These compounds are structural isomers of phthalocyanines (Pcs) in the sense that four benzene units are fused to the TAP skeleton. In contrast to MPcs (M = metal) with D[sub 4h] symmetry, both the Q[sub o-o] and Soret bands split into two as a result of the lowering of the molecular symmetry. Magnetic circular dichroism (MCD) shows Faraday B terms corresponding to the peaks and shoulders of the electronic absorption spectra, indicating that no degenerate state is included. The fluorescence quantum yield of the zinc complex is much smaller than in ZnPc with D[sub 4h] symmetry. The electronic absorption and electrochemical redox data of these complexes are reproduced by molecular orbital (MO) calculations within the framework of the Pariser-Parr-Pople (PPP) approximation. The results are compared with those of Pcs and mononaphtho-TAPs.

  3. D{sub s}{sup +} exclusive hadronic decays involving {omega}

    SciTech Connect

    Ge, J. Y.; Miller, D. H.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Hu, D.; Moziak, B.; Napolitano, J.; Ecklund, K. M.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Artuso, M.; Blusk, S.; Khalil, S.; Mountain, R.; Randrianarivony, K.

    2009-09-01

    Using data collected near the D{sub s}*{sup {+-}}D{sub s}{sup {+-}} peak production energy E{sub cm}=4170 MeV by the CLEO-c detector, we search for D{sub s}{sup +} exclusive hadronic decays involving {omega}. We find B(D{sub s}{sup +}{yields}{pi}{sup +}{omega})=(0.21{+-}0.09{+-}0.01)%, B(D{sub s}{sup +}{yields}{pi}{sup +}{pi}{sup 0}{omega})=(2.78{+-}0.65{+-}0.25)%, B(D{sub s}{sup +}{yields}{pi}{sup +}{pi}{sup +}{pi}{sup -}{omega})=(1.58{+-}0.45{+-}0.09)%, B(D{sub s}{sup +}{yields}{pi}{sup +}{eta}{omega})=(0.85{+-}0.54{+-}0.06)%, B(D{sub s}{sup +}{yields}K{sup +}{omega})<0.24%, B(D{sub s}{sup +}{yields}K{sup +}{pi}{sup 0}{omega})<0.82%, B(D{sub s}{sup +}{yields}K{sup +}{pi}{sup +}{pi}{sup -}{omega})<0.54%, and B(D{sub s}{sup +}{yields}K{sup +}{eta}{omega})<0.79%. The upper limits are at 90% confidence level.

  4. Sounder stimulated D(sub n) resonances in Jupiter's Io plasma torus

    NASA Technical Reports Server (NTRS)

    Osherovich, V. A.; Benson, R. F.; Fainberg, J.; Stone, R. G.; Macdowall, R. J.

    1993-01-01

    On February 8, 1992, the Ulysses spacecraft passed through Jupiter's Io plasma torus, where rich spectra of narrow-band resonances were stimulated by the relaxation sounder of the Ulysses unified radio and plasma wave (URAP) instrument. Since the gyrofrequency f(sub g) is comparable to the plasma frequency f(sub p) in the Io torus, it was predicted that the general classification of stimulated ionospheric D(sub n) resonances, developed for 1 is less than or equal to f(sub p)/f(sub g) is less than or equal to 8 in the Earth's topside ionosphere, should apply in the Io torus as well as the Earth's magnetosphere (Osherovich, 1989). The URAP plasmagrams (sounder spectra) in the portions of the Io torus satisfying these plasma conditions are dominated by the D(sub n) resonances for frequencies below f(sub p). On most of these plasmagrams the f(sub p) resonance is also present, but it is seldom the dominant resonance. Neither upper hybrid nor nf(sub g) resonances have been found on these plasmagrams. The identification of D(sub n) resonances has allowed both the electron density and the magnetic field amplitude to be calculated. The derived densities on the outbound pass agree well with a Voyager model of Bagenal (1992). The derived magnetic field values are close to the Goddard Space Flight Center O(sub 6) magnetic field model.

  5. TAS2R bitter taste receptors regulate thyroid function

    PubMed Central

    Clark, Adam A.; Dotson, Cedrick D.; Elson, Amanda E. T.; Voigt, Anja; Boehm, Ulrich; Meyerhof, Wolfgang; Steinle, Nanette I.; Munger, Steven D.

    2015-01-01

    Dysregulation of thyroid hormones triiodothyronine and thyroxine (T3/T4) can impact metabolism, body composition, and development. Thus, it is critical to identify novel mechanisms that impact T3/T4 production. We found that type 2 taste receptors (TAS2Rs), which are activated by bitter-tasting compounds such as those found in many foods and pharmaceuticals, negatively regulate thyroid-stimulating hormone (TSH)-dependent Ca2+ increases and TSH-dependent iodide efflux in thyrocytes. Immunohistochemical Tas2r-dependent reporter expression and real-time PCR analyses reveal that human and mouse thyrocytes and the Nthy-Ori 3-1 human thyrocyte line express several TAS2Rs. Five different agonists for thyrocyte-expressed TAS2Rs reduced TSH-dependent Ca2+ release in Nthy-Ori 3-1 cells, but not basal Ca2+ levels, in a dose-dependent manner. Ca2+ responses were unaffected by 6-n-propylthiouracil, consistent with the expression of an unresponsive variant of its cognate receptor, TAS2R38, in these cells. TAS2R agonists also inhibited basal and TSH-dependent iodide efflux. Furthermore, a common TAS2R42 polymorphism is associated with increased serum T4 levels in a human cohort. Our findings indicate that TAS2Rs couple the detection of bitter-tasting compounds to changes in thyrocyte function and T3/T4 production. Thus, TAS2Rs may mediate a protective response to overingestion of toxic materials and could serve as new druggable targets for therapeutic treatment of hypo- or hyperthyroidism.—Clark, A. A., Dotson, C. D., Elson, A. E. T., Voigt, A., Boehm, U., Meyerhof, W., Steinle, N. I., Munger, S. D. TAS2R bitter taste receptors regulate thyroid function. PMID:25342133

  6. Beam flavor dependence in the hadroproduction of D{sup {+-}} and D{sub s}{sup {+-}} mesons

    SciTech Connect

    Fermilab E769 Collaboration

    1994-07-01

    Fermilab E769, a fixed-target experiment conducted during the 1987--88 running period, yielded large numbers of charm particles. Through collisions of 250 GeV {pi}{sup {+-}}, K{sup {+-}}, and p on a multifoil target, E769 allows for studies of beam flavor dependence in the hadroproduction of charm. Through the decay modes D{sup +} {yields} K{sup {minus}}{pi}{sup +}{pi}{sup +}, D{sub s}{sup +} {yields} {phi}{pi}{sup +}, and D{sub s}{sup +} {yields} {anti K}{sup *0} K{sup +} (and charge conjugates), the authors have extracted D{sup {+-}} and D{sub s}{sup {+-}} signals for all five beam types. They report preliminary measurements of the beam dependence of the absolute production cross-sections (For Feynman x > 0) of the D{sup {+-}} and D{sub s}{sup {+-}}.

  7. Caffeine increases striatal dopamine D>2/D3 receptor availability in the human brain

    SciTech Connect

    Volkow, N. D.; Wang, G. -J.; Logan, J.; Alexoff, D.; Fowler, J. S.; Thanos, P. K.; Wong, C.; Casado, V.; Ferre, S.; Tomasi, D.

    2015-04-14

    Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [11C]raclopride (DA D>2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D>2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D>2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D>2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D>2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D>2/D3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D>2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D>2/D3 receptors.

  8. TAS2R bitter taste receptors regulate thyroid function.

    PubMed

    Clark, Adam A; Dotson, Cedrick D; Elson, Amanda E T; Voigt, Anja; Boehm, Ulrich; Meyerhof, Wolfgang; Steinle, Nanette I; Munger, Steven D

    2015-01-01

    Dysregulation of thyroid hormones triiodothyronine and thyroxine (T3/T4) can impact metabolism, body composition, and development. Thus, it is critical to identify novel mechanisms that impact T3/T4 production. We found that type 2 taste receptors (TAS2Rs), which are activated by bitter-tasting compounds such as those found in many foods and pharmaceuticals, negatively regulate thyroid-stimulating hormone (TSH)-dependent Ca(2+) increases and TSH-dependent iodide efflux in thyrocytes. Immunohistochemical Tas2r-dependent reporter expression and real-time PCR analyses reveal that human and mouse thyrocytes and the Nthy-Ori 3-1 human thyrocyte line express several TAS2Rs. Five different agonists for thyrocyte-expressed TAS2Rs reduced TSH-dependent Ca(2+) release in Nthy-Ori 3-1 cells, but not basal Ca(2+) levels, in a dose-dependent manner. Ca(2+) responses were unaffected by 6-n-propylthiouracil, consistent with the expression of an unresponsive variant of its cognate receptor, TAS2R38, in these cells. TAS2R agonists also inhibited basal and TSH-dependent iodide efflux. Furthermore, a common TAS2R42 polymorphism is associated with increased serum T4 levels in a human cohort. Our findings indicate that TAS2Rs couple the detection of bitter-tasting compounds to changes in thyrocyte function and T3/T4 production. Thus, TAS2Rs may mediate a protective response to overingestion of toxic materials and could serve as new druggable targets for therapeutic treatment of hypo- or hyperthyroidism. PMID:25342133

  9. Rubidium atomic frequency standards for GPS block 2R

    NASA Astrophysics Data System (ADS)

    Riley, William K., Jr.

    1992-06-01

    The design, improvements, test results, and progress of the Rubinium Atomic Frequency Standards (RAFS) for the GPS (Global Positioning System) Block 2R Navstar satellites are described. These satellites will replenish and upgrade the space segment of the GPS in the mid 1990's. The RAFS offer an aging rate in the low pp 10 to the 14th power/day range and a drift corrected 1 day stability in the low pp 10 to the 14th power range. The Block 2R version of these devices will have improved performance, higher reliability, smaller size, and greater radiation hardness. The GPS Block 2R atomic clocks have a 'natural frequency' configuration whereby they output a frequency of about 13.4 MHz that is a submultiple of the atomic resonance. The RAFS operate at a low fixed C field for increased stability. The unit was repackaged into a smaller 4.6 by 8.5 by 5.8 inch outline, but is somewhat heavier (12 lbs.) because of additional radiation shielding. Elimination of the ground tuning logic and the secondary loop synthesizer (with its ovenized crystal oscillator) reduced the RAFS complexity and improved its reliability to 0.80 for the 7.5 year mission. The RAFS power consumption is only 13 W at +20 C in vacuum.

  10. Biochemical characterization of nuclear receptors for vitamin D{sub 3} and glucocorticoids in prostate stroma cell microenvironment

    SciTech Connect

    Hidalgo, Alejandro A.; Montecinos, Viviana P.; Paredes, Roberto; Godoy, Alejandro S.; McNerney, Eileen M.; Tovar, Heribelt; Pantoja, Diego; Johnson, Candace; Trump, Donald; Onate, Sergio A.

    2011-08-19

    Highlights: {yields} Fibroblasts from benign and carcinoma-associated stroma were biochemically characterized for VDR and GR function as transcription factors in prostate stroma cell microenvironment. {yields} Decreased SRC-1/CBP coactivators recruitment to VDR and GR may result in hormone resistance to 1,25D{sub 3} in stromal cell microenvironment prostate cancer. {yields} 1a,25-Dyhidroxyvitamin D{sub 3} (1,25D{sub 3}) and glucocorticoids, either alone or in combination, may not be an alternative for 'some' advanced prostate cancers that fails androgen therapies. -- Abstract: The disruption of stromal cell signals in prostate tissue microenvironment influences the development of prostate cancer to androgen independence. 1{alpha},25-Dihydroxyvitamin D{sub 3} (1,25D{sub 3}) and glucocorticoids, either alone or in combination, have been investigated as alternatives for the treatment of advanced prostate cancers that fails androgen therapies. The effects of glucocorticoids are mediated by the intracellular glucocorticoid receptor (GR). Similarly, the effect of 1,25D{sub 3} is mediated by the 1,25D{sub 3} nuclear receptor (VDR). In this study, fibroblasts from benign- (BAS) and carcinoma-associated stroma (CAS) were isolated from human prostates to characterize VDR and GR function as transcription factors in prostate stroma. The VDR-mediated transcriptional activity assessed using the CYP24-luciferase reporter was limited to 3-fold induction by 1,25D{sub 3} in 9 out of 13 CAS (70%), as compared to >10-fold induction in the BAS clinical sample pair. Expression of His-tagged VDR (Ad-his-VDR) failed to recover the low transcriptional activity of the luciferase reporter in 7 out of 9 CAS. Interestingly, expression of Ad-his-VDR successfully recovered receptor-mediated induction in 2 out of the 9 CAS analyzed, suggesting that changes in the receptor protein itself was responsible for decreased response and resistance to 1,25D{sub 3} action. Conversely, VDR

  11. A study of the neutrino production of {phi} and D{sub s}{sup +} mesons

    SciTech Connect

    Agababyan, N. M.; Ammosov, V. V.; Grigoryan, N.; Gulkanyan, H.; Ivanilov, A. A.; Karamyan, Zh.; Korotkov, V. A.

    2011-02-15

    The charged current neutrino production of {phi} and D{sub s}{sup +} mesons is studied, using the data obtained with the SKAT bubble chamber exposed to the Serpukhov accelerator neutrino beam. It is found that the {phi} production occurs predominantly in the forward hemisphere of the hadronic c.m.s. (at x{sub F} > 0, x{sub F} being the Feynman variable), with the mean yield strongly exceeding the expected yield of directly produced {phi} mesons and varying from Left-Pointing-Angle-Bracket n{sub {phi}}(x{sub F} s 0) Right-Pointing-Angle-Bracket = (0.92 {+-} 0.34) Multiplication-Sign 10{sup -2} at W > 2 GeV up to (1.23 {+-} 0.53) Multiplication-Sign 10{sup -2} at W > 2.6 GeV and (1.44 {+-} 0.69) Multiplication-Sign 10{sup -2} at W > 2.9 GeV, W being the invariant mass of the hadronic system. For the first time, the inclusive yield of leading D{sub s}{sup +} mesons carrying more than z = 0.85 of the current c-quark energy is estimated: Left-Pointing-Angle-Bracket n{sub Ds}{sup +}(z > 0.85, W > 2.9 GeV) Right-Pointing-Angle-Bracket = (6.64 {+-} 1.91) Multiplication-Sign 10{sup -2}. It is shown that the shape of measured {phi} meson differential spectrum on xF is reproduced by that expected from the D{sub s}{sup +} {yields} {phi}X decays. An indication was obtained that this expected spectrum underestimates the measured {phi} yield.

  12. INTERSTELLAR DETECTION OF c-C{sub 3}D{sub 2}

    SciTech Connect

    Spezzano, S.; Bruenken, S.; Schilke, P.; Schlemmer, S.; Caselli, P.; Menten, K. M.; McCarthy, M. C.; Bizzocchi, L.; Trevino-Morales, S. P.; Aikawa, Y.

    2013-06-01

    We report the first interstellar detection of c-C{sub 3}D{sub 2}. Doubly deuterated cyclopropenylidene, a carbene, has been detected toward the starless cores TMC-1C and L1544 using the IRAM 30 m telescope. The J{sub K{sub a,K{sub c}}} = 3{sub 0,3}-2{sub 1,2}, 3{sub 1,3}-2{sub 0,2}, and 2{sub 2,1}-1{sub 1,0} transitions of this species have been observed at 3 mm in both sources. The expected 1:2 intensity ratio has been found in the 3{sub 0,3}-2{sub 1,2} and 3{sub 1,3}-2{sub 0,2} lines, belonging to the para and ortho species, respectively. We also observed lines of the main species, c-C{sub 3}H{sub 2}, singly deuterated c-C{sub 3}HD, and the species with one {sup 13}C off of the principal axis of the molecule, c-H{sup 13}CC{sub 2}H. The lines of c-C{sub 3}D{sub 2} have been observed with high signal-to-noise ratio, better than 7.5{sigma} in TMC-1C and 9{sigma} in L1544. The abundance of doubly deuterated cyclopropenylidene with respect to the normal species is found to be 0.4%-0.8% in TMC-1C and 1.2%-2.1% in L1544. The deuteration of this small hydrocarbon ring is analyzed with a comprehensive gas-grain model, the first including doubly deuterated species. The observed abundances of c-C{sub 3}D{sub 2} can be explained solely by gas-phase processes, supporting the idea that c-C{sub 3}H{sub 2} is a good indicator of gas-phase deuteration.

  13. Equation of state and thermodynamic properties of pure D[sub 2]O and D[sub 2]O + H[sub 2]O mixtures in and beyond the critical regions

    SciTech Connect

    Kiselev, S.B.; Abdulagatov, I.M.; Harvey, A.H. . Physical and Chemical Properties Div.)

    1999-03-01

    A parametric crossover model is adapted to represent the thermodynamic properties of pure D[sub 2]O in the extended critical region. The crossover equation of state for D[sub 2]O incorporates scaling laws asymptotically close to the critical point and is transformed into a regular classical expansion far from the critical point. An isomorphic generalization of the law of corresponding states is applied to the prediction of thermodynamic properties and the phase behavior of D[sub 2]O + H[sub 2]O mixtures over a wide region around the focus of vapor liquid critical points. A comparison is made with experimental data for pure D[sub 2]O and for the D[sub 2]O + H[sub 2]O mixture. The equation of state yields a good representation of thermodynamic property data in the range of temperatures 0.8[Tc](x)[le]T[le]1.5[Tc](x) and densities 0.35[rho][sub c](x)[le][rho][le]1.65 [rho][sub c](x).

  14. Equation of state and thermodynamic properties of pure D{sub 2}O and D{sub 2}O + H{sub 2}O mixtures in and beyond the critical regions

    SciTech Connect

    Kiselev, S.B.; Abdulagatov, I.M.; Harvey, A.H.

    1999-03-01

    A parametric crossover model is adapted to represent the thermodynamic properties of pure D{sub 2}O in the extended critical region. The crossover equation of state for D{sub 2}O incorporates scaling laws asymptotically close to the critical point and is transformed into a regular classical expansion far from the critical point. An isomorphic generalization of the law of corresponding states is applied to the prediction of thermodynamic properties and the phase behavior of D{sub 2}O + H{sub 2}O mixtures over a wide region around the focus of vapor liquid critical points. A comparison is made with experimental data for pure D{sub 2}O and for the D{sub 2}O + H{sub 2}O mixture. The equation of state yields a good representation of thermodynamic property data in the range of temperatures 0.8{Tc}(x){le}T{le}1.5{Tc}(x) and densities 0.35{rho}{sub c}(x){le}{rho}{le}1.65 {rho}{sub c}(x).

  15. In vitro histamine release from basophils of asthmatic and atopic individuals in D/sub 2/O

    SciTech Connect

    Tung, R.; Lichtenstein, L.M.

    1982-05-01

    It was found that spontaneous histamine release from human basophils in H/sub 2/O-based buffers is negligible; in D/sub 2/O-based buffers, however, release is observed with the cells of some donors. Analysis of this phenomenon revealed release from the basophils of 1 of 22 control individuals (5%), 15 of 47 patients with allergic rhinitis (32%), and 14 of 20 asthmatic patients (70%). The difference between both patient groups and controls and between atopics and asthmatics was highly significant. That D/sub 2/O release was not cytotoxic is suggested by the finding that 37/sup 0/ was optimal, with inhibition at 4/sup 0/C or 46/sup 0/C as well as by EDTA, 2-deoxyglucose, and dibromoacetophenone, an inhibitor of phospholipase A/sub 2/. The release mechanism was unusual in that dibutyryl cAMP and agonists that cause an increase in cAMP lead to no inhibition. No correlation was noted between the total serum IgE level (and thus the number of IgE receptors on the basophil surface) and the magnitude of D/sub 2/O release. No increase in D/sub 2/O release was observed in 17 ragweed-sensitive patients through a ragweed season. A unique property of D/sub 2/O release was the loss of reactivity by preincubating cells at 37/sup 0/C for 30 min before adding D/sub 2/O. Non-D/sub 2/O-reactive cells could be ''converted'' to D/sub 2/O-reactive cells by incubation with antigen in the whole blood phase during leukocyte isolation; these cells showed the same loss of releaseability at 37/sup 0/C and an inhibitor profile similar to D/sub 2/O-responsive cells from ragweed allergic or asthmatic patients. We suggest that D/sub 2/O-based buffers reveal, in atopic and asthmatic patients, in vivo basophil activation; whether this is due to IgE cross-links, to C split products, or to other stimuli is not yet clear.

  16. The infrared spectrum of the He–C{sub 2}D{sub 2} complex

    SciTech Connect

    Moazzen-Ahmadi, N.; McKellar, A. R. W.; Fernández, Berta; Farrelly, David

    2015-02-28

    Spectra of the helium-acetylene complex are elusive because this weakly bound system lies close to the free rotor limit. Previously, limited assignments of He–C{sub 2}D{sub 2} transitions in the R(0) region of the ν{sub 3} fundamental band (≈2440 cm{sup −1}) were published. Here, new He–C{sub 2}D{sub 2} infrared spectra of this band are obtained using a tunable optical parametric oscillator laser source to probe a pulsed supersonic slit jet expansion from a cooled nozzle, and the analysis is extended to the weaker and more difficult P(1) and R(1) regions. A term value approach is used to obtain a consistent set of “experimental” energy levels. These are compared directly with calculations using two recently reported ab initio intermolecular potential energy surfaces, which exhibit small but significant differences. Rovibrational energies for the He–C{sub 2}H{sub 2} complex are also calculated using both surfaces. A Coriolis model, useful for predicting spectral intensities, is used to interpret the energy level patterns, and a comparison with the isoelectronic complex He–CO is made.

  17. Active control of divertor asymmetry on EAST by localized D{sub 2} and Ar puffing

    SciTech Connect

    Wang Dongsheng; Luo Guangnan; Guo Houyang; Wang Huiqian; Wu Zhenwei; Wu Jinhua; Gao Wei; Wang Liang; Li Qiang

    2011-03-15

    The divertor asymmetry in particle and power fluxes has been investigated on the EAST superconducting tokamak [S. Wu and EAST Team, Fusion Eng. Des. 82, 463 (2007)] for both single null (SN) and double null (DN) divertor configurations. D{sub 2} and Ar puffing at various divertor locations has also been explored as an active means to reduce peak target heat load and control divertor asymmetry. For SN, peak heat load on the outer divertor target is 2-3 times that on the inner divertor target under typical ohmic plasma conditions. DN operation leads to a stronger in-out asymmetry favoring the outer divertor. D{sub 2} and Ar puffing promotes partial detachment near the strike points, greatly reducing peak target heat load (over 50%), while the far-SOL divertor plasma remains attached. What is remarkable is that the particle flux is even increased away from the strike points when the Bx{nabla}B drift is directed toward the divertor target, thus facilitating particle removal.

  18. Pathway of D{sup +} in sequential double ionization of D{sub 2} in an intense laser pulse

    SciTech Connect

    Vafaee, Mohsen; Shokri, Babak

    2010-05-15

    Details of the pathway for the dissociative ionization process of the ground electronic state of aligned D{sub 2}{sup +} produced from the first ionization of D{sub 2} in a short ({approx}100 fs) and intense (4.0x10{sup 14} W cm{sup -2}) 480 nm laser pulse are analyzed and visualized. The initial vibrational state of D{sub 2}{sup +} comes from the vertical transformation of the ground state of D{sub 2}. The initial wave packet in the ground electronic state of D{sub 2}{sup +} is outgoing through a dissociation-ionization channel accompanied by a strong coupling between the 1s{sigma}{sub g} and 2p{sigma}{sub u} electronic states. We show explicitly that the transition from the coupling states 1s{sigma}{sub g} and 2p{sigma}{sub u} to the ionization state is not a direct transition, but takes place through other intermediate states having some dissociative energy that results in a relatively wide internuclear distribution of the ionization state.

  19. Anti-Phospholipase A2 Receptor (PLA2R) Antibody and Glomerular PLA2R Expression in Japanese Patients with Membranous Nephropathy

    PubMed Central

    Tachibana, Shohei; Iseri, Ken; Saito, Tomohiro; Yamamoto, Yasutaka; Suzuki, Taihei; Wada, Yukihiro; Matsumoto, Kei; Shibata, Takanori

    2016-01-01

    The phospholipase A2 receptor (PLA2R) is the major target antigen (Ag) in idiopathic membranous nephropathy (IMN). Recently, several types of immunoassay systems for anti-PLA2R antibody (Ab) have been developed. However, the correlation of serum anti-PLA2R Abs and glomerular expression of PLA2R Ag, and their association with clinicopathological characteristics have yet to be proven in Japanese patients. We examined serum anti-PLA2R Abs by both ELISA and cell-based indirect immunofluorescence assay (CIIFA), and glomerular PLA2R expression by immunofluorescence (IF) in 59 biopsy-proven MN patients including IMN (n = 38) and secondary MN (SMN) (n = 21). In this study, anti-PLA2R Abs were present in 50% of IMN patients, but was absent in SMN patients. The concordance rate between ELISA and CIIFA was 100%. Serum IgG levels were significantly lower in anti-PLA2R Ab-positive patients. Serum albumin levels correlated inversely with serum anti-PLA2R Ab titers. The prevalence and intensity of glomerular staining for IgG4 by IF were significantly higher in anti-PLA2R Ab-positive patients than in -negative patients. Glomerular PLA2 Ag expression evaluated by IF was positive in 52.6% of IMN patients, but was absent in SMN patients. The concordance rate between the prevalence of glomerular PLA2R Ag expression and anti-PLA2R Ab was 84.2%. The prevalence of anti-PLA2R Abs measured by ELISA/CIIFA was equivalent to previous Japanese studies evaluated using Western blotting. These analyses showed an excellent specificity for the diagnosis of IMN, and anti-PLA2R positivity was associated with some clinicopathological features, especially glomerular IgG4-dominant deposition. PMID:27355365

  20. GPS Block 2R Time Standard Assembly (TSA) architecture

    NASA Technical Reports Server (NTRS)

    Baker, Anthony P.

    1990-01-01

    The underlying philosophy of the Global Positioning System (GPS) 2R Time Standard Assembly (TSA) architecture is to utilize two frequency sources, one fixed frequency reference source and one system frequency source, and to couple the system frequency source to the reference frequency source via a sample data loop. The system source is used to provide the basic clock frequency and timing for the space vehicle (SV) and it uses a voltage controlled crystal oscillator (VCXO) with high short term stability. The reference source is an atomic frequency standard (AFS) with high long term stability. The architecture can support any type of frequency standard. In the system design rubidium, cesium, and H2 masers outputting a canonical frequency were accommodated. The architecture is software intensive. All VCXO adjustments are digital and are calculated by a processor. They are applied to the VCXO via a digital to analog converter.

  1. Investigating two-photon double ionization of D{sub 2} by XUV-pump-XUV-probe experiments

    SciTech Connect

    Jiang, Y. H.; Kurka, M.; Kuehnel, K. U.; Toppin, M.; Schroeter, C. D.; Moshammer, R.; Rudenko, A.; Foucar, L.; Perez-Torres, J. F.; Plesiat, E.; Morales, F.; Martin, F.; Herrwerth, O.; Lezius, M.; Kling, M. F.; Jahnke, T.; Doerner, R.; Sanz-Vicario, J. L.; Tilborg, J. van; Belkacem, A.

    2010-05-15

    We used a split-mirror setup attached to a reaction microscope at the free-electron laser in Hamburg (FLASH) to perform an XUV-pump-XUV-probe experiment by tracing the ultrafast nuclear wave-packet motion in the D{sub 2}{sup +}(1s{sigma}{sub g}) with <10 fs time resolution. Comparison with time-dependent calculations shows excellent agreement with the measured vibrational period of 22{+-}4 fs in D{sub 2}{sup +}, points to the importance of accurately knowing the internuclear distance-dependent ionization probability, and paves the way to control sequential and nonsequential two-photon double-ionization contributions.

  2. Spin-dependent parameters P/sub n/000, D/sub n/0n0, K/sub n/00n, D/sub s/0s0, D/sub s/0k0, M/sub s/0sn, and M/sub s/0kn in pp elastic scattering at 579 MeV

    SciTech Connect

    Aprile, E.; Hausammann, R.; Heer, E.; Hess, R.; Lechanoine-Leluc, C.; Leo, W.R.; Morenzoni, S.; Onel, Y.; Rapin, D.; Mango, S.

    1983-06-01

    The polarization parameter P/sub n/000, the two-spin parameters D/sub n/0n0, K/sub n/00n, D/sub s/0s0, and D/sub s/0k0, and the three-spin parameters M/sub s/0sn and M/sub s/0kn have been measured for pp elastic scattering at 579 MeV between 34/sup 0/ and 118/sup 0/ center-of-mass scattering angle. The experiment was performed at SIN using a polarized proton beam, a polarized butanol target, and a polarimeter for the measurement of the polarization of the scattered proton. These data form the basis for a complete experimental determination of the scattering amplitudes.

  3. High orbital angular momentum states in H/sub 2/ and D/sub 2/

    SciTech Connect

    Herzberg, G.; Jungen, C.

    1982-12-15

    A characteristic group of lines observed in the infrared emission spectrum of H/sub 2/ has been identified as representing the transitions between the 5g and the 4f group of levels. Because of nearly complete uncoupling of l from the molecular axis the appearance of this group of lines is very different from a normal band spectrum. An analysis was possible on the basis of ab initio computations of the spectrum using the knowledge of the vibrational levels, quadrupole moment, and the polarizability of the H/sup +//sub 2/ core. The validity of the assignments was further corroborated by agreement of the predicted spectra of D/sub 2/ with the observed spectra. In addition, similar transitions corresponding to 4f--3d have been observed.

  4. High-energy D/sub 2/O submillimeter laser for plasma diagnostics

    SciTech Connect

    Semet, A.; Johnson, L.C.; Mansfield, D.K.

    1983-01-01

    A narrow line optically pumped D/sub 2/O laser operating at 385 ..mu..m has delivered more than 5 J in pulses longer than 3 ..mu..sec using a large aperture unstable resonator cavity design. Pulse levels which are > 1 J and 1 ..mu..sec are necessary for a single shot ion temperature measurement by Thomson scattering in large tokamaks. Experiments have, for the most part, been conducted at a 360 J, 5 ..mu..sec CO/sub 2/ laser pump level where high efficiency (approx. 2.5 J at 385 ..mu..m) has been obtained. These are the highest energies reported to date in the far infrared. In addition, the pulse length has been extended beyond the vibrational relaxation time.

  5. Studies on the analysis of 25-hydroxyvitamin D{sub 3} by isotope-dilution liquid chromatography–tandem mass spectrometry using enzyme-assisted derivatisation

    SciTech Connect

    Abdel-Khalik, Jonas; Crick, Peter J.; Carter, Graham D.; Makin, Hugh L.; Wang, Yuqin; Griffiths, William J.

    2014-04-11

    Highlights: • New method for the analysis of 25-hydroxyvitamin D{sub 3} exploiting Girard P derivatisation. • Method also applicable to vitamin D{sub 3}, 1α,25- and 24,25-dihydroxyvitamin D{sub 3}. • By modification of the method 3-epi-25-hydroxyvitamin D{sub 3} can also be analysed. - Abstract: The total serum concentration of 25-hydroxyvitamins D (25-hydroxyvitamin D{sub 3} and 25-hydroxyvitamin D{sub 2}) is currently used as an indicator of vitamins D status. Vitamins D insufficiency is claimed to be associated with multiple diseases, thus accurate and precise reference methods for the quantification of 25-hydroxyvitamins D are needed. Here we present a novel enzyme-assisted derivatisation method for the analysis of vitamins D metabolites in adult serum utilising 25-[26,26,26,27,27,27-{sup 2}H{sub 6}]hydroxyvitamin D{sub 3} as the internal standard. Extraction of 25-hydroxyvitamins D from serum is performed with acetonitrile, which is shown to be more efficient than ethanol. Cholesterol oxidase is used to oxidize the 3β-hydroxy group in the vitamins D metabolites followed by derivatisation of the newly formed 3-oxo group with Girard P reagent. 17β-Hydroxysteroid dehydrogenase type 10 is shown to oxidize selectively the 3α-hydroxy group in the 3α-hydroxy epimer of 25-hydroxyvitamin D{sub 3}. Quantification is achieved by isotope-dilution liquid chromatography–tandem mass spectrometry. Recovery experiments for 25-hydroxyvitamin D{sub 3} performed on adult human serum give recovery of 102–106%. Furthermore in addition to 25-hydroxyvitamin D{sub 3}, 24,25-dihydroxyvitamin D{sub 3} and other uncharacterised dihydroxy metabolites, were detected in adult human serum.

  6. Experimental studies on the formation of D{sub 2}O and D{sub 2}O{sub 2} by implantation of energetic D{sup +} ions into oxygen ices

    SciTech Connect

    Bennett, Chris J.; Ennis, Courtney P.; Kaiser, Ralf I.

    2014-02-20

    The formation of water (H{sub 2}O) in the interstellar medium is intrinsically linked to grain-surface chemistry; thought to involve reactions between atomic (or molecular) hydrogen with atomic oxygen (O), molecular oxygen (O{sub 2}), and ozone (O{sub 3}). Laboratory precedent suggests that H{sub 2}O is produced efficiently when O{sub 2} ices are exposed to H atoms (∼100 K). This leads to the sequential generation of the hydroxyperoxyl radical (HO{sub 2}), then hydrogen peroxide (H{sub 2}O{sub 2}), and finally H{sub 2}O and a hydroxyl radical (OH); despite a barrier of ∼2300 K for the last step. Recent detection of the four involved species toward ρ Oph A supports this general scenario; however, the precise formation mechanism remains undetermined. Here, solid O{sub 2} ice held at 12 K is exposed to a monoenergetic beam of 5 keV D{sup +} ions. Products formed during the irradiation period are monitored through FTIR spectroscopy. O{sub 3} is observed through seven archetypal absorptions. Three additional bands found at 2583, 2707, and 1195 cm {sup –1} correspond to matrix isolated DO{sub 2} (ν{sub 1}) and D{sub 2}O{sub 2} (ν{sub 1}, ν{sub 5}), and D{sub 2}O (ν{sub 2}), respectively. During subsequent warming, the O{sub 2} ice sublimates, revealing a broad band at 2472 cm{sup –1} characteristic of amorphous D{sub 2}O (ν{sub 1}, ν{sub 3}). Sublimating D{sub 2}, D{sub 2}O, D{sub 2}O{sub 2}, and O{sub 3} products were confirmed through their subsequent detection via quadrupole mass spectrometry. Reaction schemes based on both thermally accessible and suprathermally induced chemistries were developed to fit the observed temporal profiles are used to elucidate possible reaction pathways for the formation of D{sub 2}-water. Several alternative schemes to the hydrogenation pathway (O{sub 2}→HO{sub 2}→H{sub 2}O{sub 2}→H{sub 2}O) were identified; their astrophysical implications are briefly discussed.

  7. Correlation dynamics between electrons and ions in the fragmentation of D{sub 2} molecules by short laser pulses

    SciTech Connect

    Tong, X.M.; Zhao, Z.X.; Lin, C.D.

    2003-10-01

    We studied the recollision dynamics between the electrons and D{sub 2}{sup +} ions following the tunneling ionization of D{sub 2} molecules in an intense short pulse laser field. The returning electron collisionally excites the D{sub 2}{sup +} ion to excited electronic states; from there D{sub 2}{sup +} can dissociate or be further ionized by the laser field, resulting in D{sup +}+D or D{sup +}+D{sup +}, respectively. We modeled the fragmentation dynamics and calculated the resulting kinetic-energy spectrum of D{sup +} to compare with recent experiments. Since the recollision time is locked to the tunneling ionization time which occurs only within a fraction of an optical cycle, the peaks in the D{sup +} kinetic-energy spectra provide a measure of the time when the recollision occurs. This collision dynamics forms the basis of the molecular clock where the clock can be read with attosecond precision, as first proposed by Corkum and co-workers. By analyzing each of the elementary processes leading to the fragmentation quantitatively, we identified how the molecular clock is to be read from the measured kinetic-energy spectra of D{sup +} and what laser parameters are to be used to measure the clock more accurately.

  8. Lifetime of the 7s6d {sup 1}D{sub 2} atomic state of radium.

    SciTech Connect

    Trimble, W. L.; Sulai, I. A.; Ahmad, I.; Bailey, K.; Graner, B.; Greene, J. P.; Holt, R. J.; Korsch, W.; Lu, Z.-T.; Mueller, P.; O'Connor, T. P.; Physics; Univ. of Chicago; Univ. of Kentucky

    2009-01-01

    The lifetime of the 7s6d {sup 1}D{sub 2} state of atomic radium is determined to be 385(45) {mu}s using cold {sup 226}Ra atoms prepared in a magneto-optical trap. The {sup 1}D{sub 2} state is populated from the decay of the {sup 1}P{sub 1} state which is excited by a pulse of 483 nm light. The decay of the {sup 1}D{sub 2} state is observed by detecting delayed fluorescence at 714 nm from the last step in the decay sequence {sup 1}P{sub 1}-{sup 1}D{sub 2}-{sup 3}P{sub 1}-{sup 1}S{sub 0}. The measured lifetime is compared to a number of theoretical calculations. An improved value of the 7s7p {sup 1}P{sub 1} level of 20 715.598(6) cm{sup -1} is obtained.

  9. Further evidence of no linkage between schizophrenia and the dopamine D{sub 3} receptor gene locus

    SciTech Connect

    Nanko, S.; Fukuda, R.; Hattori, M.

    1994-09-15

    The dopamine hypothesis of schizophrenia proposed that dopaminergic pathways are involved in the etiology of the disease. In particular, interest among psychiatrists has focused on the D{sub 2} receptor because of its affinity to antipsychotic drugs. Recently a new dopamine receptor gene has been cloned and named the dopamine D{sub 3} receptor. The D{sub 3} receptor is a potential site for antipsychotic drug action and may be involved in the pathophysiology of schizophrenia. We have carried out a linkage study between the susceptibility gene for schizophrenia and polymorphism of the dopamine D{sub 3} receptor gene in two Japanese pedigrees. The LOD scores were negative for all genetic models and for all affective status at a recombination fraction {theta} = 0. Linkage of DRD{sub 3} has been excluded for the model 1 (dominant model) and the model 3 (recessive model). The LOD score was -3.43 at {theta} = 0 for model 1 (dominant model) and broad definition of affected status. These results were consistent with previous studies. 19 refs., 2 figs., 3 tabs.

  10. Improved measurement of absolute branching fraction of D{sub s}{sup +}{yields}{tau}{sup +}{nu}{sub {tau}}

    SciTech Connect

    Onyisi, P. U. E.; Rosner, J. L.; Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Galik, R. S.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Hunt, J. M.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Ledoux, J.; Mahlke-Krueger, H.

    2009-03-01

    We have studied the leptonic decay D{sub s}{sup +}{yields}{tau}{sup +}{nu}{sub {tau}}, via the decay channel {tau}{sup +}{yields}e{sup +}{nu}{sub e}{nu}{sub {tau}}, using a sample of tagged D{sub s}{sup +} decays collected near the D{sub s}*{sup {+-}}D{sub s}{sup {+-}} peak production energy in e{sup +}e{sup -} collisions with the CLEO-c detector. We obtain B(D{sub s}{sup +}{yields}{tau}{sup +}{nu}{sub {tau}})=(5.30{+-}0.47{+-}0.22)% and determine the decay constant f{sub D{sub s}}=(252.5{+-}11.1{+-}5.2) MeV, where the first uncertainties are statistical and the second are systematic.

  11. Local deuterium order in apparently disordered Laves phase deuteride YFe{sub 2}D{sub 4.2}

    SciTech Connect

    Ropka, J.; Cerny, R.; Paul-Boncour, V.

    2011-09-15

    Deuterium short-range order in cubic Laves phase deuteride YFe{sub 2}D{sub 4.2} was studied by neutron (ToF) powder diffraction experiments and Pair Distribution Function (PDF) analysis between 290 and 400 K. The minimal allowed D-D distance of 2.1 A in a metal deuteride (Switendick rule) has been experimentally proved in the HT-disordered phase YFe{sub 2}D{sub 4.2}. It has been found that the distribution of deuterium atoms around the iron is not random, and cannot be explained only by applying the Switendick rule. The first coordination sphere of iron atoms in the high temperature (HT)-disordered phase resembles between 350 and 400 K the coordination observed in the low temperature (LT)-ordered phase. Reversed Monte Carlo modeling of the Pair Distribution Function of the HT-disordered phase prefers the coordination FeD{sub 5} and FeD{sub 4} in agreement with the LT-ordered phase. - Graphical abstract: Deuterium short-range order in cubic Laves phase deuteride YFe{sub 2}D{sub 4.2} was studied by ToF neutron powder diffraction experiments and Pair Distribution Function analysis between 290 and 400 K. It has been found that the distribution of deuterium atoms around the iron is not random, and cannot be explained only by applying the Switendick rule. The first coordination sphere of iron atoms in the HT-disordered phase resembles that of the LT-ordered phase. Highlights: > Switendick rule has been experimentally proved in YFe{sub 2}D{sub 4.2}. > The distribution of deuterium in YFe{sub 2}D{sub 4.2} cannot be explained only by Switendick rule. > The first coordination sphere of iron in the disordered phase resembles the ordered one.

  12. D2R DNA Transfer Into the Nucleus Accumbens Attenuates Cocaine Self-Administration in Rats

    PubMed Central

    THANOS, PANAYOTIS K.; MICHAELIDES, MICHAEL; UMEGAKI, HIROYUKI; VOLKOW, NORA D.

    2009-01-01

    Dopamine (DA) D2 receptor (D2R) agonists and antagonists can modulate self-administration behavior, conditioned place preference, and locomotor responses to cocaine. Low levels of D2R have also been observed in cocaine addicted subjects and in non human primates after chronic cocaine exposures. Prior studies had shown that D2R upregulation in the nucleus accumbens (NAc) in rodents trained to self-administer alcohol markedly attenuated alcohol preference and intake. Here we assess the effects of D2R upregulation in the NAc on cocaine intake in rats trained to self-administer cocaine. Following 2 weeks of i.v. cocaine self-administration (CSA), rats were stereotaxically treated with an adenovirus that carried the D2R gene to upregulate D2R in the NAc. D2R vector treatment resulted in a significant decrease (75%) in cocaine infusions and lever presses (70%) for cocaine. This effect lasted 6 days before cocaine consumption returned to baseline levels, which corresponds roughly to the time it takes D2R to return to baseline levels. These findings show that CSA and D2R in the NAc are negatively correlated and suggest that cocaine intake is modulated in part by D2R levels in NAc. Thus strategies aimed at increasing D2R expression in NAc may be beneficial in treating cocaine abuse and addiction. PMID:18418874

  13. Bitterness of the non-nutritive sweetener acesulfame potassium varies with polymorphisms in TAS2R9 and TAS2R31.

    PubMed

    Allen, Alissa L; McGeary, John E; Knopik, Valerie S; Hayes, John E

    2013-06-01

    Demand for nonnutritive sweeteners continues to increase due to their ability to provide desirable sweetness with minimal calories. Acesulfame potassium and saccharin are well-studied nonnutritive sweeteners commonly found in food products. Some individuals report aversive sensations from these sweeteners, such as bitter and metallic side tastes. Recent advances in molecular genetics have provided insight into the cause of perceptual differences across people. For example, common alleles for the genes TAS2R9 and TAS2R38 explain variable response to the bitter drugs ofloxacin in vitro and propylthiouracil in vivo. Here, we wanted to determine whether differences in the bitterness of acesulfame potassium could be predicted by common polymorphisms (genetic variants) in bitter taste receptor genes (TAS2Rs). We genotyped participants (n = 108) for putatively functional single nucleotide polymorphisms in 5 TAS2Rs and asked them to rate the bitterness of 25 mM acesulfame potassium on a general labeled magnitude scale. Consistent with prior reports, we found 2 single nucleotide polymorphisms in TAS2R31 were associated with acesulfame potassium bitterness. However, TAS2R9 alleles also predicted additional variation in acesulfame potassium bitterness. Conversely, single nucleotide polymorphisms in TAS2R4, TAS2R38, and near TAS2R16 were not significant predictors. Using 1 single nucleotide polymorphism each from TAS2R9 and TAS2R31, we modeled the simultaneous influence of these single nucleotide polymorphisms on acesulfame potassium bitterness; together, these 2 single nucleotide polymorphisms explained 13.4% of the variance in perceived bitterness. These data suggest multiple polymorphisms within TAS2Rs contribute to the ability to perceive the bitterness from acesulfame potassium. PMID:23599216

  14. Bitterness of the Non-nutritive Sweetener Acesulfame Potassium Varies With Polymorphisms in TAS2R9 and TAS2R31

    PubMed Central

    2013-01-01

    Demand for nonnutritive sweeteners continues to increase due to their ability to provide desirable sweetness with minimal calories. Acesulfame potassium and saccharin are well-studied nonnutritive sweeteners commonly found in food products. Some individuals report aversive sensations from these sweeteners, such as bitter and metallic side tastes. Recent advances in molecular genetics have provided insight into the cause of perceptual differences across people. For example, common alleles for the genes TAS2R9 and TAS2R38 explain variable response to the bitter drugs ofloxacin in vitro and propylthiouracil in vivo. Here, we wanted to determine whether differences in the bitterness of acesulfame potassium could be predicted by common polymorphisms (genetic variants) in bitter taste receptor genes (TAS2Rs). We genotyped participants (n = 108) for putatively functional single nucleotide polymorphisms in 5 TAS2Rs and asked them to rate the bitterness of 25 mM acesulfame potassium on a general labeled magnitude scale. Consistent with prior reports, we found 2 single nucleotide polymorphisms in TAS2R31 were associated with acesulfame potassium bitterness. However, TAS2R9 alleles also predicted additional variation in acesulfame potassium bitterness. Conversely, single nucleotide polymorphisms in TAS2R4, TAS2R38, and near TAS2R16 were not significant predictors. Using 1 single nucleotide polymorphism each from TAS2R9 and TAS2R31, we modeled the simultaneous influence of these single nucleotide polymorphisms on acesulfame potassium bitterness; together, these 2 single nucleotide polymorphisms explained 13.4% of the variance in perceived bitterness. These data suggest multiple polymorphisms within TAS2Rs contribute to the ability to perceive the bitterness from acesulfame potassium. PMID:23599216

  15. Possible association between the dopamine D{sub 3} receptor gene and bipolar affective disorder

    SciTech Connect

    Parsian, A.; Chakraverty, S.; Todd, R.D.

    1995-06-19

    A variety of studies have reported possible genetic associations between bipolar affective disorder and different loci using relative risk (case-control) comparisons. An alternative approach is to construct a contrast group using parental alleles which were not transmitted to an affected individual. We have used both approaches to test for possible associations between alleles of the dopamine D{sub 3} receptor gene and bipolar affective disorder. For relative risk studies, the probands of multiple incidence bipolar affective disorder families have been compared to alcoholic and psychiatrically normal contrast groups. Nontransmitted allele approaches have used bipolar affective disorder and alcoholic probands in which both parents were available for genotyping. Using the BalI restriction enzyme site polymorphism of Lannfelt et al., we have found no differences in the allele or genotype frequencies for bipolar vs. alcoholic or psychiatrically normal controls. In contrast, we have found evidence for an increased frequency of allele 1 and allele 1 containing genotypes in transmitted alleles from bipolar families. 21 refs., 4 tabs.

  16. Newly observed D{sub sJ}(3040) and the radial excitations of P-wave charmed-strange mesons

    SciTech Connect

    Sun Zhifeng; Liu Xiang

    2009-10-01

    Inspired by the newly observed D{sub sJ}(3040){sup +} state, in this work we systemically study the two-body strong decays of P-wave charmed-strange mesons with the first radial excitation. Under the assignment of 1{sup +}(j{sup P}=(1/2){sup +}), i.e. the first radial excitation of D{sub s1}(2460){sup +}, we find that the width of D{sub sJ}(3040){sup +} is close to the lower limit of the BABAR measurement. This indicates that it is reasonable to interpret D{sub sJ}(3040){sup +} as the first radial excitation of D{sub s1}(2460){sup +}. Our calculation further predicts that 0{sup -}+1{sup -} channels, e.g., D{sup +}K*{sup 0}, D{sup 0}K*{sup +}, and D{sub s}{sup +}{phi}, are important for the search for D{sub sJ}(3040){sup +}. To help future experiments find the remaining three P-wave charmed-strange mesons with the first radial excitation, we present the predictions for the strong decays of these three P-wave charmed-strange mesons.

  17. Coherent excitation of the 5D{sub 5/2} level of ultra-cold rubidium atoms with short laser pulses

    SciTech Connect

    Snigirev, S A; Golovizin, A A; Vishnyakova, G A; Akimov, A V; Sorokin, V N; Kolachevskii, N N

    2012-08-31

    We demonstrate the use of stimulated Raman adiabatic passage (STIRAP) for population transfer from the ground state to the 5D{sub 5/2} level (5S{sub 1/2} {yields} 5P{sub 3/2} {yields} 5D{sub 5/2}) in laser-cooled {sup 87}Rb atoms and examine the influence of the time delay between laser pulses, pulse height, pulse duration and frequency detuning from resonance on the efficiency of Rb atom excitation to the 5D{sub 5/2} level. In our experiments, the pulse duration was varied widely (30 - 200 ns), which allowed us to assess the effect of spontaneous decay on the population of the 5D{sub 5/2} level (natural lifetime, 300 ns). We performed numerical calculations with allowance for spontaneous decay from the 5P{sub 3/2} and 5D{sub 5/2} levels and compared the results to experimental data, which allowed the population of the 5D{sub 5/2} level to be determined. The maximum population of the 5D{sub 5/2} level in the region under excitation was 80 % of the total number of rubidium atoms. (cooling of atoms)

  18. Mechanisms of optical losses in the {sup 5}D{sub 4} and {sup 5}D{sub 3} levels in Tb{sup 3+} doped low silica calcium aluminosilicate glasses

    SciTech Connect

    Santos, J. F. M. dos; Terra, I. A. A.; Nunes, L. A. O.; Catunda, T.; Astrath, N. G. C.; Guimarães, F. B.; Baesso, M. L.

    2015-02-07

    Trivalent Tb-doped materials exhibit strong emission in the green and weak emission in the UV-blue levels. Usually, this behavior is attributed to the cross relaxation (CR) process. In this paper, the luminescence properties of Tb{sup 3+}-doped low silica calcium aluminosilicate glasses are analyzed for UV (λ{sub exc} = 325 nm) and visible (488 nm) excitations. Under 325 nm excitation, the intensity of green luminescence increases proportionally to Tb{sup 3+} concentration. However, the blue luminescence intensity is strongly reduced with the increase of concentration from 0.5–15.0 wt. %. In the case of 488 nm excitation, a saturation behavior of the green emission is observed at intensities two orders of magnitude smaller than expected for bleaching of the ground state population. Using a rate equation model, we showed that this behavior can be explained by an excited state absorption cross section two orders of magnitude larger than the ground state absorption. The blue emission is much weaker than expected from our rate equations (325 nm and 488 nm excitation). We concluded that only the CR process cannot explain the overall feature of measured luminescence quenching in the wide range of Tb{sup 3+} concentrations. Cooperative upconversion from a pair of excited ions ({sup 5}D{sub 3}:{sup 5}D{sub 3} or {sup 5}D{sub 3}:{sup 5}D{sub 4}) and other mechanisms involving upper lying states (4f5d, charge transfer, host matrix, defects, etc.) may play a significant role.

  19. Complete active space second order perturbation theory (CASPT2) study of N({sup 2}D) + H{sub 2}O reaction paths on D{sub 1} and D{sub 0} potential energy surfaces: Direct and roaming pathways

    SciTech Connect

    Isegawa, Miho; Liu, Fengyi; Maeda, Satoshi; Morokuma, Keiji

    2014-10-21

    We report reaction paths starting from N({sup 2}D) + H{sub 2}O for doublet spin states, D{sub 0} and D{sub 1}. The potential energy surfaces are explored in an automated fashion using the global reaction route mapping strategy. The critical points and reaction paths have been fully optimized at the complete active space second order perturbation theory level taking all valence electrons in the active space. In addition to direct dissociation pathways that would be dominant, three roaming processes, two roaming dissociation, and one roaming isomerization: (1) H{sub 2}ON → H–O(H)N → H–HON → NO({sup 2}Π) + H{sub 2}, (2) cis-HNOH → HNO–H → H–HNO → NO + H{sub 2}, (3) H{sub 2}NO → H–HNO → HNO–H → trans-HNOH, are confirmed on the D{sub 0} surface.

  20. Effects of the rotational excitation of D{sub 2} and of the potential energy surface on the H{sup +}+D{sub 2}{yields}HD+D{sup +} reaction

    SciTech Connect

    Gonzalez-Lezana, T.; Honvault, P.; Jambrina, P. G.; Aoiz, F. J.; Launay, J.-M.

    2009-07-28

    The H{sup +}+D{sub 2}{yields}HD+D{sup +} reaction has been theoretically investigated by means of an exact quantum mechanical approach, a quasiclassical trajectory method, and two statistical methods based in the propagation of either wave functions or trajectories. The study addresses the possible changes on the overall dynamics of the title reaction when the D{sub 2} diatom is rotationally excited to its v=0, j=1 state. In addition, the reactivity for the ground rotational state on two different potential energy surfaces (PESs), namely, the surface by Aguado et al. [J. Chem. Phys. 112, 1240 (2000)] and the PES by Kamisaka et al. [J. Chem. Phys. 116, 654 (2002)], is examined. Reaction probabilities and cross sections at 0.524 and 0.1 eV collision energies are calculated. The major differences with respect to the reaction initiated with D{sub 2} in its ground rovibrational state are observed for the lowest collision energy E{sub c}=0.1 eV. Differential cross sections have been found to depend to some extend on the PES employed. In addition, at E{sub c}=0.1 eV further discrepancies in the total and rotational cross sections are noticeable.

  1. Lifetimes of the metastable {sup 2}D{sub 3/2,5/2} states in Ca{sup +}, Sr{sup +}, and Ba{sup +}

    SciTech Connect

    Sahoo, B. K.; Islam, Md. R.; Das, B. P.; Chaudhuri, R. K.; Mukherjee, D.

    2006-12-15

    Atomic properties involving the low-lying excited {sup 2}D{sub 3/2,5/2} states in alkaline-earth-metal ions are of current interest in many different applications ranging from tests of physics beyond the standard model to astrophysics. We have used the relativistic coupled-cluster theory to perform accurate calculations of the lifetimes of the lowest excited {sup 2}D{sub 3/2} and {sup 2}D{sub 5/2} states in singly ionized calcium, strontium, and barium. The importance of electron correlation in these calculations is emphasized. Our results are compared with the available experimental and theoretical data.

  2. Radiolabelled D/sub 2/ agonists as prolactinoma imaging agents: Progress report for period February 1, 1987-January 31, 1988

    SciTech Connect

    Otto, C.A.

    1987-11-07

    Three D/sub 2/ agonists, /sup 3/H-DHEC, /sup 3/H-BrCr and /sup 3/H-ADTN, were evaluated with /sup 3/H-DHEC showing the most promise as a potential prolactinoma imaging agent. Concentration vs time plots for all three compounds in normal and in DES-treated pituitary tissue are reported. The exceptional D/sub 2/ receptor affinity of N-0437 has prompted synthetic efforts towards preparation of iodo-N-0437 in spite of a lack of preliminary tissue distribution data. An evaluation of /sup 18/F-FDG uptake in the prolactinoma model and as a muscarinic ligand in control animals were evaluated. 2 refs., 3 figs.

  3. Extended impurity potential in a d{sub x{sup 2}{minus}y{sup 2}} superconductor

    SciTech Connect

    Kampf, A.P.; Devereaux, T.P.

    1997-08-01

    We investigate the role of a finite potential range of a nonmagnetic impurity for the local density of states in a d{sub x{sup 2}{minus}y{sup 2}} superconductor. Impurity-induced subgap resonances are modified by the appearance of further scattering channels beyond the s-wave scattering limit. The structure of the local density of states (DOS) in the vicinity of the impurity is significantly enhanced and therefore improves the possibility for observing the characteristic anisotropic spatial modulation of the local DOS in a d{sub x{sup 2}{minus}y{sup 2}} superconductor by scanning tunneling microscopy. {copyright} {ital 1997} {ital The American Physical Society}

  4. The Study of the Nuclear Motion in D{sub 2}{sup +} Molecular Ion By Using the Harmonic Spectra

    SciTech Connect

    Daniele, R.; Castiglia, G.; Corso, P. P.; Fiordilino, E.; Orlando, G.; Persico, F.; Morales, F.

    2007-12-26

    In this paper we show how it is possible to investigate the nuclei dynamics of a D{sub 2}{sup +} molecular ion by using the high harmonic generation spectra emitted by the system when subjected to an intense laser field. In particular, the emitted spectra contains, in addition to the usual odd harmonic peaks, additional satellite peaks whose frequency spacing is equal to the vibrational frequency of the nuclei.

  5. Low-temperature softening of some Raman modes in BEDT-TTF and d{sub 8}-BEDT-TTF.

    SciTech Connect

    Lin, Y.; Eldridge, J. E.; Williams, J. M.; Kini, A. M.; Wang, H. H.; Univ. of British Columbia

    1999-02-01

    We report the temperature-dependent frequencies of the strong features in the Raman spectra of neutral BEDT-TTF and d{sub 8}-BEDT-TTF. We note an unusual softening of the features due to the modes involving the C-H vibrations in the terminal ethylene groups, as well as one mode involving the central double-bonded carbon atoms. We relate these softenings to the increased bending of the neutral molecule at low temperatures.

  6. Bradykinin inhibits oxidative stress-induced senescence of endothelial progenitor cells through the B2R/AKT/RB and B2R/EGFR/RB signal pathways.

    PubMed

    Fu, Cong; Li, Bing; Sun, Yuning; Ma, Genshan; Yao, Yuyu

    2015-09-22

    Circulating endothelial progenitor cells (EPCs) have multiple protective effects that facilitate repair of damage to tissues and organs. However, while various stressors are known to impair EPC function, the mechanisms of oxidative stress-induced EPC senescence remains unknown. We demonstrated that B2 receptor (B2R) expression on circulating CD34(+) cells was significantly reduced in patients with diabetes mellitus (DM) as compared to healthy controls. Furthermore, CD34(+) cell B2R expression in patients with DM was inversely correlated with plasma myeloperoxidase concentrations. Bradykinin (BK) treatment decreased human EPC (hEPC) senescence and intracellular oxygen radical production, resulting in reduced retinoblastoma 1 (RB) RNA expression in H2O2-induced senescent hEPCs and a reversal of the B2R downregulation that is normally observed in senescent cells. Furthermore, BK treatment of H2O2-exposed cells leads to elevated phosphorylation of RB, AKT, and cyclin D1 compared with H2O2-treatment alone. Antagonists of B2R, PI3K, and EGFR signaling pathways and B2R siRNA blocked BK protective effects. In summary, this study demonstrates that BK significantly inhibits oxidative stress-induced hEPC senescence though B2R-mediated activation of PI3K and EGFR signaling pathways. PMID:26360782

  7. Rovibrational molecular populations, atoms, and negative ions in H/sub 2/ and D/sub 2/ magnetic multicusp discharges

    SciTech Connect

    Pealat, M.; Taran, J.E.; Bacal, M.; Hillion, F.

    1985-06-01

    Coherent anti-Stokes Raman scattering is applied to the study of rovibrational populations in magnetic multicusp H/sub 2/ and D/sub 2/ discharges. This subject is of interest to negative hydrogen ion formation by volume plasma processes. The populations of high-lying rotational states (J>5) in the vibrational levels v = 0, 1, and 2 are found to be significantly higher than expected from the Boltzmann law. In H/sub 2/ the net populations of the first four vibrational levels follow approximately the Boltzmann law, with the vibrational temperature of 2390 K (in a 90 V-10 A discharge at 55 ..mu..bar). In similar discharge conditions, the population of the state v = 3 in D/sub 2/ is higher than expected from the Boltzmann law. In the presence of the discharge a deficiency in H/sub 2/ and D/sub 2/ molecule density was observed and was attributed to the possible presence of H and D atoms. This was verified by an independent measurement of the atomic fraction and temperature. The density of negative ions, measured by the photodetachment technique, is also reported.

  8. {mu}-{tau} symmetry and charged lepton mass hierarchy in a supersymmetric D{sub 4} model

    SciTech Connect

    Hagedorn, C.; Ziegler, R.

    2010-09-01

    In this paper we discuss a supersymmetric D{sub 4}xZ{sub 5} model which leads to vanishing reactor mixing angle {theta}{sub 13}=0 and maximal atmospheric mixing {theta}{sub 23}={pi}/4 in the lepton sector at leading order, due to the preservation of nontrivial distinct D{sub 4} subgroups in the charged lepton and neutrino sectors, respectively. The solar mixing angle {theta}{sub 12} remains undetermined and is expected to be of order one. Since right-handed charged leptons transform as singlets under D{sub 4}, the charged lepton mass hierarchy can be naturally accounted for. The model predicts inverted mass hierarchy for neutrinos. Additionally, we show that, unlike in most of the other models of this type, all vacuum expectation values of gauge singlets (flavons) can be determined through mass parameters of the superpotential. Next-to-leading order corrections to lepton masses and mixings are calculated and shown to be under control; in particular, the corrections to {theta}{sub 23}={pi}/4 and {theta}{sub 13}=0 are of the order of the generic expansion parameter {epsilon}{approx_equal}0.04 and arise dominantly from the charged lepton sector.

  9. Observation of rotationally mediated focused inelastic resonances in D{sub 2} scattering from Cu(001)

    SciTech Connect

    Bertino, M.F.; Miret-Artes, S.; Toennies, J.P.; Benedek, G.

    1997-10-01

    Rotationally mediated focused inelastic resonances (RMFIR{close_quote}s) in the angular distributions of D{sub 2} scattered from Cu(001) are observed. The FIR effect involves a phonon-assisted focusing of an incident beam of arbitrary energy and direction into a final channel of one single well-defined energy and direction. Surprisingly for an incident energy E{sub i}=27meV the RMFIR conditions for the scattered beam coincide with the kinematic conditions required for a further elastic selective adsorption mechanism called the rotationally mediated critical kinematic (RMCK) effect. By taking advantage of the RMFIR and elastic RMCK effects, three effective bound states of energy {epsilon}{sub n,J}={minus}21.5meV, {minus}12.4meV, and {minus}10.3meV are determined. They are attributed to the lowest bound states {epsilon}{sub 0}={minus}28.9meV and {epsilon}{sub 1}={minus}19.8meV combined with the rotational excitation energy for J=1 to be B{sub rot}J(J+1)=7.41meV, respectively, and {epsilon}{sub 3}={minus}10.3meV combined with the rotational ground state (J=0). While the {epsilon}{sub 1} and {epsilon}{sub 3} states appear as maxima in the angular distribution at RMFIR conditions, the {epsilon}{sub 0} yields a striking minimum which represents the first evidence of what we call an anti-FIR feature. Theoretical arguments to explain the different FIR signatures observed are provided. A fit of a phenomenological interaction potential to the experimental bound-state values yields a value for the well depth D=32.5meV which is somewhat deeper than that found previously. {copyright} {ital 1997} {ital The American Physical Society}

  10. D{sub 2} dopamine receptor gene and behavioral characteristics in nicotine dependence

    SciTech Connect

    Noble, E.P.; Fitch, R.J.; Syndulko, K.

    1994-09-01

    The D{sub 2} dopamine receptor (DRD2) A1 allele has been recently associated with nicotine dependence. In the present study, TaqI A alleles (the minor A1 and the major A2 allele) of the DRD2 were determined in medically-ill subjects. The sample was composed of 41 non-smokers (N), 69 ex-smokers (X) and 63 active smokers (A). The relationships of DRD2 alleles to personality (Eysenick`s Addictive Personality [AP]), depression and nicotine dependence (Fagerstroem) scores were ascertained. A significant (P = 0.002) group effect prevailed in the AP scores, with the A group having the highest scores. Moreover, a significant (P = 0.025) allele by group interaction was found, with A1 allelic subjects in group A showing the highest AP scores. Significant group effects were also found in both the depression (P = 0.0004) and the nicotine dependence (P = 0.0003) scores, with the A group again showing the highest scores. However, in contrast to the AP scores, no significant allele by group interaction was found either in the depression or the nicotine dependence scores. In conclusion, the present findings suggest a role for the DRD2 gene in personality of smokers. However, relationship of the DRD2 gene to the degree of depression or nicotine dependence was not found. The data indicate the importance of using behavioral and genetic variables in dissecting the complex set of variables associated with the smoking habit, and thus in achieving a better understanding of the biobehavioral bases of this addiction.

  11. Quinine Bitterness and Grapefruit Liking Associate with Allelic Variants in TAS2R31.

    PubMed

    Hayes, John E; Feeney, Emma L; Nolden, Alissa A; McGeary, John E

    2015-07-01

    Multiple psychophysical gene-association studies suggest a single nucleotide polymorphism (SNP) within the bitter receptor gene TAS2R19 on chromosome 12 may be functional. Previously, the Arg299Cys SNP (rs10772420) has been associated with differential bitterness of quinine and differential liking for grapefruit juice. However, quinine does not activate TAS2R19 in vitro; likewise, limonin and naringin, bitter compounds in grapefruit, do not activate TAS2R19 in vitro. Here, we examined quinine bitterness (whole-mouth swish-and-spit stimuli and regionally delivered quinine across 4 loci) and remembered liking for grapefruit juice to test whether they associate with SNPs in another nearby gene, TASR2R31. We observed SNP-phenotype associations between whole-mouth quinine bitterness and self-reported liking for grapefruit juice with SNPs in TAS2R31, and regional quinine bitterness followed a similar trend, but did not reach significance. Present data provide independent replication of prior associations reported for TAS2R19. However, we also observed strong linkage disequilibrium (LD) between TAS2R19 and TAS2R31 SNPs. When present data are considered in light of existing functional expression data, this suggests phenotypic associations reported previously for rs10772420 may potentially be due to LD between this SNP and polymorphism(s) in, or closer to, TAS2R31. If confirmed, this would reduce the number of TAS2Rs with putatively functional polymorphisms to 5. PMID:26024668

  12. Quinine Bitterness and Grapefruit Liking Associate with Allelic Variants in TAS2R31

    PubMed Central

    Feeney, Emma L.; Nolden, Alissa A.; McGeary, John E.

    2015-01-01

    Multiple psychophysical gene-association studies suggest a single nucleotide polymorphism (SNP) within the bitter receptor gene TAS2R19 on chromosome 12 may be functional. Previously, the Arg299Cys SNP (rs10772420) has been associated with differential bitterness of quinine and differential liking for grapefruit juice. However, quinine does not activate TAS2R19 in vitro; likewise, limonin and naringin, bitter compounds in grapefruit, do not activate TAS2R19 in vitro. Here, we examined quinine bitterness (whole-mouth swish-and-spit stimuli and regionally delivered quinine across 4 loci) and remembered liking for grapefruit juice to test whether they associate with SNPs in another nearby gene, TASR2R31. We observed SNP–phenotype associations between whole-mouth quinine bitterness and self-reported liking for grapefruit juice with SNPs in TAS2R31, and regional quinine bitterness followed a similar trend, but did not reach significance. Present data provide independent replication of prior associations reported for TAS2R19. However, we also observed strong linkage disequilibrium (LD) between TAS2R19 and TAS2R31 SNPs. When present data are considered in light of existing functional expression data, this suggests phenotypic associations reported previously for rs10772420 may potentially be due to LD between this SNP and polymorphism(s) in, or closer to, TAS2R31. If confirmed, this would reduce the number of TAS2Rs with putatively functional polymorphisms to 5. PMID:26024668

  13. Uptake of (/sup 3/H)vitamin D/sub 3/ from low and high density lipoproteins by cultured human fibroblasts

    SciTech Connect

    Shireman, R.B.; Williams, D.; Remsen, J.F.

    1986-03-01

    The plasma distribution and cellular uptake of (/sup 3/H)vitamin D/sub 3/ was studied in vitro using cultured human fibroblasts. Incubation of (/sup 3/H)vitamin D/sub 3/ (cholecalciferol) with plasma followed by sequential ultracentrifugal fractionation of the lipoproteins indicated that 2-4% of the radioactivity associated with the very low density lipoprotein (VLDL), 12% with low density lipoprotein (LDL), and approximately 60% with the high density lipoprotein (HDL). The remaining radioactivity, 25%, was associated with the sedimented plasma fractions. By comparison, an average of 86% of the radioactivity from (/sup 3/H) 1,25-dihydroxycholecalciferol associated with the sedimented plasma fractions. The uptake of (/sup 3/H)vitamin D/sub 3/ from plasma, LDL, or HDL was studied in cultured human cells; uptake by normal fibroblasts was greatest from LDL and least from plasma. The cellular association of vitamin D/sub 3/ was time, concentration, and temperature dependent. At a concentration of 50 ..mu..g LDL/ml of medium, the uptake of (/sup 3/H)vitamin D/sub 3/ from LDL at 37/sup 0/C was rapid and reached a maximum at approximately 4 hr; it was slower from HDL but continued to increase slowly up to 24 hr. The significance of these in vitro findings is uncertain since much of the vitamin D/sub 3/ absorbed from the intestine reportedly associates with chylomicrons and is rapidly taken up by the liver.

  14. Uptake of technetium-99m methylene diphosphonate by fractured and osteoporotic bone after a pulse dose of Vitamin D/sub 3/. [Rats

    SciTech Connect

    Carr, E.A. Jr.; Carroll, M.; Montes, M.; Zielezny, M.

    1985-04-01

    The effect of a pulse dose of Vitamin D/sub 3/ on uptake of (/sup 99m/Tc)MDP by fractured and osteoporotic bone, respectively, was compared with D/sub 3/'s effect on uptake by normal bone in rats. At 4, 7, and 14 days, respectively, after femoral fracture, basal uptake was significantly increased at the fracture site by 336.8, 276.1, and 183.5%, respectively, over the contralateral control site. D/sub 3/-treated rats had lower uptakes than untreated controls at all three fracture sites and at 12 of 15 normal bone sites but analysis of variance showed the uptake differences were not significant. Cortisone-induced osteoporosis caused a significant decrease in basal uptake. The decrease occurred in all nine bone areas studied. D/sub 3/ caused a significant increase in uptake by these osteoporotic bones, but a significant decrease in uptake by the same bones in normal controls. Thus, D/sub 3/ had an effect on uptake by the bone lesion, osteoporosis, that differed from D/sub 3/'s effect on uptake by fracture or normal bone.

  15. Involvement of 1,25D{sub 3}-MARRS (membrane associated, rapid response steroid-binding), a novel vitamin D receptor, in growth inhibition of breast cancer cells

    SciTech Connect

    Richard, Cynthia L.; Farach-Carson, Mary C.; Rohe, Ben; Nemere, Ilka; Meckling, Kelly A.

    2010-03-10

    In addition to classical roles in calcium homeostasis and bone development, 1,25 dihydroxyvitamin D{sub 3} [1,25(OH){sub 2}D{sub 3}] inhibits the growth of several cancer types, including breast cancer. Although cellular effects of 1,25(OH){sub 2}D{sub 3} traditionally have been attributed to activation of a nuclear vitamin D receptor (VDR), a novel receptor for 1,25(OH){sub 2}D{sub 3} called 1,25D{sub 3}-MARRS (membrane-associated, rapid response steroid-binding) protein was identified recently. The purpose of this study was to determine if the level of 1,25D{sub 3}-MARRS expression modulates 1,25(OH){sub 2}D{sub 3} activity in breast cancer cells. Relative levels of 1,25D{sub 3}-MARRS protein in MCF-7, MDA MB 231, and MCF-10A cells were estimated by real-time RT-PCR and Western blotting. To determine if 1,25D{sub 3}-MARRS receptor was involved in the growth inhibitory effects of 1,25(OH){sub 2}D{sub 3} in MCF-7 cells, a ribozyme construct designed to knock down 1,25D{sub 3}-MARRS mRNA was stably transfected into MCF-7 cells. MCF-7 clones in which 1,25D{sub 3}-MARRS receptor expression was reduced showed increased sensitivity to 1,25(OH){sub 2}D{sub 3} ( IC{sub 50} 56 {+-} 24 nM) compared to controls (319 {+-} 181 nM; P < 0.05). Reduction in 1,25D{sub 3}-MARRS receptor lengthened the doubling time in transfectants treated with 1,25(OH){sub 2}D{sub 3}. Knockdown of 1,25D{sub 3}-MARRS receptor also increased the sensitivity of MCF-7 cells to the vitamin D analogs KH1060 and MC903, but not to unrelated agents (all-trans retinoic acid, paclitaxel, serum/glucose starvation, or the isoflavone, pomiferin). These results suggest that 1,25D{sub 3}-MARRS receptor expression interferes with the growth inhibitory activity of 1,25(OH){sub 2}D{sub 3} in breast cancer cells, possibly through the nuclear VDR. Further research should examine the potential for pharmacological or natural agents that modify 1,25D{sub 3}-MARRS expression or activity as anticancer agents.

  16. Somatic Mutations in CCK2R Alter Receptor Activity that Promote Oncogenic Phenotypes

    PubMed Central

    Willard, Melinda D.; Lajiness, Mary E.; Wulur, Isabella H.; Feng, Bo; Swearingen, Michelle L.; Uhlik, Mark T.; Kinzler, Kenneth W.; Velculescu, Victor E.; Sjöblom, Tobias; Markowitz, Sanford D.; Powell, Steven M.; Vogelstein, Bert; Barber, Thomas D.

    2013-01-01

    The roles of cholecystokinin 2 receptor (CCK2R) in numerous physiologic processes in the gastrointestinal tract and central nervous system are ‘well documented. There has been some evidence that CCK2R alterations play a role in cancers, but the functional significance of these alterations for tumorigenesis is unknown. We have identified six mutations in CCK2R among a panel of 140 colorectal cancers and 44 gastric cancers. We show that these mutations increase receptor activity, activate multiple downstream signaling pathways, increase cell migration, and promote angiogenesis. Our findings suggest that somatic mutations in CCK2R may promote tumorigenesis through deregulated receptor activity and highlight the importance of evaluating CCK2R inhibitors to block both the normal and mutant forms of the receptor. PMID:22516348

  17. Dopamine D{sub 3} receptor gene: Organization transcript variants, and polymorphism associated with schizophrenia

    SciTech Connect

    Griffon, N.; Pilon, C.; Martres, M.P.

    1996-02-16

    DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D{sub 3} receptor gene (DRD3). Its coding sequence contains 6 exons and stretches over 40,000 base pairs. The complete DRD3 transcript and three shorter variants, in which the second and/or third exon are deleted, were detected in similar proportions in brains from four controls and three psychiatric patients. The Msp I polymorphism was localized in the fifth intron of the gene, 40,000 base pairs downstream the Bal I polymorphism and a PCR-based method was developed for genotyping this polymorphism. The distributions of the Msp I and Bal I genotypes were not independent in 297 individuals ({chi}{sup 2} = 10.5, df = 4, P = 0.03), but only a weak association was found between allele 1 of the Bal I polymorphism and allele 2 of the Msp I polymorphism ({chi}{sup 2} = 3.99, df = 1, P = 0.04). The previously reported association between homozygosity at both alleles of the Bal I polymorphism and schizophrenia was presently maintained in an extended sample, comprising 119 DSM-III-R chronic schizophrenics and 85 controls ({chi}{sup 2}= 5.3, df = 1, P = 0.02) and found more important in males than in females. The presence of the Bal I allele 2 is associated with an early age at onset, particularly in males (df = 35, t value = 2.6, P = 0.014). In the same sample, allelic frequencies, genotype counts, and proportion of homozygotes for the Msp I polymorphism did not differ between schizophrenics and controls ({chi}{sup 2}= 0.06, df = 1, P = 0.80, {chi}{sup 2} = 0.22, df = 1, P = 0.90 and {chi}{sup 2} = 0.16, df = 1, P = 0.69, respectively). The large distance of the Msp I polymorphism from the Bal I polymorphism and its localization in the 3{prime} part of the gene may explain the discrepant results obtained with the two polymorphisms. 36 refs., 2 figs., 4 tabs.

  18. Implantation of energetic D{sup +} ions into carbon dioxide ices and implications for our solar system: formation of D{sub 2}O and D{sub 2}CO{sub 3}

    SciTech Connect

    Bennett, Chris J.; Ennis, Courtney P.; Kaiser, Ralf I.

    2014-10-10

    Carbon dioxide (CO{sub 2}) ices were irradiated with energetic D{sup +} ions to simulate the exposure of oxygen-bearing solar system ices to energetic protons from the solar wind and magnetospheric sources. The formation of species was observed online and in situ by exploiting FTIR spectroscopy. Molecular products include ozone (O{sub 3}), carbon oxides (CO{sub 3}(C {sub 2v}, D {sub 3h}), CO{sub 4}, CO{sub 5}, CO{sub 6}), D2-water (D{sub 2}O), and D2-carbonic acid (D{sub 2}CO{sub 3}). Species released into the gas phase were sampled via a quadrupole mass spectrometer, and possible minor contributions from D2-formaldehyde (D{sub 2}CO), D4-methanol (CD{sub 3}OD), and D2-formic acid (DCOOD) were additionally identified. The feasibility of several reaction networks was investigated by determining their ability to fit the observed temporal column densities of 10 key species that were quantified during the irradiation period. Directly relevant to the CO{sub 2}-bearing ices of comets, icy satellites in the outer solar system, and the ice caps on Mars, this work illustrates for the first time that D2-water is formed as a product of the exposure of CO{sub 2} ices to D{sup +} ions. These findings provide strong support for water formation from oxygen-bearing materials via non-thermal hydrogen atoms, and predict reaction pathways that are likely to be unfolding on the surfaces of asteroids and the Moon.

  19. Measurement of the pseudoscalar decay constant f{sub D{sub s}} using D{sub s}{sup +}{yields}{tau}{sup +}{nu}, {tau}{sup +}{yields}{rho}{sup +}{nu} decays

    SciTech Connect

    Naik, P.; Rademacker, J.; Asner, D. M.; Edwards, K. W.; Randrianarivony, K.; Reed, J.; Robichaud, A. N.; Tatishvili, G.; White, E. J.; Briere, R. A.; Vogel, H.; Onyisi, P. U. E.; Rosner, J. L.; Alexander, J. P.; Cassel, D. G.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, S. W.; Hartill, D. L.

    2009-12-01

    Analyzing 600 pb{sup -1} of e{sup +}e{sup -} collisions at 4170 MeV center-of-mass energy with the CLEO-c detector, we measure the branching fraction B(D{sub s}{sup +}{yields}{tau}{sup +}{nu})=(5.52{+-}0.57{+-}0.21)% using the {tau}{sup +}{yields}{rho}{sup +}{nu} decay mode. Combining with other CLEO measurements of B(D{sub s}{sup +}{yields}{tau}{sup +}{nu}) we determine the pseudoscalar decay constant f{sub D{sub s}}=(259.7{+-}7.8{+-}3.4) MeV consistent with the value obtained from our D{sub s}{sup +}{yields}{mu}{sup +}{nu} measurement of (257.6{+-}10.3{+-}4.3) MeV. Combining these measurements we find a value of f{sub D{sub s}}=(259.0{+-}6.2{+-}3.0) MeV, that differs from the most accurate prediction based on unquenched lattice gauge theory of (241{+-}3) MeV by 2.4 standard deviations. We also present the first measurements of B(D{sub s}{sup +}{yields}K{sup 0}{pi}{sup +}{pi}{sup 0})=(1.00{+-}0.18{+-}0.04)%, and B(D{sub s}{sup +}{yields}{pi}{sup +}{pi}{sup 0}{pi}{sup 0})=(0.65{+-}0.13{+-}0.03)%, and measure a new value for B(D{sub s}{sup +}{yields}{eta}{rho}{sup +})=(8.9{+-}0.6{+-}0.5)%.

  20. Expansion and diversification of the Populus R2R3-MYB family of transcription factors.

    PubMed

    Wilkins, Olivia; Nahal, Hardeep; Foong, Justin; Provart, Nicholas J; Campbell, Malcolm M

    2009-02-01

    The R2R3-MYB proteins comprise one of the largest families of transcription factors in plants. R2R3-MYB family members regulate plant-specific processes, such as the elaboration of specialized cell types, including xylem, guard cells, trichomes, and root hairs, and the biosynthesis of specialized branches of metabolism, including phenylpropanoid biosynthesis. As such, R2R3-MYB family members are hypothesized to contribute to the emergence of evolutionary innovations that have arisen in specific plant lineages. As a first step in determining the role played by R2R3-MYB family members in the emergence of lineage-specific innovations in the genus Populus, the entire Populus trichocarpa R2R3-MYB family was characterized. The Populus R2R3-MYB complement is much larger than that found in other angiosperms with fully sequenced genomes. Phylogenetic analyses, together with chromosome placement, showed that the expansion of the Populus R2R3-MYB family was not only attributable to whole genome duplication but also involved selective expansion of specific R2R3-MYB clades. Expansion of the Populus R2R3-MYB family prominently involved members with expression patterns that suggested a role in specific components of Populus life history, including wood formation and reproductive development. An expandable compendium of microarray-based expression data (PopGenExpress) and associated Web-based tools were developed to better enable within- and between-species comparisons of Populus R2R3-MYB gene expression. This resource, which includes intuitive graphic visualization of gene expression data across multiple tissues, organs, and treatments, is freely available to, and expandable by, scientists wishing to better understand the genome biology of Populus, an ecologically dominant and economically important forest tree genus. PMID:19091872

  1. An Alternative Laboratory Designed to Address Ethical Concerns Associated with Traditional "TAS2R38" Student Genotyping

    ERIC Educational Resources Information Center

    LaBonte, Michelle L.; Beers, Melissa A.

    2015-01-01

    The "TAS2R38" alleles that code for the PAV/AVI T2R38 proteins have long been viewed as benign taste receptor variants. However, recent studies have demonstrated an expanding and medically relevant role for "TAS2R38." The AVI variant of T2R38 is associated with an increased risk of both colorectal cancer and "Pseudomonas…

  2. An ODIP Effort to Map R2R Ocean Data Terms to International Vocabularies

    NASA Astrophysics Data System (ADS)

    Ferreira, R.; Stocks, K. I.; Arko, R. A.

    2014-12-01

    The diverseness of terminology used in describing ocean data creates a barrier to 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 U.S. 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 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 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 within R2R or are specific to the U.S. The goal of this student project is to crosswalk local/national vocabularies to authoritative international ones, where they exist, or to vocabularies widely used by ODIP partners. Specifically, R2R developed the following crosswalks: UNOLS ports to SeaDataNet Ports Gazetteer, R2R Device Models to NVS SeaVoX Device Catalog, R2R Organizations to the European Directory of Marine Organizations (EDMO), and R2R chief scientist names to well known professional identifiers such as ORCID, Research Gate, Linkedin, etc. Mappings were done in simple spreadsheets using synonymy relationships, and will be published as part of the R2R Linked Data resources. The level of success in crosswalking was variable. All ports are successfully mapped. Both organizations and device models have initial mappings and R2R has added new terms to EDMO and SeaVoX Device Catalog vocabularies allowing for nearly complete coverage of

  3. Spatiotemporal Imaging of Ultrafast Molecular Motion: Collapse and Revival of the D{sub 2}{sup +} Nuclear Wave Packet

    SciTech Connect

    Ergler, Th.; Rudenko, A.; Zrost, K.; Schroeter, C. D.; Moshammer, R.; Ullrich, J.; Feuerstein, B.

    2006-11-10

    We report on a real-time imaging of the ultrafast D{sub 2}{sup +} rovibrational nuclear wave-packet motion performed using a combination of a pump-probe setup with 7 fs laser pulses and a 'reaction-microscope' spectrometer. We observe fast dephasing (collapse) of the vibrational wave packet and its subsequent revival and prove rotational excitation in ultrashort laser pulses. Channel-selective Fourier analysis of the wave packet's long-term ({approx}3000 fs) evolution allows us to resolve its individual constituents, revealing unique information on the mechanisms of strong-field ionization and dissociation.

  4. Tunneling between de Sitter and anti-de Sitter black holes in a noncommutative D{sub 3}-brane formalism

    SciTech Connect

    Kar, Supriya

    2006-12-15

    We obtain de Sitter (dS) and anti-de Sitter (AdS) generalized Reissner-Nordstrom-like black hole geometries in a curved D{sub 3}-brane framework, underlying a noncommutative gauge theory on the brane world. The noncommutative scaling limit is explored to investigate a possible tunneling of an AdS vacuum in string theory to dS vacuum in its low energy gravity theory. The Hagedorn transition is invoked into its self-dual gauge theory to decouple the gauge nonlinearity from the dS geometry, which in turn is shown to describe a pure dS vacuum.

  5. Chemical genetic analysis reveals the effects of NMU2R on the expression of peptide hormones.

    PubMed

    Fang, Liyan; Zhang, Mancang; Li, Chunxia; Dong, Suzhen; Hu, Yinghe

    2006-08-14

    Neuromedin U 2 receptor (NMU2R) plays important roles for the regulation of food intake and body weight. However, the molecular mechanism underlying the action of NMU2R has not been clearly defined. We have taken chemical genetic approach to examine the involvement of peptides in the regulation of NMU2R effects. A cell-based reporter gene assay has been developed and used for the screening of human NMU2R agonist. Three natural product compounds, EUK2010, EUK2011 and EUK2012, were identified that could activate the reporter gene expression in the cell-based functional assay. Although these compounds showed high EC50 at hundreds micro-molar range, in vitro pharmacological analysis suggested that they were specific agonists for the human NMU2R. The natural compounds could decrease food intake and lead to the reduction of body weight in different animal models. To understand the molecular basis of the NMU2R regulation of food intake and body weight, we examined the expression of a number of key genes in hypothalamus and adipose tissues after oral administration of EUK2010 in mice. Our results demonstrated that the expression levels of a number of neuropeptide genes were altered after the treatment of EUK2010. Interestingly, EUK2010 increased the expression of Leptin in white fat. These results suggested that these peptides may participate in the regulation of NMU2R effects in mice. PMID:16781063

  6. Clinical Significance of sIL-2R Levels in B-Cell Lymphomas

    PubMed Central

    Yoshida, Noriaki; Oda, Miyo; Kuroda, Yoshiaki; Katayama, Yuta; Okikawa, Yoshiko; Masunari, Taro; Fujiwara, Megumu; Nishisaka, Takashi; Sasaki, Naomi; Sadahira, Yoshito; Mihara, Keichiro; Asaoku, Hideki; Matsui, Hirotaka; Seto, Masao; Kimura, Akiro; Arihiro, Koji; Sakai, Akira

    2013-01-01

    Elevated soluble interleukin-2 receptor (sIL-2R) in sera is observed in patients with malignant lymphoma (ML). Therefore, sIL-2R is commonly used as a diagnostic and prognostic marker for ML, but the mechanisms responsible for the increase in sIL-2R levels in patients with B-cell lymphomas have not yet been elucidated. We first hypothesized that lymphoma cells expressing IL-2R and some proteinases such as matrix metalloproteinases (MMPs) in the tumor microenvironment can give rise to increased sIL-2R in sera. However, flow cytometric studies revealed that few lymphoma cells expressed IL-2R α chain (CD25) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and most CD25-expressing cells in the tumor were T-cells. Distinct correlations between CD25 expression on B-lymphoma cells and sIL-2R levels were not observed. We then confirmed that MMP-9 plays an important role in producing sIL-2R in functional studies. Immunohistochemical (IHC) analysis also revealed that MMP-9 is mainly derived from tumor-associated macrophages (TAMs). We therefore evaluated the number of CD68 and CD163 positive macrophages in the tumor microenvironment using IHC analysis. A positive correlation between the levels of sIL-2R in sera and the numbers of CD68 positive macrophages in the tumor microenvironment was confirmed in FL and extranodal DLBCL. These results may be useful in understanding the pathophysiology of B-cell lymphomas. PMID:24236041

  7. Molecular characterization, tissue expression profile and SNP analysis of porcine GLP2R.

    PubMed

    Chai, Y L; Ma, H M; Jiang, J

    2015-01-01

    Glucagon-like peptide-2 receptor (GLP2R), a member of the G-protein-coupled receptor family, plays an important role in intramuscular fat formation. Little is known, however, about porcine GLP2R. In the present study, GLP2R was cloned, and its expression in pig muscle characterized. By rapid amplification of cDNA ends, gene sequence was obtained from Shaziling pigs. Full-length cDNA was 1868 bp, including an open reading frame 1665 bp in length, encoding 554 amino acids, and 203 bp at the 3' end. The GLP2R homology between porcine and other species was performed using bioinformatics techniques to construct a phylogenetic tree. Porcine GLP2R was most closely related to those from Orcinus orca and Ovis aries, and most distantly related to those from Chrysemys picta, Taeniopygia guttata, and Falco peregrinus. Real-time PCR analysis showed expression of porcine GLP2R in 10 different tissues from 25-day-old Yorkshire and Shaziling piglets, with expression levels being highest in the longissimus dorsi muscle and lowest in kidney. For each pig breed, expression level in longissimus dorsi muscle was highest among ten tissues (P < 0.05). Between the two breeds, GLP2R expression levels were significant in pancreas, the crureus and longissimus dorsi muscles (P < 0.05). A single SNP of porcine GLP2R, A343G, was identified, and genotypes were determined by PCR-RFLP. This study provides an insight into the function of GLP2R in swine. PMID:26505446

  8. Rebaudioside A and Rebaudioside D bitterness do not covary with Acesulfame K bitterness or polymorphisms in TAS2R9 and TAS2R31

    PubMed Central

    Allen, Alissa L.; McGeary, John E.; Hayes, John E.

    2013-01-01

    In order to reduce calories in foods and beverages, the food industry routinely uses non-nutritive sweeteners. Unfortunately, many are synthetically derived, and many consumers have a strong preference for natural sweeteners, irrespective of the safety data on synthetic non-nutritive sweeteners. Additionally, many non-nutritive sweeteners elicit aversive side tastes such as bitter and metallic in addition to sweetness. Bitterness thresholds of acesulfame-K (AceK) and saccharin are known to vary across bitter taste receptors polymorphisms in TAS2R31. RebA has shown to activate hTAS2R4 and hTAS2R14 in vitro. Here we examined bitterness and sweetness perception of natural and synthetic non-nutritive sweeteners. In a follow-up to a previous gene-association study, participants (n=122) who had been genotyped previously rated sweet, bitter and metallic sensations from rebaudioside A (RebA), rebaudioside D (RebD), aspartame, sucrose and gentiobiose in duplicate in a single session. For comparison, we also present sweet and bitter ratings of AceK collected in the original experiment for the same participants. At similar sweetness levels, aspartame elicited less bitterness than RebD, which was significantly less bitter than RebA. The bitterness of RebA and RebD showed wide variability across individuals, and bitterness ratings for these compounds were correlated. However, RebA and RebD bitterness did not covary with AceK bitterness. Likewise, single nucleotide polymorphisms (SNPs) shown previously to explain variation in the suprathreshold bitterness of AceK (rs3741845 in TAS2R9 and rs10772423 in TAS2R31) did not explain variation in RebA and RebD bitterness. Because RebA activates hT2R4 and hT2R14, a SNP in TAS2R4 previously associated with variation in bitterness perception was included here; there are no known functional SNPs for TAS2R14. In present data, a putatively functional SNP (rs2234001) in TAS2R4 did not explain variation in RebA or RebD bitterness. Collectively

  9. Rebaudioside A and Rebaudioside D bitterness do not covary with Acesulfame K bitterness or polymorphisms in TAS2R9 and TAS2R31.

    PubMed

    Allen, Alissa L; McGeary, John E; Hayes, John E

    2013-09-01

    In order to reduce calories in foods and beverages, the food industry routinely uses non-nutritive sweeteners. Unfortunately, many are synthetically derived, and many consumers have a strong preference for natural sweeteners, irrespective of the safety data on synthetic non-nutritive sweeteners. Additionally, many non-nutritive sweeteners elicit aversive side tastes such as bitter and metallic in addition to sweetness. Bitterness thresholds of acesulfame-K (AceK) and saccharin are known to vary across bitter taste receptors polymorphisms in TAS2R31. RebA has shown to activate hTAS2R4 and hTAS2R14 in vitro. Here we examined bitterness and sweetness perception of natural and synthetic non-nutritive sweeteners. In a follow-up to a previous gene-association study, participants (n=122) who had been genotyped previously rated sweet, bitter and metallic sensations from rebaudioside A (RebA), rebaudioside D (RebD), aspartame, sucrose and gentiobiose in duplicate in a single session. For comparison, we also present sweet and bitter ratings of AceK collected in the original experiment for the same participants. At similar sweetness levels, aspartame elicited less bitterness than RebD, which was significantly less bitter than RebA. The bitterness of RebA and RebD showed wide variability across individuals, and bitterness ratings for these compounds were correlated. However, RebA and RebD bitterness did not covary with AceK bitterness. Likewise, single nucleotide polymorphisms (SNPs) shown previously to explain variation in the suprathreshold bitterness of AceK (rs3741845 in TAS2R9 and rs10772423 in TAS2R31) did not explain variation in RebA and RebD bitterness. Because RebA activates hT2R4 and hT2R14, a SNP in TAS2R4 previously associated with variation in bitterness perception was included here; there are no known functional SNPs for TAS2R14. In present data, a putatively functional SNP (rs2234001) in TAS2R4 did not explain variation in RebA or RebD bitterness. Collectively

  10. Genotype-specific regulation of oral innate immunity by T2R38 taste receptor.

    PubMed

    Gil, Sucheol; Coldwell, Susan; Drury, Jeanie L; Arroyo, Fabiola; Phi, Tran; Saadat, Sanaz; Kwong, Danny; Chung, Whasun Oh

    2015-12-01

    The bitter taste receptor T2R38 has been shown to regulate mucosal innate immune responses in the upper airway epithelium. Furthermore, SNPs in T2R38 influence the sensitivity to 6-n-propylthiouracil (PROP) and are associated with caries risk/protection. However, no study has been reported on the role of T2R38 in the innate immune responses to oral bacteria. We hypothesize that T2R38 regulates oral innate immunity and that this regulation is genotype-specific. Primary gingival epithelial cells carrying three common genotypes, PAV/PAV (PROP super-taster), AVI/PAV (intermediate) and AVI/AVI (non-taster) were stimulated with cariogenic bacteria Streptococcus mutans, periodontal pathogen Porphyromonas gingivalis or non-pathogen Fusobacterium nucleatum. QRT-PCR analyzed T2R38 mRNA, and T2R38-specific siRNA and ELISA were utilized to evaluate induction of hBD-2 (antimicrobial peptide), IL-1α and IL-8 in various donor-lines. Experiments were set up in duplicate and repeated three times. T2R38 mRNA induction in response to S. mutans was highest in PAV/PAV (4.3-fold above the unstimulated controls; p<0.05), while lowest in AVI/AVI (1.2-fold). In PAV/PAV, hBD-2 secretion in response to S. mutans was decreased by 77% when T2R38 was silenced. IL-1α secretion was higher in PAV/PAV compared to AVI/PAV or AVI/AVI with S. mutans stimulation, but it was reduced by half when T2R38 was silenced (p<0.05). In response to P. gingivalis, AVI/AVI showed 4.4-fold increase (p<0.05) in T2R38 expression, whereas the levels in PAV/PAV and AVI/PAV remained close to that of the controls. Secretion levels of IL-1α and IL-8 decreased in AVI/AVI in response to P. gingivalis when T2R38 was silenced (p<0.05), while the changes were not significant in PAV/PAV. Our data suggest that the regulation of gingival innate immunity by T2R38 is genotype-dependent and that the ability to induce a high level of hBD-2 by PAV/PAV carriers may be a reason for protection against caries in this group. PMID

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

    NASA Astrophysics Data System (ADS)

    Ferreira, Renata; Stocks, Karen; Arko, Robert

    2014-05-01

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

  12. Prolonged P300 latency in children with the D[sub 2] dopamine receptor A1 allele

    SciTech Connect

    Noble, E.P.; Berman, S.M.; Ozkaragoz, T.Z.; Ritchie, T. )

    1994-04-01

    Previous studies have indicated the presence of a hereditary component in the generation of the P300, or P3, a late positive component of the event-related potential. Moreover, the dopaminergic system has been implicated in the P3. In the present study, 98 healthy Caucasian boys, mean age of 12.5 years and of above-average intelligence, were studied. The sample was composed of 32 sons of active alcoholic (SAA) fathers, 36 sons of recovering alcoholic (SRA) fathers, and 30 sons of social drinker (SSD) fathers, with none of them having yet begun to consume alcohol or other drugs. TaqI A D[sub 2] dopamine receptor alleles (A1 and A2) were determined. A significant difference in the frequency of the A1 allele was found among these three groups of boys, with the SAA group having the highest A1 allele frequency (.313), followed by the SRA (.139) and the SSD (.133) groups. The relationship of the A1 and A2 alleles to P3 amplitude and latency was also determined. The results showed no significant difference in P3 amplitude between boys with the A1 and A2 allele. However, P3 latency was significantly longer in the total sample of boys with the A1 allele compared with those carrying the A2 allele. These findings suggest that polymorphism of the D[sub 2] dopamine receptor gene is an important determinant of P3 latency. 84 refs., 2 figs., 3 tabs.

  13. Assay and properties of rat yolk sac 25-hydroxyvitamin D/sub 3/ 1. cap alpha. -hydroxylase

    SciTech Connect

    Paulson, S.K.; Phelps, M.; DeLuca, H.F.

    1986-11-04

    An in vitro assay has been developed for the rat yolk sac 25-hydroxyvitamin D/sub 3/ 1..cap alpha..-hydroxylase (1..cap alpha..-hydroxylase). The subcellular location and some properties of the enzyme are described. 1,25-Dihydroxyvitamin D/sub 3/ produced from incubations of yolk sac homogenates was extracted, purified by Sephadex LH-20 chromatography and straight- and reverse-phase high-performance liquid chromatography (HPLC), and measured by a competitive binding assay using chick intestinal receptor. The reaction is linear with time for up to 45 min at a substrate concentration of 80 ..mu..M and 4-6 mg/mL microsomal protein. The enzyme, located in the microsomes, requires molecular oxygen and NADPH. Metyrapone (1 x 10/sup -3/ M) was found to inhibit 1-hydroxylation, but a 90% carbon monoxide-10% oxygen atmosphere did not, leaving open the question of involvement of cytochrome P-450. Diphenyl-p-phenylenediamine, a lipid peroxidase inhibitor, inhibited 1..cap alpha..-hydroxylation.

  14. Dissociation of H{sub 2}{sup +} and D{sub 2}{sup +} in an intense laser field

    SciTech Connect

    Ludwig, J.; Rottke, H.; Sandner, W.

    1997-09-01

    We report experimental investigations on dissociation of H{sub 2} and D{sub 2} in intense subpicosecond laser pulses at 1053 and 526.5 nm. Intensities in the range from {approx}5{times}10{sup 13} up to {approx}5{times}10{sup 14} W/cm{sup 2} were applied. The kinetic-energy distributions of the photoions H{sup +} and D{sup +}, which change dramatically with the light pulse peak intensity, give a detailed insight into the dissociation mechanisms. At 526.5 nm and low light intensity, ions from bond-softening dissociation and probably seven-photon resonant dissociative multiphoton ionization dominate the spectra. The resonant intermediate states are Rydberg states of the neutral molecules. At 1053 nm, above-threshold dissociation makes the main contribution to the spectra. Independent of the excitation wavelength, Coulomb explosion dissociation is found in the high-intensity limit. H{sub 2}{sup +} and D{sub 2}{sup +} photoionization, triggering this process, proceeds in the quasistatic limit by preferred tunnel or above-barrier ionization in a limited range of internuclear separations around 7.5 a.u. The ion kinetic-energy distributions seem to indicate that at 526.5 nm ionization starts from molecular ions light stabilized in a certain range of internuclear distances. In contrast, at 1053 nm, ionization seems to start from dissociating molecular ions. {copyright} {ital 1997} {ital The American Physical Society}

  15. Mechanisms for the near-UV photodissociation of CH{sub 3}I on D{sub 2}O/Cu(110)

    SciTech Connect

    Miller, E. R.; Muirhead, G. D.; Jensen, E. T.

    2013-02-28

    The system of CH{sub 3}I adsorbed on submonolayer, monolayer, and multilayer thin films of D{sub 2}O on Cu(110) has been studied by measuring the time of flight (TOF) distributions of the desorbing CH{sub 3} fragments after photodissociation using linearly polarized {lambda} = 248 nm light. For multilayer D{sub 2}O films (2-120 ML), the photodissociation is dominated by neutral photodissociation via the 'A-band' absorption of CH{sub 3}I. The polarization and angle dependent variation in the observed TOF spectra of the CH{sub 3} photofragments find that dissociation is largely via the {sup 3}Q{sub 0} excited state, but that also a contribution via the {sup 1}Q{sub 1} excitation can be identified. The photodissociation results also indicate that the CH{sub 3}I adsorbed on D{sub 2}O forms close-packed islands at submonolayer coverages, with a mixture of C-I bond axis orientations. For monolayer and submonolayer quantities of D{sub 2}O we have observed a contribution to CH{sub 3}I photodissociation via dissociative electron attachment (DEA) by photoelectrons. The observed DEA is consistent with delocalized photoelectrons from the substrate causing the observed dissociation- we do not find evidence for an enhanced DEA mechanism via the temporary solvation of photoelectrons in localized states of the D{sub 2}O ice.

  16. Genome-Wide Identification and Characterization of R2R3MYB Family in Cucumis sativus

    PubMed Central

    Li, Qiang; Zhang, Cunjia; Li, Jing; Wang, Lina; Ren, Zhonghai

    2012-01-01

    Background The R2R3MYB proteins comprise one of the largest families of transcription factors in plants. Although genome-wide analysis of this family has been carried out in some species, little is known about R2R3MYB genes in cucumber (Cucumis sativus L.). Principal Findings This study has identified 55 R2R3MYB genes in the latest cucumber genome and the CsR2R3MYB family contained the smallest number of identified genes compared to other species that have been studied due to the absence of recent gene duplication events. These results were also supported by genome distribution and gene duplication analysis. Phylogenetic analysis showed that they could be classified into 11 subgroups. The evolutionary relationships and the intron - exon organizations that showed similarities with Arabidopsis, Vitis and Glycine R2R3MYB proteins were also analyzed and suggested strong gene conservation but also the expansions of particular functional genes during the evolution of the plant species. In addition, we found that 8 out of 55 (∼14.54%) cucumber R2R3MYB genes underwent alternative splicing events, producing a variety of transcripts from a single gene, which illustrated the extremely high complexity of transcriptome regulation. Tissue-specific expression profiles showed that 50 cucumber R2R3MYB genes were expressed in at least one of the tissues and the other 5 genes showed very low expression in all tissues tested, which suggested that cucumber R2R3MYB genes took part in many cellular processes. The transcript abundance level analysis during abiotic conditions (NaCl, ABA and low temperature treatments) identified a group of R2R3MYB genes that responded to one or more treatments. Conclusions This study has produced a comparative genomics analysis of the cucumber R2R3MYB gene family and has provided the first steps towards the selection of CsR2R3MYB genes for cloning and functional dissection that can be used in further studies to uncover their roles in cucumber growth and

  17. Anti-PLA2R Antibodies in Chinese Patients with Membranous Nephropathy.

    PubMed

    Li, Xin; Wei, Dong; Zhou, Zhanmei; Wang, Baoguo; Xu, Ya; Pan, Jie; Yang, Chunli; Lu, Jie; Qiu, Yurong

    2016-01-01

    BACKROUND ~This study used two standardized methods to evaluate anti-PLA2R antibody in serum of primary membranous nephropathy (PMN) among Chinese patients to determine  Anti-PLA2R antibody distribution and whether immunological reactivity reflected by antibody titer correlates with kidney function parameters. MATERIAL AND METHOD ~Overall, 82 subjects with biopsy-proven primary membranous nephropathy (PMN) , 22 cases with secondary membranous nephropathy (SMN), 40 non-MN patients with established glomerulonephritis, 20 healthy volunteers were recruited from the Division of Nephrology, Nanfang Hospital, China. Anti-PLA2R antibody in the serum of each patient was evaluated by both recombinant cell-based indirect immunofluorescence assay (RC-IFA) and enzyme linked immunosorbent assay (ELISA). Kidney function was assessed by proteinuria for 24 hours, serum albumin, blood urea nitrogen (BUN), serum creatine, serum cystatin C. We assessed the correlation between anti-PLA2R antibody levels and clinical parameter in the PMN patients. RESULTS ~ Fifty-three patients with PMN (64.6%) were positive for anti-PLA2R antibody. The level of antibody determined by RC-IFA ranged from 1:10 to 1:1000 and 0 to 1423 RU/ml by ELISA. The two anti-PLA2R test systems correlated very well with each other and reached an agreement of 95.7% for PMN patients. The level of antibody detected by ELISA in patients with PMN also significantly correlated with proteinuria and nephritic-range proteinuria (> 3.5g/day) . CONCLUSIONS ~Anti-PLA2R antibody is sensitive and extremely specific for diagnosis of Chinese patients with primary membranous nephropathy. Concentration of autoantibody against PLA2R is an ideal marker for monitoring the activity of immunological disease. PMID:27179439

  18. Amino Acid Derivatives as Bitter Taste Receptor (T2R) Blockers*

    PubMed Central

    Pydi, Sai P.; Sobotkiewicz, Tyler; Billakanti, Rohini; Bhullar, Rajinder P.; Loewen, Michele C.; Chelikani, Prashen

    2014-01-01

    In humans, the 25 bitter taste receptors (T2Rs) are activated by hundreds of structurally diverse bitter compounds. However, only five antagonists or bitter blockers are known. In this study, using molecular modeling guided site-directed mutagenesis, we elucidated the ligand-binding pocket of T2R4. We found seven amino acids located in the extracellular side of transmembrane 3 (TM3), TM4, extracellular loop 2 (ECL2), and ECL3 to be involved in T2R4 binding to its agonist quinine. ECL2 residues Asn-173 and Thr-174 are essential for quinine binding. Guided by a molecular model of T2R4, a number of amino acid derivatives were screened for their ability to bind to T2R4. These predictions were tested by calcium imaging assays that led to identification of γ-aminobutryic acid (GABA) and Nα,Nα-bis(carboxymethyl)-l-lysine (BCML) as competitive inhibitors of quinine-activated T2R4 with an IC50 of 3.2 ± 0.3 μm and 59 ± 18 nm, respectively. Interestingly, pharmacological characterization using a constitutively active mutant of T2R4 reveals that GABA acts as an antagonist, whereas BCML acts as an inverse agonist on T2R4. Site-directed mutagenesis confirms that the two novel bitter blockers share the same orthosteric site as the agonist quinine. The signature residues Ala-90 and Lys-270 play important roles in interacting with BCML and GABA, respectively. This is the first report to characterize a T2R endogenous antagonist and an inverse agonist. The novel bitter blockers will facilitate physiological studies focused on understanding the roles of T2Rs in extraoral tissues. PMID:25059668

  19. A potent antibrowning agent from pine needles of Cedrus deodara: 2R,3R-dihydromyricetin.

    PubMed

    Liang, Xue; Wu, Yan-Ping; Qiu, Jing-Hong; Zhong, Kai; Gao, Hong

    2014-09-01

    This article focuses on finding the novel antibrowning agents from the pine needles of Cedrus deodara and studying its antibrowning effect. By bioassay guide of tyrosinase inhibitory activity, the main active compound was isolated and purified from 50% methanol extract of pine needles of C. deodara through macroporous resin Diaion HP-20 column chromatography and high-performance liquid chromatography. Based on mass and nuclear magnetic resonance data, the active compound was identified as 2R,3R-dihydromyricetin, which showed the potent monophenolase and diphenolase inhibitory activities. Moreover, 2R,3R-dihydromyricetin exhibited a strong ABTS radical scavenging activity with a dose-dependent manner. The antibrowning efficacy of 2R,3R-dihydromyricetin was evaluated by monitoring the changes of L*, a*, and b* values and total color difference (△E) on fresh-cut apple slices. It was found that 2R,3R-dihydromyricetin was effective in inhibiting the browning of apple slices treated with a concentration as low as 0.05% at 25 °C for 24 h. Its antibrowning effect was significantly better than ascorbic acid (0.5%) alone. Furthermore, 2R,3R-dihydromyricetin showed a good synergistic antibrowning effect with ascorbic acid. This is the first report that 2R,3R-dihydromyricetin from pine needles of C. deodara may be used as a potential antibrowning agent in protecting against food browning. PMID:25163933

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

    NASA Astrophysics Data System (ADS)

    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.

  1. An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution.

    PubMed

    Williams, Christopher; Hoppe, Hans-Jürgen; Rezgui, Dellel; Strickland, Madeleine; Forbes, Briony E; Grutzner, Frank; Frago, Susana; Ellis, Rosamund Z; Wattana-Amorn, Pakorn; Prince, Stuart N; Zaccheo, Oliver J; Nolan, Catherine M; Mungall, Andrew J; Jones, E Yvonne; Crump, Matthew P; Hassan, A Bassim

    2012-11-30

    Placental development and genomic imprinting coevolved with parental conflict over resource distribution to mammalian offspring. The imprinted genes IGF2 and IGF2R code for the growth promoter insulin-like growth factor 2 (IGF2) and its inhibitor, mannose 6-phosphate (M6P)/IGF2 receptor (IGF2R), respectively. M6P/IGF2R of birds and fish do not recognize IGF2. In monotremes, which lack imprinting, IGF2 specifically bound M6P/IGF2R via a hydrophobic CD loop. We show that the DNA coding the CD loop in monotremes functions as an exon splice enhancer (ESE) and that structural evolution of binding site loops (AB, HI, FG) improved therian IGF2 affinity. We propose that ESE evolution led to the fortuitous acquisition of IGF2 binding by M6P/IGF2R that drew IGF2R into parental conflict; subsequent imprinting may then have accelerated affinity maturation. PMID:23197533

  2. Modulation of bitter taste perception by a small molecule hTAS2R antagonist

    PubMed Central

    Slack, Jay P.; Brockhoff, Anne; Batram, Claudia; Menzel, Susann; Sonnabend, Caroline; Born, Stephan; Galindo, Maria Mercedes; Kohl, Susann; Thalmann, Sophie; Ostopovici-Halip, Liliana; Simons, Christopher T.; Ungureanu, Ioana; Duineveld, Kees; Bologa, Cristian G.; Behrens, Maik; Furrer, Stefan; Oprea, Tudor I.; Meyerhof, Wolfgang

    2010-01-01

    Summary Human bitter taste is mediated by the hTAS2R family of G protein-coupled receptors [1-4]. The discovery of the hTAS2Rs enables the potential to develop specific bitter receptor antagonists that could be beneficial as chemical probes to examine the role of bitter receptor function in gustatory and non-gustatory tissues. In addition, they could have widespread utility in food and beverages fortified with vitamins, antioxidants and other nutraceuticals since many of these have unwanted bitter aftertastes. We employed a high-throughput screening approach to discover a novel bitter receptor antagonist (GIV3727) that inhibits activation of hTAS2R31 by saccharin and acesulfame K, two common artificial sweeteners. Pharmacological analyses revealed that GIV3727 likely acts as an orthosteric, insurmountable antagonist of hTAS2R31. Surprisingly, we also found that this compound could inhibit five additional hTAS2Rs, including the closely related receptor hTAS2R43. Molecular modeling and site-directed mutagenesis studies suggest that two residues in helix seven are important for antagonist activity in hTAS2R43/31. In human sensory trials, GIV3727 significantly reduced the bitterness associated with the two sulphonamide sweeteners, indicating that TAS2R antagonists are active in vivo. Our results demonstrate that small molecule bitter receptor antagonists can effectively reduce the bitter taste qualities of foods, beverages, and pharmaceuticals. PMID:20537538

  3. PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis

    PubMed Central

    Cheng, Yong-Sheng; Seibert, Oksana; Klöting, Nora; Dietrich, Arne; Straßburger, Katrin; Fernández-Veledo, Sonia; Vendrell, Joan J.; Zorzano, Antonio; Blüher, Matthias; Herzig, Stephan; Berriel Diaz, Mauricio; Teleman, Aurelio A.

    2015-01-01

    In mammals, the liver plays a central role in maintaining carbohydrate and lipid homeostasis by acting both as a major source and a major sink of glucose and lipids. In particular, when dietary carbohydrates are in excess, the liver converts them to lipids via de novo lipogenesis. The molecular checkpoints regulating the balance between carbohydrate and lipid homeostasis, however, are not fully understood. Here we identify PPP2R5C, a regulatory subunit of PP2A, as a novel modulator of liver metabolism in postprandial physiology. Inactivation of PPP2R5C in isolated hepatocytes leads to increased glucose uptake and increased de novo lipogenesis. These phenotypes are reiterated in vivo, where hepatocyte specific PPP2R5C knockdown yields mice with improved systemic glucose tolerance and insulin sensitivity, but elevated circulating triglyceride levels. We show that modulation of PPP2R5C levels leads to alterations in AMPK and SREBP-1 activity. We find that hepatic levels of PPP2R5C are elevated in human diabetic patients, and correlate with obesity and insulin resistance in these subjects. In sum, our data suggest that hepatic PPP2R5C represents an important factor in the functional wiring of energy metabolism and the maintenance of a metabolically healthy state. PMID:26440364

  4. Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.

    PubMed

    Loveday, Chey; Tatton-Brown, Katrina; Clarke, Matthew; Westwood, Isaac; Renwick, Anthony; Ramsay, Emma; Nemeth, Andrea; Campbell, Jennifer; Joss, Shelagh; Gardner, McKinlay; Zachariou, Anna; Elliott, Anna; Ruark, Elise; van Montfort, Rob; Rahman, Nazneen

    2015-09-01

    Overgrowth syndromes comprise a group of heterogeneous disorders characterised by excessive growth parameters, often in association with intellectual disability. To identify new causes of human overgrowth, we have been undertaking trio-based exome sequencing studies in overgrowth patients and their unaffected parents. Prioritisation of functionally relevant genes with multiple unique de novo mutations revealed four mutations in protein phosphatase 2A (PP2A) regulatory subunit B family genes protein phosphatase 2, regulatory Subunit B', beta (PPP2R5B); protein phosphatase 2, regulatory Subunit B', gamma (PPP2R5C); and protein phosphatase 2, regulatory Subunit B', delta (PPP2R5D). This observation in 3 related genes in 111 individuals with a similar phenotype is greatly in excess of the expected number, as determined from gene-specific de novo mutation rates (P = 1.43 × 10(-10)). Analysis of exome-sequencing data from a follow-up series of overgrowth probands identified a further pathogenic mutation, bringing the total number of affected individuals to 5. Heterozygotes shared similar phenotypic features including increased height, increased head circumference and intellectual disability. The mutations clustered within a region of nine amino acid residues in the aligned protein sequences (P = 1.6 × 10(-5)). We mapped the mutations onto the crystal structure of the PP2A holoenzyme complex to predict their molecular and functional consequences. These studies suggest that the mutations may affect substrate binding, thus perturbing the ability of PP2A to dephosphorylate particular protein substrates. PP2A is a major negative regulator of v-akt murine thymoma viral oncogene homolog 1 (AKT). Thus, our data further expand the list of genes encoding components of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signalling cascade that are disrupted in human overgrowth conditions. PMID:25972378

  5. Vibrational relaxation of a triatomic molecular impurity: D{sub 2}O in vitreous As{sub 2}S{sub 3}

    SciTech Connect

    Rella, C.W.; Schwettman, H.A.; Engholm, J.R.

    1995-12-31

    Measurements of the relaxation of the D{sub 2}O stretch mode in vitreous As{sub 2}S{sub 3} are presented. Because the bending mode of the molecule offers an intra-molecular decay channel for the stretch mode, the decay scheme of the D{sub 2}O molecule is more complex than that of diatomic molecules. The asymmetric stretch mode of D{sub 2}O has a frequency of 2680 cm{sup -1}. To study the relaxation of this mode we applied a pump-probe technique, using intense psec; pulses of the Stanford Free Electron Laser. Due to the small cross-section of the vibrational mode, successful efforts were made to improve the signal to noise ratio by using a laser stabilization system and a tightly focused beam to increase the intensity, by averaging the signal with a kHz repetition rate and by using samples with an optimized D{sub 2}O concentration. A rapid relaxation rate on the order of 5 x 10{sup 9} sec{sup -1} at low temperature is found that increases with temperature. Recalling that the bending mode of the D{sub 2}O molecule has a frequency of 1170 cm{sup -1}, one would expect a decay in a third order process, involving two quanta of the bending mode plus a vibrational host quanta with a frequency of 340 cm{sup -1}, which coincides with a fundamental frequency of the pyramidal building blocks of the glassy As{sub 2}S{sub 3} host. Instead, we find from the temperature dependence of the relaxation rate that the D{sub 2}O stretching mode relaxes in a higher order process. This indicates that the relaxation dynamics of small molecules is more complex than generally assumed.

  6. Anti-PLA2R Antibodies in Chinese Patients with Membranous Nephropathy

    PubMed Central

    Li, Xin; Wei, Dong; Zhou, Zhanmei; Wang, Baoguo; Xu, Ya; Pan, Jie; Yang, Chunli; Lu, Jie; Qiu, Yurong

    2016-01-01

    Background This study used 2 standardized methods to evaluate anti-PLA2R antibody in sera of Chinese patients with primary membranous nephropathy (PMN) and to determine whether immunological reactivity reflected by antibody titer correlates with kidney function parameters. Material/Methods Overall, 82 subjects with biopsy-proven primary membranous nephropathy (PMN), 22 cases with secondary membranous nephropathy (SMN), 40 non-MN patients with established glomerulonephritis, and 20 healthy volunteers were recruited from the Division of Nephrology, Nanfang Hospital, China. Anti-PLA2R antibody in the serum of each patient was evaluated by both recombinant cell-based indirect immunofluorescence assay (RC-IFA) and enzyme-linked immunosorbent assay (ELISA). Kidney function was assessed by proteinuria for 24 hours, serum albumin, blood urea nitrogen (BUN), serum creatine, and serum cystatin C. We assessed the correlation between anti-PLA2R antibody levels and clinical parameters in the PMN patients. Results Fifty-three patients with PMN (64.6%) were positive for anti-PLA2R antibody. The level of antibody determined by RC-IFA ranged from 1: 10 to 1: 1000 and 0 to 1423 RU/ml by ELISA. The 2 anti-PLA2R test systems correlated very well with each other and reached an agreement of 95.7% for PMN patients. The level of antibody detected by ELISA in patients with PMN was also significantly correlated with proteinuria and nephritic-range proteinuria (>3.5 g/day). Conclusions Anti-PLA2R antibody is sensitive and extremely specific for diagnosis of Chinese patients with primary membranous nephropathy. Concentration of autoantibody against PLA2R may be an ideal marker for monitoring the activity of immunological disease. PMID:27179439

  7. Soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease: outcome and clinical implications.

    PubMed Central

    Viviani, S.; Camerini, E.; Bonfante, V.; Santoro, A.; Balzarotti, M.; Fornier, M.; Devizzi, L.; Verderio, P.; Valagussa, P.; Bonadonna, G.

    1998-01-01

    The aim of this study was to assess the prognostic role of soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease (HD) both in the achievement of complete remission (CR) and in predicting disease relapse. Between August 1988 and June 1993 sIL-2R serum levels were measured in 174 untreated patients; in 137 of them evaluation was repeated at the end of treatment and in 132 also during the follow-up. Baseline sIL-2R levels (mean+/-standard error) were significantly higher in patients than in 65 healthy control subjects (1842+/-129 U ml(-1) vs 420+/-10 U ml(-10, P< 0.0001). At the end of treatment 135 out of 137 evaluated patients achieved complete response (CR) and their mean sIL-2R serum levels were significantly lower than those at diagnosis (635+/-19 U ml(-1) vs 1795+/-122 U ml(-1), P=0.0001). After a median follow-up of 5 years, sIL-2R remained low in 114 patients in continuous CR, while they increased in 9 out of 12 patients (75%) who relapsed. However, a temporary increase was also observed in six patients (5%) still in CR. Treatment outcome in terms of freedom from progression was linearly related to sIL-2R levels. Our study confirms that patients with untreated HD have increased baseline levels of sIL-2R compared with healthy subjects and that their pretreatment values may be an indication of disease outcome similar to other conventional prognostic factors, such as number of involved sites, presence of B symptoms and extranodal extent. PMID:9528846

  8. Reactivity of C{sub 10}H{sub 7}{sup +} and C{sub 10}D{sub 7}{sup +} with H{sub 2} and D{sub 2}

    SciTech Connect

    Ascenzi, D.; Bassi, D.; Franceschi, P.; Hadjar, O.; Tosi, P.; Di Stefano, M.; Rosi, M.; Sgamellotti, A.

    2004-10-08

    We have investigated, both theoretically and experimentally, the reactions of naphthylium C{sub 10}H{sub 7}{sup +} and d-naphthylium C{sub 10}D{sub 7}{sup +} ions with H{sub 2} and D{sub 2}. Cross sections as functions of the collision energy have been measured for a variety of reaction channels. Theoretical calculations have been carried out at the density functional theory level which utilizes the hybrid functional B3LYP and the split-valence 6-31G* basis set. The key features of the potential energy surfaces and the relevant thermochemical parameters have been calculated and they provide insights on the reaction mechanisms. The bimolecular reactivity of C{sub 10}H{sub 7}{sup +} with H{sub 2} is dominated by the production of naphthalene cation C{sub 10}H{sub 8}{sup +}. The reaction is not a direct atom-abstraction process, but instead it proceeds via the formation of a stable intermediate complex C{sub 10}H{sub 9}{sup +} of {sigma} type geometry, with a significant mobility of hydrogen along the ring. This mobility allows the scrambling of the hydrogen atoms and causes the successive statistical fragmentation of the complex into a variety of product channels. Elimination of one H(D) atom appears to be favored over elimination of one H{sub 2} or HD molecule. Alternatively, the intermediate complex can be stabilized either by collision with a third body or by emission of a photon.

  9. Finite density of states in a mixed state of a d{sub x{sup 2}{minus}y{sup 2}}+id{sub xy} superconductor

    SciTech Connect

    Mao, W.; Balatsky, A.V.

    1999-03-01

    We have calculated the density of states of quasiparticles in a d{sub x{sup 2}{minus}y{sup 2}}+id{sub xy} superconductor, and show that in the mixed state the quasiparticle spectrum remains gapless because of the Doppler shift by superflow. It was found that if the d{sub xy} order gap {Delta}{sub 1}{proportional_to}{radical} (H) as suggested by experiments, then thermal conductivity {kappa}{proportional_to}{radical} (H) in accord with experimental data at lowest temperatures. {copyright} {ital 1999} {ital The American Physical Society}

  10. Imprinting of opossum Igf2r in the absence of differential methylation and air.

    PubMed

    Weidman, Jennifer R; Dolinoy, Dana C; Maloney, Kristin A; Cheng, Jan-Fang; Jirtle, Randy L

    2006-01-01

    Phylogenetic comparison of extant mammals with divergent imprint status is a powerful method for identifying critical components of imprint regulation at individual loci. The entire genomic region of Igf2r in the imprinted marsupials, Didelphis virginiana and Monodelphis domestica, and the non-imprinted monotreme, Ornithorhynchus anatinus, was isolated and sequenced. Genetic and epigenetic comparisons of over 160 kb of sequence were then performed in five distinct mammalian species. Surprisingly, opossum Igf2r is imprinted and maternally expressed despite the absence of the intron 2 CpG island (CpG2), antisense Igf2r RNA (Air) and differential methylation of the promoter (CpG1) required for imprinting of this gene in mice. These findings demonstrate that the genomic elements necessary for imprinted Igf2r expression in eutherians are not required for imprinting of this locus in metatherians. Thus, the regulatory mechanisms of Igf2r imprinting did not evolve convergently within the Therian subclass of mammals. PMID:17998818

  11. The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14.

    PubMed

    Levit, Anat; Nowak, Stefanie; Peters, Maximilian; Wiener, Ayana; Meyerhof, Wolfgang; Behrens, Maik; Niv, Masha Y

    2014-03-01

    Bitter taste receptors (TAS2Rs) mediate aversive response to toxic food, which is often bitter. These G-protein-coupled receptors are also expressed in extraoral tissues, and emerge as novel targets for therapeutic indications such as asthma and infection. Our goal was to identify ligands of the broadly tuned TAS2R14 among clinical drugs. Molecular properties of known human bitter taste receptor TAS2R14 agonists were incorporated into pharmacophore- and shape-based models and used to computationally predict additional ligands. Predictions were tested by calcium imaging of TAS2R14-transfected HEK293 cells. In vitro testing of the virtual screening predictions resulted in 30-80% success rates, and 15 clinical drugs were found to activate the TAS2R14. hERG potassium channel, which is predominantly expressed in the heart, emerged as a common off-target of bitter drugs. Despite immense chemical diversity of known TAS2R14 ligands, novel ligands and previously unknown polypharmacology of drugs were unraveled by in vitro screening of computational predictions. This enables rational repurposing of traditional and standard drugs for bitter taste signaling modulation for therapeutic indications. PMID:24285091

  12. Assessment of cholecystokinin 2 receptor (CCK2R) in neoplastic tissue

    PubMed Central

    Roy, Jyoti; Putt, Karson S.; Coppola, Domenico; Leon, Marino E.; Khalil, Farah K.; Centeno, Barbara A.; Clark, Noel; Stark, Valerie E.; Morse, David L.; Low, Philip S.

    2016-01-01

    The expression of cholecystokinin 2 receptor (CCK2R, CCKBR or gastrin receptor) has been reported on a diverse range of cancers such as colorectal, liver, lung, pancreatic, ovarian, stomach, thyroid and numerous neuroendocrine/carcinoid tumors. Some cancers of the colorectum, lung, pancreas and thyroid have been shown to overexpress CCK2R in relation to normal matched tissues of the same organ. This reported overexpression has led to the development of a number of CCK2R-ligand targeted imaging and therapeutic agents. However, no comprehensive study comparing the expression of CCK2R in multiple cancers to multiple normal tissues has been performed. Herein, we report the immunohistochemical analysis of cancer samples from gastrointestinal stromal tumor (GIST), hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC), pancreatic adenocarcinoma, and thyroid cancer against multiple normal tissue samples from esophagus, liver, lung, pancreas, stomach, spleen and thyroid. These results show that CCK2R expression is present in nearly all cancer and normal samples tested and that none of the cancer samples had expression that was statistically greater than that of all of the normal samples. PMID:26910279

  13. SL(2,R) duality-symmetric action for electromagnetic theory with electric and magnetic sources

    SciTech Connect

    Lee, Choonkyu; Min, Hyunsoo

    2013-12-15

    For the SL(2,R) duality-invariant generalization of Maxwell electrodynamics in the presence of both electric and magnetic sources, we formulate a local, manifestly duality-symmetric, Zwanziger-type action by introducing a pair of four-potentials A{sup μ} and B{sup μ} in a judicious way. On the two potentials A{sup μ} and B{sup μ} the SL(2,R) duality transformation acts in a simple linear manner. In quantum theory including charged source fields, this action can be recast as a SL(2,Z)-invariant action. Also given is a Zwanziger-type action for SL(2,R) duality-invariant Born–Infeld electrodynamics which can be important for D-brane dynamics in string theory. -- Highlights: •We formulate a local, manifestly duality-symmetric, Zwanziger-type action. •Maxwell electrodynamics is generalized to include dilaton and axion fields. •SL(2,R) symmetry is manifest. •We formulate a local, manifestly duality-symmetric, nonlinear Born–Infeld action with SL(2,R) symmetry.

  14. Lack of association between obsessive-compulsive disorder and the dopamine D{sub 3} receptor gene: Some preliminary considerations

    SciTech Connect

    Catalano, M.; Sciuto, G.; Di Bella, D.

    1994-09-15

    Controversial results possibly suggesting an association between Tourette`s syndrome (TS) and excess of homozygosity at an Msc I polymorphism in the Dopamine D{sub 3} receptor (DRD{sub 3}) gene have recently been reported. Since a relationship between obsessive-compulsive disorder (OCD) and Tourette`s syndrome (TS) has been suggested, in this study we assessed the frequency of this 2-allele polymorphism in a sample of 97 OCD patients and in 97 control subjects. No statistically significant differences in allele or genotype frequencies were found. Thus this mutation in the coding sequence of the DRD{sub 3} gene is unlikely to confer susceptibility to OCD. 28 refs., 21 tabs.

  15. Multiphoton fragmentation of H{sub 2}{sup +} and D{sub 2}{sup +} with coherent and incoherent fields

    SciTech Connect

    Miret-Artes, S.; Micha, D.A.

    1995-10-01

    A theory of molecular photofragmentation is developed for coherent and incoherent light and for the case where dissociation lifetimes of field-induced resonances are shorter than pulse lengths. Using a mixed representation for the transition operator (a description of the initial state of the field with the coherent representation and of the final state with the number representation), we show how observables are modified at different field regimes by Poisson distributions. Applications to H{sub 2}{sup +} and D{sub 2}{sup +} are presented and discussed. They include line shapes and final distributions of kinetic energies for weak, intermediate, and strong fields. Results show that the interference of resonance states plays an important role even after averages over the field phases have been carried out to account for incoherent effects.

  16. Doppler-free spectroscopy on the Cs D>1 line with a dual-frequency laser.

    PubMed

    Hafiz, Moustafa Abdel; Coget, Grégoire; De Clercq, Emeric; Boudot, Rodolphe

    2016-07-01

    We report on Doppler-free laser spectroscopy in a Cs vapor cell using a dual-frequency laser system tuned on the Cs D>1 line. Using counter-propagating beams with crossed linear polarizations, an original sign reversal of the usual saturated absorption dip and large increase in Doppler-free atomic absorption is observed. This phenomenon is explained by coherent population trapping (CPT) effects. The impact of laser intensity and light polarization on absorption profiles is reported in both single-frequency and dual-frequency regimes. In the latter, frequency stabilization of two diode lasers was performed, yielding a beat note fractional frequency stability at the level of 3×10-12 at 1 s averaging time. These performances are about an order of magnitude better than those obtained using a conventional single-frequency saturated absorption scheme. PMID:27367081

  17. Probing Majorana neutrinos in rare K and D, D{sub s}, B, B{sub c} meson decays

    SciTech Connect

    Cvetic, G.; Dib, Claudio; Kang, Sin Kyu; Kim, C. S.

    2010-09-01

    We study lepton number violating decays of charged K, D, D{sub s}, B, and B{sub c} mesons of the form M{sup +}{yields}M{sup '-}l{sup +}l{sup +}, induced by the existence of Majorana neutrinos. These processes provide information complementary to neutrinoless double nuclear beta decays, and are sensitive to neutrino masses and lepton mixing. We explore neutrino mass ranges m{sub N} from below 1 eV to several hundred GeV. We find that in many cases the branching ratios are prohibitively small, however in the intermediate range m{sub {pi}<}m{sub N}

  18. Frustrated tunneling ionization during laser-induced D{sub 2} fragmentation: Detection of excited metastable D{sup *} atoms

    SciTech Connect

    McKenna, J.; Zeng, S.; Hua, J. J.; Sayler, A. M.; Zohrabi, M.; Johnson, Nora G.; Gaire, B.; Carnes, K. D.; Esry, B. D.; Ben-Itzhak, I.

    2011-10-15

    In a recent Letter, Manschwetus et al.[Phys. Rev. Lett. 102, 113002 (2009)] reported evidence of electron recapture during strong-field fragmentation of H{sub 2}--explained using a frustrated tunneling ionization model. Unusually, the signature of this process was detection of excited H{sup *} atoms. We report here an extensive study of this process in D{sub 2}. Our measurements encompass a study of the pulse duration, intensity, ellipticity, and angular distribution dependence of D{sup *} formation. While we find that the mechanism suggested by Manschwetus et al. is consistent with our experimental data, our theoretical work shows that electron recollision excitation cannot be completely ruled out as an alternative mechanism for D{sup *} production.

  19. Structural change in dopamine D{sub 2} receptor gene in a patient with neuroleptic malignant syndrome

    SciTech Connect

    Ram, A.; Cao, Q.; Gershon, E.S.

    1995-06-19

    Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome. Therefore, we examined the complete coding sequences of the dopamine D{sub 2} receptor (DRD2) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS. Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequence differences. We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG{r_arrow}TCG) of exon 7 of the DRD2 gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS. 25 refs., 1 fig.

  20. Purification, characterization, and directed evolution study of a vitamin D{sub 3} hydroxylase from Pseudonocardia autotrophica

    SciTech Connect

    Fujii, Yoshikazu; Kabumoto, Hiroki; Nishimura, Kenji; Fujii, Tadashi; Yanai, Satoshi; Takeda, Koji; Tamura, Noriko; Arisawa, Akira; Tamura, Tomohiro

    2009-07-24

    Vitamin D{sub 3} (VD{sub 3}) is a fat-soluble prohormone that plays a crucial role in bone metabolism, immunity, and control of cell proliferation and cell differentiation in mammals. The actinomycete Pseudonocardia autotrophica is capable of bioconversion of VD{sub 3} into its physiologically active forms, namely, 25(OH)VD{sub 3} or 1{alpha},25(OH){sub 2}VD{sub 3}. In this study, we isolated and characterized Vdh (vitamin D{sub 3} hydroxylase), which hydroxylates VD{sub 3} from P. autotrophica NBRC 12743. The vdh gene encodes a protein containing 403 amino acids with a molecular weight of 44,368 Da. This hydroxylase was found to be homologous with the P450 belonging to CYP107 family. Vdh had the same ratio of the V{sub max} values for VD{sub 3} 25-hydroxylation and 25(OH)VD{sub 3} 1{alpha}-hydroxylation, while other enzymes showed preferential regio-specific hydroxylation on VD{sub 3}. We characterized a collection of Vdh mutants obtained by random mutagenesis and obtained a Vdh-K1 mutant by the combination of four amino acid substitutions. Vdh-K1 showed one-order higher VD{sub 3} 25-hydroxylase activity than the wild-type enzyme. Biotransformation of VD{sub 3} into 25(OH)VD{sub 3} was successfully accomplished with a Vdh-expressed recombinant strain of actinobacterium Rhodococcus erythropolis. Vdh may be a useful enzyme for the production of physiologically active forms of VD{sub 3} by a single cytochrome P450.

  1. SO(4)-->SU(2)R global symmetry properties of six-dimensional grand-unified theories

    NASA Astrophysics Data System (ADS)

    Fayet, P.

    1987-07-01

    We exhibit a global SU(2)×SU(2)'~SO(4) invariance of six-dimensional supersymmetric GUTs. After the elctroweak breaking, this invariance gets reduced to an SU(2)R subgroup which extends the U(1) R-invariance of 6D theories and acts on the single 6D Weyl supersymmetry generator. Gauge bosons, leptons and quarks are SU(2)R isosinglets; inos, sleptons and squarks isodoublets; and Higgs bosons, generally isotriplets. The W+/- and Z masses appear, in six dimensions, as an effect of the breaking of this global SO(4) symmetry. This may provide a reason for the extremely small value of the ration mw/mGUT. The residual SU(2)R symmetry may then be used to trigger the supersymmetry breaking in four dimensions. Laboratoire Propre du Centre National de la Recherche Scientifique, associé à l'Ecole Normale Supériure et à l'Université de Paris Sud.

  2. The SO (2 r) 2 string functions as q-diagrams

    NASA Astrophysics Data System (ADS)

    Genish, Arel; Gepner, Doron

    2015-08-01

    We discuss our conjecture for simply laced Lie algebras level two string functions of mark one fundamental weights and prove it for the SO (2 r) algebra. To prove our conjecture we introduce q-diagrams and examine the diagrammatic interpretations of known identities by Euler, Cauchy, Heine, Jacobi and Ramanujan. Interestingly, the diagrammatic approach implies these identities are related in the sense that they represent the first few terms in an infinite series of diagrammatic identities. Furthermore, these diagrammatic identities entail all the identities needed to prove our conjecture as well as generalise it to all SO (2 r) level two string functions. As such, our main objective is proving these series of diagrammatic identities thus extending the works mentioned and establishing our conjecture for the SO (2 r) level two string functions.

  3. Quantum conformal mechanics emerging from unitary representations of SL(2 , R)

    NASA Astrophysics Data System (ADS)

    Andrzejewski, Krzysztof

    2016-04-01

    The quantum mechanics of one degree of freedom exhibiting the exact conformal SL(2 , R) symmetry is presented. The starting point is the classification of the unitary irreducible representations of the SL(2 , R) group (or, to some extent, its universal covering). The coordinate representation is defined as the basis diagonalizing the special conformal generator K ˆ . As a particular case one obtains the AFF (de Alfaro et al., 1976) system with positive coupling constant. It is shown that for the negative coupling the conformal quantum mechanics in AFF form can be immersed into well-defined quantum theory with global action of SL(2 , R) as a symmetry group. It is indicated how the resulting theory emerges from the canonical/geometric quantization of the Hamiltonian dynamics on the relevant coadjoint orbits.

  4. Cross-reactivity of anti-PLA2R1 autoantibodies to rabbit and mouse PLA2R1 antigens and development of two novel ELISAs with different diagnostic performances in idiopathic membranous nephropathy.

    PubMed

    Seitz-Polski, Barbara; Dolla, Guillaume; Payré, Christine; Tomas, Nicola M; Lochouarn, Marine; Jeammet, Louise; Mariat, Christophe; Krummel, Thierry; Burtey, Stéphane; Courivaud, Cécile; Schlumberger, Wolfgang; Zorzi, Kévin; Benzaken, Sylvia; Bernard, Ghislaine; Esnault, Vincent L M; Lambeau, Gérard

    2015-11-01

    About 70% of patients with idiopathic membranous nephropathy (iMN) have autoantibodies to the phospholipase A2 receptor PLA2R1. We screened sera from iMN patients for their cross-reactivity to human (h), rabbit (rb) and mouse (m) PLA2R1 by western blot (WB) and antigen-specific ELISAs. All iMN patients recognized hPLA2R1 and rbPLA2R1 by WB, and a rbPLA2R1 ELISA was as sensitive as the standardized hPLA2R1 ELISA to monitor anti-PLA2R1 in patients with active disease or in drug-induced remission. In contrast, only 51% of patients were reactive to mPLA2R1 by WB, and a maximum of 78% were weakly to highly positive in the mPLA2R1 ELISA, suggesting that iMN patients exhibit different subsets of anti-PLA2R1 autoantibodies against epitopes that are shared or not among PLA2R1 orthologs. In a cohort of 41 patients with a mean follow-up of 42 months from anti-PLA2R1 assay, the detection of anti-mPLA2R1 autoantibodies was an independent predictor of clinical outcome in multivariate analysis (p = 0.009), and a ROC curve analysis identified a threshold of 605 RU/mL above which 100% of patients (12 patients) had a poor renal outcome (p < 0.001). A similar threshold could not be defined in hPLA2R1 and rbPLA2R1 ELISAs. We conclude that rbPLA2R1 is an alternative antigen to hPLA2R1 to measure anti-PLA2R1 in active disease while mPLA2R1 is a unique antigen that can detect a subset of anti-PLA2R1 autoantibodies present at high levels (>605 RU/mL) only in iMN patients at risk of poor prognosis, and is thus useful to predict iMN outcome. PMID:26296473

  5. IGF-2R-mediated signaling results in hypertrophy of cultured cardiomyocytes from fetal sheep.

    PubMed

    Wang, Kimberley C W; Brooks, Doug A; Botting, Kimberley J; Morrison, Janna L

    2012-06-01

    Activation of the insulin-like growth factor-1 receptor (IGF-1R) is known to play a role in cardiomyocyte hypertrophy. While IGF-2R is understood to be a clearance receptor for IGF-2, there is also evidence that it may play a role in the induction of pathological cardiomyocyte hypertrophy. It is not known whether IGF-2R activates cardiomyocyte hypertrophy during growth of the fetal heart. Fetal sheep hearts (125 ± 0.4 days gestation) were dissected, and the cardiomyocytes isolated from the left and right ventricles for culturing. Cultured cardiomyocytes were treated with either LONG R(3)IGF-1, an IGF-1R agonist; picropodophyllin, an IGF-1R autophosphorylation inhibitor; U0126, an inhibitor of extracellular signal-regulated protein kinase (ERK); Leu(27)IGF-2, an IGF-2R agonist; Gö6976, a protein kinase C inhibitor; KN-93, an inhibitor of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII); or KN-92, an L-type calcium channel inhibitor and negative control for KN-93. The cross-sectional area of cultured cardiomyocytes was determined relative to control cardiomyocytes treated with serum-free culture medium. IGF-1R and IGF-2R activation each resulted in ERK signaling, but IGF-2R activation alone induced CaMKII signaling, resulting in hypertrophy of cardiomyocytes in the late gestation sheep fetus. These data suggest that changes in the intrauterine environment that result in increased cardiac IGF-2R may also lead to cardiomyocyte hypertrophy in the fetus and potentially an increased risk of cardiovascular disease in adult life. PMID:22441800

  6. Rolling Deck to Repository (R2R): Automated Magnetic and Gravity Quality Assessment and Data Reduction

    NASA Astrophysics Data System (ADS)

    Morton, J. J.; O'Hara, S.; Ferrini, V.; Arko, R. A.

    2010-12-01

    With its global capability and diverse array of sensors, the academic research fleet is an integral component of ocean exploration. The Rolling Deck to Repository (R2R) Program provides a central shore-side gateway for underway data from the U.S. academic research fleet. In addition to ensuring preservation and documentation of routine underway data, R2R is also developing automated quality assessment (QA) tools for a variety of underway data types. Routine post-cruise QA will enable prompt feedback to shipboard operators and to provide the science community with sufficient background information for data analysis. Based on community feedback, R2R will perform data reduction to generate enhanced data products for select data types including gravity and magnetics. In the development of these tools, R2R seeks input from the scientific community, engaging specialists for each data type and requesting feedback from operators and scientists to deliver the most relevant and useful metadata. Development of data acquisition best practices that are being assembled within the community for some data types will also be important components of R2R QA development. Protocols for gravity and magnetics QA will include the development of guidelines for minimal and optimal metadata for each data type that will enable data reduction and optimize data re-use. Metadata including instrument specifications, navigational offsets, and calibration information will be important inputs for both data reduction and QA. Data reduction will include merging these geophysical data types with high-quality R2R-generated navigation data products, cleaning the data and applying instrument corrections. Automated routines that are being developed will then be used to assess data quality, ultimately producing a Quality Assessment Certificate (QAC) that will provide the science community with quality information in an easily accessible and understandable format. We present progress to date and invite

  7. In vivo inflammation imaging using a CB2R-targeted near infrared fluorescent probe

    PubMed Central

    Zhang, Shaojuan; Shao, Pin; Ling, Xiaoxi; Yang, Ling; Hou, Weizhou; Thorne, Steve H; Beaino, Wissam; Anderson, Carolyn J; Ding, Ying; Bai, Mingfeng

    2015-01-01

    Chronic inflammation is considered as a critical cause of a host of disorders, such as cancer, rheumatoid arthritis, atherosclerosis, and neurodegenerative diseases, although the exact mechanism is yet to be explored. Imaging tools that can specifically target inflammation are therefore important to help reveal the role of inflammation in disease progression, and allows for developing new therapeutic strategies to ultimately improve patient care. The purpose of this study was to develop a new in vivo inflammation imaging approach by targeting the cannabinoid receptor type 2 (CB2R), an emerging inflammation biomarker, using a unique near infrared (NIR) fluorescent probe. Herein, we report the first in vivo CB2R-targeted NIR inflammation imaging study using a synthetic fluorescent probe developed in our laboratory, NIR760-mbc94. In vitro binding assay and fluorescence microscopy study indicate NIR760-mbc94 specifically binds towards CB2R in mouse RAW264.7 macrophage cells. Furthermore, in vivo imaging was performed using a Complete Freund’s Adjuvant (CFA)-induced inflammation mouse model. NIR760-mbc94 successfully identified inflamed tissues and the probe uptake was blocked by a CB2R ligand, SR144528. Additionally, immunofluorescence staining in cryosectioned tissues validated the NIR760-mbc94 uptake in inflamed tissues. In conclusion, this study reports the first in vivo CB2R-targeted inflammation imaging using an NIR fluorescent probe. Specific targeting of NIR760-mbc94 has been demonstrated in macrophage cells, as well as a CFA-induced inflammation mouse model. The combined evidence indicates that NIR760-mbc94 is a promising inflammation imaging probe. Moreover, in vivo CB2R-targeted fluorescence imaging may have potential in the study of inflammation-related diseases. PMID:26069858

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

    NASA Astrophysics Data System (ADS)

    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

  9. Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy.

    PubMed

    Seitz-Polski, Barbara; Dolla, Guillaume; Payré, Christine; Girard, Christophe A; Polidori, Joel; Zorzi, Kevin; Birgy-Barelli, Eléonore; Jullien, Perrine; Courivaud, Cécile; Krummel, Thierry; Benzaken, Sylvia; Bernard, Ghislaine; Burtey, Stéphane; Mariat, Christophe; Esnault, Vincent L M; Lambeau, Gérard

    2016-05-01

    The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR (n=23), CysRC1 (n=14), and CysRC1C7 (n=32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR-restricted activity were younger (P=0.008), had less nephrotic range proteinuria (P=0.02), and exhibited a higher rate of spontaneous remission (P=0.03) and lower rates of renal failure progression (P=0.002) and ESRD (P=0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio >4 g/g or eGFR<45 ml/min per 1.73 m(2) at end of follow-up). High anti-PLA2R1 activity and epitope spreading beyond the CysR epitope were independent risk factors of poor renal prognosis in multivariable Cox regression analysis. Epitope spreading during follow-up associated with disease worsening (n=3), whereas reverse spreading from a CysRC1C7 profile back to a CysR profile associated with favorable outcome (n=1). We conclude that analysis of the PLA2R1 epitope profile and spreading is a powerful tool for monitoring disease severity and stratifying patients by renal prognosis. PMID:26567246

  10. Screening the dopamine D{sub 1} receptor gene in 131 schizophrenics and eight alcoholics: Identification of polymorphisms but lack of functionally significant sequence changes

    SciTech Connect

    Liu, Qiang; Sommer, S.S.; Sobell, J.L.

    1995-04-24

    To determine whether mutations in the D{sub 1} dopamine receptor (D{sub 1}DR) gene are associated with schizophrenia, the coding sequence was examined in 106 Caucasian, 11 African-American, 8 Asian, and 6 Native American patients. Approximately 350 kb of genomic sequence was screened by dideoxy fingerprinting, a method related to single strand conformational polymorphism (SSCP) analysis that detects virtually 100% of sequence changes. One polymorphism was identified in Asians and one in Caucasians, but neither altered 421 the amino acid sequence (Leu{sup 66}, and Ser{sup 421}, respectively). In addition, a previously reported polymorphism in the 5{prime} untranslated region of exon 2 at bp -48 was found to be common, with an allele frequency of approximately 40% in Caucasians of Western European descent. Based on the fact that no sequence changes of likely functional significance were identified, these data suggest that mutations affecting the structure of the D{sub 1} dopamine receptor protein are uncommon and are unlikely to contribute significantly to the genetic predisposition to schizophrenia. The D{sub 1}DR gene also was examined in eight alcoholics, including 3 African-Americans and 1 Native American, but no sequence changes were identified. 35 refs., 1 fig., 3 tabs.

  11. Recalculation of the Critical Size and Multiplication Constant of a Homogeneous UO{sub 2}-D{sub 2}O Mixtures

    DOE R&D Accomplishments Database

    Wigner, E. P.; Weinberg, A. M.; Stephenson, J.

    1944-02-11

    The multiplication constant and optimal concentration of a slurry pile is recalculated on the basis of Mitchell's experiments on resonance absorption. The smallest chain reacting unit contains 45 to 55 m{sup 3}of d{sub 2}O. (auth).

  12. Recalculation of the Critical Size and Multiplication Constant of a Homogeneous UO{sub 2} - D{sub 2}O Mixtures

    DOE R&D Accomplishments Database

    Wigner, E. P.; Weinberg, A. M.; Stephenson, J.

    1944-02-11

    The multiplication constant and optimal concentration of a slurry pile is recalculated on the basis of Mitchell`s experiments on resonance absorption. The smallest chain reacting unit contains 45 to 55 m{sup 3}of D{sub 2}O. (auth)

  13. MODEL-INDEPENDENT DETERMINATION OF CURVATURE PARAMETER USING H(z) AND D{sub A} (z) DATA PAIRS FROM BAO MEASUREMENTS

    SciTech Connect

    Li, Yun-Long; Li, Ti-Pei; Li, Shi-Yu; Zhang, Tong-Jie

    2014-07-01

    We present a model-independent determination of the curvature parameter Ω {sub k} using the Hubble parameter H(z) and the angular diameter distance D{sub A} (z) from recent baryon acoustic oscillation (BAO) measurements. Each H(z) and D{sub A} (z) pair from a BAO measurement can constrain a curvature parameter. The accuracy of the curvature measurement improves with increased redshift of H(z) and D{sub A} (z) data. By using the H(z) and D{sub A} (z) pair derived from a BAO Lyman α forest measurement at z = 2.36, the Ω {sub k} is confined to be –0.05 ± 0.06, which is consistent with the curvature of −0.037{sub −0.042}{sup +0.044} constrained by the nine year Wilkinson Microwave Anisotropy Probe data only. Considering future BAO measurements, at least one order of magnitude improvement of this curvature measurement can be expected.

  14. New integrable sl (2, R) -generalization of the classical Wadati-Konno-Ichikawa hierarchy

    NASA Astrophysics Data System (ADS)

    Zhu, Haiyan; Yu, Shuimeng; Shen, Shoufeng; Ma, Wen-Xiu

    2015-05-01

    With the aid of symbolic computation by Maple, a new integrable generalization of the classical Wadati-Konno-Ichikawa hierarchy is derived from a corresponding matrix spectral problem associated with the Lie algebra sl (2, R) . Each equation in the resulting hierarchy has a bi-Hamiltonian structure furnished by the trace identity, and possesses infinitely many independent commuting symmetries and conservation laws.

  15. Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal

    PubMed Central

    Risso, Davide S.; Mezzavilla, Massimo; Pagani, Luca; Robino, Antonietta; Morini, Gabriella; Tofanelli, Sergio; Carrai, Maura; Campa, Daniele; Barale, Roberto; Caradonna, Fabio; Gasparini, Paolo; Luiselli, Donata; Wooding, Stephen; Drayna, Dennis

    2016-01-01

    The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes. PMID:27138342

  16. Ricci curvature of Diff S/sup 1//SL(2,R)

    SciTech Connect

    Bowick, M.J.; Lahiri, A.

    1988-09-01

    Previous calculations of the Ricci curvature for the manifold Diff Diff(S/sup 1/)/S/sup 1/ are extended to Diff(S/sup 1/)/SL(2R). These manifolds are distinguished by being coadjoint orbits of Diff(S/sup 1/) which admit compatible symphectic and complex structures, making them Kaehler manifolds.

  17. Evaluation of Mecp2(R308/Y) mutant mice as a model to study fetal programming

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA (CpG) methylation is altered at candidate loci after prenatal modification of dietary methyl donor supply. Mecp2(R308/Y) mutant mice, with a truncating mutation of the methyl-CpG-binding protein 2 gene which models Rett syndrome, have increased weight gain on a high methyl donor diet. Rett syndr...

  18. Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal.

    PubMed

    Risso, Davide S; Mezzavilla, Massimo; Pagani, Luca; Robino, Antonietta; Morini, Gabriella; Tofanelli, Sergio; Carrai, Maura; Campa, Daniele; Barale, Roberto; Caradonna, Fabio; Gasparini, Paolo; Luiselli, Donata; Wooding, Stephen; Drayna, Dennis

    2016-01-01

    The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes. PMID:27138342

  19. Angiotensin II type 2 receptor (AT2R) in renal and cardiovascular disease.

    PubMed

    Chow, Bryna S M; Allen, Terri J

    2016-08-01

    Angiotensin II (Ang II) is well-considered to be the principal effector of the renin-angiotensin system (RAS), which binds with strong affinity to the angiotensin II type 1 (AT1R) and type 2 (AT2R) receptor subtype. However, activation of both receptors is likely to stimulate different signalling mechanisms/pathways and produce distinct biological responses. The haemodynamic and non-haemodynamic effects of Ang II, including its ability to regulate blood pressure, maintain water-electrolyte balance and promote vasoconstriction and cellular growth are well-documented to be mediated primarily by the AT1R. However, its biological and functional effects mediated through the AT2R subtype are still poorly understood. Recent studies have emphasized that activation of the AT2R regulates tissue and organ development and provides in certain context a potential counter-regulatory mechanism against AT1R-mediated actions. Thus, this review will focus on providing insights into the biological role of the AT2R, in particular its actions within the renal and cardiovascular system. PMID:27358027

  20. Cataloging with AACR2R and USMARC: For Books, Computer Files, Serials, Sound Recordings, Videorecordings.

    ERIC Educational Resources Information Center

    Fritz, Deborah A.

    Machine-Readable Cataloging (MARC) is the dominant format for the bibliographic cataloging of all types of library materials. This source cross references "Anglo-American Cataloging Rules, 2nd ed., 1988 revision" (AACR2R), MARC tags/subfields, and interpretations for Library of Congress rules for each of the major media categories. This book…

  1. 6-Methoxyflavanones as Bitter Taste Receptor Blockers for hTAS2R39

    PubMed Central

    Roland, Wibke S. U.; Gouka, Robin J.; Gruppen, Harry; Driesse, Marianne; van Buren, Leo; Smit, Gerrit; Vincken, Jean-Paul

    2014-01-01

    Many (dietary) bitter compounds, e.g. flavonoids, activate bitter receptor hTAS2R39 in cell-based assays. Several flavonoids, amongst which some flavanones, are known not to activate this receptor. As certain flavanones are known to mask bitter taste sensorially, flavanones might act as bitter receptor antagonists. Fourteen flavanones were investigated for their potential to reduce activation of hTAS2R39 by epicatechin gallate (ECG), one of the main bitter compounds occurring in green tea. Three flavanones showed inhibitory behavior towards the activation of hTAS2R39 by ECG: 4′-fluoro-6-methoxyflavanone, 6,3′-dimethoxyflavanone, and 6-methoxyflavanone (in order of decreasing potency). The 6-methoxyflavanones also inhibited activation of hTAS2R14 (another bitter receptor activated by ECG), though to a lesser extent. Dose-response curves of ECG at various concentrations of the full antagonist 4′-fluoro-6-methoxyflavanone and wash-out experiments indicated reversible insurmountable antagonism. The same effect was observed for the structurally different agonist denatonium benzoate. PMID:24722342

  2. Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal

    NASA Astrophysics Data System (ADS)

    Risso, Davide S.; Mezzavilla, Massimo; Pagani, Luca; Robino, Antonietta; Morini, Gabriella; Tofanelli, Sergio; Carrai, Maura; Campa, Daniele; Barale, Roberto; Caradonna, Fabio; Gasparini, Paolo; Luiselli, Donata; Wooding, Stephen; Drayna, Dennis

    2016-05-01

    The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes.

  3. Subspecialization of R2R3-MYB Repressors for Anthocyanin and Proanthocyanidin Regulation in Forage Legumes

    PubMed Central

    Albert, Nick W.

    2015-01-01

    The synthesis of anthocyanin pigments and proanthocyanidins (condensed tannins) is regulated by MYB-bHLH-WDR (MBW) transcription factor complexes in all angiosperms studied to date. Tr-MYB133 and Tr-MYB134 were isolated from Trifolium repens and encode R2R3-MYBs that antagonize the activity of MBW activation complexes. These two genes are conserved in other legume species, and form two sub-clades within the larger anthocyanin/proanthocyanidin clade of MYB repressors. However, unlike petunia and Arabidopsis, these R2R3-MYB repressors do not prevent ectopic accumulation of anthocyanins or proanthocyanidins. Instead, they are expressed when anthocyanins or proanthocyanidins are being synthesized, and provide feedback regulation to MBW complexes. This feedback occurs because Tr-MYB133 and Tr-MYB134 are themselves regulated by MBW complexes. Tr-MYB133 is regulated by MBW complexes containing anthocyanin-related R2R3-MYB proteins (Tr-RED LEAF), while Tr-MYB134 is regulated by complexes containing the proanthocyanidin R2R3-MYBs (Tr-MYB14). Other features of the MBW gene regulation networks are also conserved within legumes, including the ability for the anthocyanin MBW complexes to activate the expression of the AN1/TT8 clade bHLH factor. The regulation of Tr-MYB133 and Tr-MYB134 by distinct, pathway-specific MBW complexes has resulted in subspecialization for controlling anthocyanin or proanthocyanidin synthesis. PMID:26779194

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

    PubMed

    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. PMID:27408811

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

    NASA Astrophysics Data System (ADS)

    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

  6. Rolling Deck to Repository (R2R): Research Cruise Event Logging System Update

    NASA Astrophysics Data System (ADS)

    Maffei, A. R.; Chandler, C. L.; Stolp, L.

    2010-12-01

    Data gathered aboard research vessels coordinated by the University-National Oceanographic Laboratory System (UNOLS) represent an important component of the overall oceanographic data collection. The Rolling Deck to Repository (R2R) project aims to improve access to basic shipboard data and ultimately reduce the work required to provide that access. The ultimate vision of R2R is to assist in transforming the academic fleet into an integrated global observing system. One of the coordinated subprojects within the R2R project is the development of a shipboard scientific event logging system that incorporates best practice guidelines, controlled vocabularies, a cruise metadata schema, and a scientific event log. The event log application will use new and existing components to generate a digital text file with a fleet-wide agreed upon format. A cruise event logging system enables researchers to record digitally all scientific sampling events and assign a unique event identifier to each entry. Decades of work conducted within large coordinated ocean research programs (JGOFS, GLOBEC, WOCE and RIDGE) have shown that creation of a shipboard sampling event log can facilitate greatly the ingestion of these data into oceanographic repositories and subsequent integration of data sets from individual investigators. An event logger application, based on ELOG, has been developed and is being tested by scientists at sea. An important aspect of this project is the development of a controlled vocabulary and ontology for documenting the scientific sampling events that occur during a research cruise. The controlled vocabulary development is being influenced by similar efforts in other communities. In addition, a Web application is being developed for oceanographers to use to pre-configure the R2R event logger application with vocabulary terms and entry forms appropriate to the specific needs of their upcoming research cruise. Results and lessons learned from the R2R event logger

  7. Involvement of angiotensin II type 2 receptor (AT2R) signaling in human pancreatic ductal adenocarcinoma (PDAC): a novel AT2R agonist effectively attenuates growth of PDAC grafts in mice

    PubMed Central

    Ishiguro, Susumu; Yoshimura, Kiyoshi; Tsunedomi, Ryouichi; Oka, Masaaki; Takao, Sonshin; Inui, Makoto; Kawabata, Atsushi; Wall, Terrahn; Magafa, Vassiliki; Cordopatis, Paul; Tzakos, Andreas G; Tamura, Masaaki

    2015-01-01

    We have recently discovered the potential involvement of angiotensin II type 2 receptor (AT2R) signaling in pancreatic cancer using AT2R deficient mice. To examine the involvement of AT2R expression in human PDAC, expressions of AT2R as well as the major angiotensin II receptor (type 1 receptor, AT1R) in human PDAC and adjacent normal tissue was evaluated by immunohistochemistry and real time PCR using surgically dissected human PDAC specimens. In immunohistochemical analysis, relatively strong AT1R expression was detected consistently in both normal pancreas and PDAC areas, whereas moderate AT2R expression was detected in 78.5% of PDAC specimens and 100% of normal area of the pancreas. AT1R, but not AT2R, mRNA levels were significantly higher in the PDAC area than in the normal pancreas. AT2R mRNA levels showed a negative correlation trend with overall survival. In cell cultures, treatment with a novel AT2R agonist significantly attenuated both murine and human PDAC cell growth with negligible cytotoxicity in normal epithelial cells. In a mouse study, administrations of the AT2R agonist in tumor surrounding connective tissue markedly attenuated growth of only AT2R expressing PAN02 murine PDAC grafts in syngeneic mice. The AT2R agonist treatment induced apoptosis primarily in tumor cells but not in stromal cells. Taken together, our findings offer clinical and preclinical evidence for the involvement of AT2R signaling in PDAC development and pinpoint that the novel AT2R agonist could serve as an effective therapeutic for PDAC treatment. PMID:25756513

  8. Cryptochron C2r.2r-1 recorded 2.51 Ma in the Koolau Volcano at Halawa, Oahu, Hawaii, USA: Paleomagnetic and 40Ar/ 39Ar evidence

    NASA Astrophysics Data System (ADS)

    Herrero-Bervera, Emilio; Browne, Edward J.; Valet, Jean Pierre; Singer, Brad S.; Jicha, Brian R.

    2007-02-01

    flow sites at different stratigraphic levels yields isochrons between 2.64 ± 0.23 to 2.37 ± 0.17 Ma with a weighted mean age of 2.514 ± 0.039 Ma, which, combined with the overall reversed polarity and the absence of polarity reversals, strongly suggests that the excursion corresponds to Cryptochron C2r.2r-1 [S. Candle and D.V. Kent, A New Geomagnetic Polarity Time Scale for the Late Cretaceous and Cenozoic, Jour. Geophys Res., 100(1995), 6093-6095.]. Current dating is insufficiently precise to unambiguously define this excursion as a Microchron (< 10 kyr). This is potentially the first terrestrial record of Cryptochron C2r.2r-1 and the age is 2-3% older than in the reported timescale [S. Candle and D.V. Kent, A New Geomagnetic Polarity Time Scale for the Late Cretaceous and Cenozoic, Jour. Geophys Res., 100(1995), 6093-6095.]. Our finding places important constraints on the evolution of the entire Koolau shield edifice, since most of the lavas recorded a reversed polarity.

  9. Photoaffinity labeling of serum vitamin D binding protein by 3-deoxy-3-azido-25-hydroxyvitamin D/sub 3/

    SciTech Connect

    Link, R.P.; Kutner, A.; Schnoes, H.K.; DeLuca, H.F.

    1986-05-01

    3-Deoxy-3-azido-25-hydroxyvitamin D/sub 3/ (3-Az-25-OH-D/sub 3/) was covalently incorporated into the 25-hydroxyvitamin D/sub 3/ (25-OH-D/sub 3/) binding site of purified human serum vitamin D binding protein (hDBP). Competition experiments showed that 3-Az-25-OH-D/sub 3/ and 25-OH-D/sub 3/ bound at the same site. A K/sub I/ of 80 nM was determined from 3-Az-25-OH-D/sub 33/ inhibition of 25-OH-D/sub 3/ binding to hDBP. 3-Az-25-OH-(26,27-/sup 3/H)D/sub 3/, prepared from 25-OH-(26,27-/sup 3/H)D/sub 3/, bound reversibly to hDBP in the dark. Scatchard analysis of the data indicated a single class of sites with a K/sub D. app/ of 0.71 nM and a B/sub max/ of 0.11 nM for 3-Az-25-OH-(26,27-/sup 3/H)D/sub 3/ as compared to a K/sub D. app/ of 0.37 nM and a B/sub max/ of 0.43 nM for 25-OH-(26,27-/sup 3/H)D/sub 3/. The stability of 25-OH-D/sub 3/ binding to hDBP was tested under the UV irradiation conditions required for photoactivation of 3-Az-25-OH-D/sub 3/. After 3 minutes of medium intensity, short wavelength (254 nm) UV irradiation, 40-50% of the previously bound 25-OH-(26,27-/sup 3/H)D/sub 3/ was retained by hDBP and 60% of the unliganded protein was capable of subsequently binding 25-OH-(26,27-/sup 3/H)D/sub 3/. Maximum specific covalent incorporation of 3-Az-25-OH-(26,27-/sup 3/H)D/sub 3/ by hDBP was after 3 to 5 minutes of irradiation. As much as 7.5% of the initially reversibly bound 3-Az-25-OH-(26,27-/sup 3/H)D/sub 3/ could be covalently bound to the 25-OH-D/sub 3/ binding site of hDBP.

  10. The inflammatory mediator leukotriene D{sub 4} induces subcellular β-catenin translocation and migration of colon cancer cells

    SciTech Connect

    Salim, Tavga; Sand-Dejmek, Janna; Sjölander, Anita

    2014-02-15

    The abnormal activation of the Wnt/β-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of β-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D{sub 4} (LTD{sub 4}) exerts its effects through the CysLT{sub 1} receptor. We previously reported an upregulation of CysLT{sub 1}R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD{sub 4} on Wnt/β-catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD{sub 4} stimulation led to an increase in β-catenin expression, β-catenin nuclear translocation and the subsequent transcription of MYC and CCND1. Furthermore, LTD{sub 4} significantly reduced the expression of E-cadherin and β-catenin at the plasma membrane and increased the migration and proliferation of HCT116 colon cancer cells. The effects of LTD{sub 4} can be blocked by the inhibition of CysLT{sub 1}R. Furthermore, LTD{sub 4} induced the inhibition of glycogen synthase kinase 3 (GSK)-3β activity, indicating a crosstalk between the G-protein-coupled receptor CysLT{sub 1} and the Wnt/β-catenin pathway. In conclusion, LTD{sub 4}, which can be secreted from macrophages and leukocytes in the tumor microenvironment, induces β-catenin translocation and the activation of β-catenin target genes, resulting in the increased proliferation and migration of colon cancer cells. - Highlights: • Leukotriene D{sub 4} (LTD{sub 4}) lowers membrane β-catenin but increases nuclear β-catenin levels in colon cancer cells. • In agreement, LTD{sub 4} triggers inactivation of GSK-3β, activation of TCF/LEF and increased expression of Cyclin D1 and c-Myc. • LTD{sub 4} also caused a significant reduction in the expression of E-cadherin and an increased migration of colon cancer cells.

  11. Photodissociation spectroscopy of Ca{sup +}(H{sub 2}O) and Ca{sup +}(D{sub 2}O)

    SciTech Connect

    Scurlock, C.T.; Reddic, E.; Duncan, M.A.

    1996-12-31

    Electronic spectra are observed for the mono-solvated metal cation complexes Ca{sup +}-H{sub 2}O and Ca{sup +}-D{sub 2}O using Resonance Enhanced Photodissociation Spectroscopy. The clusters are produced in a laser vaporization/supersonic expansion source and the mass-analyzed product ion is observed using a time-of-flight mass spectrometer. Both Ca{sup +} and CaOH{sup +} (or CaOD{sup +}) dissociation products are observed on sharp resonances. The observed features are assigned to the (2){sup 2}B{sub 2}{l_arrow}X{sup 2}A, and (2){sup 2}B{sub 1}{l_arrow}X{sup 1}A, transitions, with vibrational progressions in the Ca-OH, stretching mode. Spectroscopic constants are Ca{sup +}-H{sub 2}O: (2){sup 2}B{sub 2}{l_arrow}X{sup 2}A{sub 1} (T{sub 0}= 21,464 cm{sup -1}, {Delta}G{sub 1/2}=357.9 cm{sup -1}) and (2){sup 2}B{sub 2}{l_arrow}X{sup 2}A{sub 1} (T{sub 0}=22,273 cm{sup -1}, {Delta}G{sub 1/2}335.9 cm{sup -1}); and Ca{sup +}-D{sub 2}O: (2){sup 2}B{sub 2}{l_arrow}X{sup 2}A{sub 1} (T{sub 0}=21,447 cm{sup -1}, {Delta}G{sub {1/2}}=350.9 cm{sup -1}) and (2){sup 2}B{sub 2}{l_arrow}X{sup 2}A{sub 1} (T{sub 0}=22,261 cm{sup -1}, {Delta}G{sub {1/2}}=324.1 cm{sup -1}). These transitions are rotationally resolved about the a- principal axis, and confirm the structure of the complex to possess C{sub 2v} symmetry. In addition the Ca{sup +}-OH{sub 2} bond distance is determined to be 2.22 {Angstrom} and the H-O-H bond angle 106.8{degrees} in the ground state.

  12. The Octopamine Receptor Octβ2R Regulates Ovulation in Drosophila melanogaster

    PubMed Central

    Fernandez, Ana; Sabandal, John Martin; Lee, Hyun-Gwan; Evans, Peter; Han, Kyung-An

    2014-01-01

    Oviposition is induced upon mating in most insects. Ovulation is a primary step in oviposition, representing an important target to control insect pests and vectors, but limited information is available on the underlying mechanism. Here we report that the beta adrenergic-like octopamine receptor Octβ2R serves as a key signaling molecule for ovulation and recruits protein kinase A and Ca2+/calmodulin-sensitive kinase II as downstream effectors for this activity. We found that the octβ2r homozygous mutant females are sterile. They displayed normal courtship, copulation, sperm storage and post-mating rejection behavior but were unable to lay eggs. We have previously shown that octopamine neurons in the abdominal ganglion innervate the oviduct epithelium. Consistently, restored expression of Octβ2R in oviduct epithelial cells was sufficient to reinstate ovulation and full fecundity in the octβ2r mutant females, demonstrating that the oviduct epithelium is a major site of Octβ2R’s function in oviposition. We also found that overexpression of the protein kinase A catalytic subunit or Ca2+/calmodulin-sensitive protein kinase II led to partial rescue of octβ2r’s sterility. This suggests that Octβ2R activates cAMP as well as additional effectors including Ca2+/calmodulin-sensitive protein kinase II for oviposition. All three known beta adrenergic-like octopamine receptors stimulate cAMP production in vitro. Octβ1R, when ectopically expressed in the octβ2r’s oviduct epithelium, fully reinstated ovulation and fecundity. Ectopically expressed Octβ3R, on the other hand, partly restored ovulation and fecundity while OAMB-K3 and OAMB-AS that increase Ca2+ levels yielded partial rescue of ovulation but not fecundity deficit. These observations suggest that Octβ2R have distinct signaling capacities in vivo and activate multiple signaling pathways to induce egg laying. The findings reported here narrow the knowledge gap and offer insight into novel strategies for

  13. (2R,3S,2'' R,3''R)-manniflavanone, a new gastrointestinal smooth muscle L-type calcium channel inhibitor, which underlies the spasmolytic properties of Garcinia buchananii stem bark extract.

    PubMed

    Balemba, Onesmo B; Stark, Timo D; Lösch, Sofie; Patterson, Savannah; McMillan, John S; Mawe, Gary M; Hofmann, Thomas

    2014-01-01

    Garcinia buchananii Baker stem bark extract (GBB) is a traditional medication of diarrhea and dysentery in sub-Saharan Africa. It is believed that GBB causes gastrointestinal smooth muscle relaxation. The aim of this study was to determine whether GBB has spasmolytic actions and identify compounds underlying these actions. Calcium (Ca(2+)) imaging was used to analyze the effect of GBB on Ca(2+) flashes and Ca(2+) waves in guinea pig gallbladder and distal colon smooth muscle. Intracellular microelectrode recording was used to determine the effect of GBB, six fractions of GBB, M1-5 and M7, and (2R,3S,2'' R,3''R)-manniflavanone, a compound isolated from M3 on action potentials in gallbladder smooth muscle. The technique was also used to analyze the effect of GBB, M3, and (2R,3S,2'' R,3''R)-manniflavanone on action potentials in the circular muscle of mouse and guinea pig distal colons, and the effect of GBB and (2R,3S,2''R,3'' R)-manniflavanone on slow waves in porcine ileum. GBB inhibited Ca(2+) flashes and Ca(2+) waves. GBB, M3 and (2R,3 S,2''R,3''R)-manniflavanone inhibited action potentials. L-type Ca(2+) channel activator Bay K 8644 increased the discharge of action potentials in mouse colon but did not trigger or increase action potentials in the presence of GBB and (2R,3S,2''R,3'' R)-manniflavanone. GBB and (2R,3S,2'' R,3''R)-manniflavanone inhibited action potentials in the presence of Bay K 8644. GBB and (2R,3 S,2''R,3''R)-manniflavanone reduced the amplitude but did not alter the frequency of slow waves in the porcine ileum. In conclusion, GBB and (2R,3S,2'' R,3''R)-manniflavanone relax smooth muscle by inhibiting L-type Ca(2+) channels, thus have potential for use as therapies of gastrointestinal smooth muscle spasms, and arrhythmias. PMID:26081368

  14. Communication: The origin of rotational enhancement effect for the reaction of H{sub 2}O{sup +} + H{sub 2} (D{sub 2})

    SciTech Connect

    Li, Anyang; Li, Yongle; Guo, Hua; Lau, Kai-Chung; Xu, Yuntao; Xiong, Bo; Chang, Yih-Chung; Ng, C. Y.

    2014-01-07

    We have measured the absolute integral cross sections (σ’s) for H{sub 3}O{sup +} formed by the reaction of rovibrationally selected H{sub 2}O{sup +}(X{sup 2}B{sub 1}; v{sub 1}{sup +}v{sub 2}{sup +}v{sub 3}{sup +} = 000; N{sup +}{sub Ka}{sup +}{sub Kc}{sup +} = 0{sub 00}, 1{sub 11}, and 2{sub 11}) ion with H{sub 2} at the center-of-mass collision energy (E{sub cm}) range of 0.03–10.00 eV. The σ(0{sub 00}), σ(1{sub 11}), and σ(2{sub 11}) values thus obtained reveal rotational enhancements at low E{sub cm} < 0.50 eV, in agreement with the observation of the previous study of the H{sub 2}O{sup +}(X{sup 2}B{sub 1}) + D{sub 2} reaction. This Communication presents important progress concerning the high-level ab initio quantum calculation of the potential energy surface for the H{sub 2}O{sup +}(X{sup 2}B{sub 1}) + H{sub 2} (D{sub 2}) reactions, which has provided valuable insight into the origin of the rotational enhancement effect. Governed by the charge and dipole-induced-multipole interactions, the calculation shows that H{sub 2} (D{sub 2}) approaches the H end of H{sub 2}O{sup +}(X{sup 2}B{sub 1}) in the long range, whereas chemical force in the short range favors the orientation of H{sub 2} (D{sub 2}) toward the O side of H{sub 2}O{sup +}. The reorientation of H{sub 2}O{sup +} reactant ion facilitated by rotational excitation thus promotes the H{sub 2}O{sup +} + H{sub 2} (D{sub 2}) reaction along the minimum energy pathway, rendering the observed rotational enhancement effects. The occurrence of this effect at low E{sub cm} indicates that the long range charge and dipole-induced-multipole interactions of the colliding pair play a significant role in the dynamics of the exothermic H{sub 2}O{sup +} + H{sub 2} (D{sub 2}) reactions.

  15. Spectroscopic investigations and ab initio computations of the dye Chromotrope 2R

    NASA Astrophysics Data System (ADS)

    Snehalatha, M.; Ravikumar, C.; Hubert Joe, I.

    2009-07-01

    Detailed analysis of the NIR FT-Raman, FT-IR and UV-visible spectra of the dye Chromotrope 2R (C2R) has been performed. The optimized geometry of the dye is theoretically computed with the HF and DFT levels using the standard 6-31G(d) and LANL2DZ basis sets. Optimized geometry and vibrational spectra indicate that the major species in the solid state are the trans form of hydrogen bonded hydrazone tautomer. The effect of H-bonding in stabilizing a particular type of structure is also discussed. The most preferred trans-configuration for its photochemical activity has been demonstrated on the basis of torsional potential energy surface (PES) scan studies. The optimized geometries and calculated vibrational wavenumbers are evaluated via comparison with experimental values. Electronic spectra are in accordance with the nature of the electronic transitions predicted by time-dependent B3LYP/DZ calculations.

  16. Linkage disequilibria at the D[sub 2] dopamine receptor locus (DRD2) in alcoholics and controls

    SciTech Connect

    Suarez, B.K.; Parsian, A.; Hampe, C.L.; Todd, R.D.; Reich, T.; Cloninger, C.R. )

    1994-01-01

    Because of its central role in the neuromodulation of appetitive behaviors, the D[sub 2] dopamine receptor gene (DRD2) has received considerable scrutiny as a possible candidate that may affect susceptibility to addictive behaviors--especially alcoholism. Association studies that compare the frequencies of anonymous restriction fragment length polymorphisms (RFLPs) in alcoholics and controls have yielded equivocal results, suggesting that any role played by this receptor will account for only part of the variation. Since these RFLPs are not located in coding regions, the hypothesis has been advanced that the association seen in some studies results from linkage disequilibrium between these markers and one or more functional DRD2 alleles that affect susceptibility. To test this hypothesis, the authors have assayed four DRD2 RFLPs that span coding regions as well as a 3[prime] flanking RFLP in an expanded sample of 88 unrelated Caucasian alcoholics and 89 unrelated race-matched controls. No significant difference for any RFLP frequency between these samples was observed, although for one marker (phD2-244), the alcoholic sample showed a significant departure from the Hardy-Weinberg equilibrium. The pattern of pairwise composite disequilibrium coefficients is broadly similar in the two samples, although when the five-marker haplotype frequencies are compared, a significant difference is revealed. This difference appears to be due to greater linkage disequilibrium of the control sample. These results do not support the involvement of the DRD2 region in the etiology of alcoholism. 64 refs., 2 figs., 6 tabs.

  17. Kinetics of deuterium exchange on resorcinol in D{sub 2}O at high pressure and high temperature

    SciTech Connect

    Bai, S.; Palmer, B.J.; Yonker, C.R.

    2000-01-13

    The kinetics of deuteration of resorcinol in pure D{sub 2}O were studied for the first time using a flow-through capillary tubular reactor with on-line, proton, and deuterium NMR detection at high temperatures and high pressure. The global rate constants for hydrogen/deuterium (H/D) exchange were determined from temperatures of 200--450 C (723 K) at a pressure of {approximately}400 bar (the critical temperature and pressure of water are 374.2 C and 218.3 bar, respectively). The H/D exchange rate in resorcinol (1,3-dihydroxybenzene) under these extreme conditions was determined using proton NMR as a function of the resorcinol residence time in a capillary tubular reactor, which also served as a high-pressure NMR cell. The {sup 1}H and {sup 2}H NMR results indicate that H/D exchange in resorcinol for the ring protons was observed at temperatures as low as 200 C. The kinetics of H/D exchange in resorcinol and the activation energy was extracted from the experimental {sup 1}H NMR data.

  18. Radiolabelled D/sub 2/ agonists as prolactinoma imaging agents: Progress report for period February 1, 1988--January 31, 1989

    SciTech Connect

    Otto, C.A.

    1988-10-15

    Targeted studies completed include the evaluation of tritiated N-0437, evaluation of /sup 35/S-cysteamine, evaluation of /sup 18/F-FDG and initiation of synthetic efforts towards the synthesis of iodinated N-0437 and pergolide analogs. The direction of the project has been changed due to several factors which include the decided lack of favorable experimental results, the excellence of results using muscarinic receptor ligands in pituitary, brain and heart and the contention of the DOE review panel that the original grant proposal was based on flawed assumptions together with their perceived lack of importance to pituitary imaging. In the final year of this grant, three studies will be completed. The first study is the continuation of synthetic efforts to prepare iodinated N-0437 and pergolide analogs for possible use as brain imaging agents. The second study is directed towards completion of biochemical evaluation of various muscarinic receptor analogs for heart, brain and (possible) pituitary imaging. The third study is to probe the use of quaternized D/sub 2/ receptor ligands for imaging peripheral dopaminergic receptors (including the pituitary). 14 refs., 1 fig., 7 tabs.

  19. Linearized method: A new approach for kinetic analysis of central dopamine D{sub 2} receptor specific binding

    SciTech Connect

    Watabe, Hiroshi; Hatazawa, Jun; Ishiwata, Kiichi; Ido, Tatsuo; Itoh, Masatoshi; Iwata, Ren; Nakamura, Takashi; Takahashi, Toshihiro; Hatano, Kentaro

    1995-12-01

    The authors proposed a new method (Linearized method) to analyze neuroleptic ligand-receptor specific binding in a human brain using positron emission tomography (PET). They derived the linear equation to solve four rate constants, k{sub 3}, k{sub 4}, k{sub 5}, k{sub 6} from PET data. This method does not demand radioactivity curve in plasma as an input function to brain, and can do fast calculations in order to determine rate constants. They also tested Nonlinearized method including nonlinear equations which is conventional analysis using plasma radioactivity corrected for ligand metabolites as an input function. The authors applied these methods to evaluate dopamine D{sub 2} receptor specific binding of [{sup 11}C] YM-09151-2. The value of B{sub max}/K{sub d} = k{sub 3}k{sub 4} obtained by Linearized method was 5.72 {+-} 3.1 which was consistent with the value of 5.78 {+-} 3.4 obtained by Nonlinearized method.

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  1. Rolling Deck to Repository (R2R): Building a Reference Cruise Catalog for the Research Fleet

    NASA Astrophysics Data System (ADS)

    Arko, R. A.; Clark, P. D.; Chandler, C. L.; Smith, S. R.

    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. A core element of this infrastructure is a master catalog of research vessels, cruises, sensor systems, underway datasets, navigation products, field reports, event logs, file formats, people, organizations, and funding awards that is maintained uniformly across the research fleet. All NSF-supported vessel operators now submit their underway cruise data and documentation directly to R2R, per the revised Division of Ocean Sciences (OCE) Sample and Data Policy published in 2011. R2R ingests this content into the fleet catalog, assigning globally unique and persistent identifiers at the cruise, dataset, and file (granule) levels. The catalog is aligned with community-standard vocabularies, working collaboratively with the NOAA Data Centers, UNOLS Office, and pan-European SeaDataNet project; and includes links to related data at other inter/national repositories. In response to community demand, we are extending the catalog to include instrument-specific metadata such as installation details, patch tests, and calibration results. The entire R2R catalog is published on the Web as "Linked Data", making it easily accessible to encourage integration with other repositories. Selected content is also published in formal metadata records according to ISO and W3C standards, suitable for submission to long-term archives. We are deploying both faceted (classification/filter) and Web map-based browse and search interfaces.

  2. Cholinergic chemosensory cells of the thymic medulla express the bitter receptor Tas2r131.

    PubMed

    Soultanova, Aichurek; Voigt, Anja; Chubanov, Vladimir; Gudermann, Thomas; Meyerhof, Wolfgang; Boehm, Ulrich; Kummer, Wolfgang

    2015-11-01

    The thymus is the site of T cell maturation which includes positive selection in the cortex and negative selection in the medulla. Acetylcholine is locally produced in the thymus and cholinergic signaling influences the T cell development. We recently described a distinct subset of medullary epithelial cells in the murine thymus which express the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT) and components of the canonical taste transduction cascade, i.e. transient receptor potential melastatin-like subtype 5 channel (TRPM5), phospholipase Cβ(2), and Gα-gustducin. Such a chemical phenotype is characteristic for chemosensory cells of mucosal surfaces which utilize bitter receptors for detection of potentially hazardous compounds and cholinergic signaling to initiate avoidance reflexes. We here demonstrate mRNA expression of bitter receptors Tas2r105, Tas2r108, and Tas2r131 in the murine thymus. Using a Tas2r131-tauGFP reporter mouse we localized the expression of this receptor to cholinergic cells expressing the downstream elements of the taste transduction pathway. These cells are distinct from the medullary thymic epithelial cells which promiscuously express tissue-restricted self-antigens during the process of negative selection, since double-labeling immunofluorescence showed no colocalization of autoimmune regulator (AIRE), the key mediator of negative selection, and TRPM5. These data demonstrate the presence of bitter taste-sensing signaling in cholinergic epithelial cells in the thymic medulla and opens a discussion as to what is the physiological role of this pathway. PMID:26102274

  3. Low expression of D2R and Wntless correlates with high motivation for heroin.

    PubMed

    Tacelosky, Diana M; Alexander, Danielle N; Morse, Megan; Hajnal, Andras; Berg, Arthur; Levenson, Robert; Grigson, Patricia S

    2015-12-01

    Drug overdose now exceeds car accidents as the leading cause of accidental death in the United States. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu-opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in the brain. That said, it is not known if alterations in the expression of these proteins relate to drug exposure and/or to the "addiction-like" behavior exhibited for the drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater addiction-like behavior for heroin in general and with a greater willingness to work for the drug in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled nonavailability of the drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for the drug rather than to differences in total drug intake per se. PMID:26501177

  4. Advanced feedback control methods in EXTRAP T2R reversed field pinch

    SciTech Connect

    Yadikin, D.; Brunsell, P. R.; Paccagnella, R.

    2006-07-15

    Previous experiments in the EXTRAP T2R reversed field pinch device have shown the possibility of suppression of multiple resistive wall modes (RWM). A feedback system has been installed in EXTRAP T2R having 100% coverage of the toroidal surface by the active coil array. Predictions based on theory and the previous experimental results show that the number of active coils should be sufficient for independent stabilization of all unstable RWMs in the EXTRAP T2R. Experiments using different feedback schemes are performed, comparing the intelligent shell, the fake rotating shell, and the mode control with complex feedback gains. Stabilization of all unstable RWMs throughout the discharge duration of t{sub d}{approx_equal}10{tau}{sub w} is seen using the intelligent shell feedback scheme. Mode rotation and the control of selected Fourier harmonics is obtained simultaneously using the mode control scheme with complex gains. Different sensor signals are studied. A feedback system with toroidal magnetic field sensors could have an advantage of lower feedback gain needed for the RWM suppression compared to the system with radial magnetic field sensors. In this study, RWM suppression is demonstrated, using also the toroidal field component as a sensor signal in the feedback system.

  5. Rolling Deck to Repository (R2R): A Research Cruise Prototype Event Logging System

    NASA Astrophysics Data System (ADS)

    Chandler, C. L.; Dorsk, A.

    2009-12-01

    Data gathered aboard research vessels coordinated by the University-National Oceanographic Laboratory System (UNOLS) represent an important component of the overall oceanographic data collection. The nascent Rolling Deck to Repository (R2R) project aims to improve access to basic shipboard data and ultimately reduce the work required to provide that access. The ultimate vision of R2R is to assist in transforming the academic fleet into an integrated global observing system. One of the coordinated subprojects within the R2R project is development of a shipboard, scientific event logging system that would incorporate best practice guidelines, a metadata schema and new and existing applications to generate a scientific sampling event log in the form of a digital text file. A cruise event logging system enables researchers to record digitally all scientific sampling events and assign a unique event identifier to each entry. Decades of work conducted within large coordinated ocean research programs (JGOFS, GLOBEC, WOCE and RIDGE) have shown that creation of a shipboard sampling event log can facilitate greatly the subsequent integration of data sets from individual investigators. A prototype event logger application, based on ELOG, has been developed and tested and results and lessons learned from this development effort will be shared.

  6. Antiausterity activity of arctigenin enantiomers: importance of (2R,3R)-absolute configuration.

    PubMed

    Awale, Suresh; Kato, Mamoru; Dibwe, Dya Fita; Li, Feng; Miyoshi, Chika; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro

    2014-01-01

    From a MeOH extract of powdered roots of Wikstroemia indica, six dibenzyl-gamma-butyrolactone-type lignans with (2S,3S)-absolute configuration [(+)-arctigenin (1), (+)-matairesinol (2), (+)-trachelogenin (3), (+)-nortrachelogenin (4), (+)-hinokinin (5), and (+)-kusunokinin (6)] were isolated, whereas three dibenzyl-gamma-butyrolactone-type lignans with (2R,3R)-absolute configuration [(-)-arctigenin (1*), (-)-matairesinol (2*), (-)-trachelogenin (3*)] were isolated from Trachelospermum asiaticum. The in vitro preferential cytotoxic activity of the nine compounds was evaluated against human pancreatic PANC-1 cancer cells in nutrient-deprived medium (NDM), but none of the six lignans (1-6) with (2S,3S)-absolute configuration showed preferential cytotoxicity. On the other hand, three lignans (1*-3*) with (2R,3R)-absolute configuration exhibited preferential cytotoxicity in a concentration-dependent manner with PC50 values of 0.54, 6.82, and 5.85 microM, respectively. Furthermore, the effect of (-)- and (+)-arctigenin was evaluated against the activation of Akt, which is a key process in the tolerance to nutrition starvation. Interestingly, only (-)-arctigenin (1*) strongly suppressed the activation of Akt. These results indicate that the (2R,3R)-absolute configuration of (-)-enantiomers should be required for the preferential cytotoxicity through the inhibition of Akt activation. PMID:24660468

  7. Advanced feedback control methods in EXTRAP T2R reversed field pinch

    NASA Astrophysics Data System (ADS)

    Yadikin, D.; Brunsell, P. R.; Paccagnella, R.

    2006-07-01

    Previous experiments in the EXTRAP T2R reversed field pinch device have shown the possibility of suppression of multiple resistive wall modes (RWM). A feedback system has been installed in EXTRAP T2R having 100% coverage of the toroidal surface by the active coil array. Predictions based on theory and the previous experimental results show that the number of active coils should be sufficient for independent stabilization of all unstable RWMs in the EXTRAP T2R. Experiments using different feedback schemes are performed, comparing the intelligent shell, the fake rotating shell, and the mode control with complex feedback gains. Stabilization of all unstable RWMs throughout the discharge duration of td≈10τw is seen using the intelligent shell feedback scheme. Mode rotation and the control of selected Fourier harmonics is obtained simultaneously using the mode control scheme with complex gains. Different sensor signals are studied. A feedback system with toroidal magnetic field sensors could have an advantage of lower feedback gain needed for the RWM suppression compared to the system with radial magnetic field sensors. In this study, RWM suppression is demonstrated, using also the toroidal field component as a sensor signal in the feedback system.

  8. Lrrk2 R1628P variant is a risk factor for essential tremor.

    PubMed

    Chao, Yin Xia; Ng, Ebonne Yulin; Tan, Louis; Prakash, Kumar M; Au, Wing-Lok; Zhao, Yi; Tan, Eng-King

    2015-01-01

    Essential tremor (ET) and Parkinson's disease (PD) are two of the most common adult onset movement disorders with overlapping clinical features. PD patients with leucine-rich repeat kinase-2 (LRRK2) mutations may present initially with an ET phenotype. To address the possibility of a common genetic link between ET and PD, we examined the association between a common LRRK2 R1628P gene variant and ET. The LRRK2 R1628P was genotyped in ET cases and matched healthy controls. A total of 1277 subjects comprising of 450 ET cases and 827 controls were included. There were 40 heterozygote (GG to CG) variant out of 450 ET cases (genotypic frequency 8.9%) and 36 heterozygote variant (GG to CG, genotypic frequency 4.3%) and one homozygote variant (GG to CC) out of 827 controls. Subjects carrying the R1628P variant had a twofold increased risk of ET (p = 0.0035, OR = 2.20 and 95% confidence interval is 1.30-3.73). Using a case control methodology, we demonstrated an association between a known PD risk variant, LRRK2 R1628P, with ET. Subjects carrying the R1628P variant had twice the risk of developing ET. The sharing of a similar gene risk variant suggests a possible pathophysiologic link between PD and ET. PMID:25761573

  9. miR-1301 promotes prostate cancer proliferation through directly targeting PPP2R2C.

    PubMed

    Bi, Dongbin; Ning, Hao; Liu, Shuai; Que, Xinxiang; Ding, Kejia

    2016-07-01

    Prostate cancer is the leading cause of cancer deaths among men in the worldwide, it's important to find new prognostic factors and therapeutic targets. microRNAs play critical roles in the development and progression of prostate cancer. Here we revealed miR-1301 promoted prostate cancer progression. miR-1301 was upregulated in prostate cancer tissues and cells, overexpression of miR-1301 promoted anchorage-dependent and -independent growth using MTT analysis, colony formation analysis and soft agar growth analysis, whereas knockdown of miR-1301 suppressed anchorage-dependent and -independent growth. We also found overexpression of miR-1301 inhibited p27 expression and promoted Cyclin D1 expression, whereas knockdown of miR-1301 reduced this effect, suggesting miR-1301 promoted the G1/S transition. These results suggested miR-1301 promoted cell proliferation of prostate cancer. microRNAs can inhibit target mRNA translation or/and induce mRNA degradation, we found tumor suppresser PPP2R2C was the target of miR-1301, simultaneous downregualtion of PPP2R2C and miR-1301 promoted anchorage-dependent and -independent growth. These findings suggested miR-1301 promoted prostate cancer proliferation by inhibiting PPP2R2C, and might a therapeutic target for prostate cancer. PMID:27261573

  10. Transfer between the cesium 6 {sup 2}P{sub 1/2} and 6 {sup 2}P{sub 3/2} levels induced by collisions with H{sub 2}, HD, D{sub 2}, CH{sub 4}, C{sub 2}H{sub 6}, CF{sub 4}, and C{sub 2}F{sub 6}

    SciTech Connect

    Pitz, Greg A.; Fox, Charles D.; Perram, Glen P.

    2011-09-15

    The cross sections of spin-orbit energy exchange between the cesium 6 {sup 2}P{sub 1/2}{r_reversible}6 {sup 2}P{sub 3/2} states induced by collisions with N{sub 2}, H{sub 2}, HD, D{sub 2}, CH{sub 4}, C{sub 2}H{sub 6}, CF{sub 4}, and C{sub 2}F{sub 6} were obtained for pressures less than 100 Torr at room temperature by means of steady-state laser-induced fluorescence techniques. The spin-orbit energy exchange rate with N{sub 2}, H{sub 2}, HD, D{sub 2}, CH{sub 4}, C{sub 2}H{sub 6}, CF{sub 4}, and C{sub 2}F{sub 6}, have been measured as {sigma}{sub 21}(6 {sup 2}P{sub 3/2}{yields}6 {sup 2}P{sub 1/2})= 16.3, 34.1, 30.0, 22.7, 21.4, 65.6, 64.8, and 137 A{sup 2} and {sigma}{sub 12}(6 {sup 2}P{sub 1/2}{yields}6 {sup 2}P{sub 3/2})= 1.8, 4.4, 4.1, 3.0, 2.9, 13.3, 9.7, and 16.3 A{sup 2}, respectively. Correlations of the spin-orbit transfer probabilities with rotational-energy defect and vibrational-energy defect have been shown.

  11. Nuclear translocation of the 1,25D{sub 3}-MARRS (membrane associated rapid response to steroids) receptor protein and NF{kappa}B in differentiating NB4 leukemia cells

    SciTech Connect

    Wu, Wenqing; Beilhartz, Greg; Roy, Yvette; Richard, Cynthia L.; Curtin, Maureen; Brown, Lauren; Cadieux, Danielle; Coppolino, Marc; Farach-Carson, Mary C.; Nemere, Ilka; Meckling, Kelly A.

    2010-04-15

    1,25 Dihydroxyvitamin D{sub 3} (1,25D{sub 3}) primes NB4 promyelocytic leukemia cells to differentiate along the monocyte/macrophage lineage through a non-genomic mechanism. Here we show that NB4 cells express high levels of the recently identified membrane receptor for 1,25D{sub 3}, which is a distinct gene product from the classical nuclear vitamin D receptor. This 57 kDa protein, named 1,25D{sub 3}-MARRS (Membrane Activated Rapid Response to Steroids)/ERp57/PIA3 appears to associate in a complex with the transcription factor, nuclear factor kappa B (NF{kappa}B). In unstimulated cells, 1,25D{sub 3}-MARRS can be co-immunoprecipitated with antibodies directed at NF{kappa}B, and NF{kappa}B is co-precipitated when antibodies against 1,25D{sub 3}-MARRS or ERp57 are used. Confocal microscopy and subcellular fractionation studies demonstrate that both 1,25D{sub 3}-MARRS and NF{kappa}B begin translocating to the nucleus within minutes of co-stimulation with 1,25D{sub 3} and phorbol ester. The predominant nuclear localization of both proteins precedes the expression of the monocyte/macrophage phenotype and suggests that this event may be critical to the differentiation pathway. This suggests a role for 1,25D{sub 3}-MARRS in the nucleus as a regulator of gene expression. Here it may also regulate the activity of NF{kappa}B and other factors with which it may be interacting.

  12. Pre- and Postsynaptic Role of Dopamine D2 Receptor DD2R in Drosophila Olfactory Associative Learning.

    PubMed

    Qi, Cheng; Lee, Daewoo

    2014-01-01

    Dopaminergic neurons in Drosophila play critical roles in diverse brain functions such as motor control, arousal, learning, and memory. Using genetic and behavioral approaches, it has been firmly established that proper dopamine signaling is required for olfactory classical conditioning (e.g., aversive and appetitive learning). Dopamine mediates its functions through interaction with its receptors. There are two different types of dopamine receptors in Drosophila: D1-like (dDA1, DAMB) and D2-like receptors (DD2R). Currently, no study has attempted to characterize the role of DD2R in Drosophila learning and memory. Using a DD2R-RNAi transgenic line, we have examined the role of DD2R, expressed in dopamine neurons (i.e., the presynaptic DD2R autoreceptor), in larval olfactory learning. The function of postsynaptic DD2R expressed in mushroom body (MB) was also studied as MB is the center for Drosophila learning, with a function analogous to that of the mammalian hippocampus. Our results showed that suppression of presynaptic DD2R autoreceptors impairs both appetitive and aversive learning. Similarly, postsynaptic DD2R in MB neurons appears to be involved in both appetitive and aversive learning. The data confirm, for the first time, that DD2R plays an important role in Drosophila olfactory learning. PMID:25422852

  13. Identification of 2R-ohnologue gene families displaying the same mutation-load skew in multiple cancers

    PubMed Central

    Tinti, Michele; Dissanayake, Kumara; Synowsky, Silvia; Albergante, Luca; MacKintosh, Carol

    2014-01-01

    The complexity of signalling pathways was boosted at the origin of the vertebrates, when two rounds of whole genome duplication (2R-WGD) occurred. Those genes and proteins that have survived from the 2R-WGD—termed 2R-ohnologues—belong to families of two to four members, and are enriched in signalling components relevant to cancer. Here, we find that while only approximately 30% of human transcript-coding genes are 2R-ohnologues, they carry 42–60% of the gene mutations in 30 different cancer types. Across a subset of cancer datasets, including melanoma, breast, lung adenocarcinoma, liver and medulloblastoma, we identified 673 2R-ohnologue families in which one gene carries mutations at multiple positions, while sister genes in the same family are relatively mutation free. Strikingly, in 315 of the 322 2R-ohnologue families displaying such a skew in multiple cancers, the same gene carries the heaviest mutation load in each cancer, and usually the second-ranked gene is also the same in each cancer. Our findings inspire the hypothesis that in certain cancers, heterogeneous combinations of genetic changes impair parts of the 2R-WGD signalling networks and force information flow through a limited set of oncogenic pathways in which specific non-mutated 2R-ohnologues serve as effectors. The non-mutated 2R-ohnologues are therefore potential therapeutic targets. These include proteins linked to growth factor signalling, neurotransmission and ion channels. PMID:24806839

  14. Rolling Deck to Repository (R2R): Building the Data Pipeline - Initial Results

    NASA Astrophysics Data System (ADS)

    Arko, R. A.; Clark, P. D.; Rioux, M. A.; McGovern, T. M.; Deering, T. W.; Hagg, R. K.; Payne, A. A.; Fischman, D. E.; Ferrini, V.

    2009-12-01

    The NSF-funded Rolling Deck to Repository (R2R) project is working with U.S. academic research vessel operators to ensure the documentation and preservation of data from routine “underway” (meteorological, geophysical, and oceanographic) sensor systems. A standard pipeline is being developed in which data are submitted by vessel operators directly to a central repository; inventoried in an integrated fleet-wide catalog; organized into discrete data sets with persistent unique identifiers; associated with essential cruise-level metadata; and delivered to the National Data Centers for archiving and dissemination. Several vessels including Atlantis, Healy, Hugh R. Sharp, Ka'imikai-O-Kanaloa, Kilo Moana, Knorr, Marcus G. Langseth, Melville, Oceanus, Roger Revelle, and Thomas G. Thompson began submitting data and documentation to R2R during the project’s pilot phase, and a repository infrastructure has been established. Cruise metadata, track maps, and data inventories are published at the R2R Web portal, with controlled vocabularies drawn from community standards (e.g. International Council for the Exploration of the Sea (ICES) ship codes). A direct connection has been established to the University-National Oceanographic Laboratory System (UNOLS) Ship Time Request and Scheduling System (STRS) via Web services to synchronize port codes and cruise schedules. A secure portal is being developed where operators may login to upload sailing orders, review data inventories, and create vessel profiles. R2R has established a standard procedure for submission of data to the National Geophysical Data Center (NGDC) that incorporates persistent unique identifiers for cruises, data sets, and individual files, using multibeam data as a test bed. Once proprietary holds are cleared and a data set is delivered to NGDC, the R2R catalog record is updated with the URL for direct download and it becomes immediately available to integration and synthesis projects such as the NSF

  15. A R2R3-MYB Transcription Factor from Epimedium sagittatum Regulates the Flavonoid Biosynthetic Pathway

    PubMed Central

    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. PMID:23936468

  16. Rolling Deck to Repository (R2R): Research Cruise Event Logger

    NASA Astrophysics Data System (ADS)

    Chandler, C. L.; Maffei, A. R.; Stolp, L.; Dubois, D. L.

    2011-12-01

    Scientific event logs, used by the science party to record scientific sampling events that occur during a research cruise, have been used in various ways for decades. An event log is very important for documenting the occurrence of a sampling event and its location, time, relative sequence, and related details. Event logging, done well, can provide important documentation about scientific data collected during a cruise, and enable more efficient use of those data by cruise participants and future researchers. When the resultant event log is a digital data file, with content generated programmatically and controlled by term vocabularies, it becomes an even more valuable addition to the full complement of data sets generated during the cruise. However, such a tool is only effective if it is used. Through field testing, several key factors were identified that encourage the use of such a tool: the ability to customize the tool to represent the science implementation plan, proposed sampling scheme, cruise personnel and instrumentation; the ability to retrieve date, time and location data automatically from the shipboard network and the ability to enter events quickly and from any location on the ship. This presentation provides an overview of both the current version 1 and soon to be released version 2 of the Rolling Deck to Repository (R2R) research cruise Event Logger system. The R2R Event Logger application is built upon a pre-existing, open-source, weblog product called ELOG (ELOG URL: http://midas.psi.ch/elog/). We provide an oceanographer's view of the full process by which: 1) the R2R Event Logger application is configured and tested to meet the unique needs of a research cruise; 2) the R2R project works with the ship operator to install the Event Logger on the ship designated for the cruise, 3) the Event Logger is configured to automatically retrieve location, time, and other pertinent information from the shipboard network; 4) a copy of the event log file is

  17. Quantum-Phase Resolved Mapping of Ground-State Vibrational D{sub 2} Wave Packets via Selective Depletion in Intense Laser Pulses

    SciTech Connect

    Ergler, Th.; Rudenko, A.; Schroeter, C. D.; Moshammer, R.; Ullrich, J.; Feuerstein, B.; Zrost, K.

    2006-09-08

    Applying 7 fs pump-probe pulses (780 nm, 4x10{sup 14} W/cm{sup 2}) we observe electronic ground-state vibrational wave packets in neutral D{sub 2} with a period of T=11.101(70) fs by following the internuclear separation (R-)dependent ionization with a sensitivity of {delta}{<=}0.02 A . The absolute phase of the wave packet's motion provides evidence for R-dependent depletion of the ground state by nonlinear ionization, to be the dominant preparation mechanism. A phase shift of about {pi} found between pure ionization (D{sub 2}{sup +}) and dissociation (D{sup +}+D) channels opens a pathway of quantum control.

  18. Deuterium absorption from the D{sub 2}O exposure of oxidized 4H-SiC (0001), (0001{sup ¯}), and (112{sup ¯}0) surfaces

    SciTech Connect

    Liu, Gang; Xu, Can; Feldman, Leonard C.; Yakshinskiy, Boris; Wielunski, Leszek; Gustafsson, Torgny; Bloch, Joseph; Dhar, Sarit

    2015-03-23

    We report results on deuterium absorption on several oxidized 4H-SiC surfaces following D{sub 2}O vapor absorption. Absorption at the oxide/semiconductor interface is strongly face dependent with an order of magnitude more deuterium on the C-face and a-face than on the Si-face, in contrast to the bulk of the oxides which show essentially no face dependence. Annealing in NO gas produces a large reduction in interfacial deuterium absorption in all cases. The reduction of the positive charge at the interface scales linearly with the interface D content. These results also scale with the variation in interface trap density (D{sub it}) and mobility on the three faces after wet oxidation annealing.

  19. Binding energies from diffusion Monte Carlo for the MB-pol H{sub 2}O and D{sub 2}O dimer: A comparison to experimental values

    SciTech Connect

    Mallory, Joel D.; Mandelshtam, Vladimir A.

    2015-10-14

    The diffusion Monte Carlo (DMC) method is applied to compute the ground state energies of the water monomer and dimer and their D{sub 2}O isotopomers using MB-pol; the most recent and most accurate ab inito-based potential energy surface (PES). MB-pol has already demonstrated excellent agreement with high level electronic structure data, as well as agreement with some experimental, spectroscopic, and thermodynamic data. Here, the DMC binding energies of (H{sub 2}O){sub 2} and (D{sub 2}O){sub 2} agree with the corresponding values obtained from velocity map imaging within, respectively, 0.01 and 0.02 kcal/mol. This work adds two more valuable data points that highlight the accuracy of the MB-pol PES.

  20. Variants of the D{sub 5} dopamine receptor gene found in patients with schizophrenia: Identification of a nonsense mutation and multiple missense changes

    SciTech Connect

    Sobell, J.L.; Lind, T.J.; Sommer, S.S.

    1994-09-01

    To determine whether mutations in the D{sub 5} dopamine receptor (D{sub 5}DR) gene are associated with schizophrenia, the gene was examined in 78 unrelated schizophrenic individuals. After amplification by the polymerase chain reaction, products were examined by dideoxy fingerprinting (ddF), a highly sensitive screening method related to single strand conformational polymorphism analysis. All samples with unusual ddF patterns were sequenced to precisely identify the sequence change. In the 156 D{sub 5}DR alleles examined, nine sequence changes were identified. Four of the nine did not affect protein structure; of these, three were silent changes and one was a transition in the 3{prime} untranslated region. The remaining five sequence changes result in protein alterations: of these, one is a missense change in a non-conserved amino acid, 3 are missense changes in amino acids that are conserved in some dopamine D{sub 5} receptors and the last is a nonsense mutation. To investigate whether the nonsense mutation was associated with schizophrenia, 400 additional schizophrenic cases of western European descent and 1914 ethnically-similar controls were screened for the change. One additional schizophrenic carrier was identified and verified by direct genomic sequencing (allele frequency: .0013), but eight carriers also were found and confirmed among the non-schizophrenics (allele frequency: .0021)(p>.25). The gene was re-examined in all newly identified carriers of the nonsense mutation by direct sequencing and/or ddF in search of additional mutations. None were identified. Family studies also were conducted to investigate possible cosegregation of the mutation with other neuropsychiatric diseases, but this was not demonstrated. Thus, the mutation does not appear to be associated with an increased risk of schizophrenia nor does an initial analysis suggest cosegregation with other neuropsychiatric disorders or symptom complexes.

  1. A KEY PHYSICAL MECHANISM FOR UNDERSTANDING THE ENIGMATIC LINEAR POLARIZATION OF THE SOLAR Ba II AND Na I D{sub 1} LINES

    SciTech Connect

    Belluzzi, Luca; Trujillo Bueno, Javier

    2013-09-10

    The linearly polarized spectrum of the solar limb radiation produced by scattering processes is of great diagnostic potential for exploring the magnetism of the solar atmosphere. This spectrum shows an impressive richness of spectral details and enigmatic Q/I signals, whose physical origin must be clearly understood before they can be exploited for diagnostic purposes. The most enduring enigma is represented by the polarization signals observed in the D{sub 1} resonance lines of Na I (5896 A) and Ba II (4934 A), which were expected to be intrinsically unpolarizable. The totality of sodium and 18% of barium have hyperfine structure (HFS), and it has been argued that the only way to produce a scattering polarization signal in such lines is through the presence of a substantial amount of atomic polarization in their lower HFS levels. The strong sensitivity of these long-lived levels to depolarizing mechanisms led to the paradoxical conclusion that the observed D{sub 1}-line polarization is incompatible with the presence in the lower solar chromosphere of inclined magnetic fields sensibly stronger than 0.01 G. Here we show that by properly taking into account the fact that the solar D{sub 1}-line radiation has a non-negligible spectral structure over the short frequency interval spanned by the HFS transitions, it is possible to produce scattering polarization signals in the D{sub 1} lines of Na I and Ba II without the need of ground-level polarization. The resulting linear polarization is not so easily destroyed by elastic collisions and/or magnetic fields.

  2. B{sub s}{yields}D{sub s}(3040) form factors and B{sub s} decays into D{sub s}(3040)

    SciTech Connect

    Li Gang; Shao Fenglan; Wang Wei

    2010-11-01

    Under the assignment of D{sub s}(3040) as a radially excited p-wave cs state with J{sup P}=1{sup +}, we compute the B{sub s}{yields}D{sub s}(3040) form factors within the covariant light-front quark model. Two classification schemes for the p-wave cs meson are adopted. We also use our results to predict the branching ratios (BRs), polarization fractions, and angular asymmetries in semileptonic B{sub s}{yields}D{sub s}(3040)l{nu} (l=e, {mu}, {tau}). The BRs are found at the order of 10{sup -3} for l=e, {mu}, and 10{sup -5} for l={tau}. We find that the polarization fractions and angular asymmetries could be useful to pin down the ambiguities in theoretical prescriptions for D{sub s}(3040). In addition, we investigate the nonleptonic B{sub s}{yields}D{sub s}(3040)M decays under the factorization method, where M denotes a charged pseudoscalar or a vector meson. The BRs of B{sub s}{yields}D{sub s}(3040){rho} and B{sub s}{yields}D{sub s}(3040)D{sub s}{sup *} reach the order of 10{sup -3}, while the other channels are typically smaller by 1-2 orders.

  3. Effects of {gamma}-secretase inhibition on the proliferation and vitamin D{sub 3} induced osteogenesis in adipose derived stem cells

    SciTech Connect

    Jing, Wei; Xiong, Zhonghua; Cai, Xiaoxiao; Huang, Yuanding; Li, Xiaoyu; Yang, Xingmei; Liu, Lei; Tang, Wei; Lin, Yunfeng; Tian, Weidong

    2010-02-12

    As a {gamma}-secretase inhibitor, DAPT has been widely used to evaluate the biological behaviors and Notch signaling pathway in various cells. This study was aimed to examine the effects of DAPT on the growth and vitamin D{sub 3} induced osteogenesis in adipose derived stem cells (ASCs). The cells were treated with or without DAPT and induced to osteoblastic lineage in the presence of vitamin D{sub 3}. Alizarin red staining and real-time PCR results indicated that the addition of DAPT to vitamin D{sub 3} treatments enhanced osteogenesis in ASCs. According to the fold increase and colony-forming unit assay results, the cells cultured in DAPT exhibited lower proliferation rate than those cultured in control medium. Hey1, expressed in the nucleus of ASCs to act as a transcriptional repressor, was downregulated when Notch signaling was inhibited by DAPT. Whereas the expression of Runx2 increased in the nucleus of osteogenic induced ASCs after DAPT treatment. This study demonstrated that DAPT reduced the proliferation and enhanced the osteogenesis in ASCs via regulation of Notch and Runx2 expression.

  4. 1,25-dihydroxyvitamin D{sub 3} impairs NF-{kappa}B activation in human naive B cells

    SciTech Connect

    Geldmeyer-Hilt, Kerstin; Heine, Guido; Hartmann, Bjoern; Baumgrass, Ria; Radbruch, Andreas; Worm, Margitta

    2011-04-22

    Highlights: {yields} In naive B cells, VDR activation by calcitriol results in reduced NF-{kappa}B p105 and p50 protein expression. {yields} Ligating the VDR with calcitriol causes reduced nuclear translocation of NF-{kappa}B p65. {yields} Reduced nuclear amount of p65 after calcitriol incubation results in reduced binding of p65 on the p105 promoter. {yields} Thus, vitamin D receptor signaling may reduce or prevent activation of B cells and unwanted immune responses, e.g. in IgE dependent diseases such as allergic asthma. -- Abstract: 1{alpha},25-dihydroxyvitamin D{sub 3} (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-{kappa}B p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-{kappa}B mediated activation of human naive B cells. Naive B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naive B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-{kappa}B activation by interference with NF-{kappa}B p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naive B cells, namely by reducing CD40 signaling.

  5. Neutron yield study of direct-drive, low-adiabat cryogenic D{sub 2} implosions on OMEGA laser system

    SciTech Connect

    Hu, S. X.; Radha, P. B.; Marozas, J. A.; Betti, R.; Collins, T. J. B.; Craxton, R. S.; Delettrez, J. A.; Edgell, D. H.; Epstein, R.; Goncharov, V. N.; Igumenshchev, I. V.; Marshall, F. J.; McCrory, R. L.; Meyerhofer, D. D.; Regan, S. P.; Sangster, T. C.; Skupsky, S.; Smalyuk, V. A.; Elbaz, Y.; Shvarts, D.

    2009-11-15

    Neutron yields of direct-drive, low-adiabat ({alpha}{approx_equal}2 to 3) cryogenic D{sub 2} target implosions on the OMEGA laser system [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] have been systematically investigated using the two-dimensional (2D) radiation hydrodynamics code DRACO[P. B. Radha et al., Phys. Plasmas 12, 056307 (2005)]. Low-mode (l{<=}12) perturbations, including initial target offset, ice-layer roughness, and laser-beam power imbalance, were found to be the primary source of yield reduction for thin-shell (5 {mu}m), low-{alpha}, cryogenic targets. The 2D simulations of thin-shell implosions track experimental measurements for different target conditions and peak laser intensities ranging from 2.5x10{sup 14}-6x10{sup 14} W/cm{sup 2}. Simulations indicate that the fusion yield is sensitive to the relative phases between the target offset and the ice-layer perturbations. The results provide a reasonable good guide to understanding the yield degradation in direct-drive, low-adiabat, cryogenic, thin-shell-target implosions. Thick-shell (10 {mu}m) implosions generally give lower yield over clean than low-l-mode DRACO simulation predictions. Simulations including the effect of laser-beam nonuniformities indicate that high-l-mode perturbations caused by laser imprinting further degrade the neutron yield of thick-shell implosions. To study ICF compression physics, these results suggest a target specification with a {<=}30 {mu}m offset and ice-roughness of {sigma}{sub rms}<3 {mu}m are required.

  6. Haplotypes of the D{sub 2} dopamine receptor gene in higher and lower alcohol consuming subjects

    SciTech Connect

    Zhang, X.; Ritchie, T.; Fitch, R.J.

    1994-09-01

    There is now a substantial body of evidence which indicates that the TaqI A D{sub 2} dopamine receptor (DRD2) minor (Al) allele is associated with alcoholism. In the present study, TaqI A DRD2 alleles and haplotypes of the DRD2 gene were determined in 307 Caucasian (non-Hispanic) subjects. These haplotypes are a combination of closely linked alleles in intron 6 and exon 7 and yield three haplotypes (1, 2, and 4) and six genotypes in Caucasians. The sample under study consisted of 54 individuals who consumed 200 or more alcoholic drinks per month (Group A) and 248 persons who drank less than 200 drinks per month (Group B). The results showed that the DRD2 A1 allele was significantly higher (P < 0.05) in Group A (48.2%) compared to group B (32.7%). Haplotype analysis in the same sample showed Group A having a significantly higher (P < 0.007) prevalence (28.4%) of the 1 haplotype than those in group B (14.0%). The results indicate both these genetic markers in the DRD2 gene are associated with higher alcohol consumption; however, the 1 haplotype appears to be a better marker for this behavior. In conclusion, haplotypes within the DRD2 gene and TaqI A DRD2 alleles (located 20-Kb from the 3{prime} coding region of this gene) are both associated with heavier alcohol consumption. These findings add further evidence to the importance of the gene in alcohol-related behaviors.

  7. Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several reports have shown that urotensin 2 (UTS2) and its receptor (UTS2R) are involved in glucose metabolism and insulin resistance, which lead to development of type 2 diabetes mellitus (T2DM) in humans. In the present study, we annotated both bovine UTS2 and UTS2R genes and identified 5 single...

  8. Genetic Variation in the TAS2R38 Bitter Taste Receptor and Gastric Cancer Risk in Koreans

    PubMed Central

    Choi, Jeong-Hwa; Lee, Jeonghee; Choi, Il Ju; Kim, Young-Woo; Ryu, Keun Won; Kim, Jeongseon

    2016-01-01

    The human TAS2R38 gene encodes a bitter taste receptor that regulates the bitterness perception and differentiation of ingested nutritional/poisonous compounds in the oral cavity and gastrointestinal tract. TAS2R38 gene variants are associated with alterations in individual sensitivity to bitter taste and food intake; hence, these genetic variants may modify the risk for diet-related diseases, including cancer. However, little is known about the association between TAS2R38 polymorphisms and gastric cancer susceptibility. The present case-control study examined the influence of TAS2R38 polymorphisms on food intake and determined whether they predict gastric cancer risk in Koreans. A total of 1,580 subjects, including 449 gastric cancer cases, were genotyped for TAS2R38 A49P, V262A, I296V and diplotypes. Dietary data were analysed to determine the total consumption of energy, fibre, vegetables, fruits, sweets, fats, alcohol and cigarettes. TAS2R38 diplotype was not associated with food, alcohol or cigarette consumption, either independent or dependent of gastric cancer phenotype. However, the PAV/AVI diplotype significantly increased gastric cancer risk (adjusted odds ratio: 1.513; 95% confidence interval: 1.148–1.994) independent of dietary intake. Findings suggest that TAS2R38 may be associated with the risk for gastric cancer in Koreans, although the TAS2R38 diplotype did not influence dietary intake. PMID:27245112

  9. CB2R orchestrates fibrogenesis through regulation of inflammatory response during the repair of skeletal muscle contusion.

    PubMed

    Zhang, Miao; Jiang, Shu-Kun; Tian, Zhi-Ling; Wang, Meng; Zhao, Rui; Wang, Lin-Lin; Li, Shan-Shan; Liu, Min; Li, Jiao-Yong; Zhang, Meng-Zhou; Guan, Da-Wei

    2015-01-01

    Skeletal muscle injuries repair typically is an overlapping event between inflammation and tissue repair. Our previous study has demonstrated that activation of cannabinoid receptor type 2 (CB2R) by JWH-133 alleviates fibrosis in the repair of rat skeletal muscle contusion. Meanwhile, accumulated data show that CB2R stimulation exerts anti-inflammatory property in sepsis and cystitis. However, the effects of CB2R on inflammatory cytokines in response to the repair of skeletal muscle contusion are still unknown. In this study, we used selective agonist or antagonist of CB2R to observe the role of CB2R on inflammation and fibrogenesis during the repair of contused skeletal muscles in rats. Our results revealed that treatment with Gp1a, a selective CB2R agonist, significantly decreased the infiltration of neutrophils and macrophages, the expression of pro-inflammatory cytokines MCP-1, TNF-α, IL-1β and IL-6, the expression of pro-fibrotic cytokines IL-4, IL-13, TGF-β and P-Smad3 while increased anti-fibrotic cytokine IL-10 production as compared with Vehicle. The opposite results were observed in the CB2R inhibition group with AM630. Our study demonstrated that CB2R orchestrates fibrogenesis through regulation of inflammatory response during the repair of skeletal muscle contusion. PMID:26097533

  10. Genetic Variation in the TAS2R38 Bitter Taste Receptor and Gastric Cancer Risk in Koreans.

    PubMed

    Choi, Jeong-Hwa; Lee, Jeonghee; Choi, Il Ju; Kim, Young-Woo; Ryu, Keun Won; Kim, Jeongseon

    2016-01-01

    The human TAS2R38 gene encodes a bitter taste receptor that regulates the bitterness perception and differentiation of ingested nutritional/poisonous compounds in the oral cavity and gastrointestinal tract. TAS2R38 gene variants are associated with alterations in individual sensitivity to bitter taste and food intake; hence, these genetic variants may modify the risk for diet-related diseases, including cancer. However, little is known about the association between TAS2R38 polymorphisms and gastric cancer susceptibility. The present case-control study examined the influence of TAS2R38 polymorphisms on food intake and determined whether they predict gastric cancer risk in Koreans. A total of 1,580 subjects, including 449 gastric cancer cases, were genotyped for TAS2R38 A49P, V262A, I296V and diplotypes. Dietary data were analysed to determine the total consumption of energy, fibre, vegetables, fruits, sweets, fats, alcohol and cigarettes. TAS2R38 diplotype was not associated with food, alcohol or cigarette consumption, either independent or dependent of gastric cancer phenotype. However, the PAV/AVI diplotype significantly increased gastric cancer risk (adjusted odds ratio: 1.513; 95% confidence interval: 1.148-1.994) independent of dietary intake. Findings suggest that TAS2R38 may be associated with the risk for gastric cancer in Koreans, although the TAS2R38 diplotype did not influence dietary intake. PMID:27245112

  11. The R2R3-Myb transcription fators of cotton: SNP characterization, chromosomal assignment, and phylogenetic analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The R2R3-Myb transcription factors are involved in many plant physiological and biochemical processes including regulation of trichome length and density in Arabidopsis. In cotton, Gossypium spp.,the developmental regulation of some R2R3-Myb transcription factors are related to fiber differentiatio...

  12. Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making.

    PubMed

    Zalocusky, Kelly A; Ramakrishnan, Charu; Lerner, Talia N; Davidson, Thomas J; Knutson, Brian; Deisseroth, Karl

    2016-03-31

    A marked bias towards risk aversion has been observed in nearly every species tested. A minority of individuals, however, instead seem to prefer risk (repeatedly choosing uncertain large rewards over certain but smaller rewards), and even risk-averse individuals sometimes opt for riskier alternatives. It is not known how neural activity underlies such important shifts in decision-making--either as a stable trait across individuals or at the level of variability within individuals. Here we describe a model of risk-preference in rats, in which stable individual differences, trial-by-trial choices, and responses to pharmacological agents all parallel human behaviour. By combining new genetic targeting strategies with optical recording of neural activity during behaviour in this model, we identify relevant temporally specific signals from a genetically and anatomically defined population of neurons. This activity occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), signalled unfavourable outcomes from the recent past at a time appropriate for influencing subsequent decisions, and also predicted subsequent choices made. Having uncovered this naturally occurring neural correlate of risk selection, we then mimicked the temporally specific signal with optogenetic control during decision-making and demonstrated its causal effect in driving risk-preference. Specifically, risk-preferring rats could be instantaneously converted to risk-averse rats with precisely timed phasic stimulation of NAc D2R cells. These findings suggest that individual differences in risk-preference, as well as real-time risky decision-making, can be largely explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes during decision-making. PMID:27007845

  13. Selection on the human bitter taste gene, TAS2R16, in Eurasian populations.

    PubMed

    Li, Hui; Pakstis, Andrew J; Kidd, Judith R; Kidd, Kenneth K

    2011-06-01

    Bitter taste is one of the most important senses alerting humans to noxious foods. In gatherer communities, sensitivity to bitterness is presumably advantageous because of various noxious plants. TAS2R16 is the gene coding the taste receptor molecules for some of the most common toxins in plants. A previous study of this gene indicated selection has increased the frequency of a derived allele in this gene that arose before the human expansion out of Africa. We have applied a different methodology for detecting selection, the Long Range Haplotype (LRH) analysis, to TAS2R16 in a larger sampling of populations from around the world. The haplotype with the derived alleles at both the functional polymorphism and a polymorphism in the regulatory region of TAS2R16 showed evidence for recent positive selection in most of the Eurasian populations, though the highest selection signal occurs in Mbuti Pygmies, an African hunter-gatherer group. In Eurasia, only populations of Mesopotamia and the southeast coast of China have no signals of selection. The evidence of recent selection found in most Eurasian populations differs from the geographic pattern seen in the earlier study of selection. One can speculate that the difference may result from a gathering lifestyle extending into the most recent 10,000 yrs and the need to recognize newly encountered bitter natural toxins as populations expanded into new environments and the biota changes with the ending of the most recent ice age. Alternatively, the promoter region variant may be a marker for altered function beyond what the derived amino acid allele conferred. PMID:21740153

  14. Transgenic LRRK2R1441G rats–a model for Parkinson disease?

    PubMed Central

    Shaikh, Komal T.; Yang, Alvin; Youshin, Ekaterina

    2015-01-01

    Parkinson disease (PD) is the most common movement disorder, characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. While the cause of this disease is largely unknown, a rare autosomal dominant familial form of PD is caused by a genetic mutation in the leucine-rich repeat kinase 2 (LRRK2) gene that presumably leads to a gain-of-function of LRRK2 kinase activity. Here, we explored the potential of over expression of this human gene in a new transgenic rat model to serve as an animal model for PD. Commercially available BAC transgenic rats expressing human LRRK2 with the familial PD mutation, R1441G, and their wild-type siblings were tested for deficits in motor function, sensorimotor gating, and higher cognitive function reminiscent of PD through the ages of 3, 6, 9 and 12 months. At 12 months of age, rats were exposed to intraperitoneal injections of the environmental toxin Paraquat or saline. Our results indicate that LRRK2R1441G transgenic rats do not show signs of neurodegeneration and do not develop significant motor or cognitive deficits until the age of 16 months. In addition, LRRK2R1441G transgenic rats did not show increased vulnerability to sub-toxic doses of Paraquat. Gene expression studies indicate that despite genomic presence and initial expression of the transgene, its expression was greatly reduced in our aged rats. We conclude that the transgenic LRRK2R1441G rat is not a valid model for studying the pathology of PD and discuss this in relation to other transgenic rat models. PMID:26020005

  15. Magnetocaloric Effect of RCo2 (R: Er, Ho, Dy) Compounds for Regenerative Magnetic Refrigeration

    NASA Astrophysics Data System (ADS)

    Matsumoto, Koichi; Kouen, Takaaki; Nishida, Ryouhei; Abe, Satoshi; Kamiya, Koji; Numazawa, Takenori

    2006-09-01

    Because of its high density, liquid hydrogen is one of the most promising forms of hydrogen for efficient, economic transport and storage. Magnetic refrigeration, which is based on the magnetocaloric effect of magnetic solids, has the potential to achieve high thermal efficiency and reduce the cost of hydrogen liquefaction. Magnetic properties of some candidate materials among RCo2 (R: rare earth) compounds have been studied. These materials have been found to have large magnetocaloric effects and suitable phase transition temperatures. Because the magnetocaloric effect is large only around the magnetic transition temperature, a series of magnetic materials with carefully designed transition temperatures is required.

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

    NASA Astrophysics Data System (ADS)

    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

  17. Synthesis and anticonvulsant activities of N-benzyl (2R)-2-acetamido-3-oxysubstituted propionamide derivatives

    PubMed Central

    Morieux, Pierre; Stables, James P.; Kohn, Harold

    2009-01-01

    Lacosamide has been submitted for regulatory approval in the United States and Europe for the treatment of epilepsy. Previous synthetic methods did not permit the elaboration of the structure–activity relationship (SAR) for the 3-oxy site in lacosamide. We report an expedient five-step stereospecific synthesis for N-benzyl (2R)-2-acetamido-3-oxysubstituted propionamide analogs beginning with d-serine methyl ester. The procedure incorporated alkyl (e.g. methyl, primary, secondary, and tertiary) and aryl groups at this position. The SAR for the 3-oxy site showed maximal activity in animal seizure models for small 3-alkoxy substituents. PMID:18789868

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

    NASA Astrophysics Data System (ADS)

    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

  19. HIGH D{sub 2}O/HDO RATIO IN THE INNER REGIONS OF THE LOW-MASS PROTOSTAR NGC 1333 IRAS2A

    SciTech Connect

    Coutens, A.; Jørgensen, J. K.; Persson, M. V.; Van Dishoeck, E. F.; Vastel, C.; Taquet, V.

    2014-09-01

    Water plays a crucial role both in the interstellar medium and on Earth. To constrain its formation mechanisms and its evolution through the star formation process, the determination of the water deuterium fractionation ratios is particularly suitable. Previous studies derived HDO/H{sub 2}O ratios in the warm inner regions of low-mass protostars. We here report a detection of the D{sub 2}O 1{sub 1,} {sub 0}-1{sub 0,} {sub 1} transition toward the low-mass protostar NGC 1333 IRAS2A with the Plateau de Bure interferometer: this represents the first interferometric detection of D{sub 2}O—and only the second solar-type protostar for which this isotopologue is detected. Using the observations of the HDO 5{sub 4,} {sub 2}-6{sub 3,} {sub 3} transition simultaneously detected and three other HDO lines previously observed, we show that the HDO line fluxes are well reproduced with a single excitation temperature of 218 ± 21 K and a source size of ∼0.''5. The D{sub 2}O/HDO ratio is ∼(1.2 ± 0.5) × 10{sup –2}, while the use of previous H{sub 2}{sup 18}O observations give an HDO/H{sub 2}O ratio of ∼(1.7 ± 0.8) × 10{sup –3}, i.e., a factor of seven lower than the D{sub 2}O/HDO ratio. These results contradict the predictions of current grain surface chemical models and indicate that either the surface deuteration processes are poorly understood or that both sublimation of grain mantles and water formation at high temperatures (≳230 K) take place in the inner regions of this source. In the second scenario, the thermal desorption of the grain mantles would explain the high D{sub 2}O/HDO ratio, while water formation at high temperature would explain significant extra production of H{sub 2}O leading to a decrease of the HDO/H{sub 2}O ratio.

  20. Biochemical Disease-Free Rate and Toxicity for Men Treated With Iodine-125 Prostate Brachytherapy With D{sub 90} {>=}180 Gy

    SciTech Connect

    Gomez-Iturriaga Pina, Alfonso; Crook, Juanita; Borg, Jette; Ma, Clement

    2010-10-01

    Purpose: Iodine-125 ({sup 125}I) prostate brachytherapy is planned with a prescribed dose of 145 Gy and minimal dose received by 90% of the prostate (D{sub 90}) of 120-125% (174-181 Gy). We examined the clinical outcomes and toxicity profile of men receiving a D{sub 90} (isodose enclosing 90% of the prostate) of {>=}180 Gy. Methods and Materials: Between March 1999 and May 2006, 129 men (17% of our total brachytherapy population) treated with {sup 125}I monotherapy for Stage T1-T2 prostate cancer received a D{sub 90} {>=}180 Gy. Implants were performed using transrectal ultrasonography and fluoroscopic guidance. The 1-month postplan dosimetry used magnetic resonance imaging-computed tomography fusion. The minimal follow-up was 2 years. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 3. Results: The median patient age was 63 years (range, 50-76), and the pretreatment prostate-specific antigen level was 5.5 ng/mL (range, 0.6-13.5). The Gleason score was {<=}6 in 125 patients and was 7 in 4 patients. The median follow-up period was 40 months (range, 24-111), and the median D{sub 90} was 186 Gy. The median minimal dose received by 30% of the urethra was 203 Gy, and the median rectal volume receiving a minimum of 100% of the prescribed dose was 0.81 cm{sup 3}. Acute Grade 2 genitourinary toxicity was seen in 5.4% and late Grade 2 in 7%. Late urinary retention (Grade 3) was seen in 2 patients (1.5%). Grade 1 rectal bleeding occurred in 9.3% and Grade 2 in 2.3%. On univariate logistic regression analysis, none of the clinical and dosimetric parameters predicted for rectal bleeding. Of 110 men who were potent before treatment, 81% remained potent 5 years after treatment. Three biochemical failures and only one local failure developed. The 5-year biochemical no evidence of disease rate using the 'nadir plus 2' definition was 96.8%. Conclusion: A D{sub 90} of {>=}180 Gy is associated with

  1. Structural synthesis of a class of 2R2T hybrid mechanisms

    NASA Astrophysics Data System (ADS)

    Tian, Chunxu; Fang, Yuefa; Guo, Sheng

    2016-01-01

    Conventional overconstrained parallel manipulators have been widely studied both in industry and academia, however the structural synthesis of hybrid mechanisms with additional constraints is seldom studied, especially for the four degrees of freedom(DOF) hybrid mechanisms. In order to develop a manipulator with additional constraints, a class of important spatial mechanisms with coupling chains(CCs) whose motion type is two rotations and two translations(2R2T) is presented. Based on screw theory, the combination of different types of limbs which are used to construct parallel mechanisms and coupling chains is proposed. The basic types of the general parallel mechanisms and geometric conditions of the kinematic chains are given using constraint synthesis method. Moreover, the 2R2T motion pattern hybrid mechanisms which are derived by adding coupling chains between different serial kinematic chains(SKCs) of the corresponding parallel mechanisms are presented. According to the constraint analysis of the mechanisms, the movement relationship of the moving platform and the kinematic chains is derived by disassembling the coupling chains. At last, fourteen novel hybrid mechanisms with two or three serial kinematic chains are presented. The proposed novel hybrid mechanisms and construction method enrich the family of the spatial mechanisms and provide an instruction to design more complex hybrid mechanisms.

  2. In-situ defect detection systems for R2R flexible PV barrier films

    NASA Astrophysics Data System (ADS)

    Gao, F.; Muhamedsalih, H.; Tang, D.; Elrawemi, M.; Blunt, L.; Jiang, X.; Edge, S.; Bird, D.; Hollis, P.

    2015-08-01

    Film processing procedures by means of Roll-to-Roll (R2R) for barrier coatings can often result in PV barrier films being manufactured with significant quantities of defects, which results in lower efficiency and a short life span. In order to improve the process yield and product efficiency, it is desirable to develop an inspection system that can detect transparent barrier film defects in the production line during film processing. Off-line detection of defects in transparent PV barrier films is difficult and time consuming. Consequently, implementing an accurate in-situ defects inspection system in the production environment is even more challenging, since the requirements on positioning, fast measurement, long term stability and robustness against environmental disturbance are demanding. This paper reports on the development and deployment of two in-situ PV barrier films defect detection systems, one based on wavelength scanning interferometry (WSI) and the other on White Light Channeled Spectral Interferometry (WLCSI), and the integration into an R2R film processing line at the Centre for Process Innovation (CPI). The paper outlines the environmental vibration strategy for both systems, and the developed auto-focusing methodology for WSI. The systems have been tested and characterised and initial results compared to laboratory-based instrumentation are presented.

  3. Spontaneous quasi single helicity regimes in EXTRAP T2R reversed-field pinch

    SciTech Connect

    Frassinetti, L.; Brunsell, P. R.; Drake, J. R.; Menmuir, S.; Cecconello, M.

    2007-11-15

    In recent years, good progress toward a better understanding and control of the plasma performance in reversed-field pinch devices has been made. These improvements consist both of the discovery of spontaneous plasma regimes, termed the quasi single helicity (QSH) regime, in which part of the plasma core is no longer stochastic, and of the development of techniques for active control of plasma instabilities. In this paper, a systematic study of spontaneous QSH in the EXTRAP T2R device [P. R. Brunsell, H. Bergsaker, M. Cecconello et al., Plasma Phys. Control. Fusion 43, 1457 (2001)] is presented. In this device, QSH states can occur spontaneously and it is associated with magnetic and thermal structures. A statistical analysis to determine the most favorable experimental conditions to have a transition to the QSH regime will be presented. The results described here are useful to understand the underlying properties of QSH regimes in view of future applications of the QSH active control in EXTRAP T2R; they are also important to have a comparison with the QSH studied in other devices.

  4. Topological charges in SL(2,R) covariant massive 11-dimensional and type IIB supergravity

    NASA Astrophysics Data System (ADS)

    Callister, Andrew K.; Smith, Douglas J.

    2009-12-01

    In this paper we construct closed expressions that correspond to the topological charges of the various 1/2-BPS states of the maximal 10- and 11-dimensional supergravity theories. These expressions are related to the structure of the supersymmetry algebras in curved spacetimes. We mainly focus on IIB supergravity and 11-dimensional supergravity in a double M9-brane background, with an emphasis on the SL(2,R) multiplet structure of the charges and how these map between theories. This includes the charges corresponding to the multiplets of 7- and 9-branes in IIB. We find that examining the possible multiplet structures of the charges provides another tool for exploring the spectrum of BPS states that appear in these theories. As a prerequisite to constructing the charges we determine the field equations and multiplet structure of the 11-dimensional gauge potentials, extending previous results on the subject. The massive gauge transformations of the fields are also discussed. We also demonstrate how these massive gauge transformations are compatible with the construction of an SL(2,R) covariant kinetic term in the 11-dimensional Kaluza-Klein monopole worldvolume action.

  5. Epigenetic modification of vomeronasal (V2r) precursor neurons by histone deacetylation.

    PubMed

    Xia, J; Broad, K D; Emson, P C; Keverne, E B

    2010-09-01

    Vomeronasal neurons undergo continuous neurogenesis throughout development and adult life. These neurons originate as stem cells in the apical zone of the lumen of the vomeronasal organ (VNO) and are described as nestin-expressing glia-like progenitor cells (Murdoch and Roskams, 2008). They then migrate horizontally along the basal zone where they differentiate into functional VNO neurons (Kaba et al., 1988). We harvested progenitor cells from the adult VNO and, after 3-6 months of invitro culture, these VNO neurons remained in a stable undifferentiated state expressing nestin, beta-tubulin III and vomeronasal type 2 (V2r), but not vomeronasal type 1 (V1r) receptors. Application of histone-deacetylase inhibitors induced development of a neural phenotype that expressed V2r receptors, a down-regulation of nestin expression and no change in any specific genetic markers associated with glial cells. Treatment with valproic acid induced extensive changes in gene expression in the axon guidance pathway. The adult VNO is known to functionally adapt throughout life as a consequence of changes in both a mouse's physiological status and its social environment. These pluripotent cultured neurons may provide valuable insights into how changes in both physiology and environment, exert epigenetic effects on vomeronasal neurons as they undergo continuous neurogenesis and development throughout the life of a mouse. PMID:20594945

  6. Age modifies the genotype-phenotype relationship for the bitter receptor TAS2R38

    PubMed Central

    2010-01-01

    Background The purpose of this study was to investigate the effect of TAS2R38 haplotypes and age on human bitter taste perception. Results Children (3 to 10 yrs), adolescents (11 to 19 yrs) and adults (mostly mothers, 20 to 55 yrs (N = 980) were measured for bitter taste thresholds for 6-n-propylthiouracil (PROP) and genotyped for three polymorphisms of the AS2R38 gene (A49P, V262A, I296V). Subjects were grouped by haplotype and age, as well as sex and race/ethnicity, and compared for PROP thresholds. Subjects with the same haplotype were similar in bitter threshold regardless of race/ethnicity (all ages) or sex (children and adolescents; all p-values > 0.05) but age was a modifier of the genotype-phenotype relationship. Specifically, AVI/PAV heterozygous children could perceive a bitter taste at lower PROP concentrations than could heterozygous adults, with the thresholds of heterozygous adolescents being intermediate (p < 0.001). Similar age effects were not observed for subjects with the PAV/PAV or AVI/AVI homozygous haplotypes (p > 0.05) perhaps because there is less variation in taste perception among these homozygotes. Conclusions These data imply that the change in PROP bitter sensitivity which occurs over the lifespan (from bitter sensitive to less so) is more common in people with a particular haplotype combination, i.e., AVI/PAV heterozygotes. PMID:20594349

  7. IGF-2R-Gαq signaling and cardiac hypertrophy in the low-birth-weight lamb.

    PubMed

    Wang, Kimberley C W; Tosh, Darran N; Zhang, Song; McMillen, I Caroline; Duffield, Jaime A; Brooks, Doug A; Morrison, Janna L

    2015-04-01

    The cardiac insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy in a heterotrimeric G protein receptor-coupled manner involving αq (Gαq) or αs (Gαs). We have previously shown increased left ventricular weight and cardiac IGF-2 and IGF-2R gene expression in low-birth-weight (LBW) compared with average-birth-weight (ABW) lambs. Here, we have investigated the cardiac expression of IGF-2 gene variants, the degree of histone acetylation, and the abundance of proteins in the IGF-2R downstream signaling pathway in ABW and LBW lambs. Samples from the left ventricle of ABW and LBW lambs were collected at 21 days of age. There was increased phospho-CaMKII protein with decreased HDAC 4 abundance in the LBW compared with ABW lambs. There was increased GATA 4 and decreased phospho-troponin I abundance in LBW compared with ABW lambs, which are markers of pathological cardiac hypertrophy and impaired or reduced contractility, respectively. There was increased histone acetylation of H3K9 at IGF-2R promoter and IGF-2R intron 2 differentially methylated region in the LBW lamb. In conclusion, histone acetylation of IGF-2R may lead to increased IGF-2R mRNA expression and subsequently mediate Gαq signaling early in life via CaMKII, resulting in an increased risk of left ventricular hypertrophy and cardiovascular disease in adult life. PMID:25632020

  8. IGF-2R-Gαq signaling and cardiac hypertrophy in the low-birth-weight lamb

    PubMed Central

    Wang, Kimberley C. W.; Tosh, Darran N.; Zhang, Song; McMillen, I. Caroline; Duffield, Jaime A.; Brooks, Doug A.

    2015-01-01

    The cardiac insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy in a heterotrimeric G protein receptor-coupled manner involving αq (Gαq) or αs (Gαs). We have previously shown increased left ventricular weight and cardiac IGF-2 and IGF-2R gene expression in low-birth-weight (LBW) compared with average-birth-weight (ABW) lambs. Here, we have investigated the cardiac expression of IGF-2 gene variants, the degree of histone acetylation, and the abundance of proteins in the IGF-2R downstream signaling pathway in ABW and LBW lambs. Samples from the left ventricle of ABW and LBW lambs were collected at 21 days of age. There was increased phospho-CaMKII protein with decreased HDAC 4 abundance in the LBW compared with ABW lambs. There was increased GATA 4 and decreased phospho-troponin I abundance in LBW compared with ABW lambs, which are markers of pathological cardiac hypertrophy and impaired or reduced contractility, respectively. There was increased histone acetylation of H3K9 at IGF-2R promoter and IGF-2R intron 2 differentially methylated region in the LBW lamb. In conclusion, histone acetylation of IGF-2R may lead to increased IGF-2R mRNA expression and subsequently mediate Gαq signaling early in life via CaMKII, resulting in an increased risk of left ventricular hypertrophy and cardiovascular disease in adult life. PMID:25632020

  9. Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis

    PubMed Central

    2013-01-01

    Background Tuberculosis is one of the leading causes of mortality throughout the world. Mycobacterium tuberculosis, the agent of human tuberculosis, has developed strategies involving proteins and other compounds called virulence factors to subvert human host defences and damage and invade the human host. Among these virulence-related proteins are the Mce proteins, which are encoded in the mce1, mce2, mce3 and mce4 operons of M. tuberculosis. The expression of the mce2 operon is negatively regulated by the Mce2R transcriptional repressor. Here we evaluated the role of Mce2R during the infection of M. tuberculosis in mice and macrophages and defined the genes whose expression is in vitro regulated by this transcriptional repressor. Results We used a specialized transduction method for generating a mce2R mutant of M. tuberculosis H37Rv. Although we found equivalent replication of the MtΔmce2R mutant and the wild type strains in mouse lungs, overexpression of Mce2R in the complemented strain (MtΔmce2RComp) significantly impaired its replication. During in vitro infection of macrophages, we observed a significantly increased association of the late endosomal marker LAMP-2 to MtΔmce2RComp-containing phagosomes as compared to MtΔmce2R and the wild type strains. Whole transcriptional analysis showed that Mce2R regulates mainly the expression of the mce2 operon, in the in vitro conditions studied. Conclusions The findings of the current study indicate that Mce2R weakly represses the in vivo expression of the mce2 operon in the studied conditions and argue for a role of the proteins encoded in Mce2R regulon in the arrest of phagosome maturation induced by M. tuberculosis. PMID:24007602

  10. CYP2R1 Mutations Impair Generation of 25-hydroxyvitamin D and Cause an Atypical Form of Vitamin D Deficiency

    PubMed Central

    Fischer, Philip R.; Singh, Ravinder J.; Roizen, Jeffrey; Levine, Michael A.

    2015-01-01

    Context: Production of the active vitamin D hormone 1,25-dihydroxyvitamin D requires hepatic 25-hydroxylation of vitamin D. The CYP2R1 gene encodes the principal vitamin D 25-hydroxylase in humans. Objective: This study aimed to determine the prevalence of CYP2R1 mutations in Nigerian children with familial rickets and vitamin D deficiency and assess the functional effect on 25-hydroxylase activity. Design and Participants: We sequenced the CYP2R1 gene in subjects with sporadic rickets and affected subjects from families in which more than one member had rickets. Main Outcome Measures: Function of mutant CYP2R1 genes as assessed in vivo by serum 25-hydroxyvitamin D values after administration of vitamin D and in vitro by analysis of mutant forms of the CYP2R1. Results: CYP2R1 sequences were normal in 27 children with sporadic rickets, but missense mutations were identified in affected members of 2 of 12 families, a previously identified L99P, and a novel K242N. In silico analyses predicted that both substitutions would have deleterious effects on the variant proteins, and in vitro studies showed that K242N and L99P had markedly reduced or complete loss of 25-hydroxylase activity, respectively. Heterozygous subjects were less affected than homozygous subjects, and oral administration of vitamin D led to significantly lower increases in serum 25-hydroxyvitamin D in heterozygous than in control subjects, whereas homozygous subjects showed negligible increases. Conclusion: These studies confirm that CYP2R1 is the principal 25-hydroxylase in humans and demonstrate that CYP2R1 alleles have dosage-dependent effects on vitamin D homeostasis. CYP2R1 mutations cause a novel form of genetic vitamin D deficiency with semidominant inheritance. PMID:25942481

  11. 1α,25 dihydroxi-vitamin D{sub 3} modulates CDK4 and CDK6 expression and localization

    SciTech Connect

    Irazoqui, Ana P.; Heim, Nadia B.; Boland, Ricardo L.; Buitrago, Claudia G.

    2015-03-27

    We recently reported that the vitamin D receptor (VDR) and p38 MAPK participate in pro-differentiation events triggered by 1α,25(OH){sub 2}-vitamin D{sub 3} [1,25D] in skeletal muscle cells. Specifically, our studies demonstrated that 1,25D promotes G0/G1 arrest of cells inducing cyclin D3 and cyclin dependent kinases inhibitors (CKIs) p21{sup Waf1/Cip1} and p27{sup Kip1} expression in a VDR and p38 MAPK dependent manner. In this work we present data indicating that cyclin-dependent kinases (CDKs) 4 and 6 also play a role in the mechanism by which 1,25D stimulates myogenesis. To investigate VDR involvement in hormone regulation of CDKs 4 and 6, we significantly reduced its expression by the use of a shRNA against mouse VDR, generating the skeletal muscle cell line C2C12-VDR. Investigation of changes in cellular cycle regulating proteins by immunoblotting showed that the VDR is involved in the 1,25D –induced CDKs 4 and 6 protein levels at 6 h of hormone treatment. CDK4 levels remains high during S phase peak and G0/G1 arrest while CDK6 expression decreases at 12 h and increases again al 24 h. The up-regulation of CDKs 4 and 6 by 1,25D (6 h) was abolished in C2C12 cells pre-treated with the ERK1/2 inhibitor, UO126. Moreover, CDKs 4 and 6 expression induced by the hormone nor was detected when α and β isoforms of p38 MAPK were inhibited by compound SB203580. Confocal images show that there is not co-localization between VDR and CDKs at 6 h of hormone treatment, however CDK4 and VDR co-localizates in nucleus after 12 h of 1,25D exposure. Of relevance, at this time 1,25D promotes CDK6 localization in a peri-nuclear ring. Our data demonstrate that the VDR, ERK1/2 and p38 MAPK are involved in the control of CDKs 4 and 6 by 1,25D in skeletal muscle cells sustaining the operation of a VDR and MAPKs –dependent mechanism in hormone modulation of myogenesis. - Highlights: • 1,25D modulates CDKs 4 and 6 expression in skeletal muscle cells. • CDK4 co

  12. Probenecid Inhibits the Human Bitter Taste Receptor TAS2R16 and Suppresses Bitter Perception of Salicin

    PubMed Central

    Greene, Tiffani A.; Alarcon, Suzanne; Thomas, Anu; Berdougo, Eli; Doranz, Benjamin J.; Breslin, Paul A. S.; Rucker, Joseph B.

    2011-01-01

    Bitter taste stimuli are detected by a diverse family of G protein-coupled receptors (GPCRs) expressed in gustatory cells. Each bitter taste receptor (TAS2R) responds to an array of compounds, many of which are toxic and can be found in nature. For example, human TAS2R16 (hTAS2R16) responds to β-glucosides such as salicin, and hTAS2R38 responds to thiourea-containing molecules such as glucosinolates and phenylthiocarbamide (PTC). While many substances are known to activate TAS2Rs, only one inhibitor that specifically blocks bitter receptor activation has been described. Here, we describe a new inhibitor of bitter taste receptors, p-(dipropylsulfamoyl)benzoic acid (probenecid), that acts on a subset of TAS2Rs and inhibits through a novel, allosteric mechanism of action. Probenecid is an FDA-approved inhibitor of the Multidrug Resistance Protein 1 (MRP1) transporter and is clinically used to treat gout in humans. Probenecid is also commonly used to enhance cellular signals in GPCR calcium mobilization assays. We show that probenecid specifically inhibits the cellular response mediated by the bitter taste receptor hTAS2R16 and provide molecular and pharmacological evidence for direct interaction with this GPCR using a non-competitive (allosteric) mechanism. Through a comprehensive analysis of hTAS2R16 point mutants, we define amino acid residues involved in the probenecid interaction that result in decreased sensitivity to probenecid while maintaining normal responses to salicin. Probenecid inhibits hTAS2R16, hTAS2R38, and hTAS2R43, but does not inhibit the bitter receptor hTAS2R31 or non-TAS2R GPCRs. Additionally, structurally unrelated MRP1 inhibitors, such as indomethacin, fail to inhibit hTAS2R16 function. Finally, we demonstrate that the inhibitory activity of probenecid in cellular experiments translates to inhibition of bitter taste perception of salicin in humans. This work identifies probenecid as a pharmacological tool for understanding the cell biology of

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

    NASA Astrophysics Data System (ADS)

    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

  14. Bitter Receptor Gene (TAS2R38), 6-n-Propylthiouracil (PROP) Bitterness and Alcohol Intake

    PubMed Central

    Duffy, Valerie B.; Davidson, Andrew C.; Kidd, Judith R.; Kidd, Kenneth K.; Speed, William C.; Pakstis, Andrew J.; Reed, Danielle R.; Snyder, Derek J.; Bartoshuk, Linda M.

    2006-01-01

    Background Phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP), chemically related compounds, are probes for genetic variation in bitter taste, although PROP is safer with less sulfurous odor. Threshold for PROP distinguishes nontasters (increased threshold) from tasters (lower threshold); perceived intensity subdivides tasters into medium tasters (PROP is bitter) and supertasters (PROP is very bitter). Compared with supertasters, nontasters have fewer taste papillae on the anterior tongue (fungiform papillae) and experience less negative (e.g., bitterness) and more positive (eg, sweetness) sensations from alcohol. We determined whether the TAS2R38 gene at 7q36 predicted PROP bitterness, alcohol sensation and use. Methods Healthy adults (53 women, 31 men; mean age 36 years)—primarily light and moderate drinkers—reported the bitterness of five PROP concentrations (0.032–3.2 mM) and intensity of 50% ethanol on the general Labeled Magnitude Scale. PROP threshold and density of fungiform papillae were also measured. Subjects had common TAS2R38 gene haplotypes [alanine-valine-isoleucine (AVI) and proline-alanine-valine (PAV)]. Results PROP bitterness varied significantly across genotypes with repeated measures ANOVA: 26 AVI/AVI homozygotes tasted less bitterness than either 37 PAV/AVI heterozygotes or 21 PAV/PAV homozygotes. The PAV/PAV group exceeded the PAV/AVI group for bitterness only for the top PROP concentrations. The elevated bitterness was musch less than if we defined the groups using psychophysical criteria. With multiple regression analyses, greater bitterness from 3.2 mM PROP was a significant predictor of greater ethanol intensity and less alcohol intake—effects separate from age and sex. Genotype was a significant predictor of alcohol intake, but not ethanol intensity. With ANOVA, AVI/AVI homozygotes reported higher alcohol use than either PAV/AVI heterozygotes or PAV/PAV homozygotes. When age effects were minimized, PROP bitterness

  15. Investigation on the magnetocaloric effect in RNi2 (R: Dy, tb) melt-spun ribbon

    NASA Astrophysics Data System (ADS)

    de Souza, M. V.

    2016-08-01

    We report a theoretical and experimental investigation on the magnetocaloric properties of the rare earth RNi2 (R=Dy,Tb) in melt-spun ribbon and bulk form. The theoretical calculations were performed using a Hamiltonian model including the Zeeman-exchange interactions and the crystalline electrical field. Thus the magnetocaloric potential was calculated in the easy magnetic axes, in order an average over all of the possible directions. The isothermal entropy-change dependence on temperature calculated was compared with available experimental data for melt-spun ribbon and bulk material. We also investigated, theoretically and experimentally, the behavior of a DyNi2 and TbNi2 composite with optimized molar proportions and discussed this in the context of the optimum regeneration Ericsson cycle.

  16. Controlled Vocabularies and Ontologies for Oceanographic Data: The R2R Eventlogger Project

    NASA Astrophysics Data System (ADS)

    Coburn, E.; Maffei, A. R.; Chandler, C. L.; Raymond, L. M.

    2012-12-01

    Research vessels coordinated by the United States University-National Oceanographic Laboratory System (US-UNOLS) collect data which is considered an important oceanographic resource. The NSF-funded Rolling Deck to Repository (R2R) project aims to improve access to this data and diminish the barriers to use. One aspect of the R2R project has been to develop a shipboard scientific event logging system, Eventlogger, that incorporates best practice guidelines, controlled vocabularies, a cruise metadata schema, and a scientific event log. This will facilitate the eventual ingestion of datasets into oceanographic data repositories for subsequent integration and synthesis by investigators. One important aspect of this system is the careful use of controlled vocabularies and ontologies. Existing ontologies, where available, will be used and others will be developed. The use of internationally-informed, consensus-driven controlled vocabularies will make datasets more interoperable, and discoverable. The R2R Eventlogger project is led by Woods Hole Oceanographic Institution (WHOI), and the management of the controlled vocabularies and mapping of these vocabularies to authoritative community vocabularies are led by the Data Librarian in the Marine Biological Laboratory/Woods Hole Oceanographic Institution (MBLWHOI) Library. The first target vocabulary is oceanographic instruments. Management of this vocabulary has thus far consisted of reconciling local community terms with the more widely used SeaDataNet Device Vocabulary terms. Rather than adopt existing terms, often the local terms are mapped by data managers in the NSF-funded Biological and Chemical Oceanographic Data Management Office (BCO-DMO) to the existing terms as they are given by investigators and often provide important information and meaning. New terms (often custom, or modified instruments) are submitted for review to the SeaDataNet community listserv for discussion and eventual incorporation into the Device

  17. D-branes and extended characters in SL(2,R)/U(1)

    NASA Astrophysics Data System (ADS)

    Fotopoulos, Angelos; Niarchos, Vasilis; Prezas, Nikolaos

    2005-03-01

    We present a detailed study of D-branes in the axially gauged SL(2/U(1) coset conformal field theory for integer level k. Our analysis is based on the modular bootstrap approach and utilizes the extended SL(2,R)/U(1) characters and the embedding of the parafermionic coset algebra in the N=2 superconformal algebra. We propose three basic classes of boundary states corresponding to D0-, D1- and D2-branes. We verify that these boundary states satisfy the Cardy consistency conditions and discuss their physical properties. The D0- and D1-branes agree with those found in earlier work by Ribault and Schomerus using different methods (descent from the Euclidean AdS model). The D2-branes are new. They are not, in general, space-filling but extend from the asymptotic circle at infinity up to a minimum distance ρ⩾0 from the tip of the cigar.

  18. Thermodynamic and transport properties of RSn2 (R=Tb-Tm, Lu, Y) single crystals

    NASA Astrophysics Data System (ADS)

    Zhao, Liang L.; Mehlman, Michael S.; Besara, Tiglet; Siegrist, Theo; Morosan, E.

    2013-09-01

    We report the anisotropic magnetization, heat capacity and resistivity measurements for isostructural RSn2 (R=Tb-Tm, Lu, Y) single crystals. The R=Tb-Tm compounds exhibit long range antiferromagnetic ordering with TN ranging from 26.3 K to 3.6 K. An additional incommensurate-to-commensurate transition at a lower critical temperature T1 is observed for R=Tb-Ho. Field-induced metamagnetic transitions have also been observed for all magnetic rare earth compounds. The resistivity has a typical metallic character with a relatively high residual resistivity ratio. Both the AFM ordering temperature and spin disordered resistivity scale with the de Gennes factor. The magnetic heat capacity data indicate partially lifted ground state degeneracies associated with crystal electric field splitting.

  19. Integrable spin chain for the SL(2,R)/U(1) black hole sigma model.

    PubMed

    Ikhlef, Yacine; Jacobsen, Jesper Lykke; Saleur, Hubert

    2012-02-24

    We introduce a spin chain based on finite-dimensional spin-1/2 SU(2) representations but with a non-Hermitian "Hamiltonian" and show, using mostly analytical techniques, that it is described at low energies by the SL(2,R)/U(1) Euclidian black hole conformal field theory. This identification goes beyond the appearance of a noncompact spectrum; we are also able to determine the density of states, and show that it agrees with the formulas in [J. Maldacena, H. Ooguri, and J. Son, J. Math. Phys. (N.Y.) 42, 2961 (2001)] and [A. Hanany, N. Prezas, and J. Troost, J. High Energy Phys. 04 (2002) 014], hence providing a direct "physical measurement" of the associated reflection amplitude. PMID:22463514

  20. An R2R3-MYB Transcription Factor Regulates Eugenol Production in Ripe Strawberry Fruit Receptacles.

    PubMed

    Medina-Puche, Laura; Molina-Hidalgo, Francisco Javier; Boersma, Maaike; Schuurink, Robert C; López-Vidriero, Irene; Solano, Roberto; Franco-Zorrilla, José-Manuel; Caballero, José Luis; Blanco-Portales, Rosario; Muñoz-Blanco, Juan

    2015-06-01

    Eugenol is a volatile phenylpropanoid that contributes to flower and ripe fruit scent. In ripe strawberry (Fragaria × ananassa) fruit receptacles, eugenol is biosynthesized by eugenol synthase (FaEGS2). However, the transcriptional regulation of this process is still unknown. We have identified and functionally characterized an R2R3 MYB transcription factor (emission of benzenoid II [FaEOBII]) that seems to be the orthologous gene of PhEOBII from Petunia hybrida, which contributes to the regulation of eugenol biosynthesis in petals. The expression of FaEOBII was ripening related and fruit receptacle specific, although high expression values were also found in petals. This expression pattern of FaEOBII correlated with eugenol content in both fruit receptacle and petals. The expression of FaEOBII was repressed by auxins and activated by abscisic acid, in parallel to the ripening process. In ripe strawberry receptacles, where the expression of FaEOBII was silenced, the expression of cinnamyl alcohol dehydrogenase1 and FaEGS2, two structural genes involved in eugenol production, was down-regulated. A subsequent decrease in eugenol content in ripe receptacles was also observed, confirming the involvement of FaEOBII in eugenol metabolism. Additionally, the expression of FaEOBII was under the control of FaMYB10, another R2R3 MYB transcription factor that regulates the early and late biosynthetic genes from the flavonoid/phenylpropanoid pathway. In parallel, the amount of eugenol in FaMYB10-silenced receptacles was also diminished. Taken together, these data indicate that FaEOBII plays a regulating role in the volatile phenylpropanoid pathway gene expression that gives rise to eugenol production in ripe strawberry receptacles. PMID:25931522

  1. Differential and integral cross sections for the rotationally inelastic scattering of methyl radicals with H{sub 2} and D{sub 2}

    SciTech Connect

    Tkáč, Ondřej; Orr-Ewing, Andrew J.; Ma, Qianli; Dagdigian, Paul J.; Rusher, Cassandra A.; Greaves, Stuart J.

    2014-05-28

    Comparisons are presented of experimental and theoretical studies of the rotationally inelastic scattering of CD{sub 3} radicals with H{sub 2} and D{sub 2} collision partners at respective collision energies of 680 ± 75 and 640 ± 60 cm{sup −1}. Close-coupling quantum-mechanical calculations performed using a newly constructed ab initio potential energy surface (PES) provide initial-to-final CD{sub 3} rotational level (n, k → n′, k′) integral and differential cross sections (ICSs and DCSs). The DCSs are compared with crossed molecular beam and velocity map imaging measurements of angular scattering distributions, which serve as a critical test of the accuracy of the new PES. In general, there is very good agreement between the experimental measurements and the calculations. The DCSs for CD{sub 3} scattering from both H{sub 2} and D{sub 2} peak in the forward hemisphere for n′ = 2–4 and shift more to sideways and backward scattering for n′ = 5. For n′ = 6–8, the DCSs are dominated by backward scattering. DCSs for a particular CD{sub 3} n → n′ transition have a similar angular dependence with either D{sub 2} or H{sub 2} as collision partner. Any differences between DCSs or ICSs can be attributed to mass effects because the PES is unchanged for CD{sub 3}−H{sub 2} and CD{sub 3}–D{sub 2} collisions. Further comparisons are drawn between the CD{sub 3}–D{sub 2} scattering and results for CD{sub 3}–He presented in our recent paper [O. Tkáč, A. G. Sage, S. J. Greaves, A. J. Orr-Ewing, P. J. Dagdigian, Q. Ma, and M. H. Alexander, Chem. Sci. 4, 4199 (2013)]. These systems have the same reduced mass, but are governed by different PESs.

  2. MODELING THE QUANTUM INTERFERENCE SIGNATURES OF THE Ba II D{sub 2} 4554 A LINE IN THE SECOND SOLAR SPECTRUM

    SciTech Connect

    Smitha, H. N.; Nagendra, K. N.; Sampoorna, M.; Stenflo, J. O. E-mail: knn@iiap.res.in E-mail: stenflo@astro.phys.ethz.ch

    2013-05-10

    Quantum interference effects play a vital role in shaping the linear polarization profiles of solar spectral lines. The Ba II D{sub 2} line at 4554 A is a prominent example, where the F-state interference effects due to the odd isotopes produce polarization profiles, which are very different from those of the even isotopes that have no F-state interference. It is therefore necessary to account for the contributions from the different isotopes to understand the observed linear polarization profiles of this line. Here we do radiative transfer modeling with partial frequency redistribution (PRD) of such observations while accounting for the interference effects and isotope composition. The Ba II D{sub 2} polarization profile is found to be strongly governed by the PRD mechanism. We show how a full PRD treatment succeeds in reproducing the observations, while complete frequency redistribution alone fails to produce polarization profiles that have any resemblance to the observed ones. However, we also find that the line center polarization is sensitive to the temperature structure of the model atmosphere. To obtain a good fit to the line center peak of the observed Stokes Q/I profile, a small modification of the FALX model atmosphere is needed, by lowering the temperature in the line-forming layers. Because of the pronounced temperature sensitivity of the Ba II D{sub 2} line it may not be a suitable tool for Hanle magnetic-field diagnostics of the solar chromosphere, because there is currently no straightforward way to separate the temperature and magnetic-field effects from each other.

  3. Disruption of the Murine Glp2r Impairs Paneth Cell Function and Increases Susceptibility to Small Bowel Enteritis

    PubMed Central

    Lee, Seung-Jun; Lee, Jennifer; Li, Karen K.; Holland, Dianne; Maughan, Heather; Guttman, David S.; Yusta, Bernardo; Drucker, Daniel J.

    2013-01-01

    Exogenous glucagon-like peptide-2 receptor (GLP-2R) activation elicits proliferative and cytoprotective responses in the gastrointestinal mucosa and ameliorates experimental small and large bowel gut injury. Nevertheless, the essential physiological role(s) of the endogenous GLP-2R remain poorly understood. We studied the importance of the GLP-2R for gut growth, epithelial cell lineage allocation, the response to mucosal injury, and host-bacterial interactions in Glp2r−/− and littermate control Glp2r+/+ mice. Glp2r−/− mice exhibit normal somatic growth and preserved small and large bowel responses to IGF-I and keratinocyte growth factor. However, Glp2r−/− mice failed to up-regulate intestinal epithelial c-fos expression in response to acute GLP-2 administration and do not exhibit changes in small bowel conductance or small or large bowel growth after administration of GLP-2R agonists. The crypt and villus compartment and the numbers and localization of Paneth, enteroendocrine, and goblet cells were comparable in Glp2r+/+ vs. Glp2r−/− mice. Although the severity and extent of colonic mucosal injury in response to 3% oral dextran sulfate was similar across Glp2r genotypes, Glp2r−/− mice exhibited significantly increased morbidity and mortality and increased bacterial translocation after induction of enteritis with indomethacin and enhanced mucosal injury in response to irinotecan. Moreover, bacterial colonization of the small bowel was significantly increased, expression of Paneth cell antimicrobial gene products was reduced, and mucosal bactericidal activity was impaired in Glp2r−/− mice. Although the Glp2r is dispensable for gut development and the response to colonic injury, Glp2r−/− mice exhibit enhanced sensitivity to small bowel injury, and abnormal host-bacterial interactions in the small bowel. PMID:22253424

  4. Design, Synthesis, and Antiplasmodial Activity of Hybrid Compounds Based on (2R,3S)-N-Benzoyl-3-phenylisoserine

    PubMed Central

    2013-01-01

    A series of hybrid compounds based on (2R,3S)-N-benzoyl-3-phenylisoserine, artemisinin, and quinoline moieties was synthesized and tested for in vitro antiplasmodial activity against erythrocytic stages of K1 and W2 strains of Plasmodium falciparum. Two hybrid compounds incorporating (2R,3S)-N-benzoyl-3-phenylisoserine and artemisinin scaffolds were 3- to 4-fold more active than dihydroartemisinin, with nanomolar IC50 values against Plasmodium falciparum K1 strain. PMID:24900723

  5. M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis

    PubMed Central

    Jamieson, Timothy A; Brizel, David M; Killian, J Keith; Oka, Yoshihiko; Jang, Hong-Seok; Fu, Xiaolong; Clough, Robert W; Vollmer, Robin T; Anscher, Mitchell S; Jirtle, Randy L

    2003-01-01

    Background The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes for a multifunctional receptor involved in lysosomal enzyme trafficking, fetal organogenesis, cytotoxic T cell-induced apoptosis and tumor suppression. The purpose of this investigation was to determine if the M6P/IGF2R tumor suppressor gene is mutated in human head and neck cancer, and if allelic loss is associated with poor patient prognosis. Methods M6P/IGF2R loss of heterozygosity in locally advanced squamous cell carcinoma of the head and neck was assessed with six different gene-specific nucleotide polymorphisms. The patients studied were enrolled in a phase 3 trial of twice daily radiotherapy with or without concurrent chemotherapy; median follow-up for surviving patients is 76 months. Results M6P/IGF2R was polymorphic in 64% (56/87) of patients, and 54% (30/56) of the tumors in these informative patients had loss of heterozygosity. M6P/IGF2R loss of heterozygosity was associated with a significantly reduced 5 year relapse-free survival (23% vs. 69%, p = 0.02), locoregional control (34% vs. 75%, p = 0.03) and cause specific survival (29% vs. 75%, p = 0.02) in the patients treated with radiotherapy alone. Concomitant chemotherapy resulted in a better outcome when compared to radiotherapy alone only in those patients whose tumors had M6P/IGF2R loss of heterozygosity. Conclusions This study provides the first evidence that M6P/IGF2R loss of heterozygosity predicts for poor therapeutic outcome in patients treated with radiotherapy alone. Our findings also indicate that head and neck cancer patients with M6P/IGF2R allelic loss benefit most from concurrent chemotherapy. PMID:12589712

  6. Abscisic Acid Acts as a Blocker of the Bitter Taste G Protein-Coupled Receptor T2R4.

    PubMed

    Pydi, Sai P; Jaggupilli, Appalaraju; Nelson, Ken M; Abrams, Suzanne R; Bhullar, Rajinder P; Loewen, Michele C; Chelikani, Prashen

    2015-04-28

    Bitter taste receptors (T2Rs) belong to the G protein-coupled receptor superfamily. In humans, 25 T2Rs mediate bitter taste sensation. In addition to the oral cavity, T2Rs are expressed in many extraoral tissues, including the central nervous system, respiratory system, and reproductive system. To understand the mechanistic roles of the T2Rs in oral and extraoral tissues, novel blockers or antagonists are urgently needed. Recently, we elucidated the binding pocket of T2R4 for its agonist quinine, and an antagonist and inhibitory neurotransmitter, γ-aminobutyric acid. This structure-function information about T2R4 led us to screen the plant hormone abscisic acid (ABA), its precursor (xanthoxin), and catabolite phaseic acid for their ability to bind and activate or inhibit T2R4. Molecular docking studies followed by functional assays involving calcium imaging confirmed that ABA is an antagonist with an IC50 value of 34.4 ± 1.1 μM. However, ABA precursor xanthoxin acts as an agonist on T2R4. Interestingly, molecular model-guided site-directed mutagenesis suggests that the T2R4 residues involved in quinine binding are also predominantly involved in binding to the novel antagonist, ABA. The antagonist ability of ABA was tested using another T2R4 agonist, yohimbine. Our results suggest that ABA does not inhibit yohimbine-induced T2R4 activity. The discovery of natural bitter blockers has immense nutraceutical and physiological significance and will help in dissecting the T2R molecular pathways in various tissues. PMID:25844797

  7. A Bg1I polymorphism for the interleukin-2 receptor gene (IL2R) on chromosome 10

    SciTech Connect

    Ardinger, R.H.; Murray, J.C. )

    1988-08-25

    pIL2R2 is a cDNA for IL2R cloned into the EcoRI site of pBR322 and encoding from the 5{prime} flanking region to exon 7. Bg1I identifies a two allele polymorphism with 17 kb and 16 kb alleles. Co-dominant inheritance was demonstrated in 6 CEPH families. SpeI shows a possible RFLP with I12R2.

  8. Tracing direct and sequential two-photon double ionization of D{sub 2} in femtosecond extreme-ultraviolet laser pulses

    SciTech Connect

    Jiang, Y. H.; Kurka, M.; Kuehnel, K. U.; Ergler, Th.; Schroeter, C. D.; Moshammer, R.; Rudenko, A.; Foucar, L.; Plesiat, E.; Perez-Torres, J. F.; Martin, F.; Herrwerth, O.; Lezius, M.; Kling, M. F.; Titze, J.; Jahnke, T.; Doerner, R.; Sanz-Vicario, J. L.; Schoeffler, M.; Tilborg, J. van

    2010-02-15

    Two-photon double ionization (TPDI) of D{sub 2} is studied for 38-eV photons at the Free Electron Laser in Hamburg (FLASH). Based on model calculations, instantaneous and sequential absorption pathways are identified as separated peaks in the measured D{sup +}+D{sup +} fragment kinetic energy release (KER) spectra. The instantaneous process appears at high KER, corresponding to ionization at the molecule's equilibrium distance, in contrast to sequential ionization mainly leading to low-KER contributions. Measured fragment angular distributions are in good agreement with theory.

  9. Repetitively pulsed VUV emitter pumped by a barrier discharge in a mixture of helium with heavy water (D{sub 2}O) vapour

    SciTech Connect

    Shuaibov, Aleksandr K; Minya, A I; Hrytsak, R V; Gomoki, Z T; Shevera, Igor' V

    2012-08-31

    A gas-discharge lamp based on a barrier discharge in a He - D{sub 2}O mixture at partial pressures p{sub D2O} = 0.04 - 0.33 kPa and p{sub He} = 10 - 60 kPa is studied. The emission spectrum of the discharge plasma contains mainly the A {yields} X and C {yields} X bands of OD hydroxyl ({lambda} = 144 - 160 nm). The intensities of these bands are optimised by varying the pressure and composition of working mixtures. (laser applications and other topics in quantum electronics)

  10. Intrathymic radioresistant stem cells follow an IL-2/IL-2R pathway during thymic regeneration after sublethal irradiation

    SciTech Connect

    Zuniga-Pfluecker, J.C.K.; Kruisbeek, A.M. )

    1990-05-15

    Sublethally irradiated mice undergo thymic regeneration which follows a phenotypic pattern of events similar to that observed during normal fetal development. Thymic regeneration after irradiation is the product of a limited pool of intrathymic radioresistant stem cells undergoing simultaneous differentiation. We show that in this model of T cell development, thymic regeneration follows a pathway in which the IL-2R is transiently expressed on CD4-/CD8- cells. IL-2R expression occurred during the exponential growth period of thymic regeneration, and IL-2R blocking prevented this explosive growth. Flow cytometry analysis revealed that the IL-2R blockade affected primarily the development of the immature CD3-/CD4-/CD8- (triple negative) cells and their ability to generate CD3+/CD4+/CD8+ or CD3+/CD4+/CD8- and CD3+/CD4-/CD8+ thymocytes. Thus, our findings demonstrate that blocking of the IL-2R resulted in an arrest in proliferation and differentiation by intrathymic radioresistant stem cells, indicating that the IL-2/IL-2R pathway is necessary for the expansion of immature triple negative T cells.

  11. A role for the intermediate affinity IL-2R in the protection against glucocorticoid-induced apoptosis.

    PubMed Central

    Rebollo, A; Pitton, C; García, A; Gómez, J; Silva, A

    1995-01-01

    Recent work has shown that T lymphocytes undergo apoptosis upon treatment with the glucocorticoid analogue dexamethasone. These cells can be protected from the effect of dexamethasone by interleukin-2 (IL-2) or IL-4. We were interested in analysing whether a transfected cell dependent on three different lymphokines could be protected by them from the effect of dexamethasone. In addition, we took advantage of our cellular system, in which we expressed intermediate- or high-affinity IL-2R independently, to analyse the role of these receptors in the protection from glucocorticoid-induced apoptosis. In this report we show that IL-2 rescues murine T cells expressing exogenous intermediate- (TS1 beta) or high-affinity (TS1 alpha beta) IL-2 receptor (IL-2R) from dexamethasone-induced apoptosis. This result suggests that intermediate-affinity IL-2R alone can replace high-affinity IL-2R for the protection from the effect of dexamethasone. In addition, IL-4 and IL-9 are rescue-factors, as well as IL-2, of glucocorticoid-treated TS1 beta and TS1 alpha beta cells. Our data suggest that the presence of the alpha-chain of the IL-2R is not required for rescue by IL-2 from the effect of dexamethasone. In addition, we show that proliferation is not required for preventing glucocorticoid-induced apoptosis. This result implies a new role for the intermediate-affinity IL-2R. Images Figure 4 Figure 7 PMID:7751021

  12. Genetic labeling of Tas1r1 and Tas2r131 taste receptor cells in mice.

    PubMed

    Voigt, Anja; Hübner, Sandra; Lossow, Kristina; Hermans-Borgmeyer, Irm; Boehm, Ulrich; Meyerhof, Wolfgang

    2012-11-01

    Characterization of the peripheral taste system relies on the identification and visualization of the different taste bud cell types. So far, genetic strategies to label taste receptor cells are limited to sweet, sour, and salty detecting cells. To visualize Tas1r1 umami and Tas2r131 bitter sensing cells, we generated animals in which the Tas1r1 and Tas2r131 open reading frames are replaced by expression cassettes containing the fluorescent proteins mCherry or hrGFP, respectively. These animals enabled us to visualize and quantify the entire oral Tas1r1 and Tas2r131 cell populations. Tas1r1-mCherry cells were predominantly detected in fungiform papillae, whereas Tas2r131-hrGFP cells, which are ~4-fold more abundant, were mainly present in foliate and vallate papillae. In the palate, both cell types were similarly distributed. Mice carrying both recombinant alleles demonstrated completely segregated Tas1r1 and Tas2r131 cell populations. Only ~50% of the entire bitter cell population expressed hrGFP, indicating that bitter taste receptor cells express a subset of the bitter receptor repertoire. In extragustatory tissues, mCherry fluorescence was observed in testis and hrGFP fluorescence in testis, thymus, vomeronasal organ, and respiratory epithelium, suggesting that only few extraoral sites express Tas2r131 and Tas1r1 receptors at levels comparable to taste tissue. PMID:23010799

  13. Resonance-enhanced multiphoton ionization (REMPI) spectroscopy of bromobenzene and its perdeuterated isotopologue: Assignment of the vibrations of the S{sub 0}, S{sub 1}, and D{sub 0}{sup +} states of bromobenzene and the S{sub 0} and D{sub 0}{sup +} states of iodobenzene

    SciTech Connect

    Andrejeva, Anna; Tuttle, William D.; Harris, Joe P.; Wright, Timothy G.

    2015-12-28

    We report vibrationally resolved spectra of the S{sub 1}←S{sub 0} transition of bromobenzene using resonance-enhanced multiphoton ionization spectroscopy. We study bromobenzene-h{sub 5} as well as its perdeuterated isotopologue, bromobenzene-d{sub 5}. The form of the vibrational modes between the isotopologues and also between the S{sub 0} and S{sub 1} electronic states is discussed for each species, allowing assignment of the bands to be achieved and the activity between states and isotopologues to be established. Vibrational bands are assigned utilizing quantum chemical calculations, previous experimental results, and isotopic shifts. Previous work and assignments of the S{sub 1} spectra are discussed. Additionally, the vibrations in the ground state cation, D{sub 0}{sup +}, are considered, since these have also been used by previous workers in assigning the excited neutral state spectra. We also examine the vibrations of iodobenzene in the S{sub 0} and D{sub 0}{sup +} states and comment on the previous assignments of these. In summary, we have been able to assign the corresponding vibrations across the whole monohalobenzene series of molecules, in the S{sub 0}, S{sub 1}, and D{sub 0}{sup +} states, gaining insight into vibrational activity and vibrational couplings.

  14. Insilico study of the A(2A)R-D (2)R kinetics and interfacial contact surface for heteromerization.

    PubMed

    Prakash, Amresh; Luthra, Pratibha Mehta

    2012-10-01

    G-protein-coupled receptors (GPCRs) are cell surface receptors. The dynamic property of receptor-receptor interactions in GPCRs modulates the kinetics of G-protein signaling and stability. In the present work, the structural and dynamic study of A(2A)R-D(2)R interactions was carried to acquire the understanding of the A(2A)R-D(2)R receptor activation and deactivation process, facilitating the design of novel drugs and therapeutic target for Parkinson's disease. The structure-based features (Alpha, Beta, SurfAlpha, and SurfBeta; GapIndex, Leakiness and Gap Volume) and slow mode model (ENM) facilitated the prediction of kinetics (K (off), K (on), and K (d)) of A(2A)R-D(2)R interactions. The results demonstrated the correlation coefficient 0.294 for K (d) and K (on) and the correlation coefficient 0.635 for K (d) and K (off), and indicated stable interfacial contacts in the formation of heterodimer. The coulombic interaction involving the C-terminal tails of the A(2A)R and intracellular loops (ICLs) of D(2)R led to the formation of interfacial contacts between A(2A)R-D(2)R. The properties of structural dynamics, ENM and KFC server-based hot-spot analysis illustrated the stoichiometry of A(2A)R-D(2)R contact interfaces as dimer. The propensity of amino acid residues involved in A(2A)R-D(2)R interaction revealed the presence of positively (R, H and K) and negatively (E and D) charged structural motif of TMs and ICL3 of A(2A)R and D(2)R at interface of dimer contact. Essentially, in silico structural and dynamic study of A(2A)R-D(2)R interactions will provide the basic understanding of the A(2A)R-D(2)R interfacial contact surface for activation and deactivation processes, and could be used as constructive model to recognize the protein-protein interactions in receptor assimilations. PMID:22278740

  15. Lipase-catalyzed resolution of (2R*,3S*)- and (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol at low temperatures and determination of the absolute configurations of the four stereoisomers.

    PubMed

    Sakai, Takashi; Liu, Yu; Ohta, Hiroshi; Korenaga, Toshinobu; Ema, Tadashi

    2005-02-18

    [reaction: see text] Lipase-catalyzed resolution of (2R*,3S*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-2, at low temperatures gave synthetically useful (2R,3S)-2 and its acetate (2S,3R)-2a with (2S)-selectivity (E = 55 at -40 degrees C), while a similar reaction of (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-3, gave (2S,3S)-3 and its acetate (2R,3R)-3a with (2R)-selectivity (E = 73 at -20 degrees C). Compound (+/-)-2 was prepared conveniently via diastereoselective addition of MeMgBr to tert-butyl 3-phenyl-2H-azirine-2-carboxylate, (+/-)-1a, which was successfully prepared by the Neber reaction of oxime tosylate of tert-butyl benzoyl acetate 7a. The tert-butyl ester was requisite to promote this reaction. For determination of the absolute configuration of (2S,3R)-2a, enantiopure (2S,3R)-2 was independently prepared in three steps involving diastereoselective methylation of 3-phenyl-2H-azirine-2-methanol, (S)-10, with MeMgBr. The absolute configuration of (2S,3S)-3 was determined by X-ray analysis of the corresponding N-(S)-2-(6-methoxy-2-naphthyl)propanoyl derivative (S,S,S)-13. PMID:15704972

  16. Interactions of Charmed Mesons with Light Pseudoscalar Mesons from Lattice QCD and Implications on the Nature of the D*s0(2317)

    SciTech Connect

    Liuming, Liu; Orginos, Kostas; Guo, Feng-Kun; Hanhart, Christoph; Meissner, Ulf-G

    2014-11-01

    We study the scattering of light pseudoscalar mesons ( p , K ) off charmed mesons ( D , D s ) in full lattice QCD. The S -wave scattering lengths are calculated using Luscher’s finite volume technique. We use a relativistic formulation for the charm quark. For the light quark, we use domain- wall fermions in the valence sector and improved Kogut-Susskind sea quarks. We calculate the scattering lengths of isospin-3/2 Dπ , D sπ , D s K , isospin-0 DK and isospin-1 DK channels on the lattice. For the chiral extrapolation, we use a chiral unitary approach to next-to-leading order, which at the same time allows us to give predictions for other channels. It turns out that our results support the interpretation of the D*s0( 2317 ) as a DK molecule. At the same time, we also update a prediction for the isospin breaking hadronic decay width G ( D*s0( 2317 )→ D sπ ) to ( 133± 22 ) keV.

  17. Ion-molecule interactions in crossed-beams. [N/sup +/-H/sub 2/; F/sup +/-H; CO/sub 2//sup +/-D/sub 2/

    SciTech Connect

    Hansen, S.G.

    1980-09-01

    Interactions of the ions N/sup +/, F/sup +/, and CO/sub 2//sup +/ with H/sub 2/ and/or its isotopes were examined using the crossed-beam technique in the low (< 4 eV) initial relative energy. For the reaction N/sup +/(/sup 3/P) + H/sub 2/ ..-->.. NH/sup +/ + H, complex formation dominates up to 1.9 eV and a substantial interaction occurs between all collision partners up to 3.6 eV. The distribution of N/sup +/ scattered nonreactively from H/sub 2/ also showed a long-lived complex channel below 1.9 eV. The reaction F/sup +/(/sup 3/P) + H/sub 2/ ..-->..FH/sup +/ + H proceeded by a direct reaction mechanism at 0.20 to 1.07 eV. The reaction CO/sub 2//sup +/ + D/sub 2/ ..-->.. DCO/sub 2//sup +/ + D gives asymmetric product distributions at 0.27 eV and above, indicating a direct reaction mechanism. Results indicated that there are probably barriers in the exit channels for DCO/sub 2//sup +/, DCO/sup +/, and D/sub 2/O/sup +/ products. The electronic state distributions of the N/sup +/, F/sup +/, and CO/sub 2//sup +/ beams was investigated using beam attenuation and total luminescence techniques.

  18. Molecular cloning and evolutionary analysis of captive forest musk deer bitter taste receptor gene T2R16.

    PubMed

    Zhao, G J; Wu, N; Li, D Y; Zeng, D J; Chen, Q; Lu, L; Feng, X L; Zhang, C L; Zheng, C L; Jie, H

    2015-01-01

    Sensing bitter tastes is crucial for most animals because it can prevent them from ingesting harmful food. This process is mainly mediated by the bitter taste receptors (T2R) that are largely expressed in the taste buds. Previous studies have identified some T2R gene repertoires. Marked variation in repertoire size has been noted among species. However, research on T2Rs is still limited and the mechanisms underlying the evolution of vertebrate T2Rs remain poorly understood. In the present study, we analyzed the structure and features of the protein encoded by the forest musk deer (Moschus berezovskii) T2R16 and submitted the gene sequence to NCBI GenBank. The results showed that the full coding DNA sequence (CDS) of musk deer T2R16 (GenBank accession No. KP677279) was 906 bp, encoding 301 amino acids, which contained ATG start codon and TGA stop codon, with a calculated molecular weight of 35.03 kDa and an isoelectric point of 9.56. The T2R16 protein receptor had seven conserved transmembrane regions. Hydrophobicity analysis showed that most amino acid residues in T2R16 protein were hydrophobic, and the grand average of hydrophobicity (GRAVY) was 0.657. Phylogenetic analysis based on this gene revealed that forest musk deer had the closest association with sheep (Ovis aries), as compared to cow (Bos taurus), Tursiops truncatus, and other species, whereas it was genetically farthest from humans (Homo sapiens). We hope these results would complement the existing data on T2R16 and encourage further research in this respect. PMID:26662411

  19. Quantitative Contribution of IL2Rγ to the Dynamic Formation of IL2-IL2R Complexes

    PubMed Central

    Ponce, Luis F.; García-Martínez, Karina; León, Kalet

    2016-01-01

    Interleukin-2 (IL2) is a growth factor for several immune cells and its function depends on its binding to IL2Rs in the cell membrane. The most accepted model for the assembling of IL2-IL2R complexes in the cell membrane is the Affinity Conversion Model (ACM). This model postulates that IL2R receptor association is sequential and dependent on ligand binding. Most likely free IL2 binds first to IL2Rα, and then this complex binds to IL2Rβ, and finally to IL2Rγ (γc). However, in previous mathematical models representing this process, the binding of γc has not been taken into account. In this work, the quantitative contribution of the number of IL2Rγ chain to the IL2-IL2R apparent binding affinity and signaling is studied. A mathematical model of the affinity conversion process including the γ chain in the dynamic, has been formulated. The model was calibrated by fitting it to experimental data, specifically, Scatchard plots obtained using human cell lines. This paper demonstrates how the model correctly explains available experimental observations. It was estimated, for the first time, the value of the kinetic coefficients of IL2-IL2R complexes interaction in the cell membrane. Moreover, the number of IL2R components in different cell lines was also estimated. It was obtained a variable distribution in the number of IL2R components depending on the cell type and the activation state. Of most significance, the study predicts that not only the number of IL2Rα and IL2Rβ, but also the number of γc determine the capacity of the cell to capture and retain IL2 in signalling complexes. Moreover, it is also showed that different cells might use different pathways to bind IL2 as consequence of its IL2R components distribution in the membrane. PMID:27195783

  20. The structure-function role of C-terminus in human bitter taste receptor T2R4 signaling.

    PubMed

    Upadhyaya, Jasbir; Singh, Nisha; Bhullar, Rajinder P; Chelikani, Prashen

    2015-07-01

    Bitter taste, in humans, is sensed by 25 G protein-coupled receptors, referred to as bitter taste receptors (T2Rs). The diverse roles of T2Rs in various extraoral tissues have implicated them as a potential target for therapeutic intervention. Structure-function studies have provided insights into the role of transmembrane and loop regions in the activation mechanism of T2Rs. However, studies aimed at deciphering the role of their carboxyl-terminus (C-terminus) are limited. In this study, we identified a KLK/R motif in the C-terminus that is conserved in 19 of the 25 T2Rs. Using site-directed mutagenesis we studied the role of 16 residues in the C-terminus of T2R4. The C-terminus of T2R4 is polybasic with 6 of the 16 residues consisting of lysines, constituting two separate KK motifs. We analyzed the effect of the C-terminus mutations on plasma membrane trafficking, and characterized their function in response to the T2R4 agonist quinine. The majority of the mutants showed defective receptor trafficking with ≤50% expression on the cell surface. Interestingly, mutation of the distal Lys296 of the KLK motif in T2R4 resulted in constitutive activity. The K296A mutant displayed five-fold basal activity over wild type T2R4, while the conservative substitution K296R showed wild type characteristics. The Lys294, Leu295 and Lys296 of the KLK motif in T2R4 were found to perform crucial roles, both, in receptor trafficking and function. Results from this study provide unique mechanistic insights into the structure-function role of the C-terminus in T2R signaling. PMID:25858111

  1. The oil palm VIRESCENS gene controls fruit colour and encodes a R2R3-MYB

    PubMed Central

    Singh, Rajinder; Low, Eng-Ti Leslie; Ooi, Leslie Cheng-Li; Ong-Abdullah, Meilina; Nookiah, Rajanaidu; Ting, Ngoot-Chin; Marjuni, Marhalil; Chan, Pek-Lan; Ithnin, Maizura; Manaf, Mohd Arif Abdul; Nagappan, Jayanthi; Chan, Kuang-Lim; Rosli, Rozana; Halim, Mohd Amin; Azizi, Norazah; Budiman, Muhammad A.; Lakey, Nathan; Bacher, Blaire; Van Brunt, Andrew; Wang, Chunyan; Hogan, Michael; He, Dong; MacDonald, Jill D.; Smith, Steven W.; Ordway, Jared M.; Martienssen, Robert A.; Sambanthamurthi, Ravigadevi

    2014-01-01

    Oil palm, a plantation crop of major economic importance in Southeast Asia, is the predominant source of edible oil worldwide. We report the identification of the VIRESCENS (VIR) gene, which controls fruit exocarp colour and is an indicator of ripeness. VIR is a R2R3-MYB transcription factor with homology to Lilium LhMYB12 and similarity to Arabidopsis PRODUCTION OF ANTHOCYANIN PIGMENT1 (PAP1). We identify five independent mutant alleles of VIR in over 400 accessions from sub-Saharan Africa that account for the dominant-negative virescens phenotype. Each mutation results in premature termination of the carboxy-terminal domain of VIR, resembling McClintock’s C1-I allele in maize. The abundance of alleles likely reflects cultural practices, by which fruits were venerated for magical and medicinal properties. The identification of VIR will allow selection of the trait at the seed or early-nursery stage, 3-6 years before fruits are produced, greatly advancing introgression into elite breeding material. PMID:24978855

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

    PubMed

    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. PMID:26377817

  3. (2R,3R)-3-O-Benzoyl-N-benzyl­tartramide1

    PubMed Central

    Madura, Izabela D.; Zachara, Janusz; Bernaś, Urszula; Hajmowicz, Halina; Synoradzki, Ludwik

    2012-01-01

    The title compound, C18H17NO6 [systematic name: (2R,3R)-4-benzyl­amino-2-benzo­yloxy-3-hy­droxy-4-oxobutanoic acid], is the first structurally characterized unsymmetrical monoamide–monoacyl tartaric acid derivative. The mol­ecule shows a staggered conformation around the tartramide Csp3—Csp3 bond with trans-oriented carboxyl and amide groups. The mol­ecular conformation is stabilized by an intra­molecular N—H⋯O hydrogen bond. In the crystal, mol­ecules are linked by O—H⋯O hydrogen bonds between the carboxyl and amide carbonyl groups, forming translational chains along [001]. Further O—H⋯O and N—H⋯O hydrogen bonds as well as weaker C—H⋯O and C—H⋯π inter­molecular inter­actions extend the supra­molecular assembly into a double-layer structure parallel to (100). There are no directional inter­actions between the double layers. PMID:22719648

  4. The oil palm VIRESCENS gene controls fruit colour and encodes a R2R3-MYB.

    PubMed

    Singh, Rajinder; Low, Eng-Ti Leslie; Ooi, Leslie Cheng-Li; Ong-Abdullah, Meilina; Nookiah, Rajanaidu; Ting, Ngoot-Chin; Marjuni, Marhalil; Chan, Pek-Lan; Ithnin, Maizura; Manaf, Mohd Arif Abdul; Nagappan, Jayanthi; Chan, Kuang-Lim; Rosli, Rozana; Halim, Mohd Amin; Azizi, Norazah; Budiman, Muhammad A; Lakey, Nathan; Bacher, Blaire; Van Brunt, Andrew; Wang, Chunyan; Hogan, Michael; He, Dong; MacDonald, Jill D; Smith, Steven W; Ordway, Jared M; Martienssen, Robert A; Sambanthamurthi, Ravigadevi

    2014-01-01

    Oil palm, a plantation crop of major economic importance in Southeast Asia, is the predominant source of edible oil worldwide. We report the identification of the virescens (VIR) gene, which controls fruit exocarp colour and is an indicator of ripeness. VIR is a R2R3-MYB transcription factor with homology to Lilium LhMYB12 and similarity to Arabidopsis production of anthocyanin pigment1 (PAP1). We identify five independent mutant alleles of VIR in over 400 accessions from sub-Saharan Africa that account for the dominant-negative virescens phenotype. Each mutation results in premature termination of the carboxy-terminal domain of VIR, resembling McClintock's C1-I allele in maize. The abundance of alleles likely reflects cultural practices, by which fruits were venerated for magical and medicinal properties. The identification of VIR will allow selection of the trait at the seed or early-nursery stage, 3-6 years before fruits are produced, greatly advancing introgression into elite breeding material. PMID:24978855

  5. Sensing developing biofilms: the bitter receptor T2R38 on myeloid cells

    PubMed Central

    Gaida, Matthias Martin; Dapunt, Ulrike; Hänsch, Gertrud Maria

    2016-01-01

    Quorum-sensing molecules, also known as autoinducer, are essential for bacterial biofilm formation. Our focus is on N-(3-oxododecanoyl)-L-homoserine lactone (AHL-12), because it is also known as an ‘interkingdom signalling molecule’, which means that it also interacts with mammalian cells. AHL-12 activates defence-relevant functions of phagocytic cells, including enhancement of phagocytosis, increased expression of adhesion receptors and induction of chemotaxis. This leads to the hypothesis that early recognition of developing biofilms might be the key to a successful host defence against biofilm infection. In that context we studied activation of phagocytic cells by AHL-12, and found that phagocytes are activated via a rather specialized receptor that was not previously described on myeloid cells, the bitter taste receptor T2R38. Taste receptors are commonly associated with cells of the gustatory system. The extragustatory expression, however, suggests an additional role, namely the sensing of the onset of bacterial biofilm infection. PMID:26782143

  6. The Evolutionary History of R2R3-MYB Proteins Across 50 Eukaryotes: New Insights Into Subfamily Classification and Expansion

    PubMed Central

    Du, Hai; Liang, Zhe; Zhao, Sen; Nan, Ming-Ge; Phan Tran, Lam-Son; Lu, Kun; Huang, Yu-Bi; Li, Jia-Na

    2015-01-01

    R2R3-MYB proteins (2R-MYBs) are one of the main transcription factor families in higher plants. Since the evolutionary history of this gene family across the eukaryotic kingdom remains unknown, we performed a comparative analysis of 2R-MYBs from 50 major eukaryotic lineages, with particular emphasis on land plants. A total of 1548 candidates were identified among diverse taxonomic groups, which allowed for an updated classification of 73 highly conserved subfamilies, including many newly identified subfamilies. Our results revealed that the protein architectures, intron patterns, and sequence characteristics were remarkably conserved in each subfamily. At least four subfamilies were derived from early land plants, 10 evolved from spermatophytes, and 19 from angiosperms, demonstrating the diversity and preferential expansion of this gene family in land plants. Moreover, we determined that their remarkable expansion was mainly attributed to whole genome and segmental duplication, where duplicates were preferentially retained within certain subfamilies that shared three homologous intron patterns (a, b, and c) even though up to 12 types of patterns existed. Through our integrated distributions, sequence characteristics, and phylogenetic tree analyses, we confirm that 2R-MYBs are old and postulate that 3R-MYBs may be evolutionarily derived from 2R-MYBs via intragenic domain duplication. PMID:26047035

  7. The Evolutionary History of R2R3-MYB Proteins Across 50 Eukaryotes: New Insights Into Subfamily Classification and Expansion.

    PubMed

    Du, Hai; Liang, Zhe; Zhao, Sen; Nan, Ming-Ge; Tran, Lam-Son Phan; Lu, Kun; Huang, Yu-Bi; Li, Jia-Na

    2015-01-01

    R2R3-MYB proteins (2R-MYBs) are one of the main transcription factor families in higher plants. Since the evolutionary history of this gene family across the eukaryotic kingdom remains unknown, we performed a comparative analysis of 2R-MYBs from 50 major eukaryotic lineages, with particular emphasis on land plants. A total of 1548 candidates were identified among diverse taxonomic groups, which allowed for an updated classification of 73 highly conserved subfamilies, including many newly identified subfamilies. Our results revealed that the protein architectures, intron patterns, and sequence characteristics were remarkably conserved in each subfamily. At least four subfamilies were derived from early land plants, 10 evolved from spermatophytes, and 19 from angiosperms, demonstrating the diversity and preferential expansion of this gene family in land plants. Moreover, we determined that their remarkable expansion was mainly attributed to whole genome and segmental duplication, where duplicates were preferentially retained within certain subfamilies that shared three homologous intron patterns (a, b, and c) even though up to 12 types of patterns existed. Through our integrated distributions, sequence characteristics, and phylogenetic tree analyses, we confirm that 2R-MYBs are old and postulate that 3R-MYBs may be evolutionarily derived from 2R-MYBs via intragenic domain duplication. PMID:26047035

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

    PubMed Central

    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

  9. Multiple charge density wave transitions in the antiferromagnets R NiC2 (R =Gd ,Tb)

    NASA Astrophysics Data System (ADS)

    Shimomura, S.; Hayashi, C.; Hanasaki, N.; Ohnuma, K.; Kobayashi, Y.; Nakao, H.; Mizumaki, M.; Onodera, H.

    2016-04-01

    X-ray scattering and electrical resistivity measurements were performed on GdNiC2 and TbNiC2. We found a set of satellite peaks characterized by q1=(0.5 ,η ,0 ) below T1, at which the resistivity shows a sharp inflection, suggesting the charge density wave (CDW) formation. The value of η decreases with decreasing temperature below T1, and then a transition to a commensurate phase with q1 C=(0.5 ,0.5 ,0 ) takes place. The diffuse scattering observed above T1 indicates the presence of soft phonon modes associated with CDW instabilities at q1 and q2=(0.5 ,0.5 ,0.5 ) . The long-range order given by q2 is developed in addition to that given by q1 C in TbNiC2, while the short-range correlation with q2 persists even at 6 K in GdNiC2. The amplitude of the q1 C lattice modulation is anomalously reduced below an antiferromagnetic transition temperature TN in GdNiC2. In contrast, the q2 order vanishes below TN in TbNiC2. We demonstrate that R NiC2 (R = rare earth) compounds exhibit similarities with respect to their CDW phenomena, and discuss the effects of magnetic transitions on CDWs. We offer a possible displacement pattern of the modulated structure characterized by q1 C and q2 in terms of frustration.

  10. Three R2R3-MYB transcription factors regulate distinct floral pigmentation patterning in Phalaenopsis spp.

    PubMed

    Hsu, Chia-Chi; Chen, You-Yi; Tsai, Wen-Chieh; Chen, Wen-Huei; Chen, Hong-Hwa

    2015-05-01

    Orchidaceae are well known for their fascinating floral morphologic features, specialized pollination, and distinctive ecological strategies. With their long-lasting flowers of various colors and pigmentation patterning, Phalaenopsis spp. have become important ornamental plants worldwide. In this study, we identified three R2R3-MYB transcription factors PeMYB2, PeMYB11, and PeMYB12. Their expression profiles were concomitant with red color formation in Phalaenopsis spp. flowers. Transient assay of overexpression of three PeMYBs verified that PeMYB2 resulted in anthocyanin accumulation, and these PeMYBs could activate the expression of three downstream structural genes Phalaenopsis spp. Flavanone 3-hydroxylase5, Phalaenopsis spp. Dihydroflavonol 4-reductase1, and Phalaenopsis spp. Anthocyanidin synthase3. In addition, these three PeMYBs participated in the distinct pigmentation patterning in a single flower, which was revealed by virus-induced gene silencing. In the sepals/petals, silencing of PeMYB2, PeMYB11, and PeMYB12 resulted in the loss of the full-red pigmentation, red spots, and venation patterns, respectively. Moreover, different pigmentation patterning was regulated by PeMYBs in the sepals/petals and lip. PeMYB11 was responsive to the red spots in the callus of the lip, and PeMYB12 participated in the full pigmentation in the central lobe of the lip. The differential pigmentation patterning was validated by RNA in situ hybridization. Additional assessment was performed in six Phalaenopsis spp. cultivars with different color patterns. The combined expression of these three PeMYBs in different ratios leads to a wealth of complicated floral pigmentation patterning in Phalaenopsis spp. PMID:25739699

  11. Kepler light-curve analysis of the blazar W2R 1926+42

    NASA Astrophysics Data System (ADS)

    Mohan, P.; Gupta, Alok C.; Bachev, Rumen; Strigachev, Anton

    2016-02-01

    We study the long term Kepler light curve of the blazar W2R 1926+42 (˜1.6 yr) which indicates a variety of variability properties during different intervals of observation. The normalized excess variance, Fvar ranges from 1.8 per cent in the quiescent phase and 43.3 per cent in the outburst phase. We find no significant deviation from linearity in the Fvar-flux relation. Time series analysis is conducted using the Fourier power spectrum and the wavelet analysis methods to study the power spectral density (PSD) shape, infer characteristic time-scales and statistically significant quasi-periodic oscillations (QPOs). A bending power law with an associated time-scale of T_B = 6.2^{+6.4}_{-3.1} hours is inferred in the PSD analysis. We obtain a black hole mass of M• = (1.5-5.9) × 107 M⊙ for the first time using Fvar and the bend time-scale for this source. From a mean outburst lifetime of days, we infer a distance from the jet base r ≤ 1.75 pc indicating that the outburst originates due to a shock. A possible QPO peaked at 9.1 d and lasting 3.4 cycles is inferred from the wavelet analysis. Assuming that the QPO is a true feature, r = (152-378)GM•/c2 and supported by the other timing analysis products such as a weighted mean PSD slope of -1.5 ± 0.2 from the PSD analysis, we argue that the observed variability and the weak and short duration QPO could be due to jet based processes including orbital features in a relativistic helical jet and others such as shocks and turbulence.

  12. Photoemission Study of the Rare Earth Intermetallic Compounds: RNi2Ge2 (R=Eu, Gd)

    SciTech Connect

    Jongik Park

    2004-12-19

    EuNi{sub 2}Ge{sub 2} and GdNi{sub 2}Ge{sub 2} are two members of the RT{sub 2}X{sub 2} (R = rare earth, T = transition metal and X = Si, Ge) family of intermetallic compounds, which has been studied since the early 1980s. These ternary rare-earth intermetallic compounds with the tetragonal ThCr{sub 2}Si{sub 2} structure are known for their wide variety of magnetic properties, Extensive studies of the RT{sub 2}X{sub 2} series can be found in Refs [ 1,2,3]. The magnetic properties of the rare-earth nickel germanides RNi{sub 2}Ge{sub 2} were recently studied in more detail [4]. The purpose of this dissertation is to investigate the electronic structure (both valence band and shallow core levels) of single crystals of EuNi{sub 2}Ge{sub 2} and GdNi{sub 2}Ge{sub 2} and to check the assumptions that the f electrons are non-interacting and, consequently, the rigid-band model for these crystals would work [11], using synchrotron radiation because, to the best of our knowledge, no photoemission measurements on those have been reported. Photoemission spectroscopy has been widely used to study the detailed electronic structure of metals and alloys, and especially angle-resolved photoemission spectroscopy (ARPES) has proven to be a powerful technique for investigating Fermi surfaces (FSs) of single-crystal compounds.

  13. Protective LRRK2 R1398H Variant Enhances GTPase and Wnt Signaling Activity

    PubMed Central

    Nixon-Abell, Jonathon; Berwick, Daniel C.; Grannó, Simone; Spain, Victoria A.; Blackstone, Craig; Harvey, Kirsten

    2016-01-01

    Mutations in LRRK2 are a common cause of familial and idiopathic Parkinson’s disease (PD). Recently, the LRRK2 GTPase domain R1398H variant was suggested in genetic studies to confer protection against PD but mechanistic data supporting this is lacking. Here, we present evidence that R1398H affects GTPase function, axon outgrowth, and Wnt signaling in a manner opposite to pathogenic LRRK2 mutations. LRRK2 R1398H GTPase domain dimerization and GTP hydrolysis were increased whereas GTP binding was reduced, leading to a decrease in active GTP-bound LRRK2. This protective variant also increased axon length of primary cortical neurones in comparison to wild-type LRRK2, whereas the R1441G LRRK2 pathogenic mutant decreased axon outgrowth. Importantly, R1398H enhanced the stimulatory effect of LRRK2 on canonical Wnt signaling whereas the G2385R risk variant, in accordance with all previously tested pathogenic LRRK2 mutants, had the opposite effect. Molecular modeling placed R1398H in close proximity to PD-causing mutations suggesting that this protective LRRK2 variant, like familial mutations, affects intramolecular RocCOR domain interactions. Thus, our data suggest that R1398H LRRK2 is a bona fide protective variant. The opposite effects of protective versus PD associated LRRK2 variants on GTPase function and canonical Wnt signaling activity also suggests that regulation of these two basic signaling mechanisms is important for neuronal function. We conclude that LRRK2 mediated Wnt signaling and GTPase function are fundamental in conferring disease susceptibility and have clear implications for therapeutic target identification. PMID:27013965

  14. P2Y2R Deficiency Attenuates Experimental Autoimmune Uveitis Development

    PubMed Central

    Relvas, Lia Judice M.; Makhoul, Maya; Dewispelaere, Remi; Caspers, Laure; Communi, Didier; Boeynaems, Jean-Marie; Robaye, Bernard; Bruyns, Catherine; Willermain, François

    2015-01-01

    We aimed to study the role of the nucleotide receptor P2Y2R in the development of experimental autoimmune uveitis (EAU). EAU was induced in P2Y2+/+ and P2Y2-/- mice by immunization with IRBP peptide or by adoptive transfer of in vitro restimulated semi-purified IRBP-specific enriched T lymphocytes from spleens and lymph nodes isolated from native C57Bl/6 or P2Y2+/+ and P2Y2-/- immunized mice. Clinical and histological scores were used to grade disease severity. Splenocytes and lymph node cell phenotypes were analyzed using flow cytometry. Semi-purified lymphocytes and MACS-purified CD4+ T lymphocytes from P2Y2+/+ and P2Y2-/- immunized mice were tested for proliferation and cytokine secretion. Our data show that clinical and histological scores were significantly decreased in IRBP-immunized P2Y2-/- mice as in P2Y2-/- mice adoptively transfered with enriched T lymphocytes from C57Bl/6 IRBP-immunized mice. In parallel, naïve C57Bl/6 mice adoptively transferred with T lymphocytes from P2Y2-/- IRBP-immunized mice also showed significantly less disease. No differences in term of spleen and lymph node cell recruitment or phenotype appeared between P2Y2-/- and P2Y2+/+ immunized mice. However, once restimulated in vitro with IRBP, P2Y2-/- T cells proliferate less and secrete less cytokines than the P2Y2+/+ one. We further found that antigen-presenting cells of P2Y2-/- immunized mice were responsible for this proliferation defect. Together our data show that P2Y2-/- mice are less susceptible to mount an autoimmune response against IRBP. Those results are in accordance with the danger model, which makes a link between autoreactive lymphocyte activation, cell migration and the release of danger signals such as extracellular nucleotides. PMID:25692550

  15. Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception.

    PubMed

    Mancuso, Giuseppe; Borgonovo, Gigliola; Scaglioni, Leonardo; Bassoli, Angela

    2015-01-01

    Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels. PMID:26501253

  16. Leading order nonadiabatic corrections to rovibrational levels of H{sub 2}, D{sub 2}, and T{sub 2}

    SciTech Connect

    Pachucki, Krzysztof; Komasa, Jacek

    2015-07-21

    An efficient computational approach to nonadiabatic effects in the hydrogen molecule (H{sub 2}, D{sub 2}, and T{sub 2}) is presented. The electronic wave function is expanded in the James-Coolidge basis set, which enables obtaining a very high accuracy of nonadiabatic potentials. A single point convergence of the potentials with growing size of the basis set reveals a relative accuracy ranging from 10{sup −8} to 10{sup −13}. An estimated accuracy of the leading nonadiabatic correction to the rovibrational energy levels is of the order of 10{sup −7} cm{sup −1}. After a significant increase in the accuracy of the Born-Oppenheimer and adiabatic calculations, the nonadiabatic results presented in this report constitute another step towards highly accurate theoretical description of the hydrogen molecule.

  17. Relative neutronic performance of proposed high-density dispersion fuels in water-moderated and D{sub 2}O-reflected research reactors

    SciTech Connect

    Bretscher, M.M.; Matos, J.E.; Snelgrove, J.L.

    1996-12-01

    This paper provides an overview of the neutronic performance of an idealized research reactor using several high density LEU fuels that are being developed by the RERTR program. High-density LEU dispersion fuels are needed for new and existing high-performance research reactors and to extend the lifetime of fuel elements in other research reactors. This paper discusses the anticipated neutronic behavior of proposed advanced fuels containing dispersions of U{sub 3}Si{sub 2}, UN, U{sub 2}Mo and several uranium alloys with Mo, or Zr and Nb. These advanced fuels are ranked based on the results of equilibrium depletion calculations for a simplified reactor model having a small H{sub 2}O-cooled core and a D{sub 2}O reflector. Plans have been developed to fabricate and irradiate several uranium alloy dispersion fuels in order to test their stability and compatibility with the matrix material and to establish practical loading limits.

  18. Patient derived mutation W257G of PPP2R1A enhances cancer cell migration through SRC-JNK-c-Jun pathway

    PubMed Central

    Jeong, Ae Lee; Han, Sora; Lee, Sunyi; Su Park, Jeong; Lu, Yiling; Yu, Shuangxing; Li, Jane; Chun, Kyung-Hee; Mills, Gordon B.; Yang, Young

    2016-01-01

    Mutation of PPP2R1A has been observed at high frequency in endometrial serous carcinomas but at low frequency in ovarian clear cell carcinoma. However, the biological role of mutation of PPP2R1A in ovarian and endometrial cancer progression remains unclear. In this study, we found that PPP2R1A expression is elevated in high-grade primary tumor patients with papillary serous tumors of the ovary. To determine whether increased levels or mutation of PPP2R1A might contribute to cancer progression, the effects of overexpression or mutation of PPP2R1A on cell proliferation, migration, and PP2A phosphatase activity were investigated using ovarian and endometrial cancer cell lines. Among the mutations, PPP2R1A-W257G enhanced cell migration in vitro through activating SRC-JNK-c-Jun pathway. Overexpression of wild type (WT) PPP2R1A increased its binding ability with B56 regulatory subunits, whereas PPP2R1A-mutations lost the ability to bind to most B56 subunits except B56δ. Total PP2A activity and PPP2R1A-associated PP2Ac activity were significantly increased in cells overexpressing PPP2R1A-WT. In addition, overexpression of PPP2R1A-WT increased cell proliferation in vitro and tumor growth in vivo. PMID:27272709

  19. Guided ion beam and theoretical study of the reactions of Os{sup +} with H{sub 2}, D{sub 2}, and HD

    SciTech Connect

    Hinton, Christopher S.; Citir, Murat; Armentrout, P. B.

    2011-12-21

    Reactions of the third-row transition metal cation Os{sup +} with H{sub 2}, D{sub 2}, and HD to form OsH{sup +} (OsD{sup +}) were studied using a guided ion beam tandem mass spectrometer. A flow tube ion source produces Os{sup +} in its {sup 6}D (6s{sup 1}5d{sup 6}) electronic ground state level. Corresponding state-specific reaction cross sections are obtained. The kinetic energy dependences of the cross sections for the endothermic formation of OsH{sup +} and OsD{sup +} are analyzed to give a 0 K bond dissociation energy of D{sub 0}(Os{sup +}-H) = 2.45 {+-} 0.10 eV. Quantum chemical calculations are performed here at several levels of theory, with B3LYP approaches generally overestimating the experimental bond energy whereas results obtained using BHLYP and CCSD(T), coupled-cluster with single, double, and perturbative triple excitations, levels show good agreement. Theory also provides the electronic structures of these species and the potential energy surfaces for reaction. Results from the reactions with HD provide insight into the reaction mechanism and indicate that Os{sup +} reacts via a direct reaction. We also compare this third-row transition metal system with the first-row and second-row congeners, Fe{sup +} and Ru{sup +}, and find that Os{sup +} reacts more efficiently with dihydrogen, forming a stronger M{sup +}-H bond. These differences can be attributed to the lanthanide contraction and relativistic effects.

  20. Guided ion beam and theoretical study of the reactions of Au{sup +} with H{sub 2}, D{sub 2}, and HD

    SciTech Connect

    Li Fengxia; Hinton, Christopher S.; Citir, Murat; Liu, Fuyi; Armentrout, P. B.

    2011-01-14

    Reactions of the late third-row transition metal cation Au{sup +} with H{sub 2}, D{sub 2}, and HD are examined using guided ion beam tandem mass spectrometry. A flow tube ion source produces Au{sup +} in its {sup 1}S (5d{sup 10}) electronic ground state level. Corresponding state-specific reaction cross sections for forming AuH{sup +} and AuD{sup +} as a function of kinetic energy are obtained and analyzed to give a 0 K bond dissociation energy of D{sub 0}(Au{sup +}-H) = 2.13 {+-} 0.11 eV. Quantum chemical calculations at the B3LYP/HW+/6-311+G(3p) and B3LYP/Def2TZVPP levels performed here show good agreement with the experimental bond energy. Theory also provides the electronic structures of these species and the reactive potential energy surfaces. We also compare this third-row transition metal system with previous results for analogous reactions of the first-row and second-row congeners, Cu{sup +} and Ag{sup +}. We find that Au{sup +} has a stronger M{sup +}-H bond, which can be explained by the lanthanide contraction and relativistic effects that alter the relative size of the valence s and d orbitals. Results from reactions with HD provide insight into the reaction mechanism and indicate that ground state Au{sup +} reacts largely via a direct mechanism, in concordance with the behavior of the lighter group 11 metal ions, but includes more statistical behavior than these metals as well.

  1. Guided ion beam and theoretical study of the reactions of Hf{sup +} with H{sub 2}, D{sub 2}, and HD

    SciTech Connect

    Hinton, Christopher S.; Armentrout, P. B.

    2010-09-28

    The kinetic energy dependences of reactions of the third-row transition metal cation Hf{sup +} with H{sub 2}, D{sub 2}, and HD were determined using a guided ion beam tandem mass spectrometer. A flow tube ion source produces Hf{sup +} in its {sup 2}D (6s{sup 2}5d{sup 1}) electronic ground state level. Corresponding state-specific reaction cross sections are obtained. The kinetic energy dependences of the cross sections for the endothermic formation of HfH{sup +} and HfD{sup +} are analyzed to give a 0 K bond dissociation energy of D{sub 0}(Hf{sup +}-H)=2.11{+-}0.08 eV. Quantum chemical calculations at several levels of theory performed here generally overestimate the experimental bond energy but results obtained using the Becke-half-and-half-LYP functional show good agreement. Theory also provides the electronic structures of these species and the reactive potential energy surfaces. Results from the reactions with HD provide insight into the reaction mechanisms and indicates that Hf{sup +} reacts via a statistical mechanism. We also compare this third-row transition metal system with the first-row and second-row congeners, Ti{sup +} and Zr{sup +}, and find that Hf{sup +} has a weaker M{sup +}-H bond. As most third-row transition metal hydride cation bonds exceed their lighter congeners, this trend is unusual but can be understood using promotion energy arguments.

  2. Nonlinear magneto-optical resonances at D{sub 1} excitation of {sup 85}Rb and {sup 87}Rb for partially resolved hyperfine F levels

    SciTech Connect

    Auzinsh, M.; Ferber, R.; Gahbauer, F.; Jarmola, A.; Kalvans, L.

    2009-05-15

    Experimental signals of nonlinear magneto-optical resonances at D{sub 1} excitation of natural rubidium in a vapor cell have been obtained and described with experimental accuracy by a detailed theoretical model based on the optical Bloch equations. The D{sub 1} transition of rubidium is a challenging system to analyze theoretically because it contains transitions that are only partially resolved under Doppler broadening. The theoretical model took into account all nearby transitions, the coherence properties of the exciting laser radiation, and the mixing of magnetic sublevels in an external magnetic field and also included averaging over the Doppler profile. The experimental signals were reproduced very well at each hyperfine transition and over a wide range of laser power densities, beam diameters, and laser detunings from the exact transition frequency. The bright resonance expected at the F{sub g}=1{yields}F{sub e}=2 transition of {sup 87}Rb has been observed. A bright resonance was observed at the F{sub g}=2{yields}F{sub e}=3 transition of {sup 85}Rb, but displaced from the exact position of the transition due to the influence of the nearby F{sub g}=2{yields}F{sub e}=2 transition, which is a dark resonance whose contrast is almost 2 orders of magnitude larger than the contrast of the bright resonance at the F{sub g}=2{yields}F{sub e}=3 transition. Even in this very delicate situation, the theoretical model described in detail the experimental signals at different laser detunings.

  3. Comparative MD Simulations Indicate a Dual Role for Arg1323.50 in Dopamine-Dependent D2R Activation

    PubMed Central

    Kling, Ralf C.; Clark, Timothy; Gmeiner, Peter

    2016-01-01

    Residue Arg3.50 belongs to the highly conserved DRY-motif of class A GPCRs, which is located at the bottom of TM3. On the one hand, Arg3.50 has been reported to help stabilize the inactive state of GPCRs, but on the other hand has also been shown to be crucial for stabilizing active receptor conformations and mediating receptor-G protein coupling. The combined results of these studies suggest that the exact function of Arg3.50 is likely to be receptor-dependent and must be characterized independently for every GPCR. Consequently, we now present comparative molecular-dynamics simulations that use our recently described inactive-state and Gα-bound active-state homology models of the dopamine D2 receptor (D2R), which are either bound to dopamine or ligand-free, performed to identify the function of Arg1323.50 in D2R. Our results are consistent with a dynamic model of D2R activation in which Arg1323.50 adopts a dual role, both by stabilizing the inactive-state receptor conformation and enhancing dopamine-dependent D2R-G protein coupling. PMID:26741139

  4. VS{sub 2}/rGO hybrid nanosheets prepared by annealing of VS{sub 4}/rGO

    SciTech Connect

    Mohan, Pandurangan; Yang, Jieun; Jena, Anirudha; Suk Shin, Hyeon

    2015-04-15

    Layered transition metal dichalcogenides and their hybrids with reduced grpahene oxide (rGO) have attracted much interest due to many potential applications for electrode materials in Li ion batteries and supercapacitors and electro-catalysts for hydrogen evolution reaction. Among them, synthesis of VS{sub 2} sheets and VS{sub 4}/rGO hybrid via a hydrothermal reaction was recently reported, whereas VS{sub 2}/rGO hybrid sheets have not been reported. In this study, we report VS{sub 2}/rGO hybrid sheets after annealing VS{sub 4}/rGO hybrid materials at 350 °C. The conversion of VS{sub 4} to VS{sub 2} on rGO sheets after annealing is attributed to a thermal cleavage of VS{sub 4}. - Highlights: • VS2/rGO hybrid sheets were obtained by annealing of VS4/rGO at 350 °C. • The phase transition from monoclinic to hexagonal is occurred. • The HER performance of VS2/rGO is investigated.

  5. Synthesis of methyl (13(2)R/S)-alkyl-pyropheophorbide a and a non-epimerized chlorophyll a mimic.

    PubMed

    Ogasawara, Shin; Tamiaki, Hitoshi

    2015-10-15

    The (13(2)R/S)-methoxycarbonyl group of methyl pheophorbides a/a' (chlorophyll a/a' derivatives) was converted to methyl, ethyl, propyl, and isopropyl groups through the C13(2)-alkylation under basic conditions followed by pyrolysis in 2,4,6-collidine with lithium iodide. All the resulting products, methyl 13(2)-alkyl-pyropheophorbides a, predominantly gave the (13(2)R)-stereoisomers with about one tenth of the (13(2)S)-epimers. Their stereochemistry was determined by 1D/2D NMR and their optical properties were characterized by visible absorption and circular dichroism spectroscopy. Methyl (13(2)R)-propyl-pyropheophorbide a was converted to (13(2)R)-propyl-pyrochlorophyll a by ester exchanging and magnesium chelating reactions. The synthetic chlorophyll a analogue showed non-epimerization at the 13(2)-position in pyridine-d5 at 40°C, while naturally occurring chlorophyll a was easily epimerized under the same conditions to give its epimeric mixture. PMID:26404409

  6. Characterization of a citrus R2R3-MYB transcription factor that regulates the flavonol and hydroxycinnamic acid biosynthesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavonols and hydroxycinnamic acids are important phenylpropanoid metabolites in plants. In this study, we isolated and characterized a citrus R2R3-MYB transcription factor CsMYBF1, encoding a protein belonging to the flavonol-specific MYB subgroup. Ectopic expression of CsMYBF1 in tomato led to an ...

  7. Maxwell's Handbook for AACR2R: Explaining and Illustrating the Anglo-American Cataloguing Rules and the 1993 Amendments.

    ERIC Educational Resources Information Center

    Maxwell, Robert L.; Maxwell, Margaret F.

    This handbook is designed to assist experienced catalogers and library school students in the application of the most commonly used rules for bibliographic description, choice of access points, and form of headings in accordance with the revised Anglo-American Cataloging Rules (AACR2R). The book is intended as a supplement to the text of the…

  8. Association of VDR and CYP2R1 Polymorphisms with Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population

    PubMed Central

    Lu, Wen-Min; Wang, Mei-Lin; Zhao, Hai-Long; Lu, Mei-Ping; Zhou, Han; Chen, Ruo-Xi; Zhang, Zheng-Dong; Shen, Chong; Cheng, Lei

    2015-01-01

    As recent studies have described an association between vitamin D and allergic rhinitis, we hypothesized that vitamin D pathway-related genes may be candidate genes for susceptibility to allergic rhinitis. Thus, we sought to evaluate whether polymorphisms in the vitamin D receptor (VDR) and CYP2R1 genes are associated with mite-sensitized persistent allergic rhinitis (PER) in a Han Chinese population. A hospital-based case-control study consisting of 519 patients with mite-sensitized PER and 447 healthy controls was conducted. Five single nucleotide polymorphisms (SNPs) in VDR and CYP2R1 were selected for genotyping. The genotype and allele frequencies of rs9729, rs2228570, rs1544410, and rs731236 in VDR as well as rs2060793 in CYP2R1 were not significantly associated with susceptibility to mite-sensitized PER. After stratification analyses, however, both the CT and CT/TT genotypes of rs2228570 in VDR exhibited a significantly decreased risk (CT: adjusted odds ratio (OR)=0.58, 95% confidence intervals (CI)=0.37-0.91; CT/TT: adjusted OR=0.61, 95% CI=0.40-0.93) of mite-sensitized PER, while the AA genotype of rs2060793 in CYP2R1 exhibited a significantly increased risk (adjusted OR=1.85, 95% CI=1.03-3.34) of PER in the age subgroup of <16 years old. Both the AG and AG/GG genotypes of rs731236 in VDR exhibited a significantly decreased risk (AG: adjusted OR=0.43, 95% CI=0.21-0.89; AG/GG: adjusted OR=0.46, 95% CI=0.23-0.94) of PER in the female subgroup. Analysis of the locus-locus interactions of VDR and CYP2R1 revealed two models that involved combined SNPs of VDR and CYP2R1 were statistically significant (P<0.05). Our data suggest that age and gender may have an impact on the association of three SNPs (rs2228570, rs731236, and rs2060793) in genes of the vitamin D pathway with the risk of mite-sensitized PER in this Chinese population. The VDR and CYP2R1 variants may be involved in genetic interactions in the pathogenesis of PER. PMID:26177022

  9. Quantitation of [5-CH3]-(2R, 4'R, 8'R)-α-Tocopherol in Humans123

    PubMed Central

    Chuang, Jennifer C.; Matel, Hosea D.; Nambiar, Krishnan P.; Kim, Seung-Hyun; Fadel, James G.; Holstege, Dirk M.; Clifford, Andrew J.

    2011-01-01

    Half-lives of α-tocopherol in plasma have been reported as 2–3 d, whereas the Elgin Study required >2 y to deplete α-tocopherol, so gaps exist in our quantitative understanding of human α-tocopherol metabolism. Therefore, 6 men and 6 women aged 27 ± 6 y (mean ± SD) ingested 1.81 nmol, 3.70 kBq of [5-14CH3]-(2R, 4'R, 8'R)-α-tocopherol. The levels of 14C in blood plasma and washed RBC were monitored frequently from 0 to 460 d while the levels of 14C in urine and feces were monitored from 0 to 21 d. Total fecal elimination (fecal + metabolic fecal) was 23.24 ± 5.81% of the 14C dose, so feces over urine was the major route of elimination of the ingested [5-14CH3]-(2R, 4′R, 8′R)-α-tocopherol, consistent with prior estimates. The half-life of α-tocopherol varied in plasma and RBC according to the duration of study. The minute dose coupled with frequent monitoring over 460 d and 21 d for blood, urine, and feces ensured the [5-14CH3]-(2R, 4'R, 8'R)-α-tocopherol (the tracer) had the chance to fully mix with the endogenous [5-14CH3]-(2R, 4'R, 8'R)-α-tocopherol (the tracee). The 14C levels in neither plasma nor RBC had returned to baseline by d 460, indicating that the t1/2 of [5-CH3]-(2R, 4′R, 8′R)-α-tocopherol in human blood was longer than prior estimates. PMID:21715470

  10. Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus.

    PubMed

    Jiang, Zhihua; Michal, Jennifer J; Tobey, David J; Wang, Zeping; Macneil, Michael D; Magnuson, Nancy S

    2008-01-01

    Several reports have shown that urotensin 2 (UTS2) and its receptor (UTS2R) are involved in glucose metabolism and insulin resistance, which lead to development of type 2 diabetes mellitus (T2DM) in humans. In the present study, we annotated both bovine UTS2 and UTS2R genes and identified 5 single nucleotide polymorphisms (SNPs) for the former gene and 14 mutations for the latter gene. Four mutations were genotyped on a Wagyu x Limousin reference population, including 6 F(1 )bulls, 113 F(1 )dams and ~250 F(2 )progeny. Among 12 phenotypes related to fat deposition and fatty acid composition, we observed that the UTS2 gene was significantly associated with the amount of skeletal saturated fatty acids, while its receptor (UTS2R) gene had significant effects on amounts of saturated and monounsaturated fatty acids, Delta(9) desaturase activity for converting 16:0 into 16:1, muscle fat (marbling) score and Longissimus Dorsi muscle area. However, in this population, these markers were not associated with subcutaneous fat depth or percent kidney, pelvic and heart fat. We also found that mutations in the promoter regions altered the promoter activities in both genes and coding SNPs might affect the mRNA stability in the UTS2R gene. Overall, our present study provides the first evidence that both UTS2 and UTS2R genes regulate skeletal muscle fat accumulation and fatty acid metabolism, thus indicating their potential pathological functions related to obesity and T2DM in humans. PMID:18463714

  11. Common Variants in CYP2R1 and GC Genes Predict Vitamin D Concentrations in Healthy Danish Children and Adults

    PubMed Central

    Nissen, Janna; Rasmussen, Lone Banke; Ravn-Haren, Gitte; Andersen, Elisabeth Wreford; Hansen, Bettina; Andersen, Rikke; Mejborn, Heddie; Madsen, Katja Howarth; Vogel, Ulla

    2014-01-01

    Environmental factors such as diet, intake of vitamin D supplements and exposure to sunlight are known to influence serum vitamin D concentrations. Genetic epidemiology of vitamin D is in its infancy and a better understanding on how genetic variation influences vitamin D concentration is needed. We aimed to analyse previously reported vitamin D-related polymorphisms in relation to serum 25(OH)D concentrations in 201 healthy Danish families with dependent children in late summer in Denmark. Serum 25(OH)D concentrations and a total of 25 SNPs in GC, VDR, CYP2R1, CYP24A1, CYP27B1, C10or88 and DHCR7/NADSYN1 genes were analysed in 758 participants. Genotype distributions were in Hardy–Weinberg equilibrium for the adult population for all the studied polymorphisms. Four SNPs in CYP2R1 (rs1562902, rs7116978, rs10741657 and rs10766197) and six SNPs in GC (rs4588, rs842999, rs2282679, rs12512631, rs16846876 and rs17467825) were statistically significantly associated with serum 25(OH)D concentrations in children, adults and all combined. Several of the SNPs were in strong linkage disequilibrium, and the associations were driven by CYP2R1-rs10741657 and rs10766197, and by GC-rs4588 and rs842999. Genetic risk score analysis showed that carriers with no risk alleles of CYP2R1-rs10741657 and rs10766197, and/or GC rs4588 and rs842999 had significantly higher serum 25(OH)D concentrations compared to carriers of all risk alleles. To conclude, our results provide supporting evidence that common polymorphisms in GC and CYP2R1 are associated with serum 25(OH)D concentrations in the Caucasian population and that certain haplotypes may predispose to lower 25(OH)D concentrations in late summer in Denmark. PMID:24587115

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Observation of the hyperfine structure of the {sup 2}S{sub 1/2}-{sup 2}D{sub 5/2} transition in {sup 87}Sr{sup +}

    SciTech Connect

    Barwood, G.P.; Gao, K.; Gill, P.; Huang, G.; Klein, H.A.

    2003-01-01

    The hyperfine structure of the {sup 2}S{sub 1/2}-{sup 2}D{sub 5/2} quadrupole transition at 674 nm in {sup 87}Sr{sup +} has been observed. The ion was confined in a Paul trap and cooled using laser radiation at 422 and 1092 nm. The quadrupole transition was observed by monitoring quantum jumps in the 422-nm fluorescence. The odd isotope of strontium has 'clock' transitions independent of the first-order Zeeman shift and the {sup 2}D{sub 5/2} state hyperfine structure constants have been determined as A{sub D{sub 5/2}}=2.1743(14) MHz and B{sub D{sub 5/2}}=49.11(6) MHz. Standard uncertainties have been added in parentheses. These values allow the second-order Zeeman shifts to be calculated. The {sup 88}Sr{sup +}-{sup 87}Sr{sup +} isotope shift for the 674-nm quadrupole transition has been measured to be 247.99(4) MHz.

  14. Reactions of vibrationally excited hydrogen and deuterium molecules with atoms and radicals. Heterogeneous relaxation of the vibrational energy of H/sub 2/ and D/sub 2/ on quartz and teflon surfaces

    SciTech Connect

    Gershenzon, Yu.M.; Ivanov, A.V.; Kucheryavyi, S.I.; Lyapunov, A.Ya.; Rozenshtein, V.B.

    1987-03-01

    The ESR method was used to measure the probability of relaxation of the vibrational energy of H/sub 2/(v = 1) and D/sub 2/(v = 1) molecules during collisions with the surfaces of quartz and F32-L and F4-D Teflons. The results indicate that this relaxation proceeds by an adsorption-phonon mechanism

  15. State-to-state photodissociation of carbonyl sulfide ({nu}{sub 2}=0,1|JlM). II. The effect of initial bending on coherence of S({sup 1}D{sub 2}) polarization

    SciTech Connect

    Brom, Alrik J. van den; Rakitzis, T. Peter; Janssen, Maurice H. M.

    2005-10-22

    Photodissociation studies using ion imaging are reported, measuring the coherence of the polarization of the S({sup 1}D{sub 2}) fragment from the photolysis of single-quantum state-selected carbonyl sulfide (OCS) at 223 and 230 nm. A hexapole state-selector focuses a molecular beam of OCS parent molecules in the ground state ({nu}{sub 2}=0 vertical bar JM=10) or in the first excited bending state ({nu}{sub 2}=1 vertical bar JlM=111). At 230 nm photolysis the Im[a{sub 1}{sup (1p}{sub arallel}{sup ,perpendicular})] moment for the fast S({sup 1}D{sub 2}) channel increases by about 50% when the initial OCS parent state changes from the vibrationless ground state to the first excited bending state. No dependence on the initial bending state is found for photolysis at 223 nm. We observe separate rings in the slow channel of the velocity distribution of S({sup 1}D{sub 2}) correlating to single CO(J) rotational states. The additional available energy for photolysis at 223 nm is found to be channeled mostly into the CO(J) rotational motion. An improved value for the OC-S bond energy D{sub 0}=4.292 eV is reported.

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

    NASA Astrophysics Data System (ADS)

    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

  17. Differential effect of 1{alpha},25-dihydroxyvitamin D{sub 3} on Hsp28 and PKC{beta} gene expression in the phorbol ester-resistant human myeloid HL-525 leukemic cells

    SciTech Connect

    Lee, Yong J.; Galoforo, S.S.; Berns, C.M.

    1997-08-01

    We investigated the effect of 1{alpha},25-dihydroxyvitamin D{sub 3} [1,25-(OH){sub 2}D{sub 3}] on the expression of the 28-kDa heat shock protein gene (hsp28) and the protein kinase C beta gene (PKC{beta}) in the human myeloid HL-60 leukemic cell variant HL-525, which is resistance to phorbol ester-induced macrophage differentiation. Northern and Western blot analysis showed little or no hsp28 gene expression in the HL-60 cell variant, HL-205, which is susceptible to such differentiation, while a relatively high basal level of hps28 gene expression was observed in the HL-525 cells. However, both cell lines demonstrated heat shock-induced expression of this gene. During treatment with 50-300 nM 1,25-(OH){sub 2}D{sub 3}, a marked reduction of hsp28 gene expression was not associated with heat shock transcription factor-heat shock element (HSF-HSE) binding activity. Our results suggest that the differential effect of 1,25-(OH){sub 2}D{sub 3} on hsp28 and PKC{beta} gene expression is due to the different sequence composition of the vitamin D response element in the in the promoter region as well as an accessory factor for each gene or that 1,25-(OH){sub 2}D{sub 3} increases PKC{beta} gene expression, which in turn negatively regulates the expression of the hsp28 gene, or vice versa.

  18. Molecular Characterization and Functional Regulation of Melanocortin 2 Receptor (MC2R) in the Sea Bass. A Putative Role in the Adaptation to Stress

    PubMed Central

    Agulleiro, Maria Josep; Sánchez, Elisa; Leal, Esther; Cortés, Raúl; Fernández-Durán, Begoña; Guillot, Raúl; Davis, Perry; Dores, Robert M.; Gallo-Payet, Nicole; Cerdá-Reverter, José Miguel

    2013-01-01

    The activation of melanocortin 2 receptor (MC2R) by ACTH mediates the signaling cascade leading to steroid synthesis in the interrenal tissue (analogous to the adrenal cortex in mammals) of fish. However, little is known about the functional regulation of this receptor in fish. In this work described, we cloned sea bass MC2R from a liver cDNA. SbMC2R requires the melanocortin 2 receptor accessory protein (MRAP) for its functional expression. Dietary cortisol but not long-term stress protocols downregulated interrenal sbMC2R expression. Data suggest the existence of a negative feedback on interrenal sbMC2R expression imposed by local or systemic glucocorticoids. This feedback could be involved in long-term stress adaptation by regulating interrenal sensitivity to ACTH. ACTH-induced MC2R activation stimulates hepatic lipolysis, suggesting that ACTH may mediate stress-induced effects upstream of cortisol release. PMID:23724142

  19. Rolling Deck to Repository (R2R): Organizing Datasets from Heterogeneous Shipboard Data into an Integrated Catalog

    NASA Astrophysics Data System (ADS)

    Clark, P. D.; Arko, R. A.; Sweeney, A.; Fischman, D.; Miller, S. P.; Stocks, K.

    2010-12-01

    The goal of the Rolling Deck to Repository (R2R; rvdata.us) program is to develop and implement a fleet-wide information management system to preserve and provide access to routine underway data collected by U.S. academic research vessels. One of the program’s primary challenges is to develop a workflow for routinely gathering data from a fleet with heterogeneous instrumentation and file systems, breaking out the data into discrete data sets, and transferring the data to the appropriate National Data Center. Because R2R expects to receive 300-400 cruises per year from a wide range of vessel classes and at least two dozen major device types, this workflow must be highly automated. R2R has developed and implemented a workflow for processing underway data: - Collection: data are provided at the end of a cruise as a cruise distribution using the mechanism preferred by the vessel operator. - Inventory: a complete inventory of each cruise distribution is created, listing the filename, date, size, and checksum. This inventory is published online by R2R. - Raw Archive: the entire original cruise distribution is transmitted securely to the National Geophysical Data Center for deep archive. - Data Breakout: data from each device are extracted from the cruise distribution according to a vessel profile yielding a discrete data set. Once a data set is broken out and any proprietary holds are cleared, it is delivered to the appropriate National Data Center for archiving and dissemination. It may also be processed further for quality assessment/quality control and/or publication of standard products. Data sets sent to a National Data Center will have unique and persistent R2R identifiers, which link to parent cruise information on the R2R site. The site will include the URL link to each data set at the National Data Center, allowing a user browsing the R2R cruise catalog to download it. Because each vessel operator typically has a customized system for naming and organizing

  20. Vegetable Intake in College-Aged Adults Is Explained by Oral Sensory Phenotypes and TAS2R38 Genotype

    PubMed Central

    Hayes, John E.; Davidson, Andrew C.; Kidd, Judith R.; Kidd, Kenneth K.; Bartoshuk, Linda M.

    2010-01-01

    Taste and oral sensations vary in humans. Some of this variation has a genetic basis, and two commonly measured phenotypes are the bitterness of propylthiouracil (PROP) and the number of fungiform papillae on the anterior tongue. While the genetic control of fungiform papilla is unclear, PROP bitterness associates with allelic variation in the taste receptor gene, TAS2R38. The two common alleles are AVI and PAV (proline, alanine, valine, and isoleucine); AVI/AVI homozygotes taste PROP as less bitter than heterozygous or homozygous PAV carriers. In this laboratory-based study, we determined whether taste of a bitter probe (quinine) and vegetable intake varied by taste phenotypes and TAS2R38 genotype in healthy adults (mean age=26 years). Vegetable intake was assessed via two validated, complementary methods: food records (Food Pyramid servings standardized to energy intake) and food frequency questionnaire (general intake question and composite vegetable groups). Quinine bitterness varied with phenotypes but not TAS2R38; quinine was more bitter to those who tasted PROP as more bitter or had more papillae. Nontasters by phenotype or genotype reported greater consumption of vegetables, regardless of type (i.e., the effect generalized to all vegetables and was not restricted to those typically thought of as being bitter). Furthermore, nontasters with more papillae reported greater vegetable consumption than nontasters with fewer papillae, suggesting that when bitterness does not predominate, more papillae enhance vegetable liking. These findings suggest that genetic variation in taste, measured by multiple phenotypes or TAS2R38 genotype, can explain differences in overall consumption of vegetables, and this was not restricted to vegetables that are predominantly bitter. PMID:21157576

  1. Kinetic properties of "dual" orexin receptor antagonists at OX1R and OX2R orexin receptors.

    PubMed

    Callander, Gabrielle E; Olorunda, Morenike; Monna, Dominique; Schuepbach, Edi; Langenegger, Daniel; Betschart, Claudia; Hintermann, Samuel; Behnke, Dirk; Cotesta, Simona; Fendt, Markus; Laue, Grit; Ofner, Silvio; Briard, Emmanuelle; Gee, Christine E; Jacobson, Laura H; Hoyer, Daniel

    2013-01-01

    Orexin receptor antagonists represent attractive targets for the development of drugs for the treatment of insomnia. Both efficacy and safety are crucial in clinical settings and thorough investigations of pharmacokinetics and pharmacodynamics can predict contributing factors such as duration of action and undesirable effects. To this end, we studied the interactions between various "dual" orexin receptor antagonists and the orexin receptors, OX1R and OX2R, over time using saturation and competition radioligand binding with [(3)H]-BBAC ((S)-N-([1,1'-biphenyl]-2-yl)-1-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)thio)acetyl)pyrrolidine-2-carboxamide). In addition, the kinetics of these compounds were investigated in cells expressing human, mouse and rat OX1R and OX2R using FLIPR® assays for calcium accumulation. We demonstrate that almorexant reaches equilibrium very slowly at OX2R, whereas SB-649868, suvorexant, and filorexant may take hours to reach steady state at both orexin receptors. By contrast, compounds such as BBAC or the selective OX2R antagonist IPSU ((2-((1H-Indol-3-yl)methyl)-9-(4-methoxypyrimidin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one) bind rapidly and reach equilibrium very quickly in binding and/or functional assays. Overall, the "dual" antagonists tested here tend to be rather unselective under non-equilibrium conditions and reach equilibrium very slowly. Once equilibrium is reached, each ligand demonstrates a selectivity profile that is however, distinct from the non-equilibrium condition. The slow kinetics of the "dual" antagonists tested suggest that in vitro receptor occupancy may be longer lasting than would be predicted. This raises questions as to whether pharmacokinetic studies measuring plasma or brain levels of these antagonists are accurate reflections of receptor occupancy in vivo. PMID:24376396

  2. Kinetic properties of “dual” orexin receptor antagonists at OX1R and OX2R orexin receptors

    PubMed Central

    Callander, Gabrielle E.; Olorunda, Morenike; Monna, Dominique; Schuepbach, Edi; Langenegger, Daniel; Betschart, Claudia; Hintermann, Samuel; Behnke, Dirk; Cotesta, Simona; Fendt, Markus; Laue, Grit; Ofner, Silvio; Briard, Emmanuelle; Gee, Christine E.; Jacobson, Laura H.; Hoyer, Daniel

    2013-01-01

    Orexin receptor antagonists represent attractive targets for the development of drugs for the treatment of insomnia. Both efficacy and safety are crucial in clinical settings and thorough investigations of pharmacokinetics and pharmacodynamics can predict contributing factors such as duration of action and undesirable effects. To this end, we studied the interactions between various “dual” orexin receptor antagonists and the orexin receptors, OX1R and OX2R, over time using saturation and competition radioligand binding with [3H]-BBAC ((S)-N-([1,1′-biphenyl]-2-yl)-1-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)thio)acetyl)pyrrolidine-2-carboxamide). In addition, the kinetics of these compounds were investigated in cells expressing human, mouse and rat OX1R and OX2R using FLIPR® assays for calcium accumulation. We demonstrate that almorexant reaches equilibrium very slowly at OX2R, whereas SB-649868, suvorexant, and filorexant may take hours to reach steady state at both orexin receptors. By contrast, compounds such as BBAC or the selective OX2R antagonist IPSU ((2-((1H-Indol-3-yl)methyl)-9-(4-methoxypyrimidin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one) bind rapidly and reach equilibrium very quickly in binding and/or functional assays. Overall, the “dual” antagonists tested here tend to be rather unselective under non-equilibrium conditions and reach equilibrium very slowly. Once equilibrium is reached, each ligand demonstrates a selectivity profile that is however, distinct from the non-equilibrium condition. The slow kinetics of the “dual” antagonists tested suggest that in vitro receptor occupancy may be longer lasting than would be predicted. This raises questions as to whether pharmacokinetic studies measuring plasma or brain levels of these antagonists are accurate reflections of receptor occupancy in vivo. PMID:24376396

  3. Clinical usefulness of autoantibodies to M-type phospholipase A2 receptor (PLA2R) for monitoring disease activity in idiopathic membranous nephropathy (IMN).

    PubMed

    Radice, Antonella; Trezzi, Barbara; Maggiore, Umberto; Pregnolato, Francesca; Stellato, Tiziana; Napodano, Pietro; Rolla, Davide; Pesce, Gianpaola; D'Amico, Marco; Santoro, Domenico; Londrino, Francesco; Ravera, Federica; Ortisi, Giuseppe; Sinico, Renato Alberto

    2016-02-01

    Autoantibodies to M-type phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (IMN). They can differentiate IMN from other glomerular diseases and primary from secondary forms of MN. Preliminary data suggest that anti-PLA2R antibody titer correlates with disease activity but more solid evidence is needed. To evaluate the performance of anti-PLA2R antibody for monitoring nephropathy activity, 149 anti-PLA2R antibody measurements were performed during the follow-up of 42 biopsy proven IMN consecutive patients. Patients were enrolled either at time of diagnosis (33 cases, inception cohort) or after diagnosis (9 patients, non-inception cohort). Anti-PLA2R detection was performed using the highly sensitive transfected cell-based indirect immunofluorescence (IIFT). Over the follow-up there was a linear time-trend of decreasing proteinuria (P<0.001), increasing serum albumin (P<0.001) and decreasing PLA2R antibody levels (P=0.002). There was a statistically significant association between changes in PLA2R antibody levels and the clinical course of PLA2R-positive IMN. The positive PLA2R serum antibody status was linearly associated with increasing proteinuria and decreasing serum albumin over time, compared with negative antibody status. Moreover, the strong correlation between the clinical conditions and PLA2R antibody levels allowed the prediction of prevalence distribution of patients with active disease, partial and complete remission. Over the course of the follow-up, the probability of halving proteinuria increased 6.5 times after disappearance of PLA2R antibodies. Our data suggest that the serial evaluation of anti-PLA2R antibodies could help in optimal timing and duration of the immunosuppressive therapy, reducing over(under)-treatment and associated side-effects. PMID:26527329

  4. De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism.

    PubMed

    Shang, Linshan; Henderson, Lindsay B; Cho, Megan T; Petrey, Donald S; Fong, Chin-To; Haude, Katrina M; Shur, Natasha; Lundberg, Julie; Hauser, Natalie; Carmichael, Jason; Innis, Jeffrey; Schuette, Jane; Wu, Yvonne W; Asaikar, Shailesh; Pearson, Margaret; Folk, Leandra; Retterer, Kyle; Monaghan, Kristin G; Chung, Wendy K

    2016-01-01

    Protein phosphatase 2A (PP2A) is a heterotrimeric protein serine/threonine phosphatase and is involved in a broad range of cellular processes. PPP2R5D is a regulatory B subunit of PP2A and plays an important role in regulating key neuronal and developmental regulation processes such as PI3K/AKT and glycogen synthase kinase 3 beta (GSK3β)-mediated cell growth, chromatin remodeling, and gene transcriptional regulation. Using whole-exome sequencing (WES), we identified four de novo variants in PPP2R5D in a total of seven unrelated individuals with intellectual disability (ID) and other shared clinical characteristics, including autism spectrum disorder, macrocephaly, hypotonia, seizures, and dysmorphic features. Among the four variants, two have been previously reported and two are novel. All four amino acids are highly conserved among the PP2A subunit family, and all change a negatively charged acidic glutamic acid (E) to a positively charged basic lysine (K) and are predicted to disrupt the PP2A subunit binding and impair the dephosphorylation capacity. Our data provides further support for PPP2R5D as a genetic cause of ID. PMID:26576547

  5. Modulation of behavior by the histaminergic system: lessons from H(1)R-and H(2)R-deficient mice.

    PubMed

    Schneider, Erich H; Neumann, Detlef; Seifert, Roland

    2014-05-01

    Besides acting in the immune system, histamine is also a neurotransmitter in the central nervous system. The H1R causes central side effects, e.g. of first generation antihistamines, antidepressants or antipsychotics and represents the component of the central histaminergic system most extensively studied in behavior experiments with knock-out mice. Central effects of H2R are similar, but only few behavioral results from knockout models are available. We summarize the behavior phenotype of H1R- and H2R-deficient mice, revealing histaminergic modulation of behaviors like locomotor activity, cognition, emotional states, arousal, sleep and wakefulness, circadian rhythm, pain perception, food intake and energy consumption, respiration and susceptibility to seizures. Knock-out models demonstrate several central effects of H1R and H2R that are not clinically and therapeutically exploited to date. We critically discuss problems and pitfalls of both the knock-out mouse technique and the pharmacological approach with receptor-selective ligands. The behavioral characterization of Hrh1(-/-)- and Hrh2(-/-)-mice is crucial, because many pharmacological agents lack the required selectivity to unequivocally address the functions of a single histamine receptor subtype. PMID:24661982

  6. Orexins and receptor OX2R in the gastroenteric apparatus of two teleostean species: Dicentrarchus labrax and Carassius auratus.

    PubMed

    D'Angelo, Livia; Castaldo, Luciana; de Girolamo, Paolo; Lucini, Carla; Paolucci, Marina; Pelagalli, Alessandra; Varricchio, Ettore; Arcamone, Nadia

    2016-08-01

    Orexin A and B peptides and the receptor OX2R were studied in sea bass and goldfish gastroenteric tract by immunoblotting combined with densitometric analysis using NIH Image J software and immunohistochemical techniques. These teleost species present a different gut organization and diverse feeding habits. Immunoblotting experiments showed one band of 16 kDa corresponding to prepro-orexin, and one band of 38 kDa corresponding to the OX2R receptor. Immunohistochemical localization of OXA and OXB was observed in the enteric nervous system throughout the gastroenteric tract of both species. OXA and OXB immunoreactive cells were found in the gastric and intestinal regions of sea bass, and were mainly found in the basal region of folds in intestinal bulb, and in the midgut and hindgut of goldfish. The distribution of OX2R was mainly detected in the mucosa of the gastroenteric tract of sea bass and goldfish. This distribution suggests an endocrine action of OXA and OXB in the gastrointestinal tract as well as involvement in the peripheral control of food intake and digestive processes in both species. This study might also serve to determine the productive factors in breeding and as a baseline for future experimental studies on the regulation of the gastroenteric functions in non-mammalian vertebrates. Anat Rec, 299:1121-1129, 2016. © 2016 Wiley Periodicals, Inc. PMID:27223125

  7. Simultaneous decolorization of reactive Orange M2R dye and reduction of chromate by Lysinibacillus sp. KMK-A.

    PubMed

    Chaudhari, Ashvini U; Tapase, Savita R; Markad, Vijaykumar L; Kodam, Kisan M

    2013-11-15

    Azo dyes constitute the largest and diverse group of dyes, widely used in number of industries that are contributing toward organic and inorganic load of effluent treatment. In the present study, Lysinibacillus sp. KMK-A was able to effectively decolorize Orange M2R dye up to 2000 mg l(-1) (Vmax of 19.6 mg l(-1) h(-1) and Km of 439 mg l(-1)) and reduce Cr(VI) up to 250 mg l(-1) (Vmax of 3.6 mg l(-1) h(-1) and Km 28.3 mg l(-1)). It also has an ability of simultaneous decolorization of Orange M2R dye (200-1000 mg l(-1)) with reduction of Cr(VI) (50-200 mg l(-1)). Significant reduction in total organic carbon content, chemical and biological oxygen demand along with spectroscopic and chromatographic analysis confirmed the biotransformation of Orange M2R. Involvement of enzymes namely azoreductase and chromate reductase was observed during biotransformation. The phyto and geno toxicity studies demonstrated that metabolites of dye degradation were non-toxic. Higher tolerance with simultaneous decolorization and detoxification of azo dyes in presence of Cr(VI) makes Lysinibacillus sp. KMK-A, a potential candidate for eco-friendly remediation of metal contaminated dye effluents. PMID:24095998

  8. De Novo Missense Variants in PPP2R5D Are Associated with Intellectual Disability, Macrocephaly, Hypotonia, and Autism

    PubMed Central

    Shang, Linshan; Henderson, Lindsay B.; Cho, Megan T.; Petrey, Donald S.; Fong, Chin-To; Haude, Katrina M.; Shur, Natasha; Lundberg, Julie; Hauser, Natalie; Carmichael, Jason; Innis, Jeffrey; Schuette, Jane; Wu, Yvonne W.; Asaikar, Shailesh; Pearson, Margaret; Folk, Leandra; Retterer, Kyle; Monaghan, Kristin G.; Chung, Wendy K.

    2016-01-01

    Protein phosphatase 2A (PP2A) is a heterotrimeric protein serine/threonine phosphatase and is involved in a broad range of cellular processes. PPP2R5D is a regulatory B subunit of PP2A and plays an important role in regulating key neuronal and developmental regulation processes such as PI3K/AKT and GSK3β-mediated cell growth, chromatin remodeling and gene transcriptional regulation. Using WES, we identified four de novo variants in PPP2R5D in a total of seven unrelated individuals with ID and other shared clinical characteristics, including autism spectrum disorder, macrocephaly, hypotonia, seizures and dysmorphic features. Among the four variant, two have been previously reported, and two are novel. All four amino acids are highly conserved among the PP2A subunit family, and all change a negatively charged acidic glutamic acid (E) to a positively charged basic lysine (K), and are predicted to disrupt the PP2A subunits binding and impair the dephosphorylation capacity. Our data provides further support for PPP2R5D as a genetic cause of ID. PMID:26576547

  9. Essential role of the m2R-RGS6-IKACh pathway in controlling intrinsic heart rate variability.

    PubMed

    Posokhova, Ekaterina; Ng, David; Opel, Aaisha; Masuho, Ikuo; Tinker, Andrew; Biesecker, Leslie G; Wickman, Kevin; Martemyanov, Kirill A

    2013-01-01

    Normal heart function requires generation of a regular rhythm by sinoatrial pacemaker cells and the alteration of this spontaneous heart rate by the autonomic input to match physiological demand. However, the molecular mechanisms that ensure consistent periodicity of cardiac contractions and fine tuning of this process by autonomic system are not completely understood. Here we examined the contribution of the m2R-I(KACh) intracellular signaling pathway, which mediates the negative chronotropic effect of parasympathetic stimulation, to the regulation of the cardiac pacemaking rhythm. Using isolated heart preparations and single-cell recordings we show that the m2R-I(KACh) signaling pathway controls the excitability and firing pattern of the sinoatrial cardiomyocytes and determines variability of cardiac rhythm in a manner independent from the autonomic input. Ablation of the major regulator of this pathway, Rgs6, in mice results in irregular cardiac rhythmicity and increases susceptibility to atrial fibrillation. We further identify several human subjects with variants in the RGS6 gene and show that the loss of function in RGS6 correlates with increased heart rate variability. These findings identify the essential role of the m2R-I(KACh) signaling pathway in the regulation of cardiac sinus rhythm and implicate RGS6 in arrhythmia pathogenesis. PMID:24204714

  10. Essential Role of the m2R-RGS6-IKACh Pathway in Controlling Intrinsic Heart Rate Variability

    PubMed Central

    Posokhova, Ekaterina; Ng, David; Opel, Aaisha; Masuho, Ikuo; Tinker, Andrew; Biesecker, Leslie G.; Wickman, Kevin; Martemyanov, Kirill A.

    2013-01-01

    Normal heart function requires generation of a regular rhythm by sinoatrial pacemaker cells and the alteration of this spontaneous heart rate by the autonomic input to match physiological demand. However, the molecular mechanisms that ensure consistent periodicity of cardiac contractions and fine tuning of this process by autonomic system are not completely understood. Here we examined the contribution of the m2R-IKACh intracellular signaling pathway, which mediates the negative chronotropic effect of parasympathetic stimulation, to the regulation of the cardiac pacemaking rhythm. Using isolated heart preparations and single-cell recordings we show that the m2R-IKACh signaling pathway controls the excitability and firing pattern of the sinoatrial cardiomyocytes and determines variability of cardiac rhythm in a manner independent from the autonomic input. Ablation of the major regulator of this pathway, Rgs6, in mice results in irregular cardiac rhythmicity and increases susceptibility to atrial fibrillation. We further identify several human subjects with variants in the RGS6 gene and show that the loss of function in RGS6 correlates with increased heart rate variability. These findings identify the essential role of the m2R-IKACh signaling pathway in the regulation of cardiac sinus rhythm and implicate RGS6 in arrhythmia pathogenesis. PMID:24204714

  11. Promoter-restricted histone code, not the differentially methylated DNA regions or antisense transcripts, marks the imprinting status of IGF2R in human and mouse.

    PubMed

    Vu, Thanh H; Li, Tao; Hoffman, Andrew R

    2004-10-01

    Imprinting of the mouse Igf2r depends upon an intronic differentially methylated DNA region (DMR) and the presence of the Air antisense transcript. However, biallelic expression of mouse Igf2r in brain occurs despite the presence of Air, and biallelic expression of human IGF2R in peripheral tissues occurs despite the presence of an intronic DMR. We examined histone modifications throughout the mouse and human Igf2r/IGF2R using chromatin immuno-precipitation (ChIP) assays in combination with quantitative real time PCR. Methylation of Lys4 and Lys9 of histone H3 in the promoter regions marks the active and silenced alleles, respectively. We measured di- and tri-methyl Lys4 and Lys9 across the Igf2r and Air promoters. While both di- and tri-methyl Lys4 marked the active Igf2r and the active Air allele, tri-methyl Lys9, but not di-methyl Lys9, marked the suppressed Air allele. We show here that enrichment of parental allele-specific histone modifications in the promoter region, rather than the presence of DNA methylation or antisense transcription, correctly identifies the tissue- and species- specific imprinting status of Igf2r/IGF2R. We discuss these findings in light of recent progress in identifying specific components of the epigenetic marks in imprinted genes. PMID:15294879

  12. Allelic Variation in TAS2R Bitter Receptor Genes Associates with Variation in Sensations from and Ingestive Behaviors toward Common Bitter Beverages in Adults

    PubMed Central

    Hayes, John E.; Wallace, Margaret R.; Knopik, Valerie S.; Herbstman, Deborah M.; Bartoshuk, Linda M.

    2011-01-01

    The 25 human bitter receptors and their respective genes (TAS2Rs) contain unusually high levels of allelic variation, which may influence response to bitter compounds in the food supply. Phenotypes based on the perceived bitterness of single bitter compounds were first linked to food preference over 50 years ago. The most studied phenotype is propylthiouracil bitterness, which is mediated primarily by the TAS2R38 gene and possibly others. In a laboratory-based study, we tested for associations between TAS2R variants and sensations, liking, or intake of bitter beverages among healthy adults who were primarily of European ancestry. A haploblock across TAS2R3, TAS2R4, and TAS2R5 explained some variability in the bitterness of espresso coffee. For grapefruit juice, variation at a TAS2R19 single nucleotide polymorphism (SNP) was associated with increased bitterness and decreased liking. An association between a TAS2R16 SNP and alcohol intake was identified, and the putative TAS2R38–alcohol relationship was confirmed, although these polymorphisms did not explain sensory or hedonic responses to sampled scotch whisky. In summary, TAS2R polymorphisms appear to influence the sensations, liking, or intake of common and nutritionally significant beverages. Studying perceptual and behavioral differences in vivo using real foods and beverages may potentially identify polymorphisms related to dietary behavior even in the absence of known ligands. PMID:21163912

  13. Protein kinase activity associated with Fc. gamma. /sub 2a/ receptor of a murine macrophage like cell line, P388D/sub 1/

    SciTech Connect

    Hirata, Y.; Suzuki, T.

    1987-12-15

    The properties of protein kinase activity associated with Fc receptor specific for IgG/sub 2a/(Fc..gamma../sub 2a/R) of a murine macrophage like cell line, P388D/sub 1/, were investigated. IgG/sub 2a/-binding protein isolated from the detergent lysate of P388D/sub 1/ cells by affinity chromatography of IgG-Sepharose was found to contain four distinct proteins of M/sub r/ 50,000, 43,000, 37,000, and 17,000, which could be autophosphorylated upon incubation with (..gamma..-/sup 32/P)ATP. The autophosphorylation of Fc..gamma../sub 2a/ receptor complex ceased when exogenous phosphate acceptors (casein or histone) were added in the reaction mixture. Phosphorylation of casein catalyzed by Fc..gamma../sub 2a/ receptor complex was dependent on casein concentration, increased with time or temperature, was dependent on the concentration of ATP and Mg/sup 2 +/, and was maximum at pH near 8. Casein phosphorylation was significantly inhibited by a high concentration of Mn/sup 2 +/ or KCl or by a small amount of heparin and was enhanced about 2-fold by protamine. Casein kinase activity associated with Fc..gamma../sub 2a/ receptor used ATP as substrate with an apparent K/sub m/ of 2 ..mu..M as well as GTP with an apparent K/sub m/ of 10 ..mu..M. Prior heating (60/sup 0/C for 15 min) or treatment with protease (trypsin or Pronase) of Fc..gamma../sub 2a/ receptor complex almost totally abolished casein kinase activity. Thin-layer chromatography of a partial acid hydrolysate of the phosphorylated casein showed that the site of phosphorylation is at a seryl residue. These results suggest that Fc..gamma../sub 2//sub a/ receptor forms a molecule complex with protein kinase, whose characteristics resemble those of type II casein kinase but are different from those of cyclic nucleotide dependent protein kinase or from those of C protein kinase.

  14. The substituent effect of 2-R-o-carborane on the photophysical properties of iridium(III) cyclometalates.

    PubMed

    Park, Jihyun; Lee, Young Hoon; Ryu, Ji Yeon; Lee, Junseong; Lee, Min Hyung

    2016-04-01

    A family of heteroleptic iridium(iii) cyclometalates, [4-(2-RCB)ppy]2Ir(acac) (3c-3g; CB = o-carboran-1-yl; ppy = 2-phenylpyridinato-C(2),N; acac = acetylacetonate; R = (i)Pr (3c), (i)Bu (3d), Ph (3e), CF3C6H4 (3f), C6F5 (3g)) with various 2-R substituted o-carboranes at the 4-position in the phenyl ring of the ppy ligand, were prepared. The X-ray crystal structure of all complexes, including 3a (R = H) and 3b (R = Me), showed that while the carboranyl C-C bond distance increases with the increasing steric effect of the 2-R substituent (3a-3d), the bond distance is more likely to be influenced by the electronic effect of the substituent for the 2-aryl substituted complexes (3e-3g). The absorption and emission bands of all complexes were red-shifted with respect to those of the parent (ppy)2Ir(acac) (4). While 3a-3d exhibited intense green phosphorescence with good quantum efficiency in toluene (ΦPL = 0.17-0.47), the complexes were poorly emissive in THF (ΦPL < 0.004). In a PMMA film, however, 3a-3d became substantially emissive (ΦPL = 0.11-0.14, 8 wt% Ir), albeit less emissive than 4 (ΦPL = 0.15). In contrast, the 2-aryl substituted 3e-3g were almost non-emissive in both the solution and solid states. All complexes underwent facile carborane-centered, electrochemical reduction (Eonset = -2.01 to -1.22 V). The potential values of these reductions increased with increases in the electron accepting ability of the 2-R group (H < alkyl < aryl) and were largely shifted anodically with respect to those of 4 and 5-carborane substituted complexes. This reduction behavior of 3a-3g implies that the LUMO contribution of 2-R-o-carborane units increases through the substitution at the 4-position of the ppy ligand and is influenced by the nature of the 2-R group, which may be responsible for facile carboranyl C-C bond variation leading to efficient quenching of the emissive excited states. PMID:26923990

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

    NASA Astrophysics Data System (ADS)

    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

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

    NASA Astrophysics Data System (ADS)

    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

  17. Cre-Mediated Recombination in Tas2r131 Cells-A Unique Way to Explore Bitter Taste Receptor Function Inside and Outside of the Taste System.

    PubMed

    Voigt, Anja; Hübner, Sandra; Döring, Linda; Perlach, Nathalie; Hermans-Borgmeyer, Irm; Boehm, Ulrich; Meyerhof, Wolfgang

    2015-11-01

    The type 2 taste receptors (Tas2rs) comprise a large family of G protein-coupled receptors that recognize compounds bitter to humans and aversive to vertebrates. Tas2rs are expressed in both gustatory and nongustatory tissues, however, identification and functional analyses of T2R-expressing cells have been difficult in most tissues. To overcome these limitations and to be able to manipulate Tas2r-expressing cells in vivo, we used gene-targeting to generate a Tas2r131-specific Cre knock-in mouse strain. We then employed a binary genetic approach to characterize Cre-mediated recombination in these animals and to investigate Tas2r131 expression during postnatal development. We demonstrate that a Cre-activated fluorescent reporter reliably visualizes Tas2r131-cells in gustatory tissue. We show that the onset of Tas2r131 as well as of α-Gustducin expression is initiated at different developmental stages depending on the type of taste bud. Furthermore, the number of Tas2r131- and α-Gustducin-expressing cells increased during postnatal development. Our results demonstrate that the Tas2r131-expressing cells constitute a subpopulation of α-Gustducin positive cells at all stages. We detected Tas2r131-expressing cells in several nongustatory tissues including lung, trachea, ovary, ganglia, and brain. Thus, the Tas2r131-Cre strain will help to dissect the functional role of Tas2r131 cells in both gustatory and nongustatory tissues in the future. PMID:26377344

  18. Vibrational mode and collision energy effects on reaction of H{sub 2}CO{sup +} with C{sub 2}D{sub 4}

    SciTech Connect

    Liu Jianbo; Devener, Brian van; Anderson, Scott L.

    2004-12-15

    We report the effects of collision energy (E{sub col}) and five different H{sub 2}CO{sup +} vibrational modes on the reaction of H{sub 2}CO{sup +} with C{sub 2}D{sub 4} over the center-of-mass E{sub col} range from 0.1 to 2.1 eV. Properties of various complexes and transition states were also examined computationally. Seven product channels are observed. Charge transfer (CT) has the largest cross section over the entire energy range, substantially exceeding the hard sphere cross section at high energies. Competing with CT are six channels involving transfer of one or more hydrogen atoms or protons and one involving formation of propanal, followed by hydrogen elimination. Despite the existence of multiple deep wells on the potential surface, all reactions go by direct mechanisms, except at the lowest collision energies, where short-lived complexes appear to be important. Statistical complex decay appears adequate to account for the product branching at low collision energies, however, even at the lowest energies, the vibrational effects are counter to statistical expectations. The pattern of E{sub col} and vibrational mode effects provide insight into factors that control reaction and interchannel competition.

  19. Energy expenditures in four men estimated by D/sub 2/ /sup 18/O method at two times. I. From 24 hr urine samples

    SciTech Connect

    Bodwell, C.E.; Miles, C.W.; Seale, J.L.; Canary, J.J.; Prather, E.S.

    1986-03-01

    Four men (I-IV) were fed controlled diets with adjustment of energy intakes until body weights were constant for 3 wks (fall (F)) or 2 wks (spring (S)) and then maintained on the same diets for 3-4 weeks after dosing with D/sub 2/ /sup 18/O. Disappearances of D and /sup 18/O, measured in 24 hour urine (21 days), were used to estimate energy expenditures (EE) compared to metabolizable energy intakes (EI) needed to maintain body wt. EI were obtained from gross energy values (bomb calorimetry) of diet composites corrected for fecal and urinary losses. One subject (IV) consumed ETOH (18-20% of total calories). Among subjects, daily EI varied from 2500 to 3100 Kcal; 21-day mean +/-S.D. body wts. were (I) 66.3 +/- 0.3(F), 67.2 +/- 0.3(S); (II) 73.6 +/- 0.2(F), 74.2 +/- 0.3 (S); (III) 80.2 +/- 0.3(F), 77.6 +/- 0.4(S); (IV) 69.4 +/- 0.4(F), 70.7 +/- 0.4(S). For I and II, F and S intakes and EE values were similar; for III, S values were lower than F values. Small changes in body composition were observed; allowing for these altered relations between EE and EI. EE values were anomalous for IV; for subjects with high intake levels of fluids/ETOH, special methodology may be needed.

  20. Role of high-lying electronic states on the angular distribution of photofragments in multiphoton dissociation of D{sub 2}{sup +} by intense laser fields

    SciTech Connect

    Sen, Sanjay; Dutta, Bibhas; Bhattacharyya, S. S.; Saha, Samir

    2003-05-01

    We have theoretically investigated the role of high lying electronic states 2p{pi}{sub u} and 3d{sigma}{sub g} on multiphoton dissociation of D{sub 2}{sup +} from initial vibrational-rotational levels v{sub i}=4,5 and J{sub i}=0,1 by linearly polarized light with wavelength 400 nm and intensity 3x10{sup 13} W/cm{sup 2}. We have found that for initial level v{sub i}=4 and J{sub i}=1, a considerable number of photofragments is ejected perpendicular to the polarization direction of the laser field. It is shown that the perpendicular dissociation is due to the (net) four-photon absorption of the ground 1s{sigma}{sub g} state to the 3d{sigma}{sub g} state through the intermediate five-photon coupling of the 1s{sigma}{sub g} and 2p{pi}{sub u} states at intense laser field with high frequency. Our computed value of the emission of D{sup +} ions in the perpendicular direction to that in the parallel direction of the laser polarization reasonably agrees with the recent experimental result of Chin and co-workers at the same laser parameters [Phys. Rev. A 62, 042708 (2000)].

  1. Association analysis of the dopamine D{sub 2} receptor gene in Tourette`s syndrome using the haplotype relative risk method

    SciTech Connect

    Noethen, M.M.; Cichon, S.; Propping, P.

    1994-09-15

    Comings et al. have recently reported a highly significant association between Tourette`s syndrome (TS) and a restriction fragment length polymorphism (RFLP) of the dopamine D{sub 2} receptor gene (DRD2) locus. The A1 allele of the DRD2 Taq I RFLP was present in 45% of the Tourette patients compared with 25% of controls. We tried to replicate this finding by using the haplotype relative risk (HRR) method for association analysis. This method overcomes a major problem of conventional case-control studies, where undetected ethnic differences between patients and controls may result in a false-positive finding, by using parental alleles not inherited by the proband as control alleles. Sixty-one nuclear families encompassing an affected child and parents were typed for the DRD2 Taq I polymorphism. No significant differences in DRD2 A1 allele frequency were observed between TS probands, sub-populations of probands classified according to tic severity, or parental control alleles. Our data do not support the hypothesis that the DRD2 locus may act as a modifying gene in the expression of the disorder in TS probands. 40 refs., 1 tab.

  2. Dopamine inhibition of anterior pituitary adenylate cyclase is mediated through the high-affinity state of the D/sub 2/ receptor

    SciTech Connect

    Borgundvaag, B.; George, S.R.

    1985-07-29

    The diterpinoid forskolin stimulated adenylate cyclase activity (measured by conversion of (/sup 3/H)-ATP to (/sup 3/H)-cAMP) in anterior pituitary from male and female rats. Inhibition of stimulated adenylate cyclase activity by potent dopaminergic agonists was demonstrable only in female anterior pituitary. The inhibition of adenylate cyclase activity displayed a typically dopaminergic rank order of agonist potencies and could be completely reversed by a specific dopamine receptor antagonist. The IC/sub 50/ values of dopamine agonist inhibition of adenylate cyclase activity correlated with equal molarity with the dissociation constant of the high-affinity dopamine agonist-detected receptor binding site and with the IC/sub 50/ values for inhibition of prolactin secretion. These findings support the hypothesis that it is the high-affinity form of the D/sub 2/ dopamine receptor in anterior pituitary which is responsible for mediating the dopaminergic function of attenuating adenylate cyclase activity. 12 references, 4 figures, 1 table.

  3. CREB Negatively Regulates IGF2R Gene Expression and Downstream Pathways to Inhibit Hypoxia-Induced H9c2 Cardiomyoblast Cell Death

    PubMed Central

    Chen, Wei-Kung; Kuo, Wei-Wen; Hsieh, Dennis Jine-Yuan; Chang, Hsin-Nung; Pai, Pei-Ying; Lin, Kuan-Ho; Pan, Lung-Fa; Ho, Tsung-Jung; Viswanadha, Vijaya Padma; Huang, Chih-Yang

    2015-01-01

    During hypoxia, gene expression is altered by various transcription factors. Insulin-like growth factor-II (IGF2) is known to be induced by hypoxia, which binds to IGF2 receptor IGF2R that acts like a G protein-coupled receptor, might cause pathological hypertrophy or activation of the mitochondria-mediated apoptosis pathway. Cyclic adenosine monophosphate (cAMP) responsive element-binding protein (CREB) is central to second messenger-regulated transcription and plays a critical role in the cardiomyocyte survival pathway. In this study, we found that IGF2R level was enhanced in H9c2 cardiomyoblasts exposed to hypoxia in a time-dependent manner but was down-regulated by CREB expression. The over-expression of CREB in H9c2 cardiomyoblasts suppressed the induction of hypoxia-induced IGF2R expression levels and reduced cell apoptosis. Gel shift assay results further indicated that CREB binds to the promoter sequence of IGF2R. With a luciferase assay method, we further observed that CREB represses IGF2R promoter activity. These results suggest that CREB plays an important role in the inhibition of IGF2R expression by binding to the IGF2R promoter and further suppresses H9c2 cardiomyoblast cell apoptosis induced by IGF2R signaling under hypoxic conditions. PMID:26610485

  4. Genome-wide identification of cassava R2R3 MYB family genes related to abscission zone separation after environmental-stress-induced abscission

    PubMed Central

    Liao, Wenbin; Yang, Yiling; Li, Yayun; Wang, Gan; Peng, Ming

    2016-01-01

    Cassava plants (Manihot esculenta Crantz) resist environmental stresses by shedding leaves in leaf pulvinus abscission zones (AZs), thus leading to adaptation to new environmental conditions. Little is known about the roles of cassava R2R3 MYB factors in regulating AZ separation. Herein, 166 cassava R2R3 MYB genes were identified. Evolutionary analysis indicated that the 166 R2R3 MYB genes could be divided into 11 subfamilies. Transcriptome analysis indicated that 26 R2R3 MYB genes were expressed in AZs across six time points during both ethylene- and water-deficit stress-induced leaf abscission. Comparative expression profile analysis of similar SOTA (Self Organizing Tree Algorithm) clusters demonstrated that 10 R2R3 MYB genes had similar expression patterns at six time points in response to both treatments. GO (Gene Ontology) annotation confirmed that all 10 R2R3 MYB genes participated in the responses to stress and ethylene and auxin stimuli. Analysis of the putative 10 R2R3 MYB promoter regions showed that those genes primarily contained ethylene- and stress-related cis-elements. The expression profiles of the genes acting downstream of the selected MYBs were confirmed to be involved in cassava abscission zone separation. All these results indicated that R2R3 MYB plays an important regulatory role in AZ separation. PMID:27573926

  5. Synthesis of (2R, 3R)-epigallocatechin-3-O-(4-hydroxybenzoate), a novel catechin from Cistus salvifolius, and evaluation of its proteasome inhibitory activities.

    PubMed

    Osanai, Kumi; Huo, Congde; Landis-Piwowar, Kristin R; Dou, Q Ping; Chan, Tak Hang

    2007-08-01

    The total and semi syntheses of (2R, 3R)-epigallocatechin-3-O-(4-hydroxybenzoate), a novel catechin from Cistus salvifolius, was accomplished. The proteasome inhibition and cytotoxic activities of the synthetic compound and its acetyl derivative were studied and compared with (2R, 3R)-epigallocatechin-3-gallate (EGCG), the active component from green tea. PMID:21152270

  6. Genome-wide identification of cassava R2R3 MYB family genes related to abscission zone separation after environmental-stress-induced abscission.

    PubMed

    Liao, Wenbin; Yang, Yiling; Li, Yayun; Wang, Gan; Peng, Ming

    2016-01-01

    Cassava plants (Manihot esculenta Crantz) resist environmental stresses by shedding leaves in leaf pulvinus abscission zones (AZs), thus leading to adaptation to new environmental conditions. Little is known about the roles of cassava R2R3 MYB factors in regulating AZ separation. Herein, 166 cassava R2R3 MYB genes were identified. Evolutionary analysis indicated that the 166 R2R3 MYB genes could be divided into 11 subfamilies. Transcriptome analysis indicated that 26 R2R3 MYB genes were expressed in AZs across six time points during both ethylene- and water-deficit stress-induced leaf abscission. Comparative expression profile analysis of similar SOTA (Self Organizing Tree Algorithm) clusters demonstrated that 10 R2R3 MYB genes had similar expression patterns at six time points in response to both treatments. GO (Gene Ontology) annotation confirmed that all 10 R2R3 MYB genes participated in the responses to stress and ethylene and auxin stimuli. Analysis of the putative 10 R2R3 MYB promoter regions showed that those genes primarily contained ethylene- and stress-related cis-elements. The expression profiles of the genes acting downstream of the selected MYBs were confirmed to be involved in cassava abscission zone separation. All these results indicated that R2R3 MYB plays an important regulatory role in AZ separation. PMID:27573926

  7. Genetic variation in the hTAS2R38 taste receptor and food consumption among Finnish adults.

    PubMed

    Sandell, Mari; Hoppu, Ulla; Mikkilä, Vera; Mononen, Nina; Kähönen, Mika; Männistö, Satu; Rönnemaa, Tapani; Viikari, Jorma; Lehtimäki, Terho; Raitakari, Olli T

    2014-11-01

    Genetic variation in bitter taste receptors, such as hTAS2R38, may affect food preferences and intake. The aim of the present study was to investigate the association between bitter taste receptor haplotypes and the consumption of vegetables, fruits, berries and sweet foods among an adult Finnish population. A cross-sectional design utilizing data from the Cardiovascular Risk in Young Finns cohort from 2007, which consisted of 1,903 men and women who were 30-45 years of age from five different regions in Finland, was employed. DNA was extracted from blood samples, and hTAS2R38 polymorphisms were determined based on three SNPs (rs713598, rs1726866 and rs10246939). Food consumption was assessed with a validated food frequency questionnaire. The prevalence of the bitter taste-sensitive (PAV/PAV) haplotype was 11.3 % and that of the insensitive (AVI/AVI) haplotype was 39.5 % among this Finnish population. PAV homozygotic women consumed fewer vegetables than did the AVI homozygotic women, 269 g/day (SD 131) versus 301 g/day (SD 187), respectively, p = 0.03 (multivariate ANOVA). Furthermore, the intake of sweet foods was higher among the PAV homozygotes of both genders. Fruit and berry consumption did not differ significantly between the haplotypes in either gender. Individuals perceive foods differently, and this may influence their patterns of food consumption. This study showed that the hTAS2R38 taste receptor gene variation was associated with vegetable and sweet food consumption among adults in a Finnish population. PMID:25303850

  8. The functional polymorphisms of VDR, GC and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases

    PubMed Central

    Inoue, N; Watanabe, M; Ishido, N; Katsumata, Y; Kagawa, T; Hidaka, Y; Iwatani, Y

    2014-01-01

    Vitamin D is a multi-functional immune regulator, and a low serum concentration of vitamin D promotes autoimmune inflammation. In this study, we evaluate the association between the prognosis of autoimmune thyroid disease (AITD) and the functional polymorphisms of genes that regulate vitamin D metabolism. For 139 Graves’ disease (GD) patients, 116 Hashimoto's disease (HD) patients and 76 control subjects, we genotyped the following polymorphisms using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP): vitamin D receptor (VDR): rs731236, rs7975232, rs2228570 and rs1544410; group-specific component (GC): rs7041 and rs4588; and CYP2R1: rs10741657. The frequency of the TT genotype for the rs731236 polymorphism was higher in GD patients than in HD patients (P = 0·0147). The frequency of the C allele for the rs7975232 polymorphism was higher in GD patients than in control subjects (P = 0·0349). The proportion of GD patients whose anti-thyrotrophin receptor antibody (TRAb) level was >51% was higher in those with the CC genotype than in those with the CA+AA genotypes (P = 0·0065). The frequency of the CC genotype for the rs2228570 polymorphism was higher in HD patients than in control subjects (P = 0·0174) and GD patients (P = 0·0149). The frequency of the Gc1Gc1 genotype for the GC polymorphism and the AG genotype for the CYP2R1 polymorphism were lower in intractable GD than in GD in remission (P = 0·0093 and 0·0268, respectively). In conclusion, genetic differences in the VDR gene may be involved in the development of AITD and the activity of GD, whereas the genetic differences in the GC and CYP2R1 genes may be involved with the intractability of GD. PMID:25046415

  9. Superconformal generalization of the chaotic inflation model λ/4φ{sup 4} - ξ/2φ{sup 2}R

    SciTech Connect

    Kallosh, Renata; Linde, Andrei E-mail: alinde@stanford.edu

    2013-06-01

    A model of chaotic inflation based on the theory of a scalar field with potential λφ{sup 4} perfectly matches the observational data if one adds to it a tiny non-minimal coupling to gravity -ξ/2φ{sup 2} R with ξ∼>0.002. We describe embedding of this model into the superconformal theory with spontaneous breaking of superconformal symmetry, and into supergravity. A model with small ξ is technically natural: setting the small parameter ξ to zero leads to a point of enhanced symmetry in the underlying superconformal theory.

  10. Strings in AdS{sub 3} and the SL(2,R) WZW Model. Part 1: The spectrum

    SciTech Connect

    Maldacena, Juan; Ooguri, Hirosi

    2000-05-19

    In this paper we study the spectrum of bosonic string theory on AdS{sub 3}. We study classical solutions of the SL(2,R) WZW model, including solutions for long strings with non-zero winding number. We show that the model has a symmetry relating string configurations with different winding numbers. We then study the Hilbert space of the WZW model, including all states related by the above symmetry. This leads to a precise description of long strings. We prove a no-ghost theorem for all the representations that are involved and discuss the scattering of the long string.

  11. Structural and magnetic properties of RTiNO{sub 2} (R=Ce, Pr, Nd) perovskite nitride oxides

    SciTech Connect

    Porter, Spencer H.; Huang, Zhenguo; Cheng, Zhenxiang; Avdeev, Maxim; Chen, Zhixin; Dou, Shixue; Woodward, Patrick M.

    2015-03-15

    Neutron powder diffraction indicates that CeTiNO{sub 2} and PrTiNO{sub 2} crystallize with orthorhombic Pnma symmetry (Ce: a=5.5580(5), b=7.8369(7), and c=5.5830(4) Å; Pr: a=5.5468(5), b=7.8142(5), and c=5.5514(5) Å) as a result of a{sup –}b{sup +}a{sup –} tilting of the titanium-centered octahedra. Careful examination of the NPD data, confirms the absence of long range anion order in both compounds, while apparent superstructure reflections seen in electron diffraction patterns provide evidence for short range anion order. Inverse magnetic susceptibility plots reveal that the RTiNO{sub 2} (R=Ce, Pr, Nd) compounds are paramagnetic with Weiss constants that vary from −28 to −42 K. Effective magnetic moments for RTiNO{sub 2} (R=Ce, Pr, Nd) are 2.43 μ{sub B}, 3.63 μ{sub B}, and 3.47 μ{sub B}, respectively, in line with values expected for free rare-earth ions. Deviations from Curie–Weiss behavior that occur below 150 K for CeTiNO{sub 2} and below 30 K for NdTiNO{sub 2} are driven by magnetic anisotropy, spin–orbit coupling, and crystal field effects. - Graphical abstract: The structure and magnetism of the oxide nitride perovskites RTiNO{sub 2} (R=Ce, Pr, Nd) have been explored. The average symmetry is shown to be Pnma with a random distribution of oxide and nitride ions and a{sup −}b{sup +}a{sup −} tilting of the titanium-centered octahedra, but electron diffraction shows evidence for short range anion order. All three compounds are paramagnetic but deviations from the Curie Weiss law are seen below 150 K for R=Ce and below 30 K for R=Nd. - Highlights: • The oxide nitride perovskites RTiNO{sub 2} (R=Ce, Pr) have been prepared and their structures determined. • Diffraction measurements indicate short range cis-order of O and N, but no long range order. • Compounds are paramagnetic with Weiss constants that vary from −28 to −42 K. • CeTiO{sub 2}N and NdTiO{sub 2}N deviate from Curie–Weiss behavior below 150 and 30 K, respectively.

  12. DNA Methylation Levels of CYP2R1 and CYP24A1 Predict Vitamin D Response Variation1, 2

    PubMed Central

    Zhou, Yu; Zhao, Lan-Juan; Xu, Xiaojing; Ye, An; Travers-Gustafson, Dianne; Zhou, Boting; Wang, Hong-Wei; Zhang, Weidong; Hamm, L. Lee; Deng, Hong-Wen; Recker, Robert R.; Lappe, Joan M.

    2013-01-01

    Factors contributing to the variability of serum 25-hydroxyvitamin D [25(OH)D] in response to a given dose of vitamin D supplementation are largely unknown. We examined whether DNA methylation levels of Cytochrome P450 (CYP) enzymes (CYP2R1, CYP24A1, CYP27A1, and CYP27B1) are potential biomarkers predicting vitamin D response variation. We randomized 446 white postmenopausal women to a calcium and vitamin D (1100 IU/day) intervention for at least 12 months. From these subjects, 18 with the highest 12-month increase in serum 25(OH)D were selected as “responders.” Another 18 with the lowest 12-month increase in serum 25(OH)D were selected as “non-responders.” DNA methylation levels between the groups were compared. To validate findings in the first study, association between DNA methylation levels and vitamin D response variation was studied in another 145 extended independent white postmenopausal women. In the first study, compared to non-responders, responders had significantly lower baseline DNA methylation levels in the promoter region of CYP2R1 (8% in the responders vs 30% in the non-responders, P=0.004), and CYP24A1 (13% in the responders vs 32% in the non-responders, P=0.001). In the validation study, for CYP2R1, baseline DNA methylation levels at eight CpG sites were negatively associated with 12-month increases in serum 25(OH)D (P<0.05). For CYP24A1, baseline DNA methylation levels at two CpG sites were also negatively associated with vitamin D response variation (r=−0.151, P=0.011; r=−0.131, P=0.025). These negative associations were consistent with the first study’s results. Our findings indicate that baseline DNA methylation levels of CYP2R1 and CYP24A1 may predict vitamin D response variation. PMID:24128439

  13. Full-scale wind-tunnel investigation of an Ayres S2R-800 Thrush Agricultural Airplane

    NASA Technical Reports Server (NTRS)

    Johnson, J. L., Jr.; Mclemore, H. C.; White, R.; Jordan, F. L., Jr.

    1979-01-01

    This paper summarizes the significant results of recent full-scale wind tunnel tests at the NASA-Langley Research Center of the Ayres S2R-800 Thrush Agricultural Aircraft. The purpose of the tests was to provide fundamental aerodynamic, performance, and stability and control information of the airplane and dispersal equipment; and to study near-field wake interaction characteristics behind the aircraft. The aerodynamic tests included the use of a propeller thrust-torque balance to measure the efficiency of the propeller in the presence of the engine and to provide data for determining slipstream interference effects and slip-stream drag.

  14. Energy of the quasi-free electron in H{sub 2}, D{sub 2}, and O{sub 2}: Probing intermolecular potentials within the local Wigner-Seitz model

    SciTech Connect

    Evans, C. M. Krynski, Kamil; Streeter, Zachary; Findley, G. L.

    2015-12-14

    We present for the first time the quasi-free electron energy V{sub 0}(ρ) for H{sub 2}, D{sub 2}, and O{sub 2} from gas to liquid densities, on noncritical isotherms and on a near critical isotherm in each fluid. These data illustrate the ability of field enhanced photoemission (FEP) to determine V{sub 0}(ρ) accurately in strongly absorbing fluids (e.g., O{sub 2}) and fluids with extremely low critical temperatures (e.g., H{sub 2} and D{sub 2}). We also show that the isotropic local Wigner-Seitz model for V{sub 0}(ρ) — when coupled with thermodynamic data for the fluid — can yield optimized parameters for intermolecular potentials, as well as zero kinetic energy electron scattering lengths.

  15. Neutron powder diffraction study of the layer organic-inorganic hybrid iron(II) methylphosphonate-hydrate, Fe[(CD{sub 3}PO{sub 3})(D{sub 2}O)

    SciTech Connect

    Leone, Philippe Bellitto, Carlo; Bauer, Elvira M.; Righini, Guido; Andre, Gilles; Bouree, Francoise

    2008-11-15

    The crystal and magnetic structures of the hybrid organic-inorganic layer compound Fe[(CD{sub 3}PO{sub 3})(D{sub 2}O)] have been studied by neutron powder diffraction as a function of temperature down to 1.5 K. The neutron diffraction pattern recorded at 200 K shows that the fully deuterated compound crystallizes in one of the two known forms of the undeuterated Fe[(CH{sub 3}PO{sub 3})(H{sub 2}O)]. The crystal structure is orthorhombic, space group Pmn2{sub 1}, with the following unit-cell parameters: a=5.7095(1) A, b=8.8053(3) A and c=4.7987(1) A; Z=2. The crystal structure remains unchanged on cooling from 200 to 1.5 K. Moreover, at low temperature, Fe[(CD{sub 3}PO{sub 3})(D{sub 2}O)] shows a commensurate magnetic structure (k=(0,0,0)). As revealed by bulk susceptibility measurements on Fe[(CH{sub 3}PO{sub 3})(H{sub 2}O)], the magnetic structure corresponds to a canted antiferromagnet with a critical temperature T{sub N}=25 K. Neutron powder diffraction reveals that below T{sub N}=23.5 K the iron magnetic moments in Fe[(CD{sub 3}PO{sub 3})(D{sub 2}O)] are antiferromagnetically coupled and oriented along the b-axis, perpendicular to the inorganic layers. No ferromagnetic component is observable in the neutron powder diffraction experiment, due to its too small value (<0.1{mu}{sub B}). - Graphical abstract: Crystal structure and magnetic structure of Fe[(CD{sub 3}PO{sub 3})(D{sub 2}O)].

  16. IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma.

    PubMed

    Wang, Chao; McKeithan, Timothy W; Gong, Qiang; Zhang, Weiwei; Bouska, Alyssa; Rosenwald, Andreas; Gascoyne, Randy D; Wu, Xiwei; Wang, Jinhui; Muhammad, Zahid; Jiang, Bei; Rohr, Joseph; Cannon, Andrew; Steidl, Christian; Fu, Kai; Li, Yuping; Hung, Stacy; Weisenburger, Dennis D; Greiner, Timothy C; Smith, Lynette; Ott, German; Rogan, Eleanor G; Staudt, Louis M; Vose, Julie; Iqbal, Javeed; Chan, Wing C

    2015-10-01

    Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of peripheral T-cell lymphoma (PTCL) with a poor prognosis. We performed targeted resequencing on 92 cases of PTCL and identified frequent mutations affecting RHOA, TET2, DNMT3A, and isocitrate dehydrogenase 2 (IDH2). Although IDH2 mutations are largely confined to AITL, mutations of the other 3 can be found in other types of PTCL, although at lower frequencies. These findings indicate a key role of epigenetic regulation in the pathogenesis of AITL. However, the epigenetic alterations induced by these mutations and their role in AITL pathogenesis are still largely unknown. We correlated mutational status with gene expression and global DNA methylation changes in AITL. Strikingly, AITL cases with IDH2(R172) mutations demonstrated a distinct gene expression signature characterized by downregulation of genes associated with TH1 differentiation (eg, STAT1 and IFNG) and a striking enrichment of an interleukin 12-induced gene signature. Ectopic expression of IDH2(R172K) in the Jurkat cell line and CD4(+) T cells led to markedly increased levels of 2-hydroxyglutarate, histone-3 lysine methylation, and 5-methylcytosine and a decrease of 5-hydroxymethylcytosine. Correspondingly, clinical samples with IDH2 mutations displayed a prominent increase in H3K27me3 and DNA hypermethylation of gene promoters. Integrative analysis of gene expression and promoter methylation revealed recurrently hypermethylated genes involved in T-cell receptor signaling and T-cell differentiation that likely contribute to lymphomagenesis in AITL. PMID:26268241

  17. Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor

    PubMed Central

    Giorgetti, Alejandro; Lanzara, Carmela; Gasparini, Paolo; Carloni, Paolo; Born, Stephan; Brockhoff, Anne; Behrens, Maik; Meyerhof, Wolfgang

    2010-01-01

    Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular docking. The predictions are validated by site-directed mutagenesis experiments that involve specific residues located in the putative binding site and trans-membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based on our measurements, we suggest that (i) residue N103 participates actively in PTC binding, in line with previous computational studies. (ii) W99, M100 and S259 contribute to define the size and shape of the binding cavity. (iii) W99 and M100, along with F255 and V296, play a key role for receptor activation, providing insights on bitter taste receptor activation not emerging from the previously reported computational models. PMID:20811630

  18. An Obesity-Predisposing Variant of the FTO Gene Regulates D2R-Dependent Reward Learning.

    PubMed

    Sevgi, Meltem; Rigoux, Lionel; Kühn, Anne B; Mauer, Jan; Schilbach, Leonhard; Hess, Martin E; Gruendler, Theo O J; Ullsperger, Markus; Stephan, Klaas Enno; Brüning, Jens C; Tittgemeyer, Marc

    2015-09-01

    Variations in the fat mass and obesity-associated (FTO) gene are linked to obesity. However, the underlying neurobiological mechanisms by which these genetic variants influence obesity, behavior, and brain are unknown. Given that Fto regulates D2/3R signaling in mice, we tested in humans whether variants in FTO would interact with a variant in the ANKK1 gene, which alters D2R signaling and is also associated with obesity. In a behavioral and fMRI study, we demonstrate that gene variants of FTO affect dopamine (D2)-dependent midbrain brain responses to reward learning and behavioral responses associated with learning from negative outcome in humans. Furthermore, dynamic causal modeling confirmed that FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic predisposition alters reward processing not only in obesity, but also in other disorders with altered D2R-dependent impulse control, such as addiction. Significance statement: Variations in the fat mass and obesity-associated (FTO) gene are associated with obesity. Here we demonstrate that variants of FTO affect dopamine-dependent midbrain brain responses and learning from negative outcomes in humans during a reward learning task. Furthermore, FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic vulnerability in reward processing can increase predisposition to obesity. PMID:26354923

  19. Variability in Human Bitter Taste Sensitivity to Chemically Diverse Compounds Can Be Accounted for by Differential TAS2R Activation.

    PubMed

    Roura, Eugeni; Aldayyani, Asya; Thavaraj, Pridhuvi; Prakash, Sangeeta; Greenway, Delma; Thomas, Walter G; Meyerhof, Wolfgang; Roudnitzky, Natacha; Foster, Simon R

    2015-07-01

    The human population displays high variation in taste perception. Differences in individual taste sensitivity may also impact on nutrient intake and overall appetite. A well-characterized example is the variable perception of bitter compounds such as 6-n-propylthiouracil (PROP) and phenylthiocarbamide (PTC), which can be accounted for at the molecular level by polymorphic variants in the specific type 2 taste receptor (TAS2R38). This phenotypic variation has been associated with influencing dietary preference and other behaviors, although the generalization of PROP/PTC taster status as a predictor of sensitivity to other tastes is controversial. Here, we proposed that the taste sensitivities of different bitter compounds would be correlated only when they activate the same bitter taste receptor. Thirty-four volunteers were exposed to 8 bitter compounds that were selected based on their potential to activate overlapping and distinct repertoires of TAS2Rs. Taste intensity ratings were evaluated using the general Labeled Magnitude Scale. Our data demonstrate a strong interaction between the intensity for bitter substances when they activate common TAS2Rs. Consequently, PROP/PTC sensitivity was not a reliable predictor of general bitter sensitivity. In addition, our findings provide a novel framework to predict taste sensitivity based on their specific T2R activation profile. PMID:25999325

  20. Characterization of two tartary buckwheat R2R3-MYB transcription factors and their regulation of proanthocyanidin biosynthesis.

    PubMed

    Bai, Yue-Chen; Li, Cheng-Lei; Zhang, Jin-Wen; Li, Shuang-Jiang; Luo, Xiao-Peng; Yao, Hui-Peng; Chen, Hui; Zhao, Hai-Xia; Park, Sang-Un; Wu, Qi

    2014-11-01

    Tartary buckwheat (Fagopyrum tataricum Gaertn.) contains high concentrations of flavonoids. The flavonoids are mainly represented by rutin, anthocyanins and proanthocyanins in tartary buckwheat. R2R3-type MYB transcription factors (TFs) play key roles in the transcriptional regulation of the flavonoid biosynthetic pathway. In this study, two TF genes, FtMYB1 and FtMYB2, were isolated from F. tataricum and characterized. The results of bioinformatic analysis indicated that the putative FtMYB1 and FtMYB2 proteins belonged to the R2R3-MYB family and displayed a high degree of similarity with TaMYB14 and AtMYB123/TT2. In vitro and in vivo evidence both showed the two proteins were located in the nucleus and exhibited transcriptional activation activities. During florescence, both FtMYB1 and FtMYB2 were more highly expressed in the flowers than any other organ. The overexpression of FtMYB1 and FtMYB2 significantly enhanced the accumulation of proanthocyanidins (PAs) and showed a strong effect on the target genes' expression in Nicotiana tabacum. The expression of dihydroflavonol-4-reductase (DFR) was upregulated to 5.6-fold higher than that of control, and the expression level was lower for flavonol synthase (FLS). To our knowledge, this is the first functional characterization of two MYB TFs from F. tataricum that control the PA pathway. PMID:24730512

  1. Relativistic multireference Fock-space coupled-cluster calculation of the forbidden 6s{sup 2} {sup 1}S{sub 0}{yields}6s5d {sup 3}D{sub 1} magnetic-dipole transition in ytterbium

    SciTech Connect

    Sur, Chiranjib; Chaudhuri, Rajat K.

    2007-07-15

    We report the forbidden 6s{sup 2} {sup 1}S{sub 0}{yields}6s5d {sup 3}D{sub 1} magnetic-dipole transition amplitude computed using multireference Fock-space coupled-cluster theory. Our computed transition matrix element (1.34x10{sup -4}){mu}{sub B} is in excellent agreement with the experimental value (1.33x10{sup -4}){mu}{sub B}. This value in combination with other known quantities will be helpful in determining the parity-nonconserving amplitude for the 6s{sup 2} {sup 1}S{sub 0}{yields}6s5d {sup 3}D{sub 1} transition in atomic Yb. To our knowledge, this calculation is the most accurate to date, and can be very important in the search for physics beyond the standard model. We further report the 6s6p {sup 3}P{sub 0}{yields}6s6p {sup 1}P{sub 1} and 6s5d {sup 3}D{sub 1}{yields}6s6p {sup 3}P{sub 0} transition matrix elements, which are also in good agreement with the earlier theoretical estimates.

  2. Determination of the binding energies of the np Rydberg states of H{sub 2}, HD, and D{sub 2} from high-resolution spectroscopic data by multichannel quantum-defect theory

    SciTech Connect

    Sprecher, Daniel; Merkt, Frédéric; Jungen, Christian

    2014-03-14

    Multichannel quantum-defect theory (MQDT) is used to calculate the electron binding energies of np Rydberg states of H{sub 2}, HD, and D{sub 2} around n = 60 at an accuracy of better than 0.5 MHz. The theory includes the effects of rovibronic channel interactions and the hyperfine structure, and has been extended to the calculation of the asymmetric hyperfine structure of Rydberg states of a heteronuclear diatomic molecule (HD). Starting values for the eigenquantum-defect parameters of MQDT were extracted from ab initio potential-energy functions for the low-lying p Rydberg states of molecular hydrogen and subsequently refined in a global weighted fit to available experimental data on the singlet and triplet Rydberg states of H{sub 2} and D{sub 2}. The electron binding energies of high-np Rydberg states derived in this work represent important quantities for future determinations of the adiabatic ionization energies of H{sub 2}, HD, and D{sub 2} at sub-MHz accuracy.

  3. Nonperturbative NN scattering in {sup 3}S{sub 1}–{sup 3}D{sub 1} channels of EFT(⁄π)

    SciTech Connect

    Yang, Ji-Feng

    2013-12-15

    The closed-form T matrices in the {sup 3}S{sub 1}–{sup 3}D{sub 1} channels of EFT(⁄π) for NN scattering with the potentials truncated at order O(Q{sup 4}) are presented with the nonperturbative divergences parametrized in a general manner. The stringent constraints imposed by the closed form of the T matrices are exploited in the underlying theory perspective and turned into virtues in the implementation of subtractions and the manifestation of power counting rules in nonperturbative regimes, leading us to the concept of EFT scenario. A number of scenarios of the EFT description of NN scattering are compared with PSA data in terms of effective range expansion and {sup 3}S{sub 1} phase shifts, showing that it is favorable to proceed in a scenario with conventional EFT couplings and sophisticated renormalization in order to have large NN scattering lengths. The informative utilities of fine tuning are demonstrated in several examples and naturally interpreted in the underlying theory perspective. In addition, some of the approaches adopted in the recent literature are also addressed in the light of EFT scenario. -- Highlights: •Closed-form unitary T matrices for NN scattering are obtained in EFT(⁄π). •Nonperturbative properties inherent in such closed-form T matrices are explored. •Nonperturbative renormalization is implemented through exploiting these properties. •Unconventional power counting of couplings is shown to be less favored by PSA data. •The ideas about nonperturbative renormalization here might have wider applications.

  4. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells

    PubMed Central

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P.; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  5. The Kiss2 receptor (Kiss2r) gene in Southern Bluefin Tuna, Thunnus maccoyii and in Yellowtail Kingfish, Seriola lalandi - functional analysis and isolation of transcript variants.

    PubMed

    Nocillado, J N; Biran, J; Lee, Y Y; Levavi-Sivan, B; Mechaly, A S; Zohar, Y; Elizur, A

    2012-10-15

    The kisspeptin system plays an essential role in reproductive function in vertebrates, particularly in the onset of puberty. We investigated the kisspeptin system in two Perciform teleosts, the Southern Bluefin Tuna (SBT; Thunnus maccoyii), and the Yellowtail Kingfish (YTK; Seriola lalandi), by characterising their kisspeptin 2 receptor (Kiss2r) genes. In addition to the full length Kiss2r cDNA sequences, we have isolated from SBT and YTK a transcript variant that retained an intron. We have further obtained three ytkKiss2r transcript variants that contained deletions. In vitro functional analysis of the full length SBT and YTK Kiss2r showed higher response to Kiss2-10 than to Kiss1-10, with stronger transduction via PKC than PKA. The full length ytkKiss2r and two deletion variants were differentially expressed in the brain of male, but not in female, juvenile YTK treated with increasing doses of Kiss2-10 peptide. In the gonads, the expression level of the ytkKiss2r transcripts did not vary significantly either in the male or female fish. This is the first time that transcript variants of the Kiss2r gene that contain deletions and show responsiveness to treatments with kisspeptin have been reported in any teleost. PMID:22824208

  6. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca(2+) oscillations in mouse pancreatic acinar cells.

    PubMed

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca(2+) signals may protect pancreatic acinar cells against Ca(2+) overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca(2+) signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca(2+) oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca(2+) oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca(2+) oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca(2+) oscillations and L-arginine-induced enhancement of Ca(2+) signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  7. Expression of the bitter receptor T2R38 in pancreatic cancer: localization in lipid droplets and activation by a bacteria-derived quorum-sensing molecule

    PubMed Central

    Gaida, Matthias M.; Mayer, Christine; Dapunt, Ulrike; Stegmaier, Sabine; Schirmacher, Peter; Wabnitz, Guido H.; Hänsch, G. Maria

    2016-01-01

    T2R38 belongs to the family of bitter receptors and was initially detected in cells of the oral cavity. We now describe expression of T2R38 in tumor cells in patients with pancreatic cancer and in tumor-derived cell lines. T2R38 is localized predominantly intracellular in association with lipid droplets, particularly with the lipid droplet membrane. The receptor can be activated by the bona fide ligand for T2R38, phenylthiourea (PTU), and by N-acetyl-dodecanoyl homoserine (AHL-12), a quorum sensing molecule of Pseudomonas aeruginosa, the latter is the only known natural ligand for T2R38. In response to PTU or AHL-12, key transcription factors are activated including phosphorylation of the MAP kinases p38 and ERK1/2, and upregulation of NFATc1. Moreover, we found increased expression of the multi-drug resistance protein 1 (also known as ABCB1), a transmembrane transporter molecule, participating in shuttling of a plethora of drugs, such as chemotherapeutics or antibiotics. In conclusion, our data indicate a new, additional function of the taste receptor T2R38 beyond sensing ‘bitter’. Moreover, because T2R38 can be stimulated by a bacteria-derived signaling molecule the receptor could link microbiota and cancer. PMID:26862855

  8. Expression of the Bitter Taste Receptor, T2R38, in Enteroendocrine Cells of the Colonic Mucosa of Overweight/Obese vs. Lean Subjects

    PubMed Central

    Latorre, Rocco; Huynh, Jennifer; Mazzoni, Maurizio; Gupta, Arpana; Bonora, Elena; Clavenzani, Paolo; Chang, Lin; Mayer, Emeran A.; De Giorgio, Roberto; Sternini, Catia

    2016-01-01

    Bitter taste receptors (T2Rs) are expressed in the mammalian gastrointestinal mucosa. In the mouse colon, T2R138 is localized to enteroendocrine cells and is upregulated by long-term high fat diet that induces obesity. The aims of this study were to test whether T2R38 expression is altered in overweight/obese (OW/OB) compared to normal weight (NW) subjects and characterize the cell types expressing T2R38, the human counterpart of mouse T2R138, in human colon. Colonic mucosal biopsies were obtained during colonoscopy from 35 healthy subjects (20 OW/OB and 15 NW) and processed for quantitative RT-PCR and immunohistochemistry using antibodies to T2R38, chromogranin A (CgA), glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), or peptide YY (PYY). T2R38 mRNA levels in the colonic mucosa of OW/OB were increased (> 2 fold) compared to NW subjects but did not reach statistical significance (P = 0.06). However, the number of T2R38 immunoreactive (IR) cells was significantly increased in OW/OB vs. NW subjects (P = 0.01) and was significantly correlated with BMI values (r = 0.7557; P = 0.001). In both OW/OB and NW individuals, all T2R38-IR cells contained CgA-IR supporting they are enteroendocrine. In both groups, T2R38-IR colocalized with CCK-, GLP1- or PYY-IR. The overall CgA-IR cell population was comparable in OW/OB and NW individuals. This study shows that T2R38 is expressed in distinct populations of enteroendocrine cells in the human colonic mucosa and supports T2R38 upregulation in OW/OB subjects. T2R38 might mediate host functional responses to increased energy balance and intraluminal changes occurring in obesity, which could involve peptide release from enteroendocrine cells. PMID:26866366

  9. Use of the SAMe-TT2R2 Score to Predict Good Anticoagulation Control with Warfarin in Chinese Patients with Atrial Fibrillation: Relationship to Ischemic Stroke Incidence

    PubMed Central

    Chan, Pak Hei; Hai, Jo Jo; Chan, Esther W.; Li, Wen Hua; Tse, Hung Fat; Wong, Ian C. K.; Lip, Gregory Y. H.; Siu, Chung Wah

    2016-01-01

    Background The efficacy and safety of warfarin therapy for stroke prevention in atrial fibrillation (AF) depends on the time in therapeutic range (TTR). We aimed to assess the predictive ability of SAMe-TT2R2 score in Chinese AF patients on warfarin, whose TTR is notoriously poor. Methods and Results This is a single-centre retrospective study. Patients with non-valvular AF on warfarin diagnosed between 1997 and 2011 were stratified according to SAMe-TT2R2 score, and TTR was calculated using Rosendaal method. The predictive power of SAMe-TT2R2 scores for good TTR i.e. >70% was assessed. We included 1,428 Chinese patients (mean age 76.2±8.7 years, 47.5% male) with non-valvular AF on warfarin. The mean and median TTR were 38.2±24.4% and 38.8% (interquartile range: 17.9% and 56.2%) respectively. TTR decreased progressively with increasing SAMe-TT2R2 score (p = 0.016). When the cut-off value of SAMe-TT2R2 score was set to 2, the sensitivity and specificity to predict TTR<70% were 85.7% and 17.8%, respectively. The corresponding positive and negative predictive values were 10.1% and 92.0%. After a mean follow-up of 4.7±3.6 years, 338 patients developed an ischemic stroke (4.96%/year). Patients with TTR≥70% had a lower annual risk of ischemic stroke of 3.67%/year compared with than those with TTR<70% (5.13%/year)(p = 0.08). Patients with SAMe-TT2R2 score ≤2 had the lowest risk of annual risk of ischemic stroke (3.49%/year) compared with those with SAMe-TT2R2 score = 3 (4.56%/year), and those with SAMe-TT2R2 score ≥4 (6.41%/year)(p<0.001). There was also a non-significant trend towards more intracranial hemorrhage with increasing SAMe-TT2R2 score. Conclusions The SAMe-TT2R2 score correlates well with TTR in Chinese AF patients, with a score >2 having high sensitivity and negative predictive values for poor TTR. Ischemic stroke risk increased progressively with increasing SAMe-TT2R2 score, consistent with poorer TTRs at high SAMe-TT2R2 scores. PMID:27010633

  10. Study of the magnetocaloric properties of the antiferromagnetic compounds RGa2 (R = Ce, Pr, Nd, Dy, Ho and Er).

    PubMed

    dos Reis, R D; da Silva, L M; dos Santos, A O; Medina, A M N; Cardoso, L P; Gandra, F G

    2010-12-01

    Magnetocaloric properties of antiferromagnetic RGa(2) (R = Ce, Pr, Nd, Dy, Ho and Er) compounds have been reported. These systems present an antiferromagnetic transition below 15 K and a field induced metamagnetic transition from the antiferromagnetic to ferromagnetic state. Our results show that the character of the magnetic field induced transition along the series affects the magnetocaloric properties. For the compounds with R = Ho, Dy and Er both negative and positive magnetocaloric effect (MCE) were observed above μ(0)ΔH = 2 T where the rate between negative and positive MCE contributions depends on how the magnetic transitions occur in these compounds. The evaluated values of maximum magnetocaloric properties of RGa(2) compounds are similar to other potential magnetic refrigerant materials reported in the literature. PMID:21406760

  11. Novel R2R Manufacturable Photonic-Enhanced Thin Film Solar Cells; January 28, 2010 -- January 31, 2011

    SciTech Connect

    Slafer, D.; Dalal, V.

    2012-03-01

    Final subcontract report for PV Incubator project 'Novel R2R Manufacturable Photonic-Enhanced Thin Film Solar Cells.' The goal of this program was to produce tandem Si cells using photonic bandgap enhancement technology developed at ISU and Lightwave Power that would have an NREL-verified efficiency of 7.5% on 0.25 cm{sup 2} area tandem junction cell on plastic substrates. This goal was met and exceeded within the timeframe and budget of the program. On smaller area cells, the efficiency was even higher, {approx}9.5% (not verified by NREL). Appropriate polymers were developed to fabricate photonic and plasmonic devices on stainless steel, Kapton and PEN substrates. A novel photonic-plasmon structure was developed which shows a promise of improving light absorption in thin film cells, a better light absorption than by any other scheme.

  12. Low-frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV-ECCO2R): an experimental study.

    PubMed

    Gattinoni, L; Kolobow, T; Tomlinson, T; Iapichino, G; Samaja, M; White, D; Pierce, J

    1978-01-01

    We describe a new form of mechanical pulmonary ventilation, low-frequency positive pressure ventilation with extracorporeal CO2 removal (LEPPV-ECCO2R). In a series of animal studies the rate of mechanical ventilation was 0.66, 1, 2, and 4 min-1 at a tidal volume of 3, 10, and 15 ml kg-1. We were able to maintain normal blood gases and normal lung volumes and lung mechanics even at the lowest ventilator rate with tidal volumes of 10 or 15 ml kg-1. Each experiment lasted 7 hours. Our data suggest a possible new dimension in the management of a difficult patient on mechanical pulmonary ventilation. PMID:30341

  13. Hysteresis in the tearing mode locking/unlocking due to resonant magnetic perturbations in EXTRAP T2R

    NASA Astrophysics Data System (ADS)

    Fridström, R.; Frassinetti, L.; Brunsell, P. R.

    2015-10-01

    The physical mechanisms behind the hysteresis in the tearing mode locking and unlocking to a resonant magnetic perturbation (RMP) are experimentally studied in EXTRAP T2R reversed-field pinch. The experiments show that the electromagnetic and the viscous torque increase with increasing perturbation amplitude until the mode locks to the wall. At the wall-locking, the plasma velocity reduction profile is peaked at the radius where the RMP is resonant. Thereafter, the viscous torque drops due to the relaxation of the velocity in the central plasma. This is the main reason for the hysteresis in the RMP locking and unlocking amplitude. The increased amplitude of the locked tearing mode produces further deepening of the hysteresis. Both experimental results are in qualitative agreement with the model in Fitzpatrick et al (2001 Phys. Plasmas 8 4489)

  14. Magnetization and transport properties of single RPd2P2 (R=Y, La-Nd, Sm-Ho, Yb)

    NASA Astrophysics Data System (ADS)

    Drachuck, Gil; Boehmer, Anna; Bud'Ko, Sergey L.; Canfield, Paul

    Single crystals of RPd2P2 (R=Y, La-Nd, Sm-Ho, Yb) were grown using a self-flux method and were characterized by room-temperature powder X-ray diffraction, anisotropic temperature and field dependent magnetization and temperature dependent in-plane resistivity. Anisotropic magnetic properties, arising mostly from crystal electric field (CEF) effects, were observed for most magnetic rare earths. The experimentally estimated CEF parameters B02 were calculated from the anisotropic paramagnetic θab and θcvalues. Ordering temperatures, as well as the polycrystalline averaged paramagnetic Curie-Weiss temperature, θave, were extracted from magnetization and resistivity measurements. Work done at Ames Laboratory was supported by US Department of Energy, Basic Energy Sciences, Division of Materials Sciences and Engineering under Contract No. DE-AC02-07CH111358.

  15. Features of structural organization and expression regulation of malate dehydrogenase isoforms from Rhodobacter sphaeroides strain 2R.

    PubMed

    Eprintsev, A T; Klimova, M A; Shikhalieva, K D; Fedorin, D N; Dzhaber, M T; Kompantseva, E I

    2009-07-01

    Two isoforms of malate dehydrogenase (MDH), dimeric and tetrameric, have been found in the purple non-sulfur bacterium Rhodobacter sphaeroides strain 2R, devoid of the glyoxylate shunt, which assimilate acetate via the citramalate cycle. Inhibitory analysis showed that the 74-kDa protein is involved in tricarboxylic acid cycle, while the 148-kDa MDH takes part in the citramalate pathway. A single gene encoding synthesis of the isologous subunits of the MDH isoforms was found during molecular-biological investigations. The appearance in the studied bacterium of the tetrameric MDH isoform during growth in the presence of acetate is probably due to the increased level of mdh gene expression, revealed by the real-time PCR, the product of which in cooperation with the citramalate cycle enzymes plays an important role in acetate assimilation. PMID:19747101

  16. EBP2R - an innovative enhanced biological nutrient recovery activated sludge system to produce growth medium for green microalgae cultivation.

    PubMed

    Valverde-Pérez, Borja; Ramin, Elham; Smets, Barth F; Plósz, Benedek Gy

    2015-01-01

    Current research considers wastewater as a source of energy, nutrients and water and not just a source of pollution. So far, mainly energy intensive physical and chemical unit processes have been developed to recover some of these resources, and less energy and resource demanding alternatives are needed. Here, we present a modified enhanced biological phosphorus removal and recovery system (referred to as EBP2R) that can produce optimal culture media for downstream micro-algal growth in terms of N and P content. Phosphorus is recovered as a P-stream by diversion of some of the effluent from the upstream anaerobic reactor. By operating the process at comparably low solids retention times (SRT), the nitrogen content of wastewater is retained as free and saline ammonia, the preferred form of nitrogen for most micro-algae. Scenario simulations were carried out to assess the capacity of the EBP2R system to produce nutrient rich organic-carbon depleted algal cultivation media of target composition. Via SRT control, the quality of the constructed cultivation media can be optimized to support a wide range of green micro-algal growth requirements. Up to 75% of the influent phosphorus can be recovered, by diverting 30% of the influent flow as a P-stream at an SRT of 5 days. Through global sensitivity analysis we find that the effluent N-to-P ratio and the P recovered are mainly dependent on the influent quality rather than on biokinetics or stoichiometry. Further research is needed to demonstrate that the system performance predicted through the model-based design can be achieved in reality. PMID:25480432

  17. Inhibition of CD25 (IL-2R alpha) expression and T-cell proliferation by polyclonal anti-thymocyte globulins.

    PubMed Central

    Bonnefoy-Berard, N; Verrier, B; Vincent, C; Revillard, J P

    1992-01-01

    Anti-lymphocyte and anti-thymocyte globulins (ATG) are currently used as immunosuppressive agents in organ transplantation. Their administration in vivo may induce not only lymphocyte depletion but also functional effects which were investigated in the present study. In vitro ATG inhibited T-cell proliferation induced by monocyte-dependent T-cell mitogens, like CD3 antibodies, phytohaemagglutinin (PHA) and concanavalin A (Con A), by monocyte-independent mitogens, like CD2 antibodies, or by protein kinase C activators (phorbol esters) associated with a calcium ionophore. The inhibitory effect of ATG was therefore not solely accounted for by a suppression of co-stimulatory signals delivered by monocytes, but rather implied a direct action on T cells. Addition of recombinant human interleukin-2 (rIL-2) did not overcome the inhibition. Suppression of T-cell proliferation by ATG was characterized by normal RNA synthesis and IL-2 secretion contrasting with markedly reduced expression of the CD25 protein [p55, the alpha-chain of interleukin-2 receptor (IL-2R)] both in cytoplasm and on T-cell membrane, as well as a decreased secretion of interferon-gamma (IFN-gamma). Northern blot analysis revealed increased levels of CD25 and IFN-gamma mRNA, suggesting a post-transcriptional inhibition of these molecules, whereas IL-2 mRNA levels were unchanged. These data demonstrate that inhibition of T-cell proliferation by ATG can be attributed primarily to a post-transcriptional defect of CD25 expression, implying a novel mechanism different from those described with other immunosuppressive agents. Blocking of T-cell proliferation in the late G1 phase of the cell cycle may contribute to the immunosuppressive activity of ATG in prophylactic treatment of allograft rejection. Images Figure 2 PMID:1398765

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

    PubMed Central

    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 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. PMID:20302676

  19. An R2R3-MYB Transcription Factor Regulates Eugenol Production in Ripe Strawberry Fruit Receptacles1

    PubMed Central

    Medina-Puche, Laura; Molina-Hidalgo, Francisco Javier; Boersma, Maaike; Schuurink, Robert C.; López-Vidriero, Irene; Solano, Roberto; Franco-Zorrilla, José-Manuel; Caballero, José Luis; Blanco-Portales, Rosario; Muñoz-Blanco, Juan

    2015-01-01

    Eugenol is a volatile phenylpropanoid that contributes to flower and ripe fruit scent. In ripe strawberry (Fragaria × ananassa) fruit receptacles, eugenol is biosynthesized by eugenol synthase (FaEGS2). However, the transcriptional regulation of this process is still unknown. We have identified and functionally characterized an R2R3 MYB transcription factor (EMISSION OF BENZENOID II [FaEOBII]) that seems to be the orthologous gene of PhEOBII from Petunia hybrida, which contributes to the regulation of eugenol biosynthesis in petals. The expression of FaEOBII was ripening related and fruit receptacle specific, although high expression values were also found in petals. This expression pattern of FaEOBII correlated with eugenol content in both fruit receptacle and petals. The expression of FaEOBII was repressed by auxins and activated by abscisic acid, in parallel to the ripening process. In ripe strawberry receptacles, where the expression of FaEOBII was silenced, the expression of CINNAMYL ALCOHOL DEHYDROGENASE1 and FaEGS2, two structural genes involved in eugenol production, was down-regulated. A subsequent decrease in eugenol content in ripe receptacles was also observed, confirming the involvement of FaEOBII in eugenol metabolism. Additionally, the expression of FaEOBII was under the control of FaMYB10, another R2R3 MYB transcription factor that regulates the early and late biosynthetic genes from the flavonoid/phenylpropanoid pathway. In parallel, the amount of eugenol in FaMYB10-silenced receptacles was also diminished. Taken together, these data indicate that FaEOBII plays a regulating role in the volatile phenylpropanoid pathway gene expression that gives rise to eugenol production in ripe strawberry receptacles. PMID:25931522

  20. A novel near-infrared fluorescence imaging probe that preferentially binds to cannabinoid receptors CB2R over CB1R

    PubMed Central

    Ling, Xiaoxi; Zhang, Shaojuan; Shao, Pin; Li, Weixia; Yang, Ling; Ding, Ying; Xu, Cong; Stella, Nephi; Bai, Mingfeng

    2015-01-01

    The type 2 cannabinoid receptors (CB2R) have gained much attention recently due to their important regulatory role in a host of pathophysiological processes. However, the exact biological function of CB2R and how this function might change depending on disease progression remains unclear and could be better studied with highly sensitive and selective imaging tools for identifying the receptors. Here we report the first near infrared fluorescence imaging probe (NIR760-XLP6) that binds preferentially to CB2R over the type 1 cannabinoid receptors (CB1R). The selectivity of the probe was demonstrated by fluorescence microscopy using DBT-CB2 and DBT-CB1 cells. Furthermore, in mouse tumor models, NIR760-XLP6 showed significantly higher uptake in DBT-CB2 than that in DBT-CB1 tumors. These findings indicate that NIR760-XLP6 is a promising imaging tool for the study of CB2R regulation. PMID:25916505

  1. Study of photo catalytic degradation of an industrial dye Ujala Supreme and Methyl Orange using SnO2-rGO composites

    NASA Astrophysics Data System (ADS)

    Rambabu, P.; Srivastava, S. K.; Turpu, G. R.

    2016-05-01

    The photo degradation nature of Methyl Orange and Ujala Supreme dyes are studied using SnO2-rGO composites. Initially, the Graphene Oxide (GO) is prepared by modified Hummers method. Then SnO2-rGO composite is prepared solgel method by taking SnCl2 and GO as precursor materials. The obtained powders are annealed in N2 ambient for two hours in a quartz tube. The structure of the obtained powder composites shows high crystallinity from XRD measurements. The Raman studies also show the D and G bands for the GO. The degradation behaviour is studied for different times with the help of UV-Vis spectrometer. The absorbance graphs reveal that the Ujala Supreme dye is degraded much faster in presence of SnO2-rGO where as Methyl Orange has shown almost no effect on degradation in presence of SnO2-rGO composite.

  2. Increased Ca2+ sensitivity of the ryanodine receptor mutant RyR2R4496C underlies catecholaminergic polymorphic ventricular tachycardia.

    PubMed

    Fernández-Velasco, María; Rueda, Angélica; Rizzi, Nicoletta; Benitah, Jean-Pierre; Colombi, Barbara; Napolitano, Carlo; Priori, Silvia G; Richard, Sylvain; Gómez, Ana María

    2009-01-30

    Cardiac ryanodine receptor (RyR2) mutations are associated with autosomal dominant catecholaminergic polymorphic ventricular tachycardia, suggesting that alterations in Ca(2+) handling underlie this disease. Here we analyze the underlying Ca(2+) release defect that leads to arrhythmia in cardiomyocytes isolated from heterozygous knock-in mice carrying the RyR2(R4496C) mutation. RyR2(R4496C-/-) littermates (wild type) were used as controls. [Ca(2+)](i) transients were obtained by field stimulation in fluo-3-loaded cardiomyocytes and viewed using confocal microscopy. In our basal recording conditions (2-Hz stimulation rate), [Ca(2+)](i) transients and sarcoplasmic reticulum Ca(2+) load were similar in wild-type and RyR2(R4496C) cells. However, paced RyR2(R4496C) ventricular myocytes presented abnormal Ca(2+) release during the diastolic period, viewed as Ca(2+) waves, consistent with the occurrence of delayed afterdepolarizations. The occurrence of this abnormal Ca(2+) release was enhanced at faster stimulation rates and by beta-adrenergic stimulation, which also induced triggered activity. Spontaneous Ca(2+) sparks were more frequent in RyR2(R4496C) myocytes, indicating increased RyR2(R4496C) activity. When permeabilized cells were exposed to different cytosolic [Ca(2+)](i), RyR2(R4496C) showed a dramatic increase in Ca(2+) sensitivity. Isoproterenol increased [Ca(2+)](i) transient amplitude and Ca(2+) spark frequency to the same extent in wild-type and RyR2(R4496C) cells, indicating that the beta-adrenergic sensitivity of RyR2(R4496C) cells remained unaltered. This effect was independent of protein expression variations because no difference was found in the total or phosphorylated RyR2 expression levels. In conclusion, the arrhythmogenic potential of the RyR2(R4496C) mutation is attributable to the increased Ca(2+) sensitivity of RyR2(R4496C), which induces diastolic Ca(2+) release and lowers the threshold for triggered activity. PMID:19096022

  3. Differential Ubiquitin Binding by the Acidic Loops of Ube2g1 and Ube2r1 Enzymes Distinguishes Their Lys-48-ubiquitylation Activities*

    PubMed Central

    Choi, Yun-Seok; Lee, Yun-Ju; Lee, Seo-Yeon; Shi, Lei; Ha, Jung-Hye; Cheong, Hae-Kap; Cheong, Chaejoon; Cohen, Robert E.; Ryu, Kyoung-Seok

    2015-01-01

    The ubiquitin E2 enzymes, Ube2g1 and Ube2r1, are able to synthesize Lys-48-linked polyubiquitins without an E3 ligase but how that is accomplished has been unclear. Although both E2s contain essential acidic loops, only Ube2r1 requires an additional C-terminal extension (184–196) for efficient Lys-48-ubiquitylation activity. The presence of Tyr-102 and Tyr-104 in the Ube2g1 acidic loop enhanced both ubiquitin binding and Lys-48-ubiquitylation and distinguished Ube2g1 from the otherwise similar truncated Ube2r11–183 (Ube2r1C). Replacement of Gln-105–Ser-106–Gly-107 in the acidic loop of Ube2r1C (Ube2r1CYGY) by the corresponding residues from Ube2g1 (Tyr-102–Gly-103–Tyr-104) increased Lys-48-ubiquitylation activity and ubiquitin binding. Two E2∼UB thioester mimics (oxyester and disulfide) were prepared to characterize the ubiquitin binding activity of the acidic loop. The oxyester but not the disulfide derivative was found to be a functional equivalent of the E2∼UB thioester. The ubiquitin moiety of the Ube2r1CC93S-[15N]UBK48R oxyester displayed two-state conformational exchange, whereas the Ube2r1CC93S/YGY-[15N]UBK48R oxyester showed predominantly one state. Together with NMR studies that compared UBK48R oxyesters of the wild-type and the acidic loop mutant (Y102G/Y104G) forms of Ube2g1, in vitro ubiquitylation assays with various mutation forms of the E2s revealed how the intramolecular interaction between the acidic loop and the attached donor ubiquitin regulates Lys-48-ubiquitylation activity. PMID:25471371

  4. Activation of type 2 cannabinoid receptors (CB2R) promotes fatty acid oxidation through the SIRT1/PGC-1α pathway

    SciTech Connect

    Zheng, Xuqin; Sun, Tao; Wang, Xiaodong

    2013-07-05

    Highlights: •TC, a CB2R specific agonist, stimulates SIRT1 activity by PKA/CREB pathway. •TC promotes PGC-1α transcriptional activity by increasing its deacetylation. •TC increases the expression of genes linked to FAO and promotes the rate of FAO. •The effects of TC in FAO are dependent on CB2R. •Suggesting CB2R as a target to treat diseases with lipid dysregulation. -- Abstract: Abnormal fatty acid oxidation has been associated with obesity and type 2 diabetes. At the transcriptional level, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) has been reported to strongly increase the ability of hormone nuclear receptors PPARα and ERRα to drive transcription of fatty acid oxidation enzymes. In this study, we report that a specific agonist of the type 2 cannabinoid receptor (CB2R) can lead to fatty acid oxidation through the PGC-1α pathway. We have found that CB2R is expressed in differentiated C2C12 myotubes, and that use of the specific agonist trans-caryophyllene (TC) stimulates sirtuin 1 (SIRT1) deacetylase activity by increasing the phosphorylation of cAMP response element-binding protein (CREB), thus leading to increased levels of PGC-1α deacetylation. This use of TC treatment increases the expression of genes linked to the fatty acid oxidation pathway in a SIRT1/PGC-1α-dependent mechanism and also drastically accelerates the rate of complete fatty acid oxidation in C2C12 myotubes, neither of which occur when CB2R mRNA is knocked down using siRNA. These results reveal that activation of CB2R by a selective agonist promotes lipid oxidation through a signaling/transcriptional pathway. Our findings imply that pharmacological manipulation of CB2R may provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation.

  5. c-kit+AT2R+ Bone Marrow Mononuclear Cell Subset Is a Superior Subset for Cardiac Protection after Myocardial Infarction

    PubMed Central

    Du, Mingjun; Zhang, Wentian; Wang, Chenxi; Lian, Feng; Xue, Song

    2016-01-01

    Although the bone marrow mononuclear cell (BMMNC) is known as an ideal cell type for cell-based therapy for MI treatment, the effective subpopulation still remains unknown. Our study aimed at identifying the optimal subset of BMMNCs suited for cardiac regeneration. In this study, we observed that MI led to (i) a significant increase of the c-kit+AT2R+ BMMNC subpopulation in mice and (ii) a modest increase of AT2R+ BMMNCs in humans. c-kit+AT2R+ and c-kit+AT2R− BMMNC subpopulations were obtained from mice after MI. Then, we cocultured cardiac H9C2 cells with c-kit+AT2R+, c-kit+AT2R−, and unfractionated BMMNCs; finally, we found that the c-kit+AT2R+ subset is superior to the c-kit+AT2R− subset in improving cardiomyocyte protection in vitro. Of note, c-kit+AT2R+ BMMNCs showed a more robust migration capacity than c-kit+AT2R− and unfractionated BMMNCs in vitro and in vivo. Additionally, compared to c-kit+AT2R− and unfractionated BMMNCs, intravenous transplantation of c-kit+AT2R+ BMMNC resulted in smaller infarct size and lower levels of inflammatory reactions in heart tissue, leading to a higher global heart function improvement. In conclusion, our results indicate that the c-kit+AT2R+ BMMNC subpopulation exerts a protective effect against MI and shows promising therapeutic possibilities with regard to the treatment of ischemic heart disease. PMID:27429622

  6. Diagnostic accuracy of PLA2R autoantibodies and glomerular staining for the differentiation of idiopathic and secondary membranous nephropathy: an updated meta-analysis

    PubMed Central

    Dai, Huanzi; Zhang, Huhai; He, Yani

    2015-01-01

    The diagnostic performance of M-type phospholipase A2 receptor (PLA2R) autoantibodies and PLA2R glomerular staining in discriminating between idiopathic membranous nephropathy (iMN) and secondary membranous nephropathy (sMN) has not been fully evaluated. We conducted an updated meta-analysis to investigate the accuracy and clinical value of serological anti-PLA2R test and histological PLA2R staining for differentiation iMN from sMN. A total of 19 studies involving 1160 patients were included in this meta-analysis. The overall sensitivity, specificity, diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) of serum anti-PLA2R were 0.68 (95% CI, 0.61–074), 0.97 (95% CI, 0.85–1.00), 73.75 (95% CI, 12.56–432.96) and 0.82 (95% CI, 0.78–0.85), respectively, with substantial heterogeneity (I2 = 86.42%). Subgroup analyses revealed the study design, publication type, study origin, assay method might account for the heterogeneity. Additionally, the overall sensitivity, specificity, DOR and AUROC of glomerular PLA2R staining were 0.78 (95% CI, 0.72–0.83), 0.91 (95% CI, 0.75–0.97), 34.70 (95% CI, 9.93–121.30) and 0.84 (95% CI, 0.81–0.87), respectively, without heterogeneity (I2 = 0%). Serological anti-PLA2R testing has diagnostic value, but it must be interpreted in context with patient clinical characteristics and histological PLA2R staining in seronegative patients is recommended. PMID:25740009

  7. Expression and Functional Activity of the Human Bitter Taste Receptor TAS2R38 in Human Placental Tissues and JEG-3 Cells.

    PubMed

    Wölfle, Ute; Elsholz, Floriana A; Kersten, Astrid; Haarhaus, Birgit; Schumacher, Udo; Schempp, Christoph M

    2016-01-01

    Bitter taste receptors (TAS2Rs) are expressed in mucous epithelial cells of the tongue but also outside the gustatory system in epithelial cells of the colon, stomach and bladder, in the upper respiratory tract, in the cornified squamous epithelium of the skin as well as in airway smooth muscle cells, in the testis and in the brain. In the present work we addressed the question if bitter taste receptors might also be expressed in other epithelial tissues as well. By staining a tissue microarray with 45 tissue spots from healthy human donors with an antibody directed against the best characterized bitter taste receptor TAS2R38, we observed an unexpected strong TAS2R38 expression in the amniotic epithelium, syncytiotrophoblast and decidua cells of the human placenta. To analyze the functionality we first determined the TAS2R38 expression in the placental cell line JEG-3. Stimulation of these cells with diphenidol, a clinically used antiemetic agent that binds TAS2Rs including TAS2R38, demonstrated the functionality of the TAS2Rs by inducing calcium influx. Restriction enzyme based detection of the TAS2R38 gene allele identified JEG-3 cells as PTC (phenylthiocarbamide)-taster cell line. Calcium influx induced by PTC in JEG-3 cells could be inhibited with the recently described TAS2R38 inhibitor probenecid and proved the specificity of the TAS2R38 activation. The expression of TAS2R38 in human placental tissues points to further new functions and hitherto unknown endogenous ligands of TAS2Rs far beyond bitter tasting. PMID:26950109

  8. Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mPFC of Adult Rats.

    PubMed

    Castillo-Gómez, Esther; Varea, Emilio; Blasco-Ibáñez, José Miguel; Crespo, Carlos; Nacher, Juan

    2016-01-01

    Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist) after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found. PMID:27110404

  9. Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mPFC of Adult Rats

    PubMed Central

    Castillo-Gómez, Esther; Varea, Emilio; Blasco-Ibáñez, José Miguel; Crespo, Carlos; Nacher, Juan

    2016-01-01

    Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist) after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found. PMID:27110404

  10. Snooker Structure-Based Pharmacophore Model Explains Differences in Agonist and Blocker Binding to Bitter Receptor hTAS2R39

    PubMed Central

    Roland, Wibke S. U.; Sanders, Marijn P. A.; van Buren, Leo; Gouka, Robin J.; Gruppen, Harry; Vincken, Jean-Paul; Ritschel, Tina

    2015-01-01

    The human bitter taste receptor hTAS2R39 can be activated by many dietary (iso)flavonoids. Furthermore, hTAS2R39 activity can be blocked by 6-methoxyflavanones, 4’-fluoro-6-methoxyflavanone in particular. A structure-based pharmacophore model of the hTAS2R39 binding pocket was built using Snooker software, which has been used successfully before for drug design of GPCRs of the rhodopsin subfamily. For the validation of the model, two sets of compounds, both of which contained actives and inactives, were used: (i) an (iso)flavonoid-dedicated set, and (ii) a more generic, structurally diverse set. Agonists were characterized by their linear binding geometry and the fact that they bound deeply in the hTAS2R39 pocket, mapping the hydrogen donor feature based on T5.45 and N3.36, analogues of which have been proposed to play a key role in activation of GPCRs. Blockers lack hydrogen-bond donors enabling contact to the receptor. Furthermore, they had a crooked geometry, which could sterically hinder movement of the TM domains upon receptor activation. Our results reveal characteristics of hTAS2R39 agonist and bitter blocker binding, which might facilitate the development of blockers suitable to counter the bitterness of dietary hTAS2R39 agonists in food applications. PMID:25729848

  11. Snooker structure-based pharmacophore model explains differences in agonist and blocker binding to bitter receptor hTAS2R39.

    PubMed

    Roland, Wibke S U; Sanders, Marijn P A; van Buren, Leo; Gouka, Robin J; Gruppen, Harry; Vincken, Jean-Paul; Ritschel, Tina

    2015-01-01

    The human bitter taste receptor hTAS2R39 can be activated by many dietary (iso)flavonoids. Furthermore, hTAS2R39 activity can be blocked by 6-methoxyflavanones, 4'-fluoro-6-methoxyflavanone in particular. A structure-based pharmacophore model of the hTAS2R39 binding pocket was built using Snooker software, which has been used successfully before for drug design of GPCRs of the rhodopsin subfamily. For the validation of the model, two sets of compounds, both of which contained actives and inactives, were used: (i) an (iso)flavonoid-dedicated set, and (ii) a more generic, structurally diverse set. Agonists were characterized by their linear binding geometry and the fact that they bound deeply in the hTAS2R39 pocket, mapping the hydrogen donor feature based on T5.45 and N3.36, analogues of which have been proposed to play a key role in activation of GPCRs. Blockers lack hydrogen-bond donors enabling contact to the receptor. Furthermore, they had a crooked geometry, which could sterically hinder movement of the TM domains upon receptor activation. Our results reveal characteristics of hTAS2R39 agonist and bitter blocker binding, which might facilitate the development of blockers suitable to counter the bitterness of dietary hTAS2R39 agonists in food applications. PMID:25729848

  12. On the Discovery of Cryptochron C2r.2r-l (ca. 2.42-2.44 Ma) Recorded on Koolau Volcano at Halawa: Evidence from Paleomagnetic and 40Ar/39Ar studies

    NASA Astrophysics Data System (ADS)

    Browne, E. J.; Herrero-Bervera, E.; Singer, B.

    2004-12-01

    indicating that the excursion may correlate with the C2r.2r-l Cryptochron of Cande and Kent [1995]. Pending further 40Ar/39Ar dating underway, this is potentially the first terrestrial record of the ca. 2.4 Ma Cryptochron, a finding that will place important constraints on the evolution of the entire Koolau shield edifice.

  13. 1987 Neutron and gamma personnel dosimeter intercomparison study using a D/sub 2/O-moderated /sup 252/Cf source

    SciTech Connect

    Swaja, R.E.; West, L.E.; Sims, C.S.; Welty, T.J.

    1989-05-01

    The thirteenth Personnel Dosimetry Intercomparison Study (i.e., PDIS 13) was conducted during April 1987 as a joint effort by Oak Ridge National Laboratory's (ORNL) Dosimetry Applications Research Group and the Southwest Radiation Calibration Center at the University of Arkansas. A total of 48 organizations (34 from the US and 14 from abroad) participated in PDIS 13. Participants submitted a total of 1,113 neutron and gamma dosimeters for this mixed field study. The dosimeters were transferred by mail and were handled by experimental personnel at ORNL and the University of Arkansas. The type of neutron dosimeter and the percentage of participants submitting that type are as follows: TLD-albedo (49%), direct interaction TLD (31%), CR-39 (17%), film (3%). The type of gamma dosimeter and the percentage of participants submitting that type are as follows: Li/sub 2/B/sub 4/O/sub 7/, alone or in combination with CaSO/sub 4/, (69%), /sup 7/LiF (28%), natural LiF (3%). Radiation exposures in PDIS 13 were limited to 0.5 and 1.5 mSv from /sup 252/Cf moderated by 15-cm of D/sub 2/O. Traditional exposures using the Health Physics Research Reactor (HPRR) were not possible due to the fact that all reactors at ORNL, including the HPRR, were shutdown by order of the Department of Energy at the time the intercomparison was performed. Planned exposures using a /sup 238/PuBe source were negated by a faulty timing mechanism. Based on accuracy and precision, direct interaction TLD dosimeters exhibited the best performance in PDIS 13 neutron measurements. They were followed, in order of best performance, by CR-39, TLD albedo, and film. The Li/sub 2/B/sub 4/O/sub 7/ type TLD dosimeters exhibited the best performance in PDIS 13 gamma measurements. They were followed by natural LiF, /sup 7/LiF, and film. 12 refs., 1 fig., 5 tabs.

  14. Co-Dopant Influence on the Persistent Luminescence of BaAl2O4:Eu2+,R3+

    NASA Astrophysics Data System (ADS)

    Rodrigues, Lucas C. V.; Hölsä, Jorma; Carvalho, José M.; Pedroso, Cássio C. S.; Lastusaari, Mika; Felinto, Maria C. F. C.; Watanabe, Shigeo; Brito, Hermi F.

    2014-04-01

    The R3+ (rare earth) co-dopants may have a surprisingly important role in persistent luminescence - enhancement of up to 1-3 orders of magnitude may be obtained in the performance of these phosphor materials - depending strongly on the R3+ ion, of course. In this work, the effects of the R3+ co-dopants in the BaAl2O4:Eu2+,R3+ materials were studied using mainly thermoluminescence (TL) and synchrotron radiation XANES methods. In BaAl2O4, the conventional and persistent luminescence both arise from the 4f7→4f65d1 transition of Eu2+, yielding blue-green emission color. The former, in the presence of humidity, turns to more bluish because of creation of an additional Eu2+ luminescence centre which is not, however, visible in persistent luminescence. The trap structure in the non-co-doped BaAl2O4:Eu2+ is rather complex with 4-5 TL bands above room temperature. With R3+ co-doping, this basic structure is modified though no drastic change can be observed. This underlines the fact that even very small changes in the trap depths can produce significant modifications in the persistent luminescence efficiency. It should be remembered that basically the persistent luminescence performance is controlled by the Boltzmann population law depending exponentially on both the temperature and trap depth. Some mechanisms for persistent luminescence have suggested the presence of either divalent R2+ or tetravalent RIV during the charging of the Eu2+ doped materials. The present XANES measurements on BaAl2O4:Eu2+,R3+ confirmed the presence of only the trivalent form of the R3+ co-dopants excluding both of these pathways. It must thus be concluded, that the energy is stored in intrinsic and extrinsic defects created by the synthesis conditions and charge compensation due to R3+ co-doping. Even though the effect of the R3+ co-dopants was carefully exploited and characterized, the differences in the effect of different R3+ ions with very similar chemical and spectroscopic properties could

  15. Rolling Deck to Repository (R2R): Next Steps in Ocean Exploration for Data Dissemination and Discovery

    NASA Astrophysics Data System (ADS)

    Miller, S. P.; Carbotte, S. M.; Stocks, K.; Ferrini, V.; Arko, R. A.; Chandler, C. L.; Maffei, A. R.; Smith, S. R.; Bourassa, M. A.; Clark, P. D.; Sweeney, A. D.; O'Hara, S. H.; Morton, J. J.

    2010-12-01

    A new era of ocean exploration brings with it a challenge to take the next step, making the discoveries available to a wider audience. Mapmakers, artists and collectors were on board the voyages of discovery of the eighteenth century, and the resulting atlases and exhibits captured the public’s imagination, laid the foundation for scientific inquiries and medical advances, and helped to fund future expeditions. While we can now rapidly disseminate data, gaps exist in the flow of data from research vessels. Many shipboard data practices are still oriented toward the era of single-investigator research in which data are brought back to the lab for individual publications. Data may be on proprietary hold for years, or worse, lost. Observatory systems and new platforms are bringing in a flood of new data, and it will be a challenge to make sense of data streams in time and space and across disciplines, organizations and nations. To encourage discussion of data management paradigms, we present initial lessons learned from the Rolling Deck to Repository (R2R) program as it begins to routinely migrate US University-National Oceanographic Laboratory System (UNOLS) and other academic shipboard data to national data centers. The UNOLS fleet consists of 21 vessels operated by 15 independent organizations, with up to 26 routine underway device types collecting data on more than 300 cruises a year. Semi-automated procedures are becoming operational to deliver shipboard data to NOAA’s National Geophysical Data Center and National Oceanographic Data Center for public distribution. Full implementation relies on establishing metadata standards based on community approved controlled vocabularies, and creating high quality standard navigational products across the fleet. The approaches, technology and procedures are intended to be coordinated with initiatives across NSF and NOAA, and with European programs such as SeaDataNet, Eurofleets and GeoSeas. Exploration is driven by

  16. Infrared spectra and tunneling dynamics of the N{sub 2}–D{sub 2}O and OC–D{sub 2}O complexes in the v{sub 2} bend region of D{sub 2}O

    SciTech Connect

    Zhu, Yu; Zheng, Rui; Li, Song; Yang, Yu; Duan, Chuanxi

    2013-12-07

    The rovibrational spectra of the N{sub 2}–D{sub 2}O and OC–D{sub 2}O complexes in the v{sub 2} bend region of D{sub 2}O have been measured in a supersonic slit jet expansion using a rapid-scan tunable diode laser spectrometer. Both a-type and b-type transitions were observed for these two complexes. All transitions are doubled, due to the heavy water tunneling within the complexes. Assuming the tunneling splittings are the same in K{sub a} = 0 and K{sub a} = 1, the band origins, all three rotational and several distortion constants of each tunneling state were determined for N{sub 2}–D{sub 2}O in the ground and excited vibrational states, and for OC–D{sub 2}O in the excited vibrational state, respectively. The averaged band origin of OC–D{sub 2}O is blueshifted by 2.241 cm{sup −1} from that of the v{sub 2} band of the D{sub 2}O monomer, compared with 1.247 cm{sup −1} for N{sub 2}–D{sub 2}O. The tunneling splitting of N{sub 2}–D{sub 2}O in the ground state is 0.16359(28) cm{sup −1}, which is about five times that of OC–D{sub 2}O. The tunneling splittings decrease by about 26% for N{sub 2}–D{sub 2}O and 23% for OC–D{sub 2}O, respectively, upon excitation of the D{sub 2}O bending vibration, indicating an increase of the tunneling barrier in the excited vibrational state. The tunneling splittings are found to have a strong dependence on intramolecular vibrational excitation as well as a weak dependence on quantum number K{sub a}.

  17. Genome-Wide Analysis of Citrus R2R3MYB Genes and Their Spatiotemporal Expression under Stresses and Hormone Treatments

    PubMed Central

    He, Shaolan; Zheng, Yongqiang; Yi, Shilai; Lv, Qiang; Deng, Lie

    2014-01-01

    The R2R3MYB proteins represent one of the largest families of transcription factors, which play important roles in plant growth and development. Although genome-wide analysis of this family has been conducted in many species, little is known about R2R3MYB genes in citrus, In this study, 101 R2R3MYB genes has been identified in the citrus (Citrus sinesis and Citrus clementina) genomes, which are almost equal to the number of rice. Phylogenetic analysis revealed that they could be subdivided into 21 subgroups. The evolutionary relationships and the intro-exon organizations were also analyzed, revealing strong gene conservation but also the expansions of particular functional genes during the plant evolution. Tissue-specific expression profiles showed that 95 citrus R2R3MYB genes were expressed in at least one tissue and the other 6 genes showed very low expression in all tissues tested, suggesting that citrus R2R3MYB genes play important roles in the development of all citrus organs. The transcript abundance level analysis during abiotic conditions (NaCl, abscisic acid, jasmonic acid, drought and low temperature) identified a group of R2R3MYB genes that responded to one or multiple treatments, which showed a promising for improving citrus adaptation to stresses. Our results provided an essential foundation for the future selection of the citrus R2R3MYB genes for cloning and functional dissection with an aim of uncovering their roles in citrus growth and development. PMID:25473954

  18. Genome-wide analysis of citrus R2R3MYB genes and their spatiotemporal expression under stresses and hormone treatments.

    PubMed

    Xie, Rangjin; Li, Yongjie; He, Shaolan; Zheng, Yongqiang; Yi, Shilai; Lv, Qiang; Deng, Lie

    2014-01-01

    The R2R3MYB proteins represent one of the largest families of transcription factors, which play important roles in plant growth and development. Although genome-wide analysis of this family has been conducted in many species, little is known about R2R3MYB genes in citrus, In this study, 101 R2R3MYB genes has been identified in the citrus (Citrus sinesis and Citrus clementina) genomes, which are almost equal to the number of rice. Phylogenetic analysis revealed that they could be subdivided into 21 subgroups. The evolutionary relationships and the intro-exon organizations were also analyzed, revealing strong gene conservation but also the expansions of particular functional genes during the plant evolution. Tissue-specific expression profiles showed that 95 citrus R2R3MYB genes were expressed in at least one tissue and the other 6 genes showed very low expression in all tissues tested, suggesting that citrus R2R3MYB genes play important roles in the development of all citrus organs. The transcript abundance level analysis during abiotic conditions (NaCl, abscisic acid, jasmonic acid, drought and low temperature) identified a group of R2R3MYB genes that responded to one or multiple treatments, which showed a promising for improving citrus adaptation to stresses. Our results provided an essential foundation for the future selection of the citrus R2R3MYB genes for cloning and functional dissection with an aim of uncovering their roles in citrus growth and development. PMID:25473954

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

    SciTech Connect

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

    1988-08-01

    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.

  20. Characterization of a Citrus R2R3-MYB Transcription Factor that Regulates the Flavonol and Hydroxycinnamic Acid Biosynthesis.

    PubMed

    Liu, Chaoyang; Long, Jianmei; Zhu, Kaijie; Liu, Linlin; Yang, Wei; Zhang, Hongyan; Li, Li; Xu, Qiang; Deng, Xiuxin

    2016-01-01

    Flavonols and hydroxycinnamic acids are important phenylpropanoid metabolites in plants. In this study, we isolated and characterized a citrus R2R3-MYB transcription factor CsMYBF1, encoding a protein belonging to the flavonol-specific MYB subgroup. Ectopic expression of CsMYBF1 in tomato led to an up-regulation of a series of genes involved in primary metabolism and the phenylpropanoid pathway, and induced a strong accumulation of hydroxycinnamic acid compounds but not the flavonols. The RNAi suppression of CsMYBF1 in citrus callus caused a down-regulation of many phenylpropanoid pathway genes and reduced the contents of hydroxycinnamic acids and flavonols. Transactivation assays indicated that CsMYBF1 activated several promoters of phenylpropanoid pathway genes in tomato and citrus. Interestingly, CsMYBF1 could activate the CHS gene promoter in citrus, but not in tomato. Further examinations revealed that the MYBPLANT cis-elements were essential for CsMYBF1 in activating phenylpropanoid pathway genes. In summary, our data indicated that CsMYBF1 possessed the function in controlling the flavonol and hydroxycinnamic acid biosynthesis, and the regulatory differences in the target metabolite accumulation between two species may be due to the differential activation of CHS promoters by CsMYBF1. Therefore, CsMYBF1 constitutes an important gene source for the engineering of specific phenylpropanoid components. PMID:27162196

  1. A new type of low blood flow ECCO2R using a hemodialysis system in apneic states.

    PubMed

    Isobe, J; Mizuno, H; Matsunobe, S; Shimizu, Y; Ikada, Y; Kishida, A

    1989-01-01

    To perform low blood flow extracorporeal CO2 removal (ECCO2R), the authors developed a device for extracorporeal circulation (ECC) equipped with a dialyzer for the elimination of CO2 as bicarbonate. The major problem with this method was the decrease in blood pH. To control blood pH and clarify the limit of CO2 elimination using this method, a study with apneic dogs was performed. Six anesthetized mongrel dogs were intubated and paralyzed with a muscle relaxant. Vascular access was achieved with a venovenous bypass. ECC was initiated under apneic oxygenation (100% O2, 10 cm H2O continuous airway pressure), and the CO2 concentration in the airway outlet was measured. The CO2 was converted to bicarbonate using systemic infusion of trihydroxy-methylamino methane (THAM), and the generated bicarbonate was removed by hemodialysis. Blood flow rate in the ECC was 15 ml/kg/min, and the duration of ECC was 5 hr. During ECC, the hemodynamic parameters of the dogs were stable, and the PaCO2 remained at about 90 mmHg with a PaO2 above 350 mmHg; CO2 elimination from the airway was negligible. PMID:2512974

  2. The soybean R2R3 MYB transcription factor GmMYB100 negatively regulates plant flavonoid biosynthesis.

    PubMed

    Yan, Junhui; Wang, Biao; Zhong, Yunpeng; Yao, Luming; Cheng, Linjing; Wu, Tianlong

    2015-09-01

    Soybean flavonoids, a group of important signaling molecules in plant-environment interaction, ubiquitously exist in soybean and are tightly regulated by many genes. Here we reported that GmMYB100, a gene encoding a R2R3 MYB transcription factor, is involved in soybean flavonoid biosynthesis. GmMYB100 is mainly expressed in flowers, leaves and immature embryo, and its level is decreased after pod ripening. Subcellular localization assay indicates that GmMYB100 is a nuclear protein. GmMYB100 has transactivation ability revealed by a yeast functional assay; whereas bioinformatic analysis suggests that GmMYB100 has a negative function in flavonoid biosynthesis. GmMYB100-overexpression represses the transcript levels of flavonoid-related genes in transgenic soybean hairy roots and Arabidopsis, and inhibits isoflavonoid (soybean) and flavonol (Arabidopsis) production in transgenic plants. Furthermore, the transcript levels of six flavonoid-related genes and flavonoid (isoflavonoid and flavone aglycones) accumulation are elevated in the GmMYB100-RNAi transgenic hairy roots. We also demonstrate that GmMYB100 protein depresses the promoter activities of soybean chalcone synthase and chalcone isomerase. These findings indicate that GmMYB100 is a negative regulator in soybean flavonoid biosynthesis pathway. PMID:26231207

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

    PubMed

    Kasajima, Ichiro; Sasaki, Katsutomo

    2016-05-01

    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. PMID:27089475

  4. Kepler Observations of Rapid Optical Variability in the BL Lac Object W2r192+42

    NASA Technical Reports Server (NTRS)

    R.Edelson; Mushotzky, R.; Vaughn, S.; Scargle, J.; Gandhi, P.; Malkan, M.; Baumgartner, W.

    2013-01-01

    We present the first Kepler monitoring of a strongly variable BL Lac, W2R1926+42. The light curve covers 181 days with approx. 0.2% errors, 30 minute sampling and >90% duty cycle, showing numerous delta-I/I > 25% flares over timescales as short as a day. The flux distribution is highly skewed and non-Gaussian. The variability shows a strong rms-flux correlation with the clearest evidence to date for non-linearity in this relation. We introduce a method to measure periodograms from the discrete autocorrelation function, an approach that may be well-suited to a wide range of Kepler data. The periodogram is not consistent with a simple power-law, but shows a flattening at frequencies below 7x10(exp -5) Hz. Simple models of the power spectrum, such as a broken power law, do not produce acceptable fits, indicating that the Kepler blazar light curve requires more sophisticated mathematical and physical descriptions than currently in use.

  5. KEPLER OBSERVATIONS OF RAPID OPTICAL VARIABILITY IN THE BL LACERTAE OBJECT W2R1926+42

    SciTech Connect

    Edelson, R.; Mushotzky, R.; Vaughan, S.; Scargle, J.; Gandhi, P.; Malkan, M.; Baumgartner, W.

    2013-03-20

    We present the first Kepler monitoring of a strongly variable BL Lac, W2R1926+42. The light curve covers 181 days with {approx}0.2% errors, 30 minute sampling and >90% duty cycle, showing numerous {delta}I/I > 25% flares over timescales as short as a day. The flux distribution is highly skewed and non-Gaussian. The variability shows a strong rms-flux correlation with the clearest evidence to date for nonlinearity in this relation. We introduce a method to measure periodograms from the discrete autocorrelation function, an approach that may be well-suited to a wide range of Kepler data. The periodogram is not consistent with a simple power-law, but shows a flattening at frequencies below 7 Multiplication-Sign 10{sup -5} Hz. Simple models of the power spectrum, such as a broken power law, do not produce acceptable fits, indicating that the Kepler blazar light curve requires more sophisticated mathematical and physical descriptions than currently in use.

  6. Secondray structure and sequence of ITS2-rDNA of the Egyptian malaria vector Anopheles pharoensis (Theobald).

    PubMed

    Wassim, Nahla M

    2014-04-01

    Out of the twelve Anophelines present in Egypt, only five species known to be malaria vectors. Anopheles (An.) pharoensis proved to be the important vector all over Egypt, especially in the Delta. Anopheles sergenti proved to be the primary vector in the Oases of the Western Desert, An. multicolor in Faiyoum, An. stephensi in the Red Sea Coast, and An. superpictus in Sinai. Genomic DNA was isolated from single adult mosquito of An. pharoensis (Sahel Sudanese form), PCR was performed to amplify ITS2 region of rDNA using specific primers for 5.8S and 28S rDNA genes. The amplicons were purified, directly sequenced and aligned to the sequence of the same region of An. gambiae, using clustalw2. The length of ITS2-rDNA of An. pharoensis was 411bp. The GC content of the ITS2 reported 53% is consistent with spacer base composition in Anopheles species. The similarity between the two species was 52% and genetic distance was 0.46.Variable simple sequence repeats (SSRs) are found at low frequency. The secondary structure of rDNA-ITS2was predicted by MFOLD and was -192; 60 to-195.32 kilocalories/mole. PMID:24961025

  7. Resistive wall mode feedback control in EXTRAP T2R with improved steady-state error and transient response

    SciTech Connect

    Brunsell, P. R.; Olofsson, K. E. J.; Frassinetti, L.; Drake, J. R.

    2007-10-15

    Experiments in the EXTRAP T2R reversed field pinch [P. R. Brunsell, H. Bergsa ring ker, M. Cecconello et al., Plasma Phys. Control. Fusion 43, 1457 (2001)] on feedback control of m=1 resistive wall modes (RWMs) are compared with simulations using the cylindrical linear magnetohydrodynamic model, including the dynamics of the active coils and power amplifiers. Stabilization of the main RWMs (n=-11,-10,-9,-8,+5,+6) is shown using modest loop gains of the order G{approx}1. However, other marginally unstable RWMs (n=-2,-1,+1,+2) driven by external field errors are only partially canceled at these gains. The experimental system stability limit is confirmed by simulations showing that the latency of the digital controller {approx}50 {mu}s is degrading the system gain margin. The transient response is improved with a proportional-plus-derivative controller, and steady-state error is improved with a proportional-plus-integral controller. Suppression of all modes is obtained at high gain G{approx}10 using a proportional-plus-integral-plus-derivative controller.

  8. MULTIPASS, a rice R2R3-type MYB transcription factor, regulates adaptive growth by integrating multiple hormonal pathways.

    PubMed

    Schmidt, Romy; Schippers, Jos H M; Mieulet, Delphine; Obata, Toshihiro; Fernie, Alisdair R; Guiderdoni, Emmanuel; Mueller-Roeber, Bernd

    2013-10-01

    Growth regulation is an important aspect of plant adaptation during environmental perturbations. Here, the role of MULTIPASS (OsMPS), an R2R3-type MYB transcription factor of rice, was explored. OsMPS is induced by salt stress and expressed in vegetative and reproductive tissues. Over-expression of OsMPS reduces growth under non-stress conditions, while knockdown plants display increased biomass. OsMPS expression is induced by abscisic acid and cytokinin, but is repressed by auxin, gibberellin and brassinolide. Growth retardation caused by OsMPS over-expression is partially restored by auxin application. Expression profiling revealed that OsMPS negatively regulates the expression of EXPANSIN (EXP) and cell-wall biosynthesis as well as phytohormone signaling genes. Furthermore, the expression of OsMPS-dependent genes is regulated by auxin, cytokinin and abscisic acid. Moreover, we show that OsMPS is a direct upstream regulator of OsEXPA4, OsEXPA8, OsEXPB2, OsEXPB3, OsEXPB6 and the endoglucanase genes OsGLU5 and OsGLU14. The multiple responses of OsMPS and its target genes to various hormones suggest an integrative function of OsMPS in the cross-talk between phytohormones and the environment to regulate adaptive growth. PMID:23855375

  9. Wind-Tunnel Investigation of a 1/5-Scale Model of the Ryan XF2R Airplane

    NASA Technical Reports Server (NTRS)

    Wong, Park Y.

    1947-01-01

    Wind-tunnel tests on a 1/5-scale model of the Ryan XF2R airplane were conducted to determine the aerodynamic characteristics of the air intake for the front power plant, a General Electric TG-100 gas turbine, and to determine the stability and control characteristics of the airplane. The results indicated low-dynamic-pressure recover3- for the air intake to the TG-100 gas turbine rith the standard propeller in operation. Propeller cuffs were designed and tested for the purpose of impoving the dynamic-pressure recovery. Data obtained with the cuffs installed and the gap between the spinner an& the cuff sealed indicated a substantial gain in dynamic pressure recovery over that obtained with the standard propeller and with the cuffed propeller unsealed. Stability and control tests were conducted with the sealed cuffs installed on the propeller. The data from these tests indicated the following unsatisfactory characteristics for the airplane: 1. Marginal static longitudinal stability. 2. Inadequate directional stability and control. 3. Rudder-pedal-force reversal in the climb condition. 4. Negative dihedral effect in the power-on approach and wave-off conditions.

  10. Synthesis of rebaudioside A from stevioside and their interaction model with hTAS2R4 bitter taste receptor.

    PubMed

    Singla, Ramit; Jaitak, Vikas

    2016-05-01

    Steviol glycosides (SG's) from Stevia rebaudiana (Bertoni) have been used as a natural low-calorie sweeteners. Its aftertaste bitterness restricts its use for human consumption and limits its application in food and pharmaceutical products. In present study, we have performed computational analysis in order to investigate the interaction of two major constituents of SG's against homology model of the hTAS2R4 receptor. Molecular simulation study was performed using stevioside and rebaudioside A revealed that, sugar moiety at the C-3'' position in rebaudioside A causes restriction of its entry into the receptor site thereby unable to trigger the bitter reception signaling cascade. Encouraged by the current finding, we have also developed a greener route using β-1,3-glucanase from Irpex lacteus for the synthesis of de-bittered rebaudioside A from stevioside. The rebaudioside A obtained was of high quality with percent conversion of 62.5%. The results here reported could be used for the synthesis of rebaudioside A which have large application in food and pharmaceutical industry. PMID:26976334

  11. Measurements and modeling of transport and impurity radial profiles in the EXTRAP T2R reversed field pinch

    SciTech Connect

    Kuldkepp, M.; Brunsell, P. R.; Cecconello, M.; Dux, R.; Menmuir, S.; Rachlew, E.

    2006-09-15

    Radial impurity profiles of oxygen in the rebuilt reversed field pinch EXTRAP T2R [P. R. Brunsell et al., Plasma Phys. Control. Fusion 43, 1457 (2001)] have been measured with a multichannel spectrometer. Absolute ion densities for oxygen peak between 1-4x10{sup 10} cm{sup -3} for a central electron density of 1x10{sup 13} cm{sup -3}. Transport simulations with the one-dimensional transport code STRAHL with a diffusion coefficient of 20 m{sup 2} s{sup -1} yield density profiles similar to those measured. Direct measurement of the ion profile evolution during pulsed poloidal current drive suggests that the diffusion coefficient is reduced by a factor {approx}2 in the core but remains unaffected toward the edge. Core transport is not significantly affected by the radial magnetic field growth seen at the edge in discharges without feedback control. This indicates that the mode core amplitude remains the same while the mode eigenfunction increases at the edge.

  12. Electronic Structure of (2√2×√2)R45^circO/Cu(001)

    NASA Astrophysics Data System (ADS)

    Stolbov, Sergey; Rahman, Talat

    2002-03-01

    The electronic structure of the (2√2×√2)R45^circ-O/Cu(001) system has been calculated using the locally self-consistent real space multiple scattering technique. The calculations have been performed for several proposed structures. On unreconstructed Cu(001), O atoms are found to produce a strong perturbation in the long-range Madelung potentials, which gets partially screened when the Cu surface undergoes a missing row reconstruction. As a result, the d-subbands of Cu atoms with different local environment have different energetic positions and, hence, different character of hybridization with the electronic states of neighboring atoms. This creates a complex combination of ionic and covalent binding between oxygen and the different Cu neighbors with a charge redistribution in which the electronic charge is delivered to O from two of its four nearest Cu neighbors and also from the next nearest Cu atom located just under the missing rows. We compare the findings here with those for the c(2× 2)O overlayer on Cu(001) and discuss the role of the electronic structure in the formation of these two superstructures.

  13. The R2R3-MYB transcription factors MYB14 and MYB15 regulate stilbene biosynthesis in Vitis vinifera.

    PubMed

    Höll, Janine; Vannozzi, Alessandro; Czemmel, Stefan; D'Onofrio, Claudio; Walker, Amanda R; Rausch, Thomas; Lucchin, Margherita; Boss, Paul K; Dry, Ian B; Bogs, Jochen

    2013-10-01

    Plant stilbenes are phytoalexins that accumulate in a small number of plant species, including grapevine (Vitis vinifera), in response to biotic and abiotic stresses and have been implicated in many beneficial effects on human health. In particular, resveratrol, the basic unit of all other complex stilbenes, has received widespread attention because of its cardio-protective, anticarcinogenic, and antioxidant properties. Although stilbene synthases (STSs), the key enzymes responsible for resveratrol biosynthesis, have been isolated and characterized from several plant species, the transcriptional regulation underlying stilbene biosynthesis is unknown. Here, we report the identification and functional characterization of two R2R3-MYB-type transcription factors (TFs) from grapevine, which regulate the stilbene biosynthetic pathway. These TFs, designated MYB14 and MYB15, strongly coexpress with STS genes, both in leaf tissues under biotic and abiotic stress and in the skin and seed of healthy developing berries during maturation. In transient gene reporter assays, MYB14 and MYB15 were demonstrated to specifically activate the promoters of STS genes, and the ectopic expression of MYB15 in grapevine hairy roots resulted in increased STS expression and in the accumulation of glycosylated stilbenes in planta. These results demonstrate the involvement of MYB14 and MYB15 in the transcriptional regulation of stilbene biosynthesis in grapevine. PMID:24151295

  14. Total date rate of multi-wavelength 2R regenerators for time-interleaved RZ-OOK signals.

    PubMed

    Zhou, Xing-yu; Wu, Bao-jian; Wen, Feng; Zhang, Hong-chao; Zhou, Heng; Qiu, Kun

    2014-09-22

    Multi-wavelength regeneration free of inter-channel crosstalk is desirable for wavelength division multiplexing (WDM) systems, especially from the cost-effectiveness point of view. This paper presents the design rules of time-interleaved multi-wavelength 2R regeneration systems based on data-pump four wave mixing (FWM) effect, and several key factors, such as FWM bandwidth, wavelength assignment, and duty cycle, are comprehensively taken into account. The total data rate of time-interleaved WDM regeneration systems along with polarization multiplexing or bidirectional transmission are discussed, which are mainly determined by temporal overlap, spectral broadening and FWM bandwidth. As two examples, an eight-wavelength unidirectional regenerator using polarization multiplexing is designed by optimizing the fiber birefringence, and a six-wavelength bidirectional regenerator is demonstrated by experiment. Each is expected to have a total data rate of about 200 Gb/s for the optical RZ-OOK signals, and the wavelength number is increased at the expense of spectral efficiency. PMID:25321764

  15. Characterization of a Citrus R2R3-MYB Transcription Factor that Regulates the Flavonol and Hydroxycinnamic Acid Biosynthesis

    PubMed Central

    Liu, Chaoyang; Long, Jianmei; Zhu, Kaijie; Liu, Linlin; Yang, Wei; Zhang, Hongyan; Li, Li; Xu, Qiang; Deng, Xiuxin

    2016-01-01

    Flavonols and hydroxycinnamic acids are important phenylpropanoid metabolites in plants. In this study, we isolated and characterized a citrus R2R3-MYB transcription factor CsMYBF1, encoding a protein belonging to the flavonol-specific MYB subgroup. Ectopic expression of CsMYBF1 in tomato led to an up-regulation of a series of genes involved in primary metabolism and the phenylpropanoid pathway, and induced a strong accumulation of hydroxycinnamic acid compounds but not the flavonols. The RNAi suppression of CsMYBF1 in citrus callus caused a down-regulation of many phenylpropanoid pathway genes and reduced the contents of hydroxycinnamic acids and flavonols. Transactivation assays indicated that CsMYBF1 activated several promoters of phenylpropanoid pathway genes in tomato and citrus. Interestingly, CsMYBF1 could activate the CHS gene promoter in citrus, but not in tomato. Further examinations revealed that the MYBPLANT cis-elements were essential for CsMYBF1 in activating phenylpropanoid pathway genes. In summary, our data indicated that CsMYBF1 possessed the function in controlling the flavonol and hydroxycinnamic acid biosynthesis, and the regulatory differences in the target metabolite accumulation between two species may be due to the differential activation of CHS promoters by CsMYBF1. Therefore, CsMYBF1 constitutes an important gene source for the engineering of specific phenylpropanoid components. PMID:27162196

  16. Doppler-free approach to optical pumping dynamics in the 6S1/2-5D>5/2 electric quadrupole transition of cesium vapor.

    PubMed

    Chan, Eng Aik; Aljunid, Syed Abdullah; Zheludev, Nikolay I; Wilkowski, David; Ducloy, Martial

    2016-05-01

    The 6S1/2-5D>5/2 electric quadrupole transition is investigated in cesium vapor at room temperature via nonlinear Doppler-free 6P-6S-5D three-level spectroscopy. Frequency-resolved studies of individual E2 hyperfine lines allow one to analyze the optical pumping dynamics, polarization selection rules, and line intensities. It opens the way to studies of transfer of light orbital angular momentum to atoms and the influence of metamaterials on E2 line spectra. PMID:27128060

  17. Resonant Auger decay of Xe{sup *} 4d{sub 5/2}{sup -1}6p: A contribution to the complete experiment from fluorescence polarization studies

    SciTech Connect

    O'Keeffe, P.; Aloiese, S.; Meyer, M.; Lohmann, B.; Kleiman, U.; Grum-Grzhimailo, A. N.

    2004-07-01

    Fluorescence polarimetry has been used to determine the relative partial-wave Auger decay widths for transitions to states of the Xe II 5p{sup 4}6p multiplet after photoexcitation of the Xe{sup *} 4d{sub 5/2}{sup -1}6p(J{sup *}=1) resonance by linearly and circularly polarized synchrotron radiation. Combination with data on the angular distribution and spin polarization of the Auger electrons, providing information on the relative phases of the amplitudes, constitutes the complete experiment on the Auger decay. Multiconfiguration relativistic calculations of the amplitudes have been performed and compared to the measurements.

  18. Direct non-Born-Oppenheimer variational calculations of all bound vibrational states corresponding to the first rotational excitation of D{sub 2} performed with explicitly correlated all-particle Gaussian functions

    SciTech Connect

    Sharkey, Keeper L.; Kirnosov, Nikita; Adamowicz, Ludwik

    2015-05-07

    Direct variational calculations where the Born-Oppenheimer approximation is not assumed are done for all rovibrational states of the D{sub 2} molecule corresponding to first excited rotational level (the N = 1 states). All-particle explicitly correlated Gaussian basis functions are used in the calculations. The exponential parameters of the Gaussians are optimized with the aid of analytically calculated energy gradient determined with respect to these parameters. The results allow to determine the ortho-para spin isomerization energies as a function of the vibrational quantum number.

  19. Novel two-step laser ablation and ionization mass spectrometry (2S-LAIMS) of actor-spectator ice layers: Probing chemical composition of D{sub 2}O ice beneath a H{sub 2}O ice layer

    SciTech Connect

    Yang, Rui Gudipati, Murthy S.

    2014-03-14

    In this work, we report for the first time successful analysis of organic aromatic analytes imbedded in D{sub 2}O ices by novel infrared (IR) laser ablation of a layered non-absorbing D{sub 2}O ice (spectator) containing the analytes and an ablation-active IR-absorbing H{sub 2}O ice layer (actor) without the analyte. With these studies we have opened up a new method for the in situ analysis of solids containing analytes when covered with an IR laser-absorbing layer that can be resonantly ablated. This soft ejection method takes advantage of the tenability of two-step infrared laser ablation and ultraviolet laser ionization mass spectrometry, previously demonstrated in this lab to study chemical reactions of polycyclic aromatic hydrocarbons (PAHs) in cryogenic ices. The IR laser pulse tuned to resonantly excite only the upper H{sub 2}O ice layer (actor) generates a shockwave upon impact. This shockwave penetrates the lower analyte-containing D{sub 2}O ice layer (spectator, a non-absorbing ice that cannot be ablated directly with the wavelength of the IR laser employed) and is reflected back, ejecting the contents of the D{sub 2}O layer into the vacuum where they are intersected by a UV laser for ionization and detection by a time-of-flight mass spectrometer. Thus, energy is transmitted from the laser-absorbing actor layer into the non-absorbing spectator layer resulting its ablation. We found that isotope cross-contamination between layers was negligible. We also did not see any evidence for thermal or collisional chemistry of PAH molecules with H{sub 2}O molecules in the shockwave. We call this “shockwave mediated surface resonance enhanced subsurface ablation” technique as “two-step laser ablation and ionization mass spectrometry of actor-spectator ice layers.” This method has its roots in the well-established MALDI (matrix assisted laser desorption and ionization) method. Our method offers more flexibility to optimize both the processes—ablation and

  20. 1,25-(OH){sub 2}-vitamin D{sub 3} prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4{sup −/−} model

    SciTech Connect

    Reiter, Florian P.; Hohenester, Simon; Nagel, Jutta M.; Wimmer, Ralf; Artmann, Renate; Wottke, Lena; Makeschin, Marie-Christine; Mayr, Doris; Rust, Christian; Trauner, Michael; Denk, Gerald U.

    2015-04-03

    Background/Purpose of the study: Vitamin D{sub 3}-deficiency is common in patients with chronic liver-disease and may promote disease progression. Vitamin D{sub 3}-administration has thus been proposed as a therapeutic approach. Vitamin D{sub 3} has immunomodulatory effects and may modulate autoimmune liver-disease such as primary sclerosing cholangitis. Although various mechanisms of action have been proposed, experimental evidence is limited. Here we test the hypothesis that active 1,25-(OH){sub 2}-vitamin D{sub 3} inhibits activation of hepatic stellate cells (HSC) in vitro and modulates liver-injury in vivo. Methods: Proliferation and activation of primary murine HSC were assessed by BrdU- and PicoGreen{sup ®}-assays, immunoblotting, immunofluorescence-microscopy, quantitative-PCR, and zymography following calcitriol-treatment. Wild-type and ATP-binding cassette transporter b4{sup −/−} (Abcb4{sup −/−})-mice received calcitriol for 4 weeks. Liver-damage, inflammation, and fibrosis were assessed by serum liver-tests, Sirius-red staining, quantitative-PCR, immunoblotting, immunohistochemistry and hydroxyproline quantification. Results: In vitro, calcitriol inhibited activation and proliferation of murine HSC as shown by reduced α-smooth muscle actin and platelet-derived growth factor-receptor-β-protein-levels, BrdU and PicoGreen®-assays. Furthermore, mRNA-levels and activity of matrix metalloproteinase 13 were profoundly increased. In vivo, calcitriol ameliorated inflammatory liver-injury reflected by reduced levels of alanine aminotransferase in Abcb4{sup −/−}-mice. In accordance, their livers had lower mRNA-levels of F4/80, tumor necrosis factor-receptor 1 and a lower count of portal CD11b positive cells. In contrast, no effect on overall fibrosis was observed. Conclusion: Calcitriol inhibits activation and proliferation of HSCs in vitro. In Abcb4{sup −/−}-mice, administration of calcitriol ameliorates inflammatory liver-damage but has

  1. Isotope shifts of the 6d{sup 2} D{sub 3/2}-7 p{sup 2} P{sub 1/2} transition in trapped short-lived {sup 209-214}Ra{sup +}

    SciTech Connect

    Giri, G. S.; Versolato, O. O.; Berg, J. E. van den; Boell, O.; Dammalapati, U.; Hoek, D. J. van der; Jungmann, K.; Kruithof, W. L.; Mueller, S.; Nunez Portela, M.; Onderwater, C. J. G.; Santra, B.; Timmermans, R. G. E.; Wansbeek, L. W.; Willmann, L.; Wilschut, H. W.

    2011-08-15

    Laser spectroscopy of short-lived radium isotopes in a linear Paul trap has been performed. The isotope shifts of the 6d{sup 2} D{sub 3/2} -7 p{sup 2} P{sub 1/2} transition in {sup 209-214}Ra{sup +}, which are sensitive to the short-range part of the atomic wave functions, were measured. The results are essential experimental input for improving the precision of atomic structure calculations. This is indispensable for parity violation in Ra{sup +} aiming at the determination of the weak mixing angle.

  2. Full Vector Analyses of Cryptochron C2r.2r-l (ca. 2.42-2.44 Ma) Recorded on Koolau Volcano at Halawa, Oahu, Hawaii: Evidence From Directions, Absolute Paleointensity Determinations and 40Ar/39Ar Studies.

    NASA Astrophysics Data System (ADS)

    Browne, E. J.; Herrero-Bervera, E.; Singer, B.

    2005-12-01

    sampled. We used the modified Thellier-Coe double heating method to determine paleointensities. pTRM checks were performed systematically one temperature step down the last pTRM acquisition in order to document magnetomineralogical changes during heating. The temperature was incremented by steps of 50o C between room temperature and 500oC and every 25-30o C. The paleointensity determinations were obtained from the slope of the Arai diagrams. Special care was taken to interpret the Arai diagrams within the same range of temperatures lower than 300oC unless a clear and unique slope would be present. Our paleointensity results indicate a near-zero reduced strength of the field during the excursional period ranging from 5 to 9 micro-Tesla. The corresponding VGPs are located off the southeast part of Africa, close to Madagascar. Initial 40Ar/39Ar incremental heating experiments on groundmass from nine flow-sites located at different stratigraphic levels yielded isochron ages ranging from 2.64+/-0.25 to 2.40+/-0.46 Ma indicating that the excursion may correlate with the C2r.2r-l Cryptochron of Cande and Kent [1995]. this is potentially the first terrestrial record of the ca. 2.4 Ma Cryptochron, a finding that will place important constraints on evolution of the entire Koolau shield edifice also.

  3. Magnetic ordering in Sc2CoSi2-type R2FeSi2 (R=Gd, Tb) and R2CoSi2 (R=Y, Gd-Er) compounds

    NASA Astrophysics Data System (ADS)

    Morozkin, A. V.; Knotko, A. V.; Yapaskurt, V. O.; Pani, M.; Nirmala, R.; Quezado, S.; Malik, S. K.

    2016-09-01

    Magnetic and magnetocaloric properties of Sc2CoSi2-type R2TSi2 (R=Gd-Er, T=Fe, Co) compounds have been studied using magnetization data. These indicate the presence of mixed ferromagnetic and antiferromagnetic interactions in these compounds. One observes a ferromagnetic transition followed by an antiferromagnetic order and a further possible spin-reorientation transition at low temperatures. Compared to Gd2{Fe, Co}Si2, the Tb2FeSi2 and {Tb-Er}2CoSi2 compounds exhibit remarkable hysteresis (for e.g. Tb2FeSi2 shows residual magnetization Mres/Tb=2.45 μB, coercive field Hcoer=14.9 kOe, and critical field Hcrit 5 kOe at 5 K) possibly due to the magnetocrystalline anisotropy of the rare earth. The R2{Fe, Co}Si2 show relatively small magnetocaloric effect (i.e. isothermal magnetic entropy change, ΔSm) around the magnetic transition temperature: the maximal value of MCE is demonstrated by Ho2CoSi2 (ΔSm=-8.1 J/kg K at 72 K and ΔSm=-9.4 J/kg K at 23 K in field change of 50 kOe) and Er2CoSi2 (ΔSm=-13.6 J/kg K at 32 K and ΔSm=-8.4 J/kg K at 12 K in field change of 50 kOe).

  4. Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant bilateral myelolipomas from patients with congenital adrenal hyperplasia

    PubMed Central

    2014-01-01

    Background Although chronic adrenocorticotropic hormone (ACTH) and androgen hyperstimulation are assumed to be involved in the pathogenesis of adrenal myelolipomas associated with poor-compliance patients with congenital adrenal hyperplasia (CAH), the expression of their receptors has not yet been demonstrated in these tumors so far. Methods We analyzed Melanocortin 2 receptor (MC2R), Androgen Receptor (AR), Leptin (LEP), and Steroidogenic factor 1 (SF1) expression using real-time qRT-PCR in two giant bilateral adrenal myelolipomas from two untreated simple virilizing CAH cases and in two sporadic adrenal myelolipomas. In addition, the X-chromosome inactivation pattern and CAG repeat numbers in AR exon 1 gene were evaluated in the 4 cases. Results The MC2R gene was overexpressed in myelolipomas from 3 out of 4 patients. AR overexpression was detected in 2 tumors: a giant bilateral myelolipoma in a CAH patient and a sporadic case. Simultaneous overexpression of AR and MC2R genes was found in two of the cases. Interestingly, the bilateral giant myelolipoma associated with CAH that had high androgen and ACTH levels but lacked MC2R and AR overexpression presented a significantly shorter AR allele compared with other tumors. In addition, X-chromosome inactivation pattern analysis showed a polyclonal origin in all tumors, suggesting a stimulatory effect as the trigger for tumor development. Conclusion These findings are the first evidence for MC2R or AR overexpression in giant bilateral myelolipomas from poor-compliance CAH patients. PMID:24884994

  5. Solvothermal fabrication of activated semi-coke supported TiO2-rGO nanocomposite photocatalysts and application for NO removal under visible light

    NASA Astrophysics Data System (ADS)

    Yang, Weiwei; Li, Chunhu; Wang, Liang; Sun, ShengNan; Yan, Xin

    2015-10-01

    The photocatalysts of activated semi-coke supported TiO2-rGO nanocomposite (TiO2-rGO/ASC) with different contents of reduced graphene oxide were fabricated by one-step solvothermal method for NO removal under visible light irradiation. It was confirmed that 8% content of reduced graphene oxide presented the best NO photooxidation performance under visible light irradiation at 70 °C with 350-400 mg/m3 NO,5% O2 and 5% relative humidity. The reasons for improved activity were discussed, alloyed with the mechanism of producing CO. Detailed structural information of TiO2-rGO/ASC photocatalysts was characterized by scanning electron microscope (SEM), energy dispersive X-ray Spectroscopy (EDX), X-ray diffraction analysis (XRD), UV-Vis diffuse reflectance spectra (UV-Vis DRS) and photoluminescence (PL), which indicated that the introduction of rGO was responsible for well dispersion, smaller crystalline size, red shift of absorption band and suppressing quick photo-induced charges recombination of TiO2-rGO/ASC photocatalysts. Optimization of operational parameters with 70 °C, 8% O2 and 8% relative humidity were also obtained. Deactivation of TiO2-rGO/ASC photocatalysts for NO removal was investigated by Fourier-transform infrared (FTIR) analysis. Regeneration experiments showed that thermal vapor regeneration would be optimal method owing to excellent regenerative capacity and inexpensive procedure.

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

    PubMed

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

    Glucagon-like peptide-1 (GLP-1) hormone is known to regulate blood glucose by an insulinotropic effect and increases proliferation as and also prevents apoptosis of pancreatic β cells. We know that GLP-1 is secreted by nutrients such as fatty acids and sweet compounds but also bitter compounds via stimulation of G-protein coupled receptors (GPCRs) in the gut. Among these, bitter compounds are multiply-contained in phytochemicals or artificial materials and perceived as ligands of various bitter taste receptors. We hypothesized that GLP-1 hormone is secreted through stimulation of a single bitter taste receptor by 1,10-phenanthroline which is known agonist of taste receptor type 2 member 5 (T2R5). To prove this hypothesis, we used the representatively well-known 1,10-phenanthroline as ligand of single receptor and evaluated the existence of T2R5 by double-labeling immunofluorescence and then 1,10-phenanthroline is able to secrete GLP-1 hormone through stimulation of T2R5 in human enteroendocrine cells. Consequently, we verify that GLP-1 hormone is colocalized with T2R5 in the human duodenum and ileum tissue and is secreted by 1,10-phenanthroline via T2R5 signal transduction in differentiated human enteroendocrine L cells. PMID:26505793

  7. Comparative mapping on the mouse and human X chromosomes of a human cDNA clone encoding the vasopressin renal-type receptor (AVP2R)

    SciTech Connect

    Faust, C.J.; Gonzales, J.C.; Seibold, A.; Birnbaumer, M.; Herman, G.E. )

    1993-02-01

    Mutation in the gene for the human renal-type vasopressin receptor (V2R) have recently been identified in patients with nephrogenic diabetes insipidus (NDI). Both V2R and NDI have been independently mapped to Xq28. Using a combination of genetic and physical mapping, we have localized the murine V2r locus to within 100 kb of L1Cam on the mouse X chromosome in a region syntenic with human Xq28. Based on conserved gene order of mouse and human loci in this region, physical mapping using DNA derived form human lymphoblasts has established that the corresponding human loci V2R and L1CAM are linked within 210 kb. The efficiency and precision of genetic mapping of V2r and other loci in the mouse suggest that it might be easier to map additional human genes in the mouse first and infer the corresponding human location. More precise physical mapping in man could then be performed using pulsed-field gel electrophoresis and/or yeast artificial chromosomes. 16 refs., 1 fig. 1 tab.

  8. Near ultraviolet photodissociation spectroscopy of Mn{sup +}(H{sub 2}O) and Mn{sup +}(D{sub 2}O)

    SciTech Connect

    Pearson, Wright L.; Copeland, Christopher; Kocak, Abdulkadir; Sallese, Zachary; Metz, Ricardo B.

    2014-11-28

    The electronic spectra of Mn{sup +}(H{sub 2}O) and Mn{sup +}(D{sub 2}O) have been measured from 30 000 to 35 000 cm{sup −1} using photodissociation spectroscopy. Transitions are observed from the {sup 7}A{sub 1} ground state in which the Mn{sup +} is in a 3d{sup 5}4s{sup 1} electronic configuration, to the {sup 7}B{sub 2} (3d{sup 5}4p{sub y}) and {sup 7}B{sub 1} (3d{sup 5}4p{sub x}) excited states with T{sub 0} = 30 210 and 32 274 cm{sup −1}, respectively. Each electronic transition has partially resolved rotational and extensive vibrational structure with an extended progression in the metal−ligand stretch at a frequency of ∼450 cm{sup −1}. There are also progressions in the in-plane bend in the {sup 7}B{sub 2} state, due to vibronic coupling, and the out-of-plane bend in the {sup 7}B{sub 1} state, where the calculation illustrates that this state is slightly non-planar. Electronic structure computations at the CCSD(T)/aug-cc-pVTZ and TD-DFT B3LYP/6-311++G(3df,3pd) level are also used to characterize the ground and excited states, respectively. These calculations predict a ground state Mn-O bond length of 2.18 Å. Analysis of the experimentally observed vibrational intensities reveals that this bond length decreases by 0.15 ± 0.015 Å and 0.14 ± 0.01 Å in the excited states. The behavior is accounted for by the less repulsive p{sub x} and p{sub y} orbitals causing the Mn{sup +} to interact more strongly with water in the excited states than the ground state. The result is a decrease in the Mn-O bond length, along with an increase in the H-O-H angle. The spectra have well resolved K rotational structure. Fitting this structure gives spin-rotation constants ε{sub aa}″ = −3 ± 1 cm{sup −1} for the ground state and ε{sub aa}′ = 0.5 ± 0.5 cm{sup −1} and ε{sub aa}′ = −4.2 ± 0.7 cm{sup −1} for the first and second excited states, respectively, and A′ = 12.8 ± 0.7 cm{sup −1} for the first excited state. Vibrationally mediated

  9. Theoretical study of electronic structure and complexation of PbII(S2COR)2 [R = Me, Et, Ph] complexes

    NASA Astrophysics Data System (ADS)

    Ghosh, Deepanwita; Bagchi, Sabyasachi; Das, Abhijit K.

    2012-01-01

    The complexes of PbII(S2COR)2 [R = Me, Et, Ph] having three possible coordination patterns S,S/S,S or S,O/S,S or S,O/S,O are studied. The formation energy and relative energy of these isomers reveal that the order of stability is S,S/S,S > S,O/S,S > S,O/S,O. Complexation energy of the isomers decreases substantially from gas phase to water. The natural bond orbital (NBO) analysis has been performed to explore the metal-ligand coordination. Similar types of metal-ligand coordinations are observed for methyl and ethyl substituent. In S/S,S/S coordination, lead mainly uses its 6p sub-shells along with 6d and 7s orbitals to coordinate with 3p sub-shells of the surrounding sulfur atoms. Significant mixing of 6p and 6d orbitals of lead is also observed. In contrast, for phenyl substituent, lead uses only its 6p sub-shells to coordinate with sulfur atoms. In S,O/S,O or S,O/S,S coordination, oxygen uses its 2s and 2p sub-shells while sulfur uses its 3p sub-shells to coordinate with 7s and 6p sub-shells of lead. The binding energy and NBO analysis of these chelates indicate that lead-sulfur (soft-soft) coordination is preferred over lead-oxygen (soft-hard). In all these chelates, valence 6s orbital of lead shows inert pair effect with no participation in chelation.

  10. Thermodynamic and transport properties of single crystalline RCo2Ge2 (R=Y, La–Nd, Sm–Tm)

    SciTech Connect

    Kong, Tai; Cunningham, Charles E.; Taufour, Valentin; Budko, Sergey L.; Buffon, Malinda L.C.; Lin, Xiao; Emmons, Heather; Canfield, Paul C.

    2014-05-01

    Single crystals of RCo2Ge2 (R=Y, La–Nd, Sm–Tm) were grown using a self-flux method and were characterized by room-temperature powder X-ray diffraction; anisotropic, temperature and field dependent magnetization; temperature and field dependent, in-plane resistivity; and specific heat measurements. In this series, the majority of the moment-bearing members order antiferromagnetically; YCo2Ge2 and LaCo2Ge2 are non-moment-bearing. Ce is trivalent in CeCo2Ge2 at high temperatures, and exhibits an enhanced electronic specific heat coefficient due to the Kondo effect at low temperatures. In addition, CeCo2Ge2 shows two low-temperature anomalies in temperature-dependent magnetization and specific heat measurements. Three members (R=Tb–Ho) have multiple phase transitions above 1.8 K. Eu appears to be divalent with total angular momentum L =0. Both EuCo2Ge2 and GdCo2Ge2 manifest essentially isotropic paramagnetic properties consistent with J =S =7/2. Clear magnetic anisotropy for rare-earth members with finite L was observed, with ErCo2Ge2 and TmCo2Ge2 manifesting planar anisotropy and the rest members manifesting axial anisotropy. The experimentally estimated crystal electric field (CEF) parameters B 20 were calculated from the anisotropic paramagnetic θ ab and θ c values and follow a trend that agrees well with theoretical predictions. The ordering temperatures, TNTN, as well as the polycrystalline averaged paramagnetic Curie–Weiss temperature, Θavg, for the heavy rare-earth members deviate from the de Gennes scaling, as the magnitude of both is the highest for Tb, which is sometimes seen for extremely axial systems. Except for SmCo2Ge2, metamagnetic transitions were observed at 1.8 K for all members that ordered antiferromagnetically.

  11. Three R2R3-MYB Transcription Factors Regulate Distinct Floral Pigmentation Patterning in Phalaenopsis spp.1[OPEN

    PubMed Central

    Hsu, Chia-Chi; Chen, You-Yi; Tsai, Wen-Chieh; Chen, Wen-Huei; Chen, Hong-Hwa

    2015-01-01

    Orchidaceae are well known for their fascinating floral morphologic features, specialized pollination, and distinctive ecological strategies. With their long-lasting flowers of various colors and pigmentation patterning, Phalaenopsis spp. have become important ornamental plants worldwide. In this study, we identified three R2R3-MYB transcription factors PeMYB2, PeMYB11, and PeMYB12. Their expression profiles were concomitant with red color formation in Phalaenopsis spp. flowers. Transient assay of overexpression of three PeMYBs verified that PeMYB2 resulted in anthocyanin accumulation, and these PeMYBs could activate the expression of three downstream structural genes Phalaenopsis spp. Flavanone 3-hydroxylase5, Phalaenopsis spp. Dihydroflavonol 4-reductase1, and Phalaenopsis spp. Anthocyanidin synthase3. In addition, these three PeMYBs participated in the distinct pigmentation patterning in a single flower, which was revealed by virus-induced gene silencing. In the sepals/petals, silencing of PeMYB2, PeMYB11, and PeMYB12 resulted in the loss of the full-red pigmentation, red spots, and venation patterns, respectively. Moreover, different pigmentation patterning was regulated by PeMYBs in the sepals/petals and lip. PeMYB11 was responsive to the red spots in the callus of the lip, and PeMYB12 participated in the full pigmentation in the central lobe of the lip. The differential pigmentation patterning was validated by RNA in situ hybridization. Additional assessment was performed in six Phalaenopsis spp. cultivars with different color patterns. The combined expression of these three PeMYBs in different ratios leads to a wealth of complicated floral pigmentation patterning in Phalaenopsis spp. PMID:25739699

  12. Thermodynamic and transport properties of single crystalline RCo2Ge2 (R=Y, La-Nd, Sm-Tm)

    NASA Astrophysics Data System (ADS)

    Kong, Tai; Cunningham, Charles E.; Taufour, Valentin; Bud'ko, Sergey L.; Buffon, Malinda L. C.; Lin, Xiao; Emmons, Heather; Canfield, Paul C.

    2014-05-01

    Single crystals of RCo2Ge2 (R=Y, La-Nd, Sm-Tm) were grown using a self-flux method and were characterized by room-temperature powder X-ray diffraction; anisotropic, temperature and field dependent magnetization; temperature and field dependent, in-plane resistivity; and specific heat measurements. In this series, the majority of the moment-bearing members order antiferromagnetically; YCo2Ge2 and LaCo2Ge2 are non-moment-bearing. Ce is trivalent in CeCo2Ge2 at high temperatures, and exhibits an enhanced electronic specific heat coefficient due to the Kondo effect at low temperatures. In addition, CeCo2Ge2 shows two low-temperature anomalies in temperature-dependent magnetization and specific heat measurements. Three members (R=Tb-Ho) have multiple phase transitions above 1.8 K. Eu appears to be divalent with total angular momentum L=0. Both EuCo2Ge2 and GdCo2Ge2 manifest essentially isotropic paramagnetic properties consistent with J=S=7/2. Clear magnetic anisotropy for rare-earth members with finite L was observed, with ErCo2Ge2 and TmCo2Ge2 manifesting planar anisotropy and the rest members manifesting axial anisotropy. The experimentally estimated crystal electric field (CEF) parameters B20 were calculated from the anisotropic paramagnetic θab and θc values and follow a trend that agrees well with theoretical predictions. The ordering temperatures, TN, as well as the polycrystalline averaged paramagnetic Curie-Weiss temperature, Θavg, for the heavy rare-earth members deviate from the de Gennes scaling, as the magnitude of both is the highest for Tb, which is sometimes seen for extremely axial systems. Except for SmCo2Ge2, metamagnetic transitions were observed at 1.8 K for all members that ordered antiferromagnetically.

  13. Measurement of B(D{sub s}{sup +}{yields}l{sup +}{nu}) and the decay constant f{sub D{sub s}{sup +}} from 600 pb{sup -1} of e{sup +}e{sup -} annihilation data near 4170 MeV

    SciTech Connect

    Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Galik, R. S.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Hunt, J. M.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Ledoux, J.; Mahlke-Krueger, H.; Mohapatra, D.; Patterson, J. R.

    2009-03-01

    We examine e{sup +}e{sup -}{yields}D{sub s}{sup -}D{sub s}*{sup +} and D{sub s}*{sup -}D{sub s}{sup +} interactions at 4170 MeV using the CLEO-c detector in order to measure the decay constant f{sub D{sub s}{sup +}} with good precision. Previously our measurements were substantially higher than the most precise lattice based QCD calculation of (241{+-}3) MeV. Here we use the D{sub s}{sup +}{yields}l{sup +}{nu} channel, where the l{sup +} designates either a {mu}{sup +} or a {tau}{sup +}, when the {tau}{sup +}{yields}{pi}{sup +}{nu}. Analyzing both modes independently, we determine B(D{sub s}{sup +}{yields}{mu}{sup +}{nu})=(0.565{+-}0.045{+-}0.017)%, and B(D{sub s}{sup +}{yields}{tau}{sup +}{nu})=(6.42{+-}0.81{+-}0.18)%. We also analyze them simultaneously to find an effective value of B{sup eff}(D{sub s}{sup +}{yields}{mu}{sup +}{nu})=(0.591{+-}0.037{+-}0.018)% and f{sub D{sub s}{sup +}}=(263.3{+-}8.2{+-}3.9) MeV. Combining with the CLEO-c value determined independently using D{sub s}{sup +}{yields}{tau}{sup +}{nu}, {tau}{sup +}{yields}e{sup +}{nu}{nu} decays, we extract f{sub D{sub s}{sup +}}=(259.5{+-}6.6{+-}3.1) MeV. Combining with our previous determination of B(D{sup +}{yields}{mu}{sup +}{nu}), we extract the ratio f{sub D{sub s}{sup +}}/f{sub D{sup +}}=1.26{+-}0.06{+-}0.02. No evidence is found for a CP asymmetry between {gamma}(D{sub s}{sup +}{yields}{mu}{sup +}{nu}) and {gamma}(D{sub s}{sup -}{yields}{mu}{sup -}{nu}); specifically the fractional difference in rates is measured to be (4.8{+-}6.1)%. Finally, we find B(D{sub s}{sup +}{yields}e{sup +}{nu})<1.2x10{sup -4} at 90% confidence level.

  14. Opposite action of R2R3-MYBs from different subgroups on key genes of the shikimate and monolignol pathways in spruce.

    PubMed

    Bomal, Claude; Duval, Isabelle; Giguère, Isabelle; Fortin, Élise; Caron, Sébastien; Stewart, Don; Boyle, Brian; Séguin, Armand; MacKay, John J

    2014-02-01

    Redundancy and competition between R2R3-MYB activators and repressors on common target genes has been proposed as a fine-tuning mechanism for the regulation of plant secondary metabolism. This hypothesis was tested in white spruce [Picea glauca (Moench) Voss] by investigating the effects of R2R3-MYBs from different subgroups on common targets from distinct metabolic pathways. Comparative analysis of transcript profiling data in spruces overexpressing R2R3-MYBs from loblolly pine (Pinus taeda L.), PtMYB1, PtMYB8, and PtMYB14, defined a set of common genes that display opposite regulation effects. The relationship between the closest MYB homologues and 33 putative target genes was explored by quantitative PCR expression profiling in wild-type P. glauca plants during the diurnal cycle. Significant Spearman's correlation estimates were consistent with the proposed opposite effect of different R2R3-MYBs on several putative target genes in a time-related and tissue-preferential manner. Expression of sequences coding for 4CL, DHS2, COMT1, SHM4, and a lipase thio/esterase positively correlated with that of PgMYB1 and PgMYB8, but negatively with that of PgMYB14 and PgMYB15. Complementary electrophoretic mobility shift assay (EMSA) and transactivation assay provided experimental evidence that these different R2R3-MYBs are able to bind similar AC cis-elements in the promoter region of Pg4CL and PgDHS2 genes but have opposite effects on their expression. Competitive binding EMSA experiments showed that PgMYB8 competes more strongly than PgMYB15 for the AC-I MYB binding site in the Pg4CL promoter. Together, the results bring a new perspective to the action of R2R3-MYB proteins in the regulation of distinct but interconnecting metabolism pathways. PMID:24336492

  15. The association between the LRRK2 R1628P variant and the risk of Parkinson's disease in Asian: a meta-analysis.

    PubMed

    Wang, Xiaoli; Zhang, Xiaona; Xue, Li; Xie, Anmu

    2016-06-01

    Many published case-control studies have investigated the association between Leucine-rich repeat kinase 2(LRRK2) R1628P and the susceptibility of Parkinson's disease (PD). However, controversial results were obtained. Herein we performed this meta-analysis to assess the association between the LRRK2 R1628P variants and the risk of PD. Up to January of 2016, 5 databases were searched to identify case-control studies involving LRRK2 R1628P variants and PD risk. A total of 5736 PD patients and 4786 controls in 14 case-control studies were included in this meta-analysis. And STATA 12.0 statistics software was used to calculate available data from each study. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated to assess the genetic association between LRRK2 R1628P polymorphism and the risk of PD. The results indicated that LRRK2 R1628P variants were increased risk of PD when all studies were pooled (C vs. G OR=1.983, 95% CI 1.640-2.399; GC+CC vs. GG OR=1.971, 95% CI 1.625-2.391). Moreover, in the subgroup analysis by ethnicity, increased risks were identified among Chinese (GC+CC vs. GG, OR=1.96, 95% CI 1.60-2.41) as well as in non-Chinese Asian races (GC+CC vs. GG, OR=2.03, 95% CI 1.13-3.65). Therefore, our results suggest that the C allele, GC and CC genotype of LRRK2 R1628P variants contribute to the susceptibility of PD in Asian. PMID:27133195

  16. Design and implementation of adaptive PI control schemes for web tension control in roll-to-roll (R2R) manufacturing.

    PubMed

    Raul, Pramod R; Pagilla, Prabhakar R

    2015-05-01

    In this paper, two adaptive Proportional-Integral (PI) control schemes are designed and discussed for control of web tension in Roll-to-Roll (R2R) manufacturing systems. R2R systems are used to transport continuous materials (called webs) on rollers from the unwind roll to the rewind roll. Maintaining web tension at the desired value is critical to many R2R processes such as printing, coating, lamination, etc. Existing fixed gain PI tension control schemes currently used in industrial practice require extensive tuning and do not provide the desired performance for changing operating conditions and material properties. The first adaptive PI scheme utilizes the model reference approach where the controller gains are estimated based on matching of the actual closed-loop tension control systems with an appropriately chosen reference model. The second adaptive PI scheme utilizes the indirect adaptive control approach together with relay feedback technique to automatically initialize the adaptive PI gains. These adaptive tension control schemes can be implemented on any R2R manufacturing system. The key features of the two adaptive schemes is that their designs are simple for practicing engineers, easy to implement in real-time, and automate the tuning process. Extensive experiments are conducted on a large experimental R2R machine which mimics many features of an industrial R2R machine. These experiments include trials with two different polymer webs and a variety of operating conditions. Implementation guidelines are provided for both adaptive schemes. Experimental results comparing the two adaptive schemes and a fixed gain PI tension control scheme used in industrial practice are provided and discussed. PMID:25555757

  17. A bitter pill for type 2 diabetes? The activation of bitter taste receptor TAS2R38 can stimulate GLP-1 release from enteroendocrine L-cells

    PubMed Central

    Pham, Hung; Hui, Hongxiang; Morvaridi, Susan; Cai, Jiena; Zhang, Sanqi; Tan, Jun; Wu, Vincent; Levin, Nancy; Knudsen, Beatrice; Goddard, William A.; Pandol, Stephen J.; Abrol, Ravinder

    2016-01-01

    The bitter taste receptor TAS2R38 is a G protein coupled receptor (GPCR) that has been found in many extra-oral locations like the gastrointestinal (GI) system, respiratory system, and brain, though its function at these locations is only beginning to be understood. To probe the receptor’s potential metabolic role, immunohistochemistry of human ileum tissues was performed, which showed that the receptor was co-localized with glucagon-like peptide 1 (GLP-1) in L-cells. In a previous study, we had modeled the structure of this receptor for its many taste-variant haplotypes (Tan et al. 2011), including the taster haplotype PAV. The structure of this haplotype was then used in a virtual ligand screening pipeline using a collection of ~2.5 million purchasable molecules from the ZINC database. Three compounds (Z7, Z3, Z1) were purchased from the top hits and tested along with PTU (known TAS2R38 agonist) in in vitro and in vivo assays. The dose-response study of the effect of PTU and Z7 on GLP-1 release using wild-type and TAS2R38 knockout HuTu-80 cells showed that the receptor TAS2R38 plays a major role in GLP-1 release due to these molecules. In vivo studies of PTU and the three compounds showed that they each increase GLP-1 release. PTU was also chemical linked to cellulose to slow its absorption and when tested in vivo, it showed an enhanced and prolonged GLP-1 release. These results suggest that the GI lumen location of TAS2R38 on the L-cell makes it a relatively safe drug target as systemic absorption is not needed for a TAS2R38 agonist drug to effect GLP-1 release. PMID:27208775

  18. A bitter pill for type 2 diabetes? The activation of bitter taste receptor TAS2R38 can stimulate GLP-1 release from enteroendocrine L-cells.

    PubMed

    Pham, Hung; Hui, Hongxiang; Morvaridi, Susan; Cai, Jiena; Zhang, Sanqi; Tan, Jun; Wu, Vincent; Levin, Nancy; Knudsen, Beatrice; Goddard, William A; Pandol, Stephen J; Abrol, Ravinder

    2016-07-01

    The bitter taste receptor TAS2R38 is a G protein coupled receptor (GPCR) that has been found in many extra-oral locations like the gastrointestinal (GI) system, respiratory system, and brain, though its function at these locations is only beginning to be understood. To probe the receptor's potential metabolic role, immunohistochemistry of human ileum tissues was performed, which showed that the receptor was co-localized with glucagon-like peptide 1 (GLP-1) in L-cells. In a previous study, we had modeled the structure of this receptor for its many taste-variant haplotypes (Tan et al. 2011), including the taster haplotype PAV. The structure of this haplotype was then used in a virtual ligand screening pipeline using a collection of ∼2.5 million purchasable molecules from the ZINC database. Three compounds (Z7, Z3, Z1) were purchased from the top hits and tested along with PTU (known TAS2R38 agonist) in in vitro and in vivo assays. The dose-response study of the effect of PTU and Z7 on GLP-1 release using wild-type and TAS2R38 knockout HuTu-80 cells showed that the receptor TAS2R38 plays a major role in GLP-1 release due to these molecules. In vivo studies of PTU and the three compounds showed that they each increase GLP-1 release. PTU was also chemical linked to cellulose to slow its absorption and when tested in vivo, it showed an enhanced and prolonged GLP-1 release. These results suggest that the GI lumen location of TAS2R38 on the L-cell makes it a relatively safe drug target as systemic absorption is not needed for a TAS2R38 agonist drug to effect GLP-1 release. PMID:27208775

  19. No evidence for a major gene effect of the dopamine D{sub 4} receptor gene in the susceptibility to Gilles de la Tourette Syndrome in five Canadian families

    SciTech Connect

    Barr, C.L.; Wigg, K.G.; Tsui, Lap-Chee

    1996-05-31

    Gilles de la Tourette Syndrome (TS) is a neuropsychiatric disorder characterized by both motor and vocal tics affecting approximately 1/10,000 females and 1/2000 males. Because of the success of neuroleptics and other agents interacting with the dopaminergic system in the suppression of tics, a defect in the dopamine system has been hypothesized in the etiology of TS. In this paper we test the hypothesis that the dopamine D{sub 4} receptor (DRD44) is linked to the genetic susceptibility to TS in five families. We tested three polymorphisms in the DRD4 gene and a polymorphism in the closely linked locus, tyrosine hydroxylase (TH). We found no evidence for linkage of DRD4 or TH to TS using an autosomal dominant model with reduced penetrance or using non-parametric methods. The presence of a mutation that results in a truncated non-functional D{sub 4} receptor protein was also tested for, but was not observed in these families. 36 refs., 1 tab.

  20. Proliferation inhibition and apoptosis induction of imatinib-resistant chronic myeloid leukemia cells via PPP2R5C down-regulation.

    PubMed

    Shen, Qi; Liu, Sichu; Chen, Yu; Yang, Lijian; Chen, Shaohua; Wu, Xiuli; Li, Bo; Lu, Yuhong; Zhu, Kanger; Li, Yangqiu

    2013-01-01

    Despite the success of imatinib and other tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) remains largely incurable, and a number of CML patients die due to Abl mutation-related drug resistance and blast crisis. The aim of this study was to evaluate proliferation inhibition and apoptosis induction by down-regulating PPP2R5C gene expression in the imatinib-sensitive and imatinib-resistant CML cell lines K562, K562R (imatinib resistant without an Abl gene mutation), 32D-Bcr-Abl WT (imatinib-sensitive murine CML cell line with a wild type Abl gene) and 32D-Bcr-Abl T315I (imatinib resistant with a T315I Abl gene mutation) and primary cells from CML patients by RNA interference. PPP2R5C siRNAs numbered 799 and 991 were obtained by chemosynthesis. Non-silencing siRNA scrambled control (SC)-treated, mock-transfected, and untreated cells were used as controls. The PPP2R5C mRNA and protein expression levels in treated CML cells were analyzed by quantitative real-time PCR and Western blotting, and in vitro cell proliferation was assayed with the cell counting kit-8 method. The morphology and percentage of apoptosis were revealed by Hoechst 33258 staining and flow cytometry (FCM). The results demonstrated that both siRNAs had the best silencing results after nucleofection in all four cell lines and primary cells. A reduction in PPP2R5C mRNA and protein levels was observed in the treated cells. The proliferation rate of the PPP2R5C-siRNA-treated CML cell lines was significantly decreased at 72 h, and apoptosis was significantly increased. Significantly higher proliferation inhibition and apoptosis induction were found in K562R cells treated with PPP2R5C-siRNA799 than K562 cells. In conclusion, the suppression of PPP2R5C by RNA interference could inhibit proliferation and effectively induce apoptosis in CML cells that were either imatinib sensitive or resistant. Down-regulating PPP2R5C gene expression might be considered as a new therapeutic target strategy

  1. Lack of Association of Clinical Factors (SAMe-TT2R2) with CYP2C9/VKORC1 Genotype and Anticoagulation Control Quality

    PubMed Central

    Park, Yun Kyung; Lee, Mi ji; Kim, Jae Ha; Kim, Suk Jae; Kim, June Soo; Lee, Soo-Youn

    2015-01-01

    Background and Purpose Advantages of new oral anticoagulations may be greater in atrial fibrillation (AF) patients of poor anticoagulation control with warfarin. The SAMe-TT2R2 scoring system, based on clinical variables, was recently developed to aid in identifying these patients. In this study, we investigated the association of this clinical composite score with genetic factors related warfarin dosing and the quality of anticoagulation control. Methods Clinical and genetic data were collected from 380 consecutive Korean patients with AF (CHA2DS2-VASc score, 3.5±1.8) who were followed for an average of 4 years. We evaluated factors associated with time in therapeutic range (TTR, INR 2-3), including the CYP2C9 and VKORC1 genotypes and the SAMe-TT2R2 score (Sex female, Age <60 years, Medical history [>two co-morbidities], Treatment [interacting drugs, e.g., amiodarone], Tobacco use within 2 years [doubled], and Race non-white [doubled]). Results The average SAMe-TT2R2 score was 3.4±0.9, range 2-7; and 153 patients (40.2%) had SAMe-TT2R2 scores ≥4. Time in specific INR ranges varied depending on the VKORC1 genotype but not with the CYP2C9 genotype or the SAMe-TT2R2 score. TTR was higher in patients with the VKORC1 1173C>T than in VKORC1 TT (61.7±16% vs. 56.7±17.4%, P=0.031). Multivariate testing showed that VKORC1 genotype but not the SAMe-TT2R2 score was significantly associated with labile INRs. There was no correlation between the SAMe-TT2R2 scores and pharmacogenetic data. Conclusions A genetic factor, but none of the common clinical and demographic factors, as combined in the SAMe-TT2R2 score, was associated with the quality of anticoagulation control in Korean patients with AF. PMID:26060806

  2. Comparative genomic analysis of the R2R3 MYB secondary cell wall regulators of Arabidopsis, poplar, rice, maize, and switchgrass

    PubMed Central

    2014-01-01

    Background R2R3 MYB proteins constitute one of the largest plant transcription factor clades and regulate diverse plant-specific processes. Several R2R3 MYB proteins act as regulators of secondary cell wall (SCW) biosynthesis in Arabidopsis thaliana (At), a dicotyledenous plant. Relatively few studies have examined SCW R2R3 MYB function in grasses, which may have diverged from dicots in terms of SCW regulatory mechanisms, as they have in cell wall composition and patterning. Understanding cell wall regulation is especially important for improving lignocellulosic bioenergy crops, such as switchgrass. Results Here, we describe the results of applying phylogenic, OrthoMCL, and sequence identity analyses to classify the R2R3 MYB family proteins from the annotated proteomes of Arabidposis, poplar, rice, maize and the initial genome (v0.0) and translated transcriptome of switchgrass (Panicum virgatum). We find that the R2R3 MYB proteins of the five species fall into 48 subgroups, including three dicot-specific, six grass-specific, and two panicoid grass-expanded subgroups. We observe four classes of phylogenetic relationships within the subgroups of known SCW-regulating MYB proteins between Arabidopsis and rice, ranging from likely one-to-one orthology (for AtMYB26, AtMYB103, AtMYB69) to no homologs identifiable (for AtMYB75). Microarray data for putative switchgrass SCW MYBs indicate that many maintain similar expression patterns with the Arabidopsis SCW regulators. However, some of the switchgrass-expanded candidate SCW MYBs exhibit differences in gene expression patterns among paralogs, consistent with subfunctionalization. Furthermore, some switchgrass representatives of grass-expanded clades have gene expression patterns consistent with regulating SCW development. Conclusions Our analysis suggests that no single comparative genomics tool is able to provide a complete picture of the R2R3 MYB protein family without leaving ambiguities, and establishing likely false

  3. Positive Selection and Functional Divergence of R2R3-MYB Paralogous Genes Expressed in Inflorescence Buds of Scutellaria Species (Labiatae)

    PubMed Central

    Huang, Bing-Hong; Pang, Erli; Chen, Yi-Wen; Cao, Huifen; Ruan, Yu; Liao, Pei-Chun

    2015-01-01

    Anthocyanin is the main pigment forming floral diversity. Several transcription factors that regulate the expression of anthocyanin biosynthetic genes belong to the R2R3-MYB family. Here we examined the transcriptomes of inflorescence buds of Scutellaria species (skullcaps), identified the expression R2R3-MYBs, and detected the genetic signatures of positive selection for adaptive divergence across the rapidly evolving skullcaps. In the inflorescence buds, seven R2R3-MYBs were identified. MYB11 and MYB16 were detected to be positively selected. The signature of positive selection on MYB genes indicated that species diversification could be affected by transcriptional regulation, rather than at the translational level. When comparing among the background lineages of Arabidopsis, tomato, rice, and Amborella, heterogeneous evolutionary rates were detected among MYB paralogs, especially between MYB13 and MYB19. Significantly different evolutionary rates were also evidenced by type-I functional divergence between MYB13 and MYB19, and the accelerated evolutionary rates in MYB19, implied the acquisition of novel functions. Another paralogous pair, MYB2/7 and MYB11, revealed significant radical amino acid changes, indicating divergence in the regulation of different anthocyanin-biosynthetic enzymes. Our findings not only showed that Scutellaria R2R3-MYBs are functionally divergent and positively selected, but also indicated the adaptive relevance of regulatory genes in floral diversification. PMID:25782156

  4. Cotton (Gossypium spp.) R2R3-MYB transcription factors SNP identification, phylo-genomic characterization, chromosome localization and linkage mapping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    R2R3-MYB transcription factors of plants are involved in the regulation of trichome length and density. Several of them are differentially expressed with initiation and expansion of cotton fibers. We report sequence phylo-genomic characterization of the six MYB genes, their chromosomal localizatio...

  5. Selective Tumor Targeting of Desacetyl Vinblastine Hydrazide and Tubulysin B via Conjugation to a Cholecystokinin 2 Receptor (CCK2R) Ligand

    PubMed Central

    2015-01-01

    As the delivery of selectively targeted cytotoxic agents via antibodies or small molecule ligands to malignancies has begun to show promise in the clinic, the need to identify and validate additional cellular targets for specific therapeutic delivery is critical. Although a multitude of cancers have been targeted using the folate receptor, PSMA, bombesin receptor, somatostatin receptor, LHRH, and αvβ3, there is a notable lack of specific small molecule ligand/receptor pairs to cellular targets found within cancers of the GI tract. Because of the selective GI tract expression of the cholecystokinin 2 receptor (CCK2R), we undertook the creation of conjugates that would deliver microtubule-disrupting drugs to malignancies through the specific targeting of CCK2R via a high affinity small molecule ligand. The cytotoxic activity of these conjugates were shown to be receptor mediated in vitro and in vivo with xenograft mouse models exhibiting delayed growth or regression of tumors that expressed CCK2R. Overall, this work demonstrates that ligands to CCK2R can be used to create selectively targeted therapeutic conjugates. PMID:26043355

  6. KIF6, LPA, TAS2R50, and VAMP8 genetic variation, low density lipoprotein cholesterol lowering response to pravastatin, and heart disease risk reduction in the elderly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Single nucleotide polymorphisms (SNPs) at the KIF6 (kinesin like protein 6, rs20455 or 719Arg), LPA (lipoprotein(a), rs3798220), TAS2R50 (taste receptor type 2, member 50, rs1376251) and VAMP8 (vesicle-associated membrane protein 8, rs1010) have previously been associated with low density lipoprotei...

  7. Positive selection and functional divergence of R2R3-MYB paralogous genes expressed in inflorescence buds of Scutellaria species (Labiatae).

    PubMed

    Huang, Bing-Hong; Pang, Erli; Chen, Yi-Wen; Cao, Huifen; Ruan, Yu; Liao, Pei-Chun

    2015-01-01

    Anthocyanin is the main pigment forming floral diversity. Several transcription factors that regulate the expression of anthocyanin biosynthetic genes belong to the R2R3-MYB family. Here we examined the transcriptomes of inflorescence buds of Scutellaria species (skullcaps), identified the expression R2R3-MYBs, and detected the genetic signatures of positive selection for adaptive divergence across the rapidly evolving skullcaps. In the inflorescence buds, seven R2R3-MYBs were identified. MYB11 and MYB16 were detected to be positively selected. The signature of positive selection on MYB genes indicated that species diversification could be affected by transcriptional regulation, rather than at the translational level. When comparing among the background lineages of Arabidopsis, tomato, rice, and Amborella, heterogeneous evolutionary rates were detected among MYB paralogs, especially between MYB13 and MYB19. Significantly different evolutionary rates were also evidenced by type-I functional divergence between MYB13 and MYB19, and the accelerated evolutionary rates in MYB19, implied the acquisition of novel functions. Another paralogous pair, MYB2/7 and MYB11, revealed significant radical amino acid changes, indicating divergence in the regulation of different anthocyanin-biosynthetic enzymes. Our findings not only showed that Scutellaria R2R3-MYBs are functionally divergent and positively selected, but also indicated the adaptive relevance of regulatory genes in floral diversification. PMID:25782156

  8. Evidence for possible involvement of IGF type II receptors (IGF2R) in regulating growth of two concomitant dominant follicles in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Regulation of multiple ovulations in monotocous species such as cattle is not well understood. Gene expression of the FSH receptor (FSHR) in granulosa (GC), and LH receptor (LHR) and IGF2R in GC and theca (TC) cells, as well as estradiol (E2) and progesterone (P4) levels in follicular fluid (FF) wer...

  9. Crystal structure of methyl (2R,3S)-3-[(tert-butyl­sulfin­yl)amino]-2-fluoro-3-phenyl­propano­ate

    PubMed Central

    Zhao, Zhiwei; Fan, Wenqiang; Zhang, Yixiang; Li, Ya

    2015-01-01

    The title compound, C14H20FNO3S, contains two chiral carbon centres and the absolute configuration has been confirmed as (2R,3S). In the crystal, adjacent mol­ecules are linked by weak C—H⋯O hydrogen bonds, generating zigzag chains along the a-axis direction. PMID:26870495

  10. Tissue Kallikrein Alleviates Cerebral Ischemia-Reperfusion Injury by Activating the B2R-ERK1/2-CREB-Bcl-2 Signaling Pathway in Diabetic Rats

    PubMed Central

    Yuan, Kunxiong; Hu, Bin; Sang, Hongfei; Xie, Yi; Xu, Lili; Cao, Qinqin; Chen, Xin; Zhao, Lingling; Liu, Xinfeng; Liu, Ling; Zhang, Renliang

    2016-01-01

    Diabetes mellitus (DM) substantially increases the risk of ischemic stroke and reduces the tolerance to ischemic insults. Tissue kallikrein (TK) has been demonstrated to protect neurons from ischemia/reperfusion (I/R) injury in orthoglycemic model by activating the bradykinin B2 receptor (B2R). Considering the differential effects of B2R or bradykinin B1 receptor (B1R) on cardioprotection and neuroprotection in I/R with or without diabetes, this study was designed to investigate the role of TK during cerebral I/R injury in streptozotocin-induced diabetic rats. Intravenous injection of TK inhibited apoptosis in neurons, alleviated edema and inflammatory reactions after focal cerebral I/R, significantly reduced the infarct volume, and improved functional recovery. These beneficial effects were accompanied by activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), cAMP response element-binding (CREB), and Bcl-2 signal proteins. Inhibition of the B2R or ERK1/2 pathway abated the effects of TK, whereas an antagonist of B1R enhanced the effects. These findings reveal that the neuroprotective effect of TK against cerebral I/R injury in streptozotocin-induced diabetic rats mainly involves the enhancement of B2R and ERK1/2-CREB-Bcl-2 signaling pathway activity.

  11. Low functional programming of renal AT{sub 2}R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    SciTech Connect

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT{sub 2}R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT{sub 1a}R)/AT{sub 2}R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT{sub 2}R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT{sub 2}R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine

  12. Bitter receptor gene (TAS2R38) P49A genotypes and their associations with aversion to vegetables and sweet/fat foods in Malaysian subjects.

    PubMed

    Ooi, Shee-Xuen; Lee, Pui-Leng; Law, Huey-Yi; Say, Yee-How

    2010-01-01

    Recently, the bitter receptor gene (TAS2R38) was identified to be responsible for phenylthiocarbamide (PTC) bitter sensitivity. Its two predominant haplotypes at three Single Nucleotide Polymorphisms (SNPs) are found to be definitive for the PTC status, which the ProAlaVal and AlaValIle haplotypes are associated with tasters and non-tasters, respectively. TAS2R38 haplotypes have been reported to influence food preferences (like cruciferous vegetables and fat foods) and cardiovascular disease risk factors. We examined, in 215 Malaysian subjects (100 males, 115 females), the association of the P49A SNP of TAS2R38 with anthropometric measurements and aversion to a list of 36 vegetables, 4 soy products, green tea and 37 sweet/fat foods. The subjects were successfully genotyped as 110 PA, 81 PP and 24 AA (with the A49 allelic frequency of 0.37), by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Ethnicity (Malay, Chinese or Indian), but not gender, was associated with the P49A TAS2R38 genotypes (p<0.001). However, no significant differences in terms of Body Mass Index, Total Body Fat, waist circumference and Waist-Hip Ratio were found between the genotypes (p<0.05). Only aversions to green tea, mayonnaise and whipped cream, but not soy products, vegetables, and other sweet/fat foods, were associated with the P49A genotypes (p<0.05). Therefore, the P49A SNP of the bitter receptor gene TAS2R38 could not serve as a predictor of anthropometric measurements and aversion to vegetables or sweet/fat foods in the sampled Malaysian subjects, and this suggests the existence of other possible factors influencing food selection among Malaysians. PMID:21147709

  13. TCP3 interacts with R2R3-MYB proteins, promotes flavonoid biosynthesis and negatively regulates the auxin response in Arabidopsis thaliana.

    PubMed

    Li, Shutian; Zachgo, Sabine

    2013-12-01

    TCP proteins belong to the plant-specific bHLH transcription factor family, and function as key regulators of diverse developmental processes. Functional redundancy amongst family members and post-transcriptional down-regulation by miRJAW of several TCP genes complicate their functional characterization. Here, we explore the role of TCP3 by analyzing transgenic plants expressing miRJAW-resistant mTCP3 and dominant-negative TCP3SRDX. Seedlings and seeds of mTCP3 plants were found to hyper-accumulate flavonols, anthocyanins and proanthocyanidins, whereas levels of proanthocyanidins were slightly reduced in TCP3SRDX plants. R2R3-MYB proteins control not only early flavonoid biosynthetic steps but also activate late flavonoid biosynthetic genes by forming ternary R2R3-MYB/bHLH/WD40 (MBW) complexes. TCP3 interacted in yeast with R2R3-MYB proteins, which was further confirmed in planta using BiFC experiments. Yeast three-hybrid assays revealed that TCP3 significantly strengthened the transcriptional activation capacity of R2R3-MYBs bound by the bHLH protein TT8. Transcriptome analysis of mTCP3 and TCP3SRDX plants supported a role for TCP3 in enhancing flavonoid biosynthesis. Moreover, several auxin-related developmental abnormalities were observed in mTCP3 plants. Transcriptome data coupled with studies of an auxin response reporter and auxin efflux carriers showed that TCP3 negatively modulates the auxin response, probably by compromising auxin transport capacity. Genetic experiments revealed that the chalcone synthase mutant tt4-11 lacking flavonoid biosynthesis abrogated the auxin-related defects caused by mTCP3. Together, these data suggest that TCP3 interactions with R2R3-MYBs lead to enhanced flavonoid production, which further negatively modulates the auxin response. PMID:24118612

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

    PubMed Central

    Kelemen, Zsolt; Sebastian, Alvaro; Xu, Wenjia; Grain, Damaris; Salsac, Fabien; Avon, Alexandra; Berger, Nathalie; Tran, Joseph; Dubreucq, Bertrand; Lurin, Claire; Lepiniec, Loïc; Contreras-Moreira, Bruno; Dubos, Christian

    2015-01-01

    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. PMID:26484765

  15. In-vitro characterization of novel and functional regulatory SNPs in the promoter region of IL2 and IL2R alpha in a Gabonese population

    PubMed Central

    2012-01-01

    Background The selection pressure imposed by the parasite has a functional consequence on the immune genes, leading to altered immune function in which regulatory T cells (Tregs) induced by parasites during infectious challenges modulate or thwart T effector cell mechanism. Methods We identified and investigated regulatory polymorphisms in the immune gene IL2 and its receptor IL2R alpha (also known as CD25) in Gabonese individuals exposed to plentiful parasitic infections. Results We identified two reported variants each for IL2 and its receptor IL2R alpha gene loci. Also identified were two novel variants, -83 /-84 CT deletions (ss410961576) for IL2 and -409C/T (ss410961577) for IL2R alpha. We further validated all identified promoter variants for their allelic gene expression using transient transfection assays. Three promoter variants of the IL2 locus revealed no significant expression of the reporter gene. The identified novel variant (ss410961577C/T) of the IL2R alpha revealed a significant higher expression of the reporter gene in comparison to the major allele (P<0.05). In addition, the rs12722616C/T variant of the IL2R alpha locus altered the transcription factor binding site TBP (TATA box binding protein) and C/EBP beta (CCAAT/enhancer binding protein beta) that are believed to regulate the Treg function. Conclusions The identification and validation of such regulatory polymorphisms in the immune genes may provide a basis for future studies on parasite susceptibility in a population where T cell functions are compromised. PMID:23217119

  16. Cumulative reaction probabilities and transition state properties: A study of the H{sup +}+H{sub 2} and H{sup +}+D{sub 2} proton exchange reactions

    SciTech Connect

    Jambrina, P. G.; Aoiz, F. J.; Eyles, C. J.; Herrero, V. J.; Saez Rabanos, V.

    2009-05-14

    Cumulative reaction probabilities (CRPs) have been calculated by accurate (converged, close coupling) quantum mechanical (QM), quasiclassical trajectory (QCT), and statistical QCT (SQCT) methods for the H{sup +}+H{sub 2} and H{sup +}+D{sub 2} reactions at collision energies up to 1.2 eV and total angular momentum J=0-4. A marked resonance structure is found in the QM CRP, most especially for the H{sub 3}{sup +} system and J=0. When the CRPs are resolved in their ortho and para contributions, a clear steplike structure is found associated with the opening of internal states of reactants and products. The comparison of the QCT results with those of the other methods evinces the occurrence of two transition states, one at the entrance and one at the exit. At low J values, except for the quantal resonance structure and the lack of quantization in the product channel, the agreement between QM and QCT is very good. The SQCT model, that reflects the steplike structure associated with the opening of initial and final states accurately, clearly tends to overestimate the value of the CRP as the collision energy increases. This effect seems more marked for the H{sup +}+D{sub 2} isotopic variant. For sufficiently high J values, the growth of the centrifugal barrier leads to an increase in the threshold of the CRP. At these high J values the discrepancy between SQCT and QCT becomes larger and is magnified with growing collision energy. The total CRPs calculated with the QCT and SQCT methods allowed the determination of the rate constant for the H{sup +}+D{sub 2} reaction. It was found that the rate, in agreement with experiment, decreases with temperature as expected for an endothermic reaction. In the range of temperatures between 200 and 500 K the differences between SQCT and QCT rate results are relatively minor. Although exact QM calculations are formidable for an exact determination of the k(T), it can be reliably expected that their value will lie between those given by

  17. Time dependent quantum dynamics study of the O{sup +}+H{sub 2}(v=0,j=0){yields}OH{sup +}+H ion-molecule reaction and isotopic variants (D{sub 2},HD)

    SciTech Connect

    Martinez, Rodrigo; Sierra, Jose Daniel; Gray, Stephen K.; Gonzalez, Miguel

    2006-10-28

    The time dependent real wave packet method using the helicity decoupling approximation was used to calculate the cross section evolution with collision energy (excitation function) of the O{sup +}+H{sub 2}(v=0,j=0){yields}OH{sup +}+H reaction and its isotopic variants with D{sub 2} and HD, using the best available ab initio analytical potential energy surface. The comparison of the calculated excitation functions with exact quantum results and experimental data showed that the present quantum dynamics approach is a very useful tool for the study of the selected and related systems, in a quite wide collision energy interval (approximately 0.0-1.1 eV), involving a much lower computational cost than the quantum exact methods and without a significant loss of accuracy in the cross sections.

  18. Effect of alkyl chain length on the conformation and order of simple ionic surfactants adsorbed at the D{sub 2}O/CCl{sub 4} interface as studied by sum-frequency vibrational spectroscopy

    SciTech Connect

    Conboy, J.C.; Messmer, M.C.; Richmond, G.L.

    1998-11-10

    The conformational order of three alkanesulfonates, sodium hexanesulfonate (HS), sodium undecanesulfonate (UDS), and sodium dodecanesulfonate (DDS), adsorbed at the D{sub 2}O/CCl{sub 4} interface are examined in detail by sum-frequency vibrational spectroscopy. An increase in surfactant concentration at the interface results in the reduction of gauche defects in the hydrocarbon chains as determined from the intensity ratio of the methyl to methylene symmetric stretch vibrational modes. The degree of disorder in the alkyl chains varies greatly with alkyl chain length. The alkyl chain of HS displays the fewest gauche defects while DDS and UDS display more disorder in their hydrocarbon chains at similar surface concentrations. This observation is interpreted as a reduction in the possible number of gauche conformations for the shorter alkyl chain.

  19. Fragmentation of doubly charged HDO, H{sub 2}O, and D{sub 2}O molecules induced by proton and monocharged fluorine beam impact at 3 keV

    SciTech Connect

    Martin, S.; Chen, L.; Brédy, R.; Bernard, J.; Cassimi, A.

    2015-03-07

    Doubly charged ions HDO{sup 2+}, H{sub 2}O{sup 2+}, and D{sub 2}O{sup 2+} were prepared selectively to triplet or singlet excited states in collisions with F{sup +} or H{sup +} projectiles at 3 keV. Excitation energies of dications following two-body or three-body dissociation channels were measured and compared with recent calculations using ab initio multi-reference configuration interaction method [Gervais et al., J. Chem. Phys. 131, 024302 (2009)]. For HDO{sup 2+}, preferential cleavage of O–H rather than O–D bond has been observed and the ratio between the populations of the fragmentation channels OD{sup +}-H{sup +} and OH{sup +}-D{sup +} were measured. The kinetic energy release has been measured and compared with previous experiments.

  20. Serum concentrations of sIL-2R, IL-6, TGF-beta1, neopterin, and zinc in chronic hepatitis C patients treated with interferon-alpha.

    PubMed

    Grüngreiff, K; Reinhold, D; Ansorge, S

    1999-12-01

    T lymphocytes and immunoregulatory cytokines play an important role in the host response to hepatitis C virus (HCV) infection. Zinc is required for a wide spectrum of immune functions, including T-cell activity. To determine the clinical significance of the cytokines sIL-2R, IL-6, TGF-beta1, neopterin, and of zinc in chronic heptatitis C virus (HCV) infection, we investigated their concentrations in the serum of 16 patients with chronic HCV infection before, during and at the end of therapy with interferon (IFN) alpha (Roferon A), and after 6 months follow-up. Elevated concentrations of sIL-2R, IL-6, TGF-beta1, and neopterin were found in the serum of all patients prior to therapy, as compared to healthy controls. sIL-2R patterns differed in responders and non-responders. While the mean concentration of sIL-2R (335.75 pg/ml) before therapy was about 40% higher in complete responders (n=4) than in controls (272.20 pg/ml), the mean concentration in non-responders (n=6) was 4-fold higher than in controls (1153.33 pg/ml). During therapy, sIL-2R levels in responders decreased by about 40%. Mean IL-6 concentrations in both complete and partial responders (n=6) decreased continuously during treatment, while mean concentrations in non-responders decreased for only a short time, and increased again after cessation of therapy. Mean levels of TGF-beta1 behaved similarly to those of IL-6. Only negligible differences in mean neopterin levels were found between responders and non-responders over the entire observation time. The mean serum zinc concentrations slightly decreased in all 3 patient groups, the greatest reduction occurring in 3 of the 4 responders. The present findings underscore the importance of the immune system in the pathogenesis of chronic HCV infection. Serum sIL-2R levels may be used as a serological marker of outcome following IFN-alpha treatment. PMID:10623433

  1. Association Analysis of Bitter Receptor Genes in Five Isolated Populations Identifies a Significant Correlation between TAS2R43 Variants and Coffee Liking

    PubMed Central

    Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M.; Pistis, Giorgio; d’Adamo, Pio; Amin, Najaf; d’Eustacchio, Angela; Navarini, Luciano; Sala, Cinzia; Karssen, Lennart C.; van Duijn, Cornelia; Toniolo, Daniela; Gasparini, Paolo

    2014-01-01

    Coffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people’s health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 people from different parts of Europe and Central Asia filled in a field questionnaire on coffee liking. They have been consequently recruited and included in the study. Eighty-eight SNPs covering the 25 TAS2R genes were selected from the available imputed ones and used to run association analysis for coffee liking. A significant association was detected with three SNP: one synonymous and two functional variants (W35S and H212R) on the TAS2R43 gene. Both variants have been shown to greatly reduce in vitro protein activity. Surprisingly the wild type allele, which corresponds to the functional form of the protein, is associated to higher liking of coffee. Since the hTAS2R43 receptor is sensible to caffeine, we verified if the detected variants produced differences in caffeine bitter perception on a subsample of people coming from the FVG cohort. We found a significant association between differences in caffeine perception and the H212R variant but not with the W35S, which suggests that the effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. No other significant association was found with other TAS2R genes. In conclusion, the present study opens new perspectives in the understanding of coffee liking. Further studies are needed to clarify the role of the TAS2R43 gene in coffee hedonics and to identify which other genes and pathways are involved in its genetics. PMID:24647340

  2. Acute binge pattern cocaine administration induces region-specific effects in D1-r- and D2-r-expressing cells in eGFP transgenic mice.

    PubMed

    Lawhorn, C; Edusei, E; Zhou, Y; Ho, A; Kreek, M J

    2013-12-01

    Cocaine addiction is driven by genetic, neurologic and environmental components. The D1-like (D1 and D5) and D2-like (D2, D3 and D4) families of dopamine receptors play an important role in modulating the effects of cocaine administration on drug-seeking behavior. The advent of bacterial artificial chromosome-eGFP (enhanced green fluorescent protein) transgenic mice that express eGFP driven by the endogenous D1-receptor (D1-r) or D2-receptor (D2-r) promoters provides a unique opportunity to distinguish between these subpopulations of cells. In an effort to identify cocaine-induced alterations in D1-r- versus D2-r-expressing cells during the initial stages of addiction, we examined cells that expressed D1-rs in Drd1-eGFP mice, or D2-rs in Drd2-eGFP mice, after an acute, 1-day binge pattern of cocaine administration. We used multiphoton confocal microscopy and Visiopharm© software, to conduct unbiased stereological counts of D1-r-labeled or D2-r-labeled cells in various striatal regions. Mice were sacrificed at 30 min and 24-h post cocaine or saline administration. Compared to saline controls, Drd1-eGFP mice that received cocaine had a higher count of D1-r-labeled cells in the dorsolateral (DL) striatum, at the 30-min and 24-h time-points. No changes in the nucleus accumbens (NAc) core or shell were observed in Drd1-eGFP mice. Drd2-eGFP mice that received cocaine had fewer D2-r-labeled cells in the DL striatum and NAc core compared to saline controls. This effect was observed at the 30-min time-point but not at 24h. Drd2-eGFP mice that received cocaine also had fewer numbers of D2-r-labeled cells in the NAc core compared to saline controls, but no significant differences in the number of D2-r-labeled cells in the NAc shell. These results suggest that acute binge pattern cocaine administration may induce region-specific alterations in D1-r or D2-receptor gene expression, and may help elucidate the differential role of dopamine receptors in the initial stages of the

  3. Hydrogen-doping stabilized metallic VO{sub 2} (R) thin films and their application to suppress Fabry-Perot resonances in the terahertz regime

    SciTech Connect

    Zhao, Yong; Pan, Xuan; Bernussi, Ayrton A.; Fan, Zhaoyang; Karaoglan-Bebek, Gulten; Holtz, Mark

    2014-06-16

    We demonstrate that catalyst-assisted hydrogen spillover doping of VO{sub 2} thin films significantly alters the metal-insulator transition characteristics and stabilizes the metallic rutile phase at room temperature. With hydrogen inserted into the VO{sub 2} lattice, high resolution X-ray diffraction reveals expansion of the V-V chain separation when compared to the VO{sub 2}(R) phase. The donated free electrons, possibly from O-H bond formation, stabilize the VO{sub 2}(R) to low temperatures. By controlling the amount of dopants to obtain mixed insulating and metallic phases, VO{sub 2} resistivity can be continuously tuned until a critical condition is achieved that suppresses Fabry-Perot resonances. Our results demonstrate that hydrogen spillover is an effective technique to tune the electrical and optical properties of VO{sub 2} thin films.

  4. Some Advantages of SUSY SU(4)×SU(2)L×SU(2)R Model in String Inspired SO(10) Gut's

    NASA Astrophysics Data System (ADS)

    Murayama, Akihiro

    A D-parity violated SUSY SU(4)×SU(2)L×SU(2)R gauge model with the Higgs sector 2\\{(4, 1, 2) +({bar 4}, 1, 2)\\} +(1, 2, 2) + some (1, 1, 1)'s is shown to have the following advantages: (i) It is a very simple solution that satisfies MX=Mstring≈0.5 × 1018 GeV and MINT≈ 5 × 1011 GeV in superstring inspired SO(10) GUT's. (ii) The proton is stable by the automatic "doublet-triplet splitting" closely connected with the D-parity violation. (iii) The minimization of SUSY one-loop effective potential in a toy model suggests that the SO(10) gauge theory tends to break dynamically down to the SU(4)×SU(2)L×SU(2)R model.

  5. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.

    PubMed

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis. PMID:25986755

  6. Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation.

    PubMed

    Hafiz, Saly; Dennis, John C; Schwartz, Dean; Judd, Robert; Tao, Ya-Xiong; Khazal, Kamel; Akingbemi, Benson; Mo, Xiu-Lei; Abdel-Mageed, Asim B; Morrison, Edward; Mansour, Mahmoud

    2012-10-01

    The melanocortin receptors (MCRs 1-5) are G protein coupled-receptors (GPCRs) that regulate food intake, inflammation, skin pigmentation, sexual function and steroidogenesis. Their peptide ligands, the melanocortins, are α-, β- and γ-melanocyte-stimulating hormone and adrenocorticotropic hormone (ACTH) all of which are secreted from the anterior pituitary gland under hypothalamic control. MC2R binds ACTH but has no affinity for the other melanocortins and is, thereby, pharmacologically different from MCRs that bind those ligands. Evidence suggests that elevated GPCRs transactivate the androgen receptor (AR), the critical mediator of prostate cell growth, and consequently promote prostate cancer cell proliferation. It may be that reduced central melanocortin signaling is coincidental with reversal of prostate cancer cachexia, but no data are available on the expression of, or the role for, MCRs in prostate cancer. Here, we show that MCR (1-5) mRNAs are expressed in androgen-dependent LNCaP and androgen-independent PC3 and DU-145 human prostate cancer cell lines. Further, MC2R, the specific target of ACTH, is expressed in LNCaP, PC3 and DU-145 cells. Among the several synthetic MCR peptide ligands that we used, only ACTH promoted concentration-dependent cell proliferation in the three cell lines as shown by MTT cell proliferation assay. In LNCaP cells, the effect was additive with testosterone stimulation and was partially blunted with SHU9119, a non-selective MCR antagonist. In the same cells, ACTH induced cAMP production and increased AR nuclear labeling in immunocytochemical assays. Our observations suggest that MC2R is involved in prostate carcinogenesis and that targeting MC2R signaling may provide a novel avenue in prostate carcinoma treatment. PMID:22842514

  7. Sex-dependent changes in brain CB1R expression and functionality and immune CB2R expression as a consequence of maternal deprivation and adolescent cocaine exposure.

    PubMed

    Llorente-Berzal, Alvaro; Assis, María A; Rubino, Tiziana; Zamberletti, Erica; Marco, Eva M; Parolaro, Daniela; Ambrosio, Emilio; Viveros, María-Paz

    2013-08-01

    Early life stress has been associated with several psychiatric disorders, including drug addiction. Actually, maternal deprivation (MD) alters the endocannabinoid system, which participates in motivation and reward for drugs, including cocaine. At youth, the rate of cocaine abuse is alarmingly increasing. Herein, we have investigated the consequences of MD and/or adolescent cocaine exposure in brain CB1Rs and CB2Rs in immune tissues. Control and maternally deprived (24h on postnatal day, pnd, 9) male and female Wistar rats were administered cocaine (8mg/kg/day) or saline during adolescence (pnd 28-42). At adulthood, [(3)H]-CP-55,940 autoradiographic binding was employed for the analysis of CB1R density and CP-55,940-stimulated [(35)S]-GTPgammaS binding for CB1R functionality; CB2R expression was analyzed by Western blotting. Sex differences in CB1R expression and functionality were found, and MD induced important and enduring sex-dependent changes. In addition, the plastic changes induced by adolescent cocaine administration in brain CB1Rs were differentially influenced by early life events. MD increased spleen CB2R expression while adolescent cocaine administration attenuated this effect; cocaine exposure also diminished CB2R expression in bone marrow. Present findings provide evidence for changes in brain CB1R expression and functionality and immune CB2R expression as a consequence of early life stress and adolescent cocaine exposure, and indicate functional interactions between both treatments, which in many regions differ between males and females. PMID:23680694

  8. Regulatory SNPs and transcriptional factor binding sites in ADRBK1, AKT3, ATF3, DIO2, TBXA2R and VEGFA

    PubMed Central

    Buroker, Norman E

    2014-01-01

    Abstract Regulatory single nucleotide polymorphisms (rSNPs) which change the transcriptional factor binding sites (TFBS) for transcriptional factors (TFs) to bind DNA were reviewed for the ADRBK1 (GRK2), AKT3, ATF3, DIO2, TBXA2R and VEGFA genes. Changes in the TFBS where TFs attach to regulate these genes may result in human sickness and disease. The highlights of this previous work were reviewed for these genes. PMID:25483406

  9. Single-nucleotide polymorphisms in the PLA2R1 gene are associated with systemic lupus erythematosus and lupus nephritis in a Chinese Han population.

    PubMed

    Li, Yuan; Zhou, Aihong; Lv, Guanting; Li, Ping; Chen, Si; Li, Jing; Wen, Xiaoting; Wu, Ziyan; Zhang, Shulan; Wang, Jibo; Zhang, Fengchun; Li, Yongzhe

    2016-02-01

    Several novel susceptibility genes for systemic lupus erythematosus (SLE) and other nephropathy have been identified in recent genome-wide association studies. Membranous nephropathy is the most common diagnosis in adults with the nephrotic syndrome, and both idiopathic membranous nephropathy (IMN) and lupus nephritis (LN) are autoimmune diseases of the kidney; they may share common disease mechanisms that overlap with genetic susceptibility. Therefore, we sought to identify genetic variants associated with IMN in SLE/LN. The PLA2R1 single-nucleotide polymorphisms rs4664308, rs3828323, rs3792189, and rs3792192 were genotyped in a cohort of 1247 SLE patients and 1174 healthy controls, using the Sequenom MassArray system method. PLA2R1 displayed a nominally significantly genetic association with SLE [for rs4664308, P = 0.02, odds ratio (OR) 1.16, 95 % confidence interval (CI) 1.02-1.31; for rs3792192, P = 7.9 × 10(-3), OR 1.18, 95 % CI 1.05-1.34] and LN (for rs4664308, P = 0.04). The frequencies of genotypes of rs3792189 and rs3828323 were significantly different between the SLE patients and controls (all P < 0.05), and the haplotype (AA) formed by rs3792189 and rs3792192 was associated with SLE (P = 0.019). This was the first study to reveal that PLA2R1 polymorphisms were associated with SLE/LN patients, indicating that PLA2R1 might be a susceptibility gene for SLE/LN in a Chinese Han population. PMID:26645973

  10. FOXP2 promotes the nuclear translocation of POT1, but FOXP2(R553H), mutation related to speech-language disorder, partially prevents it

    SciTech Connect

    Tanabe, Yuko; Fujita, Eriko; Momoi, Takashi

    2011-07-08

    Highlights: {yields} We isolated protection of telomeres 1 (POT1) as a FOXP2-associated protein by a yeast two-hybrid. {yields} FOXP2 associated and co-localized with POT1 in the nuclei. {yields} FOXP2(R553H) also co-localized with POT1 in both the cytoplasm and nuclei. {yields} FOXP2(R553H) partially prevented the nuclear translocation of POT1. {yields} FOXP2(R553H) mutation may be associated with the pathogenesis of speech-language disorder. -- Abstract: FOXP2 is a forkhead box-containing transcription factor with several recognizable sequence motifs. However, little is known about the FOXP2-associated proteins except for C-terminal binding protein (CtBP). In the present study, we attempted to isolate the FOXP2-associated protein with a yeast two-hybrid system using the C-terminal region, including the forkhead domain, as a bait probe, and identified protection of telomeres 1 (POT1) as a FOXP2-associated protein. Immunoprecipitation assay confirmed the association with FOXP2 and POT1. POT1 alone localized in the cytoplasm but co-localized with FOXP2 and the forkhead domain of FOXP2 in nuclei. However, both FOXP2 with mutated nuclear localization signals and (R553H) mutated forkhead, which is associated with speech-language disorder, prevented the nuclear translocation of POT1. These results suggest that FOXP2 is a binding partner for the nuclear translocation of POT1. As loss of POT1 function induces the cell arrest, the impaired nuclear translocation of POT1 in the developing neuronal cells may be associated with the pathogenesis of speech-language disorder with FOXP2(R553H) mutation.

  11. Identification of transgenic cloned dairy goats harboring human lactoferrin and methylation status of the imprinted gene IGF2R in their lungs.

    PubMed

    Zhang, Y L; Zhang, G M; Wan, Y J; Jia, R X; Li, P Z; Han, L; Wang, F; Huang, M R

    2015-01-01

    Dairy goat is a good model for production of transgenic proteins in milk using somatic cell nuclear transfer (SCNT). However, animals produced from SCNT are often associated with lung deficiencies. We recently produced six transgenic cloned dairy goats harboring the human lactoferrin gene, including three live transgenic clones and three deceased transgenic clones that died from respiratory failure during the perinatal period. Imprinted genes are important regulators of lung growth, and may be subjected to faulty reprogramming. In the present study, first, microsatellite analysis, PCR, and DNA sequence identification were conducted to confirm that these three dead kids were genetically identical to the transgenic donor cells. Second, the CpG island methylation profile of the imprinted insulin-like growth factor receptor (IGF2R) gene was assessed in the lungs of the three dead transgenic kids and the normally produced kids using bisulfite sequencing PCR. In addition, the relative mRNA level of IGF2R was also determined by real-time PCR. Results showed that the IGF2R gene in the lungs of the dead cloned kids showed abnormal hypermethylation and higher mRNA expression levels than the control, indicating that aberrant DNA methylation reprogramming is one of the important factors in the death of transgenic cloned animals. PMID:26400340

  12. Function search in a large transcription factor gene family in Arabidopsis: assessing the potential of reverse genetics to identify insertional mutations in R2R3 MYB genes.

    PubMed Central

    Meissner, R C; Jin, H; Cominelli, E; Denekamp, M; Fuertes, A; Greco, R; Kranz, H D; Penfield, S; Petroni, K; Urzainqui, A; Martin, C; Paz-Ares, J; Smeekens, S; Tonelli, C; Weisshaar, B; Baumann, E; Klimyuk, V; Marillonnet, S; Patel, K; Speulman, E; Tissier, A F; Bouchez, D; Jones, J J; Pereira, A; Wisman, E

    1999-01-01

    More than 92 genes encoding MYB transcription factors of the R2R3 class have been described in Arabidopsis. The functions of a few members of this large gene family have been described, indicating important roles for R2R3 MYB transcription factors in the regulation of secondary metabolism, cell shape, and disease resistance, and in responses to growth regulators and stresses. For the majority of the genes in this family, however, little functional information is available. As the first step to characterizing these genes functionally, the sequences of >90 family members, and the map positions and expression profiles of >60 members, have been determined previously. An important second step in the functional analysis of the MYB family, through a process of reverse genetics that entails the isolation of insertion mutants, is described here. For this purpose, a variety of gene disruption resources has been used, including T-DNA-insertion populations and three distinct populations that harbor transposon insertions. We report the isolation of 47 insertions into 36 distinct MYB genes by screening a total of 73 genes. These defined insertion lines will provide the foundation for subsequent detailed functional analyses for the assignment of specific functions to individual members of the R2R3 MYB gene family. PMID:10521515

  13. Association study of polymorphisms in FOXO3, AKT1 and IGF-2R genes with human longevity in a Han Chinese population.

    PubMed

    Li, Ning; Luo, Huaichao; Liu, Xiaoqi; Ma, Shi; Lin, He; Chen, Rong; Hao, Fang; Zhang, Dingding

    2016-01-01

    FOXO3, AKT1 and IGF-2R are critical members of the insulin/IGF-1 signaling pathway. Previous studies showed that polymorphisms (SNPs) in FOXO3, AKT1 and IGF-2R were associated with human longevity in Caucasian population. However, the association of these SNPs in different ethnic groups is often inconsistent. Here, we investigated the association of genetic variants in three genes with human longevity in Han Chinese population. Twelve SNPs from FOXO3, AKT1 and IGF-2R were selected and genotyped in 1202 long-lived individuals (nonagenarians and centenarians) and younger individuals. Rs9486902 of FOXO3 was found to be associated with human longevity in both genders combined in this study (allelic P = 0.002, corrected P = 0.024). The other eleven SNPs were not significantly associated with human longevity in Han Chinese population. The haplotypes TTCTT, CCTTC and CTCCT of FOXO3 as well as GGTCGG and GGTCAG of AKT1 were shown to have a significant difference between case and control (P =0.006, 2.78×10-5, 4.68×10-6, 0.003,0.005, respectively). The estimated prevalence of diabetes and prediabetes in long-lived individuals was significantly lower than in common adult populations (P = 0.001, 2.3×10-26) .Therefore, the search for longevity-associated genes provides the identification of new potential targets beneficial for the treatment of diabetes. PMID:26683100

  14. The establishment of species-specific primers for the molecular identification of ten stored-product psocids based on ITS2 rDNA.

    PubMed

    Zhao, Zi-Hua; Cui, Bing-Yi; Li, Zhi-Hong; Jiang, Fan; Yang, Qian-Qian; Kučerová, Zuzana; Stejskal, Václav; Opit, George; Cao, Yang; Li, Fu-Jun

    2016-01-01

    Psocids are important stored product pests found worldwide that can be spread through grain trade. Most stored-product psocids, including eggs, nymphs, and adults, are very small (~1 mm) and difficult to identify morphologically. Here, we collected 10 economically important stored-product Liposcelis spp. psocids (L. bostrychophila, L. entomophila, L. decolor, L. paeta, L. brunnea, L. corrodens, L. mendax, L. rufa, L. pearmani, and L. tricolor) from 35 geographical locations in 5 countries (China, Czech Republic, Denmark, Germany, and the United States). The ITS2 rDNA gene was extracted and sequenced. The interspecific genetic distance of the stored-product psocids was significantly higher than the intraspecific genetic distance according to the barcoding gap analysis. Ten pairs of species-specific primers based on the ITS2 rDNA were developed for psocid identification. The sensitivity estimation indicated that the species-specific primers could correctly amplify the target ITS2 gene and successfully identify psocids at 1.0 ng/mL. Additionally, these species-specific primers could quantify specificity and identify 10 stored-product psocids; this approach could also be used to accurately identify other stored-product psocids. This work provides a practical approach for the precise examination of 10 stored-product psocid species and also contributes to the development of an identification method using ITS2 rDNA. PMID:26880378

  15. Optimization Method to Branch and Bound Large SBO State Spaces Under Dynamic Probabilistic Risk Assessment via use of LENDIT Scales and S2R2 Sets

    SciTech Connect

    Joseph W. Nielsen; Akira Tokurio; Robert Hiromoto; Jivan Khatry

    2014-06-01

    Traditional Probabilistic Risk Assessment (PRA) methods have been developed and are quite effective in evaluating risk associated with complex systems, but lack the capability to evaluate complex dynamic systems. These time and energy scales associated with the transient may vary as a function of transition time to a different physical state. Dynamic PRA (DPRA) methods provide a more rigorous analysis of complex dynamic systems, while complete, results in issues associated with combinatorial explosion. In order to address the combinatorial complexity arising from the number of possible state configurations and discretization of transition times, a characteristic scaling metric (LENDIT – length, energy, number, distribution, information and time) is proposed as a means to describe systems uniformly and thus provide means to describe relational constraints expected in the dynamics of a complex (coupled) systems. Thus when LENDIT is used to characterize four sets – ‘state, system, resource and response’ (S2R2) – describing reactor operations (normal and off-normal), LENDIT and S2R2 in combination have the potential to ‘branch and bound’ the state space investigated by DPRA. In this paper we introduce the concept of LENDIT scales and S2R2 sets applied to a branch-and-bound algorithm and apply the methods to a station black out transient (SBO).

  16. Lepton flavor violating decays of μ and τ leptons in a gauge group SU(2)L × SU(2)R × SU(2)Y

    NASA Astrophysics Data System (ADS)

    Fayyazuddin

    2016-06-01

    The electroweak unification group SU(2)L × SU(2)R × SU(2)Y is proposed for the charged lepton flavor violating decays of the muon (μ) and tau (τ) leptons. The group SU(2)Y is in the lepton space. The left-handed leptons and antileptons are assigned to the fundamental representation (2, 2,2¯) of the semi-simple group. The gauge group SU(2)Y is spontaneously broken to U(1)Y1, where Y1 = ‑L = ±1 is the hypercharge, by introducing a scalar multiplet Σ which belongs to the triplet representation 3 of the SU(2)Y and is singlet under SU(2)L × SU(2)R. At this stage charged vector bosons Y± of SU(2)Y which mediate the lepton flavor violating decays acquire masses and are decoupled with one Higgs scalar HΣ0. The residual group SU(2)L × SU(2)R × U(1)Y1 has all the features of the left-right electroweak unification group extensively studied in the literature. The probability for lepton flavor violating decays is sin2𝜃W 1‑2sin2𝜃W2 mWL mY4.

  17. Genome Sequencing and Transposon Mutagenesis of Burkholderia seminalis TC3.4.2R3 Identify Genes Contributing to Suppression of Orchid Necrosis Caused by B. gladioli.

    PubMed

    Araújo, Welington L; Creason, Allison L; Mano, Emy T; Camargo-Neves, Aline A; Minami, Sonia N; Chang, Jeff H; Loper, Joyce E

    2016-06-01

    From a screen of 36 plant-associated strains of Burkholderia spp., we identified 24 strains that suppressed leaf and pseudobulb necrosis of orchid caused by B. gladioli. To gain insights into the mechanisms of disease suppression, we generated a draft genome sequence from one suppressive strain, TC3.4.2R3. The genome is an estimated 7.67 megabases in size, with three replicons, two chromosomes, and the plasmid pC3. Using a combination of multilocus sequence analysis and phylogenomics, we identified TC3.4.2R3 as B. seminalis, a species within the Burkholderia cepacia complex that includes opportunistic human pathogens and environmental strains. We generated and screened a library of 3,840 transposon mutants of strain TC3.4.2R3 on orchid leaves to identify genes contributing to plant disease suppression. Twelve mutants deficient in suppression of leaf necrosis were selected and the transposon insertions were mapped to eight loci. One gene is in a wcb cluster that is related to synthesi