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Sample records for p1 n1 p2

  1. Evaluation excitation functions for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si, and "1"1"3In(n,γ)"1"1"4"mIn reactions

    International Nuclear Information System (INIS)

    Zolotarev, K.I.

    2014-10-01

    Cross section data for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions are needed for solving a wide spectrum of scientific and technical tasks. The excitation function of "2"8Si(n,p)"2"8Al reaction refers to the nuclear data involved in fusion reactor design calculations. The "2"8Si(n,p)"2"8Al reaction is interesting also as the monitor reaction for measurements at fusion facilities. Activation detectors on the basis of the 31P(n,p)31Si reaction are commonly used in the reactor dosimetry. The "1"1"3In(n,γ)"1"1"4"mIn reaction is promising regarding reactor dosimetry application for two reasons. First, due to the "1"1"4"mIn decay parameters which are rather suitable for activation measurements. Half-life of "1"1"4"mIn is equal to T_1/_2 = (49.51 ± 0.01) days and gamma spectrum accompanying decay has only one line with energy 190.27 keV and intensity (15.56 ± 0.15)%. Second, the "1"1"3In(n,γ)"1"1"4"mIn reaction rate may be measured by using one activation detector simultaneously with the "1"1"5In(n,γ)"1"1"6"mIn reaction. Preliminary analysis of existing evaluated excitation functions for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions show that new evaluations are needed for all above mentioned reactions. This report is devoted to the preparation of the new evaluations of cross sections data and related covariance matrixes of uncertainties for the "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions.

  2. An unusual methylene aziridine refined in P2(1)/c and the nonstandard setting P2(1)/n.

    Science.gov (United States)

    Feast, George C; Haestier, James; Page, Lee W; Robertson, Jeremy; Thompson, Amber L; Watkin, David J

    2009-12-01

    The unusual methylene aziridine 6-tert-butyl-3-oxa-2-thia-1-azabicyclo[5.1.0]oct-6-ene 2,2-dioxide, C(9)H(15)NO(3)S, was found to crystallize with two molecules in the asymmetric unit. The structure was solved in both the approximately orthogonal and the oblique settings of space group No. 14, viz. P2(1)/n and P2(1)/c, respectively. A comparison of these results clearly displayed an increase in the correlation between coordinates in the ac plane for the oblique cell. The increase in the corresponding covariances makes a significant contribution to the standard uncertainties of derived parameters, e.g. bond lengths. Since there is yet no CIF definition for the full variance-covariance matrix, there are clear advantages to reporting the structure in the nonstandard space-group setting.

  3. On the non-existence of orthogonal instanton bundles on P^{2n+1}

    Directory of Open Access Journals (Sweden)

    Łucja Farnik

    2009-11-01

    Full Text Available In this paper we prove that there do not exist orthogonal instanton bundles on P^{2n+1} . In order to demonstrate this fact, we propose a new way of representing the invariant, introduced by L. Costa and G. Ottaviani, related to a rank 2n instanton bundle on P^{2n+1}.

  4. 1/N expansions in P(phi2)sub(4-epsilon) theory. Pt. 1

    International Nuclear Information System (INIS)

    Symanzik, K.

    1977-01-01

    1/N expansions in O(N) invariant one-scale massless P(phi vector 2 )4-epsilon theory are derived for finite and infinite bare coupling constant. Since superficially relevant (phi vector 2 )sup(m), m >= 3, interactions can hereby be transformed into interactions irrelevant for large-distance behaviour, the scale-invariant limit theory is universal. (orig.) [de

  5. Study of TiO2(1 1 0)-p(1x1), p(1x2) and p(1x3) surface structures by impact collision ion scattering spectroscopy (ICISS)

    International Nuclear Information System (INIS)

    Asari, E.; Souda, R.

    2000-01-01

    The surface structure of TiO 2 (1 1 0)-p(1x1), p(1x2) and p(1x3) were studied using impact collision ion scattering spectroscopy (ICISS). We found that (i) the height of bridging oxygen for the p(1x1) is comparative to that of bulk structure, (ii) the p(1x2) surface has the added Ti 2 O 3 unit rows proposed by Onishi et al. and also the oxygen atoms rows between Ti 2 O 3 unit rows and (iii) the p(1x3) surface is constructed with the same added Ti 2 O 3 unit rows as that in the p(1x2) surface, but the bridging oxygen rows exist between the Ti 2 O 3 unit rows

  6. Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.

    Science.gov (United States)

    Harijith, Anantha; Pendyala, Srikanth; Ebenezer, David L; Ha, Alison W; Fu, Panfeng; Wang, Yue-Ting; Ma, Ke; Toth, Peter T; Berdyshev, Evgeny V; Kanteti, Prasad; Natarajan, Viswanathan

    2016-08-01

    Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1(-/-) mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47(phox) translocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2 in hyperoxia-mediated ROS generation. In addition, p47(phox) (phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2 in the activation of p47(phox) and production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice. Copyright © 2016 the American Physiological Society.

  7. Phase diagram of ZnCr2pA12-2pS(Se)4 and Zn1-pCdpCr2S(Se)4

    International Nuclear Information System (INIS)

    Afif, K.; Benyoussef, A.; Hamedoun, M.; Hourmatallah, A.

    1999-06-01

    We compute the phase diagram of the nonmetallic compounds ZnCr2 p A1 2-2p S(Se) 4 (I[S,Se]) and Zn 1-p Cd p Cr 2 S(Se) 4 (II[S,Se]). We consider the bond-diluted Ising model on the spinel B site (S.B.S.) lattice with competitive exchange interactions, i.e. the ferromagnetic exchange interaction J 1 between nearest neighbours (n.n.) and the antiferromagnetic superexchange interaction J 2 between next-nearest neighbours' (n.n.n.) (and/or the more distant superexchange interactions J i (i > 1). Dilution and competition are found to be responsible for the spill glass phase and the percolation behaviour. (author)

  8. Study of Stark Effect in n-doped 1.55 μm InN0.92yP1-1.92yBiy/InP MQWs

    Science.gov (United States)

    Bilel, C.; Chakir, K.; Rebey, A.; Alrowaili, Z. A.

    2018-05-01

    The effect of an applied electric field on electronic band structure and optical absorption properties of n-doped InN0.92y P1-1.92y Bi y /InP multiple quantum wells (MQWs) was theoretically studied using a self-consistent calculation combined with the 16-band anti-crossing model. The incorporation of N and Bi atoms into an InP host matrix leads to rapid reduction of the band gap energy covering a large infrared range. The optimization of the well parameters, such as the well/barrier widths, N/Bi compositions and doping density, allowed us to obtain InN0.92y P1-1.92y Bi y /InP MQWs operating at the wavelength 1.55 μm. Application of the electric field causes a red-shift of the fundamental transition energy T 1 accompanied by a significant change in the spatial distribution of confined electron density. The Stark effect on the absorption coefficient of n-doped InN0.92y P1-1.92y Bi y /InP MQWs was investigated. The Bi composition of these MQWs was adjusted for each electric field value in order to maintain the wavelength emission at 1.55 μm.

  9. Reduction of Aromatic and Heterocyclic Aromatic N-Hydroxylamines by Human Cytochrome P450 2S1

    Science.gov (United States)

    Wang, Kai; Guengerich, F. Peter

    2013-01-01

    Many aromatic amines and heterocyclic aromatic amines (HAAs) are known carcinogens for animals and there is also strong evidence for some in human cancer. The activation of these compounds, including some arylamine drugs, involves N-hydroxylation, usually by cytochrome P450 enzymes (P450) in Family 1 (1A2, 1A1, and 1B1). We previously demonstrated that the bioactivation product of the anti-cancer agent 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203), an N-hydroxylamine, can be reduced by P450 2S1 to its amine precursor under anaerobic conditions and, to a lesser extent, under aerobic conditions (Wang, K., and Guengerich, F. P. (2012) Chem. Res. Toxicol. 25, 1740–1751). In the present study, we tested the hypothesis that P450 2S1 is involved in the reductive biotransformation of known carcinogenic aromatic amines and HAAs. The N-hydroxylamines of 4-aminobiphenyl (4-ABP), 2-naphthylamine (2-NA), and 2-aminofluorene (2-AF) were synthesized and found to be reduced by P450 2S1 under both anaerobic and aerobic conditions. The formation of amines due to P450 2S1 reduction also occurred under aerobic conditions but was less apparent because the competitive disproportionation reactions (of the N-hydroxylamines) also yielded amines. Further, some nitroso and nitro derivatives of the arylamines could also be reduced by P450 2S1. None of the amines tested were oxidized by P450 2S1. These results suggest that P450 2S1 may be involved in the reductive detoxication of several of the activated products of carcinogenic aromatic amines and HAAs. PMID:23682735

  10. Excitation mechanisms of 2s1/2-2p3/2 and 2p1/2-2p3/2 transitions in U82+ through U89+

    International Nuclear Information System (INIS)

    Decaux, V.; Beiersdorfer, P.; Osterheld, A.

    1994-01-01

    A model based on detailed calculations of the electron-impact excitation of n = 2 electrons in the Li- to Ne-like uranium ions was developed to interpret and explain measurements on EBIT (Electron Beam Ion Trap). While only considering the direct excitation process provided a good model for the electric dipole (El) transitions, it was necessary for the magnetic dipole (Ml) spectrum to include various additional excitation processes in the model. In particular, the model was expanded to include electron-impact excitation of n = 3 levels followed by radiative cascades. Moreover, excitation by the ionization of 2s 1/2 , 2p 1/2 , and 2p 3/2 electrons and by radiative capture of beam electrons into excited levels was added. The new model demonstrates that the dipole-forbidden lines are almost exclusively produced by indirect excitation processes

  11. Study of the quasi-free scattering at the reaction 2H(p,2p)n at Esub(p)0 = 14.1 MeV

    International Nuclear Information System (INIS)

    Helten, H.J.

    1980-01-01

    The breakup reaction 2 H(p,2p)n was studied at Ep = 14.1 MeV in complete coincidence experiments on quasifree pp scattering in a systematic range of cinematic situations of the pp-subsystem for c.m. production angles between 90 0 and 140 0 and different violation of the quasifree condition as well on interferences with final-state interaction processes. The absolute differential breakup cross section was compared with approximate solutions of the Faddeev equations with separable s-wave potentials without explicite Coulomb interaction according to Ebenhoeh. The agreement is generally good referring to the form of the spectra, but the theoretical amplitude is in the mean 20% to high. The permanent independence of the quasifree breakup from the scattering parameter asub(pp) doesn't suggest to use this process for the determination of nn-scattering lengths from the mirror reaction 2 H(n,2n)p. (orig.)

  12. Neuropharmacology of Purinergic Receptors in Human Submucous Plexus: Involvement of P2X1, P2X2, P2X3 Channels, P2Y and A3 Metabotropic Receptors in Neurotransmission

    Science.gov (United States)

    Liñán-Rico, A.; Wunderlich, JE.; Enneking, JT.; Tso, DR.; Grants, I.; Williams, KC.; Otey, A.; Michel, K.; Schemann, M.; Needleman, B.; Harzman, A.; Christofi, FL.

    2015-01-01

    Rationale The role of purinergic signaling in the human ENS is not well understood. We sought to further characterize the neuropharmacology of purinergic receptors in human ENS and test the hypothesis that endogenous purines are critical regulators of neurotransmission. Experimental Approach LSCM-Fluo-4-(Ca2+)-imaging of postsynaptic Ca2+ transients (PSCaTs) was used as a reporter of neural activity. Synaptic transmission was evoked by fiber tract electrical stimulation in human SMP surgical preparations. Pharmacological analysis of purinergic signaling was done in 1,556 neurons from 234 separate ganglia 107 patients; immunochemical labeling for P2XRs of neurons in ganglia from 19 patients. Real-time MSORT (Di-8-ANEPPS) imaging was used to test effects of adenosine on fast excitatory synaptic potentials (fEPSPs). Results Synaptic transmission is sensitive to pharmacological manipulations that alter accumulation of extracellular purines. Apyrase blocks PSCaTs in a majority of neurons. An ecto-NTPDase-inhibitor 6-N,N-diethyl-D-β,γ-dibromomethyleneATP or adenosine deaminase augments PSCaTs. Blockade of reuptake/deamination of eADO inhibits PSCaTs. Adenosine inhibits fEPSPs and PSCaTs (IC50=25μM), sensitive to MRS1220-antagonism (A3AR). A P2Y agonist ADPβS inhibits PSCaTs (IC50=111nM) in neurons without stimulatory ADPβS responses (EC50=960nM). ATP or a P2X1,2,2/3 (α,β-MeATP) agonist evokes fast, slow, biphasic Ca2+ transients or Ca2+ oscillations (EC50=400μM). PSCaTs are sensitive to P2X1 antagonist NF279. Low (20nM) or high (5μM) concentrations of P2X antagonist TNP-ATP block PSCaTs in different neurons; proportions of neurons with P2XR-ir follow the order P2X2>P2X1P2X3; P2X1+ P2X2 and P2X3+P2X2 are co-localized. RT-PCR identified mRNA-transcripts for P2X1-7,P2Y1,2,12-14R. Responsive neurons were also identified by HuC/D-ir. Conclusions Purines are critical regulators of neurotransmission in the human enteric nervous system. Purinergic signaling involves

  13. Identification of 6H1 as a P2Y purinoceptor: P2Y5.

    Science.gov (United States)

    Webb, T E; Kaplan, M G; Barnard, E A

    1996-02-06

    We have determined the identity of the orphan G-protein coupled receptor cDNA, 6H1, present in activated chicken T cells, as a subtype of P2Y purinoceptor. This identification is based on first on the degree of sequence identity shared with recently cloned members of the P2Y receptor family and second on the pharmacological profile. Upon transient expression in COS-7 cells the 6H1 receptor bound the radiolabel [35S]dATP alpha S specifically and with high affinity (Kd, 10 nM). This specific binding could be competitively displaced by a range of ligands active at P2 purinoceptors, with ATP being the most active (K (i)), 116 nM). Such competition studies have established the following rank order of activity: ATP ADP 2-methylthioATP alpha, beta-methylene ATP, UTP, thus confirming 6H1 as a member of the growing family of P2Y purinoceptors. As the fifth receptor of this type to be identified we suggest that it be named P2Y5.

  14. Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells.

    Science.gov (United States)

    Völzke, Anja; Koch, Alexander; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2014-01-01

    Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases. © 2013.

  15. Interstitial deletion 1p as a result of a de novo reciprocal 1p;2p translocation

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Jensen, P H

    1985-01-01

    A 5-month-old female patient with psychomotor retardation and minor dysmorphisms is described. Cytogenetic analysis using high-resolution banding technique revealed an interstitial deletion of the short arm of one chromosome 1 (p21----p22.2) resulting from a de novo translocation t(1;2)(p22;p25)....

  16. P-n junction diodes with polarization induced p-type graded InxGa1-xN layer

    Science.gov (United States)

    Enatsu, Yuuki; Gupta, Chirag; Keller, Stacia; Nakamura, Shuji; Mishra, Umesh K.

    2017-10-01

    In this study, p-n junction diodes with polarization induced p-type layer are demonstrated on Ga polar (0001) bulk GaN substrates. A quasi-p-type region is obtained by linearly grading the indium composition in un-doped InxGa1-xN layers from 0% to 5%, taking advantage of the piezoelectric and spontaneous polarization fields which exist in group III-nitride heterostructures grown in the typical (0001) or c-direction. The un-doped graded InxGa1-xN layers needed to be capped with a thin Mg-doped InxGa1-xN layer to make good ohmic contacts and to reduce the on-resistance of the p-n diodes. The Pol-p-n junction diodes exhibited similar characteristics compared to reference samples with traditional p-GaN:Mg layers. A rise in breakdown voltage from 30 to 110 V was observed when the thickness of the graded InGaN layer was increased from 100 to 600 nm at the same grade composition.

  17. The deexcitation of the Ar (3P2, 3p1 and 1P1) states as measured by absorption both in pure argon and in the presence of additives

    International Nuclear Information System (INIS)

    Dutuit, Odile

    1974-01-01

    The de-excitation of the 3 P 2 , 3 p 1 and 1 P 1 states of argon was studied in pure argon between 10 and 200 torr and in Ar + CO and Ar + H 2 mixtures. These states are populated after excitation of the gas by a short (20 ns) pulse of 500 keV electrons (FEBETRON). Under our experimental conditions, the relation between the measured optical density of the lines studied and the concentration of absorbing species was found to be: DO = log I 0 /I ∝ (lC) n with n = 0,4. The three body rate constants k 2 were measured for the two resonant states 3 p 1 (k 2 = (1,65 ± 0,3) x 10 -32 cm 6 s -1 ) and 1 P 1 (k 2 = (1,0 ± 0,2) x 10 -32 cm 6 s -1 ); they had not been considered in previous low pressure studies. For the metastable state 3 P 2 , the measured value of k 2 ((1,6 ± 0,3) x 10 -32 cm 6 s -1 ) is in good agreement with those found in the literature. However, our two body rate constant k 1 is about ten times higher than that found in measurements at low pressure. This difference could be due to a collision-induced emission process at high pressure. The rate constants for the quenching by CO and H 2 were measured for the metastable state 3 P 2 (1,85 and 10,5 x 10 -11 cm 3 s -1 ) and for the resonant states 3 P 1 (4,5 and 20 x 10 -11 cm 3 s -1 ) and 1 P 1 (8,5 and 33 X 10 -11 cm 3 s -1 ). Comparison of the de-excitation cross sections of resonant and metastable states should lead to a better understanding of energy transfer processes from these latter. (author) [fr

  18. cis-[1,4-Bis(diphenylphosphanylbutane-κ2P,P′]dichlorido(cyclohexane-1,2-diamine-κ2N,N′ruthenium(II dichloromethane monosolvate

    Directory of Open Access Journals (Sweden)

    Ismail Warad

    2012-05-01

    Full Text Available In the title compound, [RuCl2(C6H14N2(C28H28P2]·CH2Cl2, the RuII ion is coordinated in a slightly distorted octahedral environment, formed by two cis-oriented chloride ligands, two cis P atoms of a 1,4-bis(diphenylphosphanylbutane ligand and two cis-chelating N atoms of a bidentate cyclohexane-1,2-diamine ligand. In the crystal, pairs of molecules form inversion dimers via N—H...Cl hydrogen bonds. In addition, intramolecular N—H...Cl and weak C—H...Cl, C—H...N, N—H...π and C—H...π hydrogen bonds are observed. One of the Cl atoms of the solvent molecule is disordered over two sites with refined occupancies of 0.62 (1 and 0.38 (1.

  19. Astrophysical s-factor measurements for {sup 1}20Te(p,{gamma}){sup 1}21I and {sup 1}20Te(p,n){sup 1}20I reactions; {sup 1}20Te(p,{gamma}){sup 1}21I ve {sup 1}20Te(p,n){sup 1}20I reaksiyonlarinin astrofiziksel s-factor oelcuemleri

    Energy Technology Data Exchange (ETDEWEB)

    Gueray, R T; Oezkan, N; Yalcin, C [Kocaeli University, Kocaeli (Turkey); Goerres, J; DeBoer, R; Palumbo, A; Tan, W P; Wiescher, M [University of Notre Dame, (United States); Fueloep, Zs; Somorjai, E [Institute of Nuclear Research ATOMKI (Hungary); Lee, H Y [Argonne National Laboratory (United States)

    2009-07-01

    Astrophysical S-factors for the {sup 1}20Te(p,{gamma}){sup 1}21I and {sup 1}20Te(p,n){sup 1}20I reactions have been measured in the effective center-of-mass energies between 2.47 MeV and 7.93 MeV. Experimental data have been compared with the Hauser-Fesbach statistical model calculations obtained with the model codes NON-SMOKER and TALYS. The discrepancies between the experimental results and calculations can mainly be attributed to the optical model potentials used in the codes.

  20. Electron impact excitation-autoionisation of the (2s2)1S, (2p2)1D and (2s2p)1P autoionising states of helium

    International Nuclear Information System (INIS)

    Samardzic, O.; Hurn, J.A.; Weigold, E.; Brunger, M.J.

    1994-01-01

    The electron impact excitation of the (2s 2 ) 1 S, (2p 2 ) 1 D and (2s2p) 1 P autoionising states of helium and their subsequent radiationless decay was studied by observation of the ejected electrons. The present work was carried out at an incident energy of 94.6 eV and for ejected electron scattering angles in the range 25-135 deg C. The lineshapes observed in the present ejected electron spectra are analysed using the Shore-Balashov parametrisation. As part of the analysis procedure, numerically rigorous confidence limits were determined for the derived parameters. No previous experimental or theoretical work has been undertaken at the incident energy of the present investigation but, where possible, the resulting parameters are qualitatively compared against the 80 eV results of other experiments and theory. 37 refs., 4 figs

  1. An interesting charmonium state formation and decay: p p-bar → 1 D21 P1γ

    International Nuclear Information System (INIS)

    Anselmino, M.; Caruso, F.; Universidade do Estado, Rio de Janeiro, RJ; Murgia, F.; Negrao, M.R.

    1994-01-01

    Massless perturbative QCD forbids, at leading order, the exclusive annihilation of proton-antiproton into some charmonium states, which however, have been observed in the pp channel, indicating the significance of higher order and non perturbative effects in the few GeV energy region. The most well known cases are those of the 1 S 0 (η c ) and the 1 P 1 . The case of the 1 D 2 is considered here and a way of detecting such a state through its typical angular distribution in the radiative decay 1 D 2 -> 1 D 2 -> 1 P 1 γ is suggested. Estimates of the branching ratio BR( 1 D 2 ->pp), as given by a quark-diquark model of the nucleon, mass corrections and an instanton induced process are presented. (author). 15 refs

  2. Bis{2-[(diisopropylphosphanylamino]pyridine-κ2N1,P}copper(I hexafluoridophosphate

    Directory of Open Access Journals (Sweden)

    Özgür Öztopcu

    2010-07-01

    Full Text Available The crystal structure of the title compound, [Cu(C11H19N2P2]PF6, is composed of discrete [Cu(PN-iPr2]+ cations [PN-iPr is 2-(diisopropylphosphanylaminopyridine] and PF6− anions. The Cu(I atom is bis-chelated by two independent PN-iPr ligands. It has a distorted tetrahedral coordination by two P atoms [Cu—P = 2.2277 (4 and 2.2257 (4 Å] and two pyridine N atoms [Cu—N = 2.0763 (11 and 2.0845 (12 Å]. Bond angles about Cu vary from 85.11 (3 (P—Cu—N to 130.37 (2° (P—Cu—P. In the crystal, N—H...F hydrogen bonds link the Cu complexes and the PF6− anions into continuous chains, which show a cross-bedded spatial arrangement. In addition, several weaker C—H...F interactions contribute to the coherence of the structure.

  3. Superconductivity and fluctuations in Ba_1_–_pK_pFe_2As_2 and Ba(Fe_1_–_nCo_n)_2As_2

    International Nuclear Information System (INIS)

    Böhm, T.; Hosseinian Ahangharnejhad, R.; Technical University of Munich, Garching

    2016-01-01

    In this paper, we study the interplay of fluctuations and superconductivity in BaFe_2As_2 (Ba-122) compounds with Ba and Fe substituted by K (p doping) and Co (n doping), respectively. To this end, we measured electronic Raman spectra as a function of polarization and temperature. We observe gap excitations and fluctuations for all doping levels studied. The response from fluctuations is much stronger for Co substitution and, according to the selection rules and the temperature dependence, originates from the exchange of two critical spin fluctuations with characteristic wave vectors (±π,0) and (0,±π). At 22% K doping (p = 0.22), we find the same selection rules and spectral shape for the fluctuations but the intensity is smaller by a factor of 5. Since there exists no nematic region above the orthorhombic spin-density-wave (SDW) phase, the identification of the fluctuations via the temperature dependence is not possible. The gap excitations in the superconducting state indicate strongly anisotropic near-nodal gaps for Co substitution which make the observation of collective modes difficult. The variation with doping of the spectral weights of the A_1_g and B_1_g gap features does not support the influence of fluctuations on Cooper pairing. Thus, the observation of Bardasis–Schrieffer modes inside the nearly clean gaps on the K-doped side remains the only experimental evidence for the relevance of fluctuations for pairing.

  4. A de-novo interstitial microduplication involving 2p16.1-p15 and mirroring 2p16.1-p15 microdeletion syndrome: Clinical and molecular analysis.

    Science.gov (United States)

    Mimouni-Bloch, Aviva; Yeshaya, Josepha; Kahana, Sarit; Maya, Idit; Basel-Vanagaite, Lina

    2015-11-01

    Microdeletions of various sizes in the 2p16.1-p15 chromosomal region have been grouped together under the 2p16.1-p15 microdeletion syndrome. Children with this syndrome generally share certain features including microcephaly, developmental delay, facial dysmorphism, urogenital and skeletal abnormalities. We present a child with a de-novo interstitial 1665 kb duplication of 2p16.1-p15. Clinical features of this child are distinct from those of children with the 2p16.1-p15 microdeletion syndrome, specifically the head circumference which is within the normal range and mild intellectual disability with absence of autistic behaviors. Microduplications many times bear milder clinical phenotypes in comparison with corresponding microdeletion syndromes. Indeed, as compared to the microdeletion syndrome patients, the 2p16.1-p15 microduplication seems to have a milder cognitive effect and no effect on other body systems. Limited information available in genetic databases about cases with overlapping duplications indicates that they all have abnormal developmental phenotypes. The involvement of genes in this location including BCL11A, USP34 and PEX13, affecting fundamental developmental processes both within and outside the nervous system may explain the clinical features of the individual described in this report. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  5. Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Arun K.; Sean Fyvie, W.; Brindisi, Margherita; Steffey, Melinda; Agniswamy, Johnson; Wang, Yuan-Fang; Aoki, Manabu; Amano, Masayuki; Weber, Irene T.; Mitsuya, Hiroaki

    2017-11-01

    Design, synthesis, and evaluation of a new class of HIV-1 protease inhibitors containing diverse flexible macrocyclic P1'-P2' tethers are reported. Inhibitor 5a with a pyrrolidinone-derived macrocycle exhibited favorable enzyme inhibitory and antiviral activity (Ki = 13.2 nM, IC50 = 22 nM). Further incorporation of heteroatoms in the macrocyclic skeleton provided macrocyclic inhibitors 5m and 5o. These compounds showed excellent HIV-1 protease inhibitory (Ki = 62 pM and 14 pM, respectively) and antiviral activity (IC50 = 5.3 nM and 2.0 nM, respectively). Inhibitor 5o also remained highly potent against a DRV-resistant HIV-1 variant.

  6. Tables of Shore and Fano parameters for the helium resonances 2s/sup 2/ /sup 1/S, 2p/sup 2/ /sup 1/D, and 2s 2p /sup 1/P excited in p-He collisions E/sub p/ = 33 to 150 keV

    Energy Technology Data Exchange (ETDEWEB)

    Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Merchez, H.

    1976-02-01

    Absolute values of Shore and Fano parameters are tabulated for the helium atom 2s/sup 2/ /sup 1/S, 2p/sup 2/ /sup 1/D, and 2s 2p /sup 1/P resonances produced by a proton beam. Observations were made on the spectra of ejected electrons. The important variation of the shape of the resonances with ejection angle is illustrated for E/sub p/ = 100 keV; the variation with proton energy is shown at 30/sup 0/.

  7. Observation of the hadronic transitions χb1,2(2P)→ωΥ(1S)

    International Nuclear Information System (INIS)

    Cronin-Hennessy, D.; Park, C.S.; Park, W.; Thayer, J.B.; Thorndike, E.H.; Coan, T.E.; Gao, Y.S.; Liu, F.; Stroynowski, R.; Artuso, M.; Boulahouache, C.; Blusk, S.; Dambasuren, E.; Dorjkhaidav, O.; Mountain, R.; Muramatsu, H.; Nandakumar, R.; Skwarnicki, T.; Stone, S.; Wang, J.C.

    2004-01-01

    The CLEO Collaboration has made the first observations of hadronic transitions among bottomonium (bb-bar) states other than the dipion transitions among Υ(nS) states. In our study of Υ(3S) decays, we find a significant signal for Υ(3S)→γωΥ(1S) that is consistent with radiative decays Υ(3S)→γχ b1,2 (2P), followed by χ b1,2 (2P)→ωΥ(1S). The branching ratios we obtain are B[χ b1 (2P)→ωΥ(1S)]=(1.63 -0.31-0.15 +0.35+0.16 )% and B[χ b2 (2P)→ωΥ(1S)]=(1.10 -0.28-0.10 +0.32+0.11 )%, in which the first error is statistical and the second is systematic.

  8. Importance of sequential two-step transfer process in a ΔS = 1 and ΔT = 1 inelastic transition of 14N(p, p')14N reaction

    International Nuclear Information System (INIS)

    Aoki, Y.; Kunori, S.; Nagano, K.; Toba, Y.; Yagi, K.

    1981-01-01

    Differential cross sections and vector analyzing powers for 14 N(p, p') and 14 N(p, d) reactions have been measured at E sub(p) = 21.0 MeV to elucidate the reaction mechanism and the effective interaction for the ΔS = ΔT = 1 transition in 14 N(p, p') 14 N(2.31 MeV) reaction. The data are analyzed in terms of finite-range distorted wave Borm approximation (DWBA) which include direct, knock-on exchange and (p, d)(d, p') two-step processes. Shell model wave functions of Cohen and Kurath are used. The data for the first excited state is reasonably well explained by introducing two-step process. The two-step process explains half of the experimental intensity. Moreover vector analyzing power can hardly be explained without introducing this two-step process. Vector analyzing power of protons leading to the second excited state in 14 N is better explained by introducing macroscopic calculation. The data for 14 N(p, d) 13 N(gs) reaction are well explained by a suitable choice of deuteron optical potential. Knock-on exchange contribution is relatively small. Importance of this two-step process for ΔS = ΔT = 1 transition is discussed up to 40 MeV. (author)

  9. Closed expressions for $\\int_{0}^{1} t^{-1} log^{n-1}t log^{p}(1 - t) dt$

    CERN Document Server

    Kölbig, Kurt Siegfried

    1982-01-01

    Closed expressions for the integral integral /sub 0//sup 1/ t/sup -1/ log/sup n-1/t log/sup p/(1-t)dt, whose general form is given elsewhere, are listed for n=1(1)9, p=1(1)9. A formula is derived which allows an easy evaluation of these expressions by formula manipulation on a computer. The majority of the above expressions are given in a microfiche supplement to the paper.

  10. Determination of the 1s2{\\ell }2{{\\ell }}^{\\prime } state production ratios {{}^{4}P}^{o}/{}^{2}P, {}^{2}D/{}^{2}P and {{}^{2}P}_{+}/{{}^{2}P}_{-} from fast (1{s}^{2},1s2s\\,{}^{3}S) mixed-state He-like ion beams in collisions with H2 targets

    Science.gov (United States)

    Benis, E. P.; Zouros, T. J. M.

    2016-12-01

    New results are presented on the ratio {R}m={σ }{T2p}( {}4P)/{σ }{T2p}({}2P) concerning the production cross sections of Li-like 1s2s2p quartet and doublet P states formed in energetic ion-atom collisions by single 2p electron transfer to the metastable 1s2s {}3S component of the He-like ion beam. Spin statistics predict a value of R m = 2 independent of the collision system in disagreement with most reported measurements of {R}m≃ 1{--}9. A new experimental approach is presented for the evaluation of R m having some practical advantages over earlier approaches. It also allows for the determination of the separate contributions of ground- and metastable-state beam components to the measured spectra. Applying our technique to zero-degree Auger projectile spectra from 4.5 MeV {{{B}}}3+ (Benis et al 2002 Phys. Rev. A 65 064701) and 25.3 MeV {{{F}}}7+ (Zamkov et al 2002 Phys. Rev. A 65 062706) mixed state (1{s}2 {}1S,1s2s {}3S) He-like ion collisions with H2 targets, we report new values of {R}m=3.5+/- 0.4 for boron and {R}m=1.8+/- 0.3 for fluorine. In addition, the ratios of {}2D/{}2P and {{}2P}+/{{}2P}- populations from either the metastable and/or ground state beam component, also relevant to this analysis, are evaluated and compared to previously reported results for carbon collisions on helium (Strohschein et al 2008 Phys. Rev. A 77 022706) including a critical comparison to theory.

  11. Measurement of the $\\chi_b(3P)$ mass and of the relative rate of $\\chi_{b1}(1P)$ and $\\chi_{b2}(1P)$ production

    CERN Document Server

    Aaij, Roel; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassen, Rolf; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Belogurov, Sergey; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Bjørnstad, Pål Marius; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borgia, Alessandra; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Brambach, Tobias; van den Brand, Johannes; Bressieux, Joël; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Brown, Henry; Bursche, Albert; Busetto, Giovanni; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Ciba, Krzystof; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cojocariu, Lucian; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Counts, Ian; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pascal; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Di Canto, Angelo; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gavrilov, Gennadii; Geraci, Angelo; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Gianì, Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Hunt, Philip; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jaton, Pierre; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kelsey, Matthew; Kenyon, Ian; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kozlinskiy, Alexandr; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leo, Sabato; Leroy, Olivier; Lesiak, Tadeusz; Lespinasse, Mickael; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lopez-March, Neus; Lowdon, Peter; Lu, Haiting; Lucchesi, Donatella; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Machikhiliyan, Irina V; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martens, Aurelien; Martín Sánchez, Alexandra; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathe, Zoltan; Matteuzzi, Clara; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; McSkelly, Ben; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Moggi, Niccolò; Molina Rodriguez, Josue; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Katharina; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Nicol, Michelle; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Oggero, Serena; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Orlandea, Marius; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Arantza; Pal, Bilas Kanti; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parkes, Christopher; Parkinson, Christopher John; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Perrin-Terrin, Mathieu; Pescatore, Luca; Pesen, Erhan; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Poluektov, Anton; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Roa Romero, Diego; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz, Hugo; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Sparkes, Ailsa; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Subbiah, Vijay Kartik; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ubeda Garcia, Mario; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Whitehead, Mark; Wicht, Jean; Wiedner, Dirk; Wilkinson, Guy; Williams, Matthew; Williams, Mike; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wu, Suzhi; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Wen Chao; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zvyagin, Alexander

    2014-10-14

    The production of $\\chi_b$ mesons in proton-proton collisions is studied using a data sample collected by the LHCb detector, at centre-of-mass energies of $\\sqrt{s}=7$ and $8$ TeV and corresponding to an integrated luminosity of 3.0 fb$^{-1}$. The $\\chi_b$ mesons are identified through their decays to $\\Upsilon(1S)\\gamma$ and $\\Upsilon(2S)\\gamma$ using photons that converted to $e^+e^-$ pairs in the detector. The $\\chi_b(3P)$ meson mass, and the relative prompt production rate of $\\chi_{b1}(1P)$ and $\\chi_{b2}(1P)$ mesons as a function of the $\\Upsilon(1S)$ transverse momentum in the $\\chi_b$ rapidity range 2.0< $y$<4.5, are measured. Assuming a mass splitting between the $\\chi_{b1}(3P)$ and the $\\chi_{b2}(3P)$ states of 10.5 MeV/$c^2$, the mass of the $\\chi_{b1}(3P)$ meson is \\begin{equation*} m(\\chi_{b1}(3P))= 10515.7^{+2.2}_{-3.9}(stat) ^{+1.5}_{-2.1}(syst) MeV/c^2. \\end{equation*}

  12. Study of the rearrangement of N-alkylaniline to p-aminoalkylbencene. I. N-ethyl-l-{sup 1}4C-aniline; Estudio de la transposicion de N-alquilanilinas A p-Aminoalquilbenceno mediante {sup 1}4C

    Energy Technology Data Exchange (ETDEWEB)

    Molera, M J; Gamboa, J M; Val Cob, M del

    1961-07-01

    The rearrangement of N-ethylaniline to p-aminoethylbenzene has been studied over the temperature range 200-300 degree centigrade using different catalysts: Cl{sub 2}Co, Cl{sub 2}Zn, Cl{sub 2}Ni, Cl{sub 3}Al, Cl{sub 2}Cd and Br H.N-ethyl-1-{sup 1}4C-aniline has been synthesized from ethyl-1-{sup 1}4C-iodide and aniline and its rearrangement to p-aminoethyl-benzene proves that the ethyl group does not rearrange itself during the reaction. A scheme for the degradation of both the N-ethyl-1-{sup 1}4C aniline and the p-aminoethylbenzene produces is described. (Author) 14 refs.

  13. [μ-1,2-Bis(diphenylphosphinoethane-κ2P:P′]bis{[1,2-bis(diphenylphosphinoethane-κ2P,P′]cyanidocopper(I} methanol disolvate

    Directory of Open Access Journals (Sweden)

    Rong Wang

    2010-08-01

    Full Text Available The title centrosymmetric complex, [Cu2(CN2(C26H24P23]·2CH3OH, consists of two five-membered [Cu(dppeCN] rings [dppe is 1,2-bis(diphenylphosphinoethane] bridged by one μ2-dppe ligand, and two methanol solvent molecules. The angles around the central metal atom indicate that each CuI atom is located in the center of a distorted tetrahedron. The coordination sphere of each CuI atom is formed by three P atoms from two dppe ligands, and one C atom from the cyanide ligand. The crystal structure is stabilized by O—H...N hydrogen bonds, which are formed by the O—H donor group from methanol and the N-atom acceptor from a cyanide ligand.

  14. Saccharomyces cerevisiae GTPase complex: Gtr1p-Gtr2p regulates cell-proliferation through Saccharomyces cerevisiae Ran-binding protein, Yrb2p

    International Nuclear Information System (INIS)

    Wang Yonggang; Nakashima, Nobutaka; Sekiguchi, Takeshi; Nishimoto, Takeharu

    2005-01-01

    A Gtr1p GTPase, the GDP mutant of which suppresses both temperature-sensitive mutants of Saccharomyces cerevisiae RanGEF/Prp20p and RanGAP/Rna1p, was presently found to interact with Yrb2p, the S. cerevisiae homologue of mammalian Ran-binding protein 3. Gtr1p bound the Ran-binding domain of Yrb2p. In contrast, Gtr2p, a partner of Gtr1p, did not bind Yrb2p, although it bound Gtr1p. A triple mutant: yrb2Δ gtr1Δ gtr2Δ was lethal, while a double mutant: gtr1Δ gtr2Δ survived well, indicating that Yrb2p protected cells from the killing effect of gtr1Δ gtr2Δ. Recombinant Gtr1p and Gtr2p were purified as a complex from Escherichia coli. The resulting Gtr1p-Gtr2p complex was comprised of an equal amount of Gtr1p and Gtr2p, which inhibited the Rna1p/Yrb2 dependent RanGAP activity. Thus, the Gtr1p-Gtr2p cycle was suggested to regulate the Ran cycle through Yrb2p

  15. pOsNAR2.1:OsNAR2.1 expression enhances nitrogen uptake efficiency and grain yield in transgenic rice plants.

    Science.gov (United States)

    Chen, Jingguang; Fan, Xiaoru; Qian, Kaiyun; Zhang, Yong; Song, Miaoquan; Liu, Yu; Xu, Guohua; Fan, Xiaorong

    2017-10-01

    The nitrate (NO3-) transporter has been selected as an important gene maker in the process of environmental adoption in rice cultivars. In this work, we transferred another native OsNAR2.1 promoter with driving OsNAR2.1 gene into rice plants. The transgenic lines with exogenous pOsNAR2.1:OsNAR2.1 constructs showed enhanced OsNAR2.1 expression level, compared with wild type (WT), and 15 N influx in roots increased 21%-32% in response to 0.2 mm and 2.5 mm 15NO3- and 1.25 mm 15 NH 4 15 NO 3 . Under these three N conditions, the biomass of the pOsNAR2.1:OsNAR2.1 transgenic lines increased 143%, 129% and 51%, and total N content increased 161%, 242% and 69%, respectively, compared to WT. Furthermore in field experiments we found the grain yield, agricultural nitrogen use efficiency (ANUE), and dry matter transfer of pOsNAR2.1:OsNAR2.1 plants increased by about 21%, 22% and 21%, compared to WT. We also compared the phenotypes of pOsNAR2.1:OsNAR2.1 and pOsNAR2.1:OsNRT2.1 transgenic lines in the field, found that postanthesis N uptake differed significantly between them, and in comparison with the WT. Postanthesis N uptake (PANU) increased approximately 39% and 85%, in the pOsNAR2.1:OsNAR2.1 and pOsNAR2.1:OsNRT2.1 transgenic lines, respectively, possibly because OsNRT2.1 expression was less in the pOsNAR2.1:OsNAR2.1 lines than in the pOsNAR2.1:OsNRT2.1 lines during the late growth stage. These results show that rice NO 3 - uptake, yield and NUE were improved by increased OsNAR2.1 expression via its native promoter. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  16. Effects of background noise on inter-trial phase coherence and auditory N1-P2 responses to speech stimuli.

    Science.gov (United States)

    Koerner, Tess K; Zhang, Yang

    2015-10-01

    This study investigated the effects of a speech-babble background noise on inter-trial phase coherence (ITPC, also referred to as phase locking value (PLV)) and auditory event-related responses (AERP) to speech sounds. Specifically, we analyzed EEG data from 11 normal hearing subjects to examine whether ITPC can predict noise-induced variations in the obligatory N1-P2 complex response. N1-P2 amplitude and latency data were obtained for the /bu/syllable in quiet and noise listening conditions. ITPC data in delta, theta, and alpha frequency bands were calculated for the N1-P2 responses in the two passive listening conditions. Consistent with previous studies, background noise produced significant amplitude reduction and latency increase in N1 and P2, which were accompanied by significant ITPC decreases in all the three frequency bands. Correlation analyses further revealed that variations in ITPC were able to predict the amplitude and latency variations in N1-P2. The results suggest that trial-by-trial analysis of cortical neural synchrony is a valuable tool in understanding the modulatory effects of background noise on AERP measures. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. P2X1 receptors and the endothelium

    Directory of Open Access Journals (Sweden)

    LS Harrington

    2005-03-01

    Full Text Available Adenosine triphosphate (ATP is now established as a principle vaso-active mediator in the vasculature. Its actions on arteries are complex, and are mediated by the P2X and P2Y receptor families. It is generally accepted that ATP induces a bi-phasic response in arteries, inducing contraction via the P2X and P2Y receptors on the smooth muscle cells, and vasodilation via the actions of P2Y receptors located on the endothelium. However, a number of recent studies have placed P2X1 receptors on the endothelium of some arteries. The use of a specific P2X1 receptor ligand, a, b methylene ATP has demonstrated that P2X1 receptors also have a bi-functional role. The actions of ATP on P2X1 receptors is therefore dependant on its location, inducing contraction when located on the smooth muscle cells, and dilation when expressed on the endothelium, comparable to that of P2Y receptors.

  18. p21(Waf1/Cip1) expression and the p53/MDM2 feedback loop in gastric carcinogenesis

    NARCIS (Netherlands)

    Craanen, M. E.; Blok, P.; Offerhaus, G. J.; Meijer, G. A.; Dekker, W.; Kuipers, E. J.; Meuwissen, S. G.

    1999-01-01

    Data are non-existent regarding coincidental alterations in the expression of p53 and its downstream target genes MDM2 and p21(Waf1/Cip1) in gastric carcinogenesis. An immunohistochemical study was therefore performed to examine the interrelationships of p53, MDM2, and p21(Waf1/Cip1) expression in a

  19. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

    Science.gov (United States)

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-08-26

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

  20. Radiative lifetimes of the 2s2p2(4P) metastable levels of N III

    Science.gov (United States)

    Fang, Z.; Kwong, Victor H. S.; Parkinson, W. H.

    1993-01-01

    The radiative decay rates of N III 175 nm intersystem lines were measured in the laboratory by recording the time dependence of photon intensities emitted as the 2s2p2(4P) metastable term of N(2+) ions decay to the 2s22p(2P0) ground term. A cylindrical radio frequency ion trap was used to store the electron impact-produced N(2+) ions. The radiative decay signals were analyzed by multiexponential least-squares fits to the data. The measured radiative decay rates to the ground term are 1019(+/- 64)/s for 4P sub 1/2, 74.5(+/- 5.4)/s for 4P sub 3/2, and 308( +/- 22)/s for 4P sub 5/2. Comparisons of the measured values with theoretical values are presented.

  1. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors.

    Science.gov (United States)

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E; O'Carroll, Simon J; Graham, E Scott

    2016-01-27

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors.

  2. Controlling interface oxygen for forming Ag ohmic contact to semi-polar (1 1 -2 2) plane p-type GaN

    Science.gov (United States)

    Park, Jae-Seong; Han, Jaecheon; Seong, Tae-Yeon

    2014-11-01

    Low-resistance Ag ohmic contacts to semi-polar (1 1 -2 2) p-GaN were developed by controlling interfacial oxide using a Zn layer. The 300 °C-annealed Zn/Ag samples showed ohmic behavior with a contact resistivity of 6.0 × 10-4 Ω cm2 better than that of Ag-only contacts (1.0 × 10-3 Ω cm2). The X-ray photoemission spectroscopy (XPS) results showed that annealing caused the indiffusion of oxygen at the contact/GaN interface, resulting in the formation of different types of interfacial oxides, viz. Ga-oxide and Ga-doped ZnO. Based on the XPS and electrical results, the possible mechanisms underlying the improved electrical properties of the Zn/Ag samples are discussed.

  3. Quenching of I(2P1/2) by O3 and O(3P).

    Science.gov (United States)

    Azyazov, Valeriy N; Antonov, Ivan O; Heaven, Michael C

    2007-04-26

    Oxygen-iodine lasers that utilize electrical or microwave discharges to produce singlet oxygen are currently being developed. The discharge generators differ from conventional chemical singlet oxygen generators in that they produce significant amounts of atomic oxygen. Post-discharge chemistry includes channels that lead to the formation of ozone. Consequently, removal of I(2P1/2) by O atoms and O3 may impact the efficiency of discharge driven iodine lasers. In the present study, we have measured the rate constants for quenching of I(2P1/2) by O(3P) atoms and O3 using pulsed laser photolysis techniques. The rate constant for quenching by O3, (1.8 +/- 0.4) x 10(-12) cm3 s-1, was found to be a factor of 5 smaller than the literature value. The rate constant for quenching by O(3P) was (1.2 +/- 0.2) x 10(-11) cm3 s-1.

  4. Molecular characterization of pandemic H1N1 influenza viruses isolated from turkeys and pathogenicity of a human pH1N1 isolate in turkeys.

    Science.gov (United States)

    Berhane, Yohannes; Ojkic, Davor; Neufeld, James; Leith, Marsha; Hisanaga, Tamiko; Kehler, Helen; Ferencz, Arpad; Wojcinski, Helen; Cottam-Birt, Colleen; Suderman, Matthew; Handel, Katherine; Alexandersen, Soren; Pasick, John

    2010-12-01

    Suspected human-to-animal transmission of the 2009 pandemic H1N1 (pH1N1) virus has been reported in several animal species, including pigs, dogs, cats, ferrets, and turkeys. In this study we describe the genetic characterization of pH1N1 viruses isolated from breeder turkeys that was associated with a progressive drop in egg production. Sequence analysis of all eight gene segments from three viruses isolated from this outbreak demonstrated homology with other human and swine pH1N1 isolates. The susceptibility of turkeys to a human pH1N1 isolate was further evaluated experimentally. The 50% turkey infectious dose (TID50) for the human isolate A/Mexico/LnDRE/4487/2009 was determined by inoculating groups of 8-10-week-old turkeys with serial 10-fold dilutions of virus by oronasal and cloacal routes. We estimated the TID50 to be between 1 x 10(5) and 1 x 10(6) TCID50. The pathogenesis of pH1N1 in oronasally or cloacally inoculated juvenile turkeys was also examined. None of the turkeys exhibited clinical signs, and no significant difference in virus shedding or seroconversion was observed between the two inoculation groups. More than 50% of the turkeys in both oronasal and cloacal groups shed virus beginning at 2 days postinoculation (dpi). All birds that actively shed virus seroconverted by 14 dpi. Virus antigen was demonstrated by immunohistochemistry in the cecal tonsils and bursa of Fabricius in two of the birds that were infected by the cloacal route. Virus transmission to naive contact turkeys was at best doubtful. This report provides additional evidence that pH1N1 can cross the species barrier and cause disease outbreaks in domestic turkeys. However, it appears that the reproductive status of the host as well as environmental factors such as concurrent infections, stress, the presence or absence of litter, and stocking density may also contribute to efficient infection and transmission of this agent.

  5. Energy, fine structure, and hyperfine structure of the core-excited states 1s2s2pnp 5P (n = 2-5) and 1s2p2mp 5S (m = 2-5) for Li- ion

    International Nuclear Information System (INIS)

    Wang, Z.B.; Gou, B.C.; Chen, F.

    2006-01-01

    The relativistic energies, the oscillator strength, and the lifetimes of high-lying core-excited states 1s2s2pnp 5 P (n=2-5) and 1s2p 2 mp 5 S 0 (m=2-5) of Li - ion are calculated with the saddle-point variational method and restricted variation method. The fine structure and the hyperfine structure of the core-excited states for this system are also explored. The results are compared with other theoretical and experimental data in the literature. The energy obtained in this work are much lower than the others previously published whereas the wavelengths and radiative life-times are in agreement

  6. Calculation of parity violating effects in the 62P/sub 1/2/-72P/sub 1/2/ forbidden M1 transition in thallium

    International Nuclear Information System (INIS)

    Neuffer, D.B.

    1977-05-01

    Calculations are presented of the E1 amplitude expected in forbidden M1 transitions of Tl and Cs if parity is violated in the neutral weak e-N interaction, as proposed in a number of gauge models, including that of Weinberg and Salam. Valence electron wave functions are generated as numerical solutions to the Dirac equation in a modified Tietz central potential. These wave functions are used to calculate allowed E1 transition rates, hfs splittings, and Stark E1 transition ampitudes. These results are compared with experiment and the agreement is generally good. The relativistic Tl 6 2 P/sub 1/2/-7 2 P/sub 1/2/ M1 transition amplitude M is also calculated, and corrections due to interconfiguration interaction, Breit interaction, and hfs mixing are included. The parity violating E1 amplitude E/sub PV/ is calculated and a value for the circular dichroism in the Weinberg model delta = -2.6 x 10 -3 is obtained. Parity violating effects in other Tl transitions are discussed. Contributions to the M1 amplitude for the forbidden Cs 6 2 S/sub 1/2/-7 2 S/sub 1/2/ and 6 2 S/sub 1/2/-8 2 S/sub 1/2/ transitions and to the Cs 6 2 S/sub 1/2/ g-factor anomaly from relativistic effects, Breit interaction, interconfiguration interaction, and hfs mixing are calculated, and it is found that this current theoretical description is not entirely adequate. The parity violating E1 amplitude E/sub PV/ for the 6S/sub 1/2/-7 2 S/sub 1/2/ and 6S/sub 1/2/-8 2 S/sub 1/2/ transitions is evaluated. With a measured value M/sub expt/ and the Weinberg value Q/sub W/ = -99, a circular dichroism delta = 1.64 x 10 -4 for the 6 2 S/sub 1/2/-7 2 S/sub 1/2/ transition is found

  7. PPARγ agonists upregulate sphingosine 1-phosphate (S1P) receptor 1 expression, which in turn reduces S1P-induced [Ca(2+)]i increases in renal mesangial cells.

    Science.gov (United States)

    Koch, Alexander; Völzke, Anja; Puff, Bianca; Blankenbach, Kira; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2013-11-01

    We previously identified peroxisome proliferator-activated receptor gamma (PPARγ) agonists (thiazolidinediones, TZDs) as modulators of the sphingolipid metabolism in renal mesangial cells. TZDs upregulated sphingosine kinase 1 (SK-1) and increased the formation of intracellular sphingosine 1-phosphate (S1P), which in turn reduced the expression of pro-fibrotic connective tissue growth factor. Since S1P also acts as extracellular ligand at specific S1P receptors (S1PR, S1P1-5), we investigated here the effect of TZDs on S1PR expression in mesangial cells and evaluated the functional consequences by measuring S1P-induced increases in intracellular free Ca(2+) concentration ([Ca(2+)]i). Treatment with two different TZDs, troglitazone and rosiglitazone, enhanced S1P1 mRNA and protein expression in rat mesangial cells, whereas S1P2-5 expression levels were not altered. Upregulation of S1P1 mRNA upon TZD treatment was also detected in human mesangial cells and mouse glomeruli. PPARγ antagonism and promoter studies revealed that the TZD-dependent S1P1 mRNA induction involved a functional PPAR response element in the S1P1 promoter. Pharmacological approaches disclosed that S1P-induced [Ca(2+)]i increases in rat mesangial cells were predominantly mediated by S1P2 and S1P3. Interestingly, the transcriptional upregulation of S1P1 by TZDs resulted in a reduction of S1P-induced [Ca(2+)]i increases, which was reversed by the S1P1/3 antagonist VPC-23019, the protein kinase C (PKC) inhibitor PKC-412, and by S1P1 siRNA. These data suggest that PPARγ-dependent upregulation of S1P1 leads to an inhibition of S1P-induced Ca(2+) signaling in a PKC-dependent manner. Overall, these results reveal that TZDs not only modulate intracellular S1P levels but also regulate S1PR signaling by increasing S1P1 expression in mesangial cells. © 2013.

  8. Microglia P2Y13 Receptors Prevent Astrocyte Proliferation Mediated by P2Y1 Receptors

    Directory of Open Access Journals (Sweden)

    Clara Quintas

    2018-05-01

    Full Text Available Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog. In astrocyte cultures, ADPβS increased cell proliferation through activation of P2Y1 and P2Y12 receptors, an effect abolished in co-cultures (of astrocytes with ∼12.5% microglia. The possibility that the loss of the ADPβS-mediated effect could have been caused by a microglia-induced degradation of ADPβS or by a preferential microglial localization of P2Y1 or P2Y12 receptors was excluded. Since ADPβS also activates P2Y13 receptors, the contribution of microglial P2Y13 receptors to prevent the proliferative effect of ADPβS in co-cultures was investigated. The results obtained indicate that P2Y13 receptors are low expressed in astrocytes and mainly expressed in microglia. Furthermore, in co-cultures, ADPβS induced astroglial proliferation in the presence of the selective P2Y13 antagonist MRS 2211 (3 μM and of the selective P2Y12 antagonist AR-C66096 (0.1 μM, suggesting that activation of microglial P2Y12 and P2Y13 receptors may induce the release of messengers that inhibit astroglial proliferation mediated by P2Y1,12 receptors. In this microglia-astrocyte paracrine communication, P2Y12 receptors exert opposite effects in astroglial proliferation as a result of its cellular localization: cooperating in astrocytes with P2Y1 receptors to directly stimulate proliferation and in

  9. Improved wavelengths for the 1s2s3S1-1s2p3P0,2 transitions in helium-like Si12+

    International Nuclear Information System (INIS)

    Armour, I.A.; Myers, E.G.; Silver, J.D.; Traebert, E.; Oxford Univ.

    1979-01-01

    The wavelengths of the 1s2s 3 S 1 -1s2p 3 P 0 , 2 transitions in He-like Si 12+ have been remaesured to be 87.86 +- 0.01 nm and 81.48 +- 0.01 nm. The use of Rydberg lines for the calibration of fast beam spectra is discussed. (orig.)

  10. The sphingosine 1-phosphate receptor S1P(2) triggers hepatic wound healing

    NARCIS (Netherlands)

    Serriere-Lanneau, Valerie; Teixeira-Clerc, Fatima; Li, Liying; Schippers, Marlies; de Wries, Willie; Julien, Boris; Tran-Van-Nhieu, Jeanne; Manin, Sylvie; Poelstra, Klaas; Chun, Jerold; Carpentier, Stephane; Levade, Thierry; Mallat, Ariane; Lotersztajn, Sophie

    Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK1 and 2). We previously showed that S1P receptors (S1P(1), S1P(2), and S1P(3)) are expressed in hepatic myofibroblasts (hMF), a population of cells that triggers matrix remodeling during liver injury. Here

  11. Evaluación de la actividad de la enzima citocromo P-450 1A2 en una población colombiana

    Directory of Open Access Journals (Sweden)

    Fanny Cuesta González

    2000-02-01

    Full Text Available <p class="MsoNormal">Introducción: La enzima citocromo P450 1A2 (CYP1A2, presente en tejidos hepáticos humanos, participa en el metabolismo de fármacos tales como Clozapina, Imipramina, Teofilina y Cafeína. Estudios realizados en diferentes poblaciones han mostrado una distribución bimodal y a veces trimodal en la actividad de esta enzima. Este comportamiento ha sido relacionado con variaciones tanto del gen codificante como de las regiones reguladoras, aunque hasta el momento los resultados no son concluyentes. Además del metabolismo de fármacos, la CYP1A2 interviene en la activación de sustancias procarcinogénicas tales como N-nitrosaminas, aminas heterocíclicas y aromáticas; es conocida la correlación entre una actividad incrementada de esta enzima (metabolizadores rápidos con una mayor exposición al riesgo de cáncer.p> <p class="MsoNormal">Debido a la baja incidencia de efectos secundarios y la facilidad en la medición de los metabolitos en orina, la Cafeína es utilizada como fármaco prueba para la determinación de la actividad enzimática CYP1A2, calculando la relación entre las concentraciones molares de sus metabolitos (Actividad CYP1A2 = AFMU+MU+MX/17DMU.p> <p class="MsoNormal">En el presente estudio se evaluará la actividad de la enzima CYP1A2 en una muestra de individuos sanos, con el fin de describir su comportamiento y compararlo con el encontrado en otras poblaciones, las cuales tienen una influencia genética y ambiental diferente a la de la población colombiana.p> <p class="MsoNormal">Metodología: Una vez recolectadas las muestras de orina, se separarán de ellas los

  12. n-p Short-Range Correlations from (p,2p+n) Measurements

    Science.gov (United States)

    Tang, A.; Watson, J. W.; Aclander, J.; Alster, J.; Asryan, G.; Averichev, Y.; Barton, D.; Baturin, V.; Bukhtoyarova, N.; Carroll, A.; Gushue, S.; Heppelmann, S.; Leksanov, A.; Makdisi, Y.; Malki, A.; Minina, E.; Navon, I.; Nicholson, H.; Ogawa, A.; Panebratsev, Yu.; Piasetzky, E.; Schetkovsky, A.; Shimanskiy, S.; Zhalov, D.

    2003-01-01

    We studied the 12C(p,2p+n) reaction at beam momenta of 5.9, 8.0, and 9.0 GeV/c. For quasielastic (p,2p) events pf, the momentum of the knocked-out proton before the reaction, was compared (event by event) with pn, the coincident neutron momentum. For |pn|>kF=0.220 GeV/c (the Fermi momentum) a strong back-to-back directional correlation between pf and pn was observed, indicative of short-range n-p correlations. From pn and pf we constructed the distributions of c.m. and relative motion in the longitudinal direction for correlated pairs. We also determined that 49±13% of events with |pf|>kF had directionally correlated neutrons with |pn|>kF.

  13. Enhancement of the response to purinergic agonists in P2Y1 transfected 1321N1 cells by antagonists suramin and PPADS.

    Science.gov (United States)

    Brown, C A; Charlton, S J; Boarder, M R

    1997-03-01

    1. We have previously shown that both suramin and pyridoxal-phosphate-6-azophenyl-2',4' disulphonic acid (PPADS) act as antagonists at transfected P2Y1 receptors. Here we show that under certain experimental conditions these two P2 antagonists can enhance the response to agonists acting at these receptors. 2. The expression of either P2Y1 or P2Y2 receptors in 1321N1 human astrocytoma cells results, on a change of medium, in an elevation of basal (no added agonist) accumulation of [3H]-inositol(poly)phosphates([3H]-InsPx) compared to cells not expressing these receptors. This elevation is much greater in P2Y1 transfectants than in P2Y, transfectants. 3. Both PPADS and suramin reduced this basal level of [3H]-InsPx accumulation in the P2Y1 expressing cells. 4. When a protocol was used which required changing the culture medium, antagonists were added at a concentration which reduced the basal accumulation by about 50%, there was a significant stimulation in response to increasing concentrations of 2-methylthioadenosine 5'-triphosphate (2MeSATP), in the absence of antagonists there was no significant effect of the agonist. 5. However, when 2MeSATP was added in the absence of a change of medium and with no antagonist present, there was a several fold increase in [3H]-InsPx accumulation. These results show that a release of endogenous agonist activity (possibly ATP/ADP) from the P2Y1 expressing cells can create conditions in which a response to an agonist such as 2MeSATP can only be seen in the presence of a competitive antagonist.

  14. The effect of lycopene on the total cytochrome P450, CYP1A2 and CYP2E1

    Directory of Open Access Journals (Sweden)

    Melva Louisa

    2009-12-01

    Full Text Available Aim: Some carotenoids such as canthaxantin, astaxanthin and beta apo-8’-carotenal were reported to have modulatoryeffect on the cytochrome P450. The present study was conducted to investigate the effects of lycopene, a nonprovitamin A carotenoid, on microsomal cytochrome P450, CYP1A2 and CYP2E1.Methods: Total cytochrome P450 levels, CYP1A2 and CYP2E1-catalyzed reactions (acetanilide 4-hydroxylation and p-nitrophenol hydroxylation were studied in the liver microsomes of male Sprague Dawley rats. Microsomes were prepared using differential centrifugation combined with calcium aggregation method. Lycopene was orally administered in the dosages of 0, 25, 50 or 100 mg/kgBW/day for 14 days in a repeated fashion. Data were analyzed using ANOVA test.Results: Total cytochrome P450 level and acetanilide 4-hydroxylase activity were unaffected by any of the treatments. The CYP2E1 probe enzyme (p-nitrophenol hydroxylase was significantly reduced by repeated administration of 100mg/ kgBW/day lycopene (7.88 + 2.04 vs 12.26 + 2.77 n mol/min/mg prot.Conclusion: The present results suggest that lycopene does not affect the total cytochrome P450 or CYP1A2 activity but it inhibits the activity of CYP2E1 (p-nitrophenol hydroxylase in the rat. (Med J Indones 2009; 18: 233-8Keywords: lycopene, cytochrome P450, CYP1A2, CYP2E1

  15. Biorremediación de suelo contaminado con el pesticida 1,1,1-tricloro-2,2’bis(p-clorofenil)etano (DDT) mediante protocolos de bioestimulación y adición de surfactante

    OpenAIRE

    Betancur Corredor, Bibiana

    2013-01-01

    Resumen: El 1,1,1-tricloro-2,2’bis(p-clorofenil)etano (DDT) ha sido usado desde la segunda guerra mundial para controlar enfermedades transmitidas por insectos en humanos y animales domésticos. El uso de estos insecticidas organoclorados se ha prohibido en la mayoría de los países debido a su persistencia en el ambiente, susceptibilidad de biomagnificación y potencial toxicidad a animales superiores. La biorremediación involucra el uso de microorganismos para degradar contaminantes orgánic...

  16. Changes in the viral distribution pattern after the appearance of the novel influenza A H1N1 (pH1N1) virus in influenza-like illness patients in Peru.

    Science.gov (United States)

    Laguna-Torres, Victor Alberto; Gómez, Jorge; Aguilar, Patricia V; Ampuero, Julia S; Munayco, Cesar; Ocaña, Víctor; Pérez, Juan; Gamero, María E; Arrasco, Juan Carlos; Paz, Irmia; Chávez, Edward; Cruz, Rollin; Chavez, Jaime; Mendocilla, Silvia; Gomez, Elizabeth; Antigoni, Juana; Gonzalez, Sofía; Tejada, Cesar; Chowell, Gerardo; Kochel, Tadeusz J

    2010-07-27

    We describe the temporal variation in viral agents detected in influenza like illness (ILI) patients before and after the appearance of the ongoing pandemic influenza A (H1N1) (pH1N1) in Peru between 4-January and 13-July 2009. At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW) 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD) in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chain-reaction (rRT-PCR). We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW) 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5%) from EW 19-28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima) followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle) cities during our study period. The city of Iquitos (Jungle) had the highest number of influenza B cases and only one pH1N1 case. The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses.

  17. Changes in the viral distribution pattern after the appearance of the novel influenza A H1N1 (pH1N1 virus in influenza-like illness patients in Peru.

    Directory of Open Access Journals (Sweden)

    Victor Alberto Laguna-Torres

    Full Text Available BACKGROUND: We describe the temporal variation in viral agents detected in influenza like illness (ILI patients before and after the appearance of the ongoing pandemic influenza A (H1N1 (pH1N1 in Peru between 4-January and 13-July 2009. METHODS: At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chain-reaction (rRT-PCR. RESULTS: We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5% from EW 19-28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle cities during our study period. The city of Iquitos (Jungle had the highest number of influenza B cases and only one pH1N1 case. CONCLUSIONS: The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses.

  18. Calculations of resonances parameters for the ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) doubly excited states of helium-like ions with Z≤10 using a complex rotation method implemented in Scilab

    Science.gov (United States)

    Gning, Youssou; Sow, Malick; Traoré, Alassane; Dieng, Matabara; Diakhate, Babacar; Biaye, Mamadi; Wagué, Ahmadou

    2015-01-01

    In the present work a special computational program Scilab (Scientific Laboratory) in the complex rotation method has been used to calculate resonance parameters of ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) states of helium-like ions with Z≤10. The purpose of this study required a mathematical development of the Hamiltonian applied to Hylleraas wave function for intrashell states, leading to analytical expressions which are carried out under Scilab computational program. Results are in compliance with recent theoretical calculations.

  19. Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Stefan Bittner

    2015-07-01

    Full Text Available Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K2P5.1 (TASK2; KCNK5 channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K2P5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K2P5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K2P5.1 knockout (K2P5.1−/− mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K2P5.1−/− mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K2P3.1 and KV1.3 seems to counterbalance the deletion of K2P5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K2P5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K2P5.1-targeting drugs.

  20. Hal2p functions in Bdf1p-involved salt stress response in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Lei Chen

    Full Text Available The Saccharomyces cerevisiae Bdf1p associates with the basal transcription complexes TFIID and acts as a transcriptional regulator. Lack of Bdf1p is salt sensitive and displays abnormal mitochondrial function. The nucleotidase Hal2p detoxifies the toxic compound 3' -phosphoadenosine-5'-phosphate (pAp, which blocks the biosynthesis of methionine. Hal2p is also a target of high concentration of Na(+. Here, we reported that HAL2 overexpression recovered the salt stress sensitivity of bdf1Δ. Further evidence demonstrated that HAL2 expression was regulated indirectly by Bdf1p. The salt stress response mechanisms mediated by Bdf1p and Hal2p were different. Unlike hal2Δ, high Na(+ or Li(+ stress did not cause pAp accumulation in bdf1Δ and methionine supplementation did not recover its salt sensitivity. HAL2 overexpression in bdf1Δ reduced ROS level and improved mitochondrial function, but not respiration. Further analyses suggested that autophagy was apparently defective in bdf1Δ, and autophagy stimulated by Hal2p may play an important role in recovering mitochondrial functions and Na(+ sensitivity of bdf1Δ. Our findings shed new light towards our understanding about the molecular mechanism of Bdf1p-involved salt stress response in budding yeast.

  1. 1H(d,2p)n reaction at 2 GeV deuteron energy

    International Nuclear Information System (INIS)

    Erohuml, J.; Fodor, Z.; Koncz, P.; Seres, Z.; Perdrisat, C.F.; Punjabi, V.; Boudard, A.; Bonin, B.; Garcon, M.; Lombard, R.; Mayer, B.; Terrien, Y.; Tomasi, E.; Boivin, M.; Yonnet, J.; Bhang, H.C.; Youn, M.; Belostotsky, S.L.; Grebenuk, O.G.; Nikulin, V.N.; Kudin, L.G.

    1994-01-01

    The 1 H(d,2p)n deuteron breakup reaction was measured at 2 GeV deuteron energy in a kinematically complete experiment. Fivefold differential cross sections are given in a wide range of kinematical variables and analyzed in terms of impulse approximation and NN rescattering. The deuteron momentum density was determined and deviations were found depending on the value of the four-momentum transfer |t| in the scattering process. At low |t| the momentum densities are in good agreement with the impulse approximation whereas large discrepancies were found above q∼200 MeV/c when the four-momentum transfer was large. Various possible origins of the anomalous behavior at high q values are discussed

  2. Magnetostriction-strain-induced enhancement and modulation of photovoltaic performance in Si-p-n/TbxDy1-xFe2 composite

    International Nuclear Information System (INIS)

    Wu, Zheng; Zhang, Yihe; Fang, Cong; Ma, Ke; Lin, He; Jia, Yanmin; Chen, Jianrong; Wang, Yu; Chan, Helen Lai Wa

    2014-01-01

    High photovoltaic efficiency is a key index in the application of silicon (Si) solar cells. In this study, a composite of a photovoltaic Si p-n junction solar cell and a magnetostrictive Tb x Dy 1-x Fe 2 alloy was fabricated. By utilizing the magnetostrictive strain to modulate the energy bandgap of Si, the open-circuit voltage and the maximum photovoltaic output power of the Si p-n junction solar cell could be enhanced by ∝12% and 9.1% under a dc magnetic field of ∝250 mT, respectively. The significantly enhanced photovoltaic performance and the simple fabrication process make the Si-p-n/Tb x Dy 1-x Fe 2 composite a promising material for high-efficiency solar cell devices. The structure of the proposed Si-p-n/Tb x Dy 1-x Fe 2 laminated composite. (copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  3. A lifetime measurement of the 1s2p 3P1 level in helium-like Mg and Al

    International Nuclear Information System (INIS)

    Armour, I.A.; Silver, J.D.; Traebert, E.; Oxford Univ.

    1981-01-01

    The lifetimes of the 1s2p 3 P 1 levels of helium-like magnesium and aluminium have been measured by the beam-foil decay curve technique. The 1s 2 -1s2p transitions were observed with a curved-crystal x-ray spectrometer. Decay curves taken under systematically varied conditions have been evaluated using several techniques including a cascade model. The results are in agreement with most of the theoretical predictions. (author)

  4. The amino terminal end determines the stability and assembling capacity of eukaryotic ribosomal stalk proteins P1 and P2.

    Science.gov (United States)

    Camargo, Hendricka; Nusspaumer, Gretel; Abia, David; Briceño, Verónica; Remacha, Miguel; Ballesta, Juan P G

    2011-05-01

    The eukaryotic ribosomal proteins P1 and P2 bind to protein P0 through their N-terminal domain to form the essential ribosomal stalk. A mutational analysis points to amino acids at positions 2 and 3 as determinants for the drastic difference of Saccharomyces cerevisiae P1 and P2 half-life, and suggest different degradation mechanisms for each protein type. Moreover, the capacity to form P1/P2 heterodimers is drastically affected by mutations in the P2β four initial amino acids, while these mutations have no effect on P1β. Binding of P2β and, to a lesser extent, P1β to the ribosome is also seriously affected showing the high relevance of the amino acids in the first turn of the NTD α-helix 1 for the stalk assembly. The negative effect of some mutations on ribosome binding can be reversed by the presence of the second P1/P2 couple in the ribosome, indicating a stabilizing structural influence between the two heterodimers. Unexpectedly, some mutations totally abolish heterodimer formation but allow significant ribosome binding and, therefore, a previous P1 and P2 association seems not to be an absolute requirement for stalk assembly. Homology modeling of the protein complexes suggests that the mutated residues can affect the overall protein conformation. © The Author(s) 2011. Published by Oxford University Press.

  5. Excitation of the (2p2)1D and (2s2p)1P autoionizing states of helium by 200 eV electron impact

    International Nuclear Information System (INIS)

    Godunov, A.L.; McGuire, J.H.; Schipakov, V.S.; Crowe, A.

    2002-01-01

    We report full second Born calculations with inclusion of post-collision interactions for excitation of the (2p 2 ) 1 D and (2s2p) 1 P autoionizing states of helium by 200 eV electron impact. The calculations are compared to (e, 2e) measurements of McDonald and Crowe (McDonald D G and Crowe A 1993 J. Phys. B: At. Mol. Opt. Phys. 26 2887-97) and Lower and Weigold (Lower J and Weigold E 1990 J. Phys. B: At. Mol. Opt. Phys. 23 2819-45). It is shown that post-collision interactions or Coulomb interactions in the final state between the scattered particle, the ejected electron and the recoil ion have a strong influence on both the direct ionization and resonance profiles around the binary lobe. The second-order terms in the amplitude of double electron excitation also play an observable role under these kinematic conditions. Reasonable agreement is found between the full-scale calculations and the experimental data. (author). Letter-to-the-editor

  6. Cold-adapted influenza and recombinant adenovirus vaccines induce cross-protective immunity against pH1N1 challenge in mice.

    Directory of Open Access Journals (Sweden)

    Mark R Soboleski

    Full Text Available The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1 highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus.BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca influenza viruses from 1977 or recombinant adenoviruses (rAd expressing 1934 nucleoprotein (NP and consensus matrix 2 (M2 (NP+M2-rAd. Antibodies against the M2 ectodomain (M2e were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus.Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic.

  7. Sphingosine-1-phosphate (S1P) displays sustained S1P1 receptor agonism and signaling through S1P lyase-dependent receptor recycling.

    Science.gov (United States)

    Gatfield, John; Monnier, Lucile; Studer, Rolf; Bolli, Martin H; Steiner, Beat; Nayler, Oliver

    2014-07-01

    The sphingosine-1-phosphate (S1P) type 1 receptor (S1P1R) is a novel therapeutic target in lymphocyte-mediated autoimmune diseases. S1P1 receptor desensitization caused by synthetic S1P1 receptor agonists prevents T-lymphocyte egress from secondary lymphoid organs into the circulation. The selective S1P1 receptor agonist ponesimod, which is in development for the treatment of autoimmune diseases, efficiently reduces peripheral lymphocyte counts and displays efficacy in animal models of autoimmune disease. Using ponesimod and the natural ligand S1P, we investigated the molecular mechanisms leading to different signaling, desensitization and trafficking behavior of S1P1 receptors. In recombinant S1P1 receptor-expressing cells, ponesimod and S1P triggered Gαi protein-mediated signaling and β-arrestin recruitment with comparable potency and efficiency, but only ponesimod efficiently induced intracellular receptor accumulation. In human umbilical vein endothelial cells (HUVEC), ponesimod and S1P triggered translocation of the endogenous S1P1 receptor to the Golgi compartment. However, only ponesimod treatment caused efficient surface receptor depletion, receptor accumulation in the Golgi and degradation. Impedance measurements in HUVEC showed that ponesimod induced only short-lived Gαi protein-mediated signaling followed by resistance to further stimulation, whereas S1P induced sustained Gαi protein-mediated signaling without desensitization. Inhibition of S1P lyase activity in HUVEC rendered S1P an efficient S1P1 receptor internalizing compound and abrogated S1P-mediated sustained signaling. This suggests that S1P lyase - by facilitating S1P1 receptor recycling - is essential for S1P-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not S1P lyase substrates. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Berberine reduces fibronectin expression by suppressing the S1P-S1P2 receptor pathway in experimental diabetic nephropathy models.

    Directory of Open Access Journals (Sweden)

    Kaipeng Huang

    Full Text Available The accumulation of glomerular extracellular matrix (ECM is one of the critical pathological characteristics of diabetic renal fibrosis. Fibronectin (FN is an important constituent of ECM. Our previous studies indicate that the activation of the sphingosine kinase 1 (SphK1-sphingosine 1- phosphate (S1P signaling pathway plays a key regulatory role in FN production in glomerular mesangial cells (GMCs under diabetic condition. Among the five S1P receptors, the activation of S1P2 receptor is the most abundant. Berberine (BBR treatment also effectively inhibits SphK1 activity and S1P production in the kidneys of diabetic models, thus improving renal injury. Based on these data, we further explored whether BBR could prevent FN production in GMCs under diabetic condition via the S1P2 receptor. Here, we showed that BBR significantly down-regulated the expression of S1P2 receptor in diabetic rat kidneys and GMCs exposed to high glucose (HG and simultaneously inhibited S1P2 receptor-mediated FN overproduction. Further, BBR also obviously suppressed the activation of NF-κB induced by HG, which was accompanied by reduced S1P2 receptor and FN expression. Taken together, our findings suggest that BBR reduces FN expression by acting on the S1P2 receptor in the mesangium under diabetic condition. The role of BBR in S1P2 receptor expression regulation could closely associate with its inhibitory effect on NF-κB activation.

  9. Optical properties of lattice matched In{sub x}Ga{sub 1-x}P{sub 1-y}N{sub y} heteroepitaxial layers on GaP

    Energy Technology Data Exchange (ETDEWEB)

    Imanishi, T.; Wakahara, A.; Kim, S.M.; Yonezu, H.; Furukawa, Y. [Department of Electrical and Electron Engineering, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 411-8580 (Japan)

    2005-04-01

    Optical constants and band structure of In{sub x}Ga{sub 1-x}P{sub 1-y}N{sub y} lattice matched to GaP (100) substrate are investigated. Nitrogen concentration in the film estimated by X-ray diffraction and X-ray photoelectron spectroscopy, was 1.4%, 1.8% and 3.5%. Refractive index and transition critical points E{sub 0} ({gamma}{sub v} to {gamma}{sub c}), E{sub 1} (L{sub v} to L{sub c}) and E{sub 2} (X{sub v} to X{sub c}) are evaluated by spectroscopic ellipsometry. When N composition increases from 1.4% to 3.5%, both photoluminescence (PL) peak energy, E{sub PL}, and E{sub 0} shift to lower energy, and the energy difference {delta}E=E{sub 0}-E{sub PL} decrease from 380 meV to 110 meV. The large red-sift of E{sub PL} from the E{sub 0} suggest that the luminescence is of defect-related luminescence, and crossover point of indirect band structure estimated by the extrapolation of N-composition dependence of {delta}E is estimated to be around in In{sub 0.1}Ga{sub 0.9}P{sub 0.96}N{sub 0.04}. (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  10. Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective antagonist inhibits angiogenesis

    International Nuclear Information System (INIS)

    Fujii, Yasuyuki; Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi; Igarashi, Yasuyuki; Goitsuka, Ryo

    2012-01-01

    Highlights: ► The effect of a newly developed S1P 1 -selective antagonist on angiogenic responses. ► S1P 1 is a critical component of VEGF-related angiogenic responses. ► S1P 1 -selective antagonist showed in vitro activity to inhibit angiogenesis. ► S1P 1 -selective antagonist showed in vivo activity to inhibit angiogenesis. ► The efficacy of S1P 1 -selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P 1 ) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P 1 and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P 1 -selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P 1 antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P 1 is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  11. Modulation of the TGF-β1-induced epithelial to mesenchymal transition (EMT) mediated by P1 and P2 purine receptors in MDCK cells.

    Science.gov (United States)

    Zuccarini, Mariachiara; Giuliani, Patricia; Buccella, Silvana; Di Liberto, Valentina; Mudò, Giuseppa; Belluardo, Natale; Carluccio, Marzia; Rossini, Margherita; Condorelli, Daniele Filippo; Rathbone, Michel Piers; Caciagli, Francesco; Ciccarelli, Renata; Di Iorio, Patrizia

    2017-12-01

    Epithelial to mesenchymal transition (EMT) occurs during embryogenesis or under pathological conditions such as hypoxia, injury, chronic inflammation, or tissue fibrosis. In renal tubular epithelial cells (MDCK), TGF-β1 induces EMT by reducing or increasing epithelial or mesenchymal marker expression, respectively. In this study, we confirmed that the cAMP analogues, 8-CPT-cAMP or N6-Ph-cAMP, inhibited the TGF-β1-driven overexpression of the mesenchymal markers ZEB-1, Slug, Fibronectin, and α-SMA. Furthermore, we showed that A1, A2A, P2Y1, P2Y11, and P2X7 purine receptor agonists modulated the TGF-β1-induced EMT through the involvement of PKA and/or MAPK/ERK signaling. The stimulation of A2A receptor reduced the overexpression of the EMT-related markers, mainly through the cAMP-dependent PKA pathway, as confirmed by cell pre-treatment with Myr-PKI. Both A1 and P2Y1 receptor stimulation exacerbated the TGF-β1-driven effects, which were reduced by cell pre-treatment with the MAPK inhibitor PD98059, according to the increased ERK1/2 phosphorylation upon receptor activation. The effects induced by P2Y11 receptor activation were oppositely modulated by PKA or MAPK inhibition, in line with the dual nature of the Gs- and Gq-coupled receptor. Differently, P2X7 receptor induced, per se, similar and not additive effects compared to TGF-β1, after prolonged cell exposure to BzATP. These results suggest a putative role of purine receptors as target for anti-fibrotic agents.

  12. The Outcome for Patients With Pathologic Node-Positive Prostate Cancer Treated With Intensity Modulated Radiation Therapy and Androgen Deprivation Therapy: A Case-Matched Analysis of pN1 and pN0 Patients

    International Nuclear Information System (INIS)

    Van Hemelryk, Annelies; De Meerleer, Gert; Ost, Piet; Poelaert, Filip; De Gersem, Werner; Decaestecker, Karel; De Visschere, Pieter; Fonteyne, Valérie

    2016-01-01

    Purpose: Improved outcome is reported after surgery or external beam radiation therapy (EBRT) plus androgen deprivation therapy (ADT) for patients with lymph node (LN) positive (N1) prostate cancer (PC). Surgical series have shown that pathologic (p)N1 PC does not behave the same in all patients. The aim of this study was to perform a matched-case analysis to compare the outcome of pN1 and pN0 PC after high-dose EBRT plus ADT. Methods and Materials: Radiation therapy up to 80 Gy was delivered to the prostate with a minimal dose of 45 Gy to the pelvis for pN1 patients. After matching, Kaplan-Meier statistics were used to compare the 5-year biochemical and clinical relapse-free survival (bRFS and cRFS), prostate cancer–specific survival (PCSS), and overall survival (OS). Acute and late rectal and urinary toxicity was evaluated. Results: Sixty-nine pN1 PC patients were matched 1:1 with pN0 PC patients. The median follow-up time was 60 months. The 5-year bRFS and cRFS for pN1 versus pN0 PC patients were 65% ± 7% versus 79% ± 5% (P=.08) and 70% ± 6% versus 83% ± 5% (P=.04) respectively. No significant difference was found in bRFS or cRFS rates between low volume pN1 (≤2 positive LNs) and pN0 patients. The 5-year PCSS and OS were comparable between pN1 and pN0 PC patients: PCSS: 92% ± 4% versus 93% ± 3% (P=.66); OS: 82% ± 5% versus 80% ± 5% (P=.58). Severe toxicity was rare for both groups, although pN1 patients experienced significantly more acute grade 2 rectal toxicity. Conclusion: Primary EBRT plus 2 to 3 years of ADT is a legitimate treatment option for pN1 PC patients, especially those with ≤2 positive LNs, and this with bRFS and cRFS rates comparable to those in pN0 PC patients. For pN1 PC patients with >2 positive LNs, bRFS and cRFS are worse than in pN0 patients, but even in this subgroup, long-term disease control is obtained.

  13. The Outcome for Patients With Pathologic Node-Positive Prostate Cancer Treated With Intensity Modulated Radiation Therapy and Androgen Deprivation Therapy: A Case-Matched Analysis of pN1 and pN0 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Van Hemelryk, Annelies [Department of Urology, Ghent University Hospital, Ghent (Belgium); De Meerleer, Gert; Ost, Piet [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium); Poelaert, Filip [Department of Urology, Ghent University Hospital, Ghent (Belgium); De Gersem, Werner [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium); Decaestecker, Karel [Department of Urology, Ghent University Hospital, Ghent (Belgium); De Visschere, Pieter [Department of Radiology, Ghent University Hospital, Ghent (Belgium); Fonteyne, Valérie, E-mail: valerie.fonteyne@uzgent.be [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium)

    2016-10-01

    Purpose: Improved outcome is reported after surgery or external beam radiation therapy (EBRT) plus androgen deprivation therapy (ADT) for patients with lymph node (LN) positive (N1) prostate cancer (PC). Surgical series have shown that pathologic (p)N1 PC does not behave the same in all patients. The aim of this study was to perform a matched-case analysis to compare the outcome of pN1 and pN0 PC after high-dose EBRT plus ADT. Methods and Materials: Radiation therapy up to 80 Gy was delivered to the prostate with a minimal dose of 45 Gy to the pelvis for pN1 patients. After matching, Kaplan-Meier statistics were used to compare the 5-year biochemical and clinical relapse-free survival (bRFS and cRFS), prostate cancer–specific survival (PCSS), and overall survival (OS). Acute and late rectal and urinary toxicity was evaluated. Results: Sixty-nine pN1 PC patients were matched 1:1 with pN0 PC patients. The median follow-up time was 60 months. The 5-year bRFS and cRFS for pN1 versus pN0 PC patients were 65% ± 7% versus 79% ± 5% (P=.08) and 70% ± 6% versus 83% ± 5% (P=.04) respectively. No significant difference was found in bRFS or cRFS rates between low volume pN1 (≤2 positive LNs) and pN0 patients. The 5-year PCSS and OS were comparable between pN1 and pN0 PC patients: PCSS: 92% ± 4% versus 93% ± 3% (P=.66); OS: 82% ± 5% versus 80% ± 5% (P=.58). Severe toxicity was rare for both groups, although pN1 patients experienced significantly more acute grade 2 rectal toxicity. Conclusion: Primary EBRT plus 2 to 3 years of ADT is a legitimate treatment option for pN1 PC patients, especially those with ≤2 positive LNs, and this with bRFS and cRFS rates comparable to those in pN0 PC patients. For pN1 PC patients with >2 positive LNs, bRFS and cRFS are worse than in pN0 patients, but even in this subgroup, long-term disease control is obtained.

  14. Vibrational Fingerprints of Low-Lying Pt(n)P(2n) (n = 1-5) Cluster Structures from Global Optimization Based on Density Functional Theory Potential Energy Surfaces.

    Science.gov (United States)

    Jedidi, Abdesslem; Li, Rui; Fornasiero, Paolo; Cavallo, Luigi; Carbonniere, Philippe

    2015-12-03

    Vibrational fingerprints of small Pt(n)P(2n) (n = 1-5) clusters were computed from their low-lying structures located from a global exploration of their DFT potential energy surfaces with the GSAM code. Five DFT methods were assessed from the CCSD(T) wavenumbers of PtP2 species and CCSD relative energies of Pt2P4 structures. The eight first Pt(n)P(2n) isomers found are reported. The vibrational computations reveal (i) the absence of clear signatures made by overtone or combination bands due to very weak mechanical and electrical anharmonicities and (ii) some significant and recurrent vibrational fingerprints in correlation with the different PP bonding situations in the Pt(n)P(2n) structures.

  15. Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways*

    Science.gov (United States)

    Quint, Patrick; Ruan, Ming; Pederson, Larry; Kassem, Moustapha; Westendorf, Jennifer J.; Khosla, Sundeep; Oursler, Merry Jo

    2013-01-01

    Normal bone turnover requires tight coupling of bone resorption and bone formation to preserve bone quantity and structure. With aging and during several pathological conditions, this coupling breaks down, leading to either net bone loss or excess bone formation. To preserve or restore normal bone metabolism, it is crucial to determine the mechanisms by which osteoclasts and osteoblast precursors interact and contribute to coupling. We showed that osteoclasts produce the chemokine sphingosine 1-phosphate (S1P), which stimulates osteoblast migration. Thus, osteoclast-derived S1P may recruit osteoblasts to sites of bone resorption as an initial step in replacing lost bone. In this study we investigated the mechanisms by which S1P stimulates mesenchymal (skeletal) cell chemotaxis. S1P treatment of mesenchymal (skeletal) cells activated RhoA GTPase, but this small G protein did not contribute to migration. Rather, two S1P receptors, S1PR1 and S1PR2, coordinately promoted migration through activation of the JAK/STAT3 and FAK/PI3K/AKT signaling pathways, respectively. These data demonstrate that the chemokine S1P couples bone formation to bone resorption through activation of kinase signaling pathways. PMID:23300082

  16. Crossed molecular beam-tunable laser determination of velocity dependence of intramultiplet mixing: K(4p2P1/2)+He →K(4p2P3/2)+He

    International Nuclear Information System (INIS)

    Anderson, R.W.; Goddard, T.P.; Parravano, C.; Warner, J.

    1976-01-01

    The velocity dependence of intramultiplet mixing, K(4p 2 P 1 / 2 ) +He→K(4p 2 P 3 / 2 )+He, has been measured over the relative velocity range v=1.3--3.4 km/sec. The cross section appears to fit a linear function Q (v) =A (v-v 0 ), where a=6.3 x 10 -4 A 2 and v 0 = 7.9 x 10 4 cm/sec. The value of A is obtained by normalization to the literature thermal average cross section. The intramultiplet mixing theory of Nikitin is modified to yield Q (v) for the process. The modified theory correctly exhibits detailed balancing, and it is normalized to provide a very good fit to the observed Q (v). The magnitude of the normalization factor, however, is larger than that predicted from recent pseudopotential calculations of the excited state potentials. The temperature dependence of intramultiplet mixing is predicted. The use of laser polarization to determine the m/subj/ dependence of the process K(4p 2 P 3 / 2 +He→K(4p 2 P 1 / 2 )+He and other collision processes of excited 2 P 3 / 2 states is examined

  17. Calculations of resonances parameters for the ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) doubly excited states of helium-like ions with Z≤10 using a complex rotation method implemented in Scilab

    International Nuclear Information System (INIS)

    Gning, Youssou; Sow, Malick; Traoré, Alassane; Dieng, Matabara; Diakhate, Babacar; Biaye, Mamadi; Wagué, Ahmadou

    2015-01-01

    In the present work a special computational program Scilab (Scientific Laboratory) in the complex rotation method has been used to calculate resonance parameters of ((2s 2 ) 1 S e , (2s2p) 1,3 P 0 ) and ((3s 2 ) 1 S e , (3s3p) 1,3 P 0 ) states of helium-like ions with Z≤10. The purpose of this study required a mathematical development of the Hamiltonian applied to Hylleraas wave function for intrashell states, leading to analytical expressions which are carried out under Scilab computational program. Results are in compliance with recent theoretical calculations. - Highlights: • Resonance energy and widths computed for doubly excited states of helium-like ions. • Well-comparable results to the theoretical literature values up to Z=10. • Satisfactory agreements with theoretical calculations for widths

  18. Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness

    International Nuclear Information System (INIS)

    Young, Nicholas; Van Brocklyn, James R.

    2007-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid that signals through a family of five G-protein-coupled receptors, termed S1P 1-5 . S1P stimulates growth and invasiveness of glioma cells, and high expression levels of the enzyme that forms S1P, sphingosine kinase-1, correlate with short survival of glioma patients. In this study we examined the mechanism of S1P stimulation of glioma cell proliferation and invasion by either overexpressing or knocking down, by RNA interference, S1P receptor expression in glioma cell lines. S1P 1 , S1P 2 and S1P 3 all contribute positively to S1P-stimulated glioma cell proliferation, with S1P 1 being the major contributor. Stimulation of glioma cell proliferation by these receptors correlated with activation of ERK MAP kinase. S1P 5 blocks glioma cell proliferation, and inhibits ERK activation. S1P 1 and S1P 3 enhance glioma cell migration and invasion. S1P 2 inhibits migration through Rho activation, Rho kinase signaling and stress fiber formation, but unexpectedly, enhances glioma cell invasiveness by stimulating cell adhesion. S1P 2 also potently enhances expression of the matricellular protein CCN1/Cyr61, which has been implicated in tumor cell adhesion, and invasion as well as tumor angiogenesis. A neutralizing antibody to CCN1 blocked S1P 2 -stimulated glioma invasion. Thus, while S1P 2 decreases glioma cell motility, it may enhance invasion through induction of proteins that modulate glioma cell interaction with the extracellular matrix

  19. Is Biological Subtype Prognostic of Locoregional Recurrence Risk in Women With pT1-2N0 Breast Cancer Treated With Mastectomy?

    Energy Technology Data Exchange (ETDEWEB)

    Truong, Pauline T., E-mail: ptruong@bccancer.bc.ca [Radiation Therapy Program, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, BC (Canada); Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, BC (Canada); Sadek, Betro T. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Lesperance, Maria F. [Radiation Therapy Program, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, BC (Canada); Alexander, Cheryl S. [Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, BC (Canada); Shenouda, Mina; Raad, Rita Abi; Taghian, Alphonse G. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    2014-01-01

    Purpose: To examine locoregional and distant recurrence (LRR and DR) in women with pT1-2N0 breast cancer according to approximated subtype and clinicopathologic characteristics. Methods and Materials: Two independent datasets were pooled and analyzed. The study participants were 1994 patients with pT1-2N0M0 breast cancer, treated with mastectomy without radiation therapy. The patients were classified into 1 of 5 subtypes: luminal A (ER+ or PR+/HER 2−/grade 1-2, n=1202); luminal B (ER+ or PR+/HER 2−/grade 3, n=294); luminal HER 2 (ER+ or PR+/HER 2+, n=221); HER 2 (ER−/PR−/HER 2+, n=105) and triple-negative breast cancer (TNBC) (ER−/PR−/HER 2−, n=172). Results: The median follow-up time was 4.3 years. The 5-year Kaplan-Meier (KM) LRR were 1.8% in luminal A, 3.1% in luminal B, 1.7% in luminal HER 2, 1.9% in HER 2, and 1.9% in TNBC cohorts (P=.81). The 5-year KM DR was highest among women with TNBC: 1.8% in luminal A, 5.0% in luminal B, 2.4% in luminal HER 2, 1.1% in HER 2, and 9.6% in TNBC cohorts (P<.001). Among 172 women with TNBC, the 5-year KM LRR were 1.3% with clear margins versus 12.5% with close or positive margins (P=.04). On multivariable analysis, factors that conferred higher LRR risk were tumors >2 cm, lobular histology, and close/positive surgical margins. Conclusions: The 5-year risk of LRR in our pT1-2N0 cohort treated with mastectomy was generally low, with no significant differences observed between approximated subtypes. Among the subtypes, TNBC conferred the highest risk of DR and an elevated risk of LRR in the presence of positive or close margins. Our data suggest that although subtype alone cannot be used as the sole criterion to offer postmastectomy radiation therapy, it may reasonably be considered in conjunction with other clinicopathologic factors including tumor size, histology, and margin status. Larger cohorts and longer follow-up times are needed to define which women with node-negative disease have high postmastectomy LRR

  20. Intracellular S1P generation is essential for S1P-induced motility of human lung endothelial cells: role of sphingosine kinase 1 and S1P lyase.

    Directory of Open Access Journals (Sweden)

    Evgeny V Berdyshev

    Full Text Available BACKGROUND: Earlier we have shown that extracellular sphingosine-1-phosphate (S1P induces migration of human pulmonary artery endothelial cells (HPAECs through the activation of S1P(1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs and S1P lyase (S1PL, that regulate intracellular S1P accumulation, in HPAEC motility. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino-4-(p-Chlorophenyl Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1P(int, and attenuated S1P(ext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1P(int and potentiated motility of HPAECs to S1P(ext or serum. S1P(ext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting "inside-out" signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs. Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1P(ext or 4-deoxypyridoxine-dependent endothelial cell motility. CONCLUSIONS/SIGNIFICANCE: These results suggest S1P(ext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL.

  1. Synthesis and molecular structures of 1-hydroxyethyl-2-(p-substituted) phenoxymethyl benzimidazoles

    International Nuclear Information System (INIS)

    Wu, J.W.; Zhao, L.; Wang, Z.; Gu, H.; Chen, W.; Zhao, C.

    2016-01-01

    Five novel 1-hydroxyethyl-2-(p-substituted) phenoxymethyl benzimidazoles were synthesized by a three-step route. Under microwave irradiation, the p-substituted phenols were firstly O-carboxymethylated to prepare the corresponding p-substituted phenoxymethyl acids, which then reacted with o-phenylendiamine to get the key intermediates 2-(p-substituted) phenoxymethyl benzimidazole. Finally, the solid-liquid phase transfer catalysis method, where tetrabutyl ammonium bromide (TBAB) was used as the catalyst, was applied to synthesize the target compounds c/sub 1/-c/sub 5/ by the N-hydroxyethylation reaction with 2-chloroethyl alcohol. The structures of the obtained compounds were well characterized and confirmed by elemental analysis, MS, IR, /sup 1/H NMR, /sup 13/C NMR and single-crystal X-ray diffraction analysis. (author)

  2. LMFBR transducer performance in SLSF tests P1 and P2

    International Nuclear Information System (INIS)

    English, J.J.; Anderson, T.T.; Kuzay, T.M.; Wilson, R.E.; Pedersen, D.R.; Kaiser, W.C.; Klingler, W.B.

    1977-01-01

    The reliability and problem areas of sodium-immersed thermocouples, pressure transducers and flowmeters are presented for experiments P1 and P2 of the Sodium Loop Safety Facility (SLSF). The SLSF is a doubly-contained sodium loop situated in a core position of the Engineering Test Reactor at the Idaho National Engineering Laboratory

  3. Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Ying Yang

    2016-01-01

    Full Text Available Maturity-onset diabetes of the young (MODY is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in the HNF4α, GCK, HNF-1α, IPF-1, HNF1β, and NEUROD1 genes were carried out in this family. One HNF4A mutation (p.T130I and two HNF1A polymorphisms (p.I27L and p.S487N were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulated HNF4A expression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations in HNF4A and HNF1A genes might account for this early-onset inherited type 2 diabetes.

  4. Microwave spectroscopy of the 1 s n p P3J fine structure of high Rydberg states in 4He

    Science.gov (United States)

    Deller, A.; Hogan, S. D.

    2018-01-01

    The 1 s n p P3J fine structure of high Rydberg states in helium has been measured by microwave spectroscopy of single-photon transitions from 1 s n s S31 levels in pulsed supersonic beams. For states with principal quantum numbers in the range from n =34 to 36, the J =0 →2 and J =12 fine structure intervals were both observed. For values of n between 45 and 51 only the larger J =0 →2 interval was resolved. The experimental results are in good agreement with theoretical predictions. Detailed characterization of residual uncanceled electric and magnetic fields in the experimental apparatus and calculations of the Stark and Zeeman structures of the Rydberg states in weak fields were used to quantify systematic contributions to the uncertainties in the measurements.

  5. Is Biological Subtype Prognostic of Locoregional Recurrence Risk in Women With pT1-2N0 Breast Cancer Treated With Mastectomy?

    International Nuclear Information System (INIS)

    Truong, Pauline T.; Sadek, Betro T.; Lesperance, Maria F.; Alexander, Cheryl S.; Shenouda, Mina; Raad, Rita Abi; Taghian, Alphonse G.

    2014-01-01

    Purpose: To examine locoregional and distant recurrence (LRR and DR) in women with pT1-2N0 breast cancer according to approximated subtype and clinicopathologic characteristics. Methods and Materials: Two independent datasets were pooled and analyzed. The study participants were 1994 patients with pT1-2N0M0 breast cancer, treated with mastectomy without radiation therapy. The patients were classified into 1 of 5 subtypes: luminal A (ER+ or PR+/HER 2−/grade 1-2, n=1202); luminal B (ER+ or PR+/HER 2−/grade 3, n=294); luminal HER 2 (ER+ or PR+/HER 2+, n=221); HER 2 (ER−/PR−/HER 2+, n=105) and triple-negative breast cancer (TNBC) (ER−/PR−/HER 2−, n=172). Results: The median follow-up time was 4.3 years. The 5-year Kaplan-Meier (KM) LRR were 1.8% in luminal A, 3.1% in luminal B, 1.7% in luminal HER 2, 1.9% in HER 2, and 1.9% in TNBC cohorts (P=.81). The 5-year KM DR was highest among women with TNBC: 1.8% in luminal A, 5.0% in luminal B, 2.4% in luminal HER 2, 1.1% in HER 2, and 9.6% in TNBC cohorts (P 2 cm, lobular histology, and close/positive surgical margins. Conclusions: The 5-year risk of LRR in our pT1-2N0 cohort treated with mastectomy was generally low, with no significant differences observed between approximated subtypes. Among the subtypes, TNBC conferred the highest risk of DR and an elevated risk of LRR in the presence of positive or close margins. Our data suggest that although subtype alone cannot be used as the sole criterion to offer postmastectomy radiation therapy, it may reasonably be considered in conjunction with other clinicopathologic factors including tumor size, histology, and margin status. Larger cohorts and longer follow-up times are needed to define which women with node-negative disease have high postmastectomy LRR risks in contemporary practice

  6. Cold-Adapted Influenza and Recombinant Adenovirus Vaccines Induce Cross-Protective Immunity against pH1N1 Challenge in Mice

    Science.gov (United States)

    Soboleski, Mark R.; Gabbard, Jon D.; Price, Graeme E.; Misplon, Julia A.; Lo, Chia-Yun; Perez, Daniel R.; Ye, Jianqiang; Tompkins, S. Mark; Epstein, Suzanne L.

    2011-01-01

    Background The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1) highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus. Methodology/Principal Findings BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca) influenza viruses from 1977 or recombinant adenoviruses (rAd) expressing 1934 nucleoprotein (NP) and consensus matrix 2 (M2) (NP+M2-rAd). Antibodies against the M2 ectodomain (M2e) were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus. Conclusion/Significance Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic. PMID:21789196

  7. p - n junction diodes fabricated from isolated electrospun fibers of (P(NDI2ODT2)) and an inorganic p-doped semiconductor

    Science.gov (United States)

    Rosado, Alexander; Pinto, Nicholas

    2013-03-01

    A simple method to fabricate, under ambient conditions and within seconds, p - n diodes using an individual electrospun poly{[N, N'-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)}-(P(NDI2ODT2)) fiber and a commercially available p-doped Si/SiO2 substrate is presented. Band bending at the fiber/Si+ interface leads to asymmetric I-V characteristic curves resembling that of a diode. The diode turn-on voltage was in the range 1V and was unaffected via UV light irradiation. The rectification ratio however could be tuned reversibly thereby making this device multifunctional. In addition to being a rectifier, the advantage of our design is the complete exposure of the rectifying junction to the surrounding environment. This has the advantage of making them attractive candidates in the potential fabrication of low power, sensitive and rapid response photo-sensors. NSF

  8. A role of the sphingosine-1-phosphate (S1P)-S1P receptor 2 pathway in epithelial defense against cancer (EDAC).

    Science.gov (United States)

    Yamamoto, Sayaka; Yako, Yuta; Fujioka, Yoichiro; Kajita, Mihoko; Kameyama, Takeshi; Kon, Shunsuke; Ishikawa, Susumu; Ohba, Yusuke; Ohno, Yusuke; Kihara, Akio; Fujita, Yasuyuki

    2016-02-01

    At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)-S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells. © 2016 Yamamoto, Yako, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  9. [Role and related mechanism of S1P/S1P1 signal pathway during post conditioning of hypertrophic cardiomyocytes].

    Science.gov (United States)

    Bao, X H; Li, H X; Tao, J; Li, X M; Yang, Y N; Ma, Y T; Chen, B D

    2016-05-24

    To study the role and mechanism of sphingosine-1-phosphate (S1P)/ sphingosine-1-phosphate receptor 1(S1P1) signal pathway during post conditioning of hypertrophic cardiomyocytes. Neonatal rat cardiomyocytes were isolated and cultured, then stimulated by norepinephrine (NE) to induce cardiomyocytes hypertrophy. Using tri-gas incubator to create hypoxia and reoxygenation enviroment to mimic ischemia-reperfusion and postconditioning. Hypertrophic cardiomyoctyes were divided into five groups according to the presence or absence of various drugs and postconditiong and relevant signal pathways changes were detected: (1) IPost group (hypoxia+ postconditioning); (2) IPost+ S1P group (cells were pretreated with S1P (1 μmol/L) for 2 h before IPost); (3) IPost+ W-146+ S1P group (cells in IPost+ W-146+ S1P group were pretreated with S1P1 inhibitor W-146 (0.4 μmol/L) for 20 min); (4) IPost+ PD98059+ S1P group (cells in IPost+ S1P group were pretreated with MAPK antagonist PD98059 (125 μmol/L) for 20 min); (5) IPost+ LY-294002+ S1P group (cells in IPost+ S1P group were pretreated with PI3K antagonist LY294002 (0.1 μmol/L) for 20 min). Apoptosis was detected by flow cytometry and protein expression of relevant signal pathways were detected by Western blot. (1)Apoptosis rate was significantly increased in hypoxia/reoxygenation (27.90±4.49)% group compared with normal control group (7.97±2.18)%, which could be significantly reduced in IPost group (15.90±1.77)% (all PS1P and IPost+ S1P+ LY-294002 groups than in IPost and IPost+ S1P+ W-146 and IPost+ S1P+ PD98059 group (all PS1P and IPost+ S1P+ LY-294002 group than in IPost and IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 group (all PS1P+ W-146 and IPost+ S1P+ PD98059 groups. p-ERK1/2 and p-Akt levels in IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 were similar as in IPost group. S1P can play protective role on NE induced cardiomyocytes hypertrophy during post conditioning through downregulating caspase-3 expression and

  10. XANES study on Ruddlesdan-Popper phase, Lan+1NinO3n+1 (n = 1, 2 and ∞)

    International Nuclear Information System (INIS)

    Park, Jung-Chul; Kim, Dong-Kuk; Byeon, Song-Hu; Kim, Don

    2001-01-01

    Ruddlesden-Popper phase, La n+1 Ni n O 3n+ 1 (n = 1, 2, and ∞) compounds were prepared by citrate sol-gel method. We revealed the origin of the variation of the electrical conductivities in La n+1 Ni n O 3n+1 (n= 1, 2, and ∞) using resistivity measurements, Rietveld analysis, and X-ray absorption spectroscopy. According to the XANES spectra, it is found that the degree of 4pπ - 4pσ energy splitting between 8345 eV and 8350 eV is qualitatively proportional to the elongation of the out-of-plane Ni-O bond length. With the decrease of 4pπ-4pσ splitting, the strong hybridization of the σ-bonding between Ni-3d and O-2p orbitals creates narrow antibonding σ bands, which finally results in the lower electrical resistivity. (au)

  11. K-n and K-p elastic scattering in K-d collisions from 1.2 to 2.2 GeV/c

    International Nuclear Information System (INIS)

    Declais, Y.; Duchon, J.; Louvel, M.; Patry, J.-P.; Seguinot, J.; Baillon, P.; Bruman, C.; Ferro-Luzzi, M.; Perreau, J.-M.; Ypsilantis, T.

    1977-01-01

    This report contains the detailed description of an experiment which has determined the differential cross section of the K - n→K - n elastic scattering reaction. The results are 12 angular distributions spanning the K - n c.m. energy interval from approximately 1.86 to approximately 2.32 GeV. The measurements have been performed at the CERN PS using a beam of negative kaons with momenta from 1.2 to 2.2 GeV/c incident on a liquid deuterium target. By means of electronic apparatus the process K - d→K - n psub(s) was identified and recorded; this process is basically the same as the K - n elastic reaction insofar as the spectator proton psub(s) has low momentum. The elastic reaction was derived from the above process by taking into account the Fermi motion of the target neutron and by introducing the appropriate corrections to compensate for the effects due to the composite nature of the neutron (double-scattering, final state interaction). These results, constituting the first extensive collection of data on the pure isospin 1 anti KN state have been used in conjunction with other data in a preliminary partial wave analysis of the anti KN elastic system over the c.m. energy range from 1.84 to 2.23 GeV. Mainly for testing purposes, a similar amount of data has been collected for the K - p elastic reaction also from K - d collisions (K - d→K - p nsub(s)). (Auth.)

  12. Changes of electronic properties of p-GaN(0 0 0 1) surface after low-energy N+-ion bombardment

    Science.gov (United States)

    Grodzicki, M.; Mazur, P.; Ciszewski, A.

    2018-05-01

    The p-GaN(0 0 0 1) crystal with a relatively low acceptor concentration of 5 × 1016 cm-3 is used in these studies, which are carried out in situ under ultrahigh vacuum (UHV) by ultraviolet photoelectron spectroscopy (UPS), X-ray photoelectron spectroscopy (XPS) and low-energy electron diffraction (LEED). The p-GaN(0 0 0 1)-(1 × 1) surface is achieved by thermal cleaning. N+-ion bombardment by a 200 eV ion beam changes the surface stoichiometry, enriches it with nitrogen, and disorders it. Such modified surface layer inverts its semiconducting character from p- into n-type. The electron affinity for the already cleaned p-GaN surface and that just after bombardment shows a shift from 2.2 eV to 3.2 eV, as well as an increase of band bending at the vacuum/surface interface from 1.4 eV to 2.5 eV. Proper post-bombardment heating of the sample restores the initial atomic order of the modified layer, leaving its n-type semiconducting character unchanged. The results of the measurements are discussed based on two types of surface states concepts.

  13. Evaluation of P availability from Fe and A1 labelled (32P) phosphates

    International Nuclear Information System (INIS)

    Bittencourt, V.S.

    1975-07-01

    Synthetically Fe and A1 labelled phosphates ( 32 P) show a certain amount of available P to the plants when applied to Sao Paulo State soils. This availability decreases from considered amorphous A1-phosphate (A1-P sub(am)) to A1 phosphate with a certain cristalinity grade (A1-P sub(cr)) and than from this to Fe-P sub(am) followed by Fe-P sub(cr), and it is influenced by both the soil characteristics and mainly by the iron constituents of the samples. In this way, one can not expect that the 0,05 N 2 H SO 4 and the CHANG and JACKSON (1957a) solutions can define properly the available P of these soils. The addition of lime to the soils do not drive to a better P absorption by the plants and its effects are dubious

  14. Neuropharmacology of purinergic receptors in human submucous plexus: Involvement of P2X₁, P2X₂, P2X₃ channels, P2Y and A₃ metabotropic receptors in neurotransmission.

    Science.gov (United States)

    Liñán-Rico, A; Wunderlich, J E; Enneking, J T; Tso, D R; Grants, I; Williams, K C; Otey, A; Michel, K; Schemann, M; Needleman, B; Harzman, A; Christofi, F L

    2015-08-01

    The role of purinergic signaling in human ENS is not well understood. We sought to further characterize the neuropharmacology of purinergic receptors in human ENS and test the hypothesis that endogenous purines are critical regulators of neurotransmission. LSCM-Fluo-4/(Ca(2+))-imaging of postsynaptic Ca(2+) transients (PSCaTs) was used as a reporter of synaptic transmission evoked by fiber tract electrical stimulation in human SMP surgical preparations. Pharmacological analysis of purinergic signaling was done in 1,556 neurons (identified by HuC/D-immunoreactivity) in 235 ganglia from 107 patients; P2XR-immunoreactivity was evaluated in 19 patients. Real-time MSORT (Di-8-ANEPPS) imaging tested effects of adenosine on fast excitatory synaptic potentials (fEPSPs). Synaptic transmission is sensitive to pharmacological manipulations that alter accumulation of extracellular purines: Apyrase blocks PSCaTs in a majority of neurons. An ecto-NTPDase-inhibitor 6-N,N-diethyl-D-β,γ-dibromomethyleneATP or adenosine deaminase augments PSCaTs. Blockade of reuptake/deamination of eADO inhibits PSCaTs. Adenosine inhibits fEPSPs and PSCaTs (IC50 = 25 µM), sensitive to MRS1220-antagonism (A3AR). A P2Y agonist ADPβS inhibits PSCaTs (IC50 = 111 nM) in neurons without stimulatory ADPbS responses (EC50 = 960 nM). ATP or a P2X1,2,2/3 (α,β-MeATP) agonist evokes fast, slow, biphasic Ca(2+) transients or Ca(2+) oscillations (ATP,EC50 = 400 mM). PSCaTs are sensitive to P2X1 antagonist NF279. Low (20 nM) or high (5 µM) concentrations of P2X antagonist TNP-ATP block PSCaTs in different neurons; proportions of neurons with P2XR-immunoreactivity follow the order P2X2 > P2X1 > P2X3; P2X1 + P2X2 and P2X3 + P2X2 are co-localized. RT-PCR identified mRNA-transcripts for P2X1-7, P2Y1,2,12-14R. Purines are critical regulators of neurotransmission in human ENS. Purinergic signaling involves P2X1, P2X2, P2X3 channels, P2X1 + P2X2 co-localization and inhibitory P2Y or A3 receptors. These are

  15. Identification of the 1s2s2p 4P5/2-->1s22s 2S1/2 magnetic quadrupole inner-shell satellite line in the Ar16+ K-shell x-ray spectrum

    Science.gov (United States)

    Beiersdorfer, P.; Bitter, M.; Hey, D.; Reed, K. J.

    2002-09-01

    We have identified the dipole-forbidden 1s2s2p 4P5/2-->1s22s 2S1/2 transition in lithiumlike Ar15+ in high-resolution K-shell x-ray emission spectra recorded at the Livermore EBIT-II electron-beam ion trap and the Princeton National Spherical Tokamak Experiment. Unlike other Ar15+ satellite lines, which can be excited by dielectronic recombination, the line is exclusively excited by electron-impact excitation. Its predicted radiative rate is comparable to that of the well-known 1s2p 3P1-->1s2 1S0 magnetic quadrupole transition in heliumlike Ar16+. As a result, it can also only be observed in low-density plasma. We present calculations of the electron-impact excitation cross sections of the innershell excited Ar15+ satellite lines, including the magnetic sublevels needed for calculating the linear line polarization. We compare these calculations to the relative magnitudes of the observed 1s2s2p-->1s22s transitions and find good agreement, confirming the identification of the lithiumlike 1s2s2p 4P5/2-->1s22s 2S1/2 magnetic quadrupole line.

  16. Alfalfa mosaic virus replicase proteins P1 and P2 interact and colocalize at the vacuolar membrane

    NARCIS (Netherlands)

    Heijden, van der M.W.; Carette, J.E.; Reinhoud, P.J.; Haegi, A.; Bol, J.F.

    2001-01-01

    Replication of Alfalfa mosaic virus (AMV) RNAs depends on the virus-encoded proteins P1 and P2. P1 contains methyltransferase- and helicase-like domains, and P2 contains a polymerase-like domain. Coimmunoprecipitation experiments revealed an interaction between in vitro translated-P1 and P2 and

  17. Optical properties of lattice matched InxGa1-xP1-yNy heteroepitaxial layers on GaP

    International Nuclear Information System (INIS)

    Imanishi, T.; Wakahara, A.; Kim, S.M.; Yonezu, H.; Furukawa, Y.

    2005-01-01

    Optical constants and band structure of In x Ga 1-x P 1-y N y lattice matched to GaP (100) substrate are investigated. Nitrogen concentration in the film estimated by X-ray diffraction and X-ray photoelectron spectroscopy, was 1.4%, 1.8% and 3.5%. Refractive index and transition critical points E 0 (Γ v to Γ c ), E 1 (L v to L c ) and E 2 (X v to X c ) are evaluated by spectroscopic ellipsometry. When N composition increases from 1.4% to 3.5%, both photoluminescence (PL) peak energy, E PL , and E 0 shift to lower energy, and the energy difference ΔE=E 0 -E PL decrease from 380 meV to 110 meV. The large red-sift of E PL from the E 0 suggest that the luminescence is of defect-related luminescence, and crossover point of indirect band structure estimated by the extrapolation of N-composition dependence of ΔE is estimated to be around in In 0.1 Ga 0.9 P 0.96 N 0.04 . (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  18. Pregnane X receptor-dependent induction of the CYP3A4 gene by o,p'-1,1,1,-trichloro-2,2-bis (p-chlorophenyl)ethane.

    Science.gov (United States)

    Medina-Díaz, Irma M; Arteaga-Illán, Georgina; de León, Mario Bermudez; Cisneros, Bulmaro; Sierra-Santoyo, Adolfo; Vega, Libia; Gonzalez, Frank J; Elizondo, Guillermo

    2007-01-01

    CYP3A4, the predominant cytochrome P450 (P450) expressed in human liver and intestine, contributes to the metabolism of approximately half the drugs in clinical use today. CYP3A4 catalyzes the 6beta-hydroxylation of a number of steroid hormones and is involved in the bioactivation of environmental procarcinogens. The expression of CYP3A4 is affected by several stimuli, including environmental factors such as insecticides and pesticides. The o,p'-1,1,1,-trichloro-2,2-bis (p-chlorophenyl)ethane (DDT) isomer of DDT comprises approximately 20% of technical grade DDT, which is an organochloride pesticide. We have recently shown that o,p'-DDT exposure increases CYP3A4 mRNA levels in HepG2 cells. To determine the mechanism by which o,p'-DDT induces CYP3A4 expression, transactivation and electrophoretic mobility shift assays were carried out, revealing that o,p'-DDT activates the CYP3A4 gene promoter through the pregnane X receptor (PXR). CYP3A4 gene promoter activation resulted in both an increase in CYP3A4 mRNA levels and an increase in the total CYP3A4 activity in HepG2 cells. We also observed induction of CYP3A4 and mouse Cyp3a11 mRNA in the intestine of CYP3A4-transgenic mice after exposure to 1 mg/kg o,p'-DDT. At higher doses, a decrease of CYP3A4 inducibility was observed together with an increase in levels of interleukin 6 mRNA, a proinflammatory cytokine that strongly represses CYP3A4 transcription. The present study indicates that regulation of other genes under PXR control may be altered by o,p'-DDT exposure.

  19. Effects of perinatal combined exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) and tributyltin (TBT) on rat female reproductive system.

    Science.gov (United States)

    Makita, Yuji

    2008-05-01

    1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) is the most prevalent metabolite of DDT used as a pesticide before and tributyltin (TBT) compounds are used primarily as antifouling agents on vessels, ships, and aqua culture facilities, as they exert biocidal actions. Currently, p,p'-DDE and TBT are ubiquitously distributed in the environment and bio-accumulated in marine products, especially fish or shellfish. Thus, oral p,p'-DDE and TBT intake through marine products is demonstrated to be rather high in Japan. Consequently, the fetus and neonate will be exposed to p,p'-DDE and TBT via mother. Therefore, effects of perinatal combined exposure to p,p'-DDE and TBT on the female reproductive system after maturation have been investigated in rat female offspring of dams ingesting 125ppm p,p'-DDE (approximately 10mg/kg) and 25ppm TBT (approximately 2mg/kg) during the perinatal period from gestation to lactation. In the present study, no deleterious reproductive outcomes were recognized in p,p'-DDE and/or TBT-treated dams. In contrast, growth retardation had developed in rat female offspring following perinatal exposure to TBT and sustained even after cessation of exposures. Further, reduced ovarian weights with elevated serum follicle-stimulating hormone (FSH) concentrations were observed in the reproductive system of matured female offspring following perinatal exposure to TBT. At present, biological relevance of these alterations remains unknown, but there is a possibility that these alterations lead to reproductive malfunctions in matured female offspring. Copyright © 2007 Elsevier B.V. All rights reserved.

  20. Regulation of P2Y1 receptor traffic by sorting Nexin 1 is retromer independent.

    Science.gov (United States)

    Nisar, Shaista; Kelly, Eamonn; Cullen, Pete J; Mundell, Stuart J

    2010-04-01

    The activity and traffic of G-protein coupled receptors (GPCRs) is tightly controlled. Recent work from our laboratory has shown that P2Y(1) and P2Y(12) responsiveness is rapidly and reversibly modulated in human platelets and that the underlying mechanism requires receptor trafficking as an essential part of this process. However, little is known about the molecular mechanisms underlying P2Y receptor traffic. Sorting nexin 1 (SNX1) has been shown to regulate the endosomal sorting of cell surface receptors either to lysosomes where they are downregulated or back to the cell surface. These functions may in part be due to interactions of SNX1 with the mammalian retromer complex. In this study, we investigated the role of SNX1 in P2Y receptor trafficking. We show that P2Y(1) receptors recycle via a slow recycling pathway that is regulated by SNX1, whereas P2Y(12) receptors return to the cell surface via a rapid route that is SNX1 independent. SNX1 inhibition caused a dramatic increase in the rate of P2Y(1) receptor recycling, whereas inhibition of Vps26 and Vps35 known to be present in retromer had no effect, indicating that SNX1 regulation of P2Y(1) receptor recycling is retromer independent. In addition, inhibition of SNX4, 6 and 17 proteins did not affect P2Y(1) receptor recycling. SNX1 has also been implicated in GPCR degradation; however, we provide evidence that P2Y receptor degradation is SNX1 independent. These data describe a novel function of SNX1 in the regulation of P2Y(1) receptor recycling and suggest that SNX1 plays multiple roles in endocytic trafficking of GPCRs.

  1. Boundedness of n-Multiple Discrete Hardy Operators with Weights for 1p<∞

    Directory of Open Access Journals (Sweden)

    Aigerim Kalybay

    2013-01-01

    Full Text Available We find necessary and sufficient conditions on weighted sequences ωi, i=1,2,…,n-1, u, and v, for which the operator (Sn-1fi=∑k1=1i‍ω1,k1⋯∑kn-1=1kn-2‍ωn-1,kn-1∑j=1kn-1‍fj,i≥1, is bounded from lp,v to lq,u for 1p<∞.

  2. Sphingosine kinase 1/sphingosine-1-phosphate (S1P)/S1P receptor axis is involved in ovarian cancer angiogenesis.

    Science.gov (United States)

    Dai, Lan; Liu, Yixuan; Xie, Lei; Wu, Xia; Qiu, Lihua; Di, Wen

    2017-09-26

    Sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) signaling pathway has been implicated in a variety of pathological processes of ovarian cancer. However, the function of this axis in ovarian cancer angiogenesis remains incompletely defined. Here we provided the first evidence that SphK1/S1P/S1PR 1/3 pathway played key roles in ovarian cancer angiogenesis. The expression level of SphK1, but not SphK2, was closely correlated with the microvascular density (MVD) of ovarian cancer tissue. In vitro , the angiogenic potential and angiogenic factor secretion of ovarian cancer cells could be attenuated by SphK1, but not SphK2, blockage and were restored by the addition of S1P. Moreover, in these cells, we found S1P stimulation induced the angiogenic factor secretion via S1PR 1 and S1PR 3 , but not S1PR 2 . Furthermore, inhibition of S1PR 1/3 , but not S1PR 2 , attenuated the angiogenic potential and angiogenic factor secretion of the cells. in vivo , blockage of SphK or S1PR 1/3 could attenuate ovarian cancer angiogenesis and inhibit angiogenic factor expression in mouse models. Collectively, the current study showed a novel role of SphK1/S1P/S1PR 1/3 axis within the ovarian cancer, suggesting a new target to block ovarian cancer angiogenesis.

  3. (nBuCp)2ZrCl2-catalyzed Ethylene-4M1P Copolymerization: Copolymer Backbone Structure, Melt Behavior, and Crystallization

    KAUST Repository

    Atiqullah, Muhammad

    2016-01-08

    The judicious design of methylaluminoxane (MAO) anions expands the scope for developing industrial metallocene catalysts. Therefore, the effects of MAO anion design on the backbone structure, melt behavior, and crystallization of ethylene−4-methyl-1-pentene (E−4M1P) copolymer were investigated. Ethylene was homopolymerized, as well as copolymerized with 4M1P, using (i) MAO anion A (unsupported [MAOCl2]−) premixed with dehydroxylated silica, (nBuCp)2ZrCl2, and Me2SiCl2; and (ii) MAO anion B (Si−O−Me2Si−[MAOCl2]−) supported with (nBuCp)2ZrCl2 on Me2SiCl2-functionalized silica. Unsupported Me2SiCl2, opposite to the supported analogue, acted as a co-chain transfer agent with 4M1P. The modeling of polyethylene melting and crystallization kinetics, including critical crystallite stability, produced insightful results. This study especially illustrates how branched polyethylene can be prepared from ethylene alone using particularly one metallocene-MAO ion pair, and how a compound, that functionalizes silica as well as terminates the chain, can synthesize ethylene−α-olefin copolymers with novel structures. Hence, it unfolds prospective future research niches in polyethyne systhesis. This article is protected by copyright. All rights reserved.

  4. Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.

    Directory of Open Access Journals (Sweden)

    Donna J Curtis

    Full Text Available We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI titers, avidity indices (AI, B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1.At entry, 26 (29% subjects had pH1N1 protective HAI titers (≥1:40. pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05, but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets.HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent

  5. Reactions of R(2)P-P(SiMe(3))Li with [(R'(3)P)(2)PtCl(2)]. A general and efficient entry to phosphanylphosphinidene complexes of platinum. Syntheses and structures of [(eta(2)-P=(i)Pr(2))Pt(p-Tol(3)P)(2)], [(eta(2)-P=(t)Bu(2))Pt(p-Tol(3)P)(2)], [{eta(2)-P=(N(i)Pr(2))(2)}Pt(p-Tol(3)P)(2)] and [{(Et(2)PhP)(2)Pt}(2)P(2)].

    Science.gov (United States)

    Domańska-Babul, Wioleta; Chojnacki, Jaroslaw; Matern, Eberhard; Pikies, Jerzy

    2009-01-07

    The reactions of lithium derivatives of diphosphanes R(2)P-P(SiMe(3))Li (R = (t)Bu, (i)Pr, Et(2)N and (i)Pr(2)N) with [(R'(3)P)(2)PtCl(2)] (R'(3)P = Et(3)P, Et(2)PhP, EtPh(2)P and p-Tol(3)P) proceed in a facile manner to afford side-on bonded phosphanylphosphinidene complexes of platinum [(eta(2)-P=R(2))Pt(PR'(3))(2)]. The related reactions of Ph(2)P-P(SiMe(3))Li with [(R'(3)P)(2)PtCl(2)] did not yield [(eta(2)-P=PPh(2))Pt(PR'(3))(2)] and resulted mainly in the formation of [{(R'(3)P)(2)Pt}(2)P(2)], Ph(2)P-PLi-PPh(2), (Me(3)Si)(2)PLi and (Me(3)Si)(3)P. Crystallographic data are reported for the compounds [(eta(2)-P=R(2))Pt(p-Tol(3)P)(2)] (R = (t)Bu, (i)Pr, ((i)Pr(2)N)(2)P) and for [{(Et(2)PhP)(2)Pt}(2)P(2)].

  6. Blocking S1P interaction with S1P{sub 1} receptor by a novel competitive S1P{sub 1}-selective antagonist inhibits angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Yasuyuki, E-mail: y.fujii@po.rd.taisho.co.jp [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Igarashi, Yasuyuki [Laboratory of Biomembrane and Biofunctional Chemistry, Hokkaido University, Sapporo, Hokkaido 060-0812 (Japan); Goitsuka, Ryo [Division of Development and Aging, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022 (Japan)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  7. Quasimolecular emission near the Xe(5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance lines induced by collisions with He atoms

    Science.gov (United States)

    Alekseeva, O. S.; Devdariani, A. Z.; Grigorian, G. M.; Lednev, M. G.; Zagrebin, A. L.

    2017-02-01

    This study is devoted to the theoretical investigation of the quasimolecular emission of Xe*-He and Kr*-He collision pairs near the Xe (5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance atomic lines. The potential curves of the quasimolecules Xe(5p 56s) + He and Kr(4p 55s) + He have been obtained with the use of the effective Hamiltonian and pseudopotential methods. Based on these potential curves the processes of quasimolecular emission of Xe*+He and Kr*+He mixtures have been considered and the spectral distributions I(ħΔω) of photons emitted have been obtained in the framework of quasistatic approximation.

  8. Cytochrome P2A13 and P1A1 gene polymorphisms are associated with the occurrence of uterine leiomyoma.

    Science.gov (United States)

    Herr, D; Bettendorf, H; Denschlag, D; Keck, C; Pietrowski, D

    2006-10-01

    To investigate the association between the occurrence of uterine leiomyoma and two SNPs of the CYP 2A13 and CYP 1A1 genes. Prospective case control study with 132 women with clinically and surgically diagnosed uterine leiomyoma and 260 controls. Genotyping was performed by polymerase chain reaction (PCR) based amplification of CYP 2A13 and CYP 1A1 genes, and restriction fragment length polymorphism (RFLP) analysis. Comparing women with uterine leiomyoma and controls, we demonstrate statistical significant differences of allele frequency and genotype distribution for the CYP 1A1 polymorphism (P = 0.025 and P = 0.046, respectively). Furthermore, for the CYP 2A13 polymorphism we found a significant difference concerning allele frequency (P = 0.033). However, for the genotype distribution, only borderline significance was observed (P = 0.064). The CYP 2A13 and CYP 1A1 SNPs are associated with uterine leiomyoma in a Caucasian population and may contribute to the understanding of the pathogenic mechanisms of uterine leiomyoma.

  9. Intracellular S1P Generation Is Essential for S1P-Induced Motility of Human Lung Endothelial Cells: Role of Sphingosine Kinase 1 and S1P Lyase

    Science.gov (United States)

    Berdyshev, Evgeny V.; Gorshkova, Irina; Usatyuk, Peter; Kalari, Satish; Zhao, Yutong; Pyne, Nigel J.; Pyne, Susan; Sabbadini, Roger A.; Garcia, Joe G. N.; Natarajan, Viswanathan

    2011-01-01

    Background Earlier we have shown that extracellular sphingosine-1-phosphate (S1P) induces migration of human pulmonary artery endothelial cells (HPAECs) through the activation of S1P1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs) and S1P lyase (S1PL), that regulate intracellular S1P accumulation, in HPAEC motility. Methodology/Principal Findings Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino)-4-(p-Chlorophenyl) Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1Pint, and attenuated S1Pext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1Pint and potentiated motility of HPAECs to S1Pext or serum. S1Pext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting “inside-out” signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs). Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1Pext or 4-deoxypyridoxine-dependent endothelial cell motility. Conclusions/Significance These results suggest S1Pext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL. PMID:21304987

  10. Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration.

    Science.gov (United States)

    Koch, Alexander; Jäger, Manuel; Völzke, Anja; Grammatikos, Georgios; Zu Heringdorf, Dagmar Meyer; Huwiler, Andrea; Pfeilschifter, Josef

    2015-06-01

    Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells.

  11. PPADS and suramin as antagonists at cloned P2Y- and P2U-purinoceptors.

    Science.gov (United States)

    Charlton, S J; Brown, C A; Weisman, G A; Turner, J T; Erb, L; Boarder, M R

    1996-06-01

    1. The effect of suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) on the stimulation of phospholipase C in 1321N1 cells transfected with the human P2U-purinoceptor (h-P2U-1321N1 cells) or with the turkey P2Y-purinoceptor (t-P2Y-1321N1 cells) was investigated. 2-Methylthioadenosine triphosphate (2MeSATP) was used as the agonist at t-P2Y-1321N1 cells and uridine triphosphate (UTP) at h-P2U-1321N1 cells. 2. Suramin caused a parallel shift to the right of the concentration-response curves for 2MeSATP in the t-P2Y-1321N1 cells, yielding a Schild plot with a slope of 1.16 +/- 0.08 and a pA2 value of 5.77 +/- 0.11. 3. Suramin also caused a shift to the right of concentration-response curves for UTP in the h-P2U-1321N1 cells, and on Schild plots gave a slope different from unity (1.57 +/- 0.19) and an apparent pA2 value of 4.32 +/- 0.13. Suramin was therefore a less potent antagonist at the P2U-purinoceptor than the P2Y-purinoceptor. 4. In the presence of the ectonucleotidase inhibitor, ARL 67156 (6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP) there was no significant difference in the EC50 or shapes of curves with either cell type, and no difference in pA2 values for suramin. 5. PPADS caused an increase in the EC50 for 2MeSATP in the t-P2Y-1321N1 cells. The Schild plot had a slope different from unity (0.55 +/- 0.15) and an X-intercept corresponding to an apparent pA2 of 5.98 +/- 0.65. 6. PPADS up to 30 microM had no effect on the concentration-response curve for UTP with the h-P2U-1321N1 cells. 7. In conclusion, suramin and PPADS show clear differences in their action at the 2 receptor types, in each case being substantially more effective as an antagonist at the P2Y-purinoceptor than at the P2U-purinoceptor. Ectonucleotidase breakdown had little influence on the nature of the responses at the two receptor types, or in their differential sensitivity to suramin.

  12. Femtosecond induced transparency and absorption in the extreme ultraviolet by coherent coupling of the He 2s2p (1Po) and 2p2 (1Se) double excitation states with 800 nm light

    International Nuclear Information System (INIS)

    Loh, Z.-H.; Greene, C.H.; Leone, S.R.

    2007-01-01

    Femtosecond high-order harmonic transient absorption spectroscopy is used to observe electromagnetically induced transparency-like behavior as well as induced absorption in the extreme ultraviolet by laser dressing of the He 2s2p ( 1 P 0 ) and 2p 2 ( 1 S e ) double excitation states with an intense 800 nm field. Probing in the vicinity of the 1s 22s2p transition at 60.15 eV reveals the formation of an Autler-Townes doublet due to coherent coupling of the double excitation states. Qualitative agreement with the experimental spectra is obtained only when optical field ionization of both double excitation states into the N = 2 continuum is included in the theoretical model. Because the Fano q-parameter of the unperturbed probe transition is finite, the laser-dressed He atom exhibits both enhanced transparency and absorption at negative and positive probe energy detunings, respectively

  13. The subcellular distribution of the human ribosomal "stalk" components: P1, P2 and P0 proteins

    DEFF Research Database (Denmark)

    Tchórzewski, Marek; Krokowski, Dawid; Rzeski, Wojciech

    2003-01-01

    The ribosomal "stalk" structure is a distinct lateral protuberance located on the large ribosomal subunit in prokaryotic, as well as in eukaryotic cells. In eukaryotes, this ribosomal structure is composed of the acidic ribosomal P proteins, forming two hetero-dimers (P1/P2) attached...

  14. Excitation-energy dependence of the resonant Auger transitions to the 4p4(1D)np (n=5,6) states across the 3d3/2-15p and 3d5/2-16p resonances in Kr

    International Nuclear Information System (INIS)

    Sankari, A.; Alitalo, S.; Nikkinen, J.; Kivimaeki, A.; Aksela, S.; Aksela, H.; Fritzsche, S.

    2007-01-01

    The energy dependencies of the intensities and angular distribution parameters β of the resonant Auger final states 4p 4 ( 1 D)np (n=5,6) of Kr were determined experimentally in the excitation-energy region of the overlapping 3d 3/2 -1 5p and 3d 5/2 -1 6p resonances. The experimental results were compared with the outcome of multiconfiguration Dirac-Fock calculations. Combining experimental and calculated results allowed us to study interference effects between the direct and several resonant channels that populate the 4p 4 ( 1 D)np states. The inclusion of the direct channel was crucial in order to reproduce the observed energy behavior of the angular distribution parameters. It was also important to take into account experimentally observed shake transitions

  15. Identification of a High-Risk Group Among Patients With Oral Cavity Squamous Cell Carcinoma and pT1-2N0 Disease

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Chun-Ta [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Lin, Chien-Yu [Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Radiation Oncology, Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Sciences of Chang Gung University, Taoyuan, Taiwan (China); Fan, Kang-Hsing [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Radiation Oncology, Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Sciences of Chang Gung University, Taoyuan, Taiwan (China); Wang, Hung-Ming [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Hema-Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Ng, Shu-Hang [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Diagnostic Radiology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Lee, Li-Yu; Hsueh, Chuen [Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Chen, I-How; Huang, Shiang-Fu; Kang, Chung-Jan [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); and others

    2012-01-01

    Purpose: In the American Joint Committee on Cancer 2010 classification system, pT1-2N0 oral cavity squamous cell carcinoma (OSCC) is considered an early-stage cancer treatable with surgery alone (National Comprehensive Cancer Network 2010 guidelines). Our aim was to evaluate the feasibility of surgery alone for pT1-2N0 OSCC patients. Methods and Materials: Among 1279 previously untreated OSCC patients referred to our hospital between January 1996 and May 2008, we identified 457 consecutive patients with pT1-2N0 disease. All had radical tumor excision with neck dissection. A total of 387 patients showing pathologic margins greater than 4 mm and treated by surgery alone were included in the final analysis. All were followed up for at least 24 months after surgery or until death. The 5-year rates of control, distant metastasis, and survival were the main outcome measures. Results: The 5-year rates in the entire group of pT1-2N0 patients were as follows: local control, 91%; neck control, 92%; distant metastases, 1%; disease-free survival, 85%; disease-specific survival, 93%; and overall survival, 84%. Multivariate analysis identified poor differentiation and pathologic tumor depth of 4 mm or greater as independent risk factors for neck control, disease-free survival, and disease-specific survival. A scoring system using poor differentiation and tumor depth was formulated to define distinct prognostic groups. The presence of both poorly differentiated tumors and a tumor depth of 4 mm or greater resulted in significantly poorer 5-year neck control (p < 0.0001), disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p = 0.0046) rates. Conclusion: The combination of poor differentiation and pathologic tumor depth of 4 mm or greater identified a subset of pT1-2N0 OSCC patients with poor outcome, who may have clinical benefit from postoperative adjuvant radiotherapy.

  16. Undoped p-type GaN1-xSbx alloys: Effects of annealing

    Science.gov (United States)

    Segercrantz, N.; Baumgartner, Y.; Ting, M.; Yu, K. M.; Mao, S. S.; Sarney, W. L.; Svensson, S. P.; Walukiewicz, W.

    2016-12-01

    We report p-type behavior for undoped GaN1-xSbx alloys with x ≥ 0.06 grown by molecular beam epitaxy at low temperatures (≤400 °C). Rapid thermal annealing of the GaN1-xSbx films at temperatures >400 °C is shown to generate hole concentrations greater than 1019 cm-3, an order of magnitude higher than typical p-type GaN achieved by Mg doping. The p-type conductivity is attributed to a large upward shift of the valence band edge resulting from the band anticrossing interaction between localized Sb levels and extended states of the host matrix.

  17. Sphingosine-1-Phosphate Mediates ICAM-1-Dependent Monocyte Adhesion through p38 MAPK and p42/p44 MAPK-Dependent Akt Activation

    Science.gov (United States)

    Lin, Chih-Chung; Lee, I-Ta; Hsu, Chun-Hao; Hsu, Chih-Kai; Chi, Pei-Ling; Hsiao, Li-Der; Yang, Chuen-Mao

    2015-01-01

    Up-regulation of intercellular adhesion molecule-1 (ICAM-1) is frequently implicated in lung inflammation. Sphingosine-1-phosphate (S1P) has been shown to play a key role in inflammation via adhesion molecules induction, and then causes lung injury. However, the mechanisms underlying S1P-induced ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unclear. The effect of S1P on ICAM-1 expression was determined by Western blot and real-time PCR. The involvement of signaling pathways in these responses was investigated by using the selective pharmacological inhibitors and transfection with siRNAs. S1P markedly induced ICAM-1 expression and monocyte adhesion which were attenuated by pretreatment with the inhibitor of S1PR1 (W123), S1PR3 (CAY10444), c-Src (PP1), EGFR (AG1478), PDGFR (AG1296), MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), PI3K (LY294002), or AP-1 (Tanshinone IIA) and transfection with siRNA of S1PR1, S1PR3, c-Src, EGFR, PDGFR, p38, p42, JNK1, c-Jun, or c-Fos. We observed that S1P-stimulated p42/p44 MAPK and p38 MAPK activation was mediated via a c-Src/EGFR and PDGFR-dependent pathway. S1P caused the c-Src/EGFR/PDGFR complex formation. On the other hand, we demonstrated that S1P induced p42/p44 MAPK and p38 MAPK-dependent Akt activation. In addition, S1P-stimulated JNK1/2 phosphorylation was attenuated by SP600125 or PP1. Finally, S1P enhanced c-Fos mRNA levels and c-Jun phosphorylation. S1P-induced c-Jun activation was reduced by PP1, AG1478, AG1296, U0126, SP600125, SB202190, or LY294002. These results demonstrated that S1P-induced ICAM-1 expression and monocyte adhesion were mediated through S1PR1/3/c-Src/EGFR, PDGFR/p38 MAPK, p42/p44 MAPK/Akt-dependent AP-1 activation. PMID:25734900

  18. pH-dependent inhibition of K2P3.1 prolongs atrial refractoriness in whole hearts

    DEFF Research Database (Denmark)

    Skarsfeldt, Mark A; Jepps, Thomas A; Bomholtz, Sofia H

    2016-01-01

    In isolated human atrial cardiomyocytes, inhibition of K2P3.1 K(+) channels results in action potential (action potential duration (APD)) prolongation. It has therefore been postulated that K2P3.1 (KCNK3), together with K2P9.1 (KCNK9), could represent novel drug targets for the treatment of atrial...... fibrillation (AF). However, it is unknown whether these findings in isolated cells translate to the whole heart. The purposes of this study were to investigate the expression levels of KCNK3 and KCNK9 in human hearts and two relevant rodent models and determine the antiarrhythmic potential of K2P3.1 inhibition...... displayed a more uniform expression of KCNK3 between atria and ventricle. In voltage-clamp experiments, ML365 and A293 were found to be potent and selective inhibitors of K2P3.1, but at pH 7.4, they failed to prolong atrial APD and refractory period (effective refractory period (ERP)) in isolated perfused...

  19. Hydrogen Passivation of N(+)P and P(+)N Heteroepitaxial InP Solar Cell Structures

    Science.gov (United States)

    Chatterjee, B.; Davis, W. C.; Ringel, S. A.; Hoffman, R., Jr.

    1995-01-01

    Dislocations and related point defect complexes caused by lattice mismatch currently limit the performance of heteroepitaxial InP cells by introducing shunting paths across the active junction and by the formation of deep traps within the base region. We have previously demonstrated that plasma hydrogenation is an effective and stable means to passivate the electrical activity of such defects in specially designed heteroepitaxial InP test structures to probe hydrogen passivation at typical base depths within a cell structure. In this work, we present our results on the hydrogen passivation of actual heteroepitaxial n(+)p and p(+)n InP cell structures grown on GaAs substrates by metalorganic chemical vapor deposition (MOCVD). We have found that a 2 hour exposure to a 13.56 MHz hydrogen plasma at 275 C reduces the deep level concentration in the base regions of both n(+)p and p(+)n heteroepitaxial InP cell structures from as-grown values of 5 - 7 x 10(exp 14)/cc, down to 3 - 5 x 10(exp 12)/cc. All dopants were successfully reactivated by a 400 C, 5 minute anneal With no detectable activation of deep levels. I-V analysis indicated a subsequent approx. 100 fold decrease In reverse leakage current at -1 volt reverse bias, and an improved built in voltage for the p(+)n structures. ln addition to being passivated,dislocations are also shown to participate in secondary interactions during hydrogenation. We find that the presence of dislocations enhances hydrogen diffusion into the cell structure, and lowers the apparent dissociation energy of Zn-H complexes from 1.19 eV for homoepitaxial Zn-doped InP to 1.12 eV for heteroepitaxial Zn-doped InP. This is explained by additional hydrogen trapping at dislocations subsequent to the reactivation of Zn dopants after hydrogenation.

  20. Hydrogen passivation of N(+)-P and P(+)-N heteroepitaxial InP solar cell structures

    Science.gov (United States)

    Chatterjee, Basab; Davis, William C.; Ringel, Steve A.; Hoffman, Richard, Jr.

    1996-01-01

    Dislocations and related point defect complexes caused by lattice mismatch currently limit the performance of heteroepitaxial InP cells by introducing shunting paths across the active junction and by the formation of deep traps within the base region. We have previously demonstrated that plasma hydrogenation is an effective and stable means to passivate the electrical activity of such defects in specially designed heteroepitaxial InP test structures to probe hydrogen passivation at typical base depths within a cell structure. In this work, we present our results on the hydrogen passivation of actual heteroepitaxial n-p and p-n InP cell structures grown on GaAs substrates by metalorganic chemical vapor deposition (MOCVD). We have found that a 2 hour exposure to a 13.56 MHz hydrogen plasma at 275 C reduces the deep level concentration in the base regions of both n(+)-p and p(+)-n heteroepitaxial InP cell structures from as-grown values of 5-7 x 10(exp 14) cm(exp -3), down to 3-5 x 10(exp 12) cm(exp -3). All dopants were successfully reactivated by a 400 C, 5 minute anneal with no detectable activation of deep levels. One to five analysis indicated a subsequent approximately 100 fold decrease in reverse leakage current at -1 volt reverse bias, and an improved built in voltage for the p(+)-n structures. In addition to being passivated, dislocations are also shown to participate in secondary interactions during hydrogenation. We find that the presence of dislocations enhances hydrogen diffusion into the cell structure, and lowers the apparent dissociation energy of Zn-H complexes from 1.19 eV for homoepitaxial Zn-doped InP to 1.12 eV for heteroepitaxial Zn-doped InP. This is explained by additional hydrogen trapping at dislocations subsequent to the reactivation of Zn dopants after hydrogenation.

  1. Sodium sulfite pH-buffering effect for improved xylose-phenylalanine conversion to N-(1-deoxy-d-xylulos-1-yl)-phenylalanine during an aqueous Maillard reaction.

    Science.gov (United States)

    Cui, Heping; Duhoranimana, Emmanuel; Karangwa, Eric; Jia, Chengsheng; Zhang, Xiaoming

    2018-04-25

    The yield of the Maillard reaction intermediate (MRI), prepared in aqueous medium, is usually unsatisfactory. However, the addition of sodium sulfite could improve the conversion of xylose-phenylalanine (Xyl-Phe) to the MRI (N-(1-deoxy-d-xylulos-1-yl)-phenylalanine) in aqueous medium. Sodium sulfite (Na 2 SO 3 ) showed a significant pH-buffering effect during the Maillard reaction, which accounted for its facilitation of the N-(1-deoxy-d-xylulos-1-yl)-phenylalanine yield. The results revealed that the pH could be maintained at a relatively high level (above 7.0) for an optimized pH-buffering effect when Na 2 SO 3 (4.0%) was added before the reaction of Xyl-Phe. Thus, the conversion of Xyl-Phe to N-(1-deoxy-d-xylulos-1-yl)-phenylalanine increased from 47.23% to 74.86%. Furthermore, the addition moment of Na 2 SO 3 and corresponding solution pH were crucial factors in regulating the pH-buffering effect of Na 2 SO 3 on N-(1-deoxy-d-xylulos-1-yl)-phenylalanine yield. Based on the pH-buffering effect of Na 2 SO 3 and maintaining the optimal pH 7.4 relatively stable, the conversion of Xyl-Phe to N-(1-deoxy-d-xylulos-1-yl)-phenylalanine was successfully improved. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Conjugation of nitrated acetaminophen to Der p1 amplifies peripheral blood monocyte response to Der p1.

    Directory of Open Access Journals (Sweden)

    Ryan G Thomas

    Full Text Available An association of acetaminophen use and asthma was observed in the International Study of Asthma and Allergies in Childhood study. However there are no clear mechanisms to explain an association between acetaminophen use and immunologic pathology. In acidic conditions like those in the stomach and inflamed airway, tyrosine residues are nitrated by nitrous and peroxynitrous acids. The resulting nitrotyrosine is structurally similar to 2,4-dinitrophenol and 2,4-dinitrochlorobenzene, known haptens that enhance immune responses by covalently binding proteins. Nitrated acetaminophen shares similar molecular structure.We hypothesized the acetaminophen phenol ring undergoes nitration under acidic conditions, producing 3-nitro-acetaminophen which augments allergic responses by acting as a hapten for environmental allergens.3-nitro-acetaminophen was formed from acetaminophen in the presence of acidified nitrite, purified by high performance liquid chromatography, and assayed by gas-chromatography mass spectrometry. Purified 3-nitro-acetaminophen was reacted with Dermatophagoides pteronyssinus (Der p1 and analyzed by mass spectrometry to identify the modification site. Human peripheral blood mononuclear cells proliferation response was measured in response to 3-nitro-acetaminophen and to 3-nitro-acetaminophen-modified Der p1.Acetaminophen was modified by nitrous acid forming 3-nitro-acetaminophen over a range of different acidic conditions consistent with airway inflammation and stomach acidity. The Der p1 protein-hapten adduct creation was confirmed by liquid chromatography-mass spectrometry proteomics modifying cysteine 132. Peripheral blood mononuclear cells exposed to 3-nitro-acetaminophen-modified Der p1 had increased proliferation and cytokine production compared to acetaminophen and Der p1 alone (n = 7; p < 0.05.These data suggests 3-nitro-acetaminophen formation and reaction with Der p1 provides a mechanism by which stomach acid or infection

  3. Production of psi(2S) Mesons in p anti-p Collisions at 1.96-TeV

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, T.; /Helsinki Inst. of Phys.; Adelman, Jahred A.; /Chicago U., EFI; Akimoto, T.; /Tsukuba U.; Alvarez Gonzalez, B.; /Cantabria Inst. of Phys.; Amerio, S.; /INFN, Padua; Amidei, Dante E.; /Michigan U.; Anastassov, A.; /Northwestern U.; Annovi, Alberto; /Frascati; Antos, Jaroslav; /Comenius U.; Apollinari, G.; /Fermilab; Apresyan, A.; /Purdue U. /Waseda U.

    2009-05-01

    The authors have measured the differential cross section for the inclusive production of {psi}(2S) mesons decaying to {mu}{sup +}{mu}{sup -} that were produced in prompt or B-decay processes from p{bar p} collisions at 1.96 TeV. These measurements have been made using a data set from an integrated luminosity of 1.1 fb{sup -1} collected by the CDF II detector at Fermilab. For events with transverse momentum p{sub T}({psi}(2S)) > 2 GeV/c and rapidity |y({psi}(2S))| < 0.6 we measure the integrated inclusive cross section {sigma}(p{bar p} {yields} {psi}(2S)X) {center_dot} Br({psi}(2S) {yields} {mu}{sup +}{mu}{sup -}) to be 3.29 {+-} 0.04(stat.) {+-} 0.32(syst.) nb.

  4. Association of Sphingosine-1-phosphate (S1P)/S1P Receptor-1 Pathway with Cell Proliferation and Survival in Canine Hemangiosarcoma.

    Science.gov (United States)

    Rodriguez, A M; Graef, A J; LeVine, D N; Cohen, I R; Modiano, J F; Kim, J-H

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a key biolipid signaling molecule that regulates cell growth and survival, but it has not been studied in tumors from dogs. S1P/S1P1 signaling will contribute to the progression of hemangiosarcoma (HSA). Thirteen spontaneous HSA tissues, 9 HSA cell lines, 8 nonmalignant tissues, including 6 splenic hematomas and 2 livers with vacuolar degeneration, and 1 endothelial cell line derived from a dog with splenic hematoma were used. This was a retrospective case series and in vitro study. Samples were obtained as part of medically necessary diagnostic procedures. Microarray, qRT-PCR, immunohistochemistry, and immunoblotting were performed to examine S1P1 expression. S1P concentrations were measured by high-performance liquid chromatography/mass spectrometry. S1P signaling was evaluated by intracellular Ca(2+) mobilization; proliferation and survival were evaluated using the MTS assay and Annexin V staining. Canine HSA cells expressed higher levels of S1P1 mRNA than nonmalignant endothelial cells. S1P1 protein was present in HSA tissues and cell lines. HSA cells appeared to produce low levels of S1P, but they selectively consumed S1P from the culture media. Exogenous S1P induced an increase in intracellular calcium as well as increased proliferation and viability of HSA cells. Prolonged treatment with FTY720, an inhibitor of S1P1 , decreased S1P1 protein expression and induced apoptosis of HSA cells. S1P/S1P1 signaling pathway functions to maintain HSA cell viability and proliferation. The data suggest that S1P1 or the S1P pathway in general could be targets for therapeutic intervention for dogs with HSA. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  5. O1, P1, N2 models of the global ocean tide on an elastic earth plus surface potential and spherical harmonic decompositions for M2, S2, and K1

    Science.gov (United States)

    Parke, M. E.

    1982-01-01

    The models of M2, S2, and K1 presented in Parke and Hendershott (1980) are supplemented with models of O1, P1, and N2. The models satisfy specified elevation boundary conditions and are generated by fighting a small number of test functions to island data. Maps are presented of the geocentric tide, the induced free space potential, the induced vertical component of the solid earth tide, and the induced vertical component of the gravitational field for each new component. Maps of the tidal potential seen by an observer fixed to the surface of the solid earth are also presented for all six constituents. Spherical harmonic coefficients up to order four and the rms magnitude of the coefficients to order fifteen are presented for each constituent. The rms magnitudes of the P1 and K1 coefficients normalized by their respective equilibrium amplitudes are compared to determine the effect of the diurnal core resonance.

  6. Tables of Shore and Fano parameters for the helium resonances 2s21S, 2p21D, and 2s 2p 1P excited in p-He collisions E/sub p/ = 33 to 150 keV

    International Nuclear Information System (INIS)

    Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Merchez, H.

    1976-01-01

    Absolute values of Shore and Fano parameters are tabulated for the helium atom 2s 2 1 S, 2p 2 1 D, and 2s 2p 1 P resonances produced by a proton beam. Observations were made on the spectra of ejected electrons. The important variation of the shape of the resonances with ejection angle is illustrated for E/sub p/ = 100 keV; the variation with proton energy is shown at 30 0

  7. Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae*

    Science.gov (United States)

    Effelsberg, Daniel; Cruz-Zaragoza, Luis Daniel; Tonillo, Jason; Schliebs, Wolfgang; Erdmann, Ralf

    2015-01-01

    Proteins designated for peroxisomal protein import harbor one of two common peroxisomal targeting signals (PTS). In the yeast Saccharomyces cerevisiae, the oleate-induced PTS2-dependent import of the thiolase Fox3p into peroxisomes is conducted by the soluble import receptor Pex7p in cooperation with the auxiliary Pex18p, one of two supposedly redundant PTS2 co-receptors. Here, we report on a novel function for the co-receptor Pex21p, which cannot be fulfilled by Pex18p. The data establish Pex21p as a general co-receptor in PTS2-dependent protein import, whereas Pex18p is especially important for oleate-induced import of PTS2 proteins. The glycerol-producing PTS2 protein glycerol-3-phosphate dehydrogenase Gpd1p shows a tripartite localization in peroxisomes, in the cytosol, and in the nucleus under osmotic stress conditions. We show the following: (i) Pex21p is required for peroxisomal import of Gpd1p as well as a key enzyme of the NAD+ salvage pathway, Pnc1p; (ii) Pnc1p, a nicotinamidase without functional PTS2, is co-imported into peroxisomes by piggyback transport via Gpd1p. Moreover, the specific transport of these two enzymes into peroxisomes suggests a novel regulatory role for peroxisomes under various stress conditions. PMID:26276932

  8. Functional and molecular evidence for heteromeric association of P2Y1 receptor with P2Y2 and P2Y4 receptors in mouse granulocytes.

    Science.gov (United States)

    Ribeiro-Filho, Antonio Carlos; Buri, Marcus Vinicius; Barros, Carlos Castilho; Dreyfuss, Juliana Luporini; Nader, Helena Bonciani; Justo, Giselle Zenker; Craveiro, Rogério Bastos; Pesquero, João Bosco; Miranda, Antonio; Ferreira, Alice Teixeira; Paredes-Gamero, Edgar Julian

    2016-07-07

    All hematopoietic cells express P2 receptors, however pharmacological characteristics such as expression and affinity in granulocytes are unknown. Pharmacological characteristics of P2 receptors were evaluated by Ca(2+) measurements using Fura-2 fluorophore. P2 receptors expression were analyzed by flow cytometry and RT-PCR. P2 interaction were shown by coimmunoprecipitation, western blotting and FRET. Granulocytes were responsive to P2Y agonists, whereas P2X agonists were ineffective. Ca(2+) increase, elicited by ADP and UTP was dependent on intracellular stocks and sensitive to G-coupled receptor inhibition. Moreover, MRS2179, a specific antagonist of the P2Y1 receptor, abolished ADP response. Interestingly, ADP and UTP exhibited full heterologous desensitization, suggesting that these agonists interact with the same receptor. The heteromeric association between P2Y1 receptor and the P2Y2 and P2Y4 receptors was shown by immunoprecipitation and FRET analysis. Clear evidence of heteromeric association of P2Y receptors was found during the evaluation of P2 receptors present in mice granulocytes, which could impact in the classical pharmacology of P2Y receptors in granulocytes.

  9. Contrasting intermolecular and intramolecular exciplex formation of a 1,4-dicyano-2-methylnaphthalene-N,N-dimethyl-p-toluidine dyad.

    Science.gov (United States)

    Imoto, Mitsutaka; Ikeda, Hiroshi; Fujii, Takayuki; Taniguchi, Hisaji; Tamaki, Akihiro; Takeda, Motonori; Mizuno, Kazuhiko

    2010-05-07

    An intramolecular exciplex is formed upon excitation of the cyclohexane solution of the 1,4-dicyano-2-methylnaphthalene-N,N-dimethyl-p-toluidine dyad, but little if any intramolecular CT complex exists in the ground state of this substance in solution. In contrast, in the crystalline state, the dyad forms an intermolecular mixed-stack CT complex in the ground state and an intermolecular exciplex when it is photoexcited.

  10. Hydrogen passivation of n+p and p+n heteroepitaxial InP solar cell structures

    Science.gov (United States)

    Chatterjee, B.; Ringel, S. A.; Hoffman, R., Jr.

    1995-01-01

    High-efficiency, heteroepitaxial (HE) InP solar cells, grown on GaAs, Si or Ge substrates, are desirable for their mechanically strong, light-weight and radiation-hard properties. However, dislocations, caused by lattice mismatch, currently limit the performance of the HE cells. This occurs through shunting paths across the active photovoltaic junction and by the formation of deep levels. In previous work we have demonstrated that plasma hydrogenation is an effective and stable means to passivate the electrical activity of dislocations in specially designed HE InP test structures. In this work, we present the first report of successful hydrogen passivation in actual InP cell structures grown on GaAs substrates by metalorganic chemical vapor deposition (MOCVD). We have found that a 2 hour exposure to a 13.56 MHz hydrogen plasma at 275 C reduces the deep level concentration in HE n+n InP cell structures from as-grown values of approximately 10(exp 15)/cm(exp -3), down to 1-2 x 10(exp 13)/cm(exp -3). The deep levels in the p-type base region of the cell structure match those of our earlier p-type test structures, which were attributed to dislocations or related point defect complexes. All dopants were successfully reactivated by a 400 C, 5 minute anneal with no detectable activation of deep levels. I-V analysis indicated a subsequent approximately 10 fold decrease in reverse leakage current at -1 volt reverse bias, and no change in the forward biased series resistance of the cell structure which indicates complete reactivation of the n+ emitter. Furthermore, electrochemical C-V profiling indicates greatly enhanced passivation depth, and hence hydrogen diffusion, for heteroepitaxial structures when compared with identically processed homoepitaxial n+p InP structures. An analysis of hydrogen diffusion in dislocated InP will be discussed, along with comparisons of passivation effectiveness for n+p versus p+n heteroepitaxial cell configurations. Preliminary hydrogen

  11. Investigation on electrical properties of diffusive p-n junctions in InP and solid solutions of InAssub(x)Psub(1-x)

    International Nuclear Information System (INIS)

    Agaev, Ya.; Atabaev, Kh.; Gazakov, O.

    1977-01-01

    Diodes from InP and from solid solutions of InAssub(0.6)Psub(0.4), InAssub(0.5)Psub(0.5) were obtained by the diffusion of Zn. The voltage-current characteristic was measured at a direct current in the temperature range from 80 to 300 K. The rectification factor is 10 4 and 2.5 -3.0 x10 2 , respectively, for InP and InAssub(x)Psub(1-x) p-n junctions. The lifetime, the series resistance and resistance of the p-n junction at a zero bias were calculated from an analysis of the voltage-current characteristics

  12. Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae.

    Science.gov (United States)

    Effelsberg, Daniel; Cruz-Zaragoza, Luis Daniel; Tonillo, Jason; Schliebs, Wolfgang; Erdmann, Ralf

    2015-10-16

    Proteins designated for peroxisomal protein import harbor one of two common peroxisomal targeting signals (PTS). In the yeast Saccharomyces cerevisiae, the oleate-induced PTS2-dependent import of the thiolase Fox3p into peroxisomes is conducted by the soluble import receptor Pex7p in cooperation with the auxiliary Pex18p, one of two supposedly redundant PTS2 co-receptors. Here, we report on a novel function for the co-receptor Pex21p, which cannot be fulfilled by Pex18p. The data establish Pex21p as a general co-receptor in PTS2-dependent protein import, whereas Pex18p is especially important for oleate-induced import of PTS2 proteins. The glycerol-producing PTS2 protein glycerol-3-phosphate dehydrogenase Gpd1p shows a tripartite localization in peroxisomes, in the cytosol, and in the nucleus under osmotic stress conditions. We show the following: (i) Pex21p is required for peroxisomal import of Gpd1p as well as a key enzyme of the NAD(+) salvage pathway, Pnc1p; (ii) Pnc1p, a nicotinamidase without functional PTS2, is co-imported into peroxisomes by piggyback transport via Gpd1p. Moreover, the specific transport of these two enzymes into peroxisomes suggests a novel regulatory role for peroxisomes under various stress conditions. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Vibrational Fingerprints of Low-Lying PtnP2n (n = 1–5) Cluster Structures from Global Optimization Based on Density Functional Theory Potential Energy Surfaces

    KAUST Repository

    Jedidi, Abdesslem; Li, Rui; Fornasiero, Paolo; Cavallo, Luigi; Carbonniere, Philippe

    2015-01-01

    Vibrational fingerprints of small PtnP2n (n = 1–5) clusters were computed from their low-lying structures located from a global exploration of their DFT potential energy surfaces with the GSAM code. Five DFT methods were assessed from the CCSD(T) wavenumbers of PtP2 species and CCSD relative energies of Pt2P4 structures. The eight first PtnP2n isomers found are reported. The vibrational computations reveal (i) the absence of clear signatures made by overtone or combination bands due to very weak mechanical and electrical anharmonicities and (ii) some significant and recurrent vibrational fingerprints in correlation with the different PP bonding situations in the PtnP2n structures.

  14. Vibrational Fingerprints of Low-Lying PtnP2n (n = 1–5) Cluster Structures from Global Optimization Based on Density Functional Theory Potential Energy Surfaces

    KAUST Repository

    Jedidi, Abdesslem

    2015-11-13

    Vibrational fingerprints of small PtnP2n (n = 1–5) clusters were computed from their low-lying structures located from a global exploration of their DFT potential energy surfaces with the GSAM code. Five DFT methods were assessed from the CCSD(T) wavenumbers of PtP2 species and CCSD relative energies of Pt2P4 structures. The eight first PtnP2n isomers found are reported. The vibrational computations reveal (i) the absence of clear signatures made by overtone or combination bands due to very weak mechanical and electrical anharmonicities and (ii) some significant and recurrent vibrational fingerprints in correlation with the different PP bonding situations in the PtnP2n structures.

  15. Suppression of Zeeman relaxation in cold collisions of 2P1/2 atoms

    International Nuclear Information System (INIS)

    Tscherbul, T. V.; Dalgarno, A.; Buchachenko, A. A.; Lu, M.-J.; Weinstein, J. D.

    2009-01-01

    We present a combined experimental and theoretical study of angular momentum depolarization in cold collisions of 2 P atoms in the presence of an external magnetic field. We show that collision-induced Zeeman relaxation of Ga( 2 P 1/2 ) and In( 2 P 1/2 ) atoms in cold 4 He gas is dramatically suppressed compared to atoms in 2 P 3/2 states. Using rigorous quantum-scattering calculations based on ab initio interaction potentials, we demonstrate that Zeeman transitions in collisions of atoms in 2 P 1/2 electronic states occur via couplings to the 2 P 3/2 state induced by the anisotropy of the interaction potential. Our results suggest the feasibility of sympathetic cooling and magnetic trapping of 2 P 1/2 -state atoms, such as halogens, thereby opening up exciting areas of research in precision spectroscopy and cold-controlled chemistry.

  16. Wolf-Hirschhorn (4p-) syndrome: prenatal diagnosis, molecular cytogenetic characterization and association with a 1.2-Mb microduplication at 8p22-p21.3 and a 1.1-Mb microduplication at 10p15.3 in a fetus with an apparently pure 4p deletion.

    Science.gov (United States)

    Chen, Chih-Ping; Su, Yi-Ning; Chen, Yi-Yung; Su, Jun-Wei; Chern, Schu-Rern; Chen, Yu-Ting; Chen, Wen-Lin; Chen, Li-Feng; Wang, Wayseen

    2011-12-01

    To present prenatal diagnosis and molecular cytogenetic characterization of Wolf-Hirschhorn syndrome (WHS) associated with microduplications at 8p and 10p in a fetus with an apparently pure 4p deletion. A 35-year-old gravida 2, para 1 woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Her husband was 38 years of age. There was no family history of congenital malformations. Amniocentesis revealed a karyotype of 46,XY,del(4p16.1). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis revealed a 6.5-Mb deletion at 4p16.3-p16.1, a 1.2-Mb microduplication at 8p22-p21.3, and a 1.1-Mb microduplication at 10p15.3, or arr cgh 4p16.3p16.1 (0-6,531,998 bp)×1, 8p22p21.3 (18,705,388-19,940,445 bp)×3, 10p15.3 (0-1,105,065 bp)×3. Polymorphic DNA marker analysis confirmed a paternal origin of 4p deletion. Prenatal ultrasound revealed facial dysmorphism and hypospadias. The aCGH analysis of the parents revealed no genomic imbalance. Fluorescence in situ hybridization study showed an unbalanced reciprocal translocation between chromosomes 4 and 10 at bands 4p16.1 and 10p15.3. The cytogenetic result, thus, was 46,XY,der(4)t(4;10)(p16.1;p15.3),dup(8)(p21.3p22). The parents elected to terminate the pregnancy, and a 470-g malformed fetus was delivered. The present case provides evidence that an apparently pure 4p deletion can be associated with subtle chromosome imbalances in other chromosomes. Copyright © 2011. Published by Elsevier B.V.

  17. Some Diophantine equations from finite group theory: $\\Phi_m (x) = 2p^n -1$

    NARCIS (Netherlands)

    Luca, F.; Moree, P.; Weger, de B.M.M.

    2009-01-01

    We show that the equation in the title (with Fn the nth cyclotomic polynomial) has no integer solution with n = 1 in the cases (m, p) = (15, 41), (15, 5581), (10, 271). These equations arise in a recent group theoretical investigation by Z. Akhlaghi, M. Khatami and B. Khosravi.

  18. Some Diophantine equations from finite group theory: $\\Phi_m (x) = 2p^n -1$

    NARCIS (Netherlands)

    Luca, F.; Moree, P.; Weger, de B.M.M.

    2011-01-01

    We show that the equation in the title (with $\\Psi_m$ the $m$th cyclotomic polynomial) has no integer solution with $n \\geq 1$ in the cases (m,p) = (15,41), (15,5581), (10,271). These equations arise in a recent group theoretical investigation by Akhlaghi, Khosravi and Khatami.

  19. Adenine Nucleotide Analogues Locked in a Northern Methanocarba Conformation: Enhanced Stability and Potency as P2Y1 Receptor Agonists

    Science.gov (United States)

    Ravi, R. Gnana; Kim, Hak Sung; Servos, Jörg; Zimmermann, Herbert; Lee, Kyeong; Maddileti, Savitri; Boyer, José L.; Harden, T. Kendall; Jacobson, Kenneth A.

    2016-01-01

    Preference for the Northern (N) ring conformation of the ribose moiety of nucleotide 5′-triphosphate agonists at P2Y1, P2Y2, P2Y4, and P2Y11 receptors, but not P2Y6 receptors, was established using a ring-constrained methanocarba (a 3.1.0-bicyclohexane) ring as a ribose substitute (Kim et al. J. Med. Chem. 2002, 45, 208–218.). We have now combined the ring-constrained (N)-methanocarba modification of adenine nucleotides with other functionalities known to enhance potency at P2 receptors. The potency of the newly synthesized analogues was determined in the stimulation of phospholipase C through activation of turkey erythrocyte P2Y1 or human P2Y1 and P2Y2 receptors stably expressed in astrocytoma cells. An (N)-methanocarba-2-methylthio-ADP analogue displayed an EC50 at the hP2Y1 receptor of 0.40 nM and was 55-fold more potent than the corresponding triphosphate and 16-fold more potent than the riboside 5′-diphosphate. 2-Cl–(N)-methanocarba-ATP and its N6-Me analogue were also highly selective, full agonists at P2Y1 receptors. The (N)-methanocarba-2-methylthio and 2-chloromonophosphate analogues were full agonists exhibiting micromolar potency at P2Y1 receptors, while the corresponding ribosides were inactive. Although β,γ-methylene-ATP was inactive at P2Y receptors, β,γ-methylene-(N)-methanocarba-ATP was a potent hP2Y1 receptor agonist with an EC50 of 160 nM and was selective versus hP2Y2 and hP2Y4 receptors. The rates of hydrolysis of Northern (N) and Southern (S) methanocarba analogues of AMP by rat 5′-ectonucleotidase were negligible. The rates of hydrolysis of the corresponding triphosphates by recombinant rat NTPDase1 and 2 were studied. Both isomers were hydrolyzed by NTPDase 1 at about half the rate of ATP hydrolysis. The (N) isomer was hardly hydrolyzed by NTPDase 2, while the (S) isomer was hydrolyzed at one-third of the rate of ATP hydrolysis. This suggests that new, more stable and selective nucleotide agonists may be designed on the basis of

  20. A Comparative Study of the Inclusion Complexes of 2-[5'-benzylidene-2'-phenyl-4'-oxo-1', 3'-thiazolidine]-1, 3-benzothiazole and 2-[5'-(p-N,N-dimethylamino- benzylidene-2'-phenyl-4'-oxo-1', 3'-thiazolidine]-1, 3-benzothiazole withβ-Cyclodextrin

    Directory of Open Access Journals (Sweden)

    S. Panda

    2011-01-01

    Full Text Available The compounds 2-[5'-benzylidene-2'-phenyl-4'-oxo-1', 3'-thiazolidine]-1, 3-benzothiazole and 2-[5'-(p-N,N-dimethylamino- benzylidene-2'-phenyl-4'-oxo-1', 3'-thiazolidine]-1, 3-benzothiazole have been synthesized in their purest forms starting from 2-aminobenzothiazole. The inclusion complexes of the above compounds have been prepared with β-cyclodextrin to increase their solubility and bioaccessibility in polar medium. The formation of inclusion complexes have been ascertained by study of spectral characteristic before and after inclusion complex formation. The stability of inclusion complexes and nature of interaction between the host and guest are known from the determination of thermodynamic parameters. Further the antibacterial and antifungal activities of the compounds are determined which is found to increase significantly after inclusion complex formation

  1. Scutellarin inhibits cytochrome P450 isoenzyme 1A2 (CYP1A2) in rats.

    Science.gov (United States)

    Jian, Tun-Yu; He, Jian-Chang; He, Gong-Hao; Feng, En-Fu; Li, Hong-Liang; Bai, Min; Xu, Gui-Li

    2012-08-01

    Scutellarin is the most important flavone glycoside in the herbal drug Erigeron breviscapus (Vant.) Hand.-Mazz. It is used frequently in the clinic to treat ischemic vascular diseases in China. However, the direct relationship between scutellarin and cytochrome P450 (CYP450) is unclear. The present study investigated the in vitro and in vivo effects of scutellarin on cytochrome P450 1A2 (CYP 1A2) metabolism. According to in vitro experiments, scutellarin (10-250 µM) decreased the formation of 4-acetamidophenol in a concentration-dependent manner, with an IC₅₀ value of 108.20 ± 0.657 µM. Furthermore, scutellarin exhibited a weak mixed-type inhibition against the activity of CYP1A2 in rat liver microsomes, with a K(i) value of 95.2 µM. Whereas in whole animal studies, scutellarin treatment for 7 days (at 5, 15, 30 mg/kg, i.p.) decreased the clearance (CL), and increased the T(1/2) (at 15, 30 mg/kg, i.p.), it did not affect the V(d) of phenacetin. Scutellarin treatment (at 5, 15, 30 mg/kg, i.p.) increased the AUC(0-∞) by 14.3%, 67.3% and 159.2%, respectively. Scutellarin at 30 mg/kg also weakly inhibited CYP1A2 activity, in accordance with our in vitro study. Thus, the results indicate that CYP1A2 is inhibited directly, but weakly, by scutellarin in vivo, and provide useful information on the safe and effective use of scutellarin in clinical practice. Copyright © 2012 John Wiley & Sons, Ltd.

  2. Identification of a High-Risk Group Among Patients With Oral Cavity Squamous Cell Carcinoma and pT12N0 Disease

    International Nuclear Information System (INIS)

    Liao, Chun-Ta; Lin, Chien-Yu; Fan, Kang-Hsing; Wang, Hung-Ming; Ng, Shu-Hang; Lee, Li-Yu; Hsueh, Chuen; Chen, I-How; Huang, Shiang-Fu; Kang, Chung-Jan

    2012-01-01

    Purpose: In the American Joint Committee on Cancer 2010 classification system, pT12N0 oral cavity squamous cell carcinoma (OSCC) is considered an early-stage cancer treatable with surgery alone (National Comprehensive Cancer Network 2010 guidelines). Our aim was to evaluate the feasibility of surgery alone for pT12N0 OSCC patients. Methods and Materials: Among 1279 previously untreated OSCC patients referred to our hospital between January 1996 and May 2008, we identified 457 consecutive patients with pT12N0 disease. All had radical tumor excision with neck dissection. A total of 387 patients showing pathologic margins greater than 4 mm and treated by surgery alone were included in the final analysis. All were followed up for at least 24 months after surgery or until death. The 5-year rates of control, distant metastasis, and survival were the main outcome measures. Results: The 5-year rates in the entire group of pT12N0 patients were as follows: local control, 91%; neck control, 92%; distant metastases, 1%; disease-free survival, 85%; disease-specific survival, 93%; and overall survival, 84%. Multivariate analysis identified poor differentiation and pathologic tumor depth of 4 mm or greater as independent risk factors for neck control, disease-free survival, and disease-specific survival. A scoring system using poor differentiation and tumor depth was formulated to define distinct prognostic groups. The presence of both poorly differentiated tumors and a tumor depth of 4 mm or greater resulted in significantly poorer 5-year neck control (p < 0.0001), disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p = 0.0046) rates. Conclusion: The combination of poor differentiation and pathologic tumor depth of 4 mm or greater identified a subset of pT12N0 OSCC patients with poor outcome, who may have clinical benefit from postoperative adjuvant radiotherapy.

  3. Generation and characterization of polyclonal antibodies specific to N-terminal extension of p85 isoform of ribosomal protein S6 kinase 1 (p85 S6K1

    Directory of Open Access Journals (Sweden)

    Savinska L. O.

    2015-08-01

    Full Text Available Aim. Generation of polyclonal antibodies specific to the ribosomal protein S6 kinase isoform – p85S6K1 and directed to the N-terminal (1–23 aa extension of p85S6K1. Methods. Animal immunization with synthetic (1–23 aa peptide, ELISA, Western blot, Immunoprecipitation, immunofluorescent analysis. Results. Polyclonal antibodies have been generated, which specifically recognize only p85 but not p70 isoform of S6K1 in western blot, immunoprecipitation and immunofluorescence analysis. Conclusions. The obtained antibodies can be recommended for studies on the p85S6K1 and other S6K1 isoforms possessing the N-terminal extension – the identification of binding protein partners, analysis of subcellular localization under different physiological conditions, elucidation of the signal transduction pathways involving different S6K1 isoforms.

  4. Temperature-dependent thermal and thermoelectric properties of n -type and p -type S c1 -xM gxN

    Science.gov (United States)

    Saha, Bivas; Perez-Taborda, Jaime Andres; Bahk, Je-Hyeong; Koh, Yee Rui; Shakouri, Ali; Martin-Gonzalez, Marisol; Sands, Timothy D.

    2018-02-01

    Scandium Nitride (ScN) is an emerging rocksalt semiconductor with octahedral coordination and an indirect bandgap. ScN has attracted significant attention in recent years for its potential thermoelectric applications, as a component material in epitaxial metal/semiconductor superlattices, and as a substrate for defect-free GaN growth. Sputter-deposited ScN thin films are highly degenerate n -type semiconductors and exhibit a large thermoelectric power factor of ˜3.5 ×10-3W /m -K2 at 600-800 K. Since practical thermoelectric devices require both n- and p-type materials with high thermoelectric figures-of-merit, development and demonstration of highly efficient p-type ScN is extremely important. Recently, the authors have demonstrated p-type S c1 -xM gxN thin film alloys with low M gxNy mole-fractions within the ScN matrix. In this article, we demonstrate temperature dependent thermal and thermoelectric transport properties, including large thermoelectric power factors in both n- and p-type S c1 -xM gxN thin film alloys at high temperatures (up to 850 K). Employing a combination of temperature-dependent Seebeck coefficient, electrical conductivity, and thermal conductivity measurements, as well as detailed Boltzmann transport-based modeling analyses of the transport properties, we demonstrate that p-type S c1 -xM gxN thin film alloys exhibit a maximum thermoelectric power factor of ˜0.8 ×10-3W /m -K2 at 850 K. The thermoelectric properties are tunable by adjusting the M gxNy mole-fraction inside the ScN matrix, thereby shifting the Fermi energy in the alloy films from inside the conduction band in case of undoped n -type ScN to inside the valence band in highly hole-doped p -type S c1 -xM gxN thin film alloys. The thermal conductivities of both the n- and p-type films were found to be undesirably large for thermoelectric applications. Thus, future work should address strategies to reduce the thermal conductivity of S c1 -xM gxN thin-film alloys, without affecting

  5. Synthesis and reactivity of TADDOL-based chiral Fe(II) PNP pincer complexes-solution equilibria between κ(2)P,N- and κ(3)P,N,P-bound PNP pincer ligands.

    Science.gov (United States)

    Holzhacker, Christian; Stöger, Berthold; Carvalho, Maria Deus; Ferreira, Liliana P; Pittenauer, Ernst; Allmaier, Günter; Veiros, Luis F; Realista, Sara; Gil, Adrià; Calhorda, Maria José; Müller, Danny; Kirchner, Karl

    2015-08-07

    Treatment of anhydrous FeX2 (X = Cl, Br) with 1 equiv. of the asymmetric chiral PNP pincer ligands PNP-R,TAD (R = iPr, tBu) with an R,R-TADDOL (TAD) moiety afforded complexes of the general formula [Fe(PNP)X2]. In the solid state these complexes adopt a tetrahedral geometry with the PNP ligand coordinated in κ(2)P,N-fashion, as shown by X-ray crystallography and Mössbauer spectroscopy. Magnetization studies led to a magnetic moment very close to 4.9μB reflecting the expected four unpaired d-electrons (quintet ground state). In solution there are equilibria between [Fe(κ(3)P,N,P-PNP-R,TAD)X2] and [Fe(κ(2)P,N-PNP-R,TAD)X2] complexes, i.e., the PNP-R,TAD ligand is hemilabile. At -50 °C these equilibria are slow and signals of the non-coordinated P-TAD arm of the κ(2)P,N-PNP-R,TAD ligand can be detected by (31)P{(1)H} NMR spectroscopy. Addition of BH3 to a solution of [Fe(PNP-iPr,TAD)Cl2] leads to selective boronation of the pendant P-TAD arm shifting the equilibrium towards the four-coordinate complex [Fe(κ(2)P,N-PNP-iPr,TAD(BH3))Cl2]. DFT calculations corroborate the existence of equilibria between four- and five-coordinated complexes. Addition of CO to [Fe(PNP-iPr,TAD)X2] in solution yields the diamagnetic octahedral complexes trans-[Fe(κ(3)P,N,P-PNP-iPr,TAD)(CO)X2], which react further with Ag(+) salts in the presence of CO to give the cationic complexes trans-[Fe(κ(3)P,N,P-PNP-iPr,TAD)(CO)2X](+). CO addition most likely takes place at the five coordinate complex [Fe(κ(3)P,N,P-PNP-iPr,TAD)X2]. The mechanism for the CO addition was also investigated by DFT and the most favorable path obtained corresponds to the rearrangement of the pincer ligand first from a κ(2)P,N- to a κ(3)P,N,P-coordination mode followed by CO coordination to [Fe(κ(3)P,N,P-PNP-iPr,TAD)X2]. Complexes bearing tBu substituents do not react with CO. Moreover, in the solid state none of the tetrahedral complexes are able to bind CO.

  6. Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation.

    Science.gov (United States)

    Tsai, Hsing-Chuan; Han, May H

    2016-07-01

    Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases.

  7. Peak response wavelengths of p- and n-type InxGa1-xAs-InP quantum well infrared photodetectors

    International Nuclear Information System (INIS)

    Fu, Y.; Willander, M.; Sengupta, D.K.

    2005-01-01

    p- and n-type In x Ga 1-x As-InP quantum wells are suitable for multi-color infrared photodetector applications in atmospheric windows due to improved barrier quality and carrier-transport properties. We apply the k.p method to study the energy band structures and optical transition properties, which show that the peak response wavelengths of p- and n-type In x Ga 1-x As-InP quantum well infrared photodetectors (QWIPs) are determined not only by the energy distance from the ground sublevels in the quantum well to the energy band edges of extended states, but also by the characteristics of the extended states. The optical phonon scattering process converts the broad absorption spectrum of the p-QWIP from 0 to 16 μm into a short-wavelength spectrum centered at 4.5 μm. The transport of electrons in the extended states of the n-QWIP is characterized by running wave boundary conditions, resulting in a theoretically optimal absorption rate by a 8-nm-thick In 0.53 Ga 0.47 As quantum well. Moreover, a conduction-band offset of 0.5 for an In x Ga 1-x As-InP (x=0.53) heterostructure gives the best data fitting of theoretical and experimental response peaks, whereas 0.55 is generally recommended in the literature. (orig.)

  8. Measurement of Prompt ψ (2 S ) to J /ψ Yield Ratios in Pb-Pb and p -p Collisions at √{sN N }=2.76 TeV

    Science.gov (United States)

    Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Bergauer, T.; Dragicevic, M.; Erö, J.; Fabjan, C.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Kiesenhofer, W.; Knünz, V.; Krammer, M.; Krätschmer, I.; Liko, D.; Mikulec, I.; Rabady, D.; Rahbaran, B.; Rohringer, H.; Schöfbeck, R.; Strauss, J.; Taurok, A.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; Bansal, M.; Bansal, S.; Cornelis, T.; De Wolf, E. A.; Janssen, X.; Knutsson, A.; Luyckx, S.; Ochesanu, S.; Roland, B.; Rougny, R.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Blekman, F.; Blyweert, S.; D'Hondt, J.; Daci, N.; Heracleous, N.; Keaveney, J.; Lowette, S.; Maes, M.; Olbrechts, A.; Python, Q.; Strom, D.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Villella, I.; Caillol, C.; Clerbaux, B.; De Lentdecker, G.; Dobur, D.; Favart, L.; Gay, A. P. R.; Grebenyuk, A.; Léonard, A.; Mohammadi, A.; Perniè, L.; Reis, T.; Seva, T.; Thomas, L.; Vander Velde, C.; Vanlaer, P.; Wang, J.; Adler, V.; Beernaert, K.; Benucci, L.; Cimmino, A.; Costantini, S.; Crucy, S.; Dildick, S.; Fagot, A.; Garcia, G.; Mccartin, J.; Ocampo Rios, A. A.; Ryckbosch, D.; Salva Diblen, S.; Sigamani, M.; Strobbe, N.; Thyssen, F.; Tytgat, M.; Yazgan, E.; Zaganidis, N.; Basegmez, S.; Beluffi, C.; Bruno, G.; Castello, R.; Caudron, A.; Ceard, L.; Da Silveira, G. G.; Delaere, C.; du Pree, T.; Favart, D.; Forthomme, L.; Giammanco, A.; Hollar, J.; Jez, P.; Komm, M.; Lemaitre, V.; Nuttens, C.; Pagano, D.; Perrini, L.; Pin, A.; Piotrzkowski, K.; Popov, A.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Vizan Garcia, J. M.; Beliy, N.; Caebergs, T.; Daubie, E.; Hammad, G. H.; Aldá Júnior, W. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Dos Reis Martins, T.; Mora Herrera, C.; Pol, M. E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Malbouisson, H.; Matos Figueiredo, D.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santaolalla, J.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Bernardes, C. A.; Dogra, S.; Tomei, T. R. Fernandez Perez; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Aleksandrov, A.; Genchev, V.; Iaydjiev, P.; Marinov, A.; Piperov, S.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Tcholakov, V.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Hadjiiska, R.; Kozhuharov, V.; Litov, L.; Pavlov, B.; Petkov, P.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Du, R.; Jiang, C. H.; Liang, S.; Plestina, R.; Tao, J.; Wang, X.; Wang, Z.; Asawatangtrakuldee, C.; Ban, Y.; Guo, Y.; Li, Q.; Li, W.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Zhang, L.; Zou, W.; Avila, C.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Polic, D.; Puljak, I.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Kadija, K.; Luetic, J.; Mekterovic, D.; Sudic, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Bodlak, M.; Finger, M.; Finger, M.; Assran, Y.; Ellithi Kamel, A.; Mahmoud, M. A.; Radi, A.; Kadastik, M.; Murumaa, M.; Raidal, M.; Tiko, A.; Eerola, P.; Fedi, G.; Voutilainen, M.; Härkönen, J.; Karimäki, V.; Kinnunen, R.; Kortelainen, M. J.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Peltola, T.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Favaro, C.; Ferri, F.; Ganjour, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Malcles, J.; Rander, J.; Rosowsky, A.; Titov, M.; Baffioni, S.; Beaudette, F.; Busson, P.; Charlot, C.; Dahms, T.; Dalchenko, M.; Dobrzynski, L.; Filipovic, N.; Florent, A.; Granier de Cassagnac, R.; Mastrolorenzo, L.; Miné, P.; Mironov, C.; Naranjo, I. N.; Nguyen, M.; Ochando, C.; Paganini, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Veelken, C.; Yilmaz, Y.; Zabi, A.; Agram, J.-L.; Andrea, J.; Aubin, A.; Bloch, D.; Brom, J.-M.; Chabert, E. C.; Collard, C.; Conte, E.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Goetzmann, C.; Le Bihan, A.-C.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Beaupere, N.; Boudoul, G.; Bouvier, E.; Brochet, S.; Carrillo Montoya, C. A.; Chasserat, J.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fan, J.; Fay, J.; Gascon, S.; Gouzevitch, M.; Ille, B.; Kurca, T.; Lethuillier, M.; Mirabito, L.; Perries, S.; Ruiz Alvarez, J. D.; Sabes, D.; Sgandurra, L.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Xiao, H.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Bontenackels, M.; Edelhoff, M.; Feld, L.; Hindrichs, O.; Klein, K.; Ostapchuk, A.; Perieanu, A.; Raupach, F.; Sammet, J.; Schael, S.; Weber, H.; Wittmer, B.; Zhukov, V.; Ata, M.; Dietz-Laursonn, E.; Duchardt, D.; Erdmann, M.; Fischer, R.; Güth, A.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Klingebiel, D.; Knutzen, S.; Kreuzer, P.; Merschmeyer, M.; Meyer, A.; Millet, P.; Olschewski, M.; Padeken, K.; Papacz, P.; Reithler, H.; Schmitz, S. A.; Sonnenschein, L.; Teyssier, D.; Thüer, S.; Weber, M.; Cherepanov, V.; Erdogan, Y.; Flügge, G.; Geenen, H.; Geisler, M.; Haj Ahmad, W.; Heister, A.; Hoehle, F.; Kargoll, B.; Kress, T.; Kuessel, Y.; Lingemann, J.; Nowack, A.; Nugent, I. M.; Perchalla, L.; Pooth, O.; Stahl, A.; Asin, I.; Bartosik, N.; Behr, J.; Behrenhoff, W.; Behrens, U.; Bell, A. J.; Bergholz, M.; Bethani, A.; Borras, K.; Burgmeier, A.; Cakir, A.; Calligaris, L.; Campbell, A.; Choudhury, S.; Costanza, F.; Diez Pardos, C.; Dooling, S.; Dorland, T.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Flucke, G.; Garay Garcia, J.; Geiser, A.; Gunnellini, P.; Hauk, J.; Hempel, M.; Horton, D.; Jung, H.; Kalogeropoulos, A.; Kasemann, M.; Katsas, P.; Kieseler, J.; Kleinwort, C.; Krücker, D.; Lange, W.; Leonard, J.; Lipka, K.; Lobanov, A.; Lohmann, W.; Lutz, B.; Mankel, R.; Marfin, I.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Naumann-Emme, S.; Nayak, A.; Novgorodova, O.; Nowak, F.; Ntomari, E.; Perrey, H.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Ribeiro Cipriano, P. M.; Ron, E.; Sahin, M. Ö.; Salfeld-Nebgen, J.; Saxena, P.; Schmidt, R.; Schoerner-Sadenius, T.; Schröder, M.; Seitz, C.; Spannagel, S.; Vargas Trevino, A. D. R.; Walsh, R.; Wissing, C.; Aldaya Martin, M.; Blobel, V.; Centis Vignali, M.; Draeger, A. R.; Erfle, J.; Garutti, E.; Goebel, K.; Görner, M.; Haller, J.; Hoffmann, M.; Höing, R. S.; Kirschenmann, H.; Klanner, R.; Kogler, R.; Lange, J.; Lapsien, T.; Lenz, T.; Marchesini, I.; Ott, J.; Peiffer, T.; Pietsch, N.; Poehlsen, J.; Poehlsen, T.; Rathjens, D.; Sander, C.; Schettler, H.; Schleper, P.; Schlieckau, E.; Schmidt, A.; Seidel, M.; Sola, V.; Stadie, H.; Steinbrück, G.; Troendle, D.; Usai, E.; Vanelderen, L.; Barth, C.; Baus, C.; Berger, J.; Böser, C.; Butz, E.; Chwalek, T.; De Boer, W.; Descroix, A.; Dierlamm, A.; Feindt, M.; Frensch, F.; Giffels, M.; Hartmann, F.; Hauth, T.; Husemann, U.; Katkov, I.; Kornmayer, A.; Kuznetsova, E.; Lobelle Pardo, P.; Mozer, M. U.; Müller, Th.; Nürnberg, A.; Quast, G.; Rabbertz, K.; Ratnikov, F.; Röcker, S.; Simonis, H. J.; Stober, F. M.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weiler, T.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Markou, A.; Markou, C.; Psallidas, A.; Topsis-Giotis, I.; Agapitos, A.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Stiliaris, E.; Aslanoglou, X.; Evangelou, I.; Flouris, G.; Foudas, C.; Kokkas, P.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Bencze, G.; Hajdu, C.; Hidas, P.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Molnar, J.; Palinkas, J.; Szillasi, Z.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Swain, S. K.; Beri, S. B.; Bhatnagar, V.; Gupta, R.; Bhawandeep, U.; Kalsi, A. K.; Kaur, M.; Mittal, M.; Nishu, N.; Singh, J. B.; Kumar, Ashok; Kumar, Arun; Ahuja, S.; Bhardwaj, A.; Choudhary, B. C.; Kumar, A.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Sharma, V.; Banerjee, S.; Bhattacharya, S.; Chatterjee, K.; Dutta, S.; Gomber, B.; Jain, Sa.; Jain, Sh.; Khurana, R.; Modak, A.; Mukherjee, S.; Roy, D.; Sarkar, S.; Sharan, M.; Abdulsalam, A.; Dutta, D.; Kailas, S.; Kumar, V.; Mohanty, A. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Banerjee, S.; Bhowmik, S.; Chatterjee, R. M.; Dewanjee, R. K.; Dugad, S.; Ganguly, S.; Ghosh, S.; Guchait, M.; Gurtu, A.; Kole, G.; Kumar, S.; Maity, M.; Majumder, G.; Mazumdar, K.; Mohanty, G. B.; Parida, B.; Sudhakar, K.; Wickramage, N.; Bakhshiansohi, H.; Behnamian, H.; Etesami, S. M.; Fahim, A.; Goldouzian, R.; Jafari, A.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Barbone, L.; Calabria, C.; Chhibra, S. S.; Colaleo, A.; Creanza, D.; De Filippis, N.; De Palma, M.; Fiore, L.; Iaselli, G.; Maggi, G.; Maggi, M.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Selvaggi, G.; Silvestris, L.; Singh, G.; Venditti, R.; Verwilligen, P.; Zito, G.; Abbiendi, G.; Benvenuti, A. C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Primavera, F.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Travaglini, R.; Albergo, S.; Cappello, G.; Chiorboli, M.; Costa, S.; Giordano, F.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Gallo, E.; Gonzi, S.; Gori, V.; Lenzi, P.; Meschini, M.; Paoletti, S.; Sguazzoni, G.; Tropiano, A.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Ferro, F.; Lo Vetere, M.; Robutti, E.; Tosi, S.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Gerosa, R.; Ghezzi, A.; Govoni, P.; Lucchini, M. T.; Malvezzi, S.; Manzoni, R. A.; Martelli, A.; Marzocchi, B.; Menasce, D.; Moroni, L.; Paganoni, M.; Pedrini, D.; Ragazzi, S.; Redaelli, N.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; Di Guida, S.; Fabozzi, F.; Iorio, A. O. M.; Lista, L.; Meola, S.; Merola, M.; Paolucci, P.; Bellato, M.; Biasotto, M.; Bisello, D.; Branca, A.; Carlin, R.; Checchia, P.; Dall'Osso, M.; Dorigo, T.; Fanzago, F.; Galanti, M.; Gasparini, F.; Gasparini, U.; Gozzelino, A.; Kanishchev, K.; Lacaprara, S.; Margoni, M.; Meneguzzo, A. T.; Pazzini, J.; Pozzobon, N.; Ronchese, P.; Simonetto, F.; Torassa, E.; Tosi, M.; Triossi, A.; Ventura, S.; Zucchetta, A.; Zumerle, G.; Gabusi, M.; Ratti, S. P.; Riccardi, C.; Salvini, P.; Vitulo, P.; Biasini, M.; Bilei, G. M.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Mantovani, G.; Menichelli, M.; Romeo, F.; Saha, A.; Santocchia, A.; Spiezia, A.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Broccolo, G.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Donato, S.; Fiori, F.; Foà, L.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Martini, L.; Messineo, A.; Moon, C. S.; Palla, F.; Rizzi, A.; Savoy-Navarro, A.; Serban, A. T.; Spagnolo, P.; Squillacioti, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Vernieri, C.; Barone, L.; Cavallari, F.; D'imperio, G.; Del Re, D.; Diemoz, M.; Grassi, M.; Jorda, C.; Longo, E.; Margaroli, F.; Meridiani, P.; Micheli, F.; Nourbakhsh, S.; Organtini, G.; Paramatti, R.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Soffi, L.; Traczyk, P.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bellan, R.; Biino, C.; Cartiglia, N.; Casasso, S.; Costa, M.; Degano, A.; Demaria, N.; Finco, L.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Musich, M.; Obertino, M. M.; Ortona, G.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Potenza, A.; Romero, A.; Ruspa, M.; Sacchi, R.; Solano, A.; Staiano, A.; Tamponi, U.; Belforte, S.; Candelise, V.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Gobbo, B.; La Licata, C.; Marone, M.; Montanino, D.; Schizzi, A.; Umer, T.; Zanetti, A.; Chang, S.; Kropivnitskaya, A.; Nam, S. K.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Kong, D. J.; Lee, S.; Oh, Y. D.; Park, H.; Sakharov, A.; Son, D. C.; Kim, T. J.; Kim, J. Y.; Song, S.; Choi, S.; Gyun, D.; Hong, B.; Jo, M.; Kim, H.; Kim, Y.; Lee, B.; Lee, K. S.; Park, S. K.; Roh, Y.; Choi, M.; Kim, J. H.; Park, I. C.; Park, S.; Ryu, G.; Ryu, M. S.; Choi, Y.; Choi, Y. K.; Goh, J.; Kim, D.; Kwon, E.; Lee, J.; Seo, H.; Yu, I.; Juodagalvis, A.; Komaragiri, J. R.; Md Ali, M. A. B.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-de La Cruz, I.; Lopez-Fernandez, R.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Vazquez Valencia, F.; Pedraza, I.; Salazar Ibarguen, H. A.; Casimiro Linares, E.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Reucroft, S.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Khalid, S.; Khan, W. A.; Khurshid, T.; Shah, M. A.; Shoaib, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Zalewski, P.; Brona, G.; Bunkowski, K.; Cwiok, M.; Dominik, W.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Wolszczak, W.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Faccioli, P.; Ferreira Parracho, P. G.; Gallinaro, M.; Nguyen, F.; Rodrigues Antunes, J.; Seixas, J.; Varela, J.; Vischia, P.; Afanasiev, S.; Golutvin, I.; Karjavin, V.; Konoplyanikov, V.; Korenkov, V.; Kozlov, G.; Lanev, A.; Malakhov, A.; Matveev, V.; Mitsyn, V. V.; Moisenz, P.; Palichik, V.; Perelygin, V.; Shmatov, S.; Skatchkov, N.; Smirnov, V.; Tikhonenko, E.; Zarubin, A.; Golovtsov, V.; Ivanov, Y.; Kim, V.; Levchenko, P.; Murzin, V.; Oreshkin, V.; Smirnov, I.; Sulimov, V.; Uvarov, L.; Vavilov, S.; Vorobyev, A.; Vorobyev, An.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Kirsanov, M.; Krasnikov, N.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Safronov, G.; Semenov, S.; Spiridonov, A.; Stolin, V.; Vlasov, E.; Zhokin, A.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Leonidov, A.; Mesyats, G.; Rusakov, S. V.; Vinogradov, A.; Belyaev, A.; Boos, E.; Ershov, A.; Gribushin, A.; Kaminskiy, A.; Kodolova, O.; Korotkikh, V.; Lokhtin, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Snigirev, A.; Vardanyan, I.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Krychkine, V.; Petrov, V.; Ryutin, R.; Sobol, A.; Tourtchanovitch, L.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Ekmedzic, M.; Milosevic, J.; Rekovic, V.; Alcaraz Maestre, J.; Battilana, C.; Calvo, E.; Cerrada, M.; Chamizo Llatas, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Domínguez Vázquez, D.; Escalante Del Valle, A.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Merino, G.; Navarro De Martino, E.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Soares, M. S.; Albajar, C.; de Trocóniz, J. F.; Missiroli, M.; Moran, D.; Brun, H.; Cuevas, J.; Fernandez Menendez, J.; Folgueras, S.; Gonzalez Caballero, I.; Lloret Iglesias, L.; Brochero Cifuentes, J. A.; Cabrillo, I. J.; Calderon, A.; Duarte Campderros, J.; Fernandez, M.; Gomez, G.; Graziano, A.; Lopez Virto, A.; Marco, J.; Marco, R.; Martinez Rivero, C.; Matorras, F.; Munoz Sanchez, F. J.; Piedra Gomez, J.; Rodrigo, T.; Rodríguez-Marrero, A. Y.; Ruiz-Jimeno, A.; Scodellaro, L.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Auffray, E.; Auzinger, G.; Bachtis, M.; Baillon, P.; Ball, A. H.; Barney, D.; Benaglia, A.; Bendavid, J.; Benhabib, L.; Benitez, J. F.; Bernet, C.; Bianchi, G.; Bloch, P.; Bocci, A.; Bonato, A.; Bondu, O.; Botta, C.; Breuker, H.; Camporesi, T.; Cerminara, G.; Colafranceschi, S.; D'Alfonso, M.; d'Enterria, D.; Dabrowski, A.; David, A.; De Guio, F.; De Roeck, A.; De Visscher, S.; Dobson, M.; Dordevic, M.; Dupont-Sagorin, N.; Elliott-Peisert, A.; Eugster, J.; Franzoni, G.; Funk, W.; Gigi, D.; Gill, K.; Giordano, D.; Girone, M.; Glege, F.; Guida, R.; Gundacker, S.; Guthoff, M.; Hammer, J.; Hansen, M.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Kousouris, K.; Krajczar, K.; Lecoq, P.; Lourenço, C.; Magini, N.; Malgeri, L.; Mannelli, M.; Marrouche, J.; Masetti, L.; Meijers, F.; Mersi, S.; Meschi, E.; Moortgat, F.; Morovic, S.; Mulders, M.; Musella, P.; Orsini, L.; Pape, L.; Perez, E.; Perrozzi, L.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Pimiä, M.; Piparo, D.; Plagge, M.; Racz, A.; Rolandi, G.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Sharma, A.; Siegrist, P.; Silva, P.; Simon, M.; Sphicas, P.; Spiga, D.; Steggemann, J.; Stieger, B.; Stoye, M.; Takahashi, Y.; Treille, D.; Tsirou, A.; Veres, G. I.; Vlimant, J. R.; Wardle, N.; Wöhri, H. K.; Wollny, H.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Renker, D.; Rohe, T.; Bachmair, F.; Bäni, L.; Bianchini, L.; Bortignon, P.; Buchmann, M. A.; Casal, B.; Chanon, N.; Deisher, A.; Dissertori, G.; Dittmar, M.; Donegà, M.; Dünser, M.; Eller, P.; Grab, C.; Hits, D.; Lustermann, W.; Mangano, B.; Marini, A. C.; Martinez Ruiz del Arbol, P.; Meister, D.; Mohr, N.; Nägeli, C.; Nessi-Tedaldi, F.; Pandolfi, F.; Pauss, F.; Peruzzi, M.; Quittnat, M.; Rebane, L.; Rossini, M.; Starodumov, A.; Takahashi, M.; Theofilatos, K.; Wallny, R.; Weber, H. A.; Amsler, C.; Canelli, M. F.; Chiochia, V.; De Cosa, A.; Hinzmann, A.; Hreus, T.; Kilminster, B.; Lange, C.; Millan Mejias, B.; Ngadiuba, J.; Robmann, P.; Ronga, F. J.; Taroni, S.; Verzetti, M.; Yang, Y.; Cardaci, M.; Chen, K. H.; Ferro, C.; Kuo, C. M.; Lin, W.; Lu, Y. J.; Volpe, R.; Yu, S. S.; Chang, P.; Chang, Y. H.; Chang, Y. W.; Chao, Y.; Chen, K. F.; Chen, P. H.; Dietz, C.; Grundler, U.; Hou, W.-S.; Kao, K. Y.; Lei, Y. J.; Liu, Y. F.; Lu, R.-S.; Majumder, D.; Petrakou, E.; Tzeng, Y. M.; Wilken, R.; Asavapibhop, B.; Srimanobhas, N.; Suwonjandee, N.; Adiguzel, A.; Bakirci, M. N.; Cerci, S.; Dozen, C.; Dumanoglu, I.; Eskut, E.; Girgis, S.; Gokbulut, G.; Gurpinar, E.; Hos, I.; Kangal, E. E.; Kayis Topaksu, A.; Onengut, G.; Ozdemir, K.; Ozturk, S.; Polatoz, A.; Sogut, K.; Sunar Cerci, D.; Tali, B.; Topakli, H.; Vergili, M.; Akin, I. V.; Bilin, B.; Bilmis, S.; Gamsizkan, H.; Karapinar, G.; Ocalan, K.; Sekmen, S.; Surat, U. E.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Isildak, B.; Kaya, M.; Kaya, O.; Bahtiyar, H.; Barlas, E.; Cankocak, K.; Vardarlı, F. I.; Yücel, M.; Levchuk, L.; Sorokin, P.; Brooke, J. J.; Clement, E.; Cussans, D.; Flacher, H.; Frazier, R.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Meng, Z.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Senkin, S.; Smith, V. J.; Williams, T.; Belyaev, A.; Brew, C.; Brown, R. M.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Womersley, W. J.; Worm, S. D.; Baber, M.; Bainbridge, R.; Buchmuller, O.; Burton, D.; Colling, D.; Cripps, N.; Cutajar, M.; Dauncey, P.; Davies, G.; Della Negra, M.; Dunne, P.; Ferguson, W.; Fulcher, J.; Futyan, D.; Gilbert, A.; Hall, G.; Iles, G.; Jarvis, M.; Karapostoli, G.; Kenzie, M.; Lane, R.; Lucas, R.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mathias, B.; Nash, J.; Nikitenko, A.; Pela, J.; Pesaresi, M.; Petridis, K.; Raymond, D. M.; Rogerson, S.; Rose, A.; Seez, C.; Sharp, P.; Tapper, A.; Vazquez Acosta, M.; Virdee, T.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Leggat, D.; Leslie, D.; Martin, W.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Dittmann, J.; Hatakeyama, K.; Kasmi, A.; Liu, H.; Scarborough, T.; Charaf, O.; Cooper, S. I.; Henderson, C.; Rumerio, P.; Avetisyan, A.; Bose, T.; Fantasia, C.; Lawson, P.; Richardson, C.; Rohlf, J.; Sperka, D.; St. John, J.; Sulak, L.; Alimena, J.; Berry, E.; Bhattacharya, S.; Christopher, G.; Cutts, D.; Demiragli, Z.; Dhingra, N.; Ferapontov, A.; Garabedian, A.; Heintz, U.; Kukartsev, G.; Laird, E.; Landsberg, G.; Luk, M.; Narain, M.; Segala, M.; Sinthuprasith, T.; Speer, T.; Swanson, J.; Breedon, R.; Breto, G.; Calderon De La Barca Sanchez, M.; Chauhan, S.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Gardner, M.; Ko, W.; Lander, R.; Miceli, T.; Mulhearn, M.; Pellett, D.; Pilot, J.; Ricci-Tam, F.; Searle, M.; Shalhout, S.; Smith, J.; Squires, M.; Stolp, D.; Tripathi, M.; Wilbur, S.; Yohay, R.; Cousins, R.; Everaerts, P.; Farrell, C.; Hauser, J.; Ignatenko, M.; Rakness, G.; Takasugi, E.; Valuev, V.; Weber, M.; Babb, J.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Hanson, G.; Heilman, J.; Ivova Rikova, M.; Jandir, P.; Kennedy, E.; Lacroix, F.; Liu, H.; Long, O. R.; Luthra, A.; Malberti, M.; Nguyen, H.; Olmedo Negrete, M.; Shrinivas, A.; Sumowidagdo, S.; Wimpenny, S.; Andrews, W.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; D'Agnolo, R. T.; Evans, D.; Holzner, A.; Kelley, R.; Klein, D.; Lebourgeois, M.; Letts, J.; Macneill, I.; Olivito, D.; Padhi, S.; Palmer, C.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Sudano, E.; Tadel, M.; Tu, Y.; Vartak, A.; Welke, C.; Würthwein, F.; Yagil, A.; Yoo, J.; Barge, D.; Bradmiller-Feld, J.; Campagnari, C.; Danielson, T.; Dishaw, A.; Flowers, K.; Franco Sevilla, M.; Geffert, P.; George, C.; Golf, F.; Gouskos, L.; Incandela, J.; Justus, C.; Mccoll, N.; Richman, J.; Stuart, D.; To, W.; West, C.; Apresyan, A.; Bornheim, A.; Bunn, J.; Chen, Y.; Di Marco, E.; Duarte, J.; Mott, A.; Newman, H. B.; Pena, C.; Rogan, C.; Spiropulu, M.; Timciuc, V.; Wilkinson, R.; Xie, S.; Zhu, R. Y.; Azzolini, V.; Calamba, A.; Carlson, B.; Ferguson, T.; Iiyama, Y.; Paulini, M.; Russ, J.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Ford, W. T.; Gaz, A.; Luiggi Lopez, E.; Nauenberg, U.; Smith, J. G.; Stenson, K.; Ulmer, K. A.; Wagner, S. R.; Alexander, J.; Chatterjee, A.; Chu, J.; Dittmer, S.; Eggert, N.; Mirman, N.; Nicolas Kaufman, G.; Patterson, J. R.; Ryd, A.; Salvati, E.; Skinnari, L.; Sun, W.; Teo, W. D.; Thom, J.; Thompson, J.; Tucker, J.; Weng, Y.; Winstrom, L.; Wittich, P.; Winn, D.; Abdullin, S.; Albrow, M.; Anderson, J.; Apollinari, G.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gao, Y.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Hanlon, J.; Hare, D.; Harris, R. M.; Hirschauer, J.; Hooberman, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Kaadze, K.; Klima, B.; Kreis, B.; Kwan, S.; Linacre, J.; Lincoln, D.; Lipton, R.; Liu, T.; Lykken, J.; Maeshima, K.; Marraffino, J. M.; Martinez Outschoorn, V. I.; Maruyama, S.; Mason, D.; McBride, P.; Mishra, K.; Mrenna, S.; Musienko, Y.; Nahn, S.; Newman-Holmes, C.; O'Dell, V.; Prokofyev, O.; Sexton-Kennedy, E.; Sharma, S.; Soha, A.; Spalding, W. J.; Spiegel, L.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vidal, R.; Whitbeck, A.; Whitmore, J.; Yang, F.; Acosta, D.; Avery, P.; Bourilkov, D.; Carver, M.; Cheng, T.; Curry, D.; Das, S.; De Gruttola, M.; Di Giovanni, G. P.; Field, R. D.; Fisher, M.; Furic, I. K.; Hugon, J.; Konigsberg, J.; Korytov, A.; Kypreos, T.; Low, J. F.; Matchev, K.; Milenovic, P.; Mitselmakher, G.; Muniz, L.; Rinkevicius, A.; Shchutska, L.; Snowball, M.; Yelton, J.; Zakaria, M.; Hewamanage, S.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Adams, T.; Askew, A.; Bochenek, J.; Diamond, B.; Haas, J.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Prosper, H.; Veeraraghavan, V.; Weinberg, M.; Baarmand, M. M.; Hohlmann, M.; Kalakhety, H.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Bazterra, V. E.; Berry, D.; Betts, R. R.; Bucinskaite, I.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Khalatyan, S.; Kurt, P.; Moon, D. H.; O'Brien, C.; Silkworth, C.; Turner, P.; Varelas, N.; Albayrak, E. A.; Bilki, B.; Clarida, W.; Dilsiz, K.; Duru, F.; Haytmyradov, M.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Rahmat, R.; Sen, S.; Tan, P.; Tiras, E.; Wetzel, J.; Yetkin, T.; Yi, K.; Barnett, B. A.; Blumenfeld, B.; Bolognesi, S.; Fehling, D.; Gritsan, A. V.; Maksimovic, P.; Martin, C.; Swartz, M.; Baringer, P.; Bean, A.; Benelli, G.; Bruner, C.; Gray, J.; Kenny, R. P.; Malek, M.; Murray, M.; Noonan, D.; Sanders, S.; Sekaric, J.; Stringer, R.; Wang, Q.; Wood, J. S.; Barfuss, A. F.; Chakaberia, I.; Ivanov, A.; Khalil, S.; Makouski, M.; Maravin, Y.; Saini, L. K.; Shrestha, S.; Skhirtladze, N.; Svintradze, I.; Gronberg, J.; Lange, D.; Rebassoo, F.; Wright, D.; Baden, A.; Belloni, A.; Calvert, B.; Eno, S. C.; Gomez, J. A.; Hadley, N. J.; Kellogg, R. G.; Kolberg, T.; Lu, Y.; Marionneau, M.; Mignerey, A. C.; Pedro, K.; Skuja, A.; Tonjes, M. B.; Tonwar, S. C.; Apyan, A.; Barbieri, R.; Bauer, G.; Busza, W.; Cali, I. A.; Chan, M.; Di Matteo, L.; Dutta, V.; Gomez Ceballos, G.; Goncharov, M.; Gulhan, D.; Klute, M.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Ma, T.; Paus, C.; Ralph, D.; Roland, C.; Roland, G.; Stephans, G. S. F.; Stöckli, F.; Sumorok, K.; Velicanu, D.; Veverka, J.; Wyslouch, B.; Yang, M.; Zanetti, M.; Zhukova, V.; Dahmes, B.; Gude, A.; Kao, S. C.; Klapoetke, K.; Kubota, Y.; Mans, J.; Pastika, N.; Rusack, R.; Singovsky, A.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Bose, S.; Claes, D. R.; Dominguez, A.; Gonzalez Suarez, R.; Keller, J.; Knowlton, D.; Kravchenko, I.; Lazo-Flores, J.; Malik, S.; Meier, F.; Snow, G. R.; Dolen, J.; Godshalk, A.; Iashvili, I.; Kharchilava, A.; Kumar, A.; Rappoccio, S.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Haley, J.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Trocino, D.; Wang, R.-J.; Wood, D.; Zhang, J.; Hahn, K. A.; Kubik, A.; Mucia, N.; Odell, N.; Pollack, B.; Pozdnyakov, A.; Schmitt, M.; Stoynev, S.; Sung, K.; Velasco, M.; Won, S.; Brinkerhoff, A.; Chan, K. M.; Drozdetskiy, A.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Luo, W.; Lynch, S.; Marinelli, N.; Pearson, T.; Planer, M.; Ruchti, R.; Valls, N.; Wayne, M.; Wolf, M.; Woodard, A.; Antonelli, L.; Brinson, J.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Hill, C.; Hughes, R.; Kotov, K.; Ling, T. Y.; Puigh, D.; Rodenburg, M.; Smith, G.; Winer, B. L.; Wolfe, H.; Wulsin, H. W.; Driga, O.; Elmer, P.; Hebda, P.; Hunt, A.; Koay, S. A.; Lujan, P.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Piroué, P.; Quan, X.; Saka, H.; Stickland, D.; Tully, C.; Werner, J. S.; Zenz, S. C.; Zuranski, A.; Brownson, E.; Mendez, H.; Ramirez Vargas, J. E.; Barnes, V. E.; Benedetti, D.; Bolla, G.; Bortoletto, D.; De Mattia, M.; Hu, Z.; Jha, M. K.; Jones, M.; Jung, K.; Kress, M.; Leonardo, N.; Lopes Pegna, D.; Maroussov, V.; Merkel, P.; Miller, D. H.; Neumeister, N.; Radburn-Smith, B. C.; Shi, X.; Shipsey, I.; Silvers, D.; Svyatkovskiy, A.; Wang, F.; Xie, W.; Xu, L.; Yoo, H. D.; Zablocki, J.; Zheng, Y.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Ecklund, K. M.; Geurts, F. J. M.; Li, W.; Michlin, B.; Padley, B. P.; Redjimi, R.; Roberts, J.; Zabel, J.; Betchart, B.; Bodek, A.; Covarelli, R.; de Barbaro, P.; Demina, R.; Eshaq, Y.; Ferbel, T.; Garcia-Bellido, A.; Goldenzweig, P.; Han, J.; Harel, A.; Khukhunaishvili, A.; Petrillo, G.; Vishnevskiy, D.; Ciesielski, R.; Demortier, L.; Goulianos, K.; Lungu, G.; Mesropian, C.; Arora, S.; Barker, A.; Chou, J. P.; Contreras-Campana, C.; Contreras-Campana, E.; Duggan, D.; Ferencek, D.; Gershtein, Y.; Gray, R.; Halkiadakis, E.; Hidas, D.; Kaplan, S.; Lath, A.; Panwalkar, S.; Park, M.; Patel, R.; Salur, S.; Schnetzer, S.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Rose, K.; Spanier, S.; York, A.; Bouhali, O.; Castaneda Hernandez, A.; Eusebi, R.; Flanagan, W.; Gilmore, J.; Kamon, T.; Khotilovich, V.; Krutelyov, V.; Montalvo, R.; Osipenkov, I.; Pakhotin, Y.; Perloff, A.; Roe, J.; Rose, A.; Safonov, A.; Sakuma, T.; Suarez, I.; Tatarinov, A.; Akchurin, N.; Cowden, C.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Kovitanggoon, K.; Kunori, S.; Lee, S. W.; Libeiro, T.; Volobouev, I.; Appelt, E.; Delannoy, A. G.; Greene, S.; Gurrola, A.; Johns, W.; Maguire, C.; Mao, Y.; Melo, A.; Sharma, M.; Sheldon, P.; Snook, B.; Tuo, S.; Velkovska, J.; Arenton, M. W.; Boutle, S.; Cox, B.; Francis, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Lin, C.; Neu, C.; Wood, J.; Clarke, C.; Harr, R.; Karchin, P. E.; Kottachchi Kankanamge Don, C.; Lamichhane, P.; Sturdy, J.; Belknap, D. A.; Carlsmith, D.; Cepeda, M.; Dasu, S.; Dodd, L.; Duric, S.; Friis, E.; Hall-Wilton, R.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Lazaridis, C.; Levine, A.; Loveless, R.; Mohapatra, A.; Ojalvo, I.; Perry, T.; Pierro, G. A.; Polese, G.; Ross, I.; Sarangi, T.; Savin, A.; Smith, W. H.; Vuosalo, C.; Woods, N.; CMS Collaboration

    2014-12-01

    The ratio between the prompt ψ (2 S ) and J /ψ yields, reconstructed via their decays into μ+μ-, is measured in Pb-Pb and p -p collisions at √{sN N }=2.76 TeV . The analysis is based on Pb-Pb and p -p data samples collected by CMS at the Large Hadron Collider, corresponding to integrated luminosities of 150 μ b-1 and 5.4 pb-1 , respectively. The double ratio of measured yields (Nψ (2 S )/NJ /ψ)Pb -Pb/(Nψ (2 S )/NJ /ψ)p -p is computed in three Pb-Pb collision centrality bins and two kinematic ranges: one at midrapidity, |y | <1.6 , covering the transverse momentum range 6.5 <pT<30 GeV /c , and the other at forward rapidity, 1.6 <|y | <2.4 , extending to lower pT values, 3 <pT<30 GeV /c . The centrality-integrated double ratio changes from 0.45 ±0.13 (stat) ±0.07 (syst) in the first range to 1.67 ±0.34 (stat) ±0.27 (syst) in the second. This difference is most pronounced in the most central collisions.

  9. Sphingosine-1-Phosphate (S1P) Lyase Inhibition Causes Increased Cardiac S1P Levels and Bradycardia in Rats.

    Science.gov (United States)

    Harris, Christopher M; Mittelstadt, Scott; Banfor, Patricia; Bousquet, Peter; Duignan, David B; Gintant, Gary; Hart, Michelle; Kim, Youngjae; Segreti, Jason

    2016-10-01

    Inhibition of the sphingosine-1-phosphate (S1P)-catabolizing enzyme S1P lyase (S1PL) elevates the native ligand of S1P receptors and provides an alternative mechanism for immune suppression to synthetic S1P receptor agonists. S1PL inhibition is reported to preferentially elevate S1P in lymphoid organs. Tissue selectivity could potentially differentiate S1PL inhibitors from S1P receptor agonists, the use of which also results in bradycardia, atrioventricular block, and hypertension. But it is unknown if S1PL inhibition would also modulate cardiac S1P levels or cardiovascular function. The S1PL inhibitor 6-[(2R)-4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile was used to determine the relationship in rats between drug concentration, S1P levels in select tissues, and circulating lymphocytes. Repeated oral doses of the S1PL inhibitor fully depleted circulating lymphocytes after 3 to 4 days of treatment in rats. Full lymphopenia corresponded to increased levels of S1P of 100- to 1000-fold in lymph nodes, 3-fold in blood (but with no change in plasma), and 9-fold in cardiac tissue. Repeated oral dosing of the S1PL inhibitor in telemeterized, conscious rats resulted in significant bradycardia within 48 hours of drug treatment, comparable in magnitude to the bradycardia induced by 3 mg/kg fingolimod. These results suggest that S1PL inhibition modulates cardiac function and does not provide immune suppression with an improved cardiovascular safety profile over fingolimod in rats. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  10. Quasifree (p ,p N ) scattering of light neutron-rich nuclei near N =14

    Science.gov (United States)

    Díaz Fernández, P.; Alvarez-Pol, H.; Crespo, R.; Cravo, E.; Atar, L.; Deltuva, A.; Aumann, T.; Avdeichikov, V.; Beceiro-Novo, S.; Bemmerer, D.; Benlliure, J.; Bertulani, C. A.; Boillos, J. M.; Boretzky, K.; Borge, M. J. G.; Caamaño, M.; Cabanelas, P.; Caesar, C.; Casarejos, E.; Catford, W.; Cederkäll, J.; Chartier, M.; Chulkov, L. V.; Cortina-Gil, D.; Datta Pramanik, U.; Dillmann, I.; Elekes, Z.; Enders, J.; Ershova, O.; Estradé, A.; Farinon, F.; Fernández-Domínguez, B.; Fraile, L. M.; Freer, M.; Galaviz, D.; Geissel, H.; Gernhäuser, R.; Golubev, P.; Göbel, K.; Hagdahl, J.; Heftrich, T.; Heil, M.; Heine, M.; Heinz, A.; Henriques, A.; Holl, M.; Hufnagel, A.; Ignatov, A.; Johansson, H. T.; Jonson, B.; Jurčiukonis, D.; Kalantar-Nayestanaki, N.; Kanungo, R.; Kelic-Heil, A.; Knyazev, A.; Kröll, T.; Kurz, N.; Labiche, M.; Langer, C.; Le Bleis, T.; Lemmon, R.; Lindberg, S.; Machado, J.; Marganiec, J.; Moro, A. M.; Movsesyan, A.; Nacher, E.; Najafi, A.; Nikolskii, E.; Nilsson, T.; Nociforo, C.; Panin, V.; Paschalis, S.; Perea, A.; Petri, M.; Pietras, B.; Pietri, S.; Plag, R.; Reifarth, R.; Ribeiro, G.; Rigollet, C.; Rossi, D.; Röder, M.; Savran, D.; Scheit, H.; Simon, H.; Sorlin, O.; Syndikus, I.; Taylor, J. T.; Tengblad, O.; Thies, R.; Togano, Y.; Vandebrouck, M.; Velho, P.; Volkov, V.; Wagner, A.; Wamers, F.; Weick, H.; Wheldon, C.; Wilson, G.; Winfield, J. S.; Woods, P.; Yakorev, D.; Zhukov, M.; Zilges, A.; Zuber, K.; R3B Collaboration

    2018-02-01

    Background: For many years, quasifree scattering reactions in direct kinematics have been extensively used to study the structure of stable nuclei, demonstrating the potential of this approach. The R 3B collaboration has performed a pilot experiment to study quasifree scattering reactions in inverse kinematics for a stable 12C beam. The results from that experiment constitute the first quasifree scattering results in inverse and complete kinematics. This technique has lately been extended to exotic beams to investigate the evolution of shell structure, which has attracted much interest due to changes in shell structure if the number of protons or neutrons is varied. Purpose: In this work we investigate for the first time the quasifree scattering reactions (p ,p n ) and (p ,2 p ) simultaneously for the same projectile in inverse and complete kinematics for radioactive beams with the aim to study the evolution of single-particle properties from N =14 to N =15 . Method: The structure of the projectiles 23O, 22O, and 21N has been studied simultaneously via (p ,p n ) and (p ,2 p ) quasifree knockout reactions in complete inverse kinematics, allowing the investigation of proton and neutron structure at the same time. The experimental data were collected at the R3B -LAND setup at GSI at beam energies of around 400 MeV/u. Two key observables have been studied to shed light on the structure of those nuclei: the inclusive cross sections and the corresponding momentum distributions. Conclusions: The knockout reactions (p ,p n ) and (p ,2 p ) with radioactive beams in inverse kinematics have provided important and complementary information for the study of shell evolution and structure. For the (p ,p n ) channels, indications of a change in the structure of these nuclei moving from N =14 to N =15 have been observed, i.e., from the 0 d5 /2 shell to the 1 s1 /2 . This supports previous observations of a subshell closure at N =14 for neutron-rich oxygen isotopes and its weakening

  11. The 2H(p,2p)n reaction at 508 MeV. Part I

    International Nuclear Information System (INIS)

    Punjabi, V.; Perdrisat, C.F.; Aniol, K.A.; Epstein, M.B.; Huber, J.P.; Margaziotis, D.J.; Bracco, A.; Davis, C.A.; Gubler, H.P.; Lee, W.P.; Poffenberger, P.R.; van Oers, W.T.H.; Postma, H.; Sebel, H.J.; Stetz, A.W.

    1988-09-01

    Differential cross sections for the reaction 2 H(p,2p)n at T p = 507 and 508 MeV are presented. The proton angle pairs chosen were 41.5 degrees with 41.4 and 50.0, 30.1 degrees with 44.0, 53,75, 61.0, and 68.0, 38.1 degrees -38.0 degrees, 44.1 degrees - 44.0 degrees, 47.1 degrees - 47.0 degrees and 50.0 degrees - 50.0 degrees. The data range over an energy window 100 MeV wide on one of the proton energies, the second energy being defined by the kinematic condition of a single neutron recoiling. The data are compared with the impulse approximation (IA) prediction and with the results of a nonrelativistic calculation of the six lowest-order Feynman diagrams describing the reaction. A previously known missing strength for the reaction in the small neutron recoil region is confirmed with much smaller experimental uncertainty; the missing strength persists up to 150 MeV/c neutron recoil. The onset of a systematic section excess relative to the IA near neutron recoil momentum 200 MeV is explored in detail. (Author) (37 refs., 17 figs.)

  12. Arithmetically Cohen-Macaulay sets of points in P^1 x P^1

    CERN Document Server

    Guardo, Elena

    2015-01-01

    This brief presents a solution to the interpolation problem for arithmetically Cohen-Macaulay (ACM) sets of points in the multiprojective space P^1 x P^1.  It collects the various current threads in the literature on this topic with the aim of providing a self-contained, unified introduction while also advancing some new ideas.  The relevant constructions related to multiprojective spaces are reviewed first, followed by the basic properties of points in P^1 x P^1, the bigraded Hilbert function, and ACM sets of points.  The authors then show how, using a combinatorial description of ACM points in P^1 x P^1, the bigraded Hilbert function can be computed and, as a result, solve the interpolation problem.  In subsequent chapters, they consider fat points and double points in P^1 x P^1 and demonstrate how to use their results to answer questions and problems of interest in commutative algebra.  Throughout the book, chapters end with a brief historical overview, citations of related results, and, where relevan...

  13. Isotope shift of 40,42,44,48Ca in the 4s 2S1/2 → 4p 2P3/2 transition

    Science.gov (United States)

    Gorges, C.; Blaum, K.; Frömmgen, N.; Geppert, Ch; Hammen, M.; Kaufmann, S.; Krämer, J.; Krieger, A.; Neugart, R.; Sánchez, R.; Nörtershäuser, W.

    2015-12-01

    We report on improved isotope shift measurements of the isotopes {}{40,42,{44,48}}Ca in the 4{{s}}{ }2{{{S}}}1/2\\to 4{{p}}{ }2{{{P}}}3/2 (D2) transition using collinear laser spectroscopy. Accurately known isotope shifts in the 4{{s}}{ }2{{{S}}}1/2\\to 4{{p}}{ }2{{{P}}}1/2(D1) transition were used to calibrate the ion beam energy with an uncertainty of {{Δ }}U≈ +/- 0.25 {{V}}. The accuracy in the D2 transition was improved by a factor of 5-10. A King-plot analysis of the two transitions revealed that the field shift factor in the D2 line is about 1.8(13)% larger than in the D1 transition which is ascribed to relativistic contributions of the 4{{{p}}}1/2 wave function.

  14. 2,3,7,8-Tetrachlorodibenzo-p-dioxin increases reactive oxygen species production in human endothelial cells via induction of cytochrome P4501A1

    International Nuclear Information System (INIS)

    Kopf, P.G.; Walker, M.K.

    2010-01-01

    Studies in our laboratory have demonstrated that subchronic 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) exposure of adult mice results in hypertension, cardiac hypertrophy, and reduced nitric oxide (NO)-mediated vasodilation. Moreover, increased superoxide anion production was observed in cardiovascular organs of TCDD-exposed mice and this increase contributed to the reduced NO-mediated vasodilation. Since cytochrome P4501A1 (CYP1A1) can contribute to some TCDD-induced toxicity, we tested the hypothesis that TCDD increases reactive oxygen species (ROS) in endothelial cells by the induction of CYP1A1. A concentration-response to 24 h TCDD exposure (10 pM-10 nM) was performed in confluent primary human aortic endothelial cells (HAECs). Oxidant-sensitive fluorescent probes dihydroethidium (DHE) and 2',7'-dichlorofluorescin diacetate (DCFH-DA), were used to measure superoxide anion, and hydrogen peroxide and hydroxyl radical, respectively. NO was also measured using the fluorescent probe diaminofluorescein-2 diacetate (DAF-2DA). These assessments were conducted in HAECs transfected with siRNA targeting the aryl hydrocarbon receptor (AhR), CYP1A1, or CYP1B1. TCDD concentration-dependently increased CYP1A1 and CYP1B1 mRNA, protein, and enzyme activity. Moreover, 1 nM TCDD maximally increased DHE (Cont = 1.0 ± 0.3; TCDD = 5.1 ± 1.0; p = 0.002) and DCFH-DA (Cont = 1.0 ± 0.2; TCDD = 4.1 ± 0.5; p = 0.002) fluorescence and maximally decreased DAF-2DA fluorescence (Cont = 1.0 ± 0.4; TCDD = 0.68 ± 0.1). siRNA targeting AhR and CYP1A1 significantly decreased TCDD-induced DHE (siAhR: Cont = 1.0 ± 0.1; TCDD = 1.3 ± 0.2; p = 0.093) (siCYP1A1: Cont = 1.0 ± 0.1; TCDD = 1.1 ± 0.1; p = 0.454) and DCFH-DA (siAhR: Cont = 1.0 ± 0.2; TCDD = 1.3 ± 0.3; p = 0.370) (siCYP1A1: Cont = 1.0 ± 0.1; TCDD = 1.3 ± 0.2; p = 0.114) fluorescence and increased DAF-2DA fluorescence (siAhR: Cont = 1.00 ± 0.03; TCDD = 0.97 ± 0.03; p = 0.481) (siCYP1A1: Cont = 1.00 ± 0.03; TCDD = 0.92 ± 0

  15. Cytoplasmic localization of Hug1p, a negative regulator of the MEC1 pathway, coincides with the compartmentalization of Rnr2p–Rnr4p

    Energy Technology Data Exchange (ETDEWEB)

    Ainsworth, William B. [Cain Department of Chemical Engineering, Louisiana State University, Baton Rouge, LA 70803 (United States); Hughes, Bridget Todd; Au, Wei Chun; Sakelaris, Sally [Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Kerscher, Oliver [Biology Department, The College of William and Mary, Williamsburg, VA 23185 (United States); Benton, Michael G., E-mail: benton@lsu.edu [Cain Department of Chemical Engineering, Louisiana State University, Baton Rouge, LA 70803 (United States); Basrai, Munira A., E-mail: basraim@mail.nih.gov [Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-10-04

    Highlights: •Hug1p overexpression sensitizes wild-type cells to DNA damage and hydroxyurea (HU). •Expression of Hug1p in response to HU treatment is delayed relative to Rnr3p. •MEC1 pathway genes are required for cytoplasmic localization of Hug1p. •Hug1p subcellular compartmentalization to the cytoplasm coincides with Rnr2p–Rnr4p. -- Abstract: The evolutionarily conserved MEC1 checkpoint pathway mediates cell cycle arrest and induction of genes including the RNR (Ribonucleotide reductase) genes and HUG1 (Hydroxyurea, ultraviolet, and gamma radiation) in response to DNA damage and replication arrest. Rnr complex activity is in part controlled by cytoplasmic localization of the Rnr2p–Rnr4p subunits and inactivation of negative regulators Sml1p and Dif1p upon DNA damage and hydroxyurea (HU) treatment. We previously showed that a deletion of HUG1 rescues lethality of mec1Δ and suppresses dun1Δ strains. In this study, multiple approaches demonstrate the regulatory response of Hug1p to DNA damage and HU treatment and support its role as a negative effector of the MEC1 pathway. Consistent with our hypothesis, wild-type cells are sensitive to DNA damage and HU when HUG1 is overexpressed. A Hug1 polyclonal antiserum reveals that HUG1 encodes a protein in budding yeast and its MEC1-dependent expression is delayed compared to the rapid induction of Rnr3p in response to HU treatment. Cell biology and subcellular fractionation experiments show localization of Hug1p-GFP to the cytoplasm upon HU treatment. The cytoplasmic localization of Hug1p-GFP is dependent on MEC1 pathway genes and coincides with the cytoplasmic localization of Rnr2p–Rnr4p. Taken together, the genetic interactions, gene expression, and localization studies support a novel role for Hug1p as a negative regulator of the MEC1 checkpoint response through its compartmentalization with Rnr2p–Rnr4p.

  16. In vitro reassortment between endemic H1N2 and 2009 H1N1 pandemic swine influenza viruses generates attenuated viruses.

    Directory of Open Access Journals (Sweden)

    Ben M Hause

    Full Text Available The pandemic H1N1 (pH1N1 influenza virus was first reported in humans in the spring of 2009 and soon thereafter was identified in numerous species, including swine. Reassortant viruses, presumably arising from the co-infection of pH1N1 and endemic swine influenza virus (SIV, were subsequently identified from diagnostic samples collected from swine. In this study, co-infection of swine testicle (ST cells with swine-derived endemic H1N2 (MN745 and pH1N1 (MN432 yielded two reassortant H1N2 viruses (R1 and R2, both possessing a matrix gene derived from pH1N1. In ST cells, the reassortant viruses had growth kinetics similar to the parental H1N2 virus and reached titers approximately 2 log(10 TCID(50/mL higher than the pH1N1 virus, while in A549 cells these viruses had similar growth kinetics. Intranasal challenge of pigs with H1N2, pH1N1, R1 or R2 found that all viruses were capable of infecting and transmitting between direct contact pigs as measured by real time reverse transcription PCR of nasal swabs. Lung samples were also PCR-positive for all challenge groups and influenza-associated microscopic lesions were detected by histology. Interestingly, infectious virus was detected in lung samples for pigs challenged with the parental H1N2 and pH1N1 at levels significantly higher than either reassortant virus despite similar levels of viral RNA. Results of our experiment suggested that the reassortant viruses generated through in vitro cell culture system were attenuated without gaining any selective growth advantage in pigs over the parental lineages. Thus, reassortant influenza viruses described in this study may provide a good system to study genetic basis of the attenuation and its mechanism.

  17. Synthesis and characterization of new N-(diphenylphosphino)-naphthylamine chalcogenides: X-ray structures of (1-NHC 10H 7)P(Se)Ph 2 and Ph 2P(S)OP(S)Ph 2

    KAUST Repository

    Tomah Al-Masri, Harbi; Emwas, Abdul-Hamid M.; Al-Talla, Zeyad; Al Kordi, Mohamed

    2012-01-01

    The reaction of 1-naphthylamine with one equivalent of chlorodiphenylphosphine in the presence of triethylamine gave the (1-NHC 10H 7)PPh 2 (1) ligand. Refluxing of 1 with elemental sulfur or grey selenium in toluene (1:1 molar ratio) afforded (1-NHC 10H 7)P(S)Ph 2 (2) and (1-NHC 10H 7)P(Se)Ph 2 (3), respectively. Moreover, the byproduct {Ph 2P(S)} 2O (4) was isolated from the reaction of 1 with elemental sulfur. Compounds 1-3 were identified and characterized by multinuclear ( 1H, 13C, 31P, 77Se) NMR spectroscopy, mass spectrometry, and elemental analysis. Crystal structure determinations of 3 and 4 were carried out. Copyright © 2012 Taylor and Francis Group, LLC.

  18. Synthesis and characterization of new N-(diphenylphosphino)-naphthylamine chalcogenides: X-ray structures of (1-NHC 10H 7)P(Se)Ph 2 and Ph 2P(S)OP(S)Ph 2

    KAUST Repository

    Tomah Al-Masri, Harbi

    2012-09-01

    The reaction of 1-naphthylamine with one equivalent of chlorodiphenylphosphine in the presence of triethylamine gave the (1-NHC 10H 7)PPh 2 (1) ligand. Refluxing of 1 with elemental sulfur or grey selenium in toluene (1:1 molar ratio) afforded (1-NHC 10H 7)P(S)Ph 2 (2) and (1-NHC 10H 7)P(Se)Ph 2 (3), respectively. Moreover, the byproduct {Ph 2P(S)} 2O (4) was isolated from the reaction of 1 with elemental sulfur. Compounds 1-3 were identified and characterized by multinuclear ( 1H, 13C, 31P, 77Se) NMR spectroscopy, mass spectrometry, and elemental analysis. Crystal structure determinations of 3 and 4 were carried out. Copyright © 2012 Taylor and Francis Group, LLC.

  19. Exclusive interactions in p anti-p collisions at s**(1/2) = 1.96 TeV

    International Nuclear Information System (INIS)

    Hamilton, Andrew; Alberta U.

    2006-01-01

    This thesis presents two exclusive production processes in p(bar p) collisions at √s = 1.96 TeV, using the Collider Detector Facility at Fermi National Accelerator Laboratory. An observation of exclusive e + e - production through γγ → e + e - is presented, as well as evidence for exclusive production of γγ through gg → γγ (via a quark loop). The exclusive e + e - production observation is based on 16 candidate events, with a background estimate of 2.1 -0.3 +0.7 . Each event has an e + e - pair (E T (e) > 5 GeV, |η(e)| -0.3 +0.5 (stat) ± 0.3(sys) pb, while the predicted cross section is 1.711 ± 0.008 pb. The kinematic properties of the events are consistent with the predictions of the LPAIR Monte Carlo. The evidence for exclusive γγ production consists of 3 candidate events, with a background estimate of 0.0 -0.0 +0.2 events. Each event has two photons (E T γ) > 5 GeV, |η(γ)| -0.04 +0.14 (stat) ± (sys) pb. It agrees with the theoretical prediction of 0.04 pb with a factor 3 to 5 theoretical uncertainty

  20. Overexpression of HDAC1 induces cellular senescence by Sp1/PP2A/pRb pathway

    International Nuclear Information System (INIS)

    Chuang, Jian-Ying; Hung, Jan-Jong

    2011-01-01

    Highlights: → Overexpression of HDAC1 induces Sp1 deacetylation and raises Sp1/p300 complex formation to bind to PP2Ac promoter. → Overexpression of HDAC1 strongly inhibits the phosphorylation of pRb through up-regulation of PP2A. → Overexpressed HDAC1 restrains cell proliferaction and induces cell senescence though a novel Sp1/PP2A/pRb pathway. -- Abstract: Senescence is associated with decreased activities of DNA replication, protein synthesis, and cellular division, which can result in deterioration of cellular functions. Herein, we report that the growth and division of tumor cells were significantly repressed by overexpression of histone deacetylase (HDAC) 1 with the Tet-off induced system or transient transfection. In addition, HDAC1 overexpression led to senescence through both an accumulation of hypophosphorylated active retinoblastoma protein (pRb) and an increase in the protein level of protein phosphatase 2A catalytic subunit (PP2Ac). HDAC1 overexpression also increased the level of Sp1 deacetylation and elevated the interaction between Sp1 and p300, and subsequently that Sp1/p300 complex bound to the promoter of PP2Ac, thus leading to induction of PP2Ac expression. Similar results were obtained in the HDAC1-Tet-off stable clone. Taken together, these results indicate that HDAC1 overexpression restrained cell proliferation and induced premature senescence in cervical cancer cells through a novel Sp1/PP2A/pRb pathway.

  1. Overexpression of HDAC1 induces cellular senescence by Sp1/PP2A/pRb pathway

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, Jian-Ying [Department of Pharmacology, National Cheng-Kung University, Tainan 701, Taiwan (China); Hung, Jan-Jong, E-mail: petehung@mail.ncku.edu.tw [Department of Pharmacology, National Cheng-Kung University, Tainan 701, Taiwan (China); Institute of Bioinformatics and Biosignal Transduction, National Cheng-Kung University, Tainan 701, Taiwan (China)

    2011-04-15

    Highlights: {yields} Overexpression of HDAC1 induces Sp1 deacetylation and raises Sp1/p300 complex formation to bind to PP2Ac promoter. {yields} Overexpression of HDAC1 strongly inhibits the phosphorylation of pRb through up-regulation of PP2A. {yields} Overexpressed HDAC1 restrains cell proliferaction and induces cell senescence though a novel Sp1/PP2A/pRb pathway. -- Abstract: Senescence is associated with decreased activities of DNA replication, protein synthesis, and cellular division, which can result in deterioration of cellular functions. Herein, we report that the growth and division of tumor cells were significantly repressed by overexpression of histone deacetylase (HDAC) 1 with the Tet-off induced system or transient transfection. In addition, HDAC1 overexpression led to senescence through both an accumulation of hypophosphorylated active retinoblastoma protein (pRb) and an increase in the protein level of protein phosphatase 2A catalytic subunit (PP2Ac). HDAC1 overexpression also increased the level of Sp1 deacetylation and elevated the interaction between Sp1 and p300, and subsequently that Sp1/p300 complex bound to the promoter of PP2Ac, thus leading to induction of PP2Ac expression. Similar results were obtained in the HDAC1-Tet-off stable clone. Taken together, these results indicate that HDAC1 overexpression restrained cell proliferation and induced premature senescence in cervical cancer cells through a novel Sp1/PP2A/pRb pathway.

  2. S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1.

    Science.gov (United States)

    Maeda, Yasuhiro; Yagi, Hideki; Takemoto, Kana; Utsumi, Hiroyuki; Fukunari, Atsushi; Sugahara, Kunio; Masuko, Takashi; Chiba, Kenji

    2014-05-01

    Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymic medulla. Immunohistochemical staining using anti-S1P1 antibody revealed that S1P1 is predominantly expressed on thymocytes in the thymic medulla and is strongly down-regulated even at 3h after FTY720 administration. 2-Acetyl-4-tetrahydroxybutylimidazole (THI), an S1P lyase inhibitor, also induced accumulation of mature SP thymocytes in the thymic medulla with an enlargement of the perivascular spaces (PVS). At 6h after THI administration, S1P1-expressing thymocytes reduced partially as if to form clusters and hardly existed in the proximity of CD31-expressing blood vessels in the thymic medulla, suggesting S1P lyase expression in the cells constructing thymic medullary PVS. To determine the cells expressing S1P lyase in the thymus, we newly established a mAb (YK19-2) specific for mouse S1P lyase. Immunohistochemical staining with YK19-2 revealed that S1P lyase is predominantly expressed in non-lymphoid thymic stromal cells in the thymic medulla. In the thymic medullary PVS, S1P lyase was expressed in ER-TR7-positive cells (reticular fibroblasts and pericytes) and CD31-positive vascular endothelial cells. Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1.

  3. Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Arun K.; Brindisi, Margherita; Nyalapatla, Prasanth R.; Takayama, Jun; Ella-Menye, Jean-Rene; Yashchuk, Sofiya; Agniswamy, Johnson; Wang, Yuan-Fang; Aoki, Manabu; Amano, Masayuki; Weber, Irene T.; Mitsuya, Hiroaki

    2017-10-01

    Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme Ki of 0.025 nM and antiviral IC50 of 69 nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33 Å resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27 Å resolution. These structures revealed important molecular insight into the inhibitor–HIV-1 protease interactions in the active site.

  4. Magnetostriction-strain-induced enhancement and modulation of photovoltaic performance in Si-p-n/Tb{sub x}Dy{sub 1-x}Fe{sub 2} composite

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zheng [School of Materials Science and Technology, China University of Geosciences, Beijing (China); Department of Physics and College of Geography and Environmental Sciences, Zhejiang Normal University, Jinhua (China); Zhang, Yihe [School of Materials Science and Technology, China University of Geosciences, Beijing (China); Fang, Cong; Ma, Ke; Lin, He; Jia, Yanmin; Chen, Jianrong [Department of Physics and College of Geography and Environmental Sciences, Zhejiang Normal University, Jinhua (China); Wang, Yu; Chan, Helen Lai Wa [Department of Applied Physics, The Hong Kong Polytechnic University (China)

    2014-03-15

    High photovoltaic efficiency is a key index in the application of silicon (Si) solar cells. In this study, a composite of a photovoltaic Si p-n junction solar cell and a magnetostrictive Tb{sub x}Dy{sub 1-x}Fe{sub 2} alloy was fabricated. By utilizing the magnetostrictive strain to modulate the energy bandgap of Si, the open-circuit voltage and the maximum photovoltaic output power of the Si p-n junction solar cell could be enhanced by ∝12% and 9.1% under a dc magnetic field of ∝250 mT, respectively. The significantly enhanced photovoltaic performance and the simple fabrication process make the Si-p-n/Tb{sub x}Dy{sub 1-x}Fe{sub 2} composite a promising material for high-efficiency solar cell devices. The structure of the proposed Si-p-n/Tb{sub x}Dy{sub 1-x}Fe{sub 2} laminated composite. (copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Familial partial duplication (1)(p21p31)

    Energy Technology Data Exchange (ETDEWEB)

    Hoechstetter, L.; Soukup, S.; Schorry, E.K. [Children`s Hospital Research Foundation, Cincinnati, OH (United States)

    1995-11-20

    A partial duplication (1)(p21p31), resulting from a maternal direct insertion (13,1) (q22p21p31), was found in a 30-year-old woman with mental retardation, cleft palate, and multiple minor anomalies. Two other affected and deceased relatives were presumed to have the same chromosome imbalance. Duplication 1p cases are reviewed. 8 refs., 5 figs., 1 tab.

  6. The 2s1/22p1/2 + one photon transition in hydrogen and hydrogenlike ions

    International Nuclear Information System (INIS)

    Kelsey, E.J.

    1977-01-01

    The 2s 1 / 22p 1 / 2 + one photon transition rate is calculated and discussed for hydrogen and hydrogenlike ions. It is noted that the induced transition rather than the spontaneous transition is of primary importance since it is the basis of many of the precision Lamb-shift measurements. The lack of a calculation of the transition rate other than a heuristic nonrelativistic derivation which requires a nontrivial assumption motivates the calculation presented here based on the external field approximation to quantum electrodynamics. It is found that the heuristic answer is correct in lowest order. In this derivation we see that the 2s 1 / 22p 1 / 2 + one photon transition gives an apparent contradiction to the often-stated remark that for the electric dipole matrix element there exist three equivalent representations, the ''length,'' ''velocity,'' and ''acceleration'' forms. The difficulties of an experimental determination of this transition rate using induced transitions in hydrogenlike ions are briefly noted as well as the somewhat different case of heavy muonic atoms where the spontaneous 2s 1 / 22p 1 / 2 + one photon transition has been observed

  7. Synergistic action between inhibition of P2Y12/P2Y1 and P2Y12/thrombin in ADP- and thrombin-induced human platelet activation

    Science.gov (United States)

    Nylander, Sven; Mattsson, Christer; Ramström, Sofia; Lindahl, Tomas L

    2004-01-01

    The objective of this study was to investigate if there is a synergistic effect of a combination of P2Y12 and P2Y1 inhibition and P2Y12 and thrombin inhibition, on ADP- and thrombin-induced platelet activation, respectively. The rationale being that these combinations will cause a concurrent inhibition of both Gαq and Gαi signalling.Blood from healthy volunteers was preincubated with AR-C69931MX, a reversible P2Y12 antagonist; MRS2179, a reversible P2Y1 antagonist; or melagatran, a direct reversible thrombin inhibitor; alone or in various combinations prior to activation with ADP or thrombin. Platelet function in whole blood was assessed by flow cytometry using the antibody PAC-1 to estimate the expression of active αIIbβ3 (the fibrinogen receptor GPIIb/IIIa). A synergistic effect was evaluated by comparing the concentrations in the different combinations with those of corresponding equipotent concentrations of each single inhibitor alone. The equipotent single concentrations were experimentally obtained from concentration response curves performed in parallel.A synergistic effect regarding inhibition of ADP-induced platelet activation (10 μM) was obtained with different combinations of AR-C69931MX and MRS2179.Inhibition of thrombin-induced platelet activation (2 nM) with combinations of AR-C69931MX and the thrombin inhibitor melagatran did also result in a strong synergistic effect.To our knowledge, this is the first time that data supporting a synergistic effect has been published for the inhibitor combinations described.Whether this synergistic effect in vitro also results in an improved antithrombotic effect in vivo with or without an increased risk of bleeding remains to be studied in well-conducted clinical studies. PMID:15265806

  8. Biological N2 fixation mainly controlled by Sphagnum tissue N:P ratio in ombrotrophic bogs

    Science.gov (United States)

    Zivkovic, Tatjana; Moore, Tim R.

    2017-04-01

    Most of the 18 Pg nitrogen (N) accumulated in northern nutrient-poor and Sphagnum-dominated peatlands (bogs and fens) can be attributed to N2-fixation by diazotrophs either associated with the live Sphagnum or non-symbiotically in the deeper peat such as through methane consumption close to the water table. Where atmospheric N deposition is low (Sphagnum, suggested by the increase in tissue N:P to >16. It is unclear how Sphagnum-hosted diazotrophic activity may be affected by N deposition and thus changes in N:P ratio. First, we investigated the effects of long-term addition of different sources of nitrogen (0, 1.6, 3.2 and 6.4 g N m-2 y-1as NH4Cl and NaNO3), and phosphorus (5 g P m-2 y-1as KH2PO4) on Sphagnum nutrient status (N, P and N:P ratio), net primary productivity (NPP) and Sphagnum-associated N2fixation at Mer Bleue, a temperate ombrotrophic bog. We show that N concentration in Sphagnum tissue increased with larger rates of N addition, with a stronger effect on Sphagnum from NH4 than NO3. The addition of P created a 3.5 fold increase in Sphagnum P content compared to controls. Sphagnum NPP decreased linearly with the rise in N:P ratio, while linear growth declined exponentially with increase in Sphagnum N content. Rates of N2-fixation determined in the laboratory significantly decreased in response to even the smallest addition of both N species. In contrast, the addition of P increased N2 fixation by up to 100 times compared to N treatments and up to 5-30 times compared to controls. The change in N2-fixation was best modeled by the N:P ratio, across all experimental treatments. Secondly, to test the role of N:P ratio on N2-fixation across a range of bogs, eight study sites along the latitudinal gradient from temperate, boreal to subarctic zone in eastern Canada were selected. From each bog, two predominant microptopographies, hummocks and hollows, were tested for both N2-fixation activity in the laboratory and Sphagnum tissue concentrations of N, P and N:P

  9. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

    Science.gov (United States)

    Fang, Chao; Bian, Ganlan; Ren, Pan; Xiang, Jie; Song, Jun; Yu, Caiyong; Zhang, Qian; Liu, Ling; Chen, Kun; Liu, Fangfang; Zhang, Kun; Wu, Chunfeng; Sun, Ruixia; Hu, Dan; Ju, Gong; Wang, Jian

    2018-02-08

    Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate (S1P), and it participates in several physiologic processes by activating different S1P receptors (S1PRs). However, its functions in the nervous system remain largely unclear. We explored the important role of SPNS2 in the process of retinal morphogenesis using a spns2-deficient rat model. In the absence of the functional SPNS2 transporter, we observed progressively aggravating laminar disorganization of the epithelium at the postnatal stage of retinal development. Disrupted cell polarity, delayed cell-cycle exit of retinal progenitor cells, and insufficient migration of newborn neurons were proposed in this study as potential mechanisms accounting for this structural disorder. In addition, we analyzed the expression profiles of spns2 and s1prs, and proposed that SPNS2 regulated retinal morphogenesis by establishing the S1P level in the eye and activating S1PR3 signaling. These data indicate that SPNS2 is indispensable for normal retinal morphogenesis and provide new insights on the role of S1P in the developing retina using an established in vivo model.-Fang, C., Bian, G., Ren, P., Xiang, J., Song, J., Yu, C., Zhang, Q., Liu, L., Chen, K., Liu, F., Zhang, K., Wu, C., Sun, R., Hu, D., Ju, G., Wang, J. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

  10. Garvey-Kelson mass relations and n-p interaction

    International Nuclear Information System (INIS)

    Gao Zaochun; Meng Jie; Chen Yongshou

    2001-01-01

    Two Garvey-Kelson mass relations are found to be directly related to the n-p interaction. In the case of the same nuclear core, the neutron-proton interaction energy between two neutrons and one proton ε 2n-1p is experimentally found to be close to that between one neutron and two protons ε 1n-2p , which is equivalent to the first Garvey-Kelson mass relation. The sum of ε 2n-1p and ε 1n-2p is close to the n-p interaction energy between two neutrons and two protons ε 2n-2p , which leads to the second Garvey-Kelson mass relation. An explanation of these two n-p interaction relations is presented. It is shown that both of these mass relations hold more accurately when the core is an even-even core

  11. Near-threshold electron-impact excitation of the (2p53s2)2P3/2,1/2 autoionizing states in sodium

    International Nuclear Information System (INIS)

    Borovik, A; Zatsarinny, O; Bartschat, K

    2008-01-01

    The ejected-electron excitation functions of the J = 3/2, 1/2 components of the (2p 5 3s 2 ) 2 P leading autoionizing doublet in sodium atoms were measured at an incident electron energy resolution of 0.25 eV over the incident electron energy range from the lowest excitation threshold up to 36 eV. On the basis of 56-state R-matrix (close-coupling) calculations, the observed strong near-threshold structures were classified as negative-ion resonances with likely configurations 2p 5 3s 2 3p and 2p 5 3s3p 2

  12. Patient reported outcome data following influenza A (H1N1p vaccination in the 2009–2010 season: web-based and telephone evaluation

    Directory of Open Access Journals (Sweden)

    Wade AG

    2011-10-01

    Full Text Available Alan G Wade1, Gordon M Crawford1, Neil Pumford1, Alex McConnachie21Patients Direct, 3 Todd Campus, Glasgow, UK; 2Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UKBackground: There has been worldwide interest in the safety of the pandemic influenza A (H1N1p vaccines, although limited data are available from the vaccine recipients’ perspective. This evaluation was designed to collect data from people who had received an influenza vaccination during the 2009–2010 season using a web-based data collection tool supplemented by telephone reporting (PROBE.Methods: People scheduled to receive the influenza A (H1N1p or seasonal influenza vaccines were recruited through media advertising and campaigns throughout the West of Scotland. Vaccine recipients participated in the evaluation by answering demographic and side effect questions using PROBE methodology on the day of the immunization, after 3 days, 8 days, 6 weeks, 12 weeks, and 26 weeks.Results: A total of 1103 vaccine recipients including 134 young children (0–4 years participated in the evaluation; 694 (63% received H1N1p vaccine only, 135 (12% seasonal vaccine only, 224 (20% both H1N1p and seasonal vaccines, and 50 (5% received H1N1p or seasonal vaccine with a non-influenza vaccine (eg, travel or pneumococcal. Overall, 42% of recipients reported experiencing a side effect after their baseline vaccination; the most commonly reported were general and arm side effects (>20%. Injection site discomfort/pain and flu-like symptoms were reported by 57% and 24% of recipients, respectively. A significantly higher proportion of the 960 H1N1p vaccine recipients experienced a side effect (44% vs 27%, P < 0.001 or injection site discomfort/pain (61% vs 26%, P < 0.001 than those receiving seasonal influenza vaccines. Female sex and H1N1p vaccination were associated with a significantly higher risk of injection site discomfort/pain, whereas the 70+ age group was associated with a

  13. Association with the origin recognition complex suggests a novel role for histone acetyltransferase Hat1p/Hat2p

    Directory of Open Access Journals (Sweden)

    Greenblatt Jack F

    2007-09-01

    Full Text Available Abstract Background Histone modifications have been implicated in the regulation of transcription and, more recently, in DNA replication and repair. In yeast, a major conserved histone acetyltransferase, Hat1p, preferentially acetylates lysine residues 5 and 12 on histone H4. Results Here, we report that a nuclear sub-complex consisting of Hat1p and its partner Hat2p interacts physically and functionally with the origin recognition complex (ORC. While mutational inactivation of the histone acetyltransferase (HAT gene HAT1 alone does not compromise origin firing or initiation of DNA replication, a deletion in HAT1 (or HAT2 exacerbates the growth defects of conditional orc-ts mutants. Thus, the ORC-associated Hat1p-dependent histone acetyltransferase activity suggests a novel linkage between histone modification and DNA replication. Additional genetic and biochemical evidence points to the existence of partly overlapping histone H3 acetyltransferase activities in addition to Hat1p/Hat2p for proper DNA replication efficiency. Furthermore, we demonstrated a dynamic association of Hat1p with chromatin during S-phase that suggests a role of this enzyme at the replication fork. Conclusion We have found an intriguing new association of the Hat1p-dependent histone acetyltransferase in addition to its previously known role in nuclear chromatin assembly (Hat1p/Hat2p-Hif1p. The participation of a distinct Hat1p/Hat2p sub-complex suggests a linkage of histone H4 modification with ORC-dependent DNA replication.

  14. Observation of the 1P1 state of charmonium

    International Nuclear Information System (INIS)

    Armstrong, T.A.; Bettoni, D.; Bharadwaj, V.; Biino, C.; Borreani, G.; Broemmelsiek, D.; Buzzo, A.; Calabrese, R.; Ceccucci, A.; Cester, R.; Church, M.; Dalpiaz, P.; Dalpiaz, P.F.; Dibenedetto, R.; Dimitroyannis, D.; Fabbri, M.G.; Fast, J.; Gianoli, A.; Ginsburg, C.M.; Gollwitzer, K.; Hahn, A.; Hasan, M.; Hsueh, S.; Lewis, R.; Luppi, E.; Macri, M.; Majewska, A.M.; Mandelkern, M.; Marchetto, F.; Marinelli, M.; Marques, J.; Marsh, W.; Martini, M.; Masuzawa, M.; Menichetti, E.; Migliori, A.; Mussa, R.; Palestini, S.; Pallavicini, M.; Pastrone, N.; Patrignani, C.; Peoples, J. Jr.; Pesando, L.; Petrucci, F.; Pia, M.G.; Pordes, S.; Rapidis, P.; Ray, R.; Reid, J.; Rinaudo, G.; Roccuzzo, B.; Rosen, J.; Santroni, A.; Sarmiento, M.; Savrie, M.; Scalisi, A.; Schultz, J.; Seth, K.K.; Smith, A.; Smith, G.A.; Sozzi, M.; Trokenheim, S.; Weber, M.F.; Werkema, S.; Zhang, Y.; Zhao, J.; Zioulas, G.

    1992-01-01

    We have performed a search for the 1 P 1 state of charmonium resonantly formed in bar pp annihilations, close to the center of gravity of the 3 P J states. We report results from the study of the J/ψ+π 0 and J/ψ+2π final states. We have observed a statistically significant enhancement in the bar p+p→J/ψ+π 0 cross section at √s congruent 3526.2 MeV. This enhancement has the characteristics of a narrow resonance of mass, total width, and production cross section consistent with what is expected for the 1 P 1 state. In our search we have found no candidates for the reactions bar p+p→J/ψ+π 0 +π 0 and bar p+p→J/ψ+π + +π -

  15. Functional characterisation of an engineered multidomain human P450 2E1 by molecular Lego.

    Science.gov (United States)

    Fairhead, Michael; Giannini, Silva; Gillam, Elizabeth M J; Gilardi, Gianfranco

    2005-12-01

    The human cytochrome P450s constitute an important family of monooxygenase enzymes that carry out essential roles in the metabolism of endogenous compounds and foreign chemicals. We present here results of a fusion between a human P450 enzyme and a bacterial reductase that for the first time is shown does not require the addition of lipids or detergents to achieve wild-type-like activities. The fusion enzyme, P450 2E1-BMR, contains the N-terminally modified residues 22-493 of the human P450 2E1 fused at the C-terminus to residues 473-1049 of the P450 BM3 reductase (BMR). The P450 2E1-BMR enzyme is active, self-sufficient and presents the typical marker activities of the native human P450 2E1: the hydroxylation of p-nitrophenol (KM=1.84+/-0.09 mM and kcat of 2.98+/-0.04 nmol of p-nitrocatechol formed per minute per nanomole of P450) and chlorzoxazone (KM=0.65+/-0.08 mM and kcat of 0.95+/-0.10 nmol of 6-hydroxychlorzoxazone formed per minute per nanomole of P450). A 3D model of human P450 2E1 was generated to rationalise the functional data and to allow an analysis of the surface potentials. The distribution of charges on the model of P450 2E1 compared with that of the FMN domain of BMR provides the ground for the understanding of the interaction between the fused domains. The results point the way to successfully engineer a variety of catalytically self-sufficient human P450 enzymes for drug metabolism studies in solution.

  16. Posttranscriptional regulation of the karyogamy gene by Kem1p/Xrn1p exoribonuclease and Rok1p RNA helicase of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Kim, Jaehee; Jeon, Soonmee; Yang, Yun-Seok; Kim, Jinmi

    2004-01-01

    The major biochemical activities ascribed to Kem1p/Xrn1p of Saccharomyces cerevisiae are 5'-3' exoribonuclease functioning in RNA turnover and a microtubule-binding protein. Mutational analysis has shown that Kem1p/Xrn1p participates in microtubule-related functions such as nuclear fusion (karyogamy) during mating, chromosome transmission, and spindle pole body duplication. Here, evidence is presented that Kem1p plays a specific role in nuclear fusion by affecting, at the posttranscriptional level, the pheromone induction of the karyogamy-specific transcription factor Kar4p and the expression of Rok1p, a putative RNA helicase. We found that Rok1p itself also affects the pheromone induction of Kar4p and thereby participates in nuclear fusion. Analysis of the active-site mutations, xrn1-D206A or D208A, shows that nuclear fusion as well as the Rok1p synthesis do not require the exoribonuclease activity of Kem1p. Our data provide an important insight into the gene-specific regulatory function mediated by the general RNA-modulating enzymes

  17. E2F-1-Induced p53-independent apoptosis in transgenic mice

    DEFF Research Database (Denmark)

    Holmberg, Christian Henrik; Helin, K.; Sehested, M.

    1998-01-01

    The E2F transcription factors are key targets for the retinoblastoma protein, pRB. By inactivation of E2Fs, pRB prevents progression to the S phase. To test proliferative functions of E2F, we generated transgenic mice expressing human E2F-1 and/or human DP-1. When the hydroxymethyl glutaryl...... involving increased apoptosis in the germinal epithelium. This effect was potentiated by simultaneous overexpression of DP-1. Testicular atrophy as a result of overexpression of E2F-1 and DP-1 is independent of functional p53, since p53-nullizygous transgenic mice overexpressing E2F-1 and DP-1 also suffered...

  18. Frequency metrology on the 4s(2)S(1/2)-4p(2)P(1/2) transition in Ca-40(+) for a comparison with quasar data

    NARCIS (Netherlands)

    Wolf, A.L.; van den Berg, S.A.; Gohle, C.; Salumbides, E.J.; Ubachs, W.M.G.; Eikema, K.S.E.

    2008-01-01

    High accuracy frequency metrology on the 4s S 12 2 -4p P 12 2 transition in calcium ions is performed using laser cooled and crystallized ions in a linear Paul trap. Calibration is performed with a frequency comb laser, resulting in a transition frequency of f=755 222 766.2 (1.7) MHz. The accuracy

  19. DRD2 A1 allele and P300 abnormalities in obesity

    Energy Technology Data Exchange (ETDEWEB)

    Blum, K. [Univ. of Texas Health Science Center, San Antonio, TX (United States)]|[PATH Foundation, Princeton, NJ (United States); Wood, R.; Sheridan, L.P.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1994-09-01

    Obesity is a heterogeneous and prevalent disorder having both inheritable and environmental components. The role of the dopamine system in P300 has been implicated. We genotyped 193 neuropsychiatrically ill patients with and without comorbid drug and alcohol/abuse/dependence and obesity for the prevalence of the A1 allele of the DRD2 gene. We found a significant linear trend ({chi}{sup 2} = 40.4, df=1, p<0.00001) where the percent prevalence of the A1 increased with increasing polysubstance abuse. Where the A1 allele was found in 44% of 40 obese subjects, the A1 allele prevalence was found in as much as 91% of 11 obese subjects with comorbid polysubstance abuse. 53 obese subjects having a mean body weight (BMI) of 34.6{+-}8.2 were mapped for brain electrical activity and compared with 15 controls with a BMI of 22.3{+-}3.0 (P<.001). The P3 amplitude was significantly different (two tailed; t=3.24, df=16.2, P = 0.005), whereas P3 latency was not significant. Preliminarily, we found a significant decreased P3 amplitude correlated with parental polysubstance abuse (p=0.4) with prolongation of P3 latency correlated with the three risk factors of parental substance abuse, chemical dependency and carbohydrate bingeing (P<0.02). Finally, in a small sample, the A1 allele was present in 25% of probands having 0 risk compared to 66% in those obese subjects with any risk. This work represents the first electrophysiological data to implicate P3 abnormalities in a subset of obesity and further confirms an association of the DRD2 gene and a electrophysiological marker previously indicated to have predictive value in vulnerability to addictive behaviors.

  20. Measurements of analyzing power for 2H(n,n)2H scattering at 14.1 MeV and comparisons to 2H(p,p)2H

    International Nuclear Information System (INIS)

    Tornow, W.; Byrd, R.C.; Howell, C.R.; Pedroni, R.S.; Walter, R.L.

    1983-01-01

    Data for the analyzing power A/sub y/(theta) for elastic scattering of neutrons from deuterons have been measured at 14.1 MeV for the range from 30 0 to 153 0 (c.m.) to accuracies between +- 0.003 and +- 0.006. The results are compared to previous n-d data at 14 MeV and are in significant disagreement with the most recent measurement. The present data are in excellent agreement with a Faddeev calculation by Doleschall. The data are also very similar to p-d scattering data at 14.1 MeV, although systematic deviations are observed at forward angles and near the maximum of A/sub y/(theta) at 130 0 . Recent calculations indicate that Coulomb effects can explain most of these differences, although some features will require further investigation

  1. Alfalfa mosaic virus replicase proteins, P1 and P2, localize to the tonoplast in the presence of virus RNA

    International Nuclear Information System (INIS)

    Ibrahim, Amr; Hutchens, Heather M.; Howard Berg, R.; Sue Loesch-Fries, L.

    2012-01-01

    To identify the virus components important for assembly of the Alfalfa mosaic virus replicase complex, we used live cell imaging of Arabidopsis thaliana protoplasts that expressed various virus cDNAs encoding native and GFP-fusion proteins of P1 and P2 replicase proteins and full-length virus RNAs. Expression of P1-GFP alone resulted in fluorescent vesicle-like bodies in the cytoplasm that colocalized with FM4-64, an endocytic marker, and RFP-AtVSR2, RabF2a/Rha1-mCherry, and RabF2b/Ara7-mCherry, all of which localize to multivesicular bodies (MVBs), which are also called prevacuolar compartments, that mediate traffic to the lytic vacuole. GFP-P2 was driven from the cytosol to MVBs when expressed with P1 indicating that P1 recruited GFP-P2. P1-GFP localized on the tonoplast, which surrounds the vacuole, in the presence of infectious virus RNA, replication competent RNA2, or P2 and replication competent RNA1 or RNA3. This suggests that a functional replication complex containing P1, P2, and a full-length AMV RNA assembles on MVBs to traffic to the tonoplast.

  2. Alfalfa mosaic virus replicase proteins, P1 and P2, localize to the tonoplast in the presence of virus RNA

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, Amr [Department of Botany and Plant Pathology, Purdue University, West Lafayette, IN 47907 (United States); Present address: Genomics Facility, Agricultural Genetic Engineering Research Institute, Agricultural Research Center, Giza 12619 (Egypt); Hutchens, Heather M. [Department of Botany and Plant Pathology, Purdue University, West Lafayette, IN 47907 (United States); Howard Berg, R. [Integrated Microscopy Facility, Donald Danforth Plant Science Center, Saint Louis, MO 63132 (United States); Sue Loesch-Fries, L., E-mail: loeschfr@purdue.edu [Department of Botany and Plant Pathology, Purdue University, West Lafayette, IN 47907 (United States)

    2012-11-25

    To identify the virus components important for assembly of the Alfalfa mosaic virus replicase complex, we used live cell imaging of Arabidopsis thaliana protoplasts that expressed various virus cDNAs encoding native and GFP-fusion proteins of P1 and P2 replicase proteins and full-length virus RNAs. Expression of P1-GFP alone resulted in fluorescent vesicle-like bodies in the cytoplasm that colocalized with FM4-64, an endocytic marker, and RFP-AtVSR2, RabF2a/Rha1-mCherry, and RabF2b/Ara7-mCherry, all of which localize to multivesicular bodies (MVBs), which are also called prevacuolar compartments, that mediate traffic to the lytic vacuole. GFP-P2 was driven from the cytosol to MVBs when expressed with P1 indicating that P1 recruited GFP-P2. P1-GFP localized on the tonoplast, which surrounds the vacuole, in the presence of infectious virus RNA, replication competent RNA2, or P2 and replication competent RNA1 or RNA3. This suggests that a functional replication complex containing P1, P2, and a full-length AMV RNA assembles on MVBs to traffic to the tonoplast.

  3. Search for stopped gluinos from p-anti-p collisions at s**(1/2) = 1.96 TeV

    Czech Academy of Sciences Publication Activity Database

    Abazov, V. M.; Abbott, B.; Abolins, M.; Kupčo, Alexander; Lokajíček, Miloš; Šimák, Vladislav

    2007-01-01

    Roč. 99, č. 13 (2007), 131801/1-131801/7 ISSN 0031-9007 R&D Projects: GA MŠk 1P04LA210; GA MŠk 1P05LA257 Institutional research plan: CEZ:AV0Z10100502 Keywords : supersymmetry * gluino * neutralino * D0 * DZero Subject RIV: BF - Elementary Particle s and High Energy Physics Impact factor: 6.944, year: 2007

  4. Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation

    International Nuclear Information System (INIS)

    Park, Jeong Su; Kang, Dong Hoon; Lee, Da Hyun; Bae, Soo Han

    2015-01-01

    Peroxisome proliferator-activated receptor α (PPARα) activates the β-oxidation of fatty acids in the liver. Fenofibrate is a potent agonist of PPARα and is used in the treatment of hyperlipidemia. Fenofibrate treatment often induces the production of intracellular reactive oxygen species (ROS), leading to cell death. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is an essential component of the defense mechanism against oxidative stress. However, the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in fenofibrate-induced cell death is not known. In this study, we demonstrated that fenofibrate induces Keap1 degradation and Nrf2 activation. This fenofibrate-mediated Keap1 degradation is partly dependent on autophagy. Furthermore, fenofibrate-induced Keap1 degradation followed by Nrf2 activation is mainly mediated by p62, which functions as an adaptor protein in the autophagic pathway. Consistent with these findings, ablation of p62 increased fenofibrate-mediated apoptotic cell death associated with ROS accumulation. These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. - Highlights: • Fenofibrate induces cell death by increasing ROS production. • The underlying defense mechanism against this effect is unknown. • Fenofibrate induces autophagy-dependent Keap1 degradation and Nrf2 activation. • This process is p62-dependent; lack of p62 enhanced fenofibrate-mediated apoptosis. • p62 plays a crucial role in preventing fenofibrate-induced cell death

  5. Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-09-25

    Peroxisome proliferator-activated receptor α (PPARα) activates the β-oxidation of fatty acids in the liver. Fenofibrate is a potent agonist of PPARα and is used in the treatment of hyperlipidemia. Fenofibrate treatment often induces the production of intracellular reactive oxygen species (ROS), leading to cell death. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is an essential component of the defense mechanism against oxidative stress. However, the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in fenofibrate-induced cell death is not known. In this study, we demonstrated that fenofibrate induces Keap1 degradation and Nrf2 activation. This fenofibrate-mediated Keap1 degradation is partly dependent on autophagy. Furthermore, fenofibrate-induced Keap1 degradation followed by Nrf2 activation is mainly mediated by p62, which functions as an adaptor protein in the autophagic pathway. Consistent with these findings, ablation of p62 increased fenofibrate-mediated apoptotic cell death associated with ROS accumulation. These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. - Highlights: • Fenofibrate induces cell death by increasing ROS production. • The underlying defense mechanism against this effect is unknown. • Fenofibrate induces autophagy-dependent Keap1 degradation and Nrf2 activation. • This process is p62-dependent; lack of p62 enhanced fenofibrate-mediated apoptosis. • p62 plays a crucial role in preventing fenofibrate-induced cell death.

  6. Heavy particle excitation of the 2s22p52P3/2-2s22p52P1/2 transition in fluorine-like Fe XVIII and Ni XX

    International Nuclear Information System (INIS)

    Keenan, F.P.; Reid, R.H.G.

    1989-01-01

    Cross sections and rate coefficients for excitation of the 2s 2 2p 52 P 3/2 -2s 2 2p 52 P 1/2 transition in fluorine-like Fe XVIII and Ni XX by proton (p), deuteron (d), triton (t) and α-particle (α) impact have been calculated using the close-coupled impact parameter method. At temperatures close to or below those of maximum Fe XVIII and Ni XX fractional abundance in ionisation equilibrium, the p,d and t rates are found to be comparable and are much greater than the rates due to α collisions. However, at high temperatures the situation is reversed, with the α rates being about a factor of two larger than those due to the other particles. The effects of adopting the present atomic data in calculations of the electron density or ion temperature sensitive emission line ratios are briefly discussed. (author)

  7. Photocatalytic degradation of p,p'-DDT under UV and visible light using interstitial N-doped TiO₂.

    Science.gov (United States)

    Ananpattarachai, Jirapat; Kajitvichyanukul, Puangrat

    2015-01-01

    1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (or p,p'-DDT) is one of the most persistent pesticides. It is resistant to breakdown in nature and cause the water contamination problem. In this work, a major objective was to demonstrate the application of N-doped TiO2 in degradation and mineralization of the p,p'-DDT under UV and visible light in aqueous solution. The N-doped TiO2 nanopowders were prepared by a simple modified sol-gel procedure using diethanolamine (DEA) as a nitrogen source. The catalyst characteristics were investigated using XRD, SEM, TEM, and XPS. The adsorption and photocatalytic oxidation of p,p'-DDT using the synthesized N-doped TiO2 under UV and visible light were conducted in a batch photocatalytic experiment. The kinetics and p,p'-DDT degradation performance of the N-doped TiO2 were evaluated. Results show that the N-doped TiO2 can degrade p,p'-DDT effectively under both UV and visible lights. The rate constant of the p,p'-DDT degradation under UV light was only 0.0121 min(-1), whereas the rate constant of the p,p'-DDT degradation under visible light was 0.1282 min(-1). Under visible light, the 100% degradation of p,p'-DDT were obtained from N-doped TiO2 catalyst. The reaction rate of p,p'-DDT degradation using N-doped TiO2 under visible light was sixfold higher than that under UV light. According to Langmuir-Hinshelwood model, the adsorption equilibrium constant (K) for the N-doped TiO2 under visible light was 0.03078 L mg(-1), and the apparent reaction rate constant (k) was 1.3941 mg L(-1)-min. Major intermediates detected during the p,p'-DDT degradation were p,p'-DDE, o,p'-DDE, p,p'-DDD and p,p'-DDD. Results from this work can be applied further for the breakdown of p,p'-DDT molecule in the real contaminated water using this technology.

  8. P1 and N170 components distinguish human-like and animal-like makeup stimuli.

    Science.gov (United States)

    Luo, Shuwei; Luo, Wenbo; He, Weiqi; Chen, Xu; Luo, Yuejia

    2013-06-19

    This study used event-related potentials to investigate the sensitivity of P1 and N170 components to human-like and animal-like makeup stimuli, which were derived from pictures of Peking opera characters. As predicted, human-like makeup stimuli elicited larger P1 and N170 amplitudes than did animal-like makeup stimuli. Interestingly, a right hemisphere advantage was observed for human-like but not for animal-like makeup stimuli. Dipole source analyses of 130-200-ms window showed that the bilateral fusiform face area may contribute to the differential sensitivity of the N170 component in response to human-like and animal-like makeup stimuli. The present study suggests that the amplitudes of both the P1 and the N170 are sensitive for the mouth component of face-like stimuli.

  9. Arecoline inhibits the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 1A1 activation in human hepatoma cells

    International Nuclear Information System (INIS)

    Chang, Eddy Essen; Miao Zhifeng; Lee, W.-J.; Chao, H.-R.; Li, Lih-Ann; Wang, Y.-F.; Ko, Y.-C.; Tsai, F.-Y.; Yeh, S.C.; Tsou, T.-C.

    2007-01-01

    In the present study, we investigated the effect of arecoline, a major areca nut alkaloid, on the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of cytochrome P4501A1 (CYP1A1) in a human hepatoma cell line Huh-7. We treated Huh-7 cells with 10 nM TCDD in the presence of different concentrations of arecoline (50-300 μM). Our results indicated that arecoline attenuated the TCDD-induced CYP1A1 enzyme activation with an inhibitory effect on cell proliferation. By using real-time RT-PCR, we demonstrated that arecoline inhibited the TCDD-induced activations of CYP1A1 and AhR repressor (AhRR) mRNA expression in a similar pattern. Our results revealed that arecoline inhibited AhR mRNA expression with no direct effect on CYP1A1 enzyme activity. Therefore, in our present study, the observed inhibitory effect of arecoline on CYP1A1 activation was not due to the up-regulation of AhRR or direct inhibitory effect on CYP1A1. Taken together, here we have demonstrated that arecoline attenuates the TCDD-induced CYP1A1 activation mainly via down-regulation of AhR expression in human hepatoma cells, suggesting the possible involvement of arecoline in the AhR-mediated metabolism of environmental toxicants in liver

  10. Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase.

    Science.gov (United States)

    Ebenezer, David L; Fu, Panfeng; Suryadevara, Vidyani; Zhao, Yutong; Natarajan, Viswanathan

    2017-01-01

    Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes. Here, we present data on the role of S1P lyase mediated S1P signaling in regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase expression or activity attenuated LPS-induced histone acetylation and secretion of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Δ2-hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced in the cytoplasmic compartment of the endothelial cell seems to modulate histone acetylation pattern, which is different from the nuclear SphK2/S1P signaling and inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis-induced lung inflammation. Trapping fatty aldehydes and other short chain aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid peroxidation, respectively by cell permeable agents such as phloretin or other aldehyde trapping agents may be useful in treating sepsis-induced lung inflammation via modulation of histone acetylation. . Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Measurement of the production cross section ratio $\\sigma(\\chi_{b2}(1\\mathrm{P}))/ \\sigma(\\chi_{b1}(1\\mathrm{P}))$ in pp collisions at $\\sqrt{s}$ = 8 TeV

    CERN Document Server

    Khachatryan, Vardan; Tumasyan, Armen; Adam, Wolfgang; Bergauer, Thomas; Dragicevic, Marko; Erö, Janos; Fabjan, Christian; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Hartl, Christian; Hörmann, Natascha; Hrubec, Josef; Jeitler, Manfred; Kiesenhofer, Wolfgang; Knünz, Valentin; Krammer, Manfred; Krätschmer, Ilse; Liko, Dietrich; Mikulec, Ivan; Rabady, Dinyar; Rahbaran, Babak; Rohringer, Herbert; Schöfbeck, Robert; Strauss, Josef; Taurok, Anton; Treberer-Treberspurg, Wolfgang; Waltenberger, Wolfgang; Wulz, Claudia-Elisabeth; Mossolov, Vladimir; Shumeiko, Nikolai; Suarez Gonzalez, Juan; Alderweireldt, Sara; Bansal, Monika; Bansal, Sunil; Cornelis, Tom; De Wolf, Eddi A; Janssen, Xavier; Knutsson, Albert; Luyckx, Sten; Ochesanu, Silvia; Roland, Benoit; Rougny, Romain; Van De Klundert, Merijn; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Van Spilbeeck, Alex; Blekman, Freya; Blyweert, Stijn; D'Hondt, Jorgen; Daci, Nadir; Heracleous, Natalie; Keaveney, James; Lowette, Steven; Maes, Michael; Olbrechts, Annik; Python, Quentin; Strom, Derek; Tavernier, Stefaan; Van Doninck, Walter; Van Mulders, Petra; Van Onsem, Gerrit Patrick; Villella, Ilaria; Caillol, Cécile; Clerbaux, Barbara; De Lentdecker, Gilles; Dobur, Didar; Favart, Laurent; Gay, Arnaud; Grebenyuk, Anastasia; Léonard, Alexandre; Mohammadi, Abdollah; Perniè, Luca; Reis, Thomas; Seva, Tomislav; Thomas, Laurent; Vander Velde, Catherine; Vanlaer, Pascal; Wang, Jian; Adler, Volker; Beernaert, Kelly; Benucci, Leonardo; Cimmino, Anna; Costantini, Silvia; Crucy, Shannon; Dildick, Sven; Fagot, Alexis; Garcia, Guillaume; Mccartin, Joseph; Ocampo Rios, Alberto Andres; Ryckbosch, Dirk; Salva Diblen, Sinem; Sigamani, Michael; Strobbe, Nadja; Thyssen, Filip; Tytgat, Michael; Yazgan, Efe; Zaganidis, Nicolas; Basegmez, Suzan; Beluffi, Camille; Bruno, Giacomo; Castello, Roberto; Caudron, Adrien; Ceard, Ludivine; Da Silveira, Gustavo Gil; Delaere, Christophe; Du Pree, Tristan; Favart, Denis; Forthomme, Laurent; Giammanco, Andrea; Hollar, Jonathan; Jez, Pavel; Komm, Matthias; Lemaitre, Vincent; Nuttens, Claude; Pagano, Davide; Perrini, Lucia; Pin, Arnaud; Piotrzkowski, Krzysztof; Popov, Andrey; Quertenmont, Loic; Selvaggi, Michele; Vidal Marono, Miguel; Vizan Garcia, Jesus Manuel; Beliy, Nikita; Caebergs, Thierry; Daubie, Evelyne; Hammad, Gregory Habib; Aldá Júnior, Walter Luiz; Alves, Gilvan; Brito, Lucas; Correa Martins Junior, Marcos; Dos Reis Martins, Thiago; Mora Herrera, Clemencia; Pol, Maria Elena; Carvalho, Wagner; Chinellato, Jose; Custódio, Analu; Melo Da Costa, Eliza; De Jesus Damiao, Dilson; De Oliveira Martins, Carley; Fonseca De Souza, Sandro; Malbouisson, Helena; Matos Figueiredo, Diego; Mundim, Luiz; Nogima, Helio; Prado Da Silva, Wanda Lucia; Santaolalla, Javier; Santoro, Alberto; Sznajder, Andre; Tonelli Manganote, Edmilson José; Vilela Pereira, Antonio; Bernardes, Cesar Augusto; Dogra, Sunil; Tomei, Thiago; De Moraes Gregores, Eduardo; Mercadante, Pedro G; Novaes, Sergio F; Padula, Sandra; Aleksandrov, Aleksandar; Genchev, Vladimir; Iaydjiev, Plamen; Marinov, Andrey; Piperov, Stefan; Rodozov, Mircho; Stoykova, Stefka; Sultanov, Georgi; Tcholakov, Vanio; Vutova, Mariana; Dimitrov, Anton; Glushkov, Ivan; Hadjiiska, Roumyana; Kozhuharov, Venelin; Litov, Leander; Pavlov, Borislav; Petkov, Peicho; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Chen, Mingshui; Du, Ran; Jiang, Chun-Hua; Liang, Song; Plestina, Roko; Tao, Junquan; Wang, Xianyou; Wang, Zheng; Asawatangtrakuldee, Chayanit; Ban, Yong; Guo, Yifei; Li, Qiang; Li, Wenbo; Liu, Shuai; Mao, Yajun; Qian, Si-Jin; Wang, Dayong; Zhang, Linlin; Zou, Wei; Avila, Carlos; Chaparro Sierra, Luisa Fernanda; Florez, Carlos; Gomez, Juan Pablo; Gomez Moreno, Bernardo; Sanabria, Juan Carlos; Godinovic, Nikola; Lelas, Damir; Polic, Dunja; Puljak, Ivica; Antunovic, Zeljko; Kovac, Marko; Brigljevic, Vuko; Kadija, Kreso; Luetic, Jelena; Mekterovic, Darko; Sudic, Lucija; Attikis, Alexandros; Mavromanolakis, Georgios; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Bodlak, Martin; Finger, Miroslav; Finger Jr, Michael; Assran, Yasser; Ellithi Kamel, Ali; Mahmoud, Mohammed; Radi, Amr; Kadastik, Mario; Murumaa, Marion; Raidal, Martti; Tiko, Andres; Eerola, Paula; Fedi, Giacomo; Voutilainen, Mikko; Härkönen, Jaakko; Karimäki, Veikko; Kinnunen, Ritva; Kortelainen, Matti J; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Mäenpää, Teppo; Peltola, Timo; Tuominen, Eija; Tuominiemi, Jorma; Tuovinen, Esa; Wendland, Lauri; Tuuva, Tuure; Besancon, Marc; Couderc, Fabrice; Dejardin, Marc; Denegri, Daniel; Fabbro, Bernard; Faure, Jean-Louis; Favaro, Carlotta; Ferri, Federico; Ganjour, Serguei; Givernaud, Alain; Gras, Philippe; Hamel de Monchenault, Gautier; Jarry, Patrick; Locci, Elizabeth; Malcles, Julie; Rander, John; Rosowsky, André; Titov, Maksym; Baffioni, Stephanie; Beaudette, Florian; Busson, Philippe; Charlot, Claude; Dahms, Torsten; Dalchenko, Mykhailo; Dobrzynski, Ludwik; Filipovic, Nicolas; Florent, Alice; Granier de Cassagnac, Raphael; Mastrolorenzo, Luca; Miné, Philippe; Mironov, Camelia; Naranjo, Ivo Nicolas; Nguyen, Matthew; Ochando, Christophe; Paganini, Pascal; Regnard, Simon; Salerno, Roberto; Sauvan, Jean-Baptiste; Sirois, Yves; Veelken, Christian; Yilmaz, Yetkin; Zabi, Alexandre; Agram, Jean-Laurent; Andrea, Jeremy; Aubin, Alexandre; Bloch, Daniel; Brom, Jean-Marie; Chabert, Eric Christian; Collard, Caroline; Conte, Eric; Fontaine, Jean-Charles; Gelé, Denis; Goerlach, Ulrich; Goetzmann, Christophe; Le Bihan, Anne-Catherine; Van Hove, Pierre; Gadrat, Sébastien; Beauceron, Stephanie; Beaupere, Nicolas; Boudoul, Gaelle; Bouvier, Elvire; Brochet, Sébastien; Carrillo Montoya, Camilo Andres; Chasserat, Julien; Chierici, Roberto; Contardo, Didier; Depasse, Pierre; El Mamouni, Houmani; Fan, Jiawei; Fay, Jean; Gascon, Susan; Gouzevitch, Maxime; Ille, Bernard; Kurca, Tibor; Lethuillier, Morgan; Mirabito, Laurent; Perries, Stephane; Ruiz Alvarez, José David; Sabes, David; Sgandurra, Louis; Sordini, Viola; Vander Donckt, Muriel; Verdier, Patrice; Viret, Sébastien; Xiao, Hong; Tsamalaidze, Zviad; Autermann, Christian; Beranek, Sarah; Bontenackels, Michael; Edelhoff, Matthias; Feld, Lutz; Hindrichs, Otto; Klein, Katja; Ostapchuk, Andrey; Perieanu, Adrian; Raupach, Frank; Sammet, Jan; Schael, Stefan; Weber, Hendrik; Wittmer, Bruno; Zhukov, Valery; Ata, Metin; Dietz-Laursonn, Erik; Duchardt, Deborah; Erdmann, Martin; Fischer, Robert; Güth, Andreas; Hebbeker, Thomas; Heidemann, Carsten; Hoepfner, Kerstin; Klingebiel, Dennis; Knutzen, Simon; Kreuzer, Peter; Merschmeyer, Markus; Meyer, Arnd; Millet, Philipp; Olschewski, Mark; Padeken, Klaas; Papacz, Paul; Reithler, Hans; Schmitz, Stefan Antonius; Sonnenschein, Lars; Teyssier, Daniel; Thüer, Sebastian; Weber, Martin; Cherepanov, Vladimir; Erdogan, Yusuf; Flügge, Günter; Geenen, Heiko; Geisler, Matthias; Haj Ahmad, Wael; Heister, Arno; Hoehle, Felix; Kargoll, Bastian; Kress, Thomas; Kuessel, Yvonne; Lingemann, Joschka; Nowack, Andreas; Nugent, Ian Michael; Perchalla, Lars; Pooth, Oliver; Stahl, Achim; Asin, Ivan; Bartosik, Nazar; Behr, Joerg; Behrenhoff, Wolf; Behrens, Ulf; Bell, Alan James; Bergholz, Matthias; Bethani, Agni; Borras, Kerstin; Burgmeier, Armin; Cakir, Altan; Calligaris, Luigi; Campbell, Alan; Choudhury, Somnath; Costanza, Francesco; Diez Pardos, Carmen; Dooling, Samantha; Dorland, Tyler; Eckerlin, Guenter; Eckstein, Doris; Eichhorn, Thomas; Flucke, Gero; Garay Garcia, Jasone; Geiser, Achim; Gunnellini, Paolo; Hauk, Johannes; Hempel, Maria; Horton, Dean; Jung, Hannes; Kalogeropoulos, Alexis; Kasemann, Matthias; Katsas, Panagiotis; Kieseler, Jan; Kleinwort, Claus; Krücker, Dirk; Lange, Wolfgang; Leonard, Jessica; Lipka, Katerina; Lobanov, Artur; Lohmann, Wolfgang; Lutz, Benjamin; Mankel, Rainer; Marfin, Ihar; Melzer-Pellmann, Isabell-Alissandra; Meyer, Andreas Bernhard; Mittag, Gregor; Mnich, Joachim; Mussgiller, Andreas; Naumann-Emme, Sebastian; Nayak, Aruna; Novgorodova, Olga; Nowak, Friederike; Ntomari, Eleni; Perrey, Hanno; Pitzl, Daniel; Placakyte, Ringaile; Raspereza, Alexei; Ribeiro Cipriano, Pedro M; Ron, Elias; Sahin, Mehmet Özgür; Salfeld-Nebgen, Jakob; Saxena, Pooja; Schmidt, Ringo; Schoerner-Sadenius, Thomas; Schröder, Matthias; Seitz, Claudia; Spannagel, Simon; Vargas Trevino, Andrea Del Rocio; Walsh, Roberval; Wissing, Christoph; Aldaya Martin, Maria; Blobel, Volker; Centis Vignali, Matteo; Draeger, Arne-Rasmus; Erfle, Joachim; Garutti, Erika; Goebel, Kristin; Görner, Martin; Haller, Johannes; Hoffmann, Malte; Höing, Rebekka Sophie; Kirschenmann, Henning; Klanner, Robert; Kogler, Roman; Lange, Jörn; Lapsien, Tobias; Lenz, Teresa; Marchesini, Ivan; Ott, Jochen; Peiffer, Thomas; Pietsch, Niklas; Poehlsen, Jennifer; Pöhlsen, Thomas; Rathjens, Denis; Sander, Christian; Schettler, Hannes; Schleper, Peter; Schlieckau, Eike; Schmidt, Alexander; Seidel, Markus; Sola, Valentina; Stadie, Hartmut; Steinbrück, Georg; Troendle, Daniel; Usai, Emanuele; Vanelderen, Lukas; Barth, Christian; Baus, Colin; Berger, Joram; Böser, Christian; Butz, Erik; Chwalek, Thorsten; De Boer, Wim; Descroix, Alexis; Dierlamm, Alexander; Feindt, Michael; Frensch, Felix; Giffels, Manuel; Hartmann, Frank; Hauth, Thomas; Husemann, Ulrich; Katkov, Igor; Kornmayer, Andreas; Kuznetsova, Ekaterina; Lobelle Pardo, Patricia; Mozer, Matthias Ulrich; Müller, Thomas; Nürnberg, Andreas; Quast, Gunter; Rabbertz, Klaus; Ratnikov, Fedor; Röcker, Steffen; Simonis, Hans-Jürgen; Stober, Fred-Markus Helmut; Ulrich, Ralf; Wagner-Kuhr, Jeannine; Wayand, Stefan; Weiler, Thomas; Wolf, Roger; Anagnostou, Georgios; Daskalakis, Georgios; Geralis, Theodoros; Giakoumopoulou, Viktoria Athina; Kyriakis, Aristotelis; Loukas, Demetrios; Markou, Athanasios; Markou, Christos; Psallidas, Andreas; Topsis-Giotis, Iasonas; Kesisoglou, Stilianos; Panagiotou, Apostolos; Saoulidou, Niki; Stiliaris, Efstathios; Aslanoglou, Xenofon; Evangelou, Ioannis; Flouris, Giannis; Foudas, Costas; Kokkas, Panagiotis; Manthos, Nikolaos; Papadopoulos, Ioannis; Paradas, Evangelos; Bencze, Gyorgy; Hajdu, Csaba; Hidas, Pàl; Horvath, Dezso; Sikler, Ferenc; Veszpremi, Viktor; Vesztergombi, Gyorgy; Zsigmond, Anna Julia; Beni, Noemi; Czellar, Sandor; Karancsi, János; Molnar, Jozsef; Palinkas, Jozsef; Szillasi, Zoltan; Raics, Peter; Trocsanyi, Zoltan Laszlo; Ujvari, Balazs; Swain, Sanjay Kumar; Beri, Suman Bala; Bhatnagar, Vipin; Dhingra, Nitish; Gupta, Ruchi; Bhawandeep, Bhawandeep; Kalsi, Amandeep Kaur; Kaur, Manjit; Mittal, Monika; Nishu, Nishu; Singh, Jasbir; Kumar, Ashok; Kumar, Arun; Ahuja, Sudha; Bhardwaj, Ashutosh; Choudhary, Brajesh C; Kumar, Ajay; Malhotra, Shivali; Naimuddin, Md; Ranjan, Kirti; Sharma, Varun; Banerjee, Sunanda; Bhattacharya, Satyaki; Chatterjee, Kalyanmoy; Dutta, Suchandra; Gomber, Bhawna; Jain, Sandhya; Jain, Shilpi; Khurana, Raman; Modak, Atanu; Mukherjee, Swagata; Roy, Debarati; Sarkar, Subir; Sharan, Manoj; Abdulsalam, Abdulla; Dutta, Dipanwita; Kailas, Swaminathan; Kumar, Vineet; Mohanty, Ajit Kumar; Pant, Lalit Mohan; Shukla, Prashant; Topkar, Anita; Aziz, Tariq; Banerjee, Sudeshna; Bhowmik, Sandeep; Chatterjee, Rajdeep Mohan; Dewanjee, Ram Krishna; Dugad, Shashikant; Ganguly, Sanmay; Ghosh, Saranya; Guchait, Monoranjan; Gurtu, Atul; Kole, Gouranga; Kumar, Sanjeev; Maity, Manas; Majumder, Gobinda; Mazumdar, Kajari; Mohanty, Gagan Bihari; Parida, Bibhuti; Sudhakar, Katta; Wickramage, Nadeesha; Bakhshiansohi, Hamed; Behnamian, Hadi; Etesami, Seyed Mohsen; Fahim, Ali; Goldouzian, Reza; Jafari, Abideh; Khakzad, Mohsen; Mohammadi Najafabadi, Mojtaba; Naseri, Mohsen; Paktinat Mehdiabadi, Saeid; Rezaei Hosseinabadi, Ferdos; Safarzadeh, Batool; Zeinali, Maryam; Felcini, Marta; Grunewald, Martin; Abbrescia, Marcello; Barbone, Lucia; Calabria, Cesare; Chhibra, Simranjit Singh; Colaleo, Anna; Creanza, Donato; De Filippis, Nicola; De Palma, Mauro; Fiore, Luigi; Iaselli, Giuseppe; Maggi, Giorgio; Maggi, Marcello; My, Salvatore; Nuzzo, Salvatore; Pompili, Alexis; Pugliese, Gabriella; Radogna, Raffaella; Selvaggi, Giovanna; Silvestris, Lucia; Singh, Gurpreet; Venditti, Rosamaria; Verwilligen, Piet; Zito, Giuseppe; Abbiendi, Giovanni; Benvenuti, Alberto; Bonacorsi, Daniele; Braibant-Giacomelli, Sylvie; Brigliadori, Luca; Campanini, Renato; Capiluppi, Paolo; Castro, Andrea; Cavallo, Francesca Romana; Codispoti, Giuseppe; Cuffiani, Marco; Dallavalle, Gaetano-Marco; Fabbri, Fabrizio; Fanfani, Alessandra; Fasanella, Daniele; Giacomelli, Paolo; Grandi, Claudio; Guiducci, Luigi; Marcellini, Stefano; Masetti, Gianni; Montanari, Alessandro; Navarria, Francesco; Perrotta, Andrea; Primavera, Federica; Rossi, Antonio; Rovelli, Tiziano; Siroli, Gian Piero; Tosi, Nicolò; Travaglini, Riccardo; Albergo, Sebastiano; Cappello, Gigi; Chiorboli, Massimiliano; Costa, Salvatore; Giordano, Ferdinando; Potenza, Renato; Tricomi, Alessia; Tuve, Cristina; Barbagli, Giuseppe; Ciulli, Vitaliano; Civinini, Carlo; D'Alessandro, Raffaello; Focardi, Ettore; Gallo, Elisabetta; Gonzi, Sandro; Gori, Valentina; Lenzi, Piergiulio; Meschini, Marco; Paoletti, Simone; Sguazzoni, Giacomo; Tropiano, Antonio; Benussi, Luigi; Bianco, Stefano; Fabbri, Franco; Piccolo, Davide; Ferro, Fabrizio; Lo Vetere, Maurizio; Robutti, Enrico; Tosi, Silvano; Dinardo, Mauro Emanuele; Fiorendi, Sara; Gennai, Simone; Gerosa, Raffaele; Ghezzi, Alessio; Govoni, Pietro; Lucchini, Marco Toliman; Malvezzi, Sandra; Manzoni, Riccardo Andrea; Martelli, Arabella; Marzocchi, Badder; Menasce, Dario; Moroni, Luigi; Paganoni, Marco; Pedrini, Daniele; Ragazzi, Stefano; Redaelli, Nicola; Tabarelli de Fatis, Tommaso; Buontempo, Salvatore; Cavallo, Nicola; Di Guida, Salvatore; Fabozzi, Francesco; Iorio, Alberto Orso Maria; Lista, Luca; Meola, Sabino; Merola, Mario; Paolucci, Pierluigi; Azzi, Patrizia; Bacchetta, Nicola; Bisello, Dario; Branca, Antonio; Carlin, Roberto; Checchia, Paolo; Dall'Osso, Martino; Dorigo, Tommaso; Dosselli, Umberto; Galanti, Mario; Gasparini, Fabrizio; Gasparini, Ugo; Giubilato, Piero; Gonella, Franco; Gozzelino, Andrea; Kanishchev, Konstantin; Lacaprara, Stefano; Margoni, Martino; Montecassiano, Fabio; Pazzini, Jacopo; Pozzobon, Nicola; Ronchese, Paolo; Simonetto, Franco; Tosi, Mia; Zotto, Pierluigi; Zucchetta, Alberto; Zumerle, Gianni; Gabusi, Michele; Ratti, Sergio P; Riccardi, Cristina; Salvini, Paola; Vitulo, Paolo; Biasini, Maurizio; Bilei, Gian Mario; Ciangottini, Diego; Fanò, Livio; Lariccia, Paolo; Mantovani, Giancarlo; Menichelli, Mauro; Romeo, Francesco; Saha, Anirban; Santocchia, Attilio; Spiezia, Aniello; Androsov, Konstantin; Azzurri, Paolo; Bagliesi, Giuseppe; Bernardini, Jacopo; Boccali, Tommaso; Broccolo, Giuseppe; Castaldi, Rino; Ciocci, Maria Agnese; Dell'Orso, Roberto; Donato, Silvio; Fiori, Francesco; Foà, Lorenzo; Giassi, Alessandro; Grippo, Maria Teresa; Ligabue, Franco; Lomtadze, Teimuraz; Martini, Luca; Messineo, Alberto; Moon, Chang-Seong; Palla, Fabrizio; Rizzi, Andrea; Savoy-Navarro, Aurore; Serban, Alin Titus; Spagnolo, Paolo; Squillacioti, Paola; Tenchini, Roberto; Tonelli, Guido; Venturi, Andrea; Verdini, Piero Giorgio; Vernieri, Caterina; Barone, Luciano; Cavallari, Francesca; D'imperio, Giulia; Del Re, Daniele; Diemoz, Marcella; Grassi, Marco; Jorda, Clara; Longo, Egidio; Margaroli, Fabrizio; Meridiani, Paolo; Micheli, Francesco; Nourbakhsh, Shervin; Organtini, Giovanni; Paramatti, Riccardo; Rahatlou, Shahram; Rovelli, Chiara; Santanastasio, Francesco; Soffi, Livia; Traczyk, Piotr; Amapane, Nicola; Arcidiacono, Roberta; Argiro, Stefano; Arneodo, Michele; Bellan, Riccardo; Biino, Cristina; Cartiglia, Nicolo; Casasso, Stefano; Costa, Marco; Degano, Alessandro; Demaria, Natale; Dujany, Giulio; Finco, Linda; Mariotti, Chiara; Maselli, Silvia; Migliore, Ernesto; Monaco, Vincenzo; Musich, Marco; Obertino, Maria Margherita; Ortona, Giacomo; Pacher, Luca; Pastrone, Nadia; Pelliccioni, Mario; Pinna Angioni, Gian Luca; Potenza, Alberto; Romero, Alessandra; Ruspa, Marta; Sacchi, Roberto; Solano, Ada; Staiano, Amedeo; Tamponi, Umberto; Belforte, Stefano; Candelise, Vieri; Casarsa, Massimo; Cossutti, Fabio; Della Ricca, Giuseppe; Gobbo, Benigno; La Licata, Chiara; Marone, Matteo; Montanino, Damiana; Schizzi, Andrea; Umer, Tomo; Zanetti, Anna; Chang, Sunghyun; Kropivnitskaya, Anna; Nam, Soon-Kwon; Kim, Dong Hee; Kim, Gui Nyun; Kim, Min Suk; Kong, Dae Jung; Lee, Sangeun; Oh, Young Do; Park, Hyangkyu; Sakharov, Alexandre; Son, Dong-Chul; Kim, Tae Jeong; Kim, Jae Yool; Song, Sanghyeon; Choi, Suyong; Gyun, Dooyeon; Hong, Byung-Sik; Jo, Mihee; Kim, Hyunchul; Kim, Yongsun; Lee, Byounghoon; Lee, Kyong Sei; Park, Sung Keun; Roh, Youn; Choi, Minkyoo; Kim, Ji Hyun; Park, Inkyu; Park, Sangnam; Ryu, Geonmo; Ryu, Min Sang; Choi, Young-Il; Choi, Young Kyu; Goh, Junghwan; Kim, Donghyun; Kwon, Eunhyang; Lee, Jongseok; Seo, Hyunkwan; Yu, Intae; Juodagalvis, Andrius; Komaragiri, Jyothsna Rani; Md Ali, Mohd Adli Bin; Castilla-Valdez, Heriberto; De La Cruz-Burelo, Eduard; Heredia-de La Cruz, Ivan; Lopez-Fernandez, Ricardo; Sánchez Hernández, Alberto; Carrillo Moreno, Salvador; Vazquez Valencia, Fabiola; Pedraza, Isabel; Salazar Ibarguen, Humberto Antonio; Casimiro Linares, Edgar; Morelos Pineda, Antonio; Krofcheck, David; Butler, Philip H; Reucroft, Steve; Ahmad, Ashfaq; Ahmad, Muhammad; Hassan, Qamar; Hoorani, Hafeez R; Khalid, Shoaib; Khan, Wajid Ali; Khurshid, Taimoor; Shah, Mehar Ali; Shoaib, Muhammad; Bialkowska, Helena; Bluj, Michal; Boimska, Bożena; Frueboes, Tomasz; Górski, Maciej; Kazana, Malgorzata; Nawrocki, Krzysztof; Romanowska-Rybinska, Katarzyna; Szleper, Michal; Zalewski, Piotr; Brona, Grzegorz; Bunkowski, Karol; Cwiok, Mikolaj; Dominik, Wojciech; Doroba, Krzysztof; Kalinowski, Artur; Konecki, Marcin; Krolikowski, Jan; Misiura, Maciej; Olszewski, Michał; Wolszczak, Weronika; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Faccioli, Pietro; Ferreira Parracho, Pedro Guilherme; Gallinaro, Michele; Nguyen, Federico; Rodrigues Antunes, Joao; Seixas, Joao; Varela, Joao; Vischia, Pietro; Golutvin, Igor; Gorbunov, Ilya; Karjavin, Vladimir; Konoplyanikov, Viktor; Korenkov, Vladimir; Lanev, Alexander; Malakhov, Alexander; Matveev, Viktor; Mitsyn, Valeri Valentinovitch; Moisenz, Petr; Palichik, Vladimir; Perelygin, Victor; Shmatov, Sergey; Skatchkov, Nikolai; Smirnov, Vitaly; Tikhonenko, Elena; Yuldashev, Bekhzod S; Zarubin, Anatoli; Golovtsov, Victor; Ivanov, Yury; Kim, Victor; Levchenko, Petr; Murzin, Victor; Oreshkin, Vadim; Smirnov, Igor; Sulimov, Valentin; Uvarov, Lev; Vavilov, Sergey; Vorobyev, Alexey; Vorobyev, Andrey; Andreev, Yuri; Dermenev, Alexander; Gninenko, Sergei; Golubev, Nikolai; Kirsanov, Mikhail; Krasnikov, Nikolai; Pashenkov, Anatoli; Tlisov, Danila; Toropin, Alexander; Epshteyn, Vladimir; Gavrilov, Vladimir; Lychkovskaya, Natalia; Popov, Vladimir; Safronov, Grigory; Semenov, Sergey; Spiridonov, Alexander; Stolin, Viatcheslav; Vlasov, Evgueni; Zhokin, Alexander; Andreev, Vladimir; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Leonidov, Andrey; Mesyats, Gennady; Rusakov, Sergey V; Vinogradov, Alexey; Belyaev, Andrey; Boos, Edouard; Dubinin, Mikhail; Dudko, Lev; Ershov, Alexander; Gribushin, Andrey; Klyukhin, Vyacheslav; Kodolova, Olga; Lokhtin, Igor; Obraztsov, Stepan; Petrushanko, Sergey; Savrin, Viktor; Snigirev, Alexander; Azhgirey, Igor; Bayshev, Igor; Bitioukov, Sergei; Kachanov, Vassili; Kalinin, Alexey; Konstantinov, Dmitri; Krychkine, Victor; Petrov, Vladimir; Ryutin, Roman; Sobol, Andrei; Tourtchanovitch, Leonid; Troshin, Sergey; Tyurin, Nikolay; Uzunian, Andrey; Volkov, Alexey; Adzic, Petar; Ekmedzic, Marko; Milosevic, Jovan; Rekovic, Vladimir; Alcaraz Maestre, Juan; Battilana, Carlo; Calvo, Enrique; Cerrada, Marcos; Chamizo Llatas, Maria; Colino, Nicanor; De La Cruz, Begona; Delgado Peris, Antonio; Domínguez Vázquez, Daniel; Escalante Del Valle, Alberto; Fernandez Bedoya, Cristina; Fernández Ramos, Juan Pablo; Flix, Jose; Fouz, Maria Cruz; Garcia-Abia, Pablo; Gonzalez Lopez, Oscar; Goy Lopez, Silvia; Hernandez, Jose M; Josa, Maria Isabel; Merino, Gonzalo; Navarro De Martino, Eduardo; Pérez Calero Yzquierdo, Antonio María; Puerta Pelayo, Jesus; Quintario Olmeda, Adrián; Redondo, Ignacio; Romero, Luciano; Senghi Soares, Mara; Albajar, Carmen; de Trocóniz, Jorge F; Missiroli, Marino; Moran, Dermot; Brun, Hugues; Cuevas, Javier; Fernandez Menendez, Javier; Folgueras, Santiago; Gonzalez Caballero, Isidro; Lloret Iglesias, Lara; Brochero Cifuentes, Javier Andres; Cabrillo, Iban Jose; Calderon, Alicia; Duarte Campderros, Jordi; Fernandez, Marcos; Gomez, Gervasio; Graziano, Alberto; Lopez Virto, Amparo; Marco, Jesus; Marco, Rafael; Martinez Rivero, Celso; Matorras, Francisco; Munoz Sanchez, Francisca Javiela; Piedra Gomez, Jonatan; Rodrigo, Teresa; Rodríguez-Marrero, Ana Yaiza; Ruiz-Jimeno, Alberto; Scodellaro, Luca; Vila, Ivan; Vilar Cortabitarte, Rocio; Abbaneo, Duccio; Auffray, Etiennette; Auzinger, Georg; Bachtis, Michail; Baillon, Paul; Ball, Austin; Barney, David; Benaglia, Andrea; Bendavid, Joshua; Benhabib, Lamia; Benitez, Jose F; Bernet, Colin; Bianchi, Giovanni; Bloch, Philippe; Bocci, Andrea; Bonato, Alessio; Bondu, Olivier; Botta, Cristina; Breuker, Horst; Camporesi, Tiziano; Cerminara, Gianluca; Colafranceschi, Stefano; D'Alfonso, Mariarosaria; D'Enterria, David; Dabrowski, Anne; David Tinoco Mendes, Andre; De Guio, Federico; De Roeck, Albert; De Visscher, Simon; Dobson, Marc; Dordevic, Milos; Dupont-Sagorin, Niels; Elliott-Peisert, Anna; Eugster, Jürg; Franzoni, Giovanni; Funk, Wolfgang; Gigi, Dominique; Gill, Karl; Giordano, Domenico; Girone, Maria; Glege, Frank; Guida, Roberto; Gundacker, Stefan; Guthoff, Moritz; Hammer, Josef; Hansen, Magnus; Harris, Philip; Hegeman, Jeroen; Innocente, Vincenzo; Janot, Patrick; Kousouris, Konstantinos; Krajczar, Krisztian; Lecoq, Paul; Lourenco, Carlos; Magini, Nicolo; Malgeri, Luca; Mannelli, Marcello; Marrouche, Jad; Masetti, Lorenzo; Meijers, Frans; Mersi, Stefano; Meschi, Emilio; Moortgat, Filip; Morovic, Srecko; Mulders, Martijn; Musella, Pasquale; Orsini, Luciano; Pape, Luc; Perez, Emmanuelle; Perrozzi, Luca; Petrilli, Achille; Petrucciani, Giovanni; Pfeiffer, Andreas; Pierini, Maurizio; Pimiä, Martti; Piparo, Danilo; Plagge, Michael; Racz, Attila; Rolandi, Gigi; Rovere, Marco; Sakulin, Hannes; Schäfer, Christoph; Schwick, Christoph; Sharma, Archana; Siegrist, Patrice; Silva, Pedro; Simon, Michal; Sphicas, Paraskevas; Spiga, Daniele; Steggemann, Jan; Stieger, Benjamin; Stoye, Markus; Treille, Daniel; Tsirou, Andromachi; Veres, Gabor Istvan; Vlimant, Jean-Roch; Wardle, Nicholas; Wöhri, Hermine Katharina; Wollny, Heiner; Zeuner, Wolfram Dietrich; Bertl, Willi; Deiters, Konrad; Erdmann, Wolfram; Horisberger, Roland; Ingram, Quentin; Kaestli, Hans-Christian; Kotlinski, Danek; Langenegger, Urs; Renker, Dieter; Rohe, Tilman; Bachmair, Felix; Bäni, Lukas; Bianchini, Lorenzo; Bortignon, Pierluigi; Buchmann, Marco-Andrea; Casal, Bruno; Chanon, Nicolas; Deisher, Amanda; Dissertori, Günther; Dittmar, Michael; Donegà, Mauro; Dünser, Marc; Eller, Philipp; Grab, Christoph; Hits, Dmitry; Lustermann, Werner; Mangano, Boris; Marini, Andrea Carlo; Martinez Ruiz del Arbol, Pablo; Meister, Daniel; Mohr, Niklas; Nägeli, Christoph; Nessi-Tedaldi, Francesca; Pandolfi, Francesco; Pauss, Felicitas; Peruzzi, Marco; Quittnat, Milena; Rebane, Liis; Rossini, Marco; Starodumov, Andrei; Takahashi, Maiko; Theofilatos, Konstantinos; Wallny, Rainer; Weber, Hannsjoerg Artur; Amsler, Claude; Canelli, Maria Florencia; Chiochia, Vincenzo; De Cosa, Annapaola; Hinzmann, Andreas; Hreus, Tomas; Kilminster, Benjamin; Lange, Clemens; Millan Mejias, Barbara; Ngadiuba, Jennifer; Robmann, Peter; Ronga, Frederic Jean; Taroni, Silvia; Verzetti, Mauro; Yang, Yong; Cardaci, Marco; Chen, Kuan-Hsin; Ferro, Cristina; Kuo, Chia-Ming; Lin, Willis; Lu, Yun-Ju; Volpe, Roberta; Yu, Shin-Shan; Chang, Paoti; Chang, You-Hao; Chang, Yu-Wei; Chao, Yuan; Chen, Kai-Feng; Chen, Po-Hsun; Dietz, Charles; Grundler, Ulysses; Hou, George Wei-Shu; Kao, Kai-Yi; Lei, Yeong-Jyi; Liu, Yueh-Feng; Lu, Rong-Shyang; Majumder, Devdatta; Petrakou, Eleni; Tzeng, Yeng-Ming; Wilken, Rachel; Asavapibhop, Burin; Srimanobhas, Norraphat; Suwonjandee, Narumon; Adiguzel, Aytul; Bakirci, Mustafa Numan; Cerci, Salim; Dozen, Candan; Dumanoglu, Isa; Eskut, Eda; Girgis, Semiray; Gokbulut, Gul; Gurpinar, Emine; Hos, Ilknur; Kangal, Evrim Ersin; Kayis Topaksu, Aysel; Onengut, Gulsen; Ozdemir, Kadri; Ozturk, Sertac; Polatoz, Ayse; Sogut, Kenan; Sunar Cerci, Deniz; Tali, Bayram; Topakli, Huseyin; Vergili, Mehmet; Akin, Ilina Vasileva; Bilin, Bugra; Bilmis, Selcuk; Gamsizkan, Halil; Karapinar, Guler; Ocalan, Kadir; Sekmen, Sezen; Surat, Ugur Emrah; Yalvac, Metin; Zeyrek, Mehmet; Gülmez, Erhan; Isildak, Bora; Kaya, Mithat; Kaya, Ozlem; Bahtiyar, Hüseyin; Barlas, Esra; Cankocak, Kerem; Vardarli, Fuat Ilkehan; Yücel, Mete; Levchuk, Leonid; Sorokin, Pavel; Brooke, James John; Clement, Emyr; Cussans, David; Flacher, Henning; Frazier, Robert; Goldstein, Joel; Grimes, Mark; Heath, Greg P; Heath, Helen F; Jacob, Jeson; Kreczko, Lukasz; Lucas, Chris; Meng, Zhaoxia; Newbold, Dave M; Paramesvaran, Sudarshan; Poll, Anthony; Senkin, Sergey; Smith, Vincent J; Williams, Thomas; Bell, Ken W; Belyaev, Alexander; Brew, Christopher; Brown, Robert M; Cockerill, David JA; Coughlan, John A; Harder, Kristian; Harper, Sam; Olaiya, Emmanuel; Petyt, David; Shepherd-Themistocleous, Claire; Thea, Alessandro; Tomalin, Ian R; Womersley, William John; Worm, Steven; Baber, Mark; Bainbridge, Robert; Buchmuller, Oliver; Burton, Darren; Colling, David; Cripps, Nicholas; Cutajar, Michael; Dauncey, Paul; Davies, Gavin; Della Negra, Michel; Dunne, Patrick; Ferguson, William; Fulcher, Jonathan; Futyan, David; Gilbert, Andrew; Hall, Geoffrey; Iles, Gregory; Jarvis, Martyn; Karapostoli, Georgia; Kenzie, Matthew; Lane, Rebecca; Lucas, Robyn; Lyons, Louis; Magnan, Anne-Marie; Malik, Sarah; Mathias, Bryn; Nash, Jordan; Nikitenko, Alexander; Pela, Joao; Pesaresi, Mark; Petridis, Konstantinos; Raymond, David Mark; Rogerson, Samuel; Rose, Andrew; Seez, Christopher; Sharp, Peter; Tapper, Alexander; Vazquez Acosta, Monica; Virdee, Tejinder; Cole, Joanne; Hobson, Peter R; Khan, Akram; Kyberd, Paul; Leggat, Duncan; Leslie, Dawn; Martin, William; Reid, Ivan; Symonds, Philip; Teodorescu, Liliana; Turner, Mark; Dittmann, Jay; Hatakeyama, Kenichi; Kasmi, Azeddine; Liu, Hongxuan; Scarborough, Tara; Charaf, Otman; Cooper, Seth; Henderson, Conor; Rumerio, Paolo; Avetisyan, Aram; Bose, Tulika; Fantasia, Cory; Lawson, Philip; Richardson, Clint; Rohlf, James; Sperka, David; St John, Jason; Sulak, Lawrence; Alimena, Juliette; Berry, Edmund; Bhattacharya, Saptaparna; Christopher, Grant; Cutts, David; Demiragli, Zeynep; Ferapontov, Alexey; Garabedian, Alex; Heintz, Ulrich; Kukartsev, Gennadiy; Laird, Edward; Landsberg, Greg; Luk, Michael; Narain, Meenakshi; Segala, Michael; Sinthuprasith, Tutanon; Speer, Thomas; Swanson, Joshua; Breedon, Richard; Breto, Guillermo; Calderon De La Barca Sanchez, Manuel; Chauhan, Sushil; Chertok, Maxwell; Conway, John; Conway, Rylan; Cox, Peter Timothy; Erbacher, Robin; Gardner, Michael; Ko, Winston; Lander, Richard; Miceli, Tia; Mulhearn, Michael; Pellett, Dave; Pilot, Justin; Ricci-Tam, Francesca; Searle, Matthew; Shalhout, Shalhout; Smith, John; Squires, Michael; Stolp, Dustin; Tripathi, Mani; Wilbur, Scott; Yohay, Rachel; Cousins, Robert; Everaerts, Pieter; Farrell, Chris; Hauser, Jay; Ignatenko, Mikhail; Rakness, Gregory; Takasugi, Eric; Valuev, Vyacheslav; Weber, Matthias; Babb, John; Burt, Kira; Clare, Robert; Ellison, John Anthony; Gary, J William; Hanson, Gail; Heilman, Jesse; Ivova Rikova, Mirena; Jandir, Pawandeep; Kennedy, Elizabeth; Lacroix, Florent; Liu, Hongliang; Long, Owen Rosser; Luthra, Arun; Malberti, Martina; Nguyen, Harold; Olmedo Negrete, Manuel; Shrinivas, Amithabh; Sumowidagdo, Suharyo; Wimpenny, Stephen; Andrews, Warren; Branson, James G; Cerati, Giuseppe Benedetto; Cittolin, Sergio; D'Agnolo, Raffaele Tito; Evans, David; Holzner, André; Kelley, Ryan; Klein, Daniel; Lebourgeois, Matthew; Letts, James; Macneill, Ian; Olivito, Dominick; Padhi, Sanjay; Palmer, Christopher; Pieri, Marco; Sani, Matteo; Sharma, Vivek; Simon, Sean; Sudano, Elizabeth; Tadel, Matevz; Tu, Yanjun; Vartak, Adish; Welke, Charles; Würthwein, Frank; Yagil, Avraham; Yoo, Jaehyeok; Barge, Derek; Bradmiller-Feld, John; Campagnari, Claudio; Danielson, Thomas; Dishaw, Adam; Flowers, Kristen; Franco Sevilla, Manuel; Geffert, Paul; George, Christopher; Golf, Frank; Gouskos, Loukas; Incandela, Joe; Justus, Christopher; Mccoll, Nickolas; Richman, Jeffrey; Stuart, David; To, Wing; West, Christopher; Apresyan, Artur; Bornheim, Adolf; Bunn, Julian; Chen, Yi; Di Marco, Emanuele; Duarte, Javier; Mott, Alexander; Newman, Harvey B; Pena, Cristian; Rogan, Christopher; Spiropulu, Maria; Timciuc, Vladlen; Wilkinson, Richard; Xie, Si; Zhu, Ren-Yuan; Azzolini, Virginia; Calamba, Aristotle; Carlson, Benjamin; Ferguson, Thomas; Iiyama, Yutaro; Paulini, Manfred; Russ, James; Vogel, Helmut; Vorobiev, Igor; Cumalat, John Perry; Ford, William T; Gaz, Alessandro; Luiggi Lopez, Eduardo; Nauenberg, Uriel; Smith, James; Stenson, Kevin; Ulmer, Keith; Wagner, Stephen Robert; Alexander, James; Chatterjee, Avishek; Chu, Jennifer; Dittmer, Susan; Eggert, Nicholas; Mirman, Nathan; Nicolas Kaufman, Gala; Patterson, Juliet Ritchie; Ryd, Anders; Salvati, Emmanuele; Skinnari, Louise; Sun, Werner; Teo, Wee Don; Thom, Julia; Thompson, Joshua; Tucker, Jordan; Weng, Yao; Winstrom, Lucas; Wittich, Peter; Winn, Dave; Abdullin, Salavat; Albrow, Michael; Anderson, Jacob; Apollinari, Giorgio; Bauerdick, Lothar AT; Beretvas, Andrew; Berryhill, Jeffrey; Bhat, Pushpalatha C; Burkett, Kevin; Butler, Joel Nathan; Cheung, Harry; Chlebana, Frank; Cihangir, Selcuk; Elvira, Victor Daniel; Fisk, Ian; Freeman, Jim; Gao, Yanyan; Gottschalk, Erik; Gray, Lindsey; Green, Dan; Grünendahl, Stefan; Gutsche, Oliver; Hanlon, Jim; Hare, Daryl; Harris, Robert M; Hirschauer, James; Hooberman, Benjamin; Jindariani, Sergo; Johnson, Marvin; Joshi, Umesh; Kaadze, Ketino; Klima, Boaz; Kreis, Benjamin; Kwan, Simon; Linacre, Jacob; Lincoln, Don; Lipton, Ron; Liu, Tiehui; Lykken, Joseph; Maeshima, Kaori; Marraffino, John Michael; Martinez Outschoorn, Verena Ingrid; Maruyama, Sho; Mason, David; McBride, Patricia; Mishra, Kalanand; Mrenna, Stephen; Musienko, Yuri; Nahn, Steve; Newman-Holmes, Catherine; O'Dell, Vivian; Prokofyev, Oleg; Sexton-Kennedy, Elizabeth; Sharma, Seema; Soha, Aron; Spalding, William J; Spiegel, Leonard; Taylor, Lucas; Tkaczyk, Slawek; Tran, Nhan Viet; Uplegger, Lorenzo; Vaandering, Eric Wayne; Vidal, Richard; Whitbeck, Andrew; Whitmore, Juliana; Yang, Fan; Acosta, Darin; Avery, Paul; Bourilkov, Dimitri; Carver, Matthew; Cheng, Tongguang; Curry, David; Das, Souvik; De Gruttola, Michele; Di Giovanni, Gian Piero; Field, Richard D; Fisher, Matthew; Furic, Ivan-Kresimir; Hugon, Justin; Konigsberg, Jacobo; Korytov, Andrey; Kypreos, Theodore; Low, Jia Fu; Matchev, Konstantin; Milenovic, Predrag; Mitselmakher, Guenakh; Muniz, Lana; Rinkevicius, Aurelijus; Shchutska, Lesya; Snowball, Matthew; Yelton, John; Zakaria, Mohammed; Hewamanage, Samantha; Linn, Stephan; Markowitz, Pete; Martinez, German; Rodriguez, Jorge Luis; Adams, Todd; Askew, Andrew; Bochenek, Joseph; Diamond, Brendan; Haas, Jeff; Hagopian, Sharon; Hagopian, Vasken; Johnson, Kurtis F; Prosper, Harrison; Veeraraghavan, Venkatesh; Weinberg, Marc; Baarmand, Marc M; Hohlmann, Marcus; Kalakhety, Himali; Yumiceva, Francisco; Adams, Mark Raymond; Apanasevich, Leonard; Bazterra, Victor Eduardo; Berry, Douglas; Betts, Russell Richard; Bucinskaite, Inga; Cavanaugh, Richard; Evdokimov, Olga; Gauthier, Lucie; Gerber, Cecilia Elena; Hofman, David Jonathan; Khalatyan, Samvel; Kurt, Pelin; Moon, Dong Ho; O'Brien, Christine; Silkworth, Christopher; Turner, Paul; Varelas, Nikos; Albayrak, Elif Asli; Bilki, Burak; Clarida, Warren; Dilsiz, Kamuran; Duru, Firdevs; Haytmyradov, Maksat; Merlo, Jean-Pierre; Mermerkaya, Hamit; Mestvirishvili, Alexi; Moeller, Anthony; Nachtman, Jane; Ogul, Hasan; Onel, Yasar; Ozok, Ferhat; Penzo, Aldo; Rahmat, Rahmat; Sen, Sercan; Tan, Ping; Tiras, Emrah; Wetzel, James; Yetkin, Taylan; Yi, Kai; 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Di Matteo, Leonardo; Dutta, Valentina; Gomez Ceballos, Guillelmo; Goncharov, Maxim; Gulhan, Doga; Klute, Markus; Lai, Yue Shi; Lee, Yen-Jie; Levin, Andrew; Luckey, Paul David; Ma, Teng; Paus, Christoph; Ralph, Duncan; Roland, Christof; Roland, Gunther; Stephans, George; Stöckli, Fabian; Sumorok, Konstanty; Velicanu, Dragos; Veverka, Jan; Wyslouch, Bolek; Yang, Mingming; Zanetti, Marco; Zhukova, Victoria; Dahmes, Bryan; Gude, Alexander; Kao, Shih-Chuan; Klapoetke, Kevin; Kubota, Yuichi; Mans, Jeremy; Pastika, Nathaniel; Rusack, Roger; Singovsky, Alexander; Tambe, Norbert; Turkewitz, Jared; Acosta, John Gabriel; Oliveros, Sandra; Avdeeva, Ekaterina; Bloom, Kenneth; Bose, Suvadeep; Claes, Daniel R; Dominguez, Aaron; Gonzalez Suarez, Rebeca; Keller, Jason; Knowlton, Dan; Kravchenko, Ilya; Lazo-Flores, Jose; Malik, Sudhir; Meier, Frank; Snow, Gregory R; Dolen, James; Godshalk, Andrew; Iashvili, Ia; Kharchilava, Avto; Kumar, Ashish; Rappoccio, Salvatore; Alverson, George; Barberis, Emanuela; Baumgartel, Darin; Chasco, Matthew; Haley, Joseph; Massironi, Andrea; Morse, David Michael; Nash, David; Orimoto, Toyoko; Trocino, Daniele; Wang, Ren-Jie; Wood, Darien; Zhang, Jinzhong; Hahn, Kristan Allan; Kubik, Andrew; Mucia, Nicholas; Odell, Nathaniel; Pollack, Brian; Pozdnyakov, Andrey; Schmitt, Michael Henry; Stoynev, Stoyan; Sung, Kevin; Velasco, Mayda; Won, Steven; Brinkerhoff, Andrew; Chan, Kwok Ming; Drozdetskiy, Alexey; Hildreth, Michael; Jessop, Colin; Karmgard, Daniel John; Kellams, Nathan; Lannon, Kevin; Luo, Wuming; Lynch, Sean; Marinelli, Nancy; Pearson, Tessa; Planer, Michael; Ruchti, Randy; Valls, Nil; Wayne, Mitchell; Wolf, Matthias; Woodard, Anna; Antonelli, Louis; Brinson, Jessica; Bylsma, Ben; Durkin, Lloyd Stanley; Flowers, Sean; Hill, Christopher; Hughes, Richard; Kotov, Khristian; Ling, Ta-Yung; Puigh, Darren; Rodenburg, Marissa; Smith, Geoffrey; Winer, Brian L; Wolfe, Homer; Wulsin, Howard Wells; Driga, Olga; Elmer, Peter; Hebda, Philip; Hunt, Adam; Koay, Sue Ann; Lujan, Paul; Marlow, Daniel; Medvedeva, Tatiana; Mooney, Michael; Olsen, James; Piroué, Pierre; Quan, Xiaohang; Saka, Halil; Stickland, David; Tully, Christopher; Werner, Jeremy Scott; Zenz, Seth Conrad; Zuranski, Andrzej; Brownson, Eric; Mendez, Hector; Ramirez Vargas, Juan Eduardo; Barnes, Virgil E; Benedetti, Daniele; Bolla, Gino; Bortoletto, Daniela; De Mattia, Marco; Hu, Zhen; Jha, Manoj; Jones, Matthew; Jung, Kurt; Kress, Matthew; Leonardo, Nuno; Lopes Pegna, David; Maroussov, Vassili; Merkel, Petra; Miller, David Harry; Neumeister, Norbert; Radburn-Smith, Benjamin Charles; Shi, Xin; Shipsey, Ian; Silvers, David; Svyatkovskiy, Alexey; Wang, Fuqiang; Xie, Wei; Xu, Lingshan; Yoo, Hwi Dong; Zablocki, Jakub; Zheng, Yu; Parashar, Neeti; Stupak, John; Adair, Antony; Akgun, Bora; Ecklund, Karl Matthew; Geurts, Frank JM; Li, Wei; Michlin, Benjamin; Padley, Brian Paul; Redjimi, Radia; Roberts, Jay; Zabel, James; Betchart, Burton; Bodek, Arie; Covarelli, Roberto; de Barbaro, Pawel; Demina, Regina; Eshaq, Yossof; Ferbel, Thomas; Garcia-Bellido, Aran; Goldenzweig, Pablo; Han, Jiyeon; Harel, Amnon; Khukhunaishvili, Aleko; Petrillo, Gianluca; Vishnevskiy, Dmitry; Ciesielski, Robert; Demortier, Luc; Goulianos, Konstantin; Lungu, Gheorghe; Mesropian, Christina; Arora, Sanjay; Barker, Anthony; Chou, John Paul; Contreras-Campana, Christian; Contreras-Campana, Emmanuel; Duggan, Daniel; Ferencek, Dinko; Gershtein, Yuri; Gray, Richard; Halkiadakis, Eva; Hidas, Dean; Kaplan, Steven; Lath, Amitabh; Panwalkar, Shruti; Park, Michael; Patel, Rishi; Salur, Sevil; Schnetzer, Steve; Somalwar, Sunil; Stone, Robert; Thomas, Scott; Thomassen, Peter; Walker, Matthew; Rose, Keith; Spanier, Stefan; York, Andrew; Bouhali, Othmane; Castaneda Hernandez, Alfredo; Eusebi, Ricardo; Flanagan, Will; Gilmore, Jason; Kamon, Teruki; Khotilovich, Vadim; Krutelyov, Vyacheslav; Montalvo, Roy; Osipenkov, Ilya; Pakhotin, Yuriy; Perloff, Alexx; Roe, Jeffrey; Rose, Anthony; Safonov, Alexei; Sakuma, Tai; Suarez, Indara; Tatarinov, Aysen; Akchurin, Nural; Cowden, Christopher; Damgov, Jordan; Dragoiu, Cosmin; Dudero, Phillip Russell; Faulkner, James; Kovitanggoon, Kittikul; Kunori, Shuichi; Lee, Sung Won; Libeiro, Terence; Volobouev, Igor; Appelt, Eric; Delannoy, Andrés G; Greene, Senta; Gurrola, Alfredo; Johns, Willard; Maguire, Charles; Mao, Yaxian; Melo, Andrew; Sharma, Monika; Sheldon, Paul; Snook, Benjamin; Tuo, Shengquan; Velkovska, Julia; Arenton, Michael Wayne; Boutle, Sarah; Cox, Bradley; Francis, Brian; Goodell, Joseph; Hirosky, Robert; Ledovskoy, Alexander; Li, Hengne; Lin, Chuanzhe; Neu, Christopher; Wood, John; Clarke, Christopher; Harr, Robert; Karchin, Paul Edmund; Kottachchi Kankanamge Don, Chamath; Lamichhane, Pramod; Sturdy, Jared; Belknap, Donald; Carlsmith, Duncan; Cepeda, Maria; Dasu, Sridhara; Dodd, Laura; Duric, Senka; Friis, Evan; Hall-Wilton, Richard; Herndon, Matthew; Hervé, Alain; Klabbers, Pamela; Lanaro, Armando; Lazaridis, Christos; Levine, Aaron; Loveless, Richard; Mohapatra, Ajit; Ojalvo, Isabel; Perry, Thomas; Pierro, Giuseppe Antonio; Polese, Giovanni; Ross, Ian; Sarangi, Tapas; Savin, Alexander; Smith, Wesley H; Vuosalo, Carl; Woods, Nathaniel

    2015-04-09

    A measurement of the production cross section ratio $\\sigma(\\chi_{b2}(1\\mathrm{P}))/ \\sigma(\\chi_{b1}(1\\mathrm{P}))$ is presented. The $\\chi_{b1}(1\\mathrm{P})$ and $\\chi_{b2}(1\\mathrm{P})$ bottomonium states, promptly produced in pp collisions at $\\sqrt{s}$= 8 TeV, are detected by the CMS experiment at the CERN LHC through their radiative decays $\\chi_{b1,2}(1\\mathrm{P}) \\rightarrow \\Upsilon(1\\mathrm{S}) + \\gamma$. The emitted photons are measured through their conversion to e$^+$e$^-$ pairs, whose reconstruction allows the two states to be resolved. The $\\Upsilon(1\\mathrm{S})$ is measured through its decay to two muons. An event sample corresponding to an integrated luminosity of 20.7 fb$^{-1}$ is used to measure the cross section ratio in a phase-space region defined by the photon pseudorapidity, |$\\eta^\\gamma$| < 1.0; the $\\Upsilon(1\\mathrm{S})$ rapidity, |$y^\\Upsilon$| < 1.5; and the $\\Upsilon(1\\mathrm{S})$ transverse momentum, 7 < $p_{\\mathrm{T}}^\\Upsilon$ < 40 GeV. The cross section ratio sh...

  12. Only Acyl Carrier Protein 1 (AcpP1 Functions in Pseudomonas aeruginosa Fatty Acid Synthesis

    Directory of Open Access Journals (Sweden)

    Jin-Cheng Ma

    2017-11-01

    Full Text Available The genome of Pseudomonas aeruginosa contains three open reading frames, PA2966, PA1869, and PA3334, which encode putative acyl carrier proteins, AcpP1, AcpP2, and AcpP3, respectively. In this study, we found that, although these apo-ACPs were successfully phosphopantetheinylated by P. aeruginosa phosphopantetheinyl transferase (PcpS and all holo-forms of these proteins could be acylated by Vibrio harveyi acyl-ACP synthetase (AasS, only AcpP1 could be used as a substrate for the synthesis of fatty acids, catalyzed by P. aeruginosa cell free extracts in vitro, and only acpP1 gene could restore growth in the Escherichia coliacpP mutant strain CY1877. And P. aeruginosaacpP1 could not be deleted, while disruption of acpP2 or acpP3 in the P. aeruginosa genome allowed mutant strains to grow as well as the wild type strain. These findings confirmed that only P. aeruginosa AcpP1 functions in fatty acid biosynthesis, and that acpP2 and acpP3 do not play roles in the fatty acid synthetic pathway. Moreover, disruption of acpP2 and acpP3 did not affect the ability of P. aeruginosa to produce N-acylhomoserine lactones (AHL, but replacement of P. aeruginosaacpP1 with E. coliacpP caused P. aeruginosa to reduce the production of AHL molecules, which indicated that neither P. aeruginosa AcpP2 nor AcpP3 can act as a substrate for synthesis of AHL molecules in vivo. Furthermore, replacement of acpP1 with E. coliacpP reduced the ability of P. aeruginosa to produce some exo-products and abolished swarming motility in P. aeruginosa.

  13. Preparation of p-type GaN-doped SnO2 thin films by e-beam evaporation and their applications in p-n junction

    Science.gov (United States)

    Lv, Shuliang; Zhou, Yawei; Xu, Wenwu; Mao, Wenfeng; Wang, Lingtao; Liu, Yong; He, Chunqing

    2018-01-01

    Various transparent GaN-doped SnO2 thin films were deposited on glass substrates by e-beam evaporation using GaN:SnO2 targets of different GaN weight ratios. It is interesting to find that carrier polarity of the thin films was converted from n-type to p-type with increasing GaN ratio higher than 15 wt.%. The n-p transition in GaN-doped SnO2 thin films was explained for the formation of GaSn and NO with increasing GaN doping level in the films, which was identified by Hall measurement and XPS analysis. A transparent thin film p-n junction was successfully fabricated by depositing p-type GaN:SnO2 thin film on SnO2 thin film, and a low leakage current (6.2 × 10-5 A at -4 V) and a low turn-on voltage of 1.69 V were obtained for the p-n junction.

  14. Gln3p and Nil1p regulation of invertase activity and SUC2 expression in Saccharomyces cerevisiae.

    Science.gov (United States)

    Oliveira, Edna Maria Morais; Mansure, José João; Bon, Elba Pinto da Silva

    2005-04-01

    In Saccharomyces cerevisiae, sensing and signalling pathways regulate gene expression in response to quality of carbon and nitrogen sources. One such system, the target of rapamycin (Tor) proteins, senses nutrients and uses the GATA activators Gln3p and Nil1p to regulate translation in response to low-quality carbon and nitrogen. The signal transduction, triggered in response to nitrogen nutrition that is sensed by the Tor proteins, operates via a regulatory pathway involving the cytoplasmic factor Ure2p. When carbon and nitrogen are abundant, the phosphorylated Ure2p anchors the also phosphorylated Gln3p and Nil1p in the cytoplasm. Upon a shift from high- to low-quality nitrogen or treatment with rapamycin all three proteins are dephosphorylated, causing Gln3p and Nil1p to enter the nucleus and promote transcription. The genes that code for yeast periplasmic enzymes with nutritional roles would be obvious targets for regulation by the sensing and signalling pathways that respond to quality of carbon and nitrogen sources. Indeed, previous results from our laboratory had shown that the GATA factors Gln3p, Nil1p, Dal80p, Nil2p and also the protein Ure2 regulate the expression of asparaginase II, coded by ASP3. We also had observed that the activity levels of the also periplasmic invertase, coded by SUC2, were 6-fold lower in ure2 mutant cells in comparison to wild-type cells collected at stationary phase. These results suggested similarities between the signalling pathways regulating the expression of ASP3 and SUC2. In the present work we showed that invertase levels displayed by the single nil1 and gln3 and by the double gln3nil1 mutant cells, cultivated in a sucrose-ammonium medium and collected at the exponential phase, were 6-, 10- and 60-fold higher, respectively, in comparison to their wild-type counterparts. RT-PCR data of SUC2 expression in the double-mutant cells indicated a 10-fold increase in the mRNA(SUC2) levels.

  15. Characterization of a recurrent t(1;2)(p36;p24) in human uterine leiomyoma.

    NARCIS (Netherlands)

    Rijk, A. van; Sweers, M.A.; Huys, E.; Kersten, M.; Merkx, G.F.M.; Geurts van Kessel, A.H.M.; Debiec-Rychter, M.; Schoenmakers, E.F.P.M.

    2009-01-01

    Uterine leiomyomas are the most common neoplasms in women of reproductive age. Approximately 40% of these neoplasms show recurring structural cytogenetic anomalies, including del(7)(q22), t(12;14)(q15;q24), t(1;2)(p36;p24), and anomalies affecting 6p21 or 10q22. Using positional cloning strategies,

  16. Early Outbreak of 2009 Influenza A (H1N1) in Mexico Prior to Identification of pH1N1 Virus

    Science.gov (United States)

    Hsieh, Ying-Hen; Ma, Stefan; Velasco Hernandez, Jorge X.; Lee, Vernon J.; Lim, Wei Yen

    2011-01-01

    Background In the aftermath of the global spread of 2009 influenza A (pH1N1) virus, still very little is known of the early stages of the outbreak in Mexico during the early months of the year, before the virus was identified. Methodology/Main Findings We fit a simple mathematical model, the Richards model, to the number of excess laboratory-confirmed influenza cases in Mexico and Mexico City during the first 15 weeks in 2009 over the average influenza case number of the previous five baseline years of 2004-2008 during the same period to ascertain the turning point (or the peak incidence) of a wave of early influenza infections, and to estimate the transmissibility of the virus during these early months in terms of its basic reproduction number. The results indicate that there may have been an early epidemic in Mexico City as well as in all of Mexico during February/March. Based on excess influenza cases, the estimated basic reproduction number R0 for the early outbreak was 1.59 (0.55 to 2.62) for Mexico City during weeks 5–9, and 1.25 (0.76, 1.74) for all of Mexico during weeks 5–14. Conclusions We established the existence of an early epidemic in Mexico City and in all of Mexico during February/March utilizing the routine influenza surveillance data, although the location of seeding is unknown. Moreover, estimates of R0 as well as the time of peak incidence (the turning point) for Mexico City and all of Mexico indicate that the early epidemic in Mexico City in February/March had been more transmissible (larger R0) and peaked earlier than the rest of the country. Our conclusion lends support to the possibility that the virus could have already spread to other continents prior to the identification of the virus and the reporting of lab-confirmed pH1N1 cases in North America in April. PMID:21909366

  17. P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions.

    Science.gov (United States)

    Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul; Melikyan, Gregory B

    2015-09-01

    HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF

  18. p27{sup Kip1} inhibits tissue factor expression

    Energy Technology Data Exchange (ETDEWEB)

    Breitenstein, Alexander, E-mail: alexander.breitenstein@usz.ch [Cardiology, University Heart Center, University Hospital Zurich (Switzerland); Cardiovascular Research, Physiology Institute, University of Zurich (Switzerland); Center for Integrative Human Physiology (ZHIP), University of Zurich (Switzerland); Akhmedov, Alexander; Camici, Giovanni G.; Lüscher, Thomas F.; Tanner, Felix C. [Cardiology, University Heart Center, University Hospital Zurich (Switzerland); Cardiovascular Research, Physiology Institute, University of Zurich (Switzerland); Center for Integrative Human Physiology (ZHIP), University of Zurich (Switzerland)

    2013-10-04

    Highlights: •p27{sup Kip1}regulates the expression of tissue factor at the transcriptional level. •This inhibitory effect of p27{sup Kip1} is independently of its cell regulatory action. •The current study provides new insights into a pleiotrophic function of p27{sup Kip1}. -- Abstract: Background: The cyclin-dependent kinase inhibitor (CDKI) p27{sup Kip1} regulates cell proliferation and thus inhibits atherosclerosis and vascular remodeling. Expression of tissue factor (TF), the key initator of the coagulation cascade, is associated with atherosclerosis. Yet, it has not been studied whether p27{sup Kip1} influences the expression of TF. Methods and results: p27{sup Kip1} overexpression in human aortic endothelial cells was achieved by adenoviral transfection. Cells were rendered quiescent for 24 h in 0.5% fetal-calf serum. After stimulation with TNF-α (5 ng/ml), TF protein expression and activity was significantly reduced (n = 4; P < 0.001) in cells transfected with p27{sup Kip1}. In line with this, p27{sup Kip1} overexpression reduced cytokine-induced TF mRNA expression (n = 4; P < 0.01) and TF promotor activity (n = 4; P < 0.05). In contrast, activation of the MAP kinases p38, ERK and JNK was not affected by p27{sup Kip1} overexpression. Conclusion: This in vitro study suggests that p27{sup Kip1} inhibits TF expression at the transcriptional level. These data indicate an interaction between p27{sup Kip1} and TF in important pathological alterations such as atherosclerosis and vascular remodeling.

  19. Optogalvanic transients in the 1s2,4→2p1,3 excitations of radio frequency neon plasma

    International Nuclear Information System (INIS)

    Yao, X.; Kumar, D.; McGlynn, S.P.

    1999-01-01

    The optogalvanic effects (OGE) induced by pulsed laser excitation of Ne 1s 2,4 →2p 1,3 transitions in a low power, ∼30 MHz radio frequency Ne discharge at ∼5 Torr are described. The polarity (sign) of the OGE signal is controlled by perturbations of the 1s j populations. The steady state 1s 4 population is ∼10 1 times larger than the 1s 2 population and the OGE signals for 1s 4 →2p 1,3 excitations are correspondingly stronger than those for 1s 22p 1,3 excitations. The plasma temperature is found to be ∼1000 K. The excitations 1s 2,4 →2p 3 are more efficient at signal production than the 1s 2,4 →2p 1 excitations, which is contrary to prediction. The OGE signals are consequences of: (1) perturbation and reequilibration of the metastable 1s 3 and 1s 5 populations; (2) radiatively trapped 1s 21 S 0 photons; and (3) collisionally induced 1s 2 , 1s 4 ↔1s 3 , 1s 5 energy transfer. The OGE signal components, both the ionization and photoacoustic constituents, are temporally coincident only when the immediate causative agents are trapped photons. When otherwise produced, the photoacoustic part is delayed relative to the ionization component by the time required for the acoustic wave to travel from the locus of excitation to the sensitive region(s) of the plasma. copyright 1999 American Institute of Physics

  20. A Genome-wide Association Study Provides Evidence of Sex-specific Involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 With Diabetic Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Weihua Meng

    2015-10-01

    Full Text Available Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system and it affects around 1 in 4 diabetic patients in the UK. The purpose of this genome-wide association study (GWAS was to identify genetic contributors to this disorder. Cases of neuropathic pain were defined as diabetic patients with a multiple prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain. Controls were diabetic individuals who were not prescribed any of these drugs, nor amitriptyline, carbamazepine, or nortriptyline. Overall, 961 diabetic neuropathic pain cases and 3260 diabetic controls in the Genetics of Diabetes Audit and Research Tayside (GoDARTS cohort were identified. We found a cluster in the Chr1p35.1 (ZSCAN20-TLR12P with a lowest P value of 2.74 × 10−7 at rs71647933 in females and a cluster in the Chr8p23.1, next to HMGB1P46 with a lowest P value of 8.02 × 10−7 at rs6986153 in males. Sex-specific narrow sense heritability was higher in males (30.0% than in females (14.7%. This GWAS on diabetic neuropathic pain provides evidence for the sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 with the disorder, indicating the need for further research.

  1. Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFβ cell cycle arrest

    Directory of Open Access Journals (Sweden)

    Harrison David J

    2007-11-01

    Full Text Available Abstract Background TGFβ is critical to control hepatocyte proliferation by inducing G1-growth arrest through multiple pathways leading to inhibition of E2F transcription activity. The retinoblastoma protein pRb is a key controller of E2F activity and G1/S transition which can be inhibited in viral hepatitis. It is not known whether the impairment of pRb would alter the growth inhibitory potential of TGFβ in disease. We asked how Rb-deficiency would affect responses to TGFβ-induced cell cycle arrest. Results Primary hepatocytes isolated from Rb-floxed mice were infected with an adenovirus expressing CRE-recombinase to delete the Rb gene. In control cells treatment with TGFβ prevented cells to enter S phase via decreased cMYC activity, activation of P16INK4A and P21Cip and reduction of E2F activity. In Rb-null hepatocytes, cMYC activity decreased slightly but P16INK4A was not activated and the great majority of cells continued cycling. Rb is therefore central to TGFβ-induced cell cycle arrest in hepatocytes. However some Rb-null hepatocytes remained sensitive to TGFβ-induced cell cycle arrest. As these hepatocytes expressed very high levels of P21Cip1 and P53 we investigated whether these proteins regulate pRb-independent signaling to cell cycle arrest by evaluating the consequences of disruption of p53 and p21Cip1. Hepatocytes deficient in p53 or p21Cip1 showed diminished growth inhibition by TGFβ. Double deficiency had a similar impact showing that in cells containing functional pRb; P21Cip and P53 work through the same pathway to regulate G1/S in response to TGFβ. In Rb-deficient cells however, p53 but not p21Cip deficiency had an additive effect highlighting a pRb-independent-P53-dependent effector pathway of inhibition of E2F activity. Conclusion The present results show that otherwise genetically normal hepatocytes with disabled p53, p21Cip1 or Rb genes respond less well to the antiproliferative effects of TGFβ. As the function of

  2. Magnetic-sublevel cross sections for excitation of the n 1P levels of helium by electron impact

    International Nuclear Information System (INIS)

    Csanak, G.; Cartwright, D.C.; Trajmar, S.

    1992-01-01

    First-order many-body theory has been used to calculate collision-frame magnetic-sublevel differential cross sections for electron-impact excitation of the n 1 P (n=2,3,4,5,6) levels of helium for electrons with incident energy in the 25--500-eV range. By combining results from electron-impact differential-cross-section measurements and electron-photon coincidence measurements, experimental magnetic-sublevel cross sections have also been derived for the excitation of the 2 1 P and 3 1 P levels. The theory predicts a pronounced minimum for the M=0 magnetic-sublevel differential cross section for incident electron energies around 30 eV. Our theoretical results are compared to the experimental data and some other theoretical results

  3. Insight into π-hole interactions containing the inorganic heterocyclic compounds S2N2/SN2P2.

    Science.gov (United States)

    Lu, Bo; Zhang, Xueying; Meng, Lingpeng; Zeng, Yanli

    2017-08-01

    Similar to σ-hole interactions, the π-hole interaction has attracted much attention in recent years. According to the positive electrostatic potentials above and below the surface of inorganic heterocyclic compounds S 2 N 2 and three SN 2 P 2 isomers (heterocyclic compounds 1-4), and the negative electrostatic potential outside the X atom of XH 3 (X = N, P, As), S 2 N 2 /SN 2 P 2 ⋯XH 3 (X = N, P, As) complexes were constructed and optimized at the MP2/aug-cc-pVTZ level. The X atom of XH 3 (X = N, P, As) is almost perpendicular to the ring of the heterocyclic compounds. The π-hole interaction energy becomes greater as the trend goes from 1⋯XH 3 to 4⋯XH 3 . These π-hole interactions are weak and belong to "closed-shell" noncovalent interactions. According to the energy decomposition analysis, of the three attractive terms, the dispersion energy contributes more than the electrostatic energy. The polarization effect also plays an important role in the formation of π-hole complexes, with the contrasting phenomena of decreasing electronic density in the π-hole region and increasing electric density outside the X atom of XH 3 (X = N, P, As). Graphical abstract Computed density difference plots for the complexes 3⋯NH 3 (a 1 ), 3⋯PH 3 (b 1 ), 3⋯AsH 3 (c 1 ) and electron density shifts for the complexes 3⋯NH 3 (a 2 ), 3⋯PH 3 (b 2 ),3⋯AsH 3 (c 2 ) on the 0.001 a.u. contour.

  4. The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation.

    Science.gov (United States)

    Martins, Telma S; Pereira, Clara; Canadell, David; Vilaça, Rita; Teixeira, Vítor; Moradas-Ferreira, Pedro; de Nadal, Eulàlia; Posas, Francesc; Costa, Vítor

    2018-01-01

    Iron acquisition systems have to be tightly regulated to assure a continuous supply of iron, since it is essential for survival, but simultaneously to prevent iron overload that is toxic to the cells. In budding yeast, the low‑iron sensing transcription factor Aft1p is a master regulator of the iron regulon. Our previous work revealed that bioactive sphingolipids modulate iron homeostasis as yeast cells lacking the sphingomyelinase Isc1p exhibit an upregulation of the iron regulon. In this study, we show that Isc1p impacts on iron accumulation and localization. Notably, Aft1p is activated in isc1Δ cells due to a decrease in its phosphorylation and an increase in its nuclear levels. Consistently, the expression of a phosphomimetic version of Aft1p-S210/S224 that favours its nuclear export abolished iron accumulation in isc1Δ cells. Notably, the Hog1p kinase, homologue of mammalian p38, interacts with and directly phosphorylates Aft1p at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in isc1Δ cells, which likely contributes to Aft1p dephosphorylation and consequently to Aft1p activation and iron overload in isc1Δ cells. These results suggest that alterations in sphingolipid composition in isc1Δ cells may impact on iron homeostasis by disturbing the regulation of Aft1p by Hog1p. To our knowledge, Hog1p is the first kinase reported to directly regulate Aft1p, impacting on iron homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Electron Excitation Rate Coefficients for Transitions from the IS21S Ground State to the 1S2S1,3S and 1S2P1,3P0 Excited States of Helium

    Science.gov (United States)

    Aggarwal, K. M.; Kingston, A. E.; McDowell, M. R. C.

    1984-03-01

    The available experimental and theoretical electron impact excitation cross section data for the transitions from the 1s2 1S ground state to the 1s2s 1,3S and 1s2p 1,3P0 excited states of helium are assessed. Based on this assessed data, excitation rate coefficients are calculated over a wide electron temperature range below 3.0×106K. A comparison with other published results suggests that the rates used should be lower by a factor of 2 or more.

  6. Difluorophosphoryl nitrene F2P(O)N: matrix isolation and unexpected rearrangement to F2PNO.

    Science.gov (United States)

    Zeng, Xiaoqing; Beckers, Helmut; Willner, Helge; Neuhaus, Patrik; Grote, Dirk; Sander, Wolfram

    2009-12-14

    Triplet difluorophosphoryl nitrene F(2)P(O)N (X(3)A'') was generated on ArF excimer laser irradiation (lambda=193 nm) of F(2)P(O)N(3) in solid argon matrix at 16 K, and characterized by its matrix IR, UV/Vis, and EPR spectra, in combination with DFT and CBS-QB3 calculations. On visible light irradiation (lambda>420 nm) at 16 K F(2)P(O)N reacts with molecular nitrogen and some of the azide is regenerated. UV irradiation (lambda=255 nm) of F(2)P(O)N (X(3)A'') induced a Curtius-type rearrangement, but instead of a 1,3-fluorine shift, nitrogen migration to give F(2)PON is proposed to be the first step of the photoisomerization of F(2)P(O)N into F(2)PNO (difluoronitrosophosphine). Formation of novel F(2)PNO was confirmed with (15)N- and (18)O-enriched isotopomers by IR spectroscopy and DFT calculations. Theoretical calculations predict a rather long P-N bond of 1.922 A [B3LYP/6-311+G(3df)] and low bond-dissociation energy of 76.3 kJ mol(-1) (CBS-QB3) for F(2)PNO.

  7. Organotin(IV Derivatives of 2-Acetylpyridine-N(4-Phenylthiosemicarbazone, HAP4P, and 2-Hydroxyacetophenone-N(4-Phenylthiosemicarbazone, H2DAP4P: Crystal and Molecular Structure of [SnMe2(DAP4P] and [SnBu2(DAP4P

    Directory of Open Access Journals (Sweden)

    Sousa Gerimário F. de

    2001-01-01

    Full Text Available The reactions of 2-acetylpyridine-N(4-phenylthiosemicarbazone, HAP4P, and 2-hydroxyacetophenone-N(4-phenylthiosemicarbazone, H2DAP4P, with R4-mSnXm (m = 2, 3; R = Me, nBu, Ph and X = Cl, Br led to the formation of hexa- and penta-coordinated organotin(IV complexes, which were studied by microanalysis, IR, ¹H-NMR and Mössbauer spectroscopies. The molecular structures of [SnMe2(DAP4P] and [Sn nBu2(DAP4P] were determined by single-crystal X-ray diffraction studies. In the compounds [SnClMe2(AP4P] and [SnBrMe2(AP4P], the deprotonated ligand AP4P- is N,N,S-bonded to the Sn(IV atoms, which exhibit strongly distorted octahedral coordination. The structures of [SnMe2(DAP4P] and [Sn nBu2(DAP4P] revealed that the DAP4P2- anion acts as a O,N,S-tridentate ligand. In these cases, the Sn(IV atoms adopt a strongly distorted trigonal bipyramidal configuration where the azomethine N and the two C atoms are on the equatorial plane while the O and the S atoms occupy the axial positions.

  8. Identification of rabbit cytochromes P450 2C1 and 2C2 as arachidonic acid epoxygenases.

    Science.gov (United States)

    Laethem, R M; Koop, D R

    1992-12-01

    Microsomes prepared from COS-1 cells transiently expressing rabbit cytochromes P450 2C1 and 2C2 catalyzed the metabolism of arachidonic acid to predominantly 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) when microsomal epoxide hydrolase activity was inhibited by 0.2 mM 1,2-epoxy-3,3,3-trichloropropane. P450 2C2 catalyzed the formation of 11,12-EET and 14,15-EET at a ratio of 3.0 and also produced 19-hydroxyeicosatetraenoic acid (19-HETE). The 11,12-EET, 14,15-EET, and 19-HETE represented 48.3, 15.9, and 12.8%, respectively, of the total metabolites formed. P450 2C1 produced a similar but distinct ratio of 11,12-EET to 14,15-EET (2.0) and did not produce any detectable 19-HETE. The 11,12-EET and 14,15-EET represented 63.0 and 31.1%, respectively, of the total metabolites formed. The 8,9- and 5,6-EETs were not detected with either enzyme. The ratio of the 11,12-EET to 14,15-EET was 1.5 with P450 2CAA, a P450 arachidonic acid epoxygenase (P450 2CAA) that had an amino-terminal sequence identical to that of P450 2C2 [J. Biol. Chem. 267:5552-5559 (1992)]. P450 2C1, 2C2, and 2CAA metabolized lauric acid. The ratio of omega-1- to omega-hydroxylated laurate was 3.6, 3.4, and 2.4 for P450 2CAA, P450 2C2, and P450 2C1, respectively. Purified P450 2CAA had a slightly greater apparent molecular weight than expressed P450 2C2 on sodium dodecyl sulfate-polyacrylamide gels. The results clearly establish that rabbit P450 2C1 and 2C2 are arachidonic acid epoxygenases, and they suggest that P450 2CAA and 2C2 are very similar but may not be identical isoforms.

  9. Cis-[RuCl(BzCN)(N-N)(P-P)]PF6 complexes: Synthesis and in vitro antitumor activity: (BzCN=benzonitrile; N-N=2,2'-bipyridine; 1,10-phenanthroline; P-P=1,4-bis(diphenylphosphino) butane, 1,2-bis(diphenylphosphino)ethane, or 1,1'-(diphenylphosphino)ferrocene).

    Science.gov (United States)

    Pereira, Flávia de C; Lima, Benedicto A V; de Lima, Aliny P; Pires, Wanessa C; Monteiro, Thallita; Magalhães, Lorena F; Costa, Wanderson; Graminha, Angélica E; Batista, Alzir A; Ellena, Javier; Siveira-Lacerda, Elisângela de P

    2015-08-01

    The motivation to use ruthenium complexes in cancer treatment has led our research group to synthesize complexes with this metal and test them against several types of tumor cells, yielding promising results. In this paper the results of biological tests, assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, were carried out on the complexes cis-[RuCl(BzCN)(bipy)(dppe)]PF6 (1), cis-[RuCl(BzCN)(bipy)(dppb)]PF6 (2), cis-[RuCl(BzCN)(bipy)(dppf)]PF6 (3) and cis-[RuCl(BzCN)(phen)(dppb)]PF6 (4) which are described [BzCN = b enzonitrile; bipy = 2,2'-bipyridine; phen = 1,10-phenanthroline; dppe = 1,2-bis(diphenylphosphino) ethane; dppb = 1,4-bis-(diphenylphosphino)butane; dppf = 1,1'-bis(diphenylphosphino)ferrocene]. The present study is focused on the cytotoxic activity of complexes (1)-(4) against four tumor cell lines and on the apoptosis and changes in the cell cycle and gene expression observed in the sarcoma 180 (S180) tumor cell line treated with complex (1). The results demonstrated that this complex inhibits S180 cell growth, with an IC50 of 17.02 ± 8.21 μM, while exhibiting lower cytotoxicity (IC50 = 53.73 ± 5.71 μM) towards lymphocytes (normal cells). Flow cytometry revealed that the complex inhibits the growth of tumor cells by inducing apoptosis as evidenced by an increase in the proportion of cells positive for annexin V staining and G0/G1 phase cell-cycle arrest. Further investigation showed that complex (1) induces a drop in the mitochondrial membrane potential and provokes a decrease in Bcl-2 protein expression and increase in caspase 3 activation, while the increased activation of caspase 8 caused a decrease in the gene expression in caspases 3 and 9. Increases in Tp53 and Bax expressions were also observed. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. μ-1,2-Bis(diphenylphosphinoethane-κ2P:P′-bis{[1,2-bis(diphenylphosphinoethane-κ2P,P′]bromidocopper(I} acetone disolvate

    Directory of Open Access Journals (Sweden)

    Wen-Juan Shi

    2008-10-01

    Full Text Available In the crystal structure of the title compound, [Cu2Br2(dppe3]·2CH3COCH3 [dppe is 1,2-bis(diphenylphosphinoethane, C26H24P2], the two Cu centers are bridged by a dppe ligand and each metal center carries one chelating dppe unit, with the fourth coordination site available for the Br− anion. The molecule is centrosymmetric, with the center of symmetry located between the methylene C atoms of the bridging dppe ligand. The crystal structure is stabilized by intramolecular C—H...Br hydrogen bonds and intermolecular π–π interactions, with a centroid-to-centroid distance of 3.2055 (1 Å.

  11. Interaction of integrin β4 with S1P receptors in S1P- and HGF-induced endothelial barrier enhancement.

    Science.gov (United States)

    Ni, Xiuqin; Epshtein, Yulia; Chen, Weiguo; Zhou, Tingting; Xie, Lishi; Garcia, Joe G N; Jacobson, Jeffrey R

    2014-06-01

    We previously reported sphingosine 1-phosphate (S1P) and hepatocyte growth factor (HGF) augment endothelial cell (EC) barrier function and attenuate murine acute lung inury (ALI). While the mechanisms underlying these effects are not fully understood, S1P and HGF both transactivate the S1P receptor, S1PR1 and integrin β4 (ITGB4) at membrane caveolin-enriched microdomains (CEMs). In the current study, we investigated the roles of S1PR2 and S1PR3 in S1P/HGF-mediated EC signaling and their associations with ITGB4. Our studies confirmed ITGB4 and S1PR2/3 are recruited to CEMs in human lung EC in response to either S1P (1 µM, 5 min) or HGF (25 ng/ml, 5 min). Co-immunoprecipitation experiments identified an S1P/HGF-mediated interaction of ITGB4 with both S1PR2 and S1PR3. We then employed an in situ proximity ligation assay (PLA) to confirm a direct ITGB4-S1PR3 association induced by S1P/HGF although a direct association was not detectable between S1PR2 and ITGB4. S1PR1 knockdown (siRNA), however, abrogated S1P/HGF-induced ITGB4-S1PR2 associations while there was no effect on ITGB4-S1PR3 associations. Moreover, PLA confirmed a direct association between S1PR1 and S1PR2 induced by S1P and HGF. Finally, silencing of S1PR2 significantly attenuated S1P/HGF-induced EC barrier enhancement as measured by transendothelial resistance while silencing of S1PR3 significantly augmented S1P/HGF-induced barrier enhancement. These results confirm an important role for S1PR2 and S1PR3 in S1P/HGF-mediated EC barrier responses that are associated with their complex formation with ITGB4. Our findings elucidate novel mechanisms of EC barrier regulation that may ultimately lead to new therapeutic targets for disorders characterized by increased vascular permeability including ALI. © 2013 Wiley Periodicals, Inc.

  12. Impaired P2X1 Receptor-Mediated Adhesion in Eosinophils from Asthmatic Patients.

    Science.gov (United States)

    Wright, Adam; Mahaut-Smith, Martyn; Symon, Fiona; Sylvius, Nicolas; Ran, Shaun; Bafadhel, Mona; Muessel, Michelle; Bradding, Peter; Wardlaw, Andrew; Vial, Catherine

    2016-06-15

    Eosinophils play an important role in the pathogenesis of asthma and can be activated by extracellular nucleotides released following cell damage or inflammation. For example, increased ATP concentrations were reported in bronchoalveolar lavage fluids of asthmatic patients. Although eosinophils are known to express several subtypes of P2 receptors for extracellular nucleotides, their function and contribution to asthma remain unclear. In this article, we show that transcripts for P2X1, P2X4, and P2X5 receptors were expressed in healthy and asthmatic eosinophils. The P2X receptor agonist α,β-methylene ATP (α,β-meATP; 10 μM) evoked rapidly activating and desensitizing inward currents (peak 18 ± 3 pA/pF at -60 mV) in healthy eosinophils, typical of P2X1 homomeric receptors, which were abolished by the selective P2X1 antagonist NF449 (1 μM) (3 ± 2 pA/pF). α,β-meATP-evoked currents were smaller in eosinophils from asthmatic patients (8 ± 2 versus 27 ± 5 pA/pF for healthy) but were enhanced following treatment with a high concentration of the nucleotidase apyrase (17 ± 5 pA/pF for 10 IU/ml and 11 ± 3 pA/pF for 0.32 IU/ml), indicating that the channels are partially desensitized by extracellular nucleotides. α,β-meATP (10 μM) increased the expression of CD11b activated form in eosinophils from healthy, but not asthmatic, donors (143 ± 21% and 108 ± 11% of control response, respectively). Furthermore, α,β-meATP increased healthy (18 ± 2% compared with control 10 ± 1%) but not asthmatic (13 ± 1% versus 10 ± 0% for control) eosinophil adhesion. Healthy human eosinophils express functional P2X1 receptors whose activation leads to eosinophil αMβ2 integrin-dependent adhesion. P2X1 responses are constitutively reduced in asthmatic compared with healthy eosinophils, probably as the result of an increase in extracellular nucleotide concentration. Copyright © 2016 by The American Association of Immunologists, Inc.

  13. MMP2 and MMP9 participate in S1P-induced invasion of follicular ML-1 thyroid cancer cells.

    Science.gov (United States)

    Kalhori, Veronica; Törnquist, Kid

    2015-03-15

    The bioactive lipid sphingosine-1-phosphate (S1P) has emerged as a potent inducer of cancer cell migration and invasion. Previously, we have shown that S1P induces invasion of ML-1 follicular thyroid cancer cells via S1P receptors 1 and 3 (S1P1,3). Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes used by cells for degradation of the extracellular matrix during invasion and migration. In the present study, we examined the role of MMP2 and MMP9 for S1P-induced invasion of ML-1 cells, and found that S1P regulates the secretion and activity of MMP2 and MMP9 via S1P1,3. Both pharmacological inhibitors and siRNA knockdown of MMP2 and MMP9 could attenuate S1P-induced invasion. Additionally, we show that calpains and Rac1 mediate S1P-induced secretion of MMP2 and MMP9. In conclusion, MMP2 and MMP9 participate in S1P-evoked follicular ML-1 thyroid cancer cell invasion. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Novel 1,3-diacylamidopropane-2-[bis-(2-dimethylaminoethane)] carbamate pH-sensitive lipids for cationic liposome-mediated transfection

    Science.gov (United States)

    Spelios, Michael G.

    A novel series of 1,3-diacylamidopropane-2-[bis(2-dimethylaminoethane)] carbamate analogs (1,3lb) were designed for cationic lipid-assisted transfection (lipofection). First, their physicochemical properties in self-assemblies with and without plasmid DNA (pDNA) were evaluated to examine the effects of hydrophobic tail length and degree of saturation on gene delivery and expression. Significant in vitro lipofection was induced at a nitrogen:phosphate ratio (N:P) of 4:1 by the dimyristoyl, dipalmitoyl, and dioleoyl analogs 1,3lb2, 1,3lb3, and 1,3lb5, respectively, without inclusion of neutral "lipofection enhancing" co-lipids in the cationic lipid formulations. Lipofection was reduced in the presence of co-lipids except for 1,3lb5 which maintained reporter gene expression levels at N:P 4:1 and yielded increased bioactivity at a lower NP of 2:1. Physicochemical characterization of the bioactive transfection agents (cytofectins) revealed: high hydration and in-plane elasticity of lipid monolayers by Langmuir film balance measurements; fluid lipid bilayers, with gel---liquid crystalline phase transitions below physiological temperature, by fluorescence anisotropy; lipid mixing with biomembrane-mimicking vesicles by fluorescence resonance energy transfer; efficient pDNA binding and compaction by ethidium bromide displacement; cationic liposome---nucleic acid complexes (lipoplexes) with large particle sizes (mean diameter ≥ 500 nm) and zeta potentials of positive values by dynamic light scattering and electrophoretic mobility, respectively. The results suggest that well hydrated and elastic cationic lipids forming fluid lamellar assemblies are extremely potent and minimally toxic cytofectins. Second, a comparison was made between 1,3lb2 and two derivatives, one an isomer with a shorter space between the myristoyl chains and the other the monovalent form, in an effort to delineate the biological effects of interchain distance and pH-induced polar headgroup expandability

  15. Cyclin E/Cdk2, P/CAF, and E1A regulate the transactivation of the c-myc promoter by FOXM1

    International Nuclear Information System (INIS)

    Wierstra, Inken; Alves, Juergen

    2008-01-01

    FOXM1c transactivates the c-myc promoter by binding directly to its TATA-boxes. The present study demonstrates that the transactivation of the c-myc promoter by FOXM1c is enhanced by the key proliferation signal cyclin E/Cdk2, but repressed by P/CAF and the adenoviral oncoprotein E1A. Furthermore, FOXM1c interacts with the coactivator and histone acetyltransferase P/CAF. This study shows that, on the c-myc-P1 TATA-box, FOXM1c does not function simply as normal transcription factor just binding to an unusual site. Moreover, the inhibitory N-terminus of FOXM1c does not inhibit its transrepression domain or its EDA. Others reported that a cyclin/Cdk-binding LXL-motif of the splice variant FoxM1b is required for its interaction with Cdk2, Cdk1, and p27, its phosphorylation by Cdk1 and its activation by Cdc25B. In contrast, we now demonstrate that this LXL-motif is not required for the activation of FOXM1c by cyclin D1/Cdk4, cyclin E/Cdk and cyclin A/Cdk2 or for the repression of FOXM1c by p27

  16. Role of sphingosine 1-phosphate (S1P and effects of fingolimod, an S1P receptor 1 functional antagonist in lymphocyte circulation and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Kenji Chiba

    2014-11-01

    Full Text Available Sphingosine 1-phosphate (S1P, a multi-functional phospholipid mediator, is generated from sphingosine by sphingosine kinases and binds to five known G protein-coupled S1P receptors (S1P1, S1P2, S1P3, S1P4, and S1P5. It is widely accepted that S1P receptor 1 (S1P1 plays an essential role in lymphocyte egress from the secondary lymphoid organs (SLO and thymus, because lymphocyte egress from these organs to periphery is at extremely low levels in mice lacking lymphocytic S1P1. Fingolimod hydrochloride (FTY720 is a first-in-class, orally active S1P1 functional antagonist which was discovered by chemical modification of a natural product, myriocin. Since FTY720 has a structure closely related to sphingosine, the phosphorylated FTY720 (FTY720-P is converted by sphingosine kinases and binds 4 types of S1P receptors. FTY720-P strongly induces down-regulation of S1P1 by internalization and degradation of this receptor and acts as a functional antagonist at S1P1. Consequently, FTY720 inhibits S1P1-dependent lymphocyte egress from the SLO and thymus to reduce circulating lymphocytes including autoreactive Th17 cells, and is highly effective in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. In relapsing remitting MS patients, oral FTY720 shows a superior efficacy when compared to intramuscular interferon-β-1a. Based on these data, it is presumed that modulation of the S1P-S1P1 axis provides an effective therapy for autoimmune diseases including MS.

  17. Magnetic properties and magnetocaloric effects in Mn1.2Fe0.8P1-xGex compounds

    International Nuclear Information System (INIS)

    Ou, Z Q; Wang, G F; Lin Song; Tegus, O; Brueck, E; Buschow, K H J

    2006-01-01

    We have studied the magnetic properties and magnetocaloric effects in the Mn 1.2 Fe 0.8 P 1-x Ge x compounds with x = 0.2, 0.22, 0.3, 0.4 and 0.5. X-ray diffraction patterns show that the Mn 1.2 Fe 0.8 P 1-x Ge x compounds crystallize in the hexagonal Fe 2 P-type crystal structure. The magnetic moments of the Mn 1.2 Fe 0.8 P 1-x Ge x compounds measured at 5 K and 5 T increase with increasing Ge content. The Curie temperature increases strongly and the magnetic entropy change has a maximum around 233 K for the compound with x = 0.22, which is about 19 and 31 J kg -1 K -1 for a field change of 2 and 5 T, respectively

  18. Branching ratio and angular distribution of ejected electrons from Eu 4f76p1/2 n d auto-ionizing states

    International Nuclear Information System (INIS)

    Wu Xiao-Rui; Shen Li; Zhang Kai; Dai Chang-Jian; Yang Yu-Na

    2016-01-01

    The branching ratios of ions and the angular distributions of electrons ejected from the Eu 4f 7 6p 1/2 n d auto-ionizing states are investigated with the velocity-map-imaging technique. To populate the above auto-ionizing states, the relevant bound Rydberg states have to be detected first. Two new bound Rydberg states are identified in the region between 41150 cm −1 and 44580 cm −1 , from which auto-ionization spectra of the Eu 4f 7 6p 1/2 n d states are observed with isolated core excitation method. With all preparations above, the branching ratios from the above auto-ionizing states to different final ionic states and the angular distributions of electrons ejected from these processes are measured systematically. Energy dependence of branching ratios and anisotropy parameters within the auto-ionization spectra are carefully analyzed, followed by a qualitative interpretation. (paper)

  19. Bottomonium spectroscopy and radiative transitions involving the chi(bJ)(1P, 2P) states at BABAR

    NARCIS (Netherlands)

    Lees, J. P.; Poireau, V.; Tisserand, V.; Grauges, E.; Palano, A.; Eigen, G.; Stugu, B.; Brown, D. N.; Kerth, L. T.; Kolomensky, Yu. G.; Lynch, G.; Schroeder, T.; Hearty, C.; Mattison, T. S.; McKenna, J. A.; So, R. Y.; Khan, A.; Blinov, V. E.; Buzykaev, A. R.; Druzhinin, V. P.; Golubev, V. B.; Kravchenko, E. A.; Onuchin, A. P.; Serednyakov, S. I.; Skovpen, Yu. I.; Solodov, E. P.; Todyshev, K. Yu.; Lankford, A. J.; Mandelkern, M.; Dey, B.; Gary, J. W.; Long, O.; Campagnari, C.; Sevilla, M. Franco; Hong, T. M.; Kovalskyi, D.; Richman, J. D.; West, C. A.; Eisner, A. M.; Lockman, W. S.; Vazquez, W. Panduro; Schumm, B. A.; Seiden, A.; Chao, D. S.; Echenard, B.; Flood, K. T.; Hitlin, D. G.; Miyashita, T. S.; Ongmongkolkul, P.; Roehrken, M.; Andreassen, R.; Huard, Z.; Meadows, B. T.; Pushpawela, B. G.; Sokoloff, M. D.; Sun, L.; Bloom, P. C.; Ford, W. T.; Gaz, A.; Smith, J. G.; Wagner, S. R.; Ayad, R.; Toki, W. H.; Spaan, B.; Bernard, D.; Verderi, M.; Playfer, S.; Bettoni, D.; Bozzi, C.; Calabrese, R.; Cibinetto, G.; Fioravanti, E.; Garzia, I.; Luppi, E.; Piemontese, L.; Santoro, V.; Calcaterra, A.; de Sangro, R.; Finocchiaro, G.; Martellotti, S.; Patteri, P.; Peruzzi, I. M.; Piccolo, M.; Rama, M.; Zallo, A.; Contri, R.; Lo Vetere, M.; Monge, M. R.; Passaggio, S.; Patrignani, C.; Robutti, E.; Bhuyan, B.; Prasad, V.; Adametz, A.; Uwer, U.; Lacker, M.; Dauncey, P. D.; Mallik, U.; Cochran, J.; Prell, S.; Ahmed, H.; Gritsan, A. V.; Arnaud, N.; Davier, M.; Derkach, D.; Grosdidier, G.; Le Diberder, F.; Lutz, A. M.; Malaescu, B.; Roudeau, P.; Stocchi, A.; Wormser, G.; Lange, D. J.; Wright, D. M.; Coleman, J. P.; Fry, J. R.; Gabathuler, E.; Hutchcroft, D. E.; Payne, D. J.; Touramanis, C.; Bevan, A. J.; Di Lodovico, F.; Sacco, R.; Cowan, G.; Bougher, J.; Brown, D. N.; Davis, C. L.; Denig, A. G.; Fritsch, M.; Gradl, W.; Griessinger, K.; Hafner, A.; Schubert, K. R.; Barlow, R. J.; Lafferty, G. D.; Cenci, R.; Hamilton, B.; Jawahery, A.; Roberts, D. A.; Cowan, R.; Sciolla, G.; Cheaib, R.; Patel, P. M.; Robertson, S. H.; Neri, N.; Palombo, F.; Cremaldi, L.; Godang, R.; Sonnek, P.; Summers, D. J.; Simard, M.; Taras, P.; De Nardo, G.; Onorato, G.; Sciacca, C.; Martinelli, M.; Raven, G.; Jessop, C. P.; LoSecco, J. M.; Honscheid, K.; Kass, R.; Feltresi, E.; Margoni, M.; Morandin, M.; Posocco, M.; Rotondo, M.; Simi, G.; Simonetto, F.; Stroili, R.; Akar, S.; Ben-Haim, E.; Bomben, M.; Bonneaud, G. R.; Briand, H.; Calderini, G.; Chauveau, J.; Leruste, Ph.; Marchiori, G.; Ocariz, J.; Biasini, M.; Manoni, E.; Pacetti, S.; Rossi, A.; Angelini, C.; Batignani, G.; Bettarini, S.; Carpinelli, M.; Casarosa, G.; Cervelli, A.; Chrzaszcz, M.; Forti, F.; Giorgi, M. A.; Lusiani, A.; Oberhof, B.; Paoloni, E.; Perez, A.; Rizzo, G.; Walsh, J. J.; Pegna, D. Lopes; Olsen, J.; Smith, A. J. S.; Faccini, R.; Ferrarotto, F.; Ferroni, F.; Gaspero, M.; Gioi, L. Li; Pilloni, A.; Piredda, G.; Buenger, C.; Dittrich, S.; Gruenber, O.; Hess, M.; Leddig, T.; Voss, C.; Waldi, R.; Adye, T.; Olaiya, E. O.; Wilson, F. F.; Emery, S.; Vasseur, G.; Anulli, F.; Aston, D.; Bard, D. J.; Cartaro, C.; Convery, M. R.; Dorfan, J.; Dubois-Felsmann, G. P.; Dunwoodie, W.; Ebert, M.; Field, R. C.; Fulsom, B. G.; Graham, M. T.; Hast, C.; Innes, W. R.; Kim, P.; Leith, D. W. G. S.; Lewis, P.; Lindemann, D.; Luitz, S.; Luth, V.; Lynch, H. L.; MacFarlane, D. B.; Muller, D. R.; Neal, H.; Perl, M.; Pulliam, T.; Ratcliff, B. N.; Roodman, A.; Salnikov, A. A.; Schindler, R. H.; Snyder, A.; Su, D.; Sullivan, M. K.; Va'vra, J.; Wisniewski, W. J.; Wulsin, H. W.; Purohit, M. V.; White, R. M.; Wilson, J. R.; Randle-Conde, A.; Sekula, S. J.; Bellis, M.; Burchat, P. R.; Puccio, E. M. T.; Alam, M. S.; Ernst, J. A.; Gorodeisky, R.; Guttman, N.; Peimer, D. R.; Soffer, A.; Spanier, S. M.; Ritchie, J. L.; Ruland, A. M.; Schwitters, R. F.; Wray, B. C.; Izen, J. M.; Lou, X. C.; Bianchi, F.; De Mori, F.; Filippi, A.; Gamba, D.; Lanceri, L.; Vitale, L.; Martinez-Vidal, F.; Oyanguren, A.; Villanueva-Perez, P.; Albert, J.; Banerjee, Sw.; Beaulieu, A.; Bernlochner, F. U.; Choi, H. H. F.; Kowalewski, R.; Lewczuk, M. J.; Lueck, T.; Nugent, I. M.; Roney, J. M.; Sobie, R. J.; Tasneem, N.; Gershon, T. J.; Harrison, P. F.; Latham, T. E.; Band, H. R.; Dasu, S.; Pan, Y.; Prepost, R.

    2014-01-01

    We use (121±1) million Υ(3S) and (98±1) million Υ(2S) mesons recorded by the BABAR detector at the PEP-II e+e− collider at SLAC to perform a study of radiative transitions involving the χbJ(1P,2P) states in exclusive decays with μ+μ−γγ final states. We reconstruct twelve channels in four cascades

  20. Photoassociation spectroscopy of 87Rb2 (5s1/2+5p1/2)0u+ long-range molecular states: Coupling with the (5s1/2+5p3/2)0u+ series analyzed using the Lu-Fano approach

    International Nuclear Information System (INIS)

    Jelassi, H.; Viaris de Lesegno, B.; Pruvost, L.

    2006-01-01

    We report on photoassociation of cold 87 Rb atoms providing the spectroscopy of (5s 1/2 +5p 1/2 )0 u + long-range molecular states, in the energy range of [-12.5, -0.7 cm -1 ] below the dissociation limit. A Lu-Fano approach coupled to the LeRoy-Bernstein formula is used to analyze the data. The Lu-Fano graph exhibits the coupling of the molecular series with the (5s 1/2 +5p 3/2 )0 u + one, which is due to spin effects in the molecule. A two-channel model involving an improved LeRoy-Bernstein formula allows us to characterize the molecular series, to localize (5s 1/2 +5p 3/2 )0 u + levels, to evaluate the coupling, and to predict the energy and width of the first predissociated level of (5s 1/2 +5p 3/2 )0 u + series. An experimental spectrum confirms the prediction

  1. PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-10-23

    p70 ribosomal S6 kinase 1 (S6K1) is an important serine/threonine kinase and downstream target of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. PF-4708671 is a specific inhibitor of S6K1, and prevents S6K1-mediated phosphorylation of the S6 protein. PF-4708671 treatment often leads to apoptotic cell death. However, the protective mechanism against PF-4708671-induced cell death has not been elucidated. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is essential for protecting cells against oxidative stress. p62, an adaptor protein in the autophagic process, enhances Nrf2 activation through the impairment of Keap1 activity. In this study, we showed that PF-4708671 induces autophagic Keap1 degradation-mediated Nrf2 activation in p62-dependent manner. Furthermore, p62-dependent Nrf2 activation plays a crucial role in protecting cells from PF-4708671-mediated apoptosis. - Highlights: • PF-4708671, a S6K1-specific inhibitor, prevents S6K1-mediated S6 phosphorylation. • However, PF-4708671 treatment often leads to apoptotic cell death. • Protective mechanism against PF-4708671-induced cell death remains to be elucidated. • PF-4708671 induced p62-dependent, autophagic Keap1 degradation-mediated Nrf2 activation. • p62-dependent Nrf2 activation protects cells from PF-4708671-mediated apoptosis.

  2. Semiconducting ZnSnN{sub 2} thin films for Si/ZnSnN{sub 2} p-n junctions

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Ruifeng [Hebei Engineering Laboratory of Photoelectronic Functional Crystals, Hebei University of Technology (HEBUT), Tianjin 300401 (China); Ningbo Institute of Material Technology and Engineering, Chinese Academy of Sciences, and Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Ningbo 315201 (China); Cao, Hongtao; Liang, Lingyan, E-mail: lly@nimte.ac.cn, E-mail: swz@hebut.edu.cn; Xie, Yufang; Zhuge, Fei; Zhang, Hongliang; Gao, Junhua; Javaid, Kashif [Ningbo Institute of Material Technology and Engineering, Chinese Academy of Sciences, and Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Ningbo 315201 (China); Liu, Caichi; Sun, Weizhong, E-mail: lly@nimte.ac.cn, E-mail: swz@hebut.edu.cn [Hebei Engineering Laboratory of Photoelectronic Functional Crystals, Hebei University of Technology (HEBUT), Tianjin 300401 (China)

    2016-04-04

    ZnSnN{sub 2} is regarded as a promising photovoltaic absorber candidate due to earth-abundance, non-toxicity, and high absorption coefficient. However, it is still a great challenge to synthesize ZnSnN{sub 2} films with a low electron concentration, in order to promote the applications of ZnSnN{sub 2} as the core active layer in optoelectronic devices. In this work, polycrystalline and high resistance ZnSnN{sub 2} films were fabricated by magnetron sputtering technique, then semiconducting films were achieved after post-annealing, and finally Si/ZnSnN{sub 2} p-n junctions were constructed. The electron concentration and Hall mobility were enhanced from 2.77 × 10{sup 17} to 6.78 × 10{sup 17 }cm{sup −3} and from 0.37 to 2.07 cm{sup 2} V{sup −1} s{sup −1}, corresponding to the annealing temperature from 200 to 350 °C. After annealing at 300 °C, the p-n junction exhibited the optimum rectifying characteristics, with a forward-to-reverse ratio over 10{sup 3}. The achievement of this ZnSnN{sub 2}-based p-n junction makes an opening step forward to realize the practical application of the ZnSnN{sub 2} material. In addition, the nonideal behaviors of the p-n junctions under both positive and negative voltages are discussed, in hope of suggesting some ideas to further improve the rectifying characteristics.

  3. Lost P1 allele in sh2 sweet corn: quantitative effects of p1 and a1 genes on concentrations of maysin, apimaysin, methoxymaysin, and chlorogenic acid in maize silk.

    Science.gov (United States)

    Guo, B Z; Zhang, Z J; Butrón, A; Widstrom, N W; Snook, M E; Lynch, R E; Plaisted, D

    2004-12-01

    In the United States, insecticide is used extensively in the production of sweet corn due to consumer demand for zero damage to ears and to a sweet corn genetic base with little or no resistance to ear-feeding insects. Growers in the southern United States depend on scheduled pesticide applications to control ear-feeding insects. In a study of quantitative genetic control over silk maysin, AM-maysin (apimaysin and methoxymaysin), and chlorogenic acid contents in an F2 population derived from GE37 (dent corn, P1A1) and 565 (sh2 sweet corn, p1a1), we demonstrate that the P1 allele from field corn, which was selected against in the development of sweet corn, has a strong epistatic interaction with the a1 allele in sh2 sweet corn. We detected that the p1 gene has significant effects (P silk maysin concentrations but also on AM-maysin, and chlorogenic acid concentrations. The a1 gene also has significant (P silk antibiotic chemicals. Successful selection from the fourth and fifth selfed backcrosses for high-maysin individuals of sweet corn homozygous for the recessive a1 allele (tightly linked to sh2) and the dominant P1 allele has been demonstrated. These selected lines have much higher (2 to 3 times) concentrations of silk maysin and other chemicals (AM-maysin and chlorogenic acid) than the donor parent GE37 and could enhance sweet corn resistance to corn earworm and reduce the number of applications of insecticide required to produce sweet corn.

  4. Fabrication of p-{beta}-Fe{sub 1{minus}x}Mn{sub x}Si{sub 2}/nSi heterostructure diode and their electrical and optical properties

    Energy Technology Data Exchange (ETDEWEB)

    Takada, T; Katsumata, H; Makita, Y; Kobayashi, N; Hasegawa, M; Uekusa, S

    1997-07-01

    The authors report on the fabrication of p-type {beta}-FeSi{sub 2} layers on n-type Si(100) substrates and the investigation of their p-n diode characteristics. Since the undoped {beta}-FeSi{sub 2} layers have typically shown n-type conductivity, the p-type layers were formed by the introduction of Mn impurity into {beta}-FeSi{sub 2} layers using two types of doping methods; one is an Electron-Beam-Deposition (EBD) procedure of Fe{sub 1{minus}x}Mn{sub x}Si{sub 2} (x < {approximately}0.1) at room temperature and subsequent annealing at 900 C for 1--120 min, where FeSi{sub 2} ingots added with Mn({approximately}10%) were used as starting materials. The other is a {sup 55}Mn{sup +}-implantation into {beta}-FeSi{sub 2} layers formed by EBD and subsequent annealing at 850 C for 1--120 min. From van der Pauw measurements, p-type {beta}-Fe{sub 1{minus}x}Mn{sub x}Si{sub 2} layers with the resistivity of 0.0036--0.031 {Omega}{center{underscore}dot}cm and hole mobility of 11.9--89.0 cm{sup 2}/V{center{underscore}dot}sec were found to be successfully formed on n-Si substrates by both doping methods. The p-n diode characteristics of these heterostructure diodes were investigated by I-V and C-V measurements. The results indicate that the carrier distribution does not agree with either ideal one-side step or one-side slop junctions, although optical transmittance and reflectance measurements indicate that the silicide/Si interface is of good quality.

  5. Correlation Among Six Biologic Factors (p53, p21WAF1, MIB-1, EGFR, HER2, and Bcl-2) and Clinical Outcomes After Curative Chemoradiation Therapy in Squamous Cell Cervical Cancer

    International Nuclear Information System (INIS)

    Yamashita, Hideomi; Murakami, Naoya; Asari, Takao; Okuma, Kae; Ohtomo, Kuni; Nakagawa, Keiichi

    2009-01-01

    Purpose: The expressions of six cell-cycle-associated proteins were analyzed in cervical squamous cell carcinomas in correlation in a search for prognostic correlations in tumors treated with concurrent chemoradiation therapy (cCRT). Methods and Materials: The expressions of p53, p21/waf1/cip1, molecular immunology borstel-1 (MIB-1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2), and Bcl-2 were studied using an immunohistochemical method in 57 cases of cervical squamous cell carcinoma treated with cCRT. Patients received cCRT between 1998 and 2005. The mean patient age was 61 years (range, 27-82 years). The number of patients with Stage II, III, and IVA disease was 18, 29, and 10, respectively. Results: The number of patients with tumors positive for p53, p21/waf1/cip1, MIB-1, EGFR, HER2, and Bcl-2 was 26, 24, 49, 26, 13, and 11, respectively; no significant correlation was noted. The 5-year overall survival rates of HER2-positive and -negative patients was 76% vs. 44%, which was of borderline significance (p = 0.0675). No significant correlation was noted between overall survival and expressions of p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2. No correlation was observed between local control and expression of any of the proteins. Conclusion: Expression of HER2 protein had a weak impact of borderline significance on overall survival in squamous cell carcinoma of the uterine cervix treated with cCRT. However, no clinical associations could be established for p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2 protein expressions.

  6. (p, p') and (p, n) reactions on halo nuclei

    International Nuclear Information System (INIS)

    Satou, Y; Nakamura, T; Fukuda, N; Sugimoto, T; Kondo, Y; Matsui, N; Hashimoto, Y; Nakabayashi, T; Okumura, T; Shinohara, M; Motobayashi, T; Yanagisawa, Y; Aoi, N; Takeuchi, S; Gomi, T; Togano, Y; Kawai, S; Sakurai, H; Ong, H J; Onishi, T K; Shimoura, S; Tamaki, M; Kobayashi, T; Otsu, H; Matsuda, Y; Endo, N; Kitayama, M; Ishihara, M

    2006-01-01

    We have measured the 1 H( 19 C, 18 C+n) 1 H and 1 H( 14 Be, 13 B+n)n reactions at 70 MeV/nucleon using the invariant mass method in inverse kinematics. A new state was identified at 1.49 MeV in 19 C. In the latter (p, n) reaction, a resonance peak corresponding to the 1.28 MeV state in 14 B recently reported in a beta-decay study was clearly observed. Forward peaked character in the differential cross section supports the 1 + assignment for this state

  7. Multi-species interactions impact the accumulation of weathered 2,2-bis (p-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE) from soil

    International Nuclear Information System (INIS)

    Kelsey, Jason W.; White, Jason C.

    2005-01-01

    The impact of interactions between the earthworms Eisenia foetida and Lumbricus terrestris and the plants Cucurbita pepo and Cucurbita maxima on the uptake of weathered p,p'-DDE from soil was determined. Although some combinations of earthworm and plant species caused significant changes in the p,p'-DDE burden in both organisms, the effects were species specific. Contaminant bioconcentration in C. pepo was increased slightly by E. foetida and by 3-fold when the plant was grown with L. terrestris. E. foetida had no effect on the contaminant BCF by C. maxima, but L. terrestris caused a 2-fold reduction in p,p'-DDE uptake by the plant. Contaminant levels in E. foetida and L. terrestris were unaffected by C. pepo. When grown with C. maxima, the concentration of p,p'-DDE decreased by approximately 4-fold and 7-fold in E. foetida and L. terrestris, respectively. The data suggest that the prediction of contaminant bioavailability should consider interactions among species. - Interactions between earthworms and plants affect both the phytoextraction and bioaccumulation of p,p'-DDE in soil

  8. A hierarchical coarse-grained (all-atom to all residue) approach to peptides (P1, P2) binding with a graphene sheet

    Science.gov (United States)

    Pandey, Ras; Kuang, Zhifeng; Farmer, Barry; Kim, Sang; Naik, Rajesh

    2012-02-01

    Recently, Kim et al. [1] have found that peptides P1: HSSYWYAFNNKT and P2: EPLQLKM bind selectively to graphene surfaces and edges respectively which are critical in modulating both the mechanical as well as electronic transport properties of graphene. Such distinctions in binding sites (edge versus surface) observed in electron micrographs were verified by computer simulation by an all-atomic model that captures the pi-pi bonding. We propose a hierarchical approach that involves input from the all-atom Molecular Dynamics (MD) study (with atomistic detail) into a coarse-grained Monte Carlo simulation to extend this study further to a larger scale. The binding energy of a free amino acid with the graphene sheet from all-atom simulation is used in the interaction parameter for the coarse-grained approach. Peptide chain executes its stochastic motion with the Metropolis algorithm. We investigate a number of local and global physical quantities and find that peptide P1 is likely to bind more strongly to graphene sheet than P2 and that it is anchored by three residues ^4Y^5W^6Y. [1] S.N. Kim et al J. Am. Chem. Soc. 133, 14480 (2011).

  9. Andrographolide induces vascular smooth muscle cell apoptosis through a SHP-1-PP2A-p38MAPK-p53 cascade.

    Science.gov (United States)

    Chen, Yu-Ying; Hsieh, Cheng-Ying; Jayakumar, Thanasekaran; Lin, Kuan-Hung; Chou, Duen-Suey; Lu, Wan-Jung; Hsu, Ming-Jen; Sheu, Joen-Rong

    2014-07-10

    The abnormal growth of vascular smooth muscle cells (VSMCs) is considered a critical pathogenic process in inflammatory vascular diseases. We have previously demonstrated that protein phosphatase 2 A (PP2A)-mediated NF-κB dephosphorylation contributes to the anti-inflammatory properties of andrographolide, a novel NF-κB inhibitor. In this study, we investigated whether andrographolide causes apoptosis, and characterized its apoptotic mechanisms in rat VSMCs. Andrographolide activated the p38 mitogen-activated protein kinase (p38MAPK), leading to p53 phosphorylation. Phosphorylated p53 subsequently transactivated the expression of Bax, a pro-apoptotic protein. Transfection with pp2a small interfering RNA (siRNA) suppressed andrographolide-induced p38MAPK activation, p53 phosphorylation, and caspase 3 activation. Andrographolide also activated the Src homology 1 domain-containing protein tyrosine phosphatase (SHP-1), and induced PP2A dephosphorylation, both of which were inhibited by the SHP-1 inhibitor sodium stibogluconate (SSG) or shp-1 siRNA. SSG or shp-1 siRNA prevented andrographolide-induced apoptosis. These results suggest that andrographolide activates the PP2A-p38MAPK-p53-Bax cascade, causing mitochondrial dysfunction and VSMC death through an SHP-1-dependent mechanism.

  10. Sphingosine kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis is involved in liver fibrosis-associated angiogenesis.

    Science.gov (United States)

    Yang, Le; Yue, Shi; Yang, Lin; Liu, Xin; Han, Zhen; Zhang, Yuanyuan; Li, Liying

    2013-07-01

    Sphingosine kinase (SphK)/sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) axis is involved in multiple biological processes, including liver fibrosis. Angiogenesis is an important pathophysiological process closely associated with liver fibrosis; however, the functional role of SphK/S1P/S1PR in this process remains incompletely defined. Bile duct ligation or carbon tetrachloride was used to induce liver fibrosis in mice. Human fibrotic samples were obtained from livers of patients undergoing liver transplantation. S1P levels in the liver were examined by HPLC. Expression of angiogenic markers, including angiopoietin 1, CD31, vascular cell adhesion molecule-1, and von Willebrand factor, was characterized by immunofluorescence, real-time RT-PCR, and Western blot in the fibrotic liver and primary mouse hepatic stellate cells (HSCs). SphK inhibitor (SKI) or S1PR antagonists were administered intraperitoneally in mice. S1P levels in the liver were closely correlated with mRNA expression of angiogenic markers. Ang1 is expressed in activated HSCs of the fibrotic liver and in primary HSCs. In HSCs, by using specific antagonists or siRNAs, we demonstrated S1P stimulation induced Ang1 expression via S1PR1 and S1PR3. In vivo, S1P reduction by SKI inhibited angiogenesis in fibrotic mice. Furthermore, S1PR1/3 antagonist significantly blocked upregulation of angiogenic markers in the injured liver, and attenuated the extent of liver fibrosis, while S1PR2 antagonist had no effect on angiogenesis, supporting the key role of S1PR1 and S1PR3 in angiogenesis underlying liver fibrosis process. SphK1/S1P/S1PR1/3 axis plays a crucial role in the angiogenic process required for fibrosis development, which may represent an effective therapeutic strategy for liver fibrosis. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  11. Theoretical study on the N-demethylation mechanism of theobromine catalyzed by P450 isoenzyme 1A2.

    Science.gov (United States)

    Tao, Jing; Kang, Yuan; Xue, Zhiyu; Wang, Yongting; Zhang, Yan; Chen, Qiu; Chen, Zeqin; Xue, Ying

    2015-09-01

    Theobromine, a widely consumed pharmacological active substance, can cause undesirable muscle stiffness, nausea and anorexia in high doses ingestion. The main N-demethylation metabolic mechanism of theobromine catalyzed by P450 isoenzyme 1A2 (CYP1A2) has been explored in this work using the unrestricted hybrid density functional method UB3LYP in conjunction with the LACVP(Fe)/6-31G (H, C, N, O, S, Cl) basis set. Single-point calculations including empirical dispersion corrections were carried out at the higher 6-311++G** basis set. Two N-demethylation pathways were characterized, i.e., 3-N and 7-N demethylations, which involve the initial N-methyl hydroxylation to form carbinolamines and the subsequent carbinolamines decomposition to yield monomethylxanthines and formaldehydes. Our results have shown that the rate-limiting N-methyl hydroxylation occurs via a hydrogen atom transfer (HAT) mechanism, which proceeds in a spin-selective mechanism (SSM) in the gas phase. The carbinolamines generated are prone to decomposition via the contiguous heteroatom-assisted proton-transfer. Strikingly, 3-N demethylation is more favorable than 7-N demethylation due to its lower free energy barrier and 7-methylxanthine therefore is the optimum product reported for the demethylation of theobromine catalyzed by CYP1A2, which are in good agreement with the experimental observation. This work has first revealed the detail N-demethylation mechanisms of theobromine at the theoretical level. It can offer more significant information for the metabolism of purine alkaloid. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Correlation between expression of p53, p21/WAF1, and MDM2 proteins and their prognostic significance in primary hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Fu Jia

    2009-12-01

    Full Text Available Abstract Background Tumor Protein p53 (p53, cyclin-dependent kinase inhibitor 1A (p21/WAF1, and murine double minute 2 (MDM2 participate in the regulation of cell growth. Altered expression of these gene products has been found in malignant tumors and has been associated with poor prognosis. Our aim was to investigate the expression of the 3 proteins in hepatocellular carcinoma (HCC and their prognostic significance. Methods We examined p53, p21/WAF1, and MDM2 expression in 181 pairs of HCC tissues and the adjacent hepatic tissues by performing immunohistochemistry and examined the expression of the 3 proteins in 7 pairs of HCC tissues and the adjacent hepatic tissues by using western blot analysis. Results The expression of p53, p21/WAF1, and MDM2 in the HCC tissues was significantly higher than those in the adjacent hepatic tissues (P P = 0.008. A statistical correlation was observed between expression of p53 and p21/WAF1 (R = 0.380, P = 0.000, p53 and MDM2 (R = 0.299, P = 0.000, p21/WAF1 and MDM2 (R = 0.285, P = 0.000 in 181 liver tissues adjacent to the tumor. Patients with a low pathologic grade HCC (I+II had a higher tendency to express p53 on tumor cells than the patients with high pathologic grade HCC (III+IV (P = 0.007. Survival analysis showed that positive p21/WAF1 expression or/and negative MDM2 expression in HCC was a predictor of better survival of patients after tumor resection (P Conclusions The proteins p53, p21/WAF1, and MDM2 were overexpressed in all the HCC cases in this study, and p53 and p21/WAF1 overexpression were positively correlated. The expression of p21/WAF1 and MDM2 can be considered as 2 useful indicators for predicting the prognosis of HCC.

  13. ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain.

    Directory of Open Access Journals (Sweden)

    Wei Sheng Chia

    Full Text Available p97/Valosin-containing protein (VCP is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD. It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell.

  14. ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain.

    Science.gov (United States)

    Chia, Wei Sheng; Chia, Diana Xueqi; Rao, Feng; Bar Nun, Shoshana; Geifman Shochat, Susana

    2012-01-01

    p97/Valosin-containing protein (VCP) is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD). It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell.

  15. 1P autoionization states of He in the elastic scattering region

    International Nuclear Information System (INIS)

    Chen, I.H.

    1975-01-01

    Following the method of Feshbach projection operator formalism, 1 P autoionization states of He in the n = 1 to n = 2 energy region was investigated. Variational functionals are constructed for solving the closed channel components and these results are compared with the absorption spectrum measured by Madden and Codling. In the open channel components the Coulomb wave function is used. Together with closed channel components, we calculate the line width of 1 P and 3 P resonance states. Comparison of these results with the previous calculation and with experimental data is also discussed

  16. H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion.

    Science.gov (United States)

    Baumann, Jan; Kouassi, Nancy Mounogou; Foni, Emanuela; Klenk, Hans-Dieter; Matrosovich, Mikhail

    2016-02-01

    The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions-T492S, N722D, R752K, and S1132F-were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. Continuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in the HA, which decreased

  17. Ruddlesden-Popper compounds (SrO)(LaFeO3)n (n = 1 and 2) as p-type semiconductors for photocatalytic hydrogen production

    International Nuclear Information System (INIS)

    Chen, Hongmei; Sun, Xiaoqin; Xu, Xiaoxiang

    2017-01-01

    Graphical abstract: Two layered ferrites LaSrFeO 4 and La 2 SrFe 2 O 7 have been investigated which demonstrate interesting p-type semconductivity and efficient hydrogen production from water. Display Omitted -- Abstract: Here we report two Ruddlesden-Popper type ferrite perovskites (SrO)(LaFeO 3 ) n (n = 1 and 2) which demonstrate p-type semiconductivity. Their crystal structure, optical absorption and other physicochemical properties have been systematically explored. Our results show that both ferrites crystallize in tetragonal symmetry with structural lamination along c axis. Efficient photocatalytic hydrogen production has been achieved for both samples under full range and visible light illumination. Better performance is noticed for LaSrFeO 4 with apparent quantum efficiency approaches 0.31% and 0.19% under full range and visible light illumination, respectively. The p-type semiconductivity is verified by their cathodic photocurrent as well as negative Mott-Schottky slop during Photoelectrochemical measurement. The relative lower activity for La 2 SrFe 2 O 7 compared to LaSrFeO 4 is likely due to its higher defect concentration which facilitates charge recombination. Both compounds exhibit anisotropic phenomenon for charge migrations according to theoretical calculations. Their p-type semiconductivity, strong visible light absorption, chemical inertness and high abundance of constituent elements signify promising applications in the field of solar energy conversion and optoelectronics.

  18. Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration.

    Science.gov (United States)

    Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter; Schulze, Tobias

    2017-01-01

    Introduction . Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P 1-5 ) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods . Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results . All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P 1 . In contrast, M1-polarized macrophages significantly downregulated S1P 4 . The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion . The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.

  19. De novo duplication of 17p13.1-p13.2 in a patient with intellectual disability and obesity.

    Science.gov (United States)

    Kuroda, Yukiko; Ohashi, Ikuko; Tominaga, Makiko; Saito, Toshiyuki; Nagai, Jun-Ichi; Ida, Kazumi; Naruto, Takuya; Masuno, Mitsuo; Kurosawa, Kenji

    2014-06-01

    17p13.1 Deletion encompassing TP53 has been described as a syndrome characterized by intellectual disability and dysmorphic features. Only one case with a 17p13.1 duplication encompassing TP53 has been reported in a patient with intellectual disability, seizures, obesity, and diabetes mellitus. Here, we present a patient with a 17p13.1 duplication who exhibited obesity and intellectual disability, similar to the previous report. The 9-year-old proposita was referred for the evaluation of intellectual disability and obesity. She also exhibited insulin resistance and liver dysfunction. She had wide palpebral fissures, upturned nostrils, a long mandible, short and slender fingers, and skin hyperpigmentation. Array comparative genomic hybridization (array CGH) detected a 3.2 Mb duplication of 17p13.1-p13.2 encompassing TP53, FXR2, NLGN2, and SLC2A4, which encodes the insulin-responsive glucose transporter 4 (GLUT4) associated with insulin-stimulated glucose uptake in adipocytes and muscle. We suggest that 17p13.1 duplication may represent a clinically recognizable condition characterized partially by a characteristic facial phenotype, developmental delay, and obesity. © 2014 Wiley Periodicals, Inc.

  20. P2X7 receptor activates extracellular signal-regulated kinases ERK1 and ERK2 independently of Ca2+ influx

    DEFF Research Database (Denmark)

    Amstrup, Jan; Novak, Ivana

    2003-01-01

    P2X7 nucleotide receptors modulate a spectrum of cellular events in various cells including epithelia, such as exocrine pancreas. Although the pharmacology and channel properties of the P2X7 receptors have been studied intensively, signal transduction pathways are relatively unknown. In this study...... we applied a heterologous expression system of rat P2X7 receptors in HEK-293 cells. We followed the receptor expression and function using the enhanced green fluorescent protein (EGFP) tag, activation of intracellular proteins and increases in cellular Ca2+. EGFP-P2X7 receptors localized...... to the plasma membrane, clusters within the membrane and intracellularly. Stimulation of P2X7 receptors in HEK-293 cells led to an activation of extracellular signal-regulated kinases ERK1 and ERK2 and this activation was seen after just 1 min of stimulation with ATP. Using C- and N-terminal P2X7-receptor...

  1. Quantum state-to-state dynamics for the quenching process of Br(2P1/2) + H2(v(i) = 0, 1, j(i) = 0).

    Science.gov (United States)

    Xie, Changjian; Jiang, Bin; Xie, Daiqian; Sun, Zhigang

    2012-03-21

    Quantum state-to-state dynamics for the quenching process Br((2)P(1/2)) + H(2)(v(i) = 0, 1, j(i) = 0) → Br((2)P(3/2)) + H(2)(v(f), j(f)) has been studied based on two-state model on the recent coupled potential energy surfaces. It was found that the quenching probabilities have some oscillatory structures due to the interference of reflected flux in the Br((2)P(1/2)) + H(2) and Br((2)P(3/2)) + H(2) channels by repulsive potential in the near-resonant electronic-to-vibrational energy transfer process. The final vibrational state resolved integral cross sections were found to be dominated by the quenching process Br((2)P(1/2)) + H(2)(v) → Br((2)P(3/2)) + H(2)(v+1) and the nonadiabatic reaction probabilities for Br((2)P(1/2)) + H(2)(v = 0, 1, j(i) = 0) are quite small, which are consistent with previous theoretical and experimental results. Our calculated total quenching rate constant for Br((2)P(1/2)) + H(2)(v(i) = 0, j(i) = 0) at room temperature is in good agreement with the available experimental data. © 2012 American Institute of Physics

  2. (+-Chlorido[(1,2,3,4-η;κP2′-2′-diphenylphosphanyl-2-diphenylphosphoryl-1,1′-binaphthyl]rhodium(I methanol monosolvate

    Directory of Open Access Journals (Sweden)

    Hans-Joachim Drexler

    2012-03-01

    Full Text Available In the title complex, [RhCl(C44H32OP2]·CH3OH, the RhI ion is coordinated by a naphthyl group of a partially oxidized 2,2′-bis(diphenylphosphanyl-1,1′-binaphthyl (BINAP ligand in a η4 mode, one P atom of the diphenylphosphanyl group and one Cl atom. The P=O group does not interact with the RhI ion but accepts an O—H...O hydrogen bond from the methanol solvent molecule.

  3. Backup Expression of the PhaP2 Phasin Compensates for phaP1 Deletion in Herbaspirillum seropedicae, Maintaining Fitness and PHB Accumulation.

    Science.gov (United States)

    Alves, Luis P S; Teixeira, Cícero S; Tirapelle, Evandro F; Donatti, Lucélia; Tadra-Sfeir, Michelle Z; Steffens, Maria B R; de Souza, Emanuel M; de Oliveira Pedrosa, Fabio; Chubatsu, Leda S; Müller-Santos, Marcelo

    2016-01-01

    Phasins are important proteins controlling poly-3-hydroxybutyrate (PHB) granules formation, their number into the cell and stability. The genome sequencing of the endophytic and diazotrophic bacterium Herbaspirillum seropedicae SmR1 revealed two homologous phasin genes. To verify the role of the phasins on PHB accumulation in the parental strain H. seropedicae SmR1, isogenic strains defective in the expression of phaP1, phaP2 or both genes were obtained by gene deletion and characterized in this work. Despite of the high sequence similarity between PhaP1 and PhaP2, PhaP1 is the major phasin in H. seropedicae, since its deletion reduced PHB accumulation by ≈50% in comparison to the parental and ΔphaP2. Upon deletion of phaP1, the expression of phaP2 was sixfold enhanced in the ΔphaP1 strain. The responsive backup expression of phaP2 partially rescued the ΔphaP1 mutant, maintaining about 50% of the parental PHB level. The double mutant ΔphaP1.2 did not accumulate PHB in any growth stage and showed a severe reduction of growth when glucose was the carbon source, a clear demonstration of negative impact in the fitness. The co-occurrence of phaP1 and phaP2 homologous in bacteria relatives of H. seropedicae, including other endophytes, indicates that the mechanism of phasin compensation by phaP2 expression may be operating in other organisms, showing that PHB metabolism is a key factor to adaptation and efficiency of endophytic bacteria.

  4. /sup 15/N(p,. cap alpha. )/sup 12/C reaction with polarized protons from 0. 34 to 1. 21 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Pepper, G H; Brown, L [Carnegie Institution of Washington, D.C. (USA). Dept. of Terrestrial Magnetism

    1976-03-29

    A polarized beam was used to measure angular distributions of the analyzing power of the /sup 15/N(p,..cap alpha..)/sup 12/C reaction at 0.34 MeV and at five energies from 0.92 to 1.21 MeV. The analyzing power can be fitted with associated Legendre polynomials, P/sub 1//sup 1/ and P/sub 2//sup 1/ sufficing to describe the results except near 1.2 MeV where P/sub 3//sup 1/ is also required. Polarization excitation functions were measured throughout the entire energy range at angles where the polynomials P/sub 2//sup 1/ and P/sub 3//sup 1/ are zero. A polarization contour map is given.

  5. [1,3-Bis(diphenylphosphinopentane-κ2P,P′]tetracarbonylchromium(0

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available In the title compound, [Cr(C29H30P2(CO4], the Cr atom is octahedrally coordinated by four carbonyl ligands and one bidentate phosphine ligand, which is bounded as a chelate in a cis position. The average Cr—P and Cr—C bond lengths are 2.377 and 1.865 Å, respectively.

  6. Studies of a series of [Ni(P(R)2N(Ph)2)2(CH3CN)]2+ complexes as electrocatalysts for H2 production: substituent variation at the phosphorus atom of the P2N2 ligand.

    Science.gov (United States)

    Kilgore, Uriah J; Stewart, Michael P; Helm, Monte L; Dougherty, William G; Kassel, W Scott; DuBois, Mary Rakowski; DuBois, Daniel L; Bullock, R Morris

    2011-11-07

    A series of [Ni(P(R)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) complexes containing the cyclic diphosphine ligands [P(R)(2)N(Ph)(2) = 1,5-diaza-3,7-diphosphacyclooctane; R = benzyl (Bn), n-butyl (n-Bu), 2-phenylethyl (PE), 2,4,4-trimethylpentyl (TP), and cyclohexyl (Cy)] have been synthesized and characterized. X-ray diffraction studies reveal that the cations of [Ni(P(Bn)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) and [Ni(P(n-Bu)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) have distorted trigonal bipyramidal geometries. The Ni(0) complex [Ni(P(Bn)(2)N(Ph)(2))(2)] was also synthesized and characterized by X-ray diffraction studies and shown to have a distorted tetrahedral structure. These complexes, with the exception of [Ni(P(Cy)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2), all exhibit reversible electron transfer processes for both the Ni(II/I) and Ni(I/0) couples and are electrocatalysts for the production of H(2) in acidic acetonitrile solutions. The heterolytic cleavage of H(2) by [Ni(P(R)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) complexes in the presence of p-anisidine or p-bromoaniline was used to determine the hydride donor abilities of the corresponding [HNi(P(R)(2)N(Ph)(2))(2)](BF(4)) complexes. However, for the catalysts with the most bulky R groups, the turnover frequencies do not parallel the driving force for elimination of H(2), suggesting that steric interactions between the alkyl substituents on phosphorus and the nitrogen atom of the pendant amines play an important role in determining the overall catalytic rate. © 2011 American Chemical Society

  7. Sp1/3 and NF-1 mediate basal transcription of the human P2X1 gene in megakaryoblastic MEG-01 cells

    Directory of Open Access Journals (Sweden)

    Ennion Steven J

    2006-03-01

    Full Text Available Abstract Background P2X1 receptors play an important role in platelet function as they can induce shape change, granule centralization and are also involved in thrombus formation. As platelets have no nuclei, the level of P2X1 expression depends on transcriptional regulation in megakaryocytes, the platelet precursor cell. Since nothing is known about the molecular mechanisms regulating megakaryocytic P2X1 expression, this study aimed to identify and functionally characterize the P2X1 core promoter utilized in the human megakaryoblastic cell line MEG-01. Results In order to identify cis-acting elements involved in the transcriptional regulation of P2X1 expression, the ability of 4.7 kb P2X1 upstream sequence to drive luciferase reporter gene expression was tested. Low promoter activity was detected in proliferating MEG-01 cells. This activity increased 20-fold after phorbol-12-myristate-13-acetate (PMA induced differentiation. A transcription start site was detected 365 bp upstream of the start codon by primer extension. Deletion analysis of reporter constructs indicated a core promoter located within the region -68 to +149 bp that contained two Sp1 sites (named Sp1a and Sp1b and an NF-1 site. Individual mutations of Sp1b or NF-1 binding sites severely reduced promoter activity whereas triple mutation of Sp1a, Sp1b and NF-1 sites completely abolished promoter activity in both untreated and PMA treated cells. Sp1/3 and NF-1 proteins were shown to bind their respective sites by EMSA and interaction of Sp1/3, NF-1 and TFIIB with the endogenous P2X1 core promoter in MEG-01 cells was demonstrated by chromatin immunoprecipitation. Alignment of P2X1 genes from human, chimp, rat, mouse and dog revealed consensus Sp1a, Sp1b and NF-1 binding sites in equivalent positions thereby demonstrating evolutionary conservation of these functionally important sites. Conclusion This study has identified and characterized the P2X1 promoter utilized in MEG-01 cells and

  8. Resilience to audiogenic seizures is associated with p-ERK1/2 dephosphorylation in the subiculum of Fmr1 knockout mice

    Directory of Open Access Journals (Sweden)

    Giulia eCuria

    2013-04-01

    Full Text Available Young, but not adult, Fmr1 knockout (KO mice display audiogenic seizures (AGS that can be prevented by inhibiting extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation. In order to identify the cerebral regions involved in these phenomena, we characterized the response to AGS in Fmr1 KO mice and wild type (WT controls at postnatal day (P 45 and P90. To characterize the diverse response to AGS in various cerebral regions, we evaluated the activity markers FosB/ΔFosB and phosphorylated ERK1/2 (p-ERK1/2. Wild running (100% of tested mice followed by clonic/tonic seizures (30% were observed in P45 Fmr1 KO mice, but not in WT mice. In P90 Fmr1 KO mice, wild running was only present in 25% of tested animals. Basal FosB/ΔFosB immunoreactivity was higher (P<0.01 vs WT in the CA1 and subiculum of P45 Fmr1 KO mice. Following the AGS test, FosB/ΔFosB expression consistently increased in most of the analyzed regions in both groups at P45, but not at P90. Interestingly, FosB/ΔFosB immunoreactivity was significantly higher in P45 Fmr1 KO mice in the medial geniculate body (P<0.05 vs WT and CA3 (P<0.01. Neurons presenting with immunopositivity to p-ERK1/2 were more abundant in the subiculum of Fmr1 KO mice in control condition (P<0.05 vs WT, in both age groups. In this region, p-ERK1/2-immunopositive cells significantly decreased (-75%, P<0.01 in P90 Fmr1 KO mice exposed to the AGS test, but no changes were found in P45 mice or in other brain regions. In both age groups of WT mice, p-ERK1/2-immunopositive cells increased in the subiculum after exposure to the acoustic test. Our findings illustrate that FosB/ΔFosB markers are overexpressed in the medial geniculate body and CA3 in Fmr1 KO mice experiencing AGS, and that p-ERK1/2 is markedly decreased in the subiculum of Fmr1 KO mice resistant to AGS induction. These findings suggest that resilience to AGS is associated with dephosphorylation of p-ERK1/2 in the subiculum of mature Fmr1 KO mice.

  9. Effects of a low-energy proton irradiation on n+/p-AlInGaP solar cells

    International Nuclear Information System (INIS)

    Lee, H.S.; Yamaguchi, M.; Ekins-Daukes, N.J.; Khan, A.; Takamoto, T.; Imaizumi, M.; Ohshima, T.; Itoh, H.

    2006-01-01

    For the first time, by deep-level transient spectroscopy, 30keV proton irradiation-induced defects in n + /p-AlInGaP solar cells have been observed. After the 30keV proton irradiation, new deep-level defects such as two majority-carrier (hole) traps HP1 (E V +0.98eV, N T =3.8x10 14 cm -3 ) and HP2, and two minority-carrier (electron) traps EP1 (E C -0.71eV, N T =2.0x10 15 cm -3 ) and EP2 have been observed in p-AlInGaP. The introduction rate of majority-carrier trap center (HP1) is 380cm -1 , which is lower than that (1500cm -1 ) in 100keV proton-irradiated p-InGaP. From the minority-carrier injection annealing for HP1 defect and carrier concentration in 30keV proton-irradiated p-AlInGaP, HP1 defect is likely to act as a recombination center as well as a compensator center

  10. Hunt for the 11P1 bound state of charmonium

    International Nuclear Information System (INIS)

    Porter, F.C.

    1982-02-01

    Using the Crystal Ball detector at SPEAR, we have looked for evidence of the isospin-violating decay psi' → π 01 P 1 , where 1 P 1 is the predicted spin-singlet p-wave bound state of charmonium. For a 1 P 1 state at the predicted mass (approx. 3520 MeV), we obtain the 95% confidence level limits: BR(psi' → π 01 P 1 ) 01 P 1 )BR( 1 P 1 → γn/sub c/ < 0.14%. These limits are compared with simple theoretical predictions

  11. Smad3 deficiency leads to mandibular condyle degradation via the sphingosine 1-phosphate (S1P)/S1P3 signaling axis.

    Science.gov (United States)

    Mori, Hiroki; Izawa, Takashi; Tanaka, Eiji

    2015-10-01

    Temporomandibular joint osteoarthritis is a degenerative disease that is characterized by permanent cartilage destruction. Transforming growth factor (TGF)-β is one of the most abundant cytokines in the bone matrix and is shown to regulate the migration of osteoprogenitor cells. It is hypothesized that TGF-β/Smad3 signaling affects cartilage homeostasis by influencing sphingosine 1-phosphate (S1P)/S1P receptor signaling and chondrocyte migration. We therefore investigated the molecular mechanisms by which crosstalk may occur between TGF-β/Smad3 and S1P/S1P receptor signaling to maintain condylar cartilage and to prevent temporomandibular joint osteoarthritis. Abnormalities in the condylar subchondral bone, including dynamic changes in bone mineral density and microstructure, were observed in Smad3(-/-) mice by microcomputed tomography. Cell-free regions and proteoglycan loss characterized the cartilage degradation present, and increased numbers of apoptotic chondrocytes and matrix metalloproteinase 13(+) chondrocytes were also detected. Furthermore, expression of S1P receptor 3 (S1P3), but not S1P1 or S1P2, was significantly down-regulated in the condylar cartilage of Smad3(-/-) mice. By using RNA interference technology and pharmacologic tools, S1P was found to transactivate Smad3 in an S1P3/TGF-β type II receptor-dependent manner, and S1P3 was found to be required for TGF-β-induced migration of chondrocyte cells and downstream signal transduction via Rac1, RhoA, and Cdc42. Taken together, these results indicate that the Smad3/S1P3 signaling pathway plays an important role in the pathogenesis of temporomandibular joint osteoarthritis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  12. Meiotic and pedigree segregation analyses in carriers of t(4;8)(p16;p23.1) differing in localization of breakpoint positions at 4p subband 4p16.3 and 4p16.1.

    Science.gov (United States)

    Midro, Alina T; Zollino, Marcella; Wiland, Ewa; Panasiuk, Barbara; Iwanowski, Piotr S; Murdolo, Marina; Śmigiel, Robert; Sąsiadek, Maria; Pilch, Jacek; Kurpisz, Maciej

    2016-02-01

    The purpose of this study was to compare meiotic segregation in sperm cells from two carriers with t(4;8)(p16;p23.1) reciprocal chromosome translocations (RCTs), differing in localization of the breakpoint positions at the 4p subband-namely, 4p16.3 (carrier 1) and 4p16.1 (carrier 2)-and to compare data of the pedigree analyses performed by direct method. Three-color fluorescent in situ hybridization (FISH) on sperm cells and FISH mapping for the evaluation of the breakpoint positions, data from pedigrees, and direct segregation analysis of the pedigrees were performed. Similar proportions of normal/balanced and unbalanced sperm cells were found in both carriers. The most common was an alternate type of segregation (about 52 % and about 48 %, respectively). Unbalanced adjacent I and adjacent II karyotypes were found in similar proportions about 15 %. The direct segregation analysis (following Stengel-Rutkowski) of the pedigree of carriers of t(4;8)(p16.1;p23.1) was performed and results were compared with the data of the pedigree segregation analysis obtained earlier through the indirect method. The probability of live-born progeny with unbalanced karyotype for carriers of t(4;8)(p16.1;p23.1) was moderately high at 18.8 %-comparable to the value obtained using the indirect method for the same carriership, which was 12 %. This was, however, markedly lower than the value of 41.2 % obtained through the pedigree segregation indirect analysis estimated for carriers of t(4;8)(p16.3;p23.1), perhaps due to the unique composition of genes present within the 4p16.1-4p 16.3 region. Revealed differences in pedigree segregation analysis did not correspond to the very similar profile of meiotic segregation patterns presented by carrier 1 and carrier 2. Most probably, such discordances may be due to differences in embryo survival rates arising from different genetic backgrounds.

  13. Backup expression of the PhaP2 phasin compensates for phaP1 deletion in Herbaspirillum seropedicae, maintaining fitness and PHB accumulation

    Directory of Open Access Journals (Sweden)

    Luis Paulo Silveira Alves

    2016-05-01

    Full Text Available Phasins are important proteins controlling PHB granules formation, their number into the cell and stability. The genome sequencing of the endophytic and diazotrophic bacterium Herbaspirillum seropedicae SmR1 revealed two homologous phasin genes. To verify the role of the phasins on PHB accumulation in the parental strain H. seropedicae SmR1, isogenic strains defective in the expression of phaP1, phaP2 or both genes were obtained by gene deletion and characterized in this work. Despite of the high sequence similarity between PhaP1 and PhaP2, PhaP1 is the major phasin in H. seropedicae, since its deletion reduced PHB accumulation by ≈ 50 % in comparison to the parental and ΔphaP2. Upon deletion of phaP1, the expression of phaP2 was 6-fold enhanced in the ΔphaP1 strain. The responsive backup expression of phaP2 partially rescued the ΔphaP1 mutant, maintaining about 50% of the parental PHB level. The double mutant ΔphaP1.2 did not accumulate PHB in any growth stage and showed a severe reduction of growth when glucose was the carbon source, a clear demonstration of negative impact in the fitness. The co-occurrence of phaP1 and phaP2 homologous in bacteria relatives of H. seropedicae, including other endophytes, indicates that the mechanism of phasin compensation by phaP2 expression may be operating in other organisms, showing that PHB metabolism is a key factor to adaptation and efficiency of endophytic bacteria.

  14. Co-expression of human cytochrome P4501A1 (CYP1A1) variants and human NADPH-cytochrome P450 reductase in the baculovirus/insect cell system.

    Science.gov (United States)

    Schwarz, D; Kisselev, P; Honeck, H; Cascorbi, I; Schunck, W H; Roots, I

    2001-06-01

    1. Three human cytochrome P4501A1 (CYP1A1) variants, wild-type (CYP1A1.1), CYP1A1.2 (1462V) and CYP1A1.4 (T461N), were co-expressed with human NADPH-P450 reductase (OR) in Spodoptera frugiperda (Sf9) insect cells by baculovirus co-infection to elaborate a suitable system for studying the role of CYPA1 polymorphism in the metabolism of exogenous and endogenous substrates. 2. A wide range of conditions was examined to optimize co-expression with regard to such parameters as relative multiplicity of infection (MOI), time of harvest, haem precursor supplementation and post-translational stabilization. tinder optimized conditions, almost identical expression levels and molar OR/CYP1A1 ratios (20:1) were attained for all CYP1A1 variants. 3. Microsomes isolated from co-infected cells demonstrated ethoxyresorufin deethlylase activities (nmol/min(-1) nmol(-1) CYP1A1) of 16.0 (CYP1A1.1), 20.5 (CYP1A1.2) and 22.5 (CYP1A1.4). Pentoxyresorufin was dealkylated approximately 10-20 times slower with all enzyme variants. 4. All three CYP1A1 variants were active in metabolizing the precarcinogen benzo[a]pyrene (B[a]P), with wild-type enzyme showing the highest activity, followed by CYP1A1.4 (60%) and CYP1A1.2 (40%). Each variant produced all major metabolites including B[a]P-7,8-dihydrodiol, the precursor of the ultimate carcinogenic species. 5. These studies demonstrate that the baculovirus-mediated co-expression-by-co-infection approach all CYP1A1 variants yields functionally active enzyme systems with similar molar OR/CYP1A1 ratios, thus providing suitable preconditions to examine the metabolism of and environmental chemicals by the different CY1A1 variants.

  15. Strong decays of the 1 P and 2 D doubly charmed states

    Science.gov (United States)

    Xiao, Li-Ye; Lü, Qi-Fang; Zhu, Shi-Lin

    2018-04-01

    We perform a systematical investigation of the strong decay properties of the low-lying 1 P - and 2 D -wave doubly charmed baryons with the 3P0 quark pair creation model. The main predictions include: (i) in the Ξc c and Ωc c family, the 1 P ρ mode excitations with JP=1 /2- and 3 /2- should be the fairly narrow states, while, for the 1 P λ mode excitations, they are most likely to be moderate states with a width of Γ ˜100 MeV . (ii) The 2 Dρ ρ states mainly decay via emitting a heavy-light meson and the decay widths can reach several tens MeV if their masses are above the threshold of ΛcD or ΞcD , respectively. The 2 Dλ λ states may be broad states with a width of Γ >100 MeV .

  16. High Glucose Concentration Stimulates NHE-1 Activity in Distal Nephron Cells: the Role of the Mek/Erk1/2/p90RSK and p38MAPK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Juliana Martins da Costa-Pessoa

    2014-02-01

    Full Text Available Aims: In models of diabetes, distal nephron cells contribute to glucose uptake and oxidation. How these cells contribute to the use of glucose for the regulation of H+ extrusion remains unknown. We used Madin-Darby Canine Kidney (MDCK cells to investigate the effect of acute or chronic high glucose concentration on the abundance and activity of the Na+/H+ exchanger (NHE-1. Methods: Using RT-PCR, we also evaluated the mRNA expression for sodium glucose co-transporters SGLT1 and SGLT2. Protein abundance was analyzed using immunoblotting, and intracellular pH (pHi recovery was evaluated using microscopy in conjunction with the fluorescent probe BCECF/AM. The Na+-dependent pHi recovery rate was monitored with HOE-694 (50 µM and/or S3226 (10 µM, specific NHE-1 and NHE-3 inhibitors. Results: MDCK cells did not express the mRNA for SGLT1 or SGLT2 but did express the GLUT2, NHE-1 and NHE-3 proteins. Under control conditions, we observed a greater contribution of NHE-1 to pHi recovery relative to the other H+ transporters. Acute high glucose treatment increased the HOE-694-sensitive pHi recovery rate and p-Erk1/2 and p90RSK abundance. These parameters were reduced by PD-98059, a Mek inhibitor (1 µM. Chronic high glucose treatment also increased the HOE-694-sensitive pHi recovery rate and p-p38MAPK abundance. Both parameters were reduced by SB-203580, a p38MAPK inhibitor (10 µM. Conclusion: These results suggested that extracellular high glucose stimulated NHE-1 acutely and chronically through Mek/Erk1/2/p90RSK and p38MAPK pathways, respectively.

  17. Benzazole derivatives: V. The reactivity of some 2-p-tolyl-and 2-p-methylstyryl-benzimidazolium salts

    Directory of Open Access Journals (Sweden)

    Cernatescu Corina

    2004-01-01

    Full Text Available The reactivity of the p-substituted methyl group in 1-methyl-2-p-tolylbenzimidazolium and 1-methyl-2-p-methylstyrylbenzimidazolium iodides with p-nitroso-dimethylaniline (p-NDMA and aromatic aldehydes was studied. According to literature data on the steric effects produced by the bulky N-l methyl group, the 2-p-tolyl substituted salt does not react with p-NDMA. On the other hand, 2-p-methylstyryl substituted salts give condensation reactions, similarly to 1,2,3-trimethylbenzimidazolium iodides. The compounds obtained from the reaction with aromatic aldehydes can be used as dyeing substances, photosensitizers or as dienic monomers, due to the conjugated chain from C-2.

  18. Fis1, DLP1, and Pex11p coordinately regulate peroxisome morphogenesis

    International Nuclear Information System (INIS)

    Kobayashi, Shinta; Tanaka, Atsushi; Fujiki, Yukio

    2007-01-01

    Dynamin-like protein 1 (DLP1) and Pex11pβ function in morphogenesis of peroxisomes. In the present work, we investigated whether Fis1 is involved in fission of peroxisomes. Endogenous Fis1 was morphologically detected in peroxisomes as well as mitochondria in wild-type CHO-K1 and DLP1-defective ZP121 cells. Subcellular fractionation studies also revealed the presence of Fis1 in peroxisomes. Peroxisomal Fis1 showed the same topology, i.e., C-tail anchored membrane protein, as the mitochondrial one. Furthermore, ectopic expression of FIS1 induced peroxisome proliferation in CHO-K1 cells, while the interference of FIS1 RNA resulted in tubulation of peroxisomes, hence reducing the number of peroxisomes. Fis1 interacted with Pex11pβ, by direct binding apparently involving the C-terminal region of Pex11pβ in the interaction. Pex11pβ also interacted with each other, whereas the binding of Pex11pβ to DLP1 was not detectable. Moreover, ternary complexes comprising Fis1, Pex11pβ, and DLP1 were detected by chemical cross-linking. We also showed that the highly conserved N-terminal domain of Pex11pβ was required for the homo-oligomerization of Pex11pβ and indispensable for the peroxisome-proliferating activity. Taken together, these findings indicate that Fis1 plays important roles in peroxisome division and maintenance of peroxisome morphology in mammalian cells, possibly in a concerted manner with Pex11pβ and DLP1

  19. Toxicology and carcinogenesis studies of p,p'-dichlorophenyl sulfone (CAS No. 80-07-9) in F344/N rats and B6C3F1 mice (feed studies).

    Science.gov (United States)

    2001-09-01

    p,pN-Dichlorodiphenyl sulfone is used as a starting material in the production of polysulfones and polyethersulfones and as a component in reactive dyes in the textile industry; it is also a by-product of pesticide production. p,pN-Dichlorodiphenyl sulfone was nominated for study by the National Cancer Institute because of its history of high production and use, the prospect of increased production and use, and the absence of adequate toxicity testing. Male and female F344/N rats and B6C3F1 mice were exposed top,pN-dichlorodiphenyl sulfone (greater than 99% pure)in feed for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium,cultured Chinese hamster ovary cells, and mouse bone marrow. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were fed diets containing 0, 30, 100, 300, 1,000, or 3,000 ppm p,pN-dichlorodiphenyl sulfone (equivalent to average daily doses of approximately 2, 6, 19, 65, or 200 mgp,pN-dichlorodiphenyl sulfone/kg body weight) for 14 weeks. All rats survived until the end of the study. Mean body weights of groups exposed to 300 ppm or greater were significantly less than those of the controls. Liver weights of groups exposed to 100 ppm or greater and kidney weights of 1,000 and 3,000 ppm male rats were significantly greater than those of the controls. Centrilobular hepatocyte hypertrophy of the liver was observed in most male rats exposed to 100 ppm or greater and in all female rats exposed to 300 ppm or greater, and the severities were increased in 300 ppm males and 1,000 and 3,000 ppm males and females. The incidences of nephropathy in 1,000 and 3,000 ppm female rats were significantly increased. Dose-related increases in severity of nephropathy were observed in male rats. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were fed diets containing 0, 30, 100, 300, 1,000, or 3,000 ppm p,pN-dichlorodiphenyl sulfone (equivalent to average daily doses of approximately 3.5, 15, 50

  20. Significant Prognostic Factors for Completely Resected pN2 Non-small Cell Lung Cancer without Neoadjuvant Therapy

    Science.gov (United States)

    Nakao, Masayuki; Mun, Mingyon; Nakagawa, Ken; Nishio, Makoto; Ishikawa, Yuichi; Okumura, Sakae

    2015-01-01

    Purpose: To identify prognostic factors for pathologic N2 (pN2) non-small cell lung cancer (NSCLC) treated by surgical resection. Methods: Between 1990 and 2009, 287 patients with pN2 NSCLC underwent curative resection at the Cancer Institute Hospital without preoperative treatment. Results: The 5-year overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) rates were 46%, 55% and 24%, respectively. The median follow-up time was 80 months. Multivariate analysis identified four independent predictors for poor OS: multiple-zone mediastinal lymph node metastasis (hazard ratio [HR], 1.616; p = 0.003); ipsilateral intrapulmonary metastasis (HR, 1.042; p = 0.002); tumor size >30 mm (HR, 1.013; p = 0.002); and clinical stage N1 or N2 (HR, 1.051; p = 0.030). Multivariate analysis identified three independent predictors for poor RFS: multiple-zone mediastinal lymph node metastasis (HR, 1.457; p = 0.011); ipsilateral intrapulmonary metastasis (HR, 1.040; p = 0.002); and tumor size >30 mm (HR, 1.008; p = 0.032). Conclusion: Multiple-zone mediastinal lymph node metastasis, ipsilateral intrapulmonary metastasis, and tumor size >30 mm were common independent prognostic factors of OS, CSS, and RFS in pN2 NSCLC. PMID:25740454

  1. Bcl-2 protein expression is associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer

    International Nuclear Information System (INIS)

    Tsutsui, Shinichi; Yasuda, Kazuhiro; Suzuki, Kosuke; Takeuchi, Hideya; Nishizaki, Takashi; Higashi, Hidefumi; Era, Shoichi

    2006-01-01

    Recent experimental studies have shown that Bcl-2, which has been established as a key player in the control of apoptosis, plays a role in regulating the cell cycle and proliferation. The aim of this study was to investigate the relationship between Bcl-2 and p27 protein expression, p53 protein expression and the proliferation activity as defined by the MIB-1 counts. The prognostic implication of Bcl-2 protein expression in relation to p27 and p53 protein expressions and MIB-1 counts for breast cancer was also evaluated. The immunohistochemical expression of Bcl-2 protein was evaluated in a series of 249 invasive ductal carcinomas of the breast, in which p27 and p53 protein expressions and MIB-1 counts had been determined previously. The Bcl-2 protein expression was found to be decreased in 105 (42%) cases. A decreased Bcl-2 protein expression was significantly correlated with a nuclear grade of III, a negative estrogen receptor, a decreased p27 protein expression, a positive p53 protein expression, positive MIB-1 counts and a positive HER2 protein expression. The incidence of a nuclear grade of III and positive MIB-1 counts increased as the number of abnormal findings of Bcl-2, p27 and p53 protein expressions increased. A univariate analysis indicated a decreased Bcl-2 protein expression to be significantly (p = 0.0089) associated with a worse disease free survival (DFS), while a multivariate analysis indicated the lymph node status and MIB-1 counts to be independently significant prognostic factors for the DFS. The Bcl-2 protein expression has a close correlation with p27 and p53 protein expressions and the proliferation activity determined by MIB-1 counts in invasive ductal carcinoma of the breast. The prognostic value of Bcl-2 as well as p27 and p53 protein expressions was dependent on the proliferation activity in breast cancer

  2. Bcl-2 protein expression is associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer

    Directory of Open Access Journals (Sweden)

    Nishizaki Takashi

    2006-07-01

    Full Text Available Abstract Background Recent experimental studies have shown that Bcl-2, which has been established as a key player in the control of apoptosis, plays a role in regulating the cell cycle and proliferation. The aim of this study was to investigate the relationship between Bcl-2 and p27 protein expression, p53 protein expression and the proliferation activity as defined by the MIB-1 counts. The prognostic implication of Bcl-2 protein expression in relation to p27 and p53 protein expressions and MIB-1 counts for breast cancer was also evaluated. Methods The immunohistochemical expression of Bcl-2 protein was evaluated in a series of 249 invasive ductal carcinomas of the breast, in which p27 and p53 protein expressions and MIB-1 counts had been determined previously. Results The Bcl-2 protein expression was found to be decreased in 105 (42% cases. A decreased Bcl-2 protein expression was significantly correlated with a nuclear grade of III, a negative estrogen receptor, a decreased p27 protein expression, a positive p53 protein expression, positive MIB-1 counts and a positive HER2 protein expression. The incidence of a nuclear grade of III and positive MIB-1 counts increased as the number of abnormal findings of Bcl-2, p27 and p53 protein expressions increased. A univariate analysis indicated a decreased Bcl-2 protein expression to be significantly (p = 0.0089 associated with a worse disease free survival (DFS, while a multivariate analysis indicated the lymph node status and MIB-1 counts to be independently significant prognostic factors for the DFS. Conclusion The Bcl-2 protein expression has a close correlation with p27 and p53 protein expressions and the proliferation activity determined by MIB-1 counts in invasive ductal carcinoma of the breast. The prognostic value of Bcl-2 as well as p27 and p53 protein expressions was dependent on the proliferation activity in breast cancer.

  3. Role of Sphingosine Kinase 1 and S1P Transporter Spns2 in HGF-mediated Lamellipodia Formation in Lung Endothelium.

    Science.gov (United States)

    Fu, Panfeng; Ebenezer, David L; Berdyshev, Evgeny V; Bronova, Irina A; Shaaya, Mark; Harijith, Anantha; Natarajan, Viswanathan

    2016-12-30

    Hepatocyte growth factor (HGF) signaling via c-Met is known to promote endothelial cell motility and angiogenesis. We have previously reported that HGF stimulates lamellipodia formation and motility of human lung microvascular endothelial cells (HLMVECs) via PI3K/Akt signal transduction and reactive oxygen species generation. Here, we report a role for HGF-induced intracellular sphingosine-1-phosphate (S1P) generation catalyzed by sphingosine kinase 1 (SphK1), S1P transporter, spinster homolog 2 (Spns2), and S1P receptor, S1P 1 , in lamellipodia formation and perhaps motility of HLMVECs. HGF stimulated SphK1 phosphorylation and enhanced intracellular S1P levels in HLMVECs, which was blocked by inhibition of SphK1. HGF enhanced co-localization of SphK1/p-SphK1 with actin/cortactin in lamellipodia and down-regulation or inhibition of SphK1 attenuated HGF-induced lamellipodia formation in HLMVECs. In addition, down-regulation of Spns2 also suppressed HGF-induced lamellipodia formation, suggesting a key role for inside-out S1P signaling. The HGF-mediated phosphorylation of SphK1 and its localization in lamellipodia was dependent on c-Met and ERK1/2 signaling, but not the PI3K/Akt pathway; however, blocking PI3K/Akt signaling attenuated HGF-mediated phosphorylation of Spns2. Down-regulation of S1P 1 , but not S1P 2 or S1P 3 , with specific siRNA attenuated HGF-induced lamellipodia formation. Further, HGF enhanced association of Spns2 with S1P 1 that was blocked by inhibiting SphK1 activity with PF-543. Moreover, HGF-induced migration of HLMVECs was attenuated by down-regulation of Spns2 . Taken together, these results suggest that HGF/c-Met-mediated lamellipodia formation, and perhaps motility is dependent on intracellular generation of S1P via activation and localization of SphK1 to cell periphery and Spns2-mediated extracellular transportation of S1P and its inside-out signaling via S1P 1 . © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor.

    Science.gov (United States)

    Onuma, Takashi; Tanabe, Kumiko; Kito, Yuko; Tsujimoto, Masanori; Uematsu, Kodai; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Doi, Tomoaki; Nagase, Kiyoshi; Akamatsu, Shigeru; Tokuda, Haruhiko; Ogura, Shinji; Iwama, Toru; Kozawa, Osamu; Iida, Hiroki

    2017-08-01

    Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation. Co-stimulation with S1P and collagen suppressed collagen-induced platelet activation, but the effect was weaker than that of S1P-pretreatment. The collagen-stimulated secretion of platelet-derived growth factor (PDGF)-AB and the soluble CD40 ligand (sCD40L) release were significantly reduced by S1P. In addition, S1P suppressed the collagen-induced release of HSP27 as well as the phosphorylation of HSP27. S1P significantly suppressed the collagen-induced phosphorylation of p38 mitogen-activated protein kinase. S1P increased the levels of GTP-bound Gαi and GTP-bound Gα13 coupled to S1PPR1 and/or S1PR4. CYM50260, a selective S1PR4 agonist, but not SEW2871, a selective S1PR1 agonist, suppressed the collagen-stimulated platelet aggregation, PDGF-AB secretion and sCD40L release. In addition, CYM50260 reduced the release of phosphorylated-HSP27 by collagen as well as the phosphorylation of HSP27. The selective S1PR4 antagonist CYM50358, which failed to affect collagen-induced HSP27 phosphorylation, reversed the S1P-induced attenuation of HSP27 phosphorylation by collagen. These results strongly suggest that S1P inhibits the collagen-induced human platelet activation through S1PR4 but not S1PR1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Spectroscopy of the {sup 29}Si(p,{gamma}) reaction for E{sub p}=1.00{endash}1.75 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Vavrina, G.A.; Bybee, C.R.; Mitchell, G.E.; Moore, E.F.; Shriner, J.D. [North Carolina State University, Raleigh, North Carolina 27695 (United States); Bilpuch, E.G.; Wallace, P.M.; Westerfeldt, C.R. [Duke University, Durham, North Carolina 27708 (United States); Shriner, J.F. , Jr. [Tennessee Technological University, Cookeville, Tennessee 38505 (United States)

    1997-03-01

    The {sup 29}Si(p,{gamma}) reaction has been studied in the range E{sub p}=1.00{endash}1.75 MeV. Three previously unknown states in {sup 30}P were identified, and one state previously assigned to {sup 30}P was identified as a state in {sup 14}N. Gamma-ray strengths were determined for the three new levels, and branching ratios were measured for 17 resonances. Revised J{sup {pi}};T assignments were made for nine of these states. {copyright} {ital 1997} {ital The American Physical Society}

  6. MBL, P2X7, and SLC11A1 gene polymorphisms in patients with oropharyngeal tularemia.

    Science.gov (United States)

    Somuk, Battal Tahsin; Koc, Sema; Ates, Omer; Göktas, Göksel; Soyalic, Harun; Uysal, Ismail Onder; Gurbuzler, Levent; Sapmaz, Emrah; Sezer, Saime; Eyibilen, Ahmet

    2016-11-01

    A significant association was found of oropharyngeal tularemia with SLC11A1 allele polymorphism (INT4 G/C) and MBL2 C + 4T (P/Q). These results indicate C allele and Q allele might be a risk factor for the development of oropharyngeal tularemia. This study aimed to investigate the relationship of SLC11A1, MBL, and P2X 7 gene polymorphism with oropharyngeal tularemia. The study included totally 120 patients who were diagnosed with oropharyngeal tularemia. Frequencies of polymorphisms in the following genes were analyzed both in the patient and control groups in the study: SLC11A1 (5'(GT) n Allele 2/3, Int4 G/C, 3' UTR, D543N G/A), MBL (MBL2 C + 4T (P/Q), and P2X 7 (-762 C/T and 1513 A/C). Among all polymorphisms that were investigated in this study, SLC11A1 gene showed a significance in the distriburtion of polymorphism allelle frequency at the INT4 region. Frequency of C allele was 54 (28%) in patients with oropharyngeal tularemia, and 31 (13%) in the control group (p = 0.006 and OR = 1.96 (1.21-3.20)). An association was detected between MBL2 C + 4T (P/Q) gene polymorphism and oropharyngeal tularemia (p tularemia in this study (p > 0.05).

  7. Presence of pRI1:

    DEFF Research Database (Denmark)

    Migura, Lourdes Garcia; Hasman, Henrik; Jensen, Lars Bogø

    2009-01-01

    This study focused on the molecular characterization of a small cryptic, mobilizable plasmid (6038 bp) sequenced from an E. faecium 9631160-1 of poultry origin. Sequence analysis of pRI1 revealed seven open reading frames. pRI1 contained an IS 100% identical to ISEfa4. This insertion element...... almost identical to the repA from the pEFNP1 and pKQ10 plasmids from E. faecium was also identified. Presence of the pRI1 replication initiation gene (rep) was analyzed in a panel of 159 E. faecium isolates of human and animal origin from different European countries, of which 60 tested positive...

  8. [ital N][sub [ital p]N[ital n

    Energy Technology Data Exchange (ETDEWEB)

    Saha, M.; Sen, S. (Saha Institute of Nuclear Physics, Calcutta 700 064 (India))

    1993-02-01

    It is shown that the well known phenomenon of the saturation in the [ital B]([ital E]2;0[sub 1][sup +][r arrow]2[sub 1][sup +]), as well as the [ital E][sub 21][sup +] values near midshell in the even rare-earth and actinide nuclei, can be reproduced in the [ital N][sub [ital p]N[ital n

  9. Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation

    Science.gov (United States)

    Messias, Carolina V.; Santana-Van-Vliet, Eliane; Lemos, Julia P.; Moreira, Otacilio C.; Cotta-de-Almeida, Vinicius; Savino, Wilson; Mendes-da-Cruz, Daniella Arêas

    2016-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5). S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL) did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM) did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000–10000 nM) through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts. PMID:26824863

  10. Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation.

    Directory of Open Access Journals (Sweden)

    Carolina V Messias

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5. S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000-10000 nM through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts.

  11. A Measurement of Helicity-Frame Spin Alignment of Promptly Produced Y(nS) Mesons in p$\\bar{p}$ Collisions at 1.96 TeV

    Energy Technology Data Exchange (ETDEWEB)

    Thome, James [Carnegie Mellon Univ., Pittsburgh, PA (United States)

    2011-01-01

    Measurements of Y( nS) spin alignment have been made, using 4.9 fb-1 of data ob­tained by the CDF II detector at the Tevatron. The analysis is performed in the s-channel helicity frame on Y mesons having rapidity |YI < 0.6 and 2 < PT ≤ 40 GeV/ c via the decay channel Y ( nS) → µ+ µ- . A template method is used to correct for acceptance and trigger effects. The Y ( l S ) polarization is small and longitudinal at low PT. It is consistent with a constant at all PT · The Y(2S) and Y (3S) behaviors are similar to each other within statistics. Both have small polarization at low PT and move toward transverse polarization in the bin with PT > m(Y ).

  12. 15N Hyperpolarization of Imidazole-15N2 for Magnetic Resonance pH Sensing via SABRE-SHEATH.

    Science.gov (United States)

    Shchepin, Roman V; Barskiy, Danila A; Coffey, Aaron M; Theis, Thomas; Shi, Fan; Warren, Warren S; Goodson, Boyd M; Chekmenev, Eduard Y

    2016-06-24

    15 N nuclear spins of imidazole- 15 N 2 were hyperpolarized using NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). A 15 N NMR signal enhancement of ∼2000-fold at 9.4 T is reported using parahydrogen gas (∼50% para-) and ∼0.1 M imidazole- 15 N 2 in methanol:aqueous buffer (∼1:1). Proton binding to a 15 N site of imidazole occurs at physiological pH (p K a ∼ 7.0), and the binding event changes the 15 N isotropic chemical shift by ∼30 ppm. These properties are ideal for in vivo pH sensing. Additionally, imidazoles have low toxicity and are readily incorporated into a wide range of biomolecules. 15 N-Imidazole SABRE-SHEATH hyperpolarization potentially enables pH sensing on scales ranging from peptide and protein molecules to living organisms.

  13. Nuclear effects in protonium formation low-energy three-body reaction: p̄ + (pμ1s → (p̄pα + μ−: Strong p̄–p interaction in p̄ + (pμ1s

    Directory of Open Access Journals (Sweden)

    Sultanov Renat A.

    2016-01-01

    Full Text Available A three-charge-particle system (p̄, μ−, p+ with an additional matter-antimatter, i.e. p̄–p+, nuclear interaction is the subject of this work. Specifically, we carry out a few-body computation of the following protonium formation reaction: p̄ + (p+μ−1s → (p̄p+1s + μ−, where p+ is a proton, p̄ is an antiproton, μ− is a muon, and a bound state of p+ and its counterpart p̄ is a protonium atom: Pn = (p̄p+. The low-energy cross sections and rates of the Pn formation reaction are computed in the framework of a Faddeev-like equation formalism. The strong p̄–p+ interaction is approximately included in this calculation.

  14. Crystal structure of 2-(thiophen-2-yl)-1-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl) ethenyl]benzamide: N,N-dimethylformamide (1 : 1)

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, P. [University of Jammu, X-ray Crystallography Laboratory, Department of Physics (India); Subbulakshmi, K. N.; Narayana, B. [Mangalore University, Department of Chemistry (India); Sarojini, B. K. [Mangalore University, Industrial Chemistry Division, Department of Studies in Chemistry (India); Kant, R., E-mail: rkant.ju@gmail.com [University of Jammu, X-ray Crystallography Laboratory, Department of Physics (India)

    2016-03-15

    The title compound, 2-(thiophen-2-yl)-1-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)ethenyl] benzamide:N,N-dimethylformamide (1: 1), (C{sub 15}H{sub 11}N{sub 3}O{sub 2}S{sub 2} · C{sub 3}H{sub 7}NO), was synthesized, and its structure was established by spectral analysis and X-ray diffraction studies. The compound crystallizes in the monoclinic space group P2{sub 1}/n with a = 10.8714(7), b = 9.0497(5), c = 19.8347(13) Å, β = 91.093(5)°, Z = 4. The crystal structure is stabilized by N–H···S, C–H···O and N–H···O hydrogen bonds. The π···π interactions are also observed between the rings.

  15. Toxicological analysis of 1-P-tholiloxi-3-morpholino-2-propanol

    International Nuclear Information System (INIS)

    Rahimov, I.F.; Kimsanov, A.B.; Khaydarov, K.; Kimsanov, B.

    2005-01-01

    We have researched the toxicological analyse of 1-p-tholiloxi-3-morpholino-2-propanol on white rats during the chronic infusion. The influence of, the preparation 1-p-tholiloxi-3-morpholino-2-propanol on exponents, of the whole stable of the existence of tested animals was observed. It obviously shows that during 30 days in 25 and 50 mg/kg doses the masses of the body of the animals didn't show any phenomenon of the organisms, (allergy, anaphylaxis). The mass of a body of the tested and controlled groups of animals in same extent increased. The changes in blood there quite normal

  16. Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P)*

    Science.gov (United States)

    da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

    2016-01-01

    The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. PMID:26645686

  17. The N-Linked Outer Chain Mannans and the Dfg5p and Dcw1p Endo-α-1,6-Mannanases Are Needed for Incorporation of Candida albicans Glycoproteins into the Cell Wall

    Science.gov (United States)

    Ao, Jie; Chinnici, Jennifer L.; Maddi, Abhiram

    2015-01-01

    A biochemical pathway for the incorporation of cell wall protein into the cell wall of Neurospora crassa was recently proposed. In this pathway, the DFG-5 and DCW-1 endo-α-1,6-mannanases function to covalently cross-link cell wall protein-associated N-linked galactomannans, which are structurally related to the yeast outer chain mannans, into the cell wall glucan-chitin matrix. In this report, we demonstrate that the mannosyltransferase enzyme Och1p, which is needed for the synthesis of the N-linked outer chain mannan, is essential for the incorporation of cell wall glycoproteins into the Candida albicans cell wall. Using endoglycosidases, we show that C. albicans cell wall proteins are cross-linked into the cell wall via their N-linked outer chain mannans. We further demonstrate that the Dfg5p and Dcw1p α-1,6-mannanases are needed for the incorporation of cell wall glycoproteins into the C. albicans cell wall. Our results support the hypothesis that the Dfg5p and Dcw1p α-1,6-mannanases incorporate cell wall glycoproteins into the C. albicans cell wall by cross-linking outer chain mannans into the cell wall glucan-chitin matrix. PMID:26048011

  18. Polarization of J / psi and psi(2S) mesons produced in p anti-p collisions at s**(1/2) = 1.96-TeV

    Energy Technology Data Exchange (ETDEWEB)

    Abulencia, A.; /Illinois U., Urbana; Adelman, J.; /Chicago U.; Affolder, T.; /UC, Santa Barbara; Akimoto, T.; /Tsukuba U.; Albrow, M.G.; /Fermilab; Amerio, S.; /Padua U.; Amidei, D.; /Michigan U.; Anastassov, A.; /Rutgers U., Piscataway; Anikeev, K.; /Fermilab; Annovi, A.; /Frascati; Antos, J.; /Comenius U. /Tsukuba U.

    2007-04-01

    The authors have measured the polarizations of J/{psi} and {psi}(2S) mesons as functions of their transverse momentum p{sub T} when they are produced promptly in the rapidity range |y| < 0.6 with p{sub T} {ge} 5 GeV/c. The analysis is performed using a data sample with an integrated luminosity of about 800 pb{sup -1} collected by the CDF II detector. For both vector mesons, they find that the polarizations become increasingly longitudinal as p{sub T} increases from 5 to 30 GeV/c. These results are compared to the predictions of non-relativistic quantum chromo-dynamics and other contemporary models. The polarizations of J/{psi} and {psi}(2S) mesons from B-hadron decays are also reported.

  19. Measurement of the ratio of inclusive cross sections $\\sigma (p\\bar{p} \\rightarrow Z+2~b~\\text{jets}) / \\sigma (p\\bar{p} \\rightarrow Z+ \\text{2 jets})$ in $p\\bar{p}$ collisions at $\\sqrt s=1.96$ TeV

    CERN Document Server

    Abazov, V.M.; Acharya, Bannanje Sripath; Adams, Mark Raymond; Adams, Todd; Agnew, James P; Alexeev, Guennadi D; Alkhazov, Georgiy D; Alton, Andrew K; Askew, Andrew Warren; Atkins, Scott; Augsten, Kamil; Avila, Carlos A; Badaud, Frederique; Bagby, Linda F; Baldin, Boris; Bandurin, Dmitry V; Banerjee, Sunanda; Barberis, Emanuela; Baringer, Philip S; Bartlett, JFrederick; Bassler, Ursula Rita; Bazterra, Victor; Bean, Alice L; Begalli, Marcia; Bellantoni, Leo; Beri, Suman B; Bernardi, Gregorio; Bernhard, Ralf Patrick; Bertram, Iain A; Besancon, Marc; Beuselinck, Raymond; Bhat, Pushpalatha C; Bhatia, Sudeep; Bhatnagar, Vipin; Blazey, Gerald Charles; Blessing, Susan K; Bloom, Kenneth A; Boehnlein, Amber S; Boline, Daniel Dooley; Boos, Edward E; Borissov, Guennadi; Borysova, Maryna; Brandt, Andrew; Brandt, Oleg; Brock, Raymond L; Bross, Alan D; Brown, Duncan Paul; Bu, Xue-Bing; Buehler, Marc; Buescher, Volker; Bunichev, Viacheslav Yevgenyevich; Burdin, Sergey; Buszello, Claus Peter; Camacho-Perez, Enrique; Casey, Brendan Cameron Kieran; Castilla-Valdez, Heriberto; Caughron, Seth Aaron; Chakrabarti, Subhendu; Chan, Kwok Ming Leo; Chandra, Avdhesh; Chapon, Emilien; Chen, Guo; Cho, Sung-Woong; Choi, Suyong; Choudhary, Brajesh C; Cihangir, Selcuk; Claes, Daniel R; Clutter, Justace Randall; Cooke, Michael P; Cooper, William Edward; Corcoran, Marjorie D; Couderc, Fabrice; Cousinou, Marie-Claude; Cutts, David; Das, Amitabha; Davies, Gavin John; de Jong, Sijbrand Jan; De La Cruz-Burelo, Eduard; Deliot, Frederic; Demina, Regina; Denisov, Dmitri S; Denisov, Sergei P; Desai, Satish Vijay; Deterre, Cecile; DeVaughan, Kayle Otis; Diehl, HThomas; Diesburg, Michael; Ding, Pengfei; Dominguez, DAaron M; Dubey, Abhinav Kumar; Dudko, Lev V; Duperrin, Arnaud; Dutt, Suneel; Eads, Michael T; Edmunds, Daniel L; Ellison, John A; Elvira, VDaniel; Enari, Yuji; Evans, Harold G; Evdokimov, Valeri N; Faure, Alexandre; Feng, Lei; Ferbel, Thomas; Fiedler, Frank; Filthaut, Frank; Fisher, Wade Cameron; Fisk, HEugene; Fortner, Michael R; Fox, Harald; Fuess, Stuart C; Garbincius, Peter H; Garcia-Bellido, Aran; Garcia-Gonzalez, Jose Andres; Gavrilov, Vladimir B; Geng, Weigang; Gerber, Cecilia Elena; Gershtein, Yuri S; Ginther, George E; Gogota, Olga; Golovanov, Georgy Anatolievich; Grannis, Paul D; Greder, Sebastien; Greenlee, Herbert B; Grenier, Gerald Jean; Gris, Phillipe Luc; Grivaz, Jean-Francois; Grohsjean, Alexander; Gruenendahl, Stefan; Gruenewald, Martin Werner; Guillemin, Thibault; Gutierrez, Gaston R; Gutierrez, Phillip; Haley, Joseph Glenn Biddle; Han, Liang; Harder, Kristian; Harel, Amnon; Hauptman, John Michael; Hays, Jonathan M; Head, Tim; Hebbeker, Thomas; Hedin, David R; Hegab, Hatim; Heinson, Ann; Heintz, Ulrich; Hensel, Carsten; Heredia-De La Cruz, Ivan; Herner, Kenneth Richard; Hesketh, Gavin G; Hildreth, Michael D; Hirosky, Robert James; Hoang, Trang; Hobbs, John D; Hoeneisen, Bruce; Hogan, Julie; Hohlfeld, Mark; Holzbauer, Jenny Lyn; Howley, Ian James; Hubacek, Zdenek; Hynek, Vlastislav; Iashvili, Ia; Ilchenko, Yuriy; Illingworth, Robert A; Ito, Albert S; Jabeen, Shabnam; Jaffre, Michel J; Jayasinghe, Ayesh; Jeong, Min-Soo; Jesik, Richard L; Jiang, Peng; Johns, Kenneth Arthur; Johnson, Emily; Johnson, Marvin E; Jonckheere, Alan M; Jonsson, Per Martin; Joshi, Jyoti; Jung, Andreas Werner; Juste, Aurelio; Kajfasz, Eric; Karmanov, Dmitriy Y; Katsanos, Ioannis; Kaur, Manbir; Kehoe, Robert Leo Patrick; Kermiche, Smain; Khalatyan, Norayr; Khanov, Alexander; Kharchilava, Avto; Kharzheev, Yuri N; Kiselevich, Ivan Lvovich; Kohli, Jatinder M; Kozelov, Alexander V; Kraus, James Alexander; Kumar, Ashish; Kupco, Alexander; Kurca, Tibor; Kuzmin, Valentin Alexandrovich; Lammers, Sabine Wedam; Lebrun, Patrice; Lee, Hyeon-Seung; Lee, Seh-Wook; Lee, William M; Lei, Xiaowen; Lellouch, Jeremie; Li, Dikai; Li, Hengne; Li, Liang; Li, Qi-Zhong; Lim, Jeong Ku; Lincoln, Donald W; Linnemann, James Thomas; Lipaev, Vladimir V; Lipton, Ronald J; Liu, Huanzhao; Liu, Yanwen; Lobodenko, Alexandre; Lokajicek, Milos; Lopes de Sa, Rafael; Luna-Garcia, Rene; Lyon, Adam Leonard; Maciel, Arthur KA; Madar, Romain; Magana-Villalba, Ricardo; Malik, Sudhir; Malyshev, Vladimir L; Mansour, Jason; Martinez-Ortega, Jorge; McCarthy, Robert L; Mcgivern, Carrie Lynne; Meijer, Melvin M; Melnitchouk, Alexander S; Menezes, Diego D; Mercadante, Pedro Galli; Merkin, Mikhail M; Meyer, Arnd; Meyer, Jorg Manfred; Miconi, Florian; Mondal, Naba K; Mulhearn, Michael James; Nagy, Elemer; Narain, Meenakshi; Nayyar, Ruchika; Neal, Homer A; Negret, Juan Pablo; Neustroev, Petr V; Nguyen, Huong Thi; Nunnemann, Thomas P; Hernandez Orduna, Jose de Jesus; Osman, Nicolas Ahmed; Osta, Jyotsna; Pal, Arnab; Parashar, Neeti; Parihar, Vivek; Park, Sung Keun; Partridge, Richard A; Parua, Nirmalya; Patwa, Abid; Penning, Bjoern; Perfilov, Maxim Anatolyevich; Peters, Reinhild Yvonne Fatima; Petridis, Konstantinos; Petrillo, Gianluca; Petroff, Pierre; Pleier, Marc-Andre; Podstavkov, Vladimir M; Popov, Alexey V; Prewitt, Michelle; Price, Darren; Prokopenko, Nikolay N; Qian, Jianming; Quadt, Arnulf; Quinn, Gene Breese; Ratoff, Peter N; Razumov, Ivan A; Ripp-Baudot, Isabelle; Rizatdinova, Flera; Rominsky, Mandy Kathleen; Ross, Anthony; Royon, Christophe; Rubinov, Paul Michael; Ruchti, Randal C; Sajot, Gerard; Sanchez-Hernandez, Alberto; Sanders, Michiel P; Santos, Angelo Souza; Savage, David G; Savitskyi, Mykola; Sawyer, HLee; Scanlon, Timothy P; Schamberger, RDean; Scheglov, Yury A; Schellman, Heidi M; Schwanenberger, Christian; Schwienhorst, Reinhard H; Sekaric, Jadranka; Severini, Horst; Shabalina, Elizaveta K; Shary, Viacheslav V; Shaw, Savanna; Shchukin, Andrey A; Simak, Vladislav J; Skubic, Patrick Louis; Slattery, Paul F; Smirnov, Dmitri V; Snow, Gregory R; Snow, Joel Mark; Snyder, Scott Stuart; Soldner-Rembold, Stefan; Sonnenschein, Lars; Soustruznik, Karel; Stark, Jan; Stoyanova, Dina A; Strauss, Michael G; Suter, Louise; Svoisky, Peter V; Titov, Maxim; Tokmenin, Valeriy V; Tsai, Yun-Tse; Tsybychev, Dmitri; Tuchming, Boris; Tully, Christopher George T; Uvarov, Lev; Uvarov, Sergey L; Uzunyan, Sergey A; Van Kooten, Richard J; van Leeuwen, Willem M; Varelas, Nikos; Varnes, Erich W; Vasilyev, Igor A; Verkheev, Alexander Yurievich; Vertogradov, Leonid S; Verzocchi, Marco; Vesterinen, Mika; Vilanova, Didier; Vokac, Petr; Wahl, Horst D; Wang, Michael HLS; Warchol, Jadwiga; Watts, Gordon Thomas; Wayne, Mitchell R; Weichert, Jonas; Welty-Rieger, Leah Christine; Williams, Mark Richard James; Wilson, Graham Wallace; Wobisch, Markus; Wood, Darien Robert; Wyatt, Terence R; Xie, Yunhe; Yamada, Ryuji; Yang, Siqi; Yasuda, Takahiro; Yatsunenko, Yuriy A; Ye, Wanyu; Ye, Zhenyu; Yin, Hang; Yip, Kin; Youn, Sungwoo; Yu, Jiaming; Zennamo, Joseph; Zhao, Tianqi Gilbert; Zhou, Bing; Zhu, Junjie; Zielinski, Marek; Zieminska, Daria; Zivkovic, Lidija

    2015-03-17

    We measure the ratio of cross sections, $\\sigma(p\\bar{p}\\rightarrow Z+2~b~\\text{jets})$/$\\sigma(p\\bar{p}\\rightarrow Z+\\text{2 jets})$, for associated production of a $Z$ boson with at least two jets with transverse momentum $p_T^{\\rm jet} > 20$ GeV and pseudorapidity $|\\eta^{\\rm jet}| < 2.5$. This measurement uses data corresponding to an integrated luminosity of 9.7 fb$^{-1}$ collected by the \\DO experiment in Run II of Fermilab's Tevatron \\ppbar Collider at a center-of-mass energy of 1.96 TeV. The measured integrated ratio of $0.0236\\pm0.0043\\left(\\mbox{stat}\\right)\\pm0.0020\\left(\\mbox{syst}\\right)$ is in agreement with predictions from next-to-leading-order perturbative QCD and the Monte Carlo event generators {\\sc pythia} and {\\sc alpgen}.

  20. Heterojunction p-Cu2O/n-Ga2O3 diode with high breakdown voltage

    Science.gov (United States)

    Watahiki, Tatsuro; Yuda, Yohei; Furukawa, Akihiko; Yamamuka, Mikio; Takiguchi, Yuki; Miyajima, Shinsuke

    2017-11-01

    Heterojunction p-Cu2O/n-β-Ga2O3 diodes were fabricated on an epitaxially grown β-Ga2O3(001) layer. The reverse breakdown voltage of these p-n diodes reached 1.49 kV with a specific on-resistance of 8.2 mΩ cm2. The leakage current of the p-n diodes was lower than that of the Schottky barrier diode due to the higher barrier height against the electron. The ideality factor of the p-n diode was 1.31. It indicated that some portion of the recombination current at the interface contributed to the forward current, but the diffusion current was the dominant. The forward current more than 100 A/cm2 indicated the lower conduction band offset at the hetero-interface between Cu2O and Ga2O3 layers than that predicted from the bulk properties, resulting in such a high forward current without limitation. These results open the possibility of advanced device structures for wide bandgap Ga2O3 to achieve higher breakdown voltage and lower on-resistance.

  1. [1,4-Bis(diphenylphosphanylbutane-κ2P,P′]dibromidopalladium(II

    Directory of Open Access Journals (Sweden)

    Kwang Ha

    2014-02-01

    Full Text Available In the title complex, [PdBr2(C28H28P2], the PdII ion has a distorted cis-Br2P2 square-planar coordination geometry defined by two P atoms from the chelating 1,4-bis(diphenylphosphanylbutane ligand and two Br− anions. The four phenyl rings are inclined to the least-squares plane of the PdBr2P2 unit [maximum deviation = 0.1294 (7 Å], making dihedral angles of 66.3 (2, 87.2 (2, 68.8 (2 and 86.8 (2°. The butylene chain is in a gauche conformation, with a C—C—C—C torsion angle of 57.0 (8°. Intermolecular C—H...Br hydrogen bonds link the complex molecules into supramolecular layers in the ab plane. Weak π–π interactions, both intra- and intermolecular [shortest inter-centroid distance = 4.598 (5 Å], are also noted in the three-dimensional architecture.

  2. Quantitative and Qualitative Involvement of P3N-PIPO in Overcoming Recessive Resistance against Clover Yellow Vein Virus in Pea Carrying the cyv1 Gene

    Science.gov (United States)

    Choi, Sun Hee; Hagiwara-Komoda, Yuka; Atsumi, Go; Shimada, Ryoko; Hisa, Yusuke; Naito, Satoshi

    2013-01-01

    In pea carrying cyv1, a recessive gene for resistance to Clover yellow vein virus (ClYVV), ClYVV isolate Cl-no30 was restricted to the initially infected cells, whereas isolate 90-1 Br2 overcame this resistance. We mapped the region responsible for breaking of cyv1-mediated resistance by examining infection of cyv1 pea with chimeric viruses constructed from parts of Cl-no30 and 90-1 Br2. The breaking of resistance was attributed to the P3 cistron, which is known to produce two proteins: P3, from the main open reading frame (ORF), and P3N-PIPO, which has the N-terminal part of P3 fused to amino acids encoded by a small open reading frame (ORF) called PIPO in the +2 reading frame. We introduced point mutations that were synonymous with respect to the P3 protein but nonsynonymous with respect to the P3N-PIPO protein, and vice versa, into the chimeric viruses. Infection of plants with these mutant viruses revealed that both P3 and P3N-PIPO were involved in overcoming cyv1-mediated resistance. Moreover, P3N-PIPO quantitatively affected the virulence of Cl-no30 in cyv1 pea. Additional expression in trans of the P3N-PIPO derived from Cl-no30, using White clover mosaic virus as a vector, enabled Cl-no30 to move to systemic leaves in cyv1 pea. Susceptible pea plants infected with chimeric ClYVV possessing the P3 cistron of 90-1 Br2, and which were therefore virulent toward cyv1 pea, accumulated more P3N-PIPO than did those infected with Cl-no30, suggesting that the higher level of P3N-PIPO in infected cells contributed to the breaking of resistance by 90-1 Br2. This is the first report showing that P3N-PIPO is a virulence determinant in plants resistant to a potyvirus. PMID:23616656

  3. High-throughput screening reveals alsterpaullone, 2-cyanoethyl as a potent p27Kip1 transcriptional inhibitor.

    Directory of Open Access Journals (Sweden)

    Brandon J Walters

    Full Text Available p27Kip1 is a cell cycle inhibitor that prevents cyclin dependent kinase (CDK/cyclin complexes from phosphorylating their targets. p27Kip1 is a known tumor suppressor, as the germline loss of p27Kip1 results in sporadic pituitary formation in aged rodents, and its presence in human cancers is indicative of a poor prognosis. In addition to its role in cancer, loss of p27Kip1 results in regenerative phenotypes in some tissues and maintenance of stem cell pluripotency, suggesting that p27Kip1 inhibitors could be beneficial for tissue regeneration. Because p27Kip1 is an intrinsically disordered protein, identifying direct inhibitors of the p27Kip1 protein is difficult. Therefore, we pursued a high-throughput screening strategy to identify novel p27Kip1 transcriptional inhibitors. We utilized a luciferase reporter plasmid driven by the p27Kip1 promoter to transiently transfect HeLa cells and used cyclohexamide as a positive control for non-specific inhibition. We screened a "bioactive" library consisting of 8,904 (4,359 unique compounds, of which 830 are Food and Drug Administration (FDA approved. From this screen, we successfully identified 111 primary hits with inhibitory effect against the promoter of p27Kip1. These hits were further refined using a battery of secondary screens. Here we report four novel p27Kip1 transcriptional inhibitors, and further demonstrate that our most potent hit compound (IC50 = 200 nM Alsterpaullone 2-cyanoethyl, inhibits p27Kip1 transcription by preventing FoxO3a from binding to the p27Kip1 promoter. This screen represents one of the first attempts to identify inhibitors of p27Kip1 and may prove useful for future tissue regeneration studies.

  4. Total scattering cross-sections for the systems nH2 + nH2, pH2 + pH2, nD2 + nD2, oD2 + oD2 and HD + HD for relative energies below ten milli-electron volts

    International Nuclear Information System (INIS)

    Johnson, D.L.

    1979-01-01

    Relative total scattering cross sections for nH 2 + nH 2 , pH 2 + pH 2 , nD 2 + nD 2 , oD 2 + oD 2 , and HD + HD were measured with inclined nozzle beams derived from nozzle sources and intersecting at 21 0 . Both nozzles could be varied in temperature from 4.2K to 300K to provide the velocity range for the cross sections. The use of a parahydrogen converter allowed the measurement of the pH 2 + pH 2 and oD 2 + oD 2 cross sections. Cross sections for the H 2 + H 2 were measured over a relative velocity range of 200 m/s to 1450 m/s. The nH 2 + nH 2 results show an undulation in the velocity range between 350 m/s and 400 m/s that corresponds to a l = 3 orbiting resonance. Analysis of the pH 2 + pH 2 cross section indicates a l = 4 orbiting resonance near 586 m/s. This resonance has a peak energy of 1.79 meV and a measured energy width of 1.05 meV, both which agree well with theoretical predictions. The D 2 + D 2 cross sections have been measured in the velocity range between 190 m/s and 1000 m/s. No orbiting resonances have been observed, but in the oD 2 + oD 2 cross section a deep minimum between the l = 4 and the l = 5 resonances at low velocities is clearly suggested. Initial measurements of the HD + HD cross section suggests the presence of the l = 4 orbiting resonance near a relative velocity of 300 m/s. The experimental results for each system were normalized to the total cross sections, which were convoluted to account for experimental velocity and angular dispersions. Three different potentials were considered, but a chi-square fit of the data indicates that the Schaefer and Meyer potential, which has been theoretically obtained from first principles, provides the best overall description of the hydrogen systems in the low collisional energy range

  5. Association of glutathione S-transferase (GSTM1, T1 and P1 gene polymorphisms with type 2 diabetes mellitus in north Indian population

    Directory of Open Access Journals (Sweden)

    Bid H

    2010-01-01

    Full Text Available Background: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS and a reduction in antioxidant defense. The oxidative stress becomes evident as a result of accumulation of ROS in conditions of inflammation and Type 2 diabetes mellitus (T2DM. The genes involved in redox balance, which determines the susceptibility to T2DM remain unclear. In humans, the glutathione S-transferase (GST family comprises several classes of GST isozymes, the polymorphic variants of GSTM1, T1 and P1 genes result in decreased or loss of enzyme activity. Aims: The present study evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing T2DM in the North Indian population. Settings and Design: GSTM1, T1 and P1 polymorphisms were genotyped in 100 T2DM patients and 200 healthy controls from North India to analyze their association with T2DM susceptibility. Materials and Methods: Analysis of GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction (PCR and GSTP1 by PCR-Restriction Fragment Length Polymorphism (RFLP. Statistical Analysis: Fisher′s exact test and χ2 statistics using SPSS software (Version-15.0. Results: We observed significant association of GSTM1 null (P=0.004, OR= 2.042, 95%CI= 1.254-3.325 and GSTP1 (I/V (P=0.001, OR= 0.397, 95%CI=0.225-0.701 with T2DM and no significant association with GSTT1 (P=0.493. The combined analysis of the three genotypes GSTM1 null, T1 present and P1 (I/I demonstrated an increase in T2DM risk (P= 0.005, OR= 2.431 95% CI=1.315-4.496. Conclusions: This is the first study showing the association of a combined effect of GSTM1, T1 and P1 genotypes in a representative cohort of Indian patients with T2DM. Since significant association was seen in GSTM1 null and GSTP1 (I/V and multiple association in GSTM1 null, T1 present and P1 (I/I, these polymorphisms can be screened in the population to determine the diabetic risk.

  6. Search for anomalous production of multi-lepton events in p anti-p collisions at s**(1/2) = 1.96-TeV

    Energy Technology Data Exchange (ETDEWEB)

    Abulencia, A.; Adelman, Jahred A.; Affolder, T.; Akimoto, T.; Albrow, M.G.; Ambrose, D.; Amerio, S.; Amidei, D.; Anastassov, A.; Anikeev, K.; Annovi, A.; /Taiwan, Inst.

    2007-01-01

    The authors report a search for the anomalous production of events with multiple charged leptons in p{bar p} collisions at {radical}s = 1.96 TeV using a data sample corresponding to an integrated luminosity of 346 pb{sup -1} collected by the CDF II detector at the Fermilab Tevatron. The search is divided into three-lepton and four-or-more-lepton data samples. They observe six events in the three-lepton sample and zero events in the {ge}4-lepton sample. Both numbers of events are consistent with standard model background expectations. Within the framework of an R-parity violating supergravity model, the results are interpreted as mass limits on the lightest neutralino ({bar {chi}}{sub 1}{sup 0}) and chargino ({bar {chi}}{sub 1}{sup {+-}}) particles. For one particular choice of model parameters, the limits are M({bar {chi}}{sub 1}{sup 0}) > 110 GeV/c{sup 2} and M({bar {chi}}{sub 1}{sup {+-}}) > 203 GeV/c{sup 2} at 95% confidence level; the variation of these mass limits with model parameters is presented.

  7. Population of the 3P2,1,0 fine-structure states in the 3s and 3p photoionization of atomic chlorine

    International Nuclear Information System (INIS)

    Krause, M.O.; Caldwell, C.D.; Whitfield, S.B.; de Lange, C.A.; van der Meulen, P.

    1993-01-01

    In a high-resolution photoelectron-spectrometry study of the photoionization of chlorine atoms in both the 3s and 3p subshells, we were able to resolve contributions from ionic states with specific J values and measure the relative populations of these fine-structure components. Our photoelectron spectra, recorded at hν=29.2 eV, give ratios of 3 P 2 : 3 P 1 : 3 P 0 =100:40.59.5 for 3p photoionization and 3 P 2 : 3 P 1 =100:31 for 3s photoionization. While the results for 3p ionization are in accord with predictions based on a simple geometric analysis, the contribution of the 3 P 1 state in 3s photoionization is larger than that predicted by this simple model. The geometric predictions are also compared with results from a similar measurement of the population of the 4p -1 ( 3 P J ) states produced in the 4p ionization of Br and with earlier work on the production of 3 D 2,1,0 states in d-shell photoionization of Cu and Ag

  8. Measurement of the 22S1/2-22P3/2 fine structure interval in muonium

    International Nuclear Information System (INIS)

    Kettell, S.H.

    1990-08-01

    The (2 2 S 1/2 - 2 2 P 3/2 ) fine structure transition in muonium has been observed for the first time. The measured value is 9895 -30 +35 MHz. This measurement, when included with the theoretical value for the 2 2 P 1/2 - 2 2 P 3/2 fine structure interval, gives a value for the Lamb shift (2 2 S 1/2 - 2 2 P 1/2 ) independent of previous direct measurements. From the theoretical value for the fine structure interval, 10921.833(3) MHz, the value for the Lamb shift determined from this experiment is 1027 -35 +30 MHz and is in agreement with the prediction of quantum electrodynamics (QED) of 1047.5(3) MHz. Previous experimental values for the Lamb shift (2 2 S 1/2 -2 2 P 1/2 ) in muonium are 1070 -15 + 12 MHz and 1042 -23 +21 MHz. Combining this result with these previous results gives a new experimental value of 1058 -12 +10 for the Lamb shift in muonium. Muonium, the bound state of two structureless leptons (μ + e - ), is an ideal system for testing bound state QED because of the lack of hadronic structure as exists in the hydrogen system. The measurement makes use of the techniques of atomic beam microwave spectroscopy. Muonium atoms (μ + e - ) in the 2S states are produced by the beam-foil technique at the Clinton P. Anderson Meson Physics Facility with a low momentum, sub-surface muon beam. A variable frequency microwave field is applied to drive the atoms from the 2S to the 2P states, with the subsequent observation of the Lyman alpha photon from the decay of the 2P state to the 1S ground state. The frequency is varied from 9.0--11.0 GHz, driving the F = 0 → F = 1, F = 1, F = 1 and F = 1 → F = 2 transitions

  9. Selective coupling of the S1P3 receptor subtype to S1P-mediated RhoA activation and cardioprotection.

    Science.gov (United States)

    Yung, Bryan S; Brand, Cameron S; Xiang, Sunny Y; Gray, Charles B B; Means, Christopher K; Rosen, Hugh; Chun, Jerold; Purcell, Nicole H; Brown, Joan Heller; Miyamoto, Shigeki

    2017-02-01

    Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, is generated and released at sites of tissue injury in the heart and can act on S1P 1 , S1P 2 , and S1P 3 receptor subtypes to affect cardiovascular responses. We established that S1P causes little phosphoinositide hydrolysis and does not induce hypertrophy indicating that it does not cause receptor coupling to G q . We previously demonstrated that S1P confers cardioprotection against ischemia/reperfusion by activating RhoA and its downstream effector PKD. The S1P receptor subtypes and G proteins that regulate RhoA activation and downstream responses in the heart have not been determined. Using siRNA or pertussis toxin to inhibit different G proteins in NRVMs we established that S1P regulates RhoA activation through Gα 13 but not Gα 12 , Gα q , or Gα i . Knockdown of the three major S1P receptors using siRNA demonstrated a requirement for S1P 3 in RhoA activation and subsequent phosphorylation of PKD, and this was confirmed in studies using isolated hearts from S1P 3 knockout (KO) mice. S1P treatment reduced infarct size induced by ischemia/reperfusion in Langendorff perfused wild-type (WT) hearts and this protection was abolished in the S1P 3 KO mouse heart. CYM-51736, an S1P 3 -specific agonist, also decreased infarct size after ischemia/reperfusion to a degree similar to that achieved by S1P. The finding that S1P 3 receptor- and Gα 13 -mediated RhoA activation is responsible for protection against ischemia/reperfusion suggests that selective targeting of S1P 3 receptors could provide therapeutic benefits in ischemic heart disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-κB ligand (RANKL) expression in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Takeshita, Harunori; Kitano, Masayasu; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto; Miyazawa, Keiji; Hla, Timothy; Sano, Hajime

    2012-01-01

    Highlights: ► MH7A cells and CD4 + T cells expressed S1P1 and RANKL. ► S1P increased RANKL expression in MH7A cells and CD4 + T cells. ► The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-κB ligand (RANKL) in RA synoviocytes and CD4 + T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4 + T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4 + T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-α in MH7A cells and CD4 + T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4 + T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  11. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Takeshita, Harunori [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kitano, Masayasu, E-mail: mkitano6@hyo-med.ac.jp [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi [Department of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima Kobe, Hyogo 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Miyazawa, Keiji [Discovery Research III, Research and Development, Kissei Pharmaceutical Company, 4365-1 Hodakakashiwara, Azumino, Nagano 399-8304 (Japan); Hla, Timothy [Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Box 69, NY 10065 (United States); Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  12. Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P).

    Science.gov (United States)

    da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

    2016-01-29

    The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Enantioselective kappa opioid binding sites on the macrophage cell line, P388d sub 1

    Energy Technology Data Exchange (ETDEWEB)

    Carr, D.J.J.; Blalock, J.E. (Univ. of Alabama, Birmingham (USA)); DeCosta, B.R.; Jacobson, A.E.; Rice, K.C. (NIDDK, NIH, Bethesda, MD (USA))

    1991-01-01

    A kappa opioid binding site has been characterized on the macrophage cell line, P388d{sub 1}, using the kappa selective affinity ligand, ({sup 3H}(1S,2S)-(-)-trans-2-isothiocyanato-N-methyl-N-(2-(1-phrrolidinyl) cyclohexyl) benzeneacetamide ((-)BD166). The kappa site has a relative molecular mass (Mr) of 38,000 under nonreducing conditions and 42,000 under reducing conditions. Moreover, it exhibits enantioselectivity in that 1S,2S-(-)-trans-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)cyclohexyl) benzeneacetamide ((-)-U-50,488) blocks ({sup 3}H)95{alpha},7{alpha},8{beta})-(-)-N-methyl-N-(7-(1- pyrrolidinyl)-1-oxaspiro-(4,5)-dec-8-yl)benzeneacetamide (U-69,593) binding to P388d{sub 1} cells with an IC{sub 50} = 7.0 nM whereas 1R,2R-(+)-trans-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)cyclohexyl) benzeneacetamide ((+)U-50,488) blocks ({sup 3}H)U-69,593 binding to P388d{sub 1} cells with an IC{sub 50} = 700 nM.

  14. Target and beam-target spin asymmetries in exclusive pion electroproduction for Q2>1 GeV2. II. e p →e π0p

    Science.gov (United States)

    Bosted, P. E.; Kim, A.; Adhikari, K. P.; Adikaram, D.; Akbar, Z.; Amaryan, M. J.; Anefalos Pereira, S.; Avakian, H.; Badui, R. A.; Ball, J.; Balossino, I.; Battaglieri, M.; Bedlinskiy, I.; Biselli, A. S.; Boiarinov, S.; Briscoe, W. J.; Brooks, W. K.; Bültmann, S.; Burkert, V. D.; Cao, T.; Carman, D. S.; Celentano, A.; Chandavar, S.; Charles, G.; Chetry, T.; Ciullo, G.; Clark, L.; Colaneri, L.; Cole, P. L.; Contalbrigo, M.; Cortes, O.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Dupre, R.; Egiyan, H.; El Alaoui, A.; El Fassi, L.; Elouadrhiri, L.; Eugenio, P.; Fanchini, E.; Fedotov, G.; Fegan, S.; Fersch, R.; Filippi, A.; Fleming, J. A.; Forest, T. A.; Fradi, A.; Ghandilyan, Y.; Gilfoyle, G. P.; Girod, F. X.; Glazier, D. I.; Gohn, W.; Golovatch, E.; Gothe, R. W.; Griffioen, K. A.; Guidal, M.; Guler, N.; Hakobyan, H.; Guo, L.; Hafidi, K.; Hakobyan, H.; Hanretty, C.; Harrison, N.; Hattawy, M.; Heddle, D.; Hicks, K.; Hollis, G.; Holtrop, M.; Hughes, S. M.; Ireland, D. G.; Isupov, E. L.; Jenkins, D.; Jiang, H.; Jo, H. S.; Joo, K.; Keller, D.; Khachatryan, G.; Khandaker, M.; Kim, W.; Klei, A.; Klein, F. J.; Koirala, S.; Kubarovsky, V.; Kuhn, S. E.; Lanza, L.; Lenisa, P.; Livingston, K.; Lu, H. Y.; MacGregor, I. J. D.; Markov, N.; Mayer, M.; McCracken, M. E.; McKinnon, B.; Mineeva, T.; Mirazita, M.; Mokeev, V. I.; Montgomery, R. A.; Movsisyan, A.; Munoz Camacho, C.; Murdoch, G.; Nadel-Turonski, P.; Ni, A.; Niccolai, S.; Niculescu, G.; Osipenko, M.; Ostrovidov, A. I.; Paolone, M.; Paremuzyan, R.; Park, K.; Pasyuk, E.; Phelps, W.; Pisano, S.; Pogorelko, O.; Price, J. W.; Prok, Y.; Protopopescu, D.; Puckett, A. J. R.; Raue, B. A.; Ripani, M.; Rizzo, A.; Rosner, G.; Rossi, P.; Roy, P.; Sabatié, F.; Saini, M. S.; Schumacher, R. A.; Seder, E.; Sharabian, Y. G.; Skorodumina, Iu.; Smith, G. D.; Sokhan, D.; Sparveris, N.; Stankovic, I.; Stepanyan, S.; Stoler, P.; Strakovsky, I. I.; Strauch, S.; Taiuti, M.; Tian, Ye; Torayev, B.; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Wei, X.; Weinstein, L. B.; Zachariou, N.; Zhang, J.; Zhao, Z. W.; Zonta, I.; CLAS Collaboration

    2017-03-01

    Beam-target double-spin asymmetries and target single-spin asymmetries were measured for the exclusive π0 electroproduction reaction γ*pp π0 , expanding an analysis of the γ*pn π+ reaction from the same experiment. The results were obtained from scattering of 6-GeV longitudinally polarized electrons off longitudinally polarized protons using the CEBAF Large Acceptance Spectrometer at Jefferson Laboratory. The kinematic ranges covered are 1.1 1 2<6 GeV2. Results were obtained for about 5700 bins in W , Q2, cos(θ*) , and ϕ*. The beam-target asymmetries were found to generally be greater than zero, with relatively modest ϕ* dependence. The target asymmetries exhibit very strong ϕ* dependence, with a change in sign occurring between results at low W and high W , in contrast to π+ electroproduction. Reasonable agreement is found with phenomenological fits to previous data for W <1.6 GeV, but significant differences are seen at higher W . When combined with cross-sectional measurements, as well as π+ observables, the present results will provide powerful constraints on nucleon resonance amplitudes at moderate and large values of Q2, for resonances with masses as high as 2.4 GeV.

  15. New superhindered polydentate polyphosphine ligands P(CH2CH2P(t)Bu2)3, PhP(CH2CH2P(t)Bu2)2, P(CH2CH2CH2P(t)Bu2)3, and their ruthenium(II) chloride complexes.

    Science.gov (United States)

    Gilbert-Wilson, Ryan; Field, Leslie D; Bhadbhade, Mohan M

    2012-03-05

    The synthesis and characterization of the extremely hindered phosphine ligands, P(CH(2)CH(2)P(t)Bu(2))(3) (P(2)P(3)(tBu), 1), PhP(CH(2)CH(2)P(t)Bu(2))(2) (PhP(2)P(2)(tBu), 2), and P(CH(2)CH(2)CH(2)P(t)Bu(2))(3) (P(3)P(3)(tBu), 3) are reported, along with the synthesis and characterization of ruthenium chloro complexes RuCl(2)(P(2)P(3)(tBu)) (4), RuCl(2)(PhP(2)P(2)(tBu)) (5), and RuCl(2)(P(3)P(3)(tBu)) (6). The bulky P(2)P(3)(tBu) (1) and P(3)P(3)(tBu) (3) ligands are the most sterically encumbered PP(3)-type ligands so far synthesized, and in all cases, only three phosphorus donors are able to bind to the metal center. Complexes RuCl(2)(PhP(2)P(2)(tBu)) (5) and RuCl(2)(P(3)P(3)(tBu)) (6) were characterized by crystallography. Low temperature solution and solid state (31)P{(1)H} NMR were used to demonstrate that the structure of RuCl(2)(P(2)P(3)(tBu)) (4) is probably analogous to that of RuCl(2)(PhP(2)P(2)(tBu)) (5) which had been structurally characterized.

  16. Synthesis of P1-(11-phenoxyundecyl)-P2-(2-acetamido-2-deoxy-3-O-α-D-rhamnopyranosyl-α-D-glucopyranosyl) diphosphate and P1-(11-phenoxyundecyl)-P2-(2-acetamido-2-deoxy-3-O-β-D-galactopyranosyl-α-D-galactopyranosyl) diphosphate for the investigation of biosynthesis of O-antigenic polysaccharides in Pseudomonas aeruginosa and Escherichia coli O104.

    Science.gov (United States)

    Torgov, Vladimir; Danilov, Leonid; Utkina, Natalia; Veselovsky, Vladimir; Brockhausen, Inka

    2017-12-01

    Two new phenoxyundecyl diphosphate sugars were synthesized for the first time: P 1 -(11-phenoxyundecyl)-P 2 - (2-acetamido-2-deoxy-3-O-α-D-rhamnopyranosyl-α-D-glucopyranosyl) diphosphate and P 1 -(11-phenoxyundecyl)-P 2 -(2-acetamido-2-deoxy-3-O-β-D-galactopyranosyl-α-D-galactopyranosyl) diphosphate to study the third step of biosynthesis of the repeating units of O-antigenic polysaccharides in Pseudomonas aeruginosa and E.coli O104 respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Apaf-1 is a transcriptional target for E2F and p53

    DEFF Research Database (Denmark)

    Moroni, M C; Hickman, E S; Lazzerini Denchi, E

    2001-01-01

    between the deregulation of the pRB pathway and apoptosis. Furthermore, because the pRB pathway is functionally inactivated in most cancers, the identification of Apaf-1 as a transcriptional target for E2F might explain the increased sensitivity of tumour cells to chemotherapy. We also show that......, independently of the pRB pathway, Apaf-1 is a direct transcriptional target of p53, suggesting that p53 might sensitize cells to apoptosis by increasing Apaf-1 levels....

  18. Energies and E1, M1, E2, and M2 transition rates for states of the 2s{sup 2}2p{sup 3}, 2s2p{sup 4}, and 2p{sup 5} configurations in nitrogen-like ions between F III and Kr XXX

    Energy Technology Data Exchange (ETDEWEB)

    Rynkun, P., E-mail: pavel.rynkun@gmail.com [Department of Physics and Information Technologies, Lithuanian University of Educational Science, Studentu 39, LT-08106 Vilnius (Lithuania); Jönsson, P. [Group for Materials Science and Applied Mathematics, Malmö University, 20506 Malmö (Sweden); Gaigalas, G. [Department of Physics and Information Technologies, Lithuanian University of Educational Science, Studentu 39, LT-08106 Vilnius (Lithuania); Vilnius University, Institute of Theoretical Physics and Astronomy, A. Goštauto 12, LT-01108 Vilnius (Lithuania); Froese Fischer, C. [National Institute of Standards and Technology, Gaithersburg, MD 20899-8420 (United States)

    2014-03-15

    Based on relativistic wavefunctions from multiconfiguration Dirac–Hartree–Fock and configuration interaction calculations, E1, M1, E2, and M2 transition rates, weighted oscillator strengths, and lifetimes are evaluated for the states of the (1s{sup 2})2s{sup 2}2p{sup 3},2s2p{sup 4}, and 2p{sup 5} configurations in all nitrogen-like ions between F III and Kr XXX. The wavefunction expansions include valence, core–valence, and core–core correlation effects through single–double multireference expansions to increasing sets of active orbitals. The computed energies agree very well with experimental values, with differences of only 300–600 cm{sup −1} for the majority of the levels and ions in the sequence. Computed transitions rates are in close agreement with available data from MCHF-BP calculations by Tachiev and Froese Fischer [G.I. Tachiev, C. Froese Fischer, A and A 385 (2002) 716].

  19. Evidence of the 2s2p(1P) doubly excited state in the harmonic generation spectrum of helium

    International Nuclear Information System (INIS)

    Ngoko Djiokap, J. M.; Starace, Anthony F.

    2011-01-01

    By solving the two-active-electron time-dependent Schroedinger equation in an intense, ultrashort laser field, we investigate evidence of electron correlations in the high-order harmonic generation spectrum of helium. As the frequency of the driving laser pulse varies from 4.6 to 6.6 eV, the 13th, 11th, and 9th harmonics sequentially become resonant with the transition between the ground state and the isolated 2s2p( 1 P) autoionizing state of helium, which dramatically enhances these harmonics and changes their profiles. When each of the 9th and 13th harmonics are in resonance with this autoionizing state, there is also a low-order multiphoton resonance with a Rydberg state, resulting in a particularly large enhancement of these harmonics relative to neighboring harmonics. When the 11th harmonic is in resonance with the 2s2p( 1 P) autoionizing state, the 13th harmonic is simultaneously in resonance with numerous higher-energy autoionizing states, resulting in a competition between these two harmonics for intensity. These results demonstrate that even electron correlations occurring over a narrow energy interval can have a significant effect on strong-field processes such as harmonic generation.

  20. First-Principle Study of the Optical Properties of Dilute-P GaN1-xPx Alloys.

    Science.gov (United States)

    Borovac, Damir; Tan, Chee-Keong; Tansu, Nelson

    2018-04-16

    An investigation on the optical properties of dilute-P GaN 1-x P x alloys by First-Principle Density Functional Theory (DFT) methods is presented, for phosphorus (P) content varying from 0% up to 12.5%. Findings on the imaginary and real part of the dielectric function are analyzed and the results are compared with previously reported theoretical works on GaN. The complex refractive index, normal-incidence reflectivity and birefringence are presented and a difference in the refractive index in the visible regime between GaN and GaNP alloys of ~0.3 can be engineered by adding minute amounts of phosphorus, indicating strong potential for refractive index tunability. The optical properties of the GaN 1-x P x alloys indicate their strong potential for implementation in various III-nitride-based photonic waveguide applications and Distributed Bragg Reflectors (DBR).

  1. Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population.

    Science.gov (United States)

    Yu, H; Yan, H; Li, J; Li, Z; Zhang, X; Ma, Y; Mei, L; Liu, C; Cai, L; Wang, Q; Zhang, F; Iwata, N; Ikeda, M; Wang, L; Lu, T; Li, M; Xu, H; Wu, X; Liu, B; Yang, J; Li, K; Lv, L; Ma, X; Wang, C; Li, L; Yang, F; Jiang, T; Shi, Y; Li, T; Zhang, D; Yue, W

    2017-07-01

    Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10 -12 , odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10 -10 , OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10 -10 , OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10 -9 , OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R 2 : 1.7% ~5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.

  2. A recurrent deletion syndrome at chromosome bands 2p11.2-2p12 flanked by segmental duplications at the breakpoints and including REEP1.

    Science.gov (United States)

    Stevens, Servi J C; Blom, Eveline W; Siegelaer, Ingrid T J; Smeets, Eric E J G L

    2015-04-01

    We identified an identical and recurrent 9.4-Mbp deletion at chromosome bands 2p11.2-2p12, which occurred de novo in two unrelated patients. It is flanked at the distal and proximal breakpoints by two homologous segmental duplications consisting of low copy repeat (LCR) blocks in direct orientation, which have >99% sequence identity. Despite the fact that the deletion was almost 10 Mbp in size, the patients showed a relatively mild clinical phenotype, that is, mild-to-moderate intellectual disability, a happy disposition, speech delay and delayed motor development. Their phenotype matches with that of previously described patients. The 2p11.2-2p12 deletion includes the REEP1 gene that is associated with spastic paraplegia and phenotypic features related to this are apparent in most 2p11.2-2p12 deletion patients, but not in all. Other hemizygous genes that may contribute to the clinical phenotype include LRRTM1 and CTNNA2. We propose a recurrent but rare 2p11.2-2p12 deletion syndrome based on (1) the identical, non-random localisation of the de novo deletion breakpoints in two unrelated patients and a patient from literature, (2) the patients' phenotypic similarity and their phenotypic overlap with other 2p deletions and (3) the presence of highly identical LCR blocks flanking both breakpoints, consistent with a non-allelic homologous recombination (NAHR)-mediated rearrangement.

  3. Infection with E1B-mutant adenovirus stabilizes p53 but blocks p53 acetylation and activity through E1A

    DEFF Research Database (Denmark)

    Savelyeva, I.; Dobbelstein, M.

    2011-01-01

    to the suppression of p21 transcription. Depending on the E1A conserved region 3, E1B-defective adenovirus impaired the ability of the transcription factor Sp1 to bind the p21 promoter. Moreover, the amino terminal region of E1A, binding the acetyl transferases p300 and CREB-binding protein, blocked p53 K382...... accumulation of p53, without obvious defects in p53 localization, phosphorylation, conformation and oligomerization. Nonetheless, p53 completely failed to induce its target genes in this scenario, for example, p21/CDKN1A, Mdm2 and PUMA. Two regions of the E1A gene products independently contributed...... acetylation in infected cells. Mutating either of these E1A regions, in addition to E1B, partially restored p21 mRNA levels. Our findings argue that adenovirus attenuates p53-mediated p21 induction, through at least two E1B-independent mechanisms. Other virus species and cancer cells may employ analogous...

  4. (+-{1,2-Bis[(2R,5R-2,5-diethylphospholan-1-yl]ethane-κ2P,P′}(η4-cycloocta-1,5-dienerhodium(I tetrafluoridoborate

    Directory of Open Access Journals (Sweden)

    Stefan Schulz

    2010-11-01

    Full Text Available The title compound, [Rh(C8H12(C18H36P2]BF4, exhibits a rhodium(I complex cation with a bidentate bisphosphine ligand and a bidentate η22-coordinated cycloocta-1,5-diene ligand. The ligands form a slightly distorted square-planar coordination environment for the Rh(I atom. An intramolecular P–Rh–P bite angle of 83.91 (2° is observed. The dihedral angle between the P—Rh—P and the X—Rh—X planes (X is the centroid of a double bond is 14.0 (1°. The BF4 anion is disordered over two positions in a 0.515 (7:0.485 (7 ratio.

  5. Forward $\\pi^{+-}$ production in p-$O_2$ and p-$N_2$ interactions at 12 GeV/c

    CERN Document Server

    Catanesi, M.G.; Edgecock, R.; Ellis, M.; Gossling, C.; Bunyatov, S.; Krasnoperov, A.; Popov, B.; Tereschenko, V.; Di Capua, E.; Vidal-Sitjes, G.; Artamonov, A.; Giani, S.; Gilardoni, S.; Gorbunov, P.; Grant, A.; Grossheim, A.; Ivanchenko, A.; Ivanchenko, V.; Kayis-Topaksu, A.; Panman, J.; Papadopoulos, I.; Tcherniaev, E.; Tsukerman, I.; Wiebusch, C.; Zucchelli, P.; Blondel, A.; Borghi, S.; Morone, M.C.; Prior, G.; Schroeter, R.; Meurer, C.; Gastaldi, U.; Mills, G.B.; Graulich, J.S.; Gregoire, G.; Bonesini, M.; Ferri, F.; Kirsanov, M.; Bagulya, A.; Grichine, V.; Polukhina, N.; Palladino, V.; Coney, L.; Schmitz, D.; Barr, G.; Bobisut, F.; Gibin, D.; Guglielmi, A.; Mezzetto, M.; Dumarchez, J.; Dore, U.; Orestano, D.; Pastore, F.; Tonazzo, A.; Tortora, L.; Booth, C.; Howlett, L.; Bogomilov, M.; Kolev, D.; Tsenov, R.; Piperov, Stefan; Temnikov, P.; Apollonio, M.; Chimenti, P.; Giannini, G.; Burguet-Castell, J.; Cervera-Villanueva, A.; Gomez-Cadenas, J.J.; Martin-Albo, J.; Sorel, M.

    2008-01-01

    Measurements of double-differential charged pion production cross-sections in interactions of 12 GeV/c protons on O_2 and N_2 thin targets are presented in the kinematic range 0.5 GeV/c < p_{\\pi} < 8 GeV/c and 50 mrad < \\theta_{\\pi} < 250 mrad (in the laboratory frame) and are compared with p--C results. For p--N_2 (p--O_2) interactions the analysis is performed using 38576 (7522) reconstructed secondary pions. The analysis uses the beam instrumentation and the forward spectrometer of the HARP experiment at CERN PS. The measured cross-sections have a direct impact on the precise calculation of atmospheric neutrino fluxes and on the improved reliability of extensive air shower simulations by reducing the uncertainties of hadronic interaction models in the low energy range. In particular, the present results allow the common hypothesis that p--C data can be used to predict the p--N_2 and p--O_2 pion production cross-sections to be tested.

  6. Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial.

    Science.gov (United States)

    Nitz, Ulrike; Gluz, Oleg; Christgen, Matthias; Kates, Ronald E; Clemens, Michael; Malter, Wolfram; Nuding, Benno; Aktas, Bahriye; Kuemmel, Sherko; Reimer, Toralf; Stefek, Andrea; Lorenz-Salehi, Fatemeh; Krabisch, Petra; Just, Marianne; Augustin, Doris; Liedtke, Cornelia; Chao, Calvin; Shak, Steven; Wuerstlein, Rachel; Kreipe, Hans H; Harbeck, Nadia

    2017-10-01

    The prospective phase 3 PlanB trial used the Oncotype DX ® Recurrence Score ® (RS) to define a genomically low-risk subset of clinically high-risk pN0-1 early breast cancer (EBC) patients for treatment with adjuvant endocrine therapy (ET) alone. Here, we report five-year data evaluating the prognostic value of RS, Ki-67, and other traditional clinicopathological parameters. A central tumour bank was prospectively established within PlanB. Following an early amendment, hormone receptor (HR)+ , pN0-1 RS ≤ 11 patients were recommended to omit chemotherapy. Patients with RS ≥ 12, pN2-3, or HR-negative/HER2-negative disease were randomised to anthracycline-containing or anthracycline-free chemotherapy. Primary endpoint: disease-free survival (DFS). PlanB Clinicaltrials.gov identifier: NCT01049425. From 2009 to 2011, PlanB enrolled 3198 patients (central tumour bank, n = 3073) with the median age of 56 years, 41.1% pN+, and 32.5% grade 3 EBC. Chemotherapy was omitted in 348/404 (86.1%) eligible RS ≤ 11 patients. After 55 months of median follow-up, five-year DFS in ET-treated RS ≤ 11 patients was 94% (in both pN0 and pN1) versus 94% (RS 12-25) and 84% (RS > 25) in chemotherapy-treated patients (p 2 cm, and RS, but not IHC4 or Ki-67 were independent adverse factors. If RS was excluded, IHC4 or both Ki-67 and PR entered the model. The impact of RS was particularly pronounced in patients with intermediate Ki-67 (>10%, risk, genomically low-risk (RS ≤ 11) pN0-1 patients without adjuvant chemotherapy support using RS with standardised pathology for treatment decisions in HR+ HER2-negative EBC. Ki-67 has the potential to support patient selection for genomic testing.

  7. Discussion of isomeric ratios in (p, n) and (d, 2n) reaction

    Energy Technology Data Exchange (ETDEWEB)

    Bakhshiyan, T. M., E-mail: tiruhi44@mail.ru [Yerevan State University (Armenia)

    2016-01-15

    Isomeric ratios (IR) in the (p, n) and (d, 2n) reactions are considered. The dependence of IR values on the projectile type and energy, the target- and product-nucleus spin, the spin difference between the isomeric and ground states of products, and the product mass number is discussed. The isomeric ratios for 46 product nuclei (from {sup 44m,g}Sc to {sup 127m,g}Xe) obtained in reactions where target and product nuclei have identical mass numbers were calculated at energies from the reaction threshold to 50 MeV (with a step of ΔE = 1 MeV). The calculations in question were performed with the aid of the TALYS 1.4 code package. The calculated IR values were compared with their experimental counterparts available from the literature (EXFOR database). In the majority of cases, the calculated IR values agree well with the experimental data in question. It is noteworthy that the IR values obtained in (d, 2n) reactions are substantially greater than those in (p, n) reactions.

  8. Disrupted epithelial/macrophage crosstalk via Spinster homologue 2-mediated S1P signaling may drive defective macrophage phagocytic function in COPD.

    Directory of Open Access Journals (Sweden)

    Hai B Tran

    Full Text Available We have previously established a link between impaired phagocytic capacity and deregulated S1P signaling in alveolar macrophages from COPD subjects. We hypothesize that this defect may include a disruption of epithelial-macrophage crosstalk via Spns2-mediated intercellular S1P signaling.Primary alveolar macrophages and bronchial epithelial cells from COPD subjects and controls, cell lines, and a mouse model of chronic cigarette smoke exposure were studied. Cells were exposed to 10% cigarette smoke extract, or vehicle control. Spns2 expression and subcellular localization was studied by immunofluorescence, confocal microscopy and RT-PCR. Phagocytosis was assessed by flow-cytometry. Levels of intra- and extracellular S1P were measured by S1P [3H]-labeling.Spns2 expression was significantly increased (p<0.05 in alveolar macrophages from current-smokers/COPD patients (n = 5 compared to healthy nonsmokers (n = 8 and non-smoker lung transplant patients (n = 4. Consistent with this finding, cigarette smoke induced a significant increase in Spns2 expression in both human alveolar and THP-1 macrophages. In contrast, a remarkable Spns2 down-regulation was noted in response to cigarette smoke in 16HBE14o- cell line (p<0.001 in 3 experiments, primary nasal epithelial cells (p<0.01 in 2 experiments, and in smoke-exposed mice (p<0.001, n = 6 animals per group. Spns2 was localized to cilia in primary bronchial epithelial cells. In both macrophage and epithelial cell types, Spns2 was also found localized to cytoplasm and the nucleus, in line with a predicted bipartile Nuclear Localization Signal at the position aa282 of the human Spns2 sequence. In smoke-exposed mice, alveolar macrophage phagocytic function positively correlated with Spns2 protein expression in bronchial epithelial cells.Our data suggest that the epithelium may be the major source for extracellular S1P in the airway and that there is a possible disruption of epithelial/macrophage cross talk via

  9. A 1.1nW Energy Harvesting System with 544pW Quiescent Power for Next Generation Implants.

    Science.gov (United States)

    Bandyopadhyay, Saurav; Mercier, Patrick P; Lysaght, Andrew C; Stankovic, Konstantina M; Chandrakasan, Anantha P

    2014-12-01

    This paper presents a nW power management unit (PMU) for an autonomous wireless sensor that sustains itself by harvesting energy from the endocochlear potential (EP), the 70-100 mV electrochemical bio-potential inside the mammalian ear. Due to the anatomical constraints inside the inner ear, the total extractable power from the EP is limited to 1.1-6.25 nW. A nW boost converter is used to increase the input voltage (30-55 mV) to a higher voltage (0.8 to 1.1 V) usable by CMOS circuits in the sensor. A pW Charge Pump circuit is used to minimize the leakage in the boost converter. Further, ultra-low-power control circuits consisting of digital implementations of input impedance adjustment circuits and Zero Current Switching circuits along with Timer and Reference circuits keep the quiescent power of the PMU down to 544 pW. The designed boost converter achieves a peak power conversion efficiency of 56%. The PMU can sustain itself and a duty-cyled ultra-low power load while extracting power from the EP of a live guinea pig. The PMU circuits have been implemented on a 0.18µm CMOS process.

  10. Synthesis, in vitro pharmacologic characterization, and preclinical evaluation of N-[2-(1'-piperidinyl)ethyl]-3-[125I]iodo-4-methoxybenzamide (P[125I]MBA) for imaging breast cancer

    International Nuclear Information System (INIS)

    John, Christy S.; Bowen, Wayne D.; Fisher, Susan J.; Lim, Benjamin B.; Geyer, Brian C.; Vilner, Bertold J.; Wahl, Richard L.

    1999-01-01

    The goal of this study was to investigate the potential use of a radioiodinated benzamide, N-[2-(1'-piperidinyl)ethyl]-3-iodo[ 125 I]-4-methoxybenzamide (P[ 125 I]MBA), a sigma receptor binding radioligand for imaging breast cancer. The chemical and radiochemical syntheses of PIMBA are described. The pharmacological evaluation of PIMBA was carried out for sigma-1 and sigma-2 receptor sites. The in vivo pharmacokinetics of the radioiodinated benzamide were determined in rats and comparison of P[ 125 I]MBA with Tc-99m sestamibi were made in a rat mammary tumor model. Sigma-1 affinity (K i ) for PIMBA in guinea pig brain membranes using [ 3 H](+)pentazocine was found to be 11.82±0.68 nM, whereas sigma-2 affinity in rat liver using [ 3 H]DTG (1,3-o-di-tolylguanidine) was 206±11 nM. Sites in guinea pig brain membranes labeled by P[ 125 I]MBA showed high affinity for haloperidol, (+)-pentazocine, BD1008, and PIMBA ( K i =4.87±1.49,8.81±1.97,0.057±0.005,46.9±1.8 nM, respectively). Competition binding studies were carried out in human ductal breast carcinoma cells (T47D). A dose-dependent inhibition of specific binding was observed with several sigma ligands. K i values for the inhibition of P[ 125 I]MBA binding in T47D cells for haloperidol, N-[2-(1'-piperidinyl)]ethyl]4-iodobenzamide (IPAB), N-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP), and PIMBA were found to be 1.30±0.07, 13±1.5, 5.19±2.3, 1.06±0.5 nM, respectively. The in vitro binding data in guinea pig brain membranes and breast cancer cells confirmed binding to sigma sites. The saturation binding of P[ 125 I]MBA in T47D cells as studied by Scatchard analysis showed saturable binding, with a K d =94±7 nM and a B max =2035±305 fmol/mg of proteins. Biodistribution studies in Sprague-Dawley rats showed a rapid clearance of P[ 125 I]MBA from the normal organs. The potential of PIMBA in imaging breast cancer was evaluated in Lewis rats bearing syngeneic RMT breast cancers, a cancer that closely mimics

  11. P-type doping of GaN(000\\bar{1}) by magnesium ion implantation

    Science.gov (United States)

    Narita, Tetsuo; Kachi, Tetsu; Kataoka, Keita; Uesugi, Tsutomu

    2017-01-01

    Magnesium ion implantation has been performed on a GaN(000\\bar{1}) substrate, whose surface has a high thermal stability, thus allowing postimplantation annealing without the use of a protective layer. The current-voltage characteristics of p-n diodes fabricated on GaN(000\\bar{1}) showed distinct rectification at a turn-on voltage of about 3 V, although the leakage current varied widely among the diodes. Coimplantation with magnesium and hydrogen ions effectively suppressed the leakage currents and device-to-device variations. In addition, an electroluminescence band was observed at wavelengths shorter than 450 nm for these diodes. These results provide strong evidence that implanted magnesium ions create acceptors in GaN(000\\bar{1}).

  12. Prognostic implication of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma: a tissue microarray study

    Directory of Open Access Journals (Sweden)

    Wang Facheng

    2008-10-01

    Full Text Available Abstract Background p27Kip1 plays a major role as a negative regulator of the cell cycle. The regulation of p27Kip1 degradation is mediated by its specific ubiquitin ligase subunits S-phase kinase protein (Skp 2 and cyclin-dependent kinase subunit (Cks 1. However, little is known regarding the prognostic utility of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma. Methods Immunohistochemistry was performed for p27Kip1, Skp2 and Cks1 in tissue microarrays of 482 renal cell carcinomas with follow-up. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance. Results Immunoreactivity of p27Kip1, Skp2 and Cks1 was noted in 357, 71 and 82 patients, respectively. Skp2 and Cks1 expression were not noted in chromophobe cancers. A strong correlation was found between Skp2 and Cks1 expression (P Kip1 levels (P = 0.006 and P Kip1 expression and Skp2 expression were correlated with larger tumor size and higher stage, as well as tumor necrosis. Cks1 expression was only correlated with tumor size. In univariate analysis, low p27Kip1 expression, Skp2 and Cks1 expression were all associated with a poor prognosis, while in multivariate analysis, only low p27Kip1 expression were independent prognostic factors for both cancer specific survival and recurrence-free survival in patients with RCC. Conclusion Our results suggest that immunohistochemical expression levels of p27Kip1, Skp2 and Cks1 may serve as markers with prognostic value in renal cell carcinoma.

  13. SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity.

    Science.gov (United States)

    Lee, Soonduck; Kim, Jinsun; Jung, Samil; Li, Chengping; Yang, Young; Kim, Keun Il; Lim, Jong-Seok; Kim, Yonghwan; Cheon, Choong-Il; Lee, Myeong-Sok

    2015-03-01

    Vitamin C is considered as an important anticancer therapeutic agent although this view is debatable. In this study, we introduce a physiological mechanism demonstrating how vitamin C exerts anticancer activity that induces cell cycle arrest and apoptosis. Our previous and current data reveal that p53 tumor suppressor is the prerequisite factor for stronger anticancer effects of vitamin C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be achieved at least partly through the downregulation of the p34SEI-1 oncoprotein. Our previous study showed that p34SEI-1 increases the survival of various types of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin C treatment decreases the p34SEI-1 expression at the protein level and therefore alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase, appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent degradation, which is dependent on p53. In summary, vitamin C increases cancer cell death by inducing SIAH1-mediated polyubiquitination/degradation of the p34SEI-1 oncoprotein in a p53-dependent manner.

  14. SCO2 induces p53-mediated apoptosis by Thr845 phosphorylation of ASK-1 and dissociation of the ASK-1-Trx complex.

    Science.gov (United States)

    Madan, Esha; Gogna, Rajan; Kuppusamy, Periannan; Bhatt, Madan; Mahdi, Abbas Ali; Pati, Uttam

    2013-04-01

    p53 prevents cancer via cell cycle arrest, apoptosis, and the maintenance of genome stability. p53 also regulates energy-generating metabolic pathways such as oxidative phosphorylation (OXPHOS) and glycolysis via transcriptional regulation of SCO2 and TIGAR. SCO2, a cytochrome c oxidase assembly factor, is a metallochaperone which is involved in the biogenesis of cytochrome c oxidase subunit II. Here we have shown that SCO2 functions as an apoptotic protein in tumor xenografts, thus providing an alternative pathway for p53-mediated apoptosis. SCO2 increases the generation of reactive oxygen species (ROS) and induces dissociation of the protein complex between apoptosis signal-regulating kinase 1 (ASK-1) (mitogen-activated protein kinase kinase kinase [MAPKKK]) and its cellular inhibitor, the redox-active protein thioredoxin (Trx). Furthermore, SCO2 induces phosphorylation of ASK-1 at the Thr(845) residue, resulting in the activation of the ASK-1 kinase pathway. The phosphorylation of ASK-1 induces the activation of mitogen-activated protein kinase kinases 4 and 7 (MAP2K4/7) and MAP2K3/6, which switches the c-Jun N-terminal protein kinase (JNK)/p38-dependent apoptotic cascades in cancer cells. Exogenous addition of the SCO2 gene to hypoxic cancer cells and hypoxic tumors induces apoptosis and causes significant regression of tumor xenografts. We have thus discovered a novel apoptotic function of SCO2, which activates the ASK-1 kinase pathway in switching "on" an alternate mode of p53-mediated apoptosis. We propose that SCO2 might possess a novel tumor suppressor function via the ROS-ASK-1 kinase pathway and thus could be an important candidate for anticancer gene therapy.

  15. Measurement of the spin-forbidden decay rate (3s3d)1D2¿(3s3p)3 P2,1 in 24Mg

    DEFF Research Database (Denmark)

    Therkildsen, K. T.; Jensen, Brian Bak; Ryder, C. P.

    2009-01-01

    We have measured the spin-forbidden decay rate from (3s3d)D12¿(3s3p)P32,1 in M24g atoms trapped in a magneto-optical trap. The total decay rate, summing up both exit channels (3s3p)P31 and (3s3p)P32 , yields 196±10s-1 in excellent agreement with resent relativistic many-body calculations of Porse...

  16. Students in Differential Equations and Epidemiology Model a Campus Outbreak of pH1N1

    Directory of Open Access Journals (Sweden)

    Meredith L. Greer

    2012-08-01

    Full Text Available We describe a semester-long collaboration between a mathematics class and a biology class. Students worked together to understand and model the trajectory of the pandemic H1N1, pH1N1, outbreak across campus in fall 2009. Each course had about 30 students and was an upper-level elective for majors. Some mathematics students had taken no college-level biology, and some biology students had taken no college-level mathematics. All students had taken at least three quantitative courses, so they had some experience working with data. Our goals were to allow students to work with and model a real data set that affected them personally, to explore how the outbreak spread within our small campus, and for students to share their areas of expertise. This project created opportunities for synthesis and evaluation.  

  17. Calculation of the energy of particles emitted by the reactions {sup 3}{sub 1}T (d,n) {sup 4}{sub 2}He, D (d,n) {sup 3}{sub 2}He and D (d,p) T; Calcul de l'energie des particules emises par les reactions {sup 3}{sub 1}T (d,n) {sup 4}{sub 2}He, D (d,n) {sup 3}{sub 2}He et D (d,p) T

    Energy Technology Data Exchange (ETDEWEB)

    Oria, M; Sorriaux, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1965-07-01

    With a view to ease the work of research workers using 150 kV electrostatic accelerators, we have calculated the energy and the emission angle of particles emitted during the reactions {sub 1}{sup 3}T(d,n){sub 2}{sup 4}He, {sub 1}{sup 2}D(d,n){sub 2}{sup 3}He and {sub 1}{sup 2}D(d,p){sub 1}{sup 3}T. The results are classified in tables and arranged according to the acceleration energy of the deuterons. Since the energies considered are relatively low we have limited our study to the non-relativistic domain; this simplification results in a maximum energy variation with respect to the real energy values of 1 per cent. We give also two curves representing the variations in the total cross-sections for the reactions T (d,n){sub 2}{sup 4}He and D (d,n){sub 2}{sup 3}He. (authors) [French] De facon a faciliter la tache des experimentateurs utilisant des accelerateurs electrostatiques de 150 kV, nous avons calcule l'energie et l'angle d'emission des particules emises lors des reactions {sub 1}{sup 3}T(d,n){sub 2}{sup 4}He, {sub 1}{sup 2}D(d,n){sub 2}{sup 3}He and {sub 1}{sup 2}D(d,p){sub 1}{sup 3}T. Les resultats ont ete classes dans des tableaux, et ordonnes en fonction de l'energie d'acceleration des deuterons. Les energies considerees etant relativement peu elevees, nous avons limite notre etude au domaine non relativiste, cette simplification n'entraine qu'une variation maximale de 1 pour cent sur les valeurs reelles des energies. Nous avons joint a ce calcul deux courbes representant la variation des sections efficaces totales des reactions T (d,n){sub 2}{sup 4}He et D (d,n){sub 2}{sup 3}He. (auteurs)

  18. The tumor suppressors p33ING1 and p33ING2 interact with alien in vivo and enhance alien-mediated gene silencing.

    Science.gov (United States)

    Fegers, Inga; Kob, Robert; Eckey, Maren; Schmidt, Oliver; Goeman, Frauke; Papaioannou, Maria; Escher, Niko; von Eggeling, Ferdinand; Melle, Christian; Baniahmad, Aria

    2007-11-01

    The tumor suppressor p33ING1 is involved in DNA repair and cell cycle regulation. Furthermore, p33ING1 is a transcriptional silencer that recognizes the histone mark for trimethylated lysine 4 at histone H3. Interestingly, expression of p33ING1 and p33ING2 is able to induce premature senescence in primary human fibroblasts. The corepressor Alien is involved in gene silencing mediated by selected members of nuclear hormone receptors. In addition, Alien acts as a corepressor for E2F1, a member of the E2F cell cycle regulatory family. Furthermore, recent findings suggest that Alien is complexed with transcription factors participating in DNA repair and chromatin. Here, using a proteomic approach by surface-enhanced laser desorption ionization and mass spectrometry (SELDI-MS) combined with immunological techniques, we show that Alien interacts in vivo with the tumor suppressor p33ING1 as well as with the related tumor suppressor candidate p33ING2. The interaction of Alien with p33ING1 and p33ING2 was confirmed in vitro with GST-pull-down, suggesting a direct binding of Alien to these factors. The binding domain was mapped to a central region of Alien. Functionally, the expression of p33ING1 or p33ING2 enhances the Alien-mediated silencing, suggesting that the interaction plays a role in transcriptional regulation. Thus, the findings suggest that the identified interaction between Alien and the tumor suppressors p33ING1 and p33ING2 reveals a novel cellular protein network.

  19. Investigation of. epsilon. sub 1 and the sup 3 P sub J phase shifts in the n-p system by the measurement of polarization transfer coefficients in p-d elastic scattering

    Energy Technology Data Exchange (ETDEWEB)

    Clajus, M.; Egun, P.M.; Grueebler, W.; Hautle, P. (Eidgenoessische Technische Hochschule, Zurich (Switzerland). Inst. fuer Mittelenergiephysik); Kretschmer, W.; Rauscher, A.; Schuster, W.; Weidmann, R.; Haller, M. (Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Physikalisches Inst.); Bruno, M.; Cannata, F.; D' Agostino, M. (Istituto Nazionale di Fisica Nucleare, Bologna (Italy) Bologna Univ. (Italy). Dipt. di Fisica); Slaus, I. (Institut Rudjer Boskovic, Zagreb (Yugoslavia)); Schmelzbach, P.A. (Paul Scherrer Inst., Villigen (Switzerland)); Vuaridel, B. (Michigan Univ., Ann Arbor (USA)); Sperisen, F. (Indiana Univ., Bloomington (USA). Cyclotron Facility); Witala, H.; Cornelius, T.; Gloeckle, W. (Bochum Univ. (Germany, F.R.))

    1990-02-01

    The {sup 3}S{sub 1}-{sup 3}D{sub 1} mixing parameter {epsilon}{sub 1} and the {sup 3}P{sub J} phase shifts in the N-N system at low energy are investigated in the three nucleon system. The sensitivity of polarization transfer coefficients in p-d elastic scattering is determined by rigorous Faddeev calculations using Paris and Bonn potentials. The experimental results of K{sub y}sup(y') favours the tensor force component of the Bonn A potential. (orig.).

  20. Search for high-mass resonances decaying to e mu in p anti-p collisions at s**(1/2) = 1.96-TeV

    Energy Technology Data Exchange (ETDEWEB)

    Abulencia, A.; Acosta, D.; Adelman, Jahred A.; Affolder, T.; Akimoto, T.; Albrow, M.G.; Ambrose, D.; Amerio, S.; Amidei, D.; Anastassov, A.; Anikeev, K.; /Taiwan, Inst.

    2006-03-01

    The authors describe a general search for resonances decaying to a neutral e{mu} final state in p{bar p} collisions at a center-of-mass energy of 1.96 TeV. Using a data sample representing 344 pb{sup -1} of integrated luminosity recorded by the CDF II experiment, they compare Standard Model predictions with the number of observed events for invariant masses between 50 and 800 GeV/c{sup 2}. Finding no significant excess (5 events observed vs. 7.7 {+-} 0.8 expected for M{sub e{mu}} > 100 GeV/c{sup 2}), they set limits on sneutrino and Z{prime} masses as functions of lepton family number violating couplings.

  1. Characterization of P1 promoter activity of the β-galactoside α2,6 ...

    Indian Academy of Sciences (India)

    2012-04-05

    Apr 5, 2012 ... The level of β-galactoside α2,6-sialyltransferase I (ST6Gal I) mRNA, encoded by the gene siat1, is increased in malignant tissues. Expression is regulated by different promoters – P1, P2 and P3 – generating three mRNA isoforms. H, X and YZ. In cervical cancer tissue the mRNA isoform H, which results ...

  2. Study on (n,2n) and (n,p) reactions of strontium nucleus

    Energy Technology Data Exchange (ETDEWEB)

    Yiğit, Mustafa, E-mail: mustafayigit@aksaray.edu.tr [Aksaray University, Department of Physics, Faculty of Arts and Science, Aksaray (Turkey); Tel, Eyyup [Osmaniye Korkut Ata University, Department of Physics, Faculty of Arts and Science, Osmaniye (Turkey)

    2015-11-15

    Highlights: • The cross sections for (n,2n) and (n,p) nuclear reactions on {sup 84,86,88,90}Sr target nuclei have been investigated. • The codes ALICE/ASH, PCROSS, CEM03.01, and cross section systematics are carried out in the calculations. • Cross section calculations are given at projectile energy range from the threshold up to 30 MeV. • Obtained results are compared with each other, experimental data, and ENDF/B-VII.1 and TENDL-2014 libraries. - Abstract: The cross sections for (n,2n) and (n,p) nuclear reactions on {sup 84,86,88,90}Sr target nuclei up to 30 MeV from threshold have been investigated. The determination of the cross sections has been done employing the codes ALICE/ASH, PCROSS, CEM03.01 which taking into consideration compound and precompound emissions. Calculations have been performed by using the Weisskopf Ewing model (WEM) of compound reaction mechanism, and the Hybrid model (HM), Geometry Dependent Hybrid model (GDHM) and Full Exciton model (FEM) of precompound reaction mechanism, and Cascade Exciton model (CEM) including Cascade interactions, and the empirical and semi-emipirical systematics. In order to test the theoretical nuclear models, the data obtained from the excitation function calculations are discussed and compared with available experimental values, ENDF/B-VII.1 and TENDL-2014 libraries. Finally the new cross section results calculated in the present paper may be useful for nuclear energy applications.

  3. Vitamin D attenuates sphingosine-1-phosphate (S1P)-mediated inhibition of extravillous trophoblast migration.

    Science.gov (United States)

    Westwood, Melissa; Al-Saghir, Khiria; Finn-Sell, Sarah; Tan, Cherlyn; Cowley, Elizabeth; Berneau, Stéphane; Adlam, Daman; Johnstone, Edward D

    2017-12-01

    Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems, the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration therefore this study determined its effect on extravillous trophoblast (EVT) function. A transwell migration system was used to assess the behaviour of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and 1,25(OH) 2 D 3 . QPCR and immunolocalisation were used to demonstrate EVT S1P receptor expression. EVTs express S1P receptors 1, 2 and 3. S1P inhibited EVT migration. This effect was abolished in the presence of the specific S1PR2 inhibitor, JTE-013 (p S1P alone) whereas treatment with the S1R1/3 inhibitor, FTY720, had no effect. In other cell types S1PR2 is regulated by vitamin D; here we found that treatment with 1,25(OH) 2 D 3 for 48 or 72 h reduces S1PR2 (4-fold; S1P did not inhibit the migration of cells exposed to 1,25(OH) 2 D 3 (p S1P receptor isoforms, S1P predominantly signals through S1PR2/Gα 12/13 to activate Rho and thereby acts as potent inhibitor of EVT migration. Importantly, expression of S1PR2, and therefore S1P function, can be down-regulated by vitamin D. Our data suggest that vitamin D deficiency, which is known to be associated with PE, may contribute to the impaired trophoblast migration that underlies this condition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. H1N1, H3N2 et B à Abidjan, Côte d'Ivoire

    African Journals Online (AJOL)

    English Title: Comparative analysis of the epidemiological and clinical profiles of influenza infection due to 2009 pH1N1, H1N1, H3N2 and B viruses in Abidjan, Cote d'Ivoire. English Abstract. Influenza can have various epidemiological and clinical characteristics. This study compares the epidemio-clinical profiles of ...

  5. Spectroscopic constants and the potential energy curve of the iodine weakly bound 0+g state correlating with the I(2P1/2) + I(2P1/2) dissociation limit

    International Nuclear Information System (INIS)

    Akopyan, M E; Baturo, V V; Lukashov, S S; Poretsky, S A; Pravilov, A M

    2013-01-01

    The stepwise three-step three-colour aser excitation scheme and rotational as well as rovibrational energy transfer processes in the 0 + g state induced by collisions with He and Ar atoms are used for determination of rovibronic level energies of the weakly bound 0 + g state correlating with the I( 2 P 1/2 ) + I( 2 P 1/2 ) dissociation limit. Dunham coefficients of the state, Y i0 (i = 0–3), Y i1 (i = 0–3) and Y 02 for the v 0 g + = 0–16 and J 0 g + ≈ 14–135 ranges as well as the dissociation energy of the state, D e , and equilibrium I–I distance of the state, R e , are determined. The potential energy curve of the state constructed using these constants is also reported. (paper)

  6. Purinergic control of inflammation and thrombosis: Role of P2X1 receptors

    Directory of Open Access Journals (Sweden)

    Cécile Oury

    2015-01-01

    Full Text Available Inflammation shifts the hemostatic mechanisms in favor of thrombosis. Upon tissue damage or infection, a sudden increase of extracellular ATP occurs, that might contribute to the crosstalk between inflammation and thrombosis. On platelets, P2X1 receptors act to amplify platelet activation and aggregation induced by other platelet agonists. These receptors critically contribute to thrombus stability in small arteries. Besides platelets, studies by our group indicate that these receptors are expressed by neutrophils. They promote neutrophil chemotaxis, both in vitro and in vivo. In a laser-induced injury mouse model of thrombosis, it appears that neutrophils are required to initiate thrombus formation and coagulation activation on inflamed arteriolar endothelia. In this model, by using P2X1−/− mice, we recently showed that P2X1 receptors, expressed on platelets and neutrophils, play a key role in thrombus growth and fibrin generation. Intriguingly, in a model of endotoxemia, P2X1−/− mice exhibited aggravated oxidative tissue damage, along with exacerbated thrombocytopenia and increased activation of coagulation, which translated into higher susceptibility to septic shock. Thus, besides its ability to recruit neutrophils and platelets on inflamed endothelia, the P2X1 receptor also contributes to limit the activation of circulating neutrophils under systemic inflammatory conditions. Taken together, these data suggest that P2X1 receptors are involved in the interplay between platelets, neutrophils and thrombosis. We propose that activation of these receptors by ATP on neutrophils and platelets represents a new mechanism that regulates thrombo-inflammation.

  7. Does the delta quench Gamow-Teller strength in (p,n)- and (p vector,p vector')-reactions

    International Nuclear Information System (INIS)

    Osterfeld, F.; Schulte, A.; Udagawa, T.; Yabe, M.

    1986-01-01

    Microscopic analyses of complete forward angle intermediate energy (p,n)-, ( 3 He,t)- and (p vector,p vector')-spin-flip spectra are presented for the reactions 90 Zr(p,n), 90 Zr( 3 He,t) and 90 Zr(p vector,p vector'). It is shown that the whole spectra up to high excitation energies (E X ∝50 MeV) are the result of correlated one-particle-one-hole (1p1h) spin-isospin transitions only. The spectra reflect, therefore, the linear spin-isospin response of the target nucleus to the probing external hadronic fields. Our results suggest that the measured (p,n)-, ( 3 He,t)- and (p vector,p vector')-cross sections are compatible with the transition strength predictions as obtained from random phase approximation (RPA) calculations. This means that the Δ isobar quenching mechanism is likely to be rather small. (orig.)

  8. Mcm1p binding sites in ARG1 positively regulate Gcn4p binding and SWI/SNF recruitment

    OpenAIRE

    Yoon, Sungpil; Hinnebusch, Alan G.

    2009-01-01

    Transcription of the arginine biosynthetic gene ARG1 is activated by Gcn4p, a transcription factor induced by starvation for any amino acid. Previously we showed that Gcn4p binding stimulates the recruitment of Mcm1p and co-activator SWI/SNF to ARG1 in cells via Gcn4p induction through amino acid starvation. Here we report that Gcn4p binding is reduced by point mutations of the Mcm1p binding site and increased by overexpression of Mcm1p. This result suggests that Mcm1p plays a positive role i...

  9. Caffeic acid phenethyl ester induced cell cycle arrest and growth inhibition in androgen-independent prostate cancer cells via regulation of Skp2, p53, p21Cip1 and p27Kip1

    OpenAIRE

    Lin, Hui-Ping; Lin, Ching-Yu; Huo, Chieh; Hsiao, Ping-Hsuan; Su, Liang-Cheng; Jiang, Shih Sheng; Chan, Tzu-Min; Chang, Chung-Ho; Chen, Li-Tzong; Kung, Hsing-Jien; Wang, Horng-Dar; Chuu, Chih-Pin

    2015-01-01

    Prostate cancer (PCa) patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant prostate cancer (CRPC) within 1?3 years. Treatment with caffeic acid phenethyl ester (CAPE) suppressed cell survival and proliferation via induction of G1 or G2/M cell cycle arrest in LNCaP 104-R1, DU-145, 22Rv1, and C4?2 CRPC cells. CAPE treatment also inhibited soft agar colony formation and retarded nude mice xenograft growth of LNCaP 104-R1 cells. We identified that CAP...

  10. Evaluation of Some (n,n'), (n,γ), (n,p), (n,2n) and (n,3n) Reaction Excitation Functions for Fission and Fusion Reactor Dosimetry Applications; Evaluation of the Excitation Functions for the 54Fe(n,p)54Mn, 58Ni(n,2n)57Ni, 67Zn(n,p)67Cu, 92Mo(n,p)92mNb, 93Nb(n,γ)94Nb, 113In(n,n')113mIn, 115In(n,γ) 116mIn, and 169Tm(n,3n)167Tm Reactions. Progress Report on Research Contract No 16242

    International Nuclear Information System (INIS)

    Zolotarev, K.I.; Zolotarev, P.K.

    2013-12-01

    Cross section data for the 54 Fe(n,p) 54 Mn, 58 Ni(n,2n) 57 Ni, 67 Zn(n,p) 67 Cu, 92 Mo(n,p) 92m Nb, 93 Nb(n,γ) 94 Nb, 113 In(n,n') 113m In, 115 In(n,γ) 116m In, 169 Tm(n,3n) 167 Tm reactions are needed to solve a wide spectrum of scientific and technical tasks. Activation detectors based on these reactions may be used in the field of reactor dosimetry. Furthermore, the 54 Fe(n,p) 54 Mn reaction is often used in experimental nuclear physics as a monitor reaction for measurements of unknown cross sections by means of the activation method over the neutron energy range from 5 to 15 MeV. The 93 Nb(n,γ) 94 Nb reaction is also very promising for using in retrospective neutron dosimetry for determination of total neutron fluence during a campaign of a reactor. In the existing version of the International Reactor Dosimetry File and the new extended version named as IRDFF data for excitation functions of 67 Zn(n,p) 67 Cu, 92 Mo(n,p) 92m Nb, 113 In(n,n') 113m In, and 169 Tm(n,3n) 167 Tm reactions are absent. Data for these reactions are also absent in the JENDL/D-99 dosimetry file. Excitation functions of 67 Zn(n,p) 67 Cu and 169 Tm(n,3n) 167 Tm are presented in the TENDL-2012, EAF-2010, JENDL-4.0, JEFF-3.1/A, MENDL-2 libraries. Cross section data for the 67 Zn(n,p) 67 Cu reaction up to 20 MeV are given also in the JENDL/HE-2007 library. Excitation functions of the 92 Mo(n,p) 92m Nb and 113 In(n,n') 113m In reactions are evaluated in the EAF-2010 and JEFF-3.1/A libraries. Cross section data for the 113 In(n,n') 113m In reaction are given also in the TENDL-2010 library. It is necessary to note that neutron data in the JEFF-3.1/A and JENDL-4.0 libraries were evaluated up to 20 MeV. Neutron data in the TENDL-2012, EAF-2010, MENDL-2 and TENDL-2010 libraries had been evaluated up to 30 MeV, 60 MeV, 100 MeV and 200 MeV, respectively. Neutron cross sections in the MENDL-2, TENDL-2010 and TENDL-2012 libraries had been obtained on the basis of pure theoretical model calculations

  11. Vorinostat enhances protein stability of p27 and p21 through negative regulation of Skp2 and Cks1 in human breast cancer cells.

    Science.gov (United States)

    Uehara, Norihisa; Yoshizawa, Katsuhiko; Tsubura, Airo

    2012-07-01

    Vorinostat is a histone deacetylase inhibitor that blocks cancer cell proliferation through the regulation of cyclin-dependent kinase inhibitors. We, herein, examined the involvement of S-phase kinase-associated protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1), the components of the SCFSkp2-Cks1 (Skp1/Cul1/F-box protein) ubiquitin ligase complex, in the regulation of p27 and p21 during vorinostat-induced growth arrest of MDA-MB-231 and MCF-7 human breast cancer cells. Vorinostat significantly reduced BrdU incorporation in MDA-MB-231 and MCF-7 cells, which was associated with increased p27 and p21 protein levels without concomitant induction of p27 mRNA. Vorinostat-induced accumulation of p27 and p21 proteins was inversely correlated with the mRNA and protein levels of Skp2 and Cks1. Cycloheximide chase analysis revealed that vorinostat increased the half-life of p27 and p21 proteins. The accumulation of p27 and p21 proteins was attenuated by forced expression of Skp2 and Cks1, which conferred resistance to the vorinostat-induced S-phase reduction. These results suggest that vorinostat-induced growth arrest may be in part due to the enhanced protein stability of p27 and p21 through the downregulation of Skp2 and Cks1.

  12. Reliable measurement of the Li-like 2248Ti 1s2s2p 4P5/2o level lifetime by beam-foil and beam-two-foil experiments

    International Nuclear Information System (INIS)

    Nandi, T.; Ahmad, Nissar; Wani, A. A.; Marketos, P.

    2006-01-01

    We have determined the lifetime of the Li-like 22 48 Ti 1s2s2p 4 P 5/2 o level (210.5±13.5 ps) using data from its x-ray decay channel through beam single- and two-foil experiments, coupled to a multicomponent iterative growth and decay analysis. Theoretical lifetime estimates for this zero-nuclear-spin ion lies within the uncertainty range of our experimental results, indicating that blending contributions to this level from the He-like 1s2p 3 P 2 o and 1s2s 3 S 1 levels are eliminated within the current approach. A previously reported discrepancy between experimental and theoretical 1s2s2p 4 P 5/2 o level lifetimes in 23 51 V may, as a result, be attributed to hyperfine quenching

  13. Ceramide synthase 2 facilitates S1P-dependent egress of thymocytes into the circulation in mice.

    Science.gov (United States)

    Rieck, Michael; Kremser, Christiane; Jobin, Katarzyna; Mettke, Elisabeth; Kurts, Christian; Gräler, Markus; Willecke, Klaus; Kolanus, Waldemar

    2017-04-01

    Well-defined gradients of the lipid mediator sphingosine-1-phosphate (S1P) direct chemotactic egress of mature thymocytes from the thymus into the circulation. Although it is known that these gradients result from low S1P levels in the thymic parenchyma and high S1P concentrations at the exit sites and in the plasma, the biochemical mechanisms that regulate these differential S1P levels remain unclear. Several studies demonstrated that ceramide synthase 2 (Cers2) regulates the levels of the S1P precursor sphingosine. We, therefore, investigated whether Cers2 is involved in the regulation of S1P gradients and S1P-dependent egress into the circulation. By analyzing Cers2-deficient mice, we demonstrate that Cers2 limits the levels of S1P in thymus and blood to maintain functional S1P gradients that mediate thymocyte emigration into the circulation. This function is specific for Cers2, as we also show that Cers4 is not involved in the regulation of thymic egress. Our study identified Cers2 as an important regulator of S1P-dependent thymic egress, and thus contributes to the understanding of how S1P gradients are maintained in vivo. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Homoleptic diphosphacyclobutadiene complexes [M(η(4)-P2C2R2)2]x- (M = Fe, Co; x = 0, 1).

    Science.gov (United States)

    Wolf, Robert; Ehlers, Andreas W; Khusniyarov, Marat M; Hartl, František; de Bruin, Bas; Long, Gary J; Grandjean, Fernande; Schappacher, Falko M; Pöttgen, Rainer; Slootweg, J Chris; Lutz, Martin; Spek, Anthony L; Lammertsma, Koop

    2010-12-27

    The preparation and comprehensive characterization of a series of homoleptic sandwich complexes containing diphosphacyclobutadiene ligands are reported. Compounds [K([18]crown-6)(thf)(2)][Fe(η(4)-P(2)C(2)tBu(2))(2)] (K1), [K([18]crown-6)(thf)(2)][Co(η(4)-P(2)C(2)tBu(2))(2)] (K2), and [K([18]crown-6)(thf)(2)][Co(η(4)-P(2)C(2)Ad(2))(2)] (K3, Ad = adamantyl) were obtained from reactions of [K([18]crown-6)(thf)(2)][M(η(4)-C(14)H(10))(2)] (M = Fe, Co) with tBuC[triple bond]P (1, 2), or with AdC[triple bond]P (3). Neutral sandwiches [M(η(4)-P(2)C(2)tBu(2))(2)] (4: M = Fe 5: M = Co) were obtained by oxidizing 1 and 2 with [Cp(2)Fe]PF(6). Cyclic voltammetry and spectro-electrochemistry indicate that the two [M(η(4)-P(2)C(2)tBu(2))(2)](-)/[M(η(4)-P(2)C(2)tBu(2))(2)] moieties can be reversibly interconverted by one electron oxidation and reduction, respectively. Complexes 1-5 were characterized by multinuclear NMR, EPR (1 and 5), UV/Vis, and Mössbauer spectroscopies (1 and 4), mass spectrometry (4 and 5), and microanalysis (1-3). The molecular structures of 1-5 were determined by using X-ray crystallography. Essentially D(2d)-symmetric structures were found for all five complexes, which show the two 1,3-diphosphacyclobutadiene rings in a staggered orientation. Density functional theory calculations revealed the importance of covalent metal-ligand π bonding in 1-5. Possible oxidation state assignments for the metal ions are discussed.

  15. Histone deacetylase 3 represses p15INK4b and p21WAF1/cip1 transcription by interacting with Sp1

    International Nuclear Information System (INIS)

    Huang Weifeng; Tan Dapeng; Wang Xiuli; Han Songyan; Tan Jiang; Zhao Yanmei; Lu Jun; Huang Baiqu

    2006-01-01

    Histone deacetylase 3 (HDAC3) has been implicated to play roles in governing cell proliferation. Here we demonstrated that the overexpression of HDAC3 repressed transcription of p15 INK4b and p21 WAF1/cip1 genes in 293T cells, and that the recruitment of HDAC3 to the promoter regions of these genes was critical to this repression. We also showed that HDAC3 repressed GAL4-Sp1 transcriptional activity, and that Sp1 was co-immunoprecipitated with FLAG-tagged HDAC3. We conclude that HDAC3 can repress p15 INK4b and p21 WAF1/cip1 transcription by interacting with Sp1. Furthermore, knockdown of HDAC3 by RNAi up-regulated the transcriptional expression of p15 INK4b , but not that of p21 WAF1/cip1 , implicating the different roles of HDAC3 in repression of p15 INK4b and p21 WAF1/cip1 transcription. Data from this study indicate that the inhibition of p15 INK4b and p21 WAF1/cip1 may be one of the mechanisms by which HDAC3 participates in cell cycle regulation and oncogenesis

  16. Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk

    Science.gov (United States)

    Broderick, Peter; Chen, Bowang; Johnson, David C; Försti, Asta; Vijayakrishnan, Jayaram; Migliorini, Gabriele; Dobbins, Sara E; Holroyd, Amy; Hose, Dirk; Walker, Brian A; Davies, Faith E; Gregory, Walter A; Jackson, Graham H; Irving, Julie A; Pratt, Guy; Fegan, Chris; Fenton, James AL; Neben, Kai; Hoffmann, Per; Nöthen, Markus M; Mühleisen, Thomas W; Eisele, Lewin; Ross, Fiona M; Straka, Christian; Einsele, Hermann; Langer, Christian; Dörner, Elisabeth; Allan, James M; Jauch, Anna; Morgan, Gareth J; Hemminki, Kari; Houlston, Richard S; Goldschmidt, Hartmut

    2016-01-01

    To identify variants for multiple myeloma risk, we conducted a genome-wide association study with validation in additional series totaling 4,692 cases and 10,990 controls. We identified four risk loci at 3q26.2 (rs10936599, P=8.70x10-14), 6p21.33 (rs2285803, PSORS1C2; P= 9.67x10-11), 17p11.2 (rs4273077, TNFRSF13B; P=7.67x10-9) and 22q13.1 (rs877529, CBX7; P=7.63x10-16). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy and insight into the biological basis of predisposition. PMID:23955597

  17. catena-Poly[[[diaquacopper(II]-μ-2,2′-{[p-phenylenebis(oxymethylene]bis(pyridinium-3,1-diyl}diacetate] dibromide

    Directory of Open Access Journals (Sweden)

    Wei-Cheng Pan

    2010-06-01

    Full Text Available The title centrosymmetric coordination polymer, {[Cu(C22H20N2O6(H2O2]Br2}n, formed by the reaction of the flexible double betaine ligand 2,2′-{[p-phenylenebis(oxymethylene]bis(pyridine-3,1-diyl}diacetic acid with CuBr2, contains a Cu(II atom (overline1 symmetry which is surrounded by two water molecules and bridged by two anions in a square-planar coordination. In the crystal, polymeric zigzag chains are linked via O—H...Br interactions, forming a two-dimensional network extending parallel to (011.

  18. Sphingosine-1-Phosphate (S1P) Signaling in Neural Progenitors.

    Science.gov (United States)

    Callihan, Phillip; Alqinyah, Mohammed; Hooks, Shelley B

    2018-01-01

    Sphingosine-1-phosphate (S1P) and its receptors are important in nervous system development. Reliable in vitro human model systems are needed to further define specific roles for S1P signaling in neural development. We have described S1P-regulated signaling, survival, and differentiation in a human embryonic stem cell-derived neuroepithelial progenitor cell line (hNP1) that expresses functional S1P receptors. These cells can be further differentiated to a neuronal cell type and therefore represent a good model system to study the role of S1P signaling in human neural development. The following sections describe in detail the culture and differentiation of hNP1 cells and two assays to measure S1P signaling in these cells.

  19. Transformation of Astrocytes to a Neuroprotective Phenotype by Microglia via P2Y1 Receptor Downregulation

    Directory of Open Access Journals (Sweden)

    Youichi Shinozaki

    2017-05-01

    Full Text Available Microglia and astrocytes become reactive following traumatic brain injury (TBI. However, the coordination of this reactivity and its relation to pathophysiology are unclear. Here, we show that microglia transform astrocytes into a neuroprotective phenotype via downregulation of the P2Y1 purinergic receptor. TBI initially caused microglial activation in the injury core, followed by reactive astrogliosis in the peri-injured region and formation of a neuroprotective astrocyte scar. Equivalent changes to astrocytes were observed in vitro after injury. This change in astrocyte phenotype resulted from P2Y1 receptor downregulation, mediated by microglia-derived cytokines. In mice, astrocyte-specific P2Y1 receptor overexpression (Astro-P2Y1OE counteracted scar formation, while astrocyte-specific P2Y1 receptor knockdown (Astro-P2Y1KD facilitated scar formation, suggesting critical roles of P2Y1 receptors in the transformation. Astro-P2Y1OE and Astro-P2Y1KD mice showed increased and reduced neuronal damage, respectively. Altogether, our findings indicate that microglia-astrocyte interaction, involving a purinergic signal, is essential for the formation of neuroprotective astrocytes.

  20. Ionization Spectroscopic Measurement of nP Rydberg Levels of 87Rb Cold Atoms

    Science.gov (United States)

    Li, Yufan; Zaheeruddin, Syed; Zhao, Dongmei; Ma, Xinwen; Yang, Jie

    2018-05-01

    We created an ultracold plasma via the spontaneous ionization of cold dense Rydberg atoms of 87Rb in a magneto-optical trap (MOT), and measured the nS1/2 (n = 50-80), nP1/2 (n = 16-23), nP3/2 (n = 16-98), and nD5/2 (n = 49-96) Rydberg levels by detecting the electrons in the ultracold plasma. By fitting the energy levels of Rydberg states, the first ionization potential of 33690.950(11) cm-1 and the quantum defects of S, P, and D orbitals were obtained. The absolute transition energies of nS1/2 (n = 66-80), nP1/2 (n = 16-23), nP3/2 (n = 16-98), and nD5/2 (n = 58-96) states of 87Rb, as well as the quantum defects for p1/2 and p3/2 series, are given for the first time.

  1. μ-Sulfido-bis{[1,1′-bis(diphenylphosphanylferrocene-κ2P,P′]gold} methanol monosolvate

    Directory of Open Access Journals (Sweden)

    Takuma Itai

    2016-01-01

    Full Text Available The gold complex in title compound, [Au2Fe(C17H14P2S]·CH3OH, (I·CH3OH, is closely similar to the previously reported (I·2CHCl3, reported in the literature [Canales et al. (1996. J. Am. Chem. Soc. 118, 4839–4845]. Both crystallize in the monoclinic crystal systems but the space groups differ, P21/n for (I·CH3OH compared to P2/n for (I·2CHCl3. The two structures can be considered as polymorphs due to solvation differences. In (I·CH3OH, all atoms of the methanol solvent molecule are disordered over two sets of sites with an occupancy ratio of 0.822 (12:0.178 (12. The crystal structure features O—H...S, C—H...S hydrogen bonds and C—H...π interactions that stack the complex molecules along the a-axis direction.

  2. Proteomic characterization of plasmid pLA1 for biodegradation of polycyclic aromatic hydrocarbons in the marine bacterium, Novosphingobium pentaromativorans US6-1.

    Directory of Open Access Journals (Sweden)

    Sung Ho Yun

    Full Text Available Novosphingobium pentaromativorans US6-1 is a halophilic marine bacterium able to degrade polycyclic aromatic hydrocarbons (PAHs. Genome sequence analysis revealed that the large plasmid pLA1 present in N. pentaromativorans US6-1 consists of 199 ORFs and possess putative biodegradation genes that may be involved in PAH degradation. 1-DE/LC-MS/MS analysis of N. pentaromativorans US6-1 cultured in the presence of different PAHs and monocyclic aromatic hydrocarbons (MAHs identified approximately 1,000 and 1,400 proteins, respectively. Up-regulated biodegradation enzymes, including those belonging to pLA1, were quantitatively compared. Among the PAHs, phenanthrene induced the strongest up-regulation of extradiol cleavage pathway enzymes such as ring-hydroxylating dioxygenase, putative biphenyl-2,3-diol 1,2-dioxygenase, and catechol 2,3-dioxygenase in pLA1. These enzymes lead the initial step of the lower catabolic pathway of aromatic hydrocarbons through the extradiol cleavage pathway and participate in the attack of PAH ring cleavage, respectively. However, N. pentaromativorans US6-1 cultured with p-hydroxybenzoate induced activation of another extradiol cleavage pathway, the protocatechuate 4,5-dioxygenase pathway, that originated from chromosomal genes. These results suggest that N. pentaromativorans US6-1 utilizes two different extradiol pathways and plasmid pLA1 might play a key role in the biodegradation of PAH in N. pentaromativorans US6-1.

  3. Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation.

    Science.gov (United States)

    Yang, Weiwei; Li, Qinghua; Pan, Zhifang

    2014-01-01

    Successful placentation depends on the proper invasion of extravillous trophoblast (EVT) cells into maternal tissues. Previous reports demonstrated that S1P receptors are expressed in the EVT cells and S1P could regulate migration and function of trophoblast cells via S1P receptors. However, little is known about roles of S1P in the invasion of EVT cells. Our study was performed to investigate S1P effect on the invasion of EVT cells. We used the extravillous trophoblast cell line HTR8/SVneo cells to evaluate the effect. In vitro invasion assay was employed to determine the invasion of HTR8/SVneo cells induced by S1P. MMP-2 enzyme activity and relative level in the supernatants of HTR8/SVneo was assessed by gelatin zymography and western blot. Based on the above, siRNA and specific inhibitors were used for the intervention and study of potential signal pathways, and Real-time qPCR and western blot were used to test the mRNA and protein level of potential signal targets. We found that S1P could promote HTR8/SVneo cell invasion and upregulates activity and level of MMP-2. The promotion requires activation of MEK-ERK and is dependent on the axis of S1P/S1PR1. Our investigation of S1P may provide new insights into the molecular mechanisms of EVT invasion.

  4. Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline.

    Science.gov (United States)

    Utoh, Masahiro; Murayama, Norie; Uno, Yasuhiro; Onose, Yui; Hosaka, Shinya; Fujino, Hideki; Shimizu, Makiko; Iwasaki, Kazuhide; Yamazaki, Hiroshi

    2013-12-01

    Caffeine (1,3,7-trimethylxanthine) is a phenotyping substrate for human cytochrome P450 1A2. 3-N-Demethylation of caffeine is the main human metabolic pathway, whereas monkeys extensively mediate the 7-N-demethylation of caffeine to form pharmacological active theophylline. Roles of monkey P450 enzymes in theophylline formation from caffeine were investigated using individual monkey liver microsomes and 14 recombinantly expressed monkey P450 enzymes, and the results were compared with those for human P450 enzymes. Caffeine 7-N-demethylation activity in microsomes from 20 monkey livers was not strongly inhibited by α-naphthoflavone, quinidine or ketoconazole, and was roughly correlated with diclofenac 4'-hydroxylation activities. Monkey P450 2C9 had the highest activity for caffeine 7-N-demethylation. Kinetic analysis revealed that monkey P450 2C9 had a high Vmax/Km value for caffeine 7-N-demethylation, comparable to low Km value for monkey liver microsomes. Caffeine could dock favorably with monkey P450 2C9 modeled for 7-N-demethylation and with human P450 1A2 for 3-N-demethylation. The primary metabolite theophylline was oxidized to 8-hydroxytheophylline in similar ways by liver microsomes and by recombinant P450s in both humans and monkeys. These results collectively suggest a high activity for monkey liver P450 2C9 toward caffeine 7-N-demethylation, whereas, in humans, P450 1A2-mediated caffeine 3-N-demethylation is dominant.

  5. Down-regulation of tissue N:P ratios in terrestrial plants by elevated CO2.

    Science.gov (United States)

    Deng, Qi; Hui, Dafeng; Luo, Yiqi; Elser, James; Wang, Ying-ping; Loladze, Irakli; Zhang, Quanfa; Dennis, Sam

    2015-12-01

    Increasing atmospheric CO2 concentrations generally alter element stoichiometry in plants. However, a comprehensive evaluation of the elevated CO2 impact on plant nitrogen: phosphorus (N:P) ratios and the underlying mechanism has not been conducted. We synthesized the results from 112 previously published studies using meta-analysis to evaluate the effects of elevated CO2 on the N:P ratio of terrestrial plants and to explore the underlying mechanism based on plant growth and soil P dynamics. Our results show that terrestrial plants grown under elevated CO2 had lower N:P ratios in both above- and belowground biomass across different ecosystem types. The response ratio for plant N:P was negatively correlated with the response ratio for plant growth in croplands and grasslands, and showed a stronger relationship for P than for N. In addition, the CO2-induced down-regulation of plant N:P was accompanied by 19.3% and 4.2% increases in soil phosphatase activity and labile P, respectively, and a 10.1% decrease in total soil P. Our results show that down-regulation of plant N:P under elevated CO2 corresponds with accelerated soil P cycling. These findings should be useful for better understanding of terrestrial plant stoichiometry in response to elevated CO2 and of the underlying mechanisms affecting nutrient dynamics under climate change.

  6. Electroluminescence in quantum well heterostructures p-Al{sub x}Ga{sub 1-x}As/GaAs{sub 1-y}P{sub y}/n-Al{sub x}Ga{sub 1-x}As under uniaxial stress

    Energy Technology Data Exchange (ETDEWEB)

    Berman, Irina V. [Physics Department, San Jose State University, CA (United States); Bogdanov, Evgeniy V.; Minina, Natalia Ya.; Shirokov, Stanislav S.; Yunovich, Alexander E. [Physics Department, Lomonosov Moscow State University (Russian Federation); Kissel, Heiko [R and D Department, DILAS Diodenlaser GmbH, (Germany)

    2009-03-15

    We present new results on the influence of uniaxial stress up to P=4 kbar on the electroluminescence spectra and current-voltage characteristics of p-Al{sub x}Ga{sub 1-x}As/GaAs{sub 1-y}P{sub y}/n-Al{sub x}Ga{sub 1-x}As double heterostructures usually used in TM emitting 808 nm high-power diode lasers. With increasing stress, the emission spectra demonstrate a blue shift of up to 25 meV at a pressure of P=4 kbar, while the electroluminescence intensity increases under compression. The different behavior of the current-voltage characteristics under uniaxial stress along[110] and[1 anti 10] directions is mainly determined by the arising piezoelectric field. The results are also discussed in terms of changes in the band structure under uniaxial compression. The construction of the cryostat for optical measurements under uniaxial stress at liquid nitrogen temperature is described in the paper. (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  7. Organometallic chemical vapor deposition and characterization of ZnGe(1-x)Si(x)P2-Ge alloys on GaP substrates

    Science.gov (United States)

    Xing, G. C.; Bachmann, Klaus J.; Posthill, J. B.; Timmons, M. L.

    1993-01-01

    The epitaxial growth of ZnGe(1-x)Si(x)P2-Ge alloys on GaP substrates by open tube organometallic chemical vapor deposition (OMCVD) is reported. The chemical composition of the alloys characterized by energy dispersive X-ray spectroscopy shows that alloys with x up to 0.13 can be deposited on (001) GaP. Epitaxial growth with mirror smooth surface morphology was achieved for x less than or equal to 0.05. Transmission electron microscopy (TEM) micrographs of these alloys show specular epitaxy and the absence of microstructural defects indicating a defect density of less than 10(exp 7) cm(sup -2). Selected area electron diffraction pattern of the alloy shows that the epitaxial layer crystallizes in the chalcopyrite structure with relatively weak superlattice reflections indicating certain degree of randomness in the cation sublattice. Hall measurements show that the alloys are p-type, like the unalloyed films; the carrier concentration, however, dropped about 10 times from 2 x 10(exp 18) to 2 x 10(exp 17) cm(sup -3). Absorption measurements indicate that the band tailing in the absorption spectra of the alloy was shifted about 0.04 eV towards shorter wavelength as compared to the unalloyed material. Diodes fabricated from the n(+)-GaP/p-ZnSiP2-ZnGeP2-Ge heterostructure at x = 0.05 have a reverse break-down voltage of -10.8 V and a reverse saturation current density of approximately 6 x 10(exp -8) A/sq cm.

  8. Electrical dipole polarizability and spin M1 strength from {sup 48}Ca(p,p') data under 0; Elektrische Dipol-Polarisierbarkeit und Spin-M1-Staerke aus {sup 48}Ca(p,p')-Daten unter 0

    Energy Technology Data Exchange (ETDEWEB)

    Birkhan, Jonny Hubertus

    2016-07-01

    the experimental cross section. This could be managed by a deconvolution of the cross sections into an isoscalar and isovector part. Beside this, (p,n) data on the nucleus {sup 48}Ca were available. The data had been used to calculate the total electromagnetic M1 strength independently by the well established method for Gamow-Teller transitions. Additionally, one more (p,p') data set on the nucleus {sup 48}Ca was analysed at a projectile energy of E{sub p}=200 MeV. No contradiction could be found between the (p,p') and (p,n) results. The influence of different isoscalar quenching factors on the results was investigated. The variation of the results was not that large to become inconsistent with the (e,e') value of B(M1)=(3.9±0.3) μ{sup 2}{sub N}. Furthermore, the method of this work had been applied to (p,p') data on the nucleus {sup 208}Pb. The results could be checked against data from scattering experiments with polarised γ radiation and neutrons. The comparison did not give evidence to reject the method. The best estimate of the M1-strength in the case of the nucleus {sup 48}Ca is B(M1)=(3.82±0.26) μ{sup 2}{sub N}. Therefore, the results of this work contradict the result of a recent (γ,n) measurement which a strength of B(M1)=(6.8±0.5) μ{sup 2}{sub N} was extracted from.

  9. Simulation studies of the n{sup +}n{sup -} Si sensors having p-spray/p-stop implant for the SiD experiment

    Energy Technology Data Exchange (ETDEWEB)

    Saxena, Pooja; Ranjan, Kirti [Centre for Detector and Related Software Technology, Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India); Bhardwaj, Ashutosh, E-mail: abhardwaj@physics.du.ac.in [Centre for Detector and Related Software Technology, Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India); Shivpuri, R.K.; Bhattacharya, Satyaki [Centre for Detector and Related Software Technology, Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India)

    2011-12-01

    Silicon Detector (SiD) is one of the proposed detectors for the future International Linear Collider (ILC). In the innermost vertex of the ILC, Si micro-strip sensors will be exposed to the neutron background of around 1-1.6 Multiplication-Sign 10{sup 10} 1 MeV equivalent neutrons cm{sup -2} year{sup -1}. The p{sup +}n{sup -}n{sup +} double-sided Si strip sensors are supposed to be used as position sensitive sensors for SiD. The shortening due to electron accumulation on the n{sup +}n{sup -} side of these sensors leads to uniform spreading of signal over all the n{sup +} strips and thus ensuring good isolation between the n{sup +} strips becomes one of the major issues in these sensors. One of the possible solutions is the use of floating p-type implants introduced between the n{sup +} strips (p-stops) and another alternative is the use of uniform layer of p-type implant on the entire n-side (p-spray). However, pre-breakdown micro-discharge is reported because of the high electric field at the edge of the p-stop/p-spray. An optimization of the implant dose profile of the p-stop and p-spray is required to achieve good electrical isolation while ensuring satisfactory breakdown performance of the Si sensors. Preliminary results of the simulation study performed on the n{sup +}n{sup -} Si sensors having p-stop and p-spray using device simulation program, ATLAS, are presented.

  10. P2Y2 Receptor and EGFR Cooperate to Promote Prostate Cancer Cell Invasion via ERK1/2 Pathway.

    Science.gov (United States)

    Li, Wei-Hua; Qiu, Ying; Zhang, Hong-Quan; Tian, Xin-Xia; Fang, Wei-Gang

    2015-01-01

    As one member of G protein-coupled P2Y receptors, P2Y2 receptor can be equally activated by extracellular ATP and UTP. Our previous studies have proved that activation of P2Y2 receptor by extracellular ATP could promote prostate cancer cell invasion and metastasis in vitro and in vivo via regulating the expressions of some epithelial-mesenchymal transition/invasion-related genes (including IL-8, E-cadherin, Snail and Claudin-1), and the most significant change in expression of IL-8 was observed after P2Y2 receptor activation. However, the signaling pathway downstream of P2Y2 receptor and the role of IL-8 in P2Y2-mediated prostate cancer cell invasion remain unclear. Here, we found that extracellular ATP/UTP induced activation of EGFR and ERK1/2. After knockdown of P2Y2 receptor, the ATP -stimulated phosphorylation of EGFR and ERK1/2 was significantly suppressed. Further experiments showed that inactivation of EGFR and ERK1/2 attenuated ATP-induced invasion and migration, and suppressed ATP-mediated IL-8 production. In addition, knockdown of IL-8 inhibited ATP-mediated invasion and migration of prostate cancer cells. These findings suggest that P2Y2 receptor and EGFR cooperate to upregulate IL-8 production via ERK1/2 pathway, thereby promoting prostate cancer cell invasion and migration. Thus blocking of the P2Y2-EGFR-ERK1/2 pathway may provide effective therapeutic interventions for prostate cancer.

  11. Measurement of the $\\bar{p}p \\rightarrow \\bar{n}n$ Charge-Exchange Differential Cross-Section

    CERN Multimedia

    2002-01-01

    The aim of this proposal is a measurement of the differential cross-section of the $\\bar{p}$p $\\rightarrow$ $\\bar{n}$n charge-exchange reaction with a point-to-point precision of 1\\% in the forward direction, and an absolute normalization error of 3\\%. The high precision of the data should allow, inter alia, a determination of the $\\pi$NN coupling constant to better than 2\\%.\\\\ \\\\ The measurement will be done using the existing neutron and antineutron detectors built for experiment PS199 and liquid hydrogen target. In one week of running time, with a $\\bar{p}$ beam intensity of 3 $ 10 ^{5} $ $\\bar{p}$/sec, the reaction will be measured at a few $\\bar{p}$ momenta, in the range 500 to 900~MeV/c.

  12. Preconception serum 1,1,1-trichloro-2,2,bis(p-chlorophenyl)ethane and B-vitamin status: independent and joint effects on women's reproductive outcomes.

    Science.gov (United States)

    Ouyang, Fengxiu; Longnecker, Matthew P; Venners, Scott A; Johnson, Sara; Korrick, Susan; Zhang, Jun; Xu, Xiping; Christian, Parul; Wang, Mei-Cheng; Wang, Xiaobin

    2014-12-01

    Although preconception 1,1,1-trichloro-2,2,bis(p-chlorophenyl)ethane (DDT) exposure and B-vitamin deficiencies have each been shown to negatively affect human reproductive outcomes, little is known about their joint effect. We sought to examine whether B-vitamin sufficiency protects against adverse effects of DDT on clinical pregnancy (CP) and subclinical early pregnancy loss (EPL). We measured preconception concentrations of plasma B vitamins (vitamin B-6, vitamin B-12, and folate) and serum total DDT [sum of p,p' and o,p' isomers of DDT and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] in 291 nulligravid women from Anhui, China, who were studied in 1996-1998. The women were followed prospectively from the time they stopped contraception until CP (gestational age ≥42 d) or 12 mo (whichever occurred first). EPL was identified by using daily urinary human chorionic gonadotropin. The women were categorized according to B-vitamin status (deficiency compared with sufficiency) and DDT concentration (high compared with low). Of 291 study women, a total of 385 conceptions (31% of which ended in EPL) and 265 CPs occurred. Compared with women with adequate B-vitamins and low DDT, incidence rates of CP were reduced in women with B-vitamin deficiency and a high DDT concentration (P vitamin B-12, DDT was not associated with the incidence of CP; in contrast, in women with vitamin B-12 deficiency, high DDT was associated with a lower incidence of CP (HR: 0.44; 95% CI: 0.23, 0.84); and the test for interaction was significant (P vitamin B-12 and folate sufficiency may help protect against adverse reproductive effects of DDT exposure. Additional studies are needed to confirm our findings. © 2014 American Society for Nutrition.

  13. Synthesis of some Heterocyclic Compounds Derived from 2-Chloro-N-p-Tolylacetamide

    Directory of Open Access Journals (Sweden)

    Hanan Gh Shaaban

    2017-02-01

    Full Text Available This research includes preparation of (2-chloro-N-p-tolylacetamide (1 from the reaction of (p-aminotoluene with chloro acetyl chloride. Compound (1 reacted with thiosemi carbazide and gave compound (2, and when compound (1 reacted with semicarbazide gave compound (3. While when compound (1 reacted with thiourea it produced compound (4. Compounds (2-4 when reacted with appropriate aromatic aldehydes or ketones produced Shiff bass (5-16, which in turn reacted with chloro acetyl chloride in the present of tri ethyl amine and dioxin gave β-lactam derivatives (14-22. The structures of these compounds were characterized from their melting points, FT-IR, and NMR.

  14. For or against adjuvant trastuzumab for pT1a-bN0M0 breast cancer patients with HER2-positive tumors: a meta-analysis of published literatures.

    Directory of Open Access Journals (Sweden)

    Qiong Zhou

    Full Text Available BACKGROUND: Although the prognosis of patients with small (≤1cm tumors is generally favorable, emerging data suggests that biological behavior varies between intrinsic subtypes in such patients. Furthermore, it still remains unclear whether HER2-positive pT1a-bN0M0 patients could benefit from adjuvant trastuzumab. For further evaluation, we sought to conduct a meta-analysis so as to get a better understanding of the prognosis for HER2-positive pT1a-bN0M0 patients and their survival benefit from adjuvant trastuzumab, accordingly, offering the implications for current practice. METHODS: The PubMed database, the online proceedings of the American Society of Clinical Oncology (ASCO Annual Meetings, the online proceedings of the San Antonio Breast Cancer Symposium, and the CD proceedings of the International St. Gallen Breast Cancer Conference were searched for all relevant studies published before September 2012. Relative risks (RRs were used to compare the prognosis of different intrinsic subtypes for pT1a-bN0M0 breast cancer. Analyses were also performed to estimate the association between adjuvant trastuzumab and various survival outcomes. RESULTS: With eight eligible studies identified, this meta-analysis demonstrated a deleterious effect of HER2+ phenotype on disease-free survival (DFS; RR = 3.677, 95% CI 2.606-5.189, p <0.001 and distant disease-free survival (DDFS; RR = 3.824, 95% CI 2.249-6.501, p<0.001 as compared to HR+/HER2- subgroup. However, significant difference failed to be achieved in terms of any endpoint between HER2+ and triple negative breast cancer (TNBC. Besides, a marked improvement in DFS was observed with the addition of trastuzumab for HER2-positive pT1a-bN0M0 patients (RR = 0.323, 95% CI 0.191-0.547, p<0.001. CONCLUSION: This meta-analysis clarifies that intrinsic subtypes might be a reliable marker to predict the prognosis in pT1a-bN0M0 breast cancer. Besides, even for such early stage HER2-positive

  15. The pMSSM10 after LHC Run 1

    International Nuclear Information System (INIS)

    De Vries, K.J.; Buchmueller, O.

    2015-04-01

    We present a frequentist analysis of the parameter space of the pMSSM10, in which the following 10 soft SUSY-breaking parameters are specified independently at the mean scalar top mass scale M SUSY ≡√(m t 1 m t 2 ): the gaugino masses M 1,2,3 , the 1st-and 2nd-generation squark masses m q 1 =m q 2 , the third-generation squark mass m q 3 , a common slepton mass M l and a common trilinear mixing parameter A, the Higgs mixing parameter μ, the pseudoscalar Higgs mass M A and tan β. We use the MultiNest sampling algorithm with ∝1.2 x 10 9 points to sample the pMSSM10 parameter space. A dedicated study shows that the sensitivities to strongly-interacting SUSY masses of ATLAS and CMS searches for jets, leptons+E T signals depend only weakly on many of the other pMSSM10 parameters. With the aid of the Atom and Scorpion codes, we also implement the LHC searches for EW-interacting sparticles and light stops, so as to confront the pMSSM10 parameter space with all relevant SUSY searches. In addition, our analysis includes Higgs mass and rate measurements using the HiggsSignals code, SUSY Higgs exclusion bounds, the measurements B-physics observables, EW precision observables, the CDM density and searches for spin-independent DM scattering. We show that the pMSSM10 is able to provide a SUSY interpretation of (g-2) μ , unlike the CMSSM, NUHM1 and NUHM2. As a result, we find (omitting Higgs rates) that the minimum χ 2 /d.o.f.=20.5/18 in the pMSSM10, corresponding to a χ 2 probability of 30.8 %, to be compared with χ 2 /d.o.f.=32.8/24(31.1/23)(30.3/22) in the CMSSM (NUHM1) (NUHM2). We display 1-dimensional likelihood functions for SUSY masses, and show that they may be significantly lighter in the pMSSM10 than in the CMSSM, NUHM1 and NUHM2. We discuss the discovery potential of future LHC runs, e + e - colliders and direct detection experiments.

  16. Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets.

    Science.gov (United States)

    Vidaña, Beatriz; Martínez, Jorge; Martorell, Jaime; Montoya, María; Córdoba, Lorena; Pérez, Mónica; Majó, Natàlia

    2016-11-08

    Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques. The obtained results were then analysed in relation to viral quantification in the different anatomic areas and the histopathological lesions observed. More severe lung lesions were observed at 24 h post infection (hpi) correlating with viral antigen detection in bronchiolar and alveolar epithelial cells. However, high levels of viral RNA were detected in all anatomic compartments throughout infection. Bronchiolar areas were the first source of IFN-α and most pro-inflammatory cytokines, through the activation of RIG-I. In contrast, vascular areas contributed with the highest induction of CCL2 and other pro-inflammatory cytokines, through the activation of TLR3.

  17. HEXIM1, a New Player in the p53 Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lew, Qiao Jing; Chu, Kai Ling; Chia, Yi Ling; Cheong, Nge [Expression Engineering Group, Bioprocessing Technology Institute, A*STAR (Agency for Science, Technology and Research), 20 Biopolis Way, #06-01, Singapore 138668 (Singapore); Chao, Sheng-Hao, E-mail: jimmy_chao@bti.a-star.edu.sg [Expression Engineering Group, Bioprocessing Technology Institute, A*STAR (Agency for Science, Technology and Research), 20 Biopolis Way, #06-01, Singapore 138668 (Singapore); Department of Microbiology, National University of Singapore, Singapore 117597 (Singapore)

    2013-07-04

    Hexamethylene bisacetamide-inducible protein 1 (HEXIM1) is best known as the inhibitor of positive transcription elongation factor b (P-TEFb), which controls transcription elongation of RNA polymerase II and Tat transactivation of human immunodeficiency virus. Besides P-TEFb, several proteins have been identified as HEXIM1 binding proteins. It is noteworthy that more than half of the HEXIM1 binding partners are involved in cancers. P53 and two key regulators of the p53 pathway, nucleophosmin (NPM) and human double minute-2 protein (HDM2), are among the factors identified. This review will focus on the functional importance of the interactions between HEXIM1 and p53/NPM/HDM2. NPM and the cytoplasmic mutant of NPM, NPMc+, were found to regulate P-TEFb activity and RNA polymerase II transcription through the interaction with HEXIM1. Importantly, more than one-third of acute myeloid leukemia (AML) patients carry NPMc+, suggesting the involvement of HEXIM1 in tumorigenesis of AML. HDM2 was found to ubiquitinate HEXIM1. The HDM2-mediated ubiquitination of HEXIM1 did not lead to protein degradation of HEXIM1 but enhanced its inhibitory activity on P-TEFb. Recently, HEXIM1 was identified as a novel positive regulator of p53. HEXIM1 prevented p53 ubiquitination by competing with HDM2 in binding to p53. Taken together, the new evidence suggests a role of HEXIM1 in regulating the p53 pathway and tumorigenesis.

  18. Polymorphisms A387P in thrombospondin-4 and N700S in thrombospondin-1 perturb calcium binding sites.

    Science.gov (United States)

    Stenina, Olga I; Ustinov, Valentin; Krukovets, Irene; Marinic, Tina; Topol, Eric J; Plow, Edward F

    2005-11-01

    Recent genetic studies have associated members of the thrombospondin (TSP) gene family with premature cardiovascular disease. The disease-associated polymorphisms lead to single amino acid changes in TSP-4 (A387P) and TSP-1 (N700S). These substitutions reside in adjacent domains of these highly homologous proteins. Secondary structural predictive programs and the homology of the domains harboring these amino acid substitutions to those in other proteins pointed to potential alterations of putative Ca2+ binding sites that reside in close proximity to the polymorphic amino acids. Since Ca2+ binding is critical for the structure and function of TSP family members, direct evidence for differences in Ca2+ binding by the polymorphic forms was sought. Using synthetic peptides and purified recombinant variant fragments bearing the amino acid substitutions, we measured differences in Tb3+ luminescence as an index of Ca2+ binding. The Tb3+ binding constants placed the TSP-1 region affected by N700S polymorphism among other high-affinity Ca2+ binding sites. The affinity of Ca2+ binding was lower for peptides (3.5-fold) and recombinant fragments (10-fold) containing the S700 vs. the N700 form. In TSP-4, the P387 form acquired an additional Ca2+ binding site absent in the A387 form. The results of our study suggest that both substitutions (A387P in TSP-4 and N700S in TSP-1) alter Ca2+ binding properties. Since these substitutions exert the opposite effects on Ca2+ binding, a decrease in TSP-1 and an increase in TSP-4, the two TSP variants are likely to influence cardiovascular functions in distinct but yet pathogenic ways.

  19. NLO NRQCD disfavors the interpretation of X(3872) as {chi}{sub c1}(2P)

    Energy Technology Data Exchange (ETDEWEB)

    Butenschoen, Mathias [Wien Univ. (Austria). Fakultaet fuer Physik; He, Zhi-Guo; Kniehl, Bernd A. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

    2013-03-15

    We study {chi}{sub c1}(2P) inclusive hadroproduction at next-to-leading order (NLO) within the factorization formalism of nonrelativistic quantum chromodynamics (NRQCD), including both the color-singlet {sup 3}P{sub 1}{sup [1]} and color-octet {sup 3}S{sub 1}{sup [8]} c anti c Fock states. Assuming the recently discovered X(3872) hadron to be the 2P (1{sup ++}) charmonium state, we perform a fit to the cross sections measured by the CDF, CMS, and LHCb Collaborations. We either obtain an unacceptably high value of {chi}{sup 2} or a value of vertical stroke R{sub 2P}{sup '}(0) vertical stroke incompatible with well-established potential models. We thus conclude that NLO NRQCD is incompatible with the hypothesis X(3872){identical_to}{chi}{sub c1}(2P).

  20. Binary Oxide p-n Heterojunction Piezoelectric Nanogenerators with an Electrochemically Deposited High p-Type Cu2O Layer.

    Science.gov (United States)

    Baek, Seung Ki; Kwak, Sung Soo; Kim, Joo Sung; Kim, Sang Woo; Cho, Hyung Koun

    2016-08-31

    The high performance of ZnO-based piezoelectric nanogenerators (NGs) has been limited due to the potential screening from intrinsic electron carriers in ZnO. We have demonstrated a novel approach to greatly improve piezoelectric power generation by electrodepositing a high-quality p-type Cu2O layer between the piezoelectric semiconducting film and the metal electrode. The p-n heterojunction using only oxides suppresses the screening effect by forming an intrinsic depletion region, and thus sufficiently enhances the piezoelectric potential, compared to the pristine ZnO piezoelectric NG. Interestingly, a Sb-doped Cu2O layer has high mobility and low surface trap states. Thus, this doped layer is an attractive p-type material to significantly improve piezoelectric performance. Our results revealed that p-n junction NGs consisting of Au/ZnO/Cu2O/indium tin oxide with a Cu2O:Sb (cuprous oxide with a small amount of antimony) layer of sufficient thickness (3 μm) exhibit an extraordinarily high piezoelectric potential of 0.9 V and a maximum output current density of 3.1 μA/cm(2).

  1. Main metabolites of 1-(2-chloroethyl)-3-[1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl]-1-nitrosourea and 1-(2-chloroethyl)-3-(2',3', 4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea in rats

    International Nuclear Information System (INIS)

    Madelmont, J.C.; Moreau, M.F.; Godeneche, D.; Duprat, J.; Plagne, R.; Meyniel, G.

    1982-01-01

    The metabolism of two glycosylnitrosoureas, 1-(2-chloroethyl)-3-[1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl]-1-nitrosourea (RFCNU) and 1-(2-chloroethyl)-3-(2',3',4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea (RPCNU), has been investigated in the rat. With the label on the carboxyl moiety of RFCNU, we have shown that hydrolysis of the 4-nitrobenzoyl ester occurred to a large extent in vivo; 4-nitrobenzoic acid and its glucuronide were the major urinary metabolites. Two other minor metabolites and their glucuronides were identified as 4-aminobenzoic acid and 4-acetamidobenzoic acid. With the label on the chloroethyl moieties of RFCNU and RPCNU, we have shown that chloroethanol was a major degradation product of this alkylating part of the molecule. The concentration of chloroethanol in plasma vs. time has been determined. In urine, four metabolites derived from alkylated glutathione, namely thiodiacetic acid and its sulfoxide, N-acetylcarboxymethylcysteine, and N-acetylhydroxyethylcysteine, have been identified

  2. Diffractive Dijet Production in $\\bar{p}p$ Collisions at $\\sqrt{s}=1.96$ TeV

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, T.; /Helsinki Inst. of Phys.; Albrow, M.; /Fermilab; Alvarez Gonzalez, B.; /Oviedo U. /Cantabria Inst. of Phys.; Amerio, S.; /INFN, Padua; Amidei, D.; /Michigan U.; Anastassov, A.; /Northwestern U. /Fermilab; Annovi, A.; /Frascati; Antos, J.; /Comenius U.; Apollinari, G.; /Fermilab; Appel, J.A.; /Fermilab; Arisawa, T.; /Waseda U. /Dubna, JINR

    2012-06-01

    We report on a study of diffractive dijet production in {bar p}p collisions at {radical}s = 1.96 TeV using the CDF II detector at the Fermilab Tevatron {bar p}p collider. A data sample from 310 pb{sup -1} of integrated luminosity collected by triggering on a high transverse energy jet, E{sub T}{sup jet}, in coincidence with a recoil antiproton detected in a Roman pot spectrometer is used to measure the ratio of single-diffractive to inclusive-dijet event rates as a function of x{sup {bar p}} of the interacting parton in the antiproton, the Bjorken-x, x{sub Bj}{sup {bar p}}, and a Q{sup 2} {approx} (E{sub T}{sup jet}){sup 2} in the ranges 10{sup -3} < x{sub Bj}{sup {bar p}} < 10{sup -1} and 10{sup 2} < Q{sup 2} < 10{sup 4} GeV{sup 2}, respectively. Results are presented for the region of {bar p}-momentum-loss fraction 0.03 < {zeta}{sub {bar p}} < 0.09 and a four-momentum transfer squared t{sub {bar p}} > -4 GeV{sup 2}. The t{sub {bar p}} dependence is measured as a function of Q{sup 2} and x{sub Bj}{sup {bar p}} and compared with that of inclusive single diffraction dissociation. We find weak x{sub Bj}{sup bar p}} and Q{sup 2} dependencies in the ratio of single diffractive to inclusive event rates, and no significant Q{sup 2} dependence in the diffractive t{sub {bar p}} distributions.

  3. SUN family proteins Sun4p, Uth1p and Sim1p are secreted from Saccharomyces cerevisiae and produced dependently on oxygen level.

    Directory of Open Access Journals (Sweden)

    Evgeny Kuznetsov

    Full Text Available The SUN family is comprised of proteins that are conserved among various yeasts and fungi, but that are absent in mammals and plants. Although the function(s of these proteins are mostly unknown, they have been linked to various, often unrelated cellular processes such as those connected to mitochondrial and cell wall functions. Here we show that three of the four Saccharomyces cerevisiae SUN family proteins, Uth1p, Sim1p and Sun4p, are efficiently secreted out of the cells in different growth phases and their production is affected by the level of oxygen. The Uth1p, Sim1p, Sun4p and Nca3p are mostly synthesized during the growth phase of both yeast liquid cultures and colonies. Culture transition to slow-growing or stationary phases is linked with a decreased cellular concentration of Sim1p and Sun4p and with their efficient release from the cells. In contrast, Uth1p is released mainly from growing cells. The synthesis of Uth1p and Sim1p, but not of Sun4p, is repressed by anoxia. All four proteins confer cell sensitivity to zymolyase. In addition, Uth1p affects cell sensitivity to compounds influencing cell wall composition and integrity (such as Calcofluor white and Congo red differently when growing on fermentative versus respiratory carbon sources. In contrast, Uth1p is essential for cell resistance to boric acids irrespective of carbon source. In summary, our novel findings support the hypothesis that SUN family proteins are involved in the remodeling of the yeast cell wall during the various phases of yeast culture development and under various environmental conditions. The finding that Uth1p is involved in cell sensitivity to boric acid, i.e. to a compound that is commonly used as an important antifungal in mycoses, opens up new possibilities of investigating the mechanisms of boric acid's action.

  4. Estimation of the degree of soil P saturation from Brazilian Mehlich-1 P data and field investigations on P losses from agricultural sites in Minas Gerais.

    Science.gov (United States)

    Fischer, P; Pöthig, R; Gücker, B; Venohr, M

    The degree of phosphorus saturation (DPS) of agricultural soils is studied worldwide for risk assessment of phosphorus (P) losses. In previous studies, DPS could be reliably estimated from water-soluble P (WSP) for European and Brazilian soils. In the present study, we correlated measured WSP and Mehlich-1 P (M1P) from soils of Minas Gerais (MG) and Pernambuco (PE) (R(2) = 0.94, n = 59) to create a DPS map from monitoring data. The resulting DPS map showed high spatial variability and low values of DPS (54 ± 22%, mean and standard deviation; n = 1,827). Measured soil DPS values amounted to 63 ± 14% and resulted in relatively low dissolved P concentrations measured in a surface runoff study in MG. However, fertilizer grains on the soil surface led to high WSP values (>30 mg/kg) indicating high risks of dissolved P losses. We suppose that small Oxisol particles with Fe and Al hydroxides sorbed most of the dissolved fertilizer P in runoff so that P was mainly exported in particulate form. In soils with lower contents of P sorption and binding partners, e.g. Entisols in PE, this effect may be less dominant. Consequently, superficial fertilizer effects have to be considered in addition to DPS in risk assessment of P losses from agricultural areas in Brazil.

  5. Lithium superionic conductor Li9.42Si1.02P2.1S9.96O2.04 with Li10GeP2S12-type structure in the Li2S–P2S5–SiO2 pseudoternary system: Synthesis, electrochemical properties, and structure–composition relationships

    Directory of Open Access Journals (Sweden)

    Satoshi Hori

    2016-12-01

    Full Text Available Lithium superionic conductors with the Li10GeP2S12 (LGPS-type structure are promising materials for use as solid electrolytes in next-generation lithium batteries. A novel member of the LGPS family, Li9.42Si1.02P2.1S9.96O2.04, and its solid solutions were synthesised by quenching from 1273 K in the Li2S–P2S5–SiO2 pseudoternary system. The material exhibited an ionic conductivity as high as 3.2×10−4 S cm−1 at 298 K, as well as the high electrochemical stability to lithium metal, which was improved by the introduction of oxygen into the LGPS-type structure. An all-solid-state cell with a lithium metal anode and Li9.42Si1.02P2.1S9.96O2.04 as the separator showed excellent performance with a high coulomb efficiency of 100%. Thus, oxygen doping is an effective way of improving the electrochemical stability of LGPS-type structure.

  6. Sphingosine 1-Phosphate (S1P) Carrier-dependent Regulation of Endothelial Barrier

    Science.gov (United States)

    Wilkerson, Brent A.; Grass, G. Daniel; Wing, Shane B.; Argraves, W. Scott; Argraves, Kelley M.

    2012-01-01

    Sphingosine 1-phosphate (S1P) is a blood-borne lysosphingolipid that acts to promote endothelial cell (EC) barrier function. In plasma, S1P is associated with both high density lipoproteins (HDL) and albumin, but it is not known whether the carriers impart different effects on S1P signaling. Here we establish that HDL-S1P sustains EC barrier longer than albumin-S1P. We showed that the sustained barrier effects of HDL-S1P are dependent on signaling by the S1P receptor, S1P1, and involve persistent activation of Akt and endothelial NOS (eNOS), as well as activity of the downstream NO target, soluble guanylate cyclase (sGC). Total S1P1 protein levels were found to be higher in response to HDL-S1P treatment as compared with albumin-S1P, and this effect was not associated with increased S1P1 mRNA or dependent on de novo protein synthesis. Several pieces of evidence indicate that long term EC barrier enhancement activity of HDL-S1P is due to specific effects on S1P1 trafficking. First, the rate of S1P1 degradation, which is proteasome-mediated, was slower in HDL-S1P-treated cells as compared with cells treated with albumin-S1P. Second, the long term barrier-promoting effects of HDL-S1P were abrogated by treatment with the recycling blocker, monensin. Finally, cell surface levels of S1P1 and levels of S1P1 in caveolin-enriched microdomains were higher after treatment with HDL-S1P as compared with albumin-S1P. Together, the findings reveal S1P carrier-specific effects on S1P1 and point to HDL as the physiological mediator of sustained S1P1-PI3K-Akt-eNOS-sGC-dependent EC barrier function. PMID:23135269

  7. Split Active Asteroid P/2016 J1 (PANSTARRS)

    Energy Technology Data Exchange (ETDEWEB)

    Hui, Man-To; Jewitt, David [Department of Earth, Planetary, and Space Sciences, UCLA, 595 Charles Young Drive East, Box 951567, Los Angeles, CA 90095-1567 (United States); Du, Xinnan, E-mail: pachacoti@ucla.edu [Department of Physics and Astronomy, UCLA, 430 Portola Plaza, Box 951547, Los Angeles, CA 90095-1547 (United States)

    2017-04-01

    We present a photometric and astrometric study of the split active asteroid P/2016 J1 (PANSTARRS). The two components (hereafter J1-A and J1-B) separated either ∼1500 days (2012 May to June) or 2300 days (2010 April) prior to the current epoch, with a separation speed V {sub sep} = 0.70 ± 0.02 m s{sup −1} for the former scenario and 0.83 ± 0.06 m s{sup −1} for the latter. Keck photometry reveals that the two fragments have similar, Sun-like colors that are comparable to the colors of primitive C- and G-type asteroids. With a nominal comet-like albedo, p{sub R} = 0.04, the effective, dust-contaminated cross sections are estimated to be 2.4 km{sup 2} for J1-A and 0.5 km{sup 2} for J1-B. We estimate that the nucleus radii lie in the range 140 ≲  R {sub N} ≲ 900 m for J1-A and 40 ≲  R {sub N} ≲ 400 m for J1-B. A syndyne–synchrone simulation shows that both components have been active for 3–6 months, by ejecting dust grains at speeds ∼0.5 m s{sup −1} with rates ∼1 kg s{sup −1} for J1-A and 0.1 kg s{sup −1} for J1-B. In its present orbit, the rotational spin-up and devolatilization times of 2016 J1 are very small compared to the age of the solar system, raising the question of why this object still exists. We suggest that ice that was formerly buried within this asteroid became exposed at the surface, perhaps via a small impact, and that sublimation torques then rapidly drove it to breakup. Further disintegration events are anticipated owing to the rotational instability.

  8. Evolutionary conservation of P-selectin glycoprotein ligand-1 primary structure and function

    Directory of Open Access Journals (Sweden)

    Schapira Marc

    2007-09-01

    Full Text Available Abstract Background P-selectin glycoprotein ligand-1 (PSGL-1 plays a critical role in recruiting leukocytes in inflammatory lesions by mediating leukocyte rolling on selectins. Core-2 O-glycosylation of a N-terminal threonine and sulfation of at least one tyrosine residue of PSGL-1 are required for L- and P-selectin binding. Little information is available on the intra- and inter-species evolution of PSGL-1 primary structure. In addition, the evolutionary conservation of selectin binding site on PSGL-1 has not been previously examined in detail. Therefore, we performed multiple sequence alignment of PSGL-1 amino acid sequences of 14 mammals (human, chimpanzee, rhesus monkey, bovine, pig, rat, tree-shrew, bushbaby, mouse, bat, horse, cat, sheep and dog and examined mammalian PSGL-1 interactions with human selectins. Results A signal peptide was predicted in each sequence and a propeptide cleavage site was found in 9/14 species. PSGL-1 N-terminus is poorly conserved. However, each species exhibits at least one tyrosine sulfation site and, except in horse and dog, a T [D/E]PP [D/E] motif associated to the core-2 O-glycosylation of a N-terminal threonine. A mucin-like domain of 250–280 amino acids long was disclosed in all studied species. It lies between the conserved N-terminal O-glycosylated threonine (Thr-57 in human and the transmembrane domain, and contains a central region exhibiting a variable number of decameric repeats (DR. Interspecies and intraspecies polymorphisms were observed. Transmembrane and cytoplasmic domain sequences are well conserved. The moesin binding residues that serve as adaptor between PSGL-1 and Syk, and are involved in regulating PSGL-1-dependent rolling on P-selectin are perfectly conserved in all analyzed mammalian sequences. Despite a poor conservation of PSGL-1 N-terminal sequence, CHO cells co-expressing human glycosyltransferases and human, bovine, pig or rat PSGL-1 efficiently rolled on human L- or P

  9. The yields of 1P and 1D resonances in the He(e,2e)He+ reaction

    International Nuclear Information System (INIS)

    Lhagva, O.; Badamdamdin, R.; Strakhova, S.I.; Hehnmedeh, L.

    1991-01-01

    In the first Born approximation the dependence of the yields of the 1 P and 1 D resonances in the He(e,2e)He + reaction on the momentum transfer in the recoil peak region at incident energies E 0 =1000 eV is studied. It is shown that in a certain range of the ejection angle and for the large momentum transfer the yield of the 1 D resonance dominates over the 1 P resonance one. 12 refs.; 4 figs

  10. Inter- and intramolecular deuterium isotope effects on the cytochrome P-450-catalyzed oxidative dehalogenation of 1,1,2,2-tetrachloroethane

    International Nuclear Information System (INIS)

    Hales, D.B.; Ho, B.; Thompson, J.A.

    1987-01-01

    The oxidation of 1,1,2,2-tetrachloroethane to dichloroacetic acid was investigated with rat liver microsomes and purified cytochrome P-450. Deuterium substitution had no effect on Km values, but both the inter- and intramolecular isotope effects (kH/kD) on Vmax were in the range 5.7-6.1. The equivalence of the inter- and intramolecular values indicates that 6.0 may be a good estimate of the intrinsic isotope effect. The intermolecular kH/kD value for the conversion of 1,1,2,2-trichloroethane and its 1- 2 H analog to chloroacetic acid was 5.5. These data, and the finding that 1 atom of 18 O was incorporated into the product when TCEA was oxidized in an 18 O 2 atmosphere, support an oxidative dechlorination mechanism that involves hydrogen atom abstraction by the P-450 intermediate oxo complex

  11. Laser spectroscopy of the 4s4p(3) P-2-4s3d(1) D-2 transition on magnetically trapped calcium atoms

    NARCIS (Netherlands)

    Dammalapati, U.; Norris, I.; Burrows, C.; Riis, E.

    2011-01-01

    Laser excitation of the 4s4p(3) P-2-4s3d(1) D-2 transition in atomic calcium has been observed and the wavelength determined to 1530.5298(6) nm. The metastable 4s4p(3) P-2 atoms were magnetically trapped in the quadrupole magnetic field of a magneto-optical trap. This state represents the only

  12. Crystal Structure of the Yeast Nicotinamidase Pnc1p

    OpenAIRE

    Hu, Gang; Taylor, Alexander B.; McAlister-Henn, Lee; Hart, P. John

    2007-01-01

    The yeast nicotinamidase Pnc1p acts in transcriptional silencing by reducing levels of nicotinamide, an inhibitor of the histone deacetylase Sir2p. The Pnc1p structure was determined at 2.9 Å resolution using MAD and MIRAS phasing methods after inadvertent crystallization during the pursuit of the structure of histidine-tagged yeast isocitrate dehydrogenase (IDH). Pnc1p displays a cluster of surface histidine residues likely responsible for its co-fractionation with IDH from Ni2+-coupled chro...

  13. Search for new physics in lepton + photon + x events with 929 pb**-1 of p anti-p collisions at s**(1/2) = 1.96 TeV

    Energy Technology Data Exchange (ETDEWEB)

    Loginov, A.; /Moscow, ITEP

    2006-10-01

    The authors present results of a search in 929 {+-} 56 pb{sup -1} of p{bar p} collisions at 1.96 TeV for the anomalous production of events containing a charged lepton ({ell}, either e or {mu}) and a photon ({gamma}), both with high transverse momentum, accompanied by additional signatures, X, including missing transverse energy (E{sub T}) and additional leptons and photons. They use the same selection criteria as in the previous CDF Run I search, but with an order-magnitude larger data set, a higher p{bar p} collision energy, and the CDF II detector.

  14. Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage.

    Science.gov (United States)

    Cisneros-Mejorado, Abraham; Gottlieb, Miroslav; Cavaliere, Fabio; Magnus, Tim; Koch-Nolte, Friederich; Scemes, Eliana; Pérez-Samartín, Alberto; Matute, Carlos

    2015-05-01

    The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced their slope, and that simultaneous inhibition did not further enhance the effects of blocking either one. These results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal death that was reduced with P2X7 and pannexin-1 blockers as well as in organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently, we used transient middle cerebral artery occlusion to monitor the neuroprotective effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and their ablation in knockout mice, substantially attenuated the motor symptoms and reduced the infarct volume to ~50% of that in vehicle-treated or wild-type animals. These results show that P2X7 receptors and pannexin-1 channels are major mediators of postanoxic depolarization in neurons and of brain damage after ischemia, and that they operate in the same deleterious signaling cascade leading to neuronal and tissue demise.

  15. Computer program /P1-GAS/ calculates the P-0 and P-1 transfer matrices for neutron moderation in a monatomic gas

    Science.gov (United States)

    Collier, G.; Gibson, G.

    1968-01-01

    FORTRAN 4 program /P1-GAS/ calculates the P-O and P-1 transfer matrices for neutron moderation in a monatomic gas. The equations used are based on the conditions that there is isotropic scattering in the center-of-mass coordinate system, the scattering cross section is constant, and the target nuclear velocities satisfy a Maxwellian distribution.

  16. Contribution to π+p inelastic scattering at incoming pion energies near 1 GeV

    International Nuclear Information System (INIS)

    Deler, B.

    1969-01-01

    Results on π + p scattering at 810 and 1300 MeV incoming kinetic energy are presented. In the three-body final states (π + p → π + π 0 p or π + π + n) the N * 33 production is strongly dominant. At 1300 MeV one also observes the ρ, N * 1/2 3/2 and N * 1/2 5/2 productions. The difficulty in correctly separating these channels demands trying a more general analysis, taking simultaneously into account several processes (N * π, ρN,...). A generalized isobaric model is discussed. Assuming the interaction of particles by pairs, we can carry out a partial wave analysis of the three body final state reactions. The expansion of the differential cross section in spherical harmonics for data between 600 and 1460 MeV (compilation of data from different laboratories) leads to a simple discussion of the angular effects for different parts of the Dalitz plot. A partial wave analysis has been made below 1 GeV. The reaction p π + π 0 is correctly explained by considering only the N * 33 production. The different partial waves are in agreement with the elastic phase shift analysis, except for the wave SD1 (corresponding to the elastic wave S31) which is found to be small. Therefore, the S31 resonance appears weakly coupled to the N * 33 -π channel. (author) [fr

  17. SMV1 virus-induced CRISPR spacer acquisition from the conjugative plasmid pMGB1 in Sulfolobus solfataricus P2

    DEFF Research Database (Denmark)

    Erdmann, Susanne; Shah, Shiraz Ali; Garrett, Roger Antony

    2013-01-01

    Organisms of the crenarchaeal order Sulfolobales carry complex CRISPR (clustered regularly interspaced short palindromic repeats) adaptive immune systems. These systems are modular and show extensive structural and functional diversity, especially in their interference complexes. The primary...... targets are an exceptional range of diverse viruses, many of which propagate stably within cells and follow lytic life cycles without producing cell lysis. These properties are consistent with the difficulty of activating CRISPR spacer uptake in the laboratory, but appear to conflict with the high...... complexity and diversity of the CRISPR immune systems that are found among the Sulfolobales. In the present article, we re-examine the first successful induction of archaeal spacer acquisition in our laboratory that occurred exclusively for the conjugative plasmid pMGB1 in Sulfolobus solfataricus P2...

  18. How well do we know the quantum numbers of possible anti p p → M1M2 states

    International Nuclear Information System (INIS)

    Lanou, R.E.

    1979-01-01

    Information is available to completely analyze the p anti p → ππ reaction, allowing more global, large-scale, phenomenological analyses which combine the two experimental data sets in an energy independent, amplitude analysis which also includes pion-nucleon data. It would appear from the preliminary analyses of p anti p → M 1 M 2 angular distributions and polarizations the T-region may indeed contain some very interesting activity

  19. Suppression in the electrical hysteresis by using CaF2 dielectric layer for p-GaN MIS capacitors

    Science.gov (United States)

    Sang, Liwen; Ren, Bing; Liao, Meiyong; Koide, Yasuo; Sumiya, Masatomo

    2018-04-01

    The capacitance-voltage (C-V) hysteresis in the bidirectional measurements of the p-GaN metal-insulator-semiconductor (MIS) capacitor is suppressed by using a CaF2 dielectric layer and a post annealing treatment. The density of trapped charge states at the CaF2/p-GaN interface is dramatically reduced from 1.3 × 1013 cm2 to 1.1 × 1011/cm2 compared to that of the Al2O3/p-GaN interface with a large C-V hysteresis. It is observed that the disordered oxidized interfacial layer can be avoided by using the CaF2 dielectric. The downward band bending of p-GaN is decreased from 1.51 to 0.85 eV as a result of the low-density oxides-related trap states. Our work indicates that the CaF2 can be used as a promising dielectric layer for the p-GaN MIS structures.

  20. Exceptionally High Efficient Co-Co2P@N, P-Codoped Carbon Hybrid Catalyst for Visible Light-Driven CO2-to-CO Conversion.

    Science.gov (United States)

    Fu, Wen Gan

    2018-05-02

    Artificial photosynthesis has attracted wide attention, particularly the development of efficient solar light-driven methods to reduce CO2 to form energy-rich carbon-based products. Because CO2 reduction is an uphill process with a large energy barrier, suitable catalysts are necessary to achieve this transformation. In addition, CO2 adsorption on a catalyst and proton transfer to CO2 are two important factors for the conversion reaction,and catalysts with high surface area and more active sites are required to improve the efficiency of CO2 reduction. Here, we report a visible light-driven system for CO2-to-CO conversion that consists of a heterogeneous hybrid catalyst of Co and Co2P nanoparticles embedded in carbon nanolayers codoped with N and P (Co-Co2P@NPC) and a homogeneous Ru(II)-based complex photosensitizer. The average generation rate of CO of the system was up to 35,000 μmol h-1 g-1 with selectivity of 79.1% in 3 h. Linear CO production at an exceptionally high rate of 63,000 μmol h-1 g-1 was observed in the first hour of reaction. Inspired by this highly active catalyst, we also synthesized Co@NC and Co2P@NPC materials and explored their structure, morphology, and catalytic properties for CO2 photoreduction. The results showed that the nanoparticle size, partially adsorbed H2O molecules on the catalyst surface, and the hybrid nature of the systems influenced their photocatalytic CO2 reduction performance. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Global description of (n,p) - and (n,2n) - activation cross sections within statistical multistep theory

    International Nuclear Information System (INIS)

    Kalka, H.; Torjman, M.; Seeliger, D.; Lopez, R.

    1989-07-01

    A unique description of (n,p) and (n,2n) activation cross sections as well as emission spectra is proposed within a pure multistep approach. Calculations are presented for 8 nuclei (A=47...65) in the incident energy range from zero up to 20 MeV. (author). 42 refs, 5 figs, 1 tab

  2. Re-evaluation of microscopic and integral cross-section data for important dosimetry reactions. Re-evaluation of the excitation functions for the 24Mg(n,p)24Na, 32S(n,p)32P, 60Ni(n,p)60m+gCo, 63Cu(n,2n)62Cu, 65Cu(n,2n)64Cu, 64Zn(n,p)64Cu, 115In(n,2n)114mIn, 127I(n,2n)126I, 197Au(n,2n)196Au and 199Hg(n,n')199mHg reactions

    International Nuclear Information System (INIS)

    Zolotarev, K.I.

    2008-08-01

    Re-evaluations of cross sections and their associated covariance matrices have been carried out for ten dosimetry reactions: - excitation functions for the 63 Cu(n,2n) 62 Cu, 65 Cu(n,2n) 64 Cu, 64 Zn(n,p) 64 Cu, 115 In(n,2n) 114m In and 199 Hg(n,n') 199m Hg reactions were re-evaluated over the neutron energy range from threshold to 20 MeV; - excitation functions for the 24 Mg(n,p) 24 Na, 32 S(n,p) 32 P and 60 Ni(n,p) 60m+g Co were reevaluated in the energy range from threshold to 21 MeV; - excitation functions for the 127 I(n,2n) 126 I and 197 Au(n,2n) 196 Au reactions were reevaluated in the energy range from threshold to 32 and 40 MeV, respectively. Benchmark calculations performed for 235 U thermal fission and 252 Cf spontaneous fission neutron spectra show that the integral cross sections derived from the newly evaluated excitation functions exhibit improved agreement with related experimental data when compared with the equivalent data from the IRDF-2002 library. (author)

  3. Stereodynamics of Ne(3P2) reacting with Ar, Kr, Xe, and N2

    Science.gov (United States)

    Zou, Junwen; Gordon, Sean D. S.; Tanteri, Silvia; Osterwalder, Andreas

    2018-04-01

    Stereodynamics experiments of Ne(3P2) reacting with Ar, Kr, Xe, and N2 leading to Penning and associative ionization have been performed in a crossed molecular beam apparatus. A curved magnetic hexapole was used to state-select and polarize Ne(3P2) atoms which were then oriented in a rotatable magnetic field and crossed with a beam of Ar, Kr, Xe, or N2. The ratio of associative to Penning ionization was recorded as a function of the magnetic field direction for collision energies between 320 cm-1 and 500 cm-1. Reactivities are obtained for individual states that differ only in Ω, the projection of the neon total angular momentum vector on the inter-particle axis. The results are rationalized on the basis of a model involving a long-range and a short-range reaction mechanism. Substantially lower probability for associative ionization was observed for N2, suggesting that predissociation plays a critical role in the overall reaction pathway.

  4. Oral vaccine of Lactococcus lactis harbouring pandemic H1N1 2009 haemagglutinin1 and nisP anchor fusion protein elevates anti-HA1 sIgA levels in mice.

    Science.gov (United States)

    Joan, Stella Siaw Xiu; Pui-Fong, Jee; Song, Adelene Ai-Lian; Chang, Li-Yen; Yusoff, Khatijah; AbuBakar, Sazaly; Rahim, Raha Abdul

    2016-05-01

    An oral lactococcal-based vaccine which haboured the haemagglutinin1 (HA1) antigen fused to nisP anchor protein for the purpose of surface displaying the HA1 antigen was developed against H1N1 virus. Recombinant L. lactis strains expressed HA1-nisP fusion proteins when induced with nisin, as confirmed through western blotting. However, immunofluorescense did not detect any surface-displayed proteins, suggesting that the protein was either unsuccessfully translocated or improperly displayed. Despite this, oral administration of recombinant L. lactis strains to BALB/c mice revealed that significant levels of anti-HA1 sIgA antibodies were detected in mice fecal suspension samples of mice group NZ9000 (pNZ:HN) when compared to the negative control NZ9000 (pNZ8048) group. Specific anti-HA1 sIgA antibodies were locally produced and live recombinant lactococcal vaccine was able to elicit humoral response of BALB/c mice despite unsuccessful surface display of the HA1 epitope.

  5. Energy-Transfer Kinetics for Xe (6p[1/2]0) Atoms in Kr, Ar, Ne, and He.

    Science.gov (United States)

    He, Shan; Liu, Dong; Li, Xueyang; Chu, Junzhi; Guo, Jingwei; Liu, Jinbo; Hu, Shu; Sang, Fengting; Jin, Yuqi

    2018-06-11

    The kinetic processes for the Xe (6p[1/2] 0 ) atoms in Kr, Ar, Ne, and He buffer gases were studied. We found that Kr, Ar, and Ne atoms can be used to switch the amplified spontaneous emission (ASE) channel from 3408 nm (6p[1/2] 0 -6s'[1/2] 1 ) to 3680 nm (5d[1/2] 1 -6p[1/2] 1 ), while Xe and He atoms do not show such a phenomenon. This ASE channel switch is mainly ascribed to the fast transfer of 6p[1/2] 0 → 5d[1/2] 1 . On the basis of the rate equations for two-state coupling (energy-transfer processes between the two states are very rapid), the reason why the ASE channel switch effect normally coincides with a double exponential decay of the spontaneous emission at 828 nm (6p[1/2] 0 -6s[3/2] 1 ) is explained. The actual situations in Xe, Ar, Ne, and He follow this rule. However, the strictly single exponential decay of the spontaneous emission at 828 nm and strong ASE channel switch effect simultaneously emerge in Kr. This indicates that the transfer of 6p[1/2] 0 → 5d[1/2] 1 in Kr does not occur via two-state coupling, but via two steps of near-resonance collision through the 5s[3/2] 2 (Kr) state as the intermediate state (6p[1/2] 0 → 5s[3/2] 2 (Kr) → 5d[1/2] 1 ). In addition, we found Xe (6p[1/2] 0 ) atoms strongly tend to reach the 6p[3/2] 2 , 6p[3/2] 1 , and 6p[5/2] 2 states through the 5s[3/2] 2 (Kr) state as the intermediate state in Kr. The 5s[3/2] 2 (Kr) state plays a very important role in the energy-transfer kinetics for the Xe (6p[1/2] 0 ) atoms. Kr is probably an excellent buffer gas for laser systems based on Xe.

  6. Photoluminescence of heterostructures with GaP1−xNx and GaP1−x−yNxAsy layers grown on GaP and Si substrates by molecular-beam epitaxy

    International Nuclear Information System (INIS)

    Lazarenko, A. A.; Nikitina, E. V.; Sobolev, M. S.; Pirogov, E. V.; Denisov, D. V.; Egorov, A. Yu.

    2015-01-01

    The structural and optical properties of heterostructures containing GaP 1−x N x ternary and GaP 1−x−y N x As y quaternary alloy layers are discussed. The heterostructures are grown by molecular-beam epitaxy on GaP and Si substrates. The structures are studied by the high-resolution X-ray diffraction technique and photoluminescence measurements in a wide temperature range from 10 to 300 K. In the low-temperature photoluminescence spectra of the alloys with a low nitrogen fraction (x < 0.007), two clearly resolved narrow lines attributed to the localized states of nitrogen pairs and the phonon replicas of these lines are observed

  7. Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains.

    Science.gov (United States)

    Chou, Tsui-Fen; Bulfer, Stacie L; Weihl, Conrad C; Li, Kelin; Lis, Lev G; Walters, Michael A; Schoenen, Frank J; Lin, Henry J; Deshaies, Raymond J; Arkin, Michelle R

    2014-07-29

    The p97 AAA (ATPase associated with diverse cellular activities), also called VCP (valosin-containing protein), is an important therapeutic target for cancer and neurodegenerative diseases. p97 forms a hexamer composed of two AAA domains (D1 and D2) that form two stacked rings and an N-terminal domain that binds numerous cofactor proteins. The interplay between the three domains in p97 is complex, and a deeper biochemical understanding is needed in order to design selective p97 inhibitors as therapeutic agents. It is clear that the D2 ATPase domain hydrolyzes ATP in vitro, but whether D1 contributes to ATPase activity is controversial. Here, we use Walker A and B mutants to demonstrate that D1 is capable of hydrolyzing ATP and show for the first time that nucleotide binding in the D2 domain increases the catalytic efficiency (kcat/Km) of D1 ATP hydrolysis 280-fold, by increasing kcat 7-fold and decreasing Km about 40-fold. We further show that an ND1 construct lacking D2 but including the linker between D1 and D2 is catalytically active, resolving a conflict in the literature. Applying enzymatic observations to small-molecule inhibitors, we show that four p97 inhibitors (DBeQ, ML240, ML241, and NMS-873) have differential responses to Walker A and B mutations, to disease-causing IBMPFD mutations, and to the presence of the N domain binding cofactor protein p47. These differential effects provide the first evidence that p97 cofactors and disease mutations can alter p97 inhibitor potency and suggest the possibility of developing context-dependent inhibitors of p97. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Transcriptional profiling of extracellular amino acid sensing in Saccharomyces cerevisiae and the role of Stp1p and Stp2p

    DEFF Research Database (Denmark)

    Eckert-Boulet, Nadine; Nielsen, P.S.; Friis, Carsten

    2004-01-01

    Tdh1p and glucokinase (Glk1p), shows increased transcription levels in either or both of the mutants. Also, most of the structural genes involved in trehalose and glycogen synthesis and a few genes in the glyoxylate cycle and the pentose phosphate pathway are derepressed in the ssy1 and stp1 stp2...

  9. Characterization and complete genome sequence of a novel N4-like bacteriophage, pSb-1 infecting Shigella boydii.

    Science.gov (United States)

    Jun, Jin Woo; Yun, Sae Kil; Kim, Hyoun Joong; Chai, Ji Young; Park, Se Chang

    2014-10-01

    Shigellosis is one of major foodborne pathogens in both developed and developing countries. Although antibiotic therapy is considered an effective treatment for shigellosis, the imprudent use of antibiotics has led to the increase of multiple-antibiotic-resistant Shigella species globally. In this study, we isolated a virulent Podoviridae bacteriophage (phage), pSb-1, that infects Shigella boydii. One-step growth analysis revealed that this phage has a short latent period (15 min) and a large burst size (152.63 PFU/cell), indicating that pSb-1 has good host infectivity and effective lytic activity. The double-stranded DNA genome of pSb-1 is composed of 71,629 bp with a G + C content of 42.74%. The genome encodes 103 putative ORFs, 9 putative promoters, 21 transcriptional terminators, and one tRNA region. Genome sequence analysis of pSb-1 and comparative analysis with the homologous phage EC1-UPM, N4-like phage revealed that there is a high degree of similarity (94%, nucleotide sequence identity) between pSb-1 and EC1-UPM in 73 of the 103 ORFs of pSb-1. The results of this investigation indicate that pSb-1 is a novel virulent N4-like phage infecting S. boydii and that this phage might have potential uses against shigellosis. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  10. The (2p, 2p) 11Δg state of 6Li2: Fourier transform spectrum of the 11Δg-B1IIu transition

    International Nuclear Information System (INIS)

    Linton, C.; Martin, F.; Crozet, P.; Ross, A.J.; Bacis, R.

    1993-01-01

    The 1 1 Δ g -B 1 II u transition of 6 Li 2 has been observed in collisionally induced fluorescence following single frequency optical-optical double resonance excitation of the F 1 Σ g + state using a ring dye laser with DCM dye. Spectra of the s and a symmetry levels were obtained separately, at high resolution, in the near-infrared region using a Fourier transform spectrometer. The molecular constants (Dunham coefficients) of the 1 1 Δ g state have been calculated. Comparison of the constants and dissociation energy with ab initio calculations has shown that the 1 1 Δ g state correlates with Li(2p) + Li(2p) and has a dissociation energy of 9,579 ± 1 cm -1 . The energy transfer process responsible for excitation of the 1 1 Δ g state is discussed

  11. Arrestin scaffolds NHERF1 to the P2Y12 receptor to regulate receptor internalization.

    Science.gov (United States)

    Nisar, Shaista P; Cunningham, Margaret; Saxena, Kunal; Pope, Robert J; Kelly, Eamonn; Mundell, Stuart J

    2012-07-13

    We have recently shown in a patient with mild bleeding that the PDZ-binding motif of the platelet G protein-coupled P2Y(12) receptor (P2Y(12)R) is required for effective receptor traffic in human platelets. In this study we show for the first time that the PDZ motif-binding protein NHERF1 exerts a major role in potentiating G protein-coupled receptor (GPCR) internalization. NHERF1 interacts with the C-tail of the P2Y(12)R and unlike many other GPCRs, NHERF1 interaction is required for effective P2Y(12)R internalization. In vitro and prior to agonist stimulation P2Y(12)R/NHERF1 interaction requires the intact PDZ binding motif of this receptor. Interestingly on receptor stimulation NHERF1 no longer interacts directly with the receptor but instead binds to the receptor via the endocytic scaffolding protein arrestin. These findings suggest a novel model by which arrestin can serve as an adaptor to promote NHERF1 interaction with a GPCR to facilitate effective NHERF1-dependent receptor internalization.

  12. Enrichment of variations in KIR3DL1/S1 and KIR2DL2/L3 among H1N1/09 ICU patients: an exploratory study.

    Directory of Open Access Journals (Sweden)

    David La

    Full Text Available BACKGROUND: Infection by the pandemic influenza A (H1N1/09 virus resulted in significant pathology among specific ethnic groups worldwide. Natural Killer (NK cells are important in early innate immune responses to viral infections. Activation of NK cells, in part, depend on killer-cell immunoglobulin-like receptors (KIR and HLA class I ligand interactions. To study factors involved in NK cell dysfunction in overactive immune responses to H1N1 infection, KIR3DL1/S1 and KIR2DL2/L3 allotypes and cognate HLA ligands of H1N1/09 intensive-care unit (ICU patients were determined. METHODOLOGY AND FINDINGS: KIR3DL1/S1, KIR2DL2/L3, and HLA -B and -C of 51 H1N1/09 ICU patients and 105 H1N1-negative subjects (St. Theresa Point, Manitoba were characterized. We detected an increase of 3DL1 ligand-negative pairs (3DL1/S1(+ Bw6(+ Bw4(-, and a lack of 2DL1 HLA-C2 ligands, among ICU patients. They were also significantly enriched for 2DL2/L3 ligand-positive pairs (PVA, P=0.024, Pc=0.047; Odds Ratio:2.563, CI95%:1.109-5.923, 3DL1*00101 (Ab>VA, PSTh, P=0.034, Pc=0.268, and 3DL1*029 (Ab>STh, P=0.039, Pc=0.301. Aboriginal patients ligand-positive for 3DL1/S1 and 2DL1 had the lowest probabilities of death (R(d (R(d=28%, compared to patients that were 3DL1/S1 ligand-negative (R(d=52% or carried 3DL1*029 (R(d=52%. Relative to Caucasoids (CA, two allotypes were enriched among non-aboriginal ICU patients (NAb: 3DL1*00401 (NAb>CA, P<0.001, Pc<0.001 and 3DL1*01502 (CAP=0.012, Pc=0.156. Non-aboriginal patients with ligands for all three KIRs (3DL1/S1, 2DL2/L3, and 2DL1 had the lowest probabilities of death (R(d=36%, compared to subjects with 3DL1*01502 (R(d=48% and/or 3DL1*00401 (R(d=58%. CONCLUSIONS: Specific KIR3DL1/S1 allotypes, 3DL1/S1 and 2DL1 ligand-negative pairs, and 2DL2/L3 ligand-positive pairs were enriched among ICU patients. This suggests a possible association with NK cell dysfunction in patients with overactive immune responses to H1N1/09, leading to

  13. Generalized valence bond description of the ground states (X(1)Σg(+)) of homonuclear pnictogen diatomic molecules: N2, P2, and As2.

    Science.gov (United States)

    Xu, Lu T; Dunning, Thom H

    2015-06-09

    The ground state, X1Σg+, of N2 is a textbook example of a molecule with a triple bond consisting of one σ and two π bonds. This assignment, which is usually rationalized using molecular orbital (MO) theory, implicitly assumes that the spins of the three pairs of electrons involved in the bonds are singlet-coupled (perfect pairing). However, for a six-electron singlet state, there are five distinct ways to couple the electron spins. The generalized valence bond (GVB) wave function lifts this restriction, including all of the five spin functions for the six electrons involved in the bond. For N2, we find that the perfect pairing spin function is indeed dominant at Re but that it becomes progressively less so from N2 to P2 and As2. Although the perfect pairing spin function is still the most important spin function in P2, the importance of a quasi-atomic spin function, which singlet couples the spins of the electrons in the σ orbitals while high spin coupling those of the electrons in the π orbitals on each center, has significantly increased relative to N2 and, in As2, the perfect pairing and quasi-atomic spin couplings are on essentially the same footing. This change in the spin coupling of the electrons in the bonding orbitals down the periodic table may contribute to the rather dramatic decrease in the strengths of the Pn2 bonds from N2 to As2 as well as in the increase in their chemical reactivity and should be taken into account in more detailed analyses of the bond energies in these species. We also compare the spin coupling in N2 with that in C2, where the quasi-atomic spin coupling dominants around Re.

  14. Sphingosine-1-Phosphate and the S1P3 Receptor Initiate Neuronal Retraction via RhoA/ROCK Associated with CRMP2 Phosphorylation

    Science.gov (United States)

    Quarta, Serena; Camprubí-Robles, Maria; Schweigreiter, Rüdiger; Matusica, Dusan; Haberberger, Rainer V.; Proia, Richard L.; Bandtlow, Christine E.; Ferrer-Montiel, Antonio; Kress, Michaela

    2017-01-01

    The bioactive lipid sphingosine-1-phosphate (S1P) is an important regulator in the nervous system. Here, we explored the role of S1P and its receptors in vitro and in preclinical models of peripheral nerve regeneration. Adult sensory neurons and motor neuron-like cells were exposed to S1P in an in vitro assay, and virtually all neurons responded with a rapid retraction of neurites and growth cone collapse which were associated with RhoA and ROCK activation. The S1P1 receptor agonist SEW2871 neither activated RhoA or neurite retraction, nor was S1P-induced neurite retraction mitigated in S1P1-deficient neurons. Depletion of S1P3 receptors however resulted in a dramatic inhibition of S1P-induced neurite retraction and was on the contrary associated with a significant elongation of neuronal processes in response to S1P. Opposing responses to S1P could be observed in the same neuron population, where S1P could activate S1P1 receptors to stimulate elongation or S1P3 receptors and retraction. S1P was, for the first time in sensory neurons, linked to the phosphorylation of collapsin response-mediated protein-2 (CRMP2), which was inhibited by ROCK inhibition. The improved sensory recovery after crush injury further supported the relevance of a critical role for S1P and receptors in fine-tuning axonal outgrowth in peripheral neurons. PMID:29066950

  15. Electron-impact excitation of multiply-charged ions using energy loss in merged beams: e + Si3+(3s2S1/2) → e + Si3+(3p2P1/2,3/2)

    International Nuclear Information System (INIS)

    Wahlin, E.K.; Thompson, J.S.; Dunn, G.H.; Phaneuf, R.A.; Gregory, D.C.; Smith, A.C.H.

    1990-01-01

    For the first time absolute total cross sections for electron-impact excitation of a multiply-charged ion have been measured using an electron-energy-loss technique. Measurements were made near threshold for the process e + Si 3+ (3s 2 S 1/2 ) → e + Si 3+ (3p 2 P 1/2 , 3/2 ) -- 8.88 eV. The 10 -15 cm 2 measured cross section agrees with results of 7-state close coupling calculations to better than the ±20% (90% CL) total uncertainty of the measurements. Convoluting the theoretical curve with a Gaussian energy distribution indicates an energy width of 0.15 approx-lt ΔE approx-lt 0.20 eV. 12 refs., 2 figs

  16. Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways.

    Science.gov (United States)

    Li, Xuelian; Wang, GuoYuan; QiLi, MuGe; Liang, HaiHai; Li, TianShi; E, XiaoQiang; Feng, Ying; Zhang, Ying; Liu, Xiao; Qian, Ming; Xu, BoZhi; Shen, ZhiHang; Gitau, Samuel Chege; Zhao, DanDan; Shan, HongLi

    2018-01-01

    Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload-induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 10 mg·kg-1·day-1 of aspirin for 4 weeks. Masson staining and a collagen content assay were used to detect the effects of aspirin on cardiac fibrosis in vivo and in vitro. Western blot and qRT-PCR were applied to examine the impact of aspirin on extracellular signal-regulated kinases (Erks), p-Akt/β-catenin, SerpinE2, collagen I, and collagen III levels in the mice heart. Aspirin significantly suppressed the expression of α-smooth muscle actin (α-SMA; 1.19±0.19-fold) and collagen I (0.95±0.09-fold) in TAC mice. Aspirin, at doses of 100 and 1000 µM, also significantly suppressed angiotensin II-induced α-SMA and collagen I in cultured CFs. The enhanced phosphorylation of Erk1/2 caused by TAC (p-Erk1, 1.49±0.19-fold; p-Erk2, 1.96±0.68-fold) was suppressed by aspirin (p-Erk1, 1.04±0.15-fold; p-Erk2, 0.87±0.06-fold). SerpinE2 levels were suppressed via the Erk1/2 signalling pathway following treatment with aspirin (1.36±0.12-fold for TAC; 1.06±0.07-fold for aspirin+TAC). The p-Akt and β-catenin levels were also significantly inhibited in vivo and in vitro. Our study reveals a novel mechanism by which aspirin alleviates pressure overload-induced cardiac interstitial fibrosis in TAC mice by suppressing the p-Erk1/2 and p-Akt/β-catenin signalling pathways. © 2018 The Author(s). Published by S. Karger AG, Basel.

  17. Total (p,n), (p,γ), (p,p'γ) and differential (p,p) cross-sections measurements for /sup 61,64/Ni

    International Nuclear Information System (INIS)

    Hershberger, R.L.; Gabbard, F.; Laird, C.E.

    1985-01-01

    Absolute total (p,n) and differential elastic (p,p) cross sections have been measured for /sup 61,64/Ni in the energy range of E/sub p/ = 2 to 7 MeV. The (p,γ) and (p,p'γ) cross sections were measured from as low an energy as feasible to approximately one MeV above the (p,n) threshold. Standard optical potentials have been used with a Hauser-Feshbach model to analyze the data. The adopted model values are used to deduce a total proton strength function which displays features of the 3s single particle resonance

  18. Cross talk between MMP2-Spm-Cer-S1P and ERK1/2 in proliferation of pulmonary artery smooth muscle cells under angiotensin II stimulation.

    Science.gov (United States)

    Chowdhury, Animesh; Sarkar, Jaganmay; Pramanik, Pijush Kanti; Chakraborti, Tapati; Chakraborti, Sajal

    2016-08-01

    The aim of the present study is to establish the mechanism associated with the proliferation of PASMCs under ANG II stimulation. The results showed that treatment of PASMCs with ANG II induces an increase in cell proliferation and 100 nM was the optimum concentration for maximum increase in proliferation of the cells. Pretreatment of the cells with AT1, but not AT2, receptor antagonist inhibited ANG II induced cell proliferation. Pretreatment with pharmacological and genetic inhibitors of sphingomyelinase (SMase) and sphingosine kinase (SPHK) prevented ANG II-induced cell proliferation. ANG II has also been shown to induce SMase activity, SPHK phosphorylation and S1P production. In addition, ANG II caused an increase in proMMP-2 expression and activation, ERK1/2 phosphorylation and NADPH oxidase activation. Upon inhibition of MMP-2, SMase activity and S1P level were curbed leading to inhibition of cell proliferation. SPHK was phosphorylated by ERK1/2 during ET-1 stimulation of the cells. ANG II-induced ERK1/2 phosphorylation and proMMP-2 expression and activation in the cells were abrogated upon inhibition of NADPH oxidase activity. Overall, NADPH oxidase plays an important role in proMMP-2 expression and activation and that MMP-2 mediated SMC proliferation occurs through the involvement of Spm-Cer-S1P signaling axis under ANG II stimulation of PASMCs. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Expression analysis of the speech-related genes FoxP1 and FoxP2 and their relation to singing behavior in two songbird species

    Science.gov (United States)

    Chen, Qianqian; Heston, Jonathan B.; Burkett, Zachary D.; White, Stephanie A.

    2013-01-01

    SUMMARY Humans and songbirds are among the rare animal groups that exhibit socially learned vocalizations: speech and song, respectively. These vocal-learning capacities share a reliance on audition and cortico-basal ganglia circuitry, as well as neurogenetic mechanisms. Notably, the transcription factors Forkhead box proteins 1 and 2 (FoxP1, FoxP2) exhibit similar expression patterns in the cortex and basal ganglia of humans and the zebra finch species of songbird, among other brain regions. Mutations in either gene are associated with language disorders in humans. Experimental knock-down of FoxP2 in the basal ganglia song control region Area X during song development leads to imprecise copying of tutor songs. Moreover, FoxP2 levels decrease naturally within Area X when zebra finches sing. Here, we examined neural expression patterns of FoxP1 and FoxP2 mRNA in adult Bengalese finches, a songbird species whose songs exhibit greater sequence complexity and increased reliance on audition for maintaining their quality. We found that FoxP1 and FoxP2 expression in Bengalese finches is similar to that in zebra finches, including strong mRNA signals for both factors in multiple song control nuclei and enhancement of FoxP1 in these regions relative to surrounding brain tissue. As with zebra finches, when Bengalese finches sing, FoxP2 is behaviorally downregulated within basal ganglia Area X over a similar time course, and expression negatively correlates with the amount of singing. This study confirms that in multiple songbird species, FoxP1 expression highlights song control regions, and regulation of FoxP2 is associated with motor control of song. PMID:24006346

  20. Coronin 1B regulates S1P-induced human lung endothelial cell chemotaxis: role of PLD2, protein kinase C and Rac1 signal transduction.

    Directory of Open Access Journals (Sweden)

    Peter V Usatyuk

    Full Text Available Coronins are a highly conserved family of actin binding proteins that regulate actin-dependent processes such as cell motility and endocytosis. We found that treatment of human pulmonary artery endothelial cells (HPAECs with the bioactive lipid, sphingosine-1-phosphate (S1P rapidly stimulates coronin 1B translocation to lamellipodia at the cell leading edge, which is required for S1P-induced chemotaxis. Further, S1P-induced chemotaxis of HPAECs was attenuated by pretreatment with small interfering RNA (siRNA targeting coronin 1B (∼36%, PLD2 (∼45% or Rac1 (∼50% compared to scrambled siRNA controls. Down regulation PLD2 expression by siRNA also attenuated S1P-induced coronin 1B translocation to the leading edge of the cell periphery while PLD1 silencing had no effect. Also, S1P-induced coronin 1B redistribution to cell periphery and chemotaxis was attenuated by inhibition of Rac1 and over-expression of dominant negative PKC δ, ε and ζ isoforms in HPAECs. These results demonstrate that S1P activation of PLD2, PKC and Rac1 is part of the signaling cascade that regulates coronin 1B translocation to the cell periphery and the ensuing cell chemotaxis.

  1. Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes.

    Science.gov (United States)

    Shen, Shuijie; Li, Lei; Ding, Xinxin; Zheng, Jiang

    2014-01-21

    Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent metabolic activation. P450 2E1 and P450 2F2 are considered to be two main cytochrome P450 enzymes responsible for styrene metabolism in mice. The objective of the current study was to determine the correlation between the formation of styrene metabolites (i.e., styrene oxide and 4-vinylphenol) and pulmonary toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. A dramatic decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2-null mouse lung microsomes relative to that in the wild-type mouse lung microsomes; however, no significant difference in the production of the styrene metabolites was observed between lung microsomes obtained from Cyp2e1-null and the wild-type mice. The knockout and wild-type mice were treated with styrene (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage fluids were monitored to evaluate the pulmonary toxicity induced by styrene. Cyp2e1-null mice displayed a susceptibility to lung toxicity of styrene similar to that of the wild-type animals; however, Cyp2f2-null mice were resistant to styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are responsible for the metabolic activation of styrene. The latter enzyme plays an important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4-vinylphenol are suggested to participate in the development of lung injury induced by styrene.

  2. Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline.

    Science.gov (United States)

    Gaspar, Maria L; Chang, Yu-Fang; Jesch, Stephen A; Aregullin, Manuel; Henry, Susan A

    2017-11-10

    In the yeast Saccharomyces cerevisiae , the Opi1p repressor controls the expression of INO1 via the Opi1p/Ino2p-Ino4p regulatory circuit. Inositol depletion favors Opi1p interaction with both Scs2p and phosphatidic acid at the endoplasmic reticulum (ER) membrane. Inositol supplementation, however, favors the translocation of Opi1p from the ER into the nucleus, where it interacts with the Ino2p-Ino4p complex, attenuating transcription of INO1 A strain devoid of Scs2p ( scs2 Δ) and a mutant, OPI1FFAT , lacking the ability to interact with Scs2p were utilized to examine the specific role(s) of the Opi1p-Scs2p interaction in the regulation of INO1 expression and overall lipid metabolism. Loss of the Opi1p-Scs2p interaction reduced INO1 expression and conferred inositol auxotrophy. Moreover, inositol depletion in strains lacking this interaction resulted in Opi1p being localized to sites of lipid droplet formation, coincident with increased synthesis of triacylglycerol. Supplementation of choline to inositol-depleted growth medium led to decreased TAG synthesis in all three strains. However, in strains lacking the Opi1p-Scs2p interaction, Opi1p remained in the nucleus, preventing expression of INO1 These data support the conclusion that a specific pool of phosphatidic acid, associated with lipid droplet formation in the perinuclear ER, is responsible for the initial rapid exit of Opi1p from the nucleus to the ER and is required for INO1 expression in the presence of choline. Moreover, the mitochondria-specific phospholipid, cardiolipin, was significantly reduced in both strains compromised for Opi1p-Scs2p interaction, indicating that this interaction is required for the transfer of phosphatidic acid from the ER to the mitochondria for cardiolipin synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling.

    Science.gov (United States)

    Moon, Eunjung; Han, Jeong Eun; Jeon, Sejin; Ryu, Jong Hoon; Choi, Ji Woong; Chun, Jerold

    2015-01-01

    Initial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R) model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

  4. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling

    Directory of Open Access Journals (Sweden)

    Eunjung Moon

    2015-01-01

    Full Text Available Initial and recurrent stroke produces central nervous system (CNS damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

  5. Contribution to the study of πN → π1π2N reactions with creation of an intermediate N*3/2(1236) isobar from 0.4 to 1.5 GeV

    International Nuclear Information System (INIS)

    Merlo, J.P.

    1976-01-01

    The one pion production reaction π + p → π + pπ 0 has been studied up to 1.5 GeV. The π 0 angular distribution measured by counter techniques has been compared to bubble chamber data. Angular distributions are interpreted in the hypothesis of formation of the intermediate N * 3/2 (1236) isobar. Angular distributions for isobar production and decay in one pion production reactions πN → π 1 N * (N * → π 2 N], are calculated in chapter II. π + p → π + pπ 0 experimental results are reported and analyzed in chapter III. An estimation of the pion-isobar partial wave amplitudes in reaction π + p → π 0 N *++ 3/2 (1236) has been tempted. Comparison with π + p phase shift analyses is made. Bubble chamber data for π - p → π - π + n channel are presented at the end of chapter III. (author) [fr

  6. arXiv Longitudinal double-spin asymmetry $A_1^{\\rm p}$ and spin-dependent structure function $g_1^{\\rm p}$ of the proton at small values of $x$ and $Q^2$

    CERN Document Server

    Aghasyan, M.; The COMPASS collaboration; Alexeev, G.D.; Amoroso, A.; Andrieux, V.; Anfimov, N.V.; Anosov, V.; Antoshkin, A.; Augsten, K.; Augustyniak, W.; Austregesilo, A.; Azevedo, C.D.R.; Badełek, B.; Balestra, F.; Ball, M.; Barth, J.; Beck, R.; Bedfer, Y.; Bernhard, J.; Bicker, K.; Bielert, E.R.; Birsa, R.; Bodlak, M.; Bordalo, P.; Bradamante, F.; Bressan, A.; Büchele, M.; Burtsev, V.E.; Chang, W.-C.; Chatterjee, C.; Chiosso, M.; Choi, I.; Chumakov, A.G.; Chung, S.-U.; Cicuttin, A.; Crespo, M.L.; Dalla Torre, S.; Dasgupta, S.S.; Dasgupta, S.; Denisov, O.Yu.; Dhara, L.; Donskov, S.V.; Doshita, N.; Dreisbach, Ch.; Dünnweber, W.; Dusaev, R.R.; Dziewiecki, M.; Efremov, A.; Eversheim, P.D.; Faessler, M.; Ferrero, A.; Finger, M.; jr.,M.Finger; Fischer, H.; Franco, C.; du Fresne von Hohenesche, N.; Friedrich, J.M.; Frolov, V.; Fuchey, E.; Gautheron, F.; Gavrichtchouk, O.P.; Gerassimov, S.; Giarra, J.; Giordano, F.; Gnesi, I.; Gorzellik, M.; Grasso, A.; Gridin, A.; Grosse Perdekamp, M.; Grube, B.; Grussenmeyer, T.; Guskov, A.; Hahne, D.; Hamar, G.; von Harrach, D.; Heinsius, F.H.; Heitz, R.; Herrmann, F.; Horikawa, N.; d'Hose, N.; Hsieh, C.-Y.; Huber, S.; Ishimoto, S.; Ivanov, A.; Iwata, T.; Jary, V.; Joosten, R.; Jörg, P.; Kabuß, E.; Kerbizi, A.; Ketzer, B.; Khaustov, G.V.; Khokhlov, Yu.A.; Kisselev, Yu.; Klein, F.; Koivuniemi, J.H.; Kolosov, V.N.; Kondo, K.; Königsmann, K.; Konorov, I.; Konstantinov, V.F.; Kotzinian, A.M.; Kouznetsov, O.M.; Kral, Z.; Krämer, M.; Kremser, P.; Krinner, F.; Kroumchtein, Z.V.; Kulinich, Y.; Kunne, F.; Kurek, K.; Kurjata, R.P.; Kuznetsov, I.I.; Kveton, A.; Lednev, A.A.; Levchenko, E.A.; Levillain, M.; Levorato, S.; Lian, Y.-S.; Lichtenstadt, J.; Longo, R.; Lyubovitskij, V.E.; Maggiora, A.; Magnon, A.; Makins, N.; Makke, N.; Mallot, G.K.; Mamon, S.A.; Marianski, B.; Martin, A.; Marzec, J.; Matoušek, J.; Matsuda, H.; Matsuda, T.; Meshcheryakov, G.V.; Meyer, M.; Meyer, W.; Mikhailov, Yu.V.; Mikhasenko, M.; Mitrofanov, E.; Mitrofanov, N.; Miyachi, Y.; Moretti, A.; Nagaytsev, A.; Nerling, F.; Neyret, D.; Nový, J.; Nowak, W.-D.; Nukazuka, G.; Nunes, A.S.; Olshevsky, A.G.; Orlov, I.; Ostrick, M.; Panzieri, D.; Parsamyan, B.; Paul, S.; Peng, J.-C.; Pereira, F.; Pešek, M.; Pešková, M.; Peshekhonov, D.V.; Pierre, N.; Platchkov, S.; Pochodzalla, J.; Polyakov, V.A.; Pretz, J.; Quaresma, M.; Quintans, C.; Ramos, S.; Regali, C.; Reicherz, G.; Riedl, C.; Rogacheva, N.S.; Ryabchikov, D.I.; Rybnikov, A.; Rychter, A.; Salac, R.; Samoylenko, V.D.; Sandacz, A.; Santos, C.; Sarkar, S.; Savin, I.A.; Sawada, T.; Sbrizzai, G.; Schiavon, P.; Schmidt, K.; Schmieden, H.; Schönning, K.; Seder, E.; Selyunin, A.; Silva, L.; Sinha, L.; Sirtl, S.; Slunecka, M.; Smolik, J.; Srnka, A.; Steffen, D.; Stolarski, M.; Subrt, O.; Sulc, M.; Suzuki, H.; Szabelski, A.; Szameitat, T.; Sznajder, P.; Tasevsky, M.; Tessaro, S.; Tessarotto, F.; Thiel, A.; Tomsa, J.; Tosello, F.; Tskhay, V.; Uhl, S.; Vasilishin, B.I.; Vauth, A.; Veloso, J.; Vidon, A.; Virius, M.; Wallner, S.; Weisrock, T.; Wilfert, M.; ter Wolbeek, J.; Zaremba, K.; Zavada, P.; Zavertyaev, M.; Zemlyanichkina, E.; Ziembicki, M.

    2018-06-10

    We present a precise measurement of the proton longitudinal double-spin asymmetry A1p and the proton spin-dependent structure function g1p at photon virtualities 0.006(GeV/c)22<1(GeV/c)2 in the Bjorken x range of 4×10−52 . The results are based on data collected by the COMPASS Collaboration at CERN using muon beam energies of 160GeV and 200GeV . The statistical precision is more than tenfold better than that of the previous measurement in this region. In the whole range of x , the measured values of A1p and g1p are found to be positive. It is for the first time that spin effects are found at such low values of x .

  7. The pMSSM10 after LHC Run 1

    CERN Document Server

    de Vries, K.J.; Buchmueller, O.; Cavanaugh, R.; Citron, M.; De Roeck, A.; Dolan, M.J.; Ellis, J.R.; Flächer, H.; Heinemeyer, S.; Isidori, G.; Malik, S.; Marrouche, J.; Martinez Santos, D.; Olive, K.A.; Sakurai, K.; Weiglein, G.

    2015-01-01

    We present a frequentist analysis of the parameter space of the pMSSM10, in which the following 10 soft SUSY-breaking parameters are specified independently at the mean scalar top mass scale Msusy = Sqrt[M_stop1 M_stop2]: the gaugino masses M_{1,2,3}, the 1st-and 2nd-generation squark masses M_squ1 = M_squ2, the third-generation squark mass M_squ3, a common slepton mass M_slep and a common trilinear mixing parameter A, the Higgs mixing parameter mu, the pseudoscalar Higgs mass M_A and tan beta. We use the MultiNest sampling algorithm with 1.2 x 10^9 points to sample the pMSSM10 parameter space. A dedicated study shows that the sensitivities to strongly-interacting SUSY masses of ATLAS and CMS searches for jets, leptons + MET signals depend only weakly on many of the other pMSSM10 parameters. With the aid of the Atom and Scorpion codes, we also implement the LHC searches for EW-interacting sparticles and light stops, so as to confront the pMSSM10 parameter space with all relevant SUSY searches. In addition, ou...

  8. Hot Hole Collection and Photoelectrochemical CO2 Reduction with Plasmonic Au/p-GaN Photocathodes.

    Science.gov (United States)

    DuChene, Joseph S; Tagliabue, Giulia; Welch, Alex J; Cheng, Wen-Hui; Atwater, Harry A

    2018-04-11

    Harvesting nonequilibrium hot carriers from plasmonic-metal nanostructures offers unique opportunities for driving photochemical reactions at the nanoscale. Despite numerous examples of hot electron-driven processes, the realization of plasmonic systems capable of harvesting hot holes from metal nanostructures has eluded the nascent field of plasmonic photocatalysis. Here, we fabricate gold/p-type gallium nitride (Au/p-GaN) Schottky junctions tailored for photoelectrochemical studies of plasmon-induced hot-hole capture and conversion. Despite the presence of an interfacial Schottky barrier to hot-hole injection of more than 1 eV across the Au/p-GaN heterojunction, plasmonic Au/p-GaN photocathodes exhibit photoelectrochemical properties consistent with the injection of hot holes from Au nanoparticles into p-GaN upon plasmon excitation. The photocurrent action spectrum of the plasmonic photocathodes faithfully follows the surface plasmon resonance absorption spectrum of the Au nanoparticles and open-circuit voltage studies demonstrate a sustained photovoltage during plasmon excitation. Comparison with Ohmic Au/p-NiO heterojunctions confirms that the vast majority of hot holes generated via interband transitions in Au are sufficiently hot to inject above the 1.1 eV interfacial Schottky barrier at the Au/p-GaN heterojunction. We further investigated plasmon-driven photoelectrochemical CO 2 reduction with the Au/p-GaN photocathodes and observed improved selectivity for CO production over H 2 evolution in aqueous electrolytes. Taken together, our results offer experimental validation of photoexcited hot holes more than 1 eV below the Au Fermi level and demonstrate a photoelectrochemical platform for harvesting hot carriers to drive solar-to-fuel energy conversion.

  9. Resonant photoemission at the Ga 3p photothreshold in In xGa1-xN

    International Nuclear Information System (INIS)

    Colakerol, L.; Glans, P.-A.; Plucinski, L.; Zhang, Y.; Smith, K.E.; Zakharov, A.A.; Nyholm, R.; Cabalu, J.; Moustakas, T.D.

    2006-01-01

    Resonance effects at the Ga 3p photoabsorption threshold have been observed in photoemission spectra recorded from thin film In x Ga 1-x N alloys. The spectra display satellites of the main Ga 3d emission line, and the intensity of these satellites resonate at this threshold. The satellites are associated with a 3d 8 state, and have previously been observed for the semiconductors GaN, GaAs, and GaP. The resonance behavior has been studied for a variety of In x Ga 1-x N thin films with differing In concentration and band gap. The photon energy where the maximum resonance is observed varies with band gap within the alloy system, but does not follow the trend observed for binary Ga semiconducting compounds. We also observe that the threshold resonant energy increases slightly as the In content increases

  10. TUG1 promotes osteosarcoma tumorigenesis by upregulating EZH2 expression via miR-144-3p.

    Science.gov (United States)

    Cao, Jiaqing; Han, Xinyou; Qi, Xin; Jin, Xiangyun; Li, Xiaolin

    2017-10-01

    lncRNA-TUG1 (Taurine upregulated 1) is up-regulated and highly correlated with poor prognosis and disease status in osteosarcoma. TUG1 knockdown inhibits osteosarcoma cell proliferation, migration and invasion, and promotes apoptosis. However, its mechanism of action has not been well addressed. Growing evidence documented that lncRNA works as competing endogenous (ce)RNAs to modulate the expression and biological functions of miRNA. As a putative combining target of TUG1, miR-144-3p has been associated with the progress of osteosarcoma. To verify whether TUG1 functions through regulating miR-144-3p, the expression levels of TUG1 and miR-144-3p in osteosarcoma tissues and cell lines were determined. TUG1 was upregulated in osteosarcoma tissues and cell lines, and negatively correlated with miR-144-3p. TUG1 knockdown induced miR-144-3p expression in MG63 and U2OS cell lines. Results from dual luciferase reporter assay, RNA-binding protein immuno-precipitation (RIP) and applied biotin-avidin pull-down system confirmed TUG1 regulated miR-144-3p expression through direct binding. EZH2, a verified target of miR-144-3p was upregulated in osteosarcoma tissues and negatively correlated with miR-144-3p. EZH2 was negatively regulated by miR-144-3p and positively regulated by TUG1. Gain-and loss-of-function experiments were performed to analyze the role of TUG1, miR-144-3p and EZH2 in the migration and EMT of osteosarcoma cells. EZH2 over-expression partly abolished TUG1 knockdown or miR-144-3p overexpression induced inhibition of migration and EMT in osteosarcoma cells. In addition, TUG1 knockdown represses the activation of Wnt/β-catenin pathway, which was reversed by EZH2 over-expression. The activator of Wnt/β-catenin pathway LiCl could partially block the TUG1-knockdown induced osteosarcoma cell migration and EMT inhibition. In conclusion, our results showed that TUG1 plays an important role in osteosarcoma development through miRNA-144-3p/EZH2/Wnt/β-catenin pathway.

  11. Observation of the Decays Λ_{b}^{0}→χ_{c1}pK^{-} and Λ_{b}^{0}→χ_{c2}pK^{-}.

    Science.gov (United States)

    Aaij, R; Adeva, B; Adinolfi, M; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Andreassi, G; Andreotti, M; Andrews, J E; Appleby, R B; Archilli, F; d'Argent, P; Arnau Romeu, J; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Babuschkin, I; Bachmann, S; Back, J J; Badalov, A; Baesso, C; Baker, S; Balagura, V; Baldini, W; Baranov, A; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Baryshnikov, F; Baszczyk, M; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Beiter, A; Bel, L J; Bellee, V; Belloli, N; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Beranek, S; Berezhnoy, A; Bernet, R; Bertolin, A; Betancourt, C; Betti, F; Bettler, M-O; van Beuzekom, M; Bezshyiko, Ia; Bifani, S; Billoir, P; Birnkraut, A; Bitadze, A; Bizzeti, A; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Boettcher, T; Bondar, A; 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Vagnoni, V; Valassi, A; Valat, S; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; van Veghel, M; Velthuis, J J; Veltri, M; Veneziano, G; Venkateswaran, A; Verlage, T A; Vernet, M; Vesterinen, M; Viana Barbosa, J V; Viaud, B; Vieira, D; Vieites Diaz, M; Viemann, H; Vilasis-Cardona, X; Vitti, M; Volkov, V; Vollhardt, A; Voneki, B; Vorobyev, A; Vorobyev, V; Voß, C; de Vries, J A; Vázquez Sierra, C; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wang, J; Ward, D R; Wark, H M; Watson, N K; Websdale, D; Weiden, A; Whitehead, M; Wicht, J; Wilkinson, G; Wilkinson, M; Williams, M; Williams, M P; Williams, M; Williams, T; Wilson, F F; Wimberley, J; Winn, M A; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wraight, K; Wyllie, K; Xie, Y; Xu, Z; Yang, Z; Yang, Z; Yao, Y; Yin, H; Yu, J; Yuan, X; Yushchenko, O; Zarebski, K A; Zavertyaev, M; Zhang, L; Zhang, Y; Zhelezov, A; Zheng, Y; Zhu, X; Zhukov, V; Zonneveld, J B; Zucchelli, S

    2017-08-11

    The first observation of the decays Λ_{b}^{0}→χ_{c1}pK^{-} and Λ_{b}^{0}→χ_{c2}pK^{-} is reported using a data sample corresponding to an integrated luminosity of 3.0  fb^{-1}, collected by the LHCb experiment in pp collisions at center-of-mass energies of 7 and 8 TeV. The following ratios of branching fractions are measured: B(Λ_{b}^{0}→χ_{c1}pK^{-})/B(Λ_{b}^{0}→J/ψpK^{-})=0.242±0.014±0.013±0.009,B(Λ_{b}^{0}→χ_{c2}pK^{-})/B(Λ_{b}^{0}→J/ψpK^{-})=0.248±0.020±0.014±0.009,B(Λ_{b}^{0}→χ_{c2}pK^{-})/B(Λ_{b}^{0}→χ_{c1}pK^{-})=1.02±0.10±0.02±0.05,where the first uncertainty is statistical, the second systematic, and the third due to the uncertainty on the branching fractions of the χ_{c1}→J/ψγ and χ_{c2}→J/ψγ decays. Using both decay modes, the mass of the Λ_{b}^{0} baryon is also measured to be m_{Λ_{b}^{0}}=5619.44±0.28±0.26  MeV/c^{2}, where the first and second uncertainties are statistical and systematic, respectively.

  12. Measurements of e p →e'π+n at 1.6 2.0 GeV and extraction of nucleon resonance electrocouplings at CLAS

    Science.gov (United States)

    Park, K.; Aznauryan, I. G.; Burkert, V. D.; Adhikari, K. P.; Amaryan, M. J.; Pereira, S. Anefalos; Avakian, H.; Battaglieri, M.; Badui, R.; Bedlinskiy, I.; Biselli, A. S.; Bono, J.; Briscoe, W. J.; Brooks, W. K.; Carman, D. S.; Celentano, A.; Chandavar, S.; Charles, G.; Colaneri, L.; Cole, P. L.; Contalbrigo, M.; Cortes, O.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Doughty, D.; Dupre, R.; Egiyan, H.; Alaoui, A. El; Elouadrhiri, L.; Fassi, L. El; Eugenio, P.; Fedotov, G.; Fegan, S.; Fersch, R.; Filippi, A.; Fleming, J. A.; Garillon, B.; Garçon, M.; Gevorgyan, N.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Joo, H. S.; Goetz, J. T.; Golovatch, E.; Gothe, R. W.; Griffioen, K. A.; Guegan, B.; Guidal, M.; Guo, L.; Hakobyan, H.; Hanretty, C.; Hattawy, M.; Hicks, K.; Holtrop, M.; Hughes, S. M.; Hyde, C. E.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jenkins, D.; Jiang, H.; Jo, H. S.; Joo, K.; Joosten, S.; Keller, D.; Khandaker, M.; Kim, A.; Kim, W.; Klein, A.; Klein, F. J.; Kubarovsky, V.; Kuhn, S. E.; Kuleshov, S. V.; Lenisa, P.; Livingston, K.; Lu, H. Y.; MacGregor, I. J. D.; Markov, N.; Martinez, D.; McKinnon, B.; Mokeev, V.; Montgomery, R. A.; Moutarde, H.; Camacho, C. Munoz; Nadel-Turonski, P.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Ostrovidov, A. I.; Paolone, M.; Pasyuk, E.; Peng, P.; Phelps, W.; Phillips, J. J.; Pisano, S.; Pogorelko, O.; Price, J. W.; Procureur, S.; Prok, Y.; Protopopescu, D.; Puckett, A. J. R.; Raue, B. A.; Ripani, M.; Rizzo, A.; Rosner, G.; Rossi, P.; Roy, P.; Sabatié, F.; Salgado, C.; Schott, D.; Schumacher, R. A.; Seder, E.; Sharabian, Y. G.; Simonyan, A.; Skorodumina, Iu.; Smith, E. S.; Smith, G. D.; Sparveris, N.; Stoler, P.; Strakovsky, I. I.; Strauch, S.; Sytnik, V.; Taiuti, M.; Tang, W.; Taylor, C. E.; Tian, Ye; Trivedi, A.; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Wei, X.; Weinstein, L. B.; Wood, M. H.; Zachariou, N.; Zana, L.; Zhang, J.; Zhao, Z. W.; Zonta, I.; CLAS Collaboration

    2015-04-01

    Differential cross sections of the exclusive process e p →e'π+n were measured with good precision in the range of the photon virtuality Q2=1.8 -4.5 GeV2 and the invariant mass range of the π+n final state W =1.6 -2.0 GeV using the Continuous Electron Beam Accelerator Facility Large Acceptance Spectrometer. Data were collected with nearly complete coverage in the azimuthal and polar angles of the n π+ center-of-mass system. More than 37 000 cross-section points were measured. The contributions of the isospin I =1/2 resonances N (1675 ) 5/2-,N (1680 ) 5/2+ , and N (1710 ) 1/2+ were extracted at different values of Q2 using a single-channel, energy-dependent resonance amplitude analysis. Two different approaches, the unitary isobar model and the fixed-t dispersion relations, were employed in the analysis. We observe significant strength of the N (1675 ) 5/2- in the A1 /2 amplitude, which is in strong disagreement with quark models that predict both transverse amplitudes to be strongly suppressed. For the N (1680 ) 5/2+ we observe a slow changeover from the dominance of the A3 /2 amplitude at the real photon point (Q2=0 ) to a Q2 where A1 /2 begins to dominate. The scalar amplitude S1 /2 drops rapidly with Q2 consistent with quark model prediction. For the N (1710 ) 1/2+ resonance our analysis shows significant strength for the A1 /2 amplitude at Q2<2.5 GeV2.

  13. SUMO regulates p21Cip1 intracellular distribution and with p21Cip1 facilitates multiprotein complex formation in the nucleolus upon DNA damage.

    Science.gov (United States)

    Brun, Sonia; Abella, Neus; Berciano, Maria T; Tapia, Olga; Jaumot, Montserrat; Freire, Raimundo; Lafarga, Miguel; Agell, Neus

    2017-01-01

    We previously showed that p21Cip1 transits through the nucleolus on its way from the nucleus to the cytoplasm and that DNA damage inhibits this transit and induces the formation of p21Cip1-containing intranucleolar bodies (INoBs). Here, we demonstrate that these INoBs also contain SUMO-1 and UBC9, the E2 SUMO-conjugating enzyme. Furthermore, whereas wild type SUMO-1 localized in INoBs, a SUMO-1 mutant, which is unable to conjugate with proteins, does not, suggesting the presence of SUMOylated proteins at INoBs. Moreover, depletion of the SUMO-conjugating enzyme UBC9 or the sumo hydrolase SENP2 changed p21Cip1 intracellular distribution. In addition to SUMO-1 and p21Cip1, cell cycle regulators and DNA damage checkpoint proteins, including Cdk2, Cyclin E, PCNA, p53 and Mdm2, and PML were also detected in INoBs. Importantly, depletion of UBC9 or p21Cip1 impacted INoB biogenesis and the nucleolar accumulation of the cell cycle regulators and DNA damage checkpoint proteins following DNA damage. The impact of p21Cip1 and SUMO-1 on the accumulation of proteins in INoBs extends also to CRM1, a nuclear exportin that is also important for protein translocation from the cytoplasm to the nucleolus. Thus, SUMO and p21Cip1 regulate the transit of proteins through the nucleolus, and that disruption of nucleolar export by DNA damage induces SUMO and p21Cip1 to act as hub proteins to form a multiprotein complex in the nucleolus.

  14. Evidence for Dual Binding Sites for 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) in Insect Sodium Channels*

    Science.gov (United States)

    Du, Yuzhe; Nomura, Yoshiko; Zhorov, Boris S.; Dong, Ke

    2016-01-01

    1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), the first organochlorine insecticide, and pyrethroid insecticides are sodium channel agonists. Although the use of DDT is banned in most of the world due to its detrimental impact on the ecosystem, indoor residual spraying of DDT is still recommended for malaria control in Africa. Development of resistance to DDT and pyrethroids is a serious global obstacle for managing disease vectors. Mapping DDT binding sites is necessary for understanding mechanisms of resistance and modulation of sodium channels by structurally different ligands. The pioneering model of the housefly sodium channel visualized the first receptor for pyrethroids, PyR1, in the II/III domain interface and suggested that DDT binds within PyR1. Previously, we proposed the second pyrethroid receptor, PyR2, at the I/II domain interface. However, whether DDT binds to both pyrethroid receptor sites remains unknown. Here, using computational docking of DDT into the Kv1.2-based mosquito sodium channel model, we predict that two DDT molecules can bind simultaneously within PyR1 and PyR2. The bulky trichloromethyl group of each DDT molecule fits snugly between four helices in the bent domain interface, whereas two p-chlorophenyl rings extend into two wings of the interface. Model-driven mutagenesis and electrophysiological analysis confirmed these propositions and revealed 10 previously unknown DDT-sensing residues within PyR1 and PyR2. Our study proposes a dual DDT-receptor model and provides a structural background for rational development of new insecticides. PMID:26637352

  15. Analysis of cellular responses to aflatoxin B1 in yeast expressing human cytochrome P450 1A2 using cDNA microarrays

    International Nuclear Information System (INIS)

    Guo Yingying; Breeden, Linda L.; Fan, Wenhong; Zhao Lueping; Eaton, David L.; Zarbl, Helmut

    2006-01-01

    Aflatoxin B1 (AFB 1 ) is a potent human hepatotoxin and hepatocarcinogen produced by the mold Aspergillus flavus. In human, AFB 1 is bioactivated by cytochrome P450 (CYP450) enzymes, primarily CYP1A2, to the genotoxic epoxide that forms N 7 -guanine DNA adducts. To characterize the transcriptional responses to genotoxic insults from AFB 1 , a strain of Saccharomyces cerevisiae engineered to express human CYP1A2 was exposed to doses of AFB 1 that resulted in minimal lethality, but substantial genotoxicity. Flow cytometric analysis demonstrated a dose and time dependent S phase delay under the same treatment conditions, indicating a checkpoint response to DNA damage. Replicate cDNA microarray analyses of AFB 1 treated cells showed that about 200 genes were significantly affected by the exposure. The genes activated by AFB 1 -treatment included RAD51, DUN1 and other members of the DNA damage response signature reported in a previous study with methylmethane sulfonate and ionizing radiation [A.P. Gasch, M. Huang, S. Metzner, D. Botstein, S.J. Elledge, P.O. Brown, Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p, Mol. Biol. Cell 12 (2001) 2987-3003]. However, unlike previous studies using highly cytotoxic doses, environmental stress response genes [A.P. Gasch, P.T. Spellman, C.M. Kao, O. Carmel-Harel, M.B. Eisen, G. Storz, D. Botstein, P.O. Brown, Genomic expression programs in the response of yeast cells to environmental changes, Mol. Biol. Cell 11 (2000) 4241-4257] were largely unaffected by our dosing regimen. About half of the transcripts affected are also known to be cell cycle regulated. The most strongly repressed transcripts were those encoding the histone genes and a group of genes that are cell cycle regulated and peak in M phase and early G1. These include most of the known daughter-specific genes. The rapid and coordinated repression of histones and M/G1-specific transcripts cannot be explained by

  16. Pathophysiological Consequences of a Break in S1P1-Dependent Homeostasis of Vascular Permeability Revealed by S1P1 Competitive Antagonism.

    Science.gov (United States)

    Bigaud, Marc; Dincer, Zuhal; Bollbuck, Birgit; Dawson, Janet; Beckmann, Nicolau; Beerli, Christian; Fishli-Cavelti, Gina; Nahler, Michaela; Angst, Daniela; Janser, Philipp; Otto, Heike; Rosner, Elisabeth; Hersperger, Rene; Bruns, Christian; Quancard, Jean

    2016-01-01

    Homeostasis of vascular barriers depends upon sphingosine 1-phosphate (S1P) signaling via the S1P1 receptor. Accordingly, S1P1 competitive antagonism is known to reduce vascular barrier integrity with still unclear pathophysiological consequences. This was explored in the present study using NIBR-0213, a potent and selective S1P1 competitive antagonist. NIBR-0213 was tolerated at the efficacious oral dose of 30 mg/kg BID in the rat adjuvant-induced arthritis (AiA) model, with no sign of labored breathing. However, it induced dose-dependent acute vascular pulmonary leakage and pleural effusion that fully resolved within 3-4 days, as evidenced by MRI monitoring. At the supra-maximal oral dose of 300 mg/kg QD, NIBR-0213 impaired lung function (with increased breathing rate and reduced tidal volume) within the first 24 hrs. Two weeks of NIBR-0213 oral dosing at 30, 100 and 300 mg/kg QD induced moderate pulmonary changes, characterized by alveolar wall thickening, macrophage accumulation, fibrosis, micro-hemorrhage, edema and necrosis. In addition to this picture of chronic inflammation, perivascular edema and myofiber degeneration observed in the heart were also indicative of vascular leakage and its consequences. Overall, these observations suggest that, in the rat, the lung is the main target organ for the S1P1 competitive antagonism-induced acute vascular leakage, which appears first as transient and asymptomatic but could lead, upon chronic dosing, to lung remodeling with functional impairments. Hence, this not only raises the question of organ specificity in the homeostasis of vascular barriers, but also provides insight into the pre-clinical evaluation of a potential safety window for S1P1 competitive antagonists as drug candidates.

  17. The need to accessorize: Molecular roles of HTLV-1 p30 and HTLV-2 p28 accessory proteins in the viral life cycle

    Directory of Open Access Journals (Sweden)

    Rajaneesh eAnupam

    2013-09-01

    Full Text Available Extensive studies of HTLV-1 and HTLV-2 over the last three decades have provided detailed knowledge on viral transformation, host-viral interactions and pathogenesis. HTLV-1 is the etiological agent of adult T cell leukemia (ATL and multiple neurodegenerative and inflammatory diseases while HTLV-2 disease association remains elusive, with few infected individuals displaying neurodegenerative diseases similar to HTLV-1. The HTLV group of oncoretroviruses has a genome that encodes structural and enzymatic proteins Gag, Pro and Env, regulatory proteins Tax and Rex, and several accessory proteins from the pX region. Of these proteins, HTLV-1 p30 and HTLV-2 p28 are encoded by the open reading frame (ORF II of the pX region. Like most other accessory proteins, p30 and p28 are dispensable for in vitro viral replication and transformation but are required for efficient viral replication and persistence in vivo. Both p30 and p28 regulate viral gene expression at the post-transcriptional level whereas p30 can also function at the transcriptional level. Recently, several reports have implicated p30 and p28 in multiple cellular processes, which provide novel insight into HTLV spread and survival and ultimately pathogenesis. In this review we summarize and compare what is known about p30 and p28, highlighting their roles in viral replication and viral pathogenesis.

  18. Non-basic amino acids in the ROMK1 channels via an appropriate distance modulate PIP2 regulated pHi-gating.

    Science.gov (United States)

    Lee, Chien-Hsing; Huang, Po-Tsang; Liou, Horng-Huei; Lin, Mei-Ying; Lou, Kuo-Long; Chen, Chung-Yi

    2016-04-22

    The ROMK1 (Kir1.1) channel activity is predominantly regulated by intracellular pH (pHi) and phosphatidylinositol 4,5-bisphosphate (PIP2). Although several residues were reported to be involved in the regulation of pHi associated with PIP2 interaction, the detailed molecular mechanism remains unclear. We perform experiments in ROMK1 pHi-gating with electrophysiology combined with mutational and structural analysis. In the present study, non basic residues of C-terminal region (S219, N215, I192, L216 and L220) in ROMK1 channels have been found to mediate channel-PIP2 interaction and pHi gating. Further, our structural results show these residues with an appropriate distance to interact with membrane PIP2. Meanwhile, a cluster of basic residues (R188, R217 and K218), which was previously discovered regarding the interaction with PIP2, exists in this appropriate distance to discriminate the regulation of channel-PIP2 interaction and pHi-gating. This appropriate distance can be observed with high conservation in the Kir channel family. Our results provide insight that an appropriate distance cooperates with the electrostatics interaction of channel-PIP2 to regulate pHi-gating. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Spectroscopic constants and potential energy curve of the iodine weakly bound 1u state correlating with the I(2P1/2) + I(2P1/2) dissociation limit

    International Nuclear Information System (INIS)

    Akopyan, M E; Baturo, V V; Lukashov, S S; Poretsky, S A; Pravilov, A M

    2015-01-01

    The stepwise three-step three-color laser population of the I 21 g , ν β , J β ) rovibronic states via the B0 u + , ν B , J B rovibronic states and rovibronic levels of the 1 u (bb) and 0 g + (bb) states mixed by hyperfine interaction is used for determination of rovibronic level energies of the weakly bound I 2 (1 u (bb)) state. Dunham coefficients of the state, Y i0 (i = 0–3), Y i1 (i = 0–2), Y 02 and Y 12 for the v 1 u  = 1–5, 8, 10, 15 and J 1 u  ≈ 9–87 ranges, the dissociation energy of the state, D e , and equilibrium I–I distance, R e , as well as the potential energy curve are determined. There are aperiodicities in the excitation spectrum corresponding to the β, ν β  = 23, J β  ← 1 u (bb), ν 1u  = 4, 5, J 1u progressions in the I 2  + Rg = He, Ar mixture, namely, a great number of lines which do not coincide with the R or P line progressions. Their positions conflict with the ΔJ-even selection rule. Furthermore, they do not correspond to the ΔJ-odd progression. (paper)

  20. Essential role for SphK1/S1P signaling to regulate hypoxia-inducible factor 2α expression and activity in cancer.

    Science.gov (United States)

    Bouquerel, P; Gstalder, C; Müller, D; Laurent, J; Brizuela, L; Sabbadini, R A; Malavaud, B; Pyronnet, S; Martineau, Y; Ader, I; Cuvillier, O

    2016-03-14

    The sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) signaling pathway has been reported to modulate the expression of the canonical transcription factor hypoxia-inducible HIF-1α in multiple cell lineages. HIF-2α is also frequently overexpressed in solid tumors but its role has been mostly studied in clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, where HIF-2α has been established as a driver of a more aggressive disease. In this study, the role of SphK1/S1P signaling with regard to HIF-2α was investigated in various cancer cell models including ccRCC cells. Under hypoxic conditions or in ccRCC lacking a functional von Hippel-Lindau (VHL) gene and expressing high levels of HIF-2α, SphK1 activity controls HIF-2α expression and transcriptional activity through a phospholipase D (PLD)-driven mechanism. SphK1 silencing promotes a VHL-independent HIF-2α loss of expression and activity and reduces cell proliferation in ccRCC. Importantly, downregulation of SphK1 is associated with impaired Akt and mTOR signaling in ccRCC. Taking advantage of a monoclonal antibody neutralizing extracellular S1P, we show that inhibition of S1P extracellular signaling blocks HIF-2α accumulation in ccRCC cell lines, an effect mimicked when the S1P transporter Spns2 or the S1P receptor 1 (S1P1) is silenced. Here, we report the first evidence that the SphK1/S1P signaling pathway regulates the transcription factor hypoxia-inducible HIF-2α in diverse cancer cell lineages notably ccRCC, where HIF-2α has been established as a driver of a more aggressive disease. These findings demonstrate that SphK1/S1P signaling may act as a canonical regulator of HIF-2α expression in ccRCC, giving support to its inhibition as a therapeutic strategy that could contribute to reduce HIF-2 activity in ccRCC.

  1. The role of sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) in the trafficking of normal and malignant cells

    Science.gov (United States)

    Ratajczak, Mariusz Z.; Suszynska, Malwina; Borkowska, Sylwia; Ratajczak, Janina; Schneider, Gabriela

    2014-01-01

    Introduction A common feature of many types of cells is their responsiveness to chemotactic gradients of factors for which they express the corresponding receptors. The most studied chemoattractants so far are peptide-based growth factors and a family of cytokines endowed with strong chemotactic properties, called chemokines. However, additional evidence has accumulated that, in addition to these peptide-based chemoattractants, an important role in cell migration is played by bioactive lipids. Areas covered Solid evidence has accumulated that two bioactive phosphorylated sphingolipids that are derivatives of sphingolipid metabolism, namely sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), are potent chemoattractants for a variety of cells. In this review, we will discuss the effect of these two phosphorylated sphingolipids on the trafficking of normal and malignant cells, and, in particular, we will focus on their role in trafficking of normal hematopoietic stem/progenitor cells. Unlike other mediators, S1P under steady state conditions maintain a steep gradient between interstitial fluid and peripheral blood and lymph across the endothelial barrier, which is important in the egress of cells from bone marrow. Both S1P and C1P may be upregulated in damaged tissues, which may result in reversal of this gradient. Expert opinion S1P and C1P are important regulators of the trafficking of normal and malignant cells, and modification of their biological effects will have important applications in optimizing stem cell mobilization and homing, tissue organ/regeneration, and preventing cancer metastasis. PMID:24188167

  2. Mechanistic Studies of the Yeast Polyamine Oxidase Fms1: Kinetic Mechanism, Substrate Specificity, and pH Dependence†

    Science.gov (United States)

    Adachi, Mariya S.; Torres, Jason M.; Fitzpatrick, Paul F.

    2010-01-01

    The flavoprotein oxidase Fms1 from Saccharomyces cerevisiae catalyzes the oxidation of spermine and N1-acetylspermine to yield spermidine and 3-aminopropanal or N-acetyl-3-aminopropanal. The kinetic mechanism of the enzyme has been determined with both substrates. The initial velocity patterns are ping-pong, consistent with reduction being kinetically irreversible. Reduction of Fms1 by either substrate is biphasic. The rate constant for the rapid phase varies with the substrate concentration, with limiting rates for reduction of the enzyme of 126 and 1410 s−1 and apparent Kd values of 24.3 and 484 μM for spermine and N1-acetylspermine, respectively. The rapid phase is followed by a concentration-independent phase that is slower than turnover. The reaction of the reduced enzyme with oxygen is monophasic, with a rate constant of 402 mM−1 s−1 with spermine at 25 °C, and 204 mM−1 s−1 with N1-acetylspermine at 4 °C, pH 9.0. This step is followed by rate-limiting product dissociation. The kcat/Kamine-pH profiles are bell-shaped, with an average pKa value of 9.3 with spermine and pKa values of 8.3 and 9.6 with N1-acetylspermine. Both profiles are consistent with the active forms of substrates having two charged nitrogens. The pH profiles for the rate constant for flavin reduction show pKa values of 8.3 and 7.2 for spermine and N1-acetylspermine, respectively, for groups that must be unprotonated; these pKa values are assigned to the substrate N4. The kcat/KO2-pH profiles show pKa values of 7.5 for spermine and 6.8 for N1-acetylspermine. With both substrates, the kcat value decreases when a single residue is protonated. PMID:21067138

  3. Endoscopic extraperitoneal radical prostatectomy after radical resection of pT1-pT2 rectal cancer: a report of thirty cases.

    Science.gov (United States)

    Liu, Zhuo; Li, Dechuan; Chen, Yinbo

    2017-01-01

    Endoscopic extraperitoneal radical prostatectomy (EERPE) has gained popularity for the treatment of localized prostate cancer. However, prior complex lower abdominal or pelvic surgery can complicate subsequent EERPE. To date, there have been few reports on patients who underwent EERPE after radical resection of pT1-pT2 rectal cancer. To present our experience with EERPE in patients after radical resection of pT1-pT2 rectal carcinoma and introduce a simple and effective way to create an extraperitoneal working space. Thirty patients after radical resection of pT1-pT2 rectal carcinoma were treated with EERPE for biopsy-proven localized prostate cancer. Operation time, estimated blood loss, conversion to open surgery rate, transfusion rate and transurethral catheter time were recorded. Meanwhile, functional outcome (continence and potency) and oncological outcome were reviewed. The average operative time was 168 min. Mean blood loss was 195 ml. There was no need for conversion to open surgery or transfusion. The catheter was removed on postoperative day (POD) 7.8. After a mean follow-up time of 53.1 months, 3 patients had a prostate-specific antigen level relapse over 0.1 ng/ml. At the follow-up time, 26 patients were completely continent, and 4 needed 1-2 pads/day. Of the 6 patients who underwent neurovascular bundle preservation, none have experienced return of erections at the last follow-up time. Endoscopic extraperitoneal radical prostatectomy after radical resection of rectal carcinoma appears promising, with feasibility in experienced hands. The operative data, postoperative urinary incontinence and oncological outcomes appear encouraging, but the rate of erectile dysfunction seems to be disappointing.

  4. Analysis of the prognostic factors for low rectal cancer with the pT1-2NxM0 stage after abdominoperineal resection.

    Science.gov (United States)

    Zhang, Xing-mao; Ma, Chao; Sun, Da-yong; Wang, Zheng; Zhou, Zhi-xiang

    2015-01-01

    This study was designed to explore the factors influencing local recurrence and survival for low rectal cancer with pT1-2NxM0 stage after an abdominoperineal resection (APR). Data of 429 patients confirmed to have pT1-2NxM0 after APR were reviewed. The recurrence rate in patients with intraoperative perforation, less than 12 lymph nodes (LNs) harvested, T2 staging, and positive circumferential resection margin (CRM) was 25.1, 19.9, 9.5, and 26.1% compared with 6.9, 7.0, 0, and 5.8% in patients with no perforation, 12 or more LNs harvested, T1, and negative CRM. The 5-year survival rate in patients with age of at least 70, perforation, less than 12 LNs harvested, T2, and positive CRM was 71.1, 60.8, 58.8, 69.9, and 46.0%, but 73.4, 73.5, 73.8, 89.4, and 75.0% in patients with age less than 70, no perforation, 12 or more LNs harvested, T1, and negative CRM. Meanwhile, patients with N0, N1, and N2 had a survival rate of 90.7, 69.9, and 63.9%. Multivariate analysis showed that perforation (PCRM status (P=0.002) were associated with local recurrence, whereas age of the patients (P=0.023), N staging (PCRM status (P=0.004) were associated with survival. APR was affected by patients' age, operation performer, perforation, number of LNs harvested, T staging, N staging, differentiation, and CRM status. Perforation, number of LNs harvested, T staging, differentiation, and CRM status were independent factors for recurrence; meanwhile, age of the patients, N staging, differentiation, and CRM status were independent factors influencing survival.

  5. Measurements of the ground-state ionization energy and wavelengths for the 1snp {sup 1}P{sub 1}{sup *}-1s{sup 2} {sup 1}S{sub 0} (n=4-9) lines of Mg XI and F VIII

    Energy Technology Data Exchange (ETDEWEB)

    Pal' chikov, V.G. [Multicharged Ions Spectra Data Centre of VNIIFTRI, Mendeleevo (Russian Federation)). E-mail: vitpal@mail.ru; Ya Faenov, A.; Yu Skobelev, I. [Multicharged Ions Spectra Data Centre of VNIIFTRI, Mendeleevo (RU)] [and others

    2002-06-28

    The wavelengths of the 1snp {sup 1}P{sub 1}{sup 0}-1s{sup 2} {sup 1}S{sub 0} transitions in the He-like Mg XI (n = 4-9) and F VIII (n=4-8) have been measured in laser-produced plasmas. The accuracy of the present measurements (0.4-1.6 mA) is a large improvement over previous results. The Rydberg series is used to determine the ground-state ionization energy of F VIII and Mg XI: E{sub i}on (F VIII) 953.96{+-}0.11 eV, E{sub i}on (Mg XI)=1761.88{+-}0.15 eV. These experimental results are compared with theoretical data calculated by the 1/Z-expansion method and the HFR and MCDF approaches. Fairly good agreement between theory and experiment is observed with a precision up to 5x10{sup -5}. Radiative corrections to the 1s{sup 2} {sup 1}S{sub 0} state are analysed and compared with experiments. It is found that QED corrections to the ground-state ionization energy are significant at the present level of experimental accuracy. (author)

  6. PENERAPAN METODE RETAD UNTUK MENGURANGI WAKTU SET UP PADA MESIN MILLING P1 DAN P2 DEPARTEMEN MACHINING PT. KUBOTA INDONESIA

    Directory of Open Access Journals (Sweden)

    Sriyanto Sriyanto

    2012-02-01

    Full Text Available Pengurangan waktu produksi dalam suatu proses produksi dapat dilakukan dengan meminimalkan waktu setup pada proses produksi tersebut. Untuk mengurangi waktu setup diperlukan suatu cara untuk membantu operator dalam melaksanakan proses milling sehingga dapat meminimalkan waktu setup serta dapat menghilangkan elemen kerja yang tidak produktif tersebut. Metode RETAD (Rapid Exchange of Tooling and Dies merupakan pengembangan dari metode SMED (Single Minuite Exchange of Dies yang bertujuan mengurangi waktu setup, menghapus scrap dan rework. Dari hasil pengolahan data dan analisis untuk proses milling pada mesin Milling Vertikal P1, waktu elemen kerja membersihkan jig dari geram dapat dikurangi dari 5.53 detik sebelum perbaikan menjadi 1.54 detik setelah perbaikan dan untuk mesin Milling Vertikal P2, waktu elemen kerja membersihkan jig dari geram dapat  dikurangi dari 5.15 detik menjadi 1.54 detik. Dari hasil di atas maka dapat disimpulkan bahwa terjadi perbaikan waktu setup pada proses milling pada Mesin Milling Vertikal P1 dan P2 di Cylinder Head Line, perbandingan waktu standar proses milling dari 258.505 detik sebelum perbaikan menjadi 254.518 detik setelah perbaikan pada mesin Milling Vertikal P1 dan 256.002 detik sebelum perbaikan menjadi 252.392 detik setelah perbaikan pada mesin Milling Vertikal P2 Untuk penelitian ini hasil tersebut merupakan hasil maksimal yang dapat dicapai, namun dapat dikembangkan lebih lanjut pada mesin-mesin produksi lainnya. Kata kunci           : RETAD, waktu setup, elemen kerja

  7. p-Cu2O-shell/n-TiO2-nanowire-core heterostucture photodiodes

    Directory of Open Access Journals (Sweden)

    Hsueh Ting-Jen

    2011-01-01

    Full Text Available Abstract This study reports the deposition of cuprous oxide [Cu2O] onto titanium dioxide [TiO2] nanowires [NWs] prepared on TiO2/glass templates. The average length and average diameter of these thermally oxidized and evaporated TiO2 NWs are 0.1 to 0.4 μm and 30 to 100 nm, respectively. The deposited Cu2O fills gaps between the TiO2 NWs with good step coverage to form nanoshells surrounding the TiO2 cores. The p-Cu2O/n-TiO2 NW heterostructure exhibits a rectifying behavior with a sharp turn-on at approximately 0.9 V. Furthermore, the fabricated p-Cu2O-shell/n-TiO2-nanowire-core photodiodes exhibit reasonably large photocurrent-to-dark-current contrast ratios and fast responses.

  8. Crystal structure of the yeast nicotinamidase Pnc1p.

    Science.gov (United States)

    Hu, Gang; Taylor, Alexander B; McAlister-Henn, Lee; Hart, P John

    2007-05-01

    The yeast nicotinamidase Pnc1p acts in transcriptional silencing by reducing levels of nicotinamide, an inhibitor of the histone deacetylase Sir2p. The Pnc1p structure was determined at 2.9A resolution using MAD and MIRAS phasing methods after inadvertent crystallization during the pursuit of the structure of histidine-tagged yeast isocitrate dehydrogenase (IDH). Pnc1p displays a cluster of surface histidine residues likely responsible for its co-fractionation with IDH from Ni(2+)-coupled chromatography resins. Researchers expressing histidine-tagged proteins in yeast should be aware of the propensity of Pnc1p to crystallize, even when overwhelmed in concentration by the protein of interest. The protein assembles into extended helical arrays interwoven to form an unusually robust, yet porous superstructure. Comparison of the Pnc1p structure with those of three homologous bacterial proteins reveals a common core fold punctuated by amino acid insertions unique to each protein. These insertions mediate the self-interactions that define the distinct higher order oligomeric states attained by these molecules. Pnc1p also acts on pyrazinamide, a substrate analog converted by the nicotinamidase from Mycobacterium tuberculosis into a product toxic to that organism. However, we find no evidence for detrimental effects of the drug on yeast cell growth.

  9. Icaritin induces MC3T3-E1 subclone14 cell differentiation through estrogen receptor-mediated ERK1/2 and p38 signaling activation.

    Science.gov (United States)

    Wu, Zhidi; Ou, Ling; Wang, Chaopeng; Yang, Li; Wang, Panpan; Liu, Hengrui; Xiong, Yingquan; Sun, Kehuan; Zhang, Ronghua; Zhu, Xiaofeng

    2017-10-01

    Icaritin (ICT), a hydrolytic product of icariin from the genus Epimedium, has many indicated pharmacological and biological activities. Several studies have shown that ICT has potential osteoprotective effects, including stimulation of osteoblast differentiation and inhibition of osteoclast differentiation. However, the molecular mechanism for this anabolic action of ICT remains largely unknown. Here, we found that ICT could enhance MC3T3-E1 subclone 14 preosteoblastic cell differentiation associated with increased mRNA levels and protein expression of the differentiation markers alkaline phosphatase (ALP), type 1 collagen (COL1), osteocalcin (OC), osteoponin (OPN) and runt-related transcription factor 2 (RUNX2), and improved mineralization, confirmed by bone nodule formation and collagen synthesis. To characterize the underlying mechanisms, we examined the effect of ICT on estrogen receptor (ER) and mitogen-activated protein kinase (MAPK) signaling. ICT treatment induced p38 kinase and extracellular signal-regulated kinase 1/2 (ERK1/2) activation, but it demonstrated at the same time point no effect on activation of c-Jun N-terminal kinase (JNK). ER antagonist ICI182780, p38 antagonist SB203580 and ERK1/2 antagonist PD98059 markedly inhibited the ICT-induced the mRNA expression of ALP, COL1, OC and OPN. ICI182780 attenuated the ICT-induced phosphorylation of p38 and ERK1/2. These observations indicate a potential mechanism of osteogenic effects of ICT involving the ERK1/2 and p38 pathway activation through the ER. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. pO2 and pCO2 increment in post-dialyzer blood: the role of dialysate.

    Science.gov (United States)

    Sombolos, Kostas I; Bamichas, Gerasimos I; Christidou, Fotini N; Gionanlis, Lazaros D; Karagianni, Anna C; Anagnostopoulos, Theodoros C; Natse, Taïsir A

    2005-11-01

    Blood returning from a dialyzer during hemodialysis has a higher pO2 and pCO2 content than blood entering the dialyzer, and this has been attributed to the dialysate. The present study investigates this phenomenon. Acid-base and blood-gas parameters (pH, pO2, pCO2 and HCO3) were measured in three groups of stable chronic hemodialysis patients (A, B, and C) undergoing high-flux hemodialysis. In group A (n = 15), "arterial" (a) and "venous" (v) samples were withdrawn simultaneously before dialysis (samples A0), 5 min after circulation of the blood with the dialysate in the by-pass mode (samples A5), and 5 min after high-flux hemodialysis at a zero ultrafiltration rate (samples A10). In group B (n = 11) (a) and (v) samples were withdrawn simultaneously before dialysis (samples B0), 5 min after isolated-ultrafiltration with closed dialysate ports ("isolated-closed" ultrafiltration) (samples B5), and 5 min after high-flux hemodialysis at a zero ultrafiltration rate (samples B10). In group C (n = 14), after an initial arterial blood sample withdrawal before hemodialysis (sample C0), high-flux hemodialysis at a zero ultrafiltration rate was initiated. Five minutes later, blood and dialysate samples were withdrawn simultaneously from the hemodialysis lines (samples C5). In all cases blood and dialysate (bicarbonate) flow rates were set at 0.300 and 0.700 L/min, respectively. FLX-18 hemodialyzers (membrane PEPA 1.8 m2) were used in this study. Analysis of variance revealed significant changes only in venous samples. A comparison of arterial and venous samples revealed no differences between groups A and B before the initiation of dialysis (A0a vs. A0v and B0a vs. B0v, P = NS). The pO2 content was higher in A5v samples than in A5a samples (83.5 +/- 11.2 vs. 88.8 +/- 14.0 mm Hg, P pO2, pCO2, and HCO3 in comparison to A10v samples (P pO2 and pCO2 values in A5v and A10v samples increased by 6.3% and 12.1% and by 1.29% and 52% in comparison to corresponding values of A5a and A10

  11. MPN-1 : A computation module for the solution of transport equation in multiregions by P sub(N) method

    International Nuclear Information System (INIS)

    Yamaguchi, M.; Maiorino, J.R.

    1981-11-01

    The MPN-1, which is a computer program made in FORTRAN IV is described. The MPN-1 uses P sub(N) method to solve the one-speed, anisotropic linear steady-state transport equation in non-multiplying multiregions, slab geometry. The MPN-1 allows a maximum number of 12 regions, and maximum order of approximation, N=15. Besides, the anisotropic scattering is treated by an expansion in Legendre polynomial up to maximum degree of L=15. The boundary conditions used are: I) free surface; II) isotropic incidence; III) cosine incidence (aμ sup(α1 + bμ sup(α2) + cμ sup(α3)); IV) monodirectional incidence (delta function); V) total reflection. The required input are: order of approximation P sub(N'), average number of secondary particles in each region, external sources, thickness of each region, coefficients in a Legendre expansion of the transfer function in each region, and type of boundary conditions at the boundaries. The output are: albedo, transmission factor, disadvantage factor, total and angular fluxes and current. (Author) [pt

  12. Synthesis, in vitro pharmacologic characterization, and preclinical evaluation of N-[2-(1'-piperidinyl)ethyl]-3-[{sup 125}I]iodo-4-methoxybenzamide (P[{sup 125}I]MBA) for imaging breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    John, Christy S. E-mail: radcsj@gwumc.edu; Bowen, Wayne D.; Fisher, Susan J.; Lim, Benjamin B.; Geyer, Brian C.; Vilner, Bertold J.; Wahl, Richard L

    1999-05-01

    The goal of this study was to investigate the potential use of a radioiodinated benzamide, N-[2-(1'-piperidinyl)ethyl]-3-iodo[{sup 125}I]-4-methoxybenzamide (P[{sup 125}I]MBA), a sigma receptor binding radioligand for imaging breast cancer. The chemical and radiochemical syntheses of PIMBA are described. The pharmacological evaluation of PIMBA was carried out for sigma-1 and sigma-2 receptor sites. The in vivo pharmacokinetics of the radioiodinated benzamide were determined in rats and comparison of P[{sup 125}I]MBA with Tc-99m sestamibi were made in a rat mammary tumor model. Sigma-1 affinity (K{sub i}) for PIMBA in guinea pig brain membranes using [{sup 3}H](+)pentazocine was found to be 11.82{+-}0.68 nM, whereas sigma-2 affinity in rat liver using [{sup 3}H]DTG (1,3-o-di-tolylguanidine) was 206{+-}11 nM. Sites in guinea pig brain membranes labeled by P[{sup 125}I]MBA showed high affinity for haloperidol, (+)-pentazocine, BD1008, and PIMBA (K{sub i}=4.87{+-}1.49,8.81{+-}1.97,0.057{+-}0.005,46.9{+-}1.8 nM), respectively). Competition binding studies were carried out in human ductal breast carcinoma cells (T47D). A dose-dependent inhibition of specific binding was observed with several sigma ligands. K{sub i} values for the inhibition of P[{sup 125}I]MBA binding in T47D cells for haloperidol, N-[2-(1'-piperidinyl)]ethyl]4-iodobenzamide (IPAB), N-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP), and PIMBA were found to be 1.30{+-}0.07, 13{+-}1.5, 5.19{+-}2.3, 1.06{+-}0.5 nM, respectively. The in vitro binding data in guinea pig brain membranes and breast cancer cells confirmed binding to sigma sites. The saturation binding of P[{sup 125}I]MBA in T47D cells as studied by Scatchard analysis showed saturable binding, with a K{sub d}=94{+-}7 nM and a B{sub max}=2035{+-}305 fmol/mg of proteins. Biodistribution studies in Sprague-Dawley rats showed a rapid clearance of P[{sup 125}I]MBA from the normal organs. The potential of PIMBA in imaging breast cancer was

  13. Search for W-prime boson decaying to electron-neutrino pairs in p anti-p collisions at s**(1/2) = 1.96-TeV

    Energy Technology Data Exchange (ETDEWEB)

    Abulencia, A.; Adelman, J.; Affolder, T.; Akimoto, T.; Albrow, M.G.; Ambrose, D.; Amerio, S.; Amidei, D.; Anastassov, A.; Anikeev, K.; Annovi, A.; /Taiwan, Inst. Phys.

    2006-11-01

    The authors present the results of a search for W{prime} boson decaying to electron-neutrino pairs in p{bar p} collisions at a center-of-mass energy of 1.96 TeV, using a data sample corresponding to 205 pb{sup -1} of integrated luminosity collected by the CDF II detector at Fermilab. They observe no evidence for this decay mode and set limits on the production cross section times branching fraction, assuming the neutrinos from W{prime} boson decays to be light. If they assume the manifest left-right symmetric model, they exclude a W{prime} boson with mass less than 788 GeV/c{sup 2} at the 95% confidence level.

  14. Wilson's disease: 31P and 1H MR spectroscopy and clinical correlation

    International Nuclear Information System (INIS)

    Sinha, Sanjib; Taly, A.B.; Prashanth, L.K.; Ravishankar, S.; Vasudev, M.K.

    2010-01-01

    Proton ( 1 H) magnetic resonance spectroscopy (MRS) changes are noted in Wilson's disease (WD). However, there are no studies regarding membrane phospholipid abnormality using 31 P MRS in these patients. We aimed to analyze the striatal spectroscopic abnormalities using 31 P and 1 H MRS in WD. Forty patients of WD (treated, 29; untreated,11) and 30 controls underwent routine MR image sequences and in vivo 2-D 31 P and 1 H MRS of basal ganglia using an image-selected technique on a 1.5-T MRI scanner. Statistical analysis was done using Student's t test. The mean durations of illness and treatment were 6.2 ± 7.4 and 4.8 ± 5.9 years, respectively. MRI images were abnormal in all the patients. 1 H MRS revealed statistically significant reduction of N-acetyl aspartate (NAA)/choline (Cho) and NAA/creatine ratios in striatum ( 1 H MRS) of treated patients compared to controls. The mean values of phosphomonoesters (PME) (p 31 P MRS study. The duration of illness correlated well with increased PME/PDE [p < 0.001], PME/TPh [p < 0.05], and PDE/TPh [p < 0.05] and decreased NAA/Cho [p < 0.05] ratios. There was correlation of MRI score and reduced NAA/Cho ratio with disease severity. The PME/PDE ratio (right) was elevated in the treated group [p < 0.001] compared to untreated group. There is reduced breakdown and/or increased synthesis of membrane phospholipids and increased neuronal damage in basal ganglia in patients with WD. (orig.)

  15. Resolution of 1-n-butyl-3-methyl-3-phospholene 1-oxide with TADDOL derivatives and calcium salts of O,O'-Dibenzoyl-(2R,3R)- or O,O'-di-p-toluoyl-(2R,3R)-tartaric acid.

    Science.gov (United States)

    Bagi, Péter; Fekete, András; Kállay, Mihály; Hessz, Dóra; Kubinyi, Miklós; Holczbauer, Tamás; Czugler, Mátyás; Fogassy, Elemér; Keglevich, György

    2014-03-01

    The resolution methods applying (-)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane ("TADDOL"), (-)-(2R,3R)-α,α,α',α'-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol ("spiro-TADDOL"), as well as the acidic and neutral Ca(2+) salts of (-)-O,O'-dibenzoyl- and (-)-O,O'-di-p-toluoyl-(2R,3R)-tartaric acid were extended for the preparation of 1-n-butyl-3-methyl-3-phospholene 1-oxide in optically active form. In one case, the intermediate diastereomeric complex could be identified by single-crystal X-ray analysis. The absolute P-configuration of the enantiomers of the phospholene oxide was also determined by comparing the experimentally obtained and calculated CD spectra. © 2014 Wiley Periodicals, Inc.

  16. Temperature dependence of dark current of pSi-n(Si2)1-x(CdS)x structures

    International Nuclear Information System (INIS)

    Usmonov, Sh.N.

    2007-01-01

    Full text: The research of influence of isovalent impurity on electric and photo-electric properties of semiconductors where formative with semiconductor continuous solid solutions (CSS) of substitution presents both the fundamental and the applied application interest at the area of material science and photoelectrical properties of semiconductors. In the given work results of experimental researches (Si 2 ) 1-x (CdS) x epitaxial layers grown on c-Si substrates by a method liquid phase epitaxy are presented. The grown layers had thickness and ∼ 10 micron, n-type of conductivity with specific resistance 0,016 Ohm sm. Dependences of the dark current of pSi-n(Si 2 ) 1-x (CdS) x structures have been investigated at various values of a bias voltage. In experiment it was observed anomaly dependence of current. The current with arising of temperature begun monotonously aroused and reached some minimal value at temperature 100 C and then again starts to arise up to temperature 200 C. Arising of dark current is caused of the band-to-band thermal generation of electron-hole pairs. The voltage drop at the temperature 100 C is caused by the recharging of impurity atoms CdS. It is known, that width of the forbidden band of CdS Eg,CdS=2,48 eV more than Eg,Si=1,1 eV. Covalent bond of atoms CdS is stronger than Si-Si bond. However, when the molecule of CdS replaces two atoms of silicon in tetrahedral lattice of silicon the bonds of Cd-S become weak under influence of surrounding atoms of silicon. It causes to occurrence impurity level CdS located on Ei=1,2 eV below a valence band top of silicon. The generation of electron-hole pairs with participation of CdS impurities at the 100 C temperature is occurred under action thermal phonons. However, holes formed on impurity levels are localized and they will be recombination centers. Therefore drop of the dark current caused by dispersion of carriers on impurity centers. (authors)

  17. Intermediate nuclear structure for 2ν2β decay of 48Ca studied by (p, n) and (n, p) reactions at 300 MeV

    International Nuclear Information System (INIS)

    Sakai, H.; Yako, K.

    2009-01-01

    The two neutrino double beta (2ν2β) decay proceeds through a sequence of Gamow-Teller (GT) transitions, namely from the parent nucleus to the intermediate nucleus and then from the intermediate nucleus to the final daughter nucleus. The nuclear matrix element M 2ν for the 2ν2β - decay thus consists of the 2β - decay matrix elements for the parent nucleus decay and the 2β - decay matrix elements for the intermediate nucleus decay. These 2β - decay matrix elements can be studied experimentally through the (p, n) reaction for the parent nucleus decay and the (n, p) reaction for the intermediate nucleus decay. The 2ν2β-decay nucleus, 4 8C a is studied. The charge exchange (p, n) and (n, p) measurements at 300 MeV were performed using the neutron time-of-flight facility and the (n,p) facility, respectively, at RCNP. The (p, n) measurement on 4 8C a and the (n,p) measurement on 4 8T i provided us, for the first time, reliable B(GT - ) and B(GT + ) strength distributions up to high excitation energy of 30 MeV of the intermediate nucleus 4 8S c. The multipole decomposition analysis was applied to the angular distributions of the cross section spectra to extract the ΔL = 0 components, which are used to deduce B(GT ± ). Figure shows the double differential cross Nb sections for 4 8C a(p, n)4 8S c (left panel) and 4 8T i(n,p)4 8S c (right panel) reactions. The histograms show the results of the multi-pole decomposition analyses. It is very surprising to find sizable amount of ΔL = 0 yield, i.e. B(GT + ) strength in the highly excited energy region (> 10 MeV). The obtained B(GT ± ) distribution in 4 8S c as well as corresponding nuclear matrix elements M 2ν are compared with theoretical shell model calculation. In this talk, new results will be presented and their implication to the nuclear matrix elements for the 2ν2β-decay will be discussed (author)

  18. THE EFFECT OF A TWISTED MAGNETIC FIELD ON THE PERIOD RATIO P{sub 1}/P{sub 2} OF NONAXISYMMETRIC MAGNETOHYDRODYNAMIC WAVES

    Energy Technology Data Exchange (ETDEWEB)

    Karami, K. [Department of Physics, University of Kurdistan, Pasdaran Street, Sanandaj (Iran, Islamic Republic of); Bahari, K., E-mail: KKarami@uok.ac.ir, E-mail: K.Bahari@razi.ac.ir [Physics Department, Faculty of Science, Razi University, Kermanshah (Iran, Islamic Republic of)

    2012-10-01

    We consider nonaxisymmetric magnetohydrodynamic (MHD) modes in a zero-beta cylindrical compressible thin magnetic flux tube modeled as a twisted core surrounded by a magnetically twisted annulus, with both embedded in a straight ambient external field. The dispersion relation is derived and solved analytically and numerically to obtain the frequencies of the nonaxisymmetric MHD waves. The main result is that the twisted magnetic annulus does affect the period ratio P{sub 1}/P{sub 2} of the kink modes. For the kink modes, the magnetic twist in the annulus region can achieve deviations from P{sub 1}/P{sub 2} = 2 of the same order of magnitude as in the observations. Furthermore, the effect of the internal twist on the fluting modes is investigated.

  19. B1-induced caspase-independent apoptosis in MCF-7 cells is mediated by down-regulation of Bcl-2 via p53 binding to P2 promoter TATA box

    International Nuclear Information System (INIS)

    Liang Xin; Xu Ke; Xu Yufang; Liu Jianwen; Qian Xuhong

    2011-01-01

    The Bcl-2 family contains a panel of proteins which are conserved regulators of apoptosis in mammalian cells, like the anti-apoptotic protein Bcl-2. According to its significant role in altering susceptibility to apoptosis, the deciphering of the mechanism of Bcl-2 expression modulation may be crucial for identifying therapeutics strategies for cancer. Treatment with naphthalimide-based DNA intercalators, including M2-A and R16, generally leads to a decrease in Bcl-2 intracellular amounts. Whereas the interest for these chemotherapeutics is accompanied by advances in the fundamental understanding of their anticancer properties, the molecular mechanism underlying changes in Bcl-2 expression remains poorly understood. We report here that p53 contributes to Bcl-2 down-regulation induced by B1, a novel naphthalimide-based DNA intercalating agent. Indeed, the decrease in Bcl-2 protein levels observed during B1-induced apoptosis was correlated to the decrease in mRNA levels, as a result of the inhibition of Bcl-2 transcription and promoter activity. In this context, we evaluated p53 contribution in the Bcl-2 transcriptional down-regulation. We found a significant increase of p53 binding to P 2 promoter TATA box in MCF7 cells by chromatin immunoprecipitation. These data suggest that B1-induced caspase-independent apoptosis in MCF-7 cells is associated with the activation of p53 and the down-regulation of Bcl-2. Our study strengthens the links between p53 and Bcl-2 at a transcriptional level, upon naphthalimide-based DNA intercalator treatment. - Research highlights: → B1 induced apoptosis in MCF-7 cells, following a transcriptional decrease in Bcl-2. → B1 treatment triggered p53 activation and leads to a p53-dependent down-regulation of Bcl-2. → B1 induced significant increase of p53 binding to Bcl-2 P 2 promoter TATA box.

  20. Cross sections for the 14N(n,p0), (n,α0), and (n1) reactions from 0.5 to 15 MeV

    International Nuclear Information System (INIS)

    Morgan, G.L.

    1978-09-01

    Cross sections were measured for the 14 N(n,p 0 ) reaction from 0.5 to 7.0 MeV and for the (n,α 0 ) and (n1 ) reactions from 1 to 15 MeV and 4 to 15 MeV, respectively. The data were obtained using a gaseous scintillator containing N 2 and Xe mixtures. A linac was used as a pulsed, white neutron source with a 29-m fight path. The results of the measurement are compared to the current evaluated file for nitrogen; agreement is good for neutron energies below 8 MeV, but the measurement is substantially higher than the evaluation for neutron energies near 10 MeV

  1. Kinetics of an oxygen – iodine active medium with iodine atoms optically pumped on the {sup 2}P{sub 1/2} – {sup 2}P{sub 3/2} transition

    Energy Technology Data Exchange (ETDEWEB)

    Zagidullin, M V; Azyazov, V N [Samara Branch of the P.N. Lebedev Physical Institute, Russian Academy of Sciences, Samara (Russian Federation); Malyshev, M S [S.P. Korolev Samara State Aerospace University, Samara (Russian Federation)

    2015-08-31

    The kinetics of the processes occurring in an O{sub 2} – I{sub 2} – He – H{sub 2}O gas flow in which photodissociation of molecular iodine at a wavelength close to 500 nm and excitation of atomic iodine on the {sup 2}P{sub 1/2} – {sup 2}P{sub 3/2} transition by narrow-band radiation near 1315 nm are implemented successively has been analysed. It is shown that implementation of these processes allows one to form an oxygen – iodine medium with a high degree of dissociation of molecular iodine and a relative content of singlet oxygen O{sub 2}(a{sup 1}Δ) exceeding 10%. Having formed a supersonic gas flow with a temperature ∼100 K from this medium, one can reach a small-signal gain of about 10{sup -2} cm{sup -1} on the {sup 2}P{sub 1/2} – {sup 2}P{sub 3/2} transition in iodine atoms. The specific power per unit flow cross section in the oxygen – iodine laser with this active medium may reach ∼100 W cm{sup -2}. (active media)

  2. Evidence for Dual Binding Sites for 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) in Insect Sodium Channels.

    Science.gov (United States)

    Du, Yuzhe; Nomura, Yoshiko; Zhorov, Boris S; Dong, Ke

    2016-02-26

    1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), the first organochlorine insecticide, and pyrethroid insecticides are sodium channel agonists. Although the use of DDT is banned in most of the world due to its detrimental impact on the ecosystem, indoor residual spraying of DDT is still recommended for malaria control in Africa. Development of resistance to DDT and pyrethroids is a serious global obstacle for managing disease vectors. Mapping DDT binding sites is necessary for understanding mechanisms of resistance and modulation of sodium channels by structurally different ligands. The pioneering model of the housefly sodium channel visualized the first receptor for pyrethroids, PyR1, in the II/III domain interface and suggested that DDT binds within PyR1. Previously, we proposed the second pyrethroid receptor, PyR2, at the I/II domain interface. However, whether DDT binds to both pyrethroid receptor sites remains unknown. Here, using computational docking of DDT into the Kv1.2-based mosquito sodium channel model, we predict that two DDT molecules can bind simultaneously within PyR1 and PyR2. The bulky trichloromethyl group of each DDT molecule fits snugly between four helices in the bent domain interface, whereas two p-chlorophenyl rings extend into two wings of the interface. Model-driven mutagenesis and electrophysiological analysis confirmed these propositions and revealed 10 previously unknown DDT-sensing residues within PyR1 and PyR2. Our study proposes a dual DDT-receptor model and provides a structural background for rational development of new insecticides. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Genetic polymorphisms of cytochrome P450-1A2 (CYP1A2 among Emiratis.

    Directory of Open Access Journals (Sweden)

    Mohammad M Al-Ahmad

    Full Text Available Cytochrome P450 1A2 (CYP1A2 is one of the CYP450 mixed-function oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. In addition, significant inter-individual differences in the elimination of drugs metabolized by CYP1A2 enzyme have been observed which are largely due to the highly polymorphic nature of CYP1A2 gene. However, there are limited studies on CYP1A2 phenotypes and CYP1A2 genotypes among Emiratis and thus this study was carried out to fill this gap. Five hundred and seventy six non-smoker Emirati subjects were asked to consume a soft drink containing caffeine (a non-toxic and reliable probe for predicting CYP1A2 phenotype and then provide a buccal swab along with a spot urine sample. Taq-Man Real Time PCR was used to determine the CYP1A2 genotype of each individual. Phenotyping was carried out by analyzing the caffeine metabolites using High Performance Liquid Chromatography (HPLC analysis. We found that 1.4%, 16.3% and 82.3% of the Emirati subjects were slow, intermediate and rapid CYP1A2 metabolizers, respectively. In addition, we found that 1.4% of the subjects were homozygote for derived alleles while 16.1% were heterozygote and 82.5% were homozygote for the ancestral allele. The genotype frequency of the ancestral allele, CYP1A2*1A/*1A, is the highest in this population, followed by CYP1A2 *1A/*1C and CYP1A2 *1A/*1K genotypes, with frequencies of 0.825, 0.102 and 0.058, respectively. The degree of phenotype/genotype concordance was equal to 81.6%. The CYP1A2*1C/*1C and CYP1A2*3/*3 genotypes showed significantly the lowest enzyme phenotypic activity. The frequency of slow activity CYP1A2 enzyme alleles is very low among Emiratis which correlates with the presence of low frequencies of derived alleles in CYP1A2 gene.

  4. Activation of MEK 1/2 and p42/44 MAPK by Angiotensin II in Hepatocyte Nucleus and their Potentiation by Ethanol

    Science.gov (United States)

    Aroor, Annayya R.; Lee, Youn Ju; Shukla, Shivendra D.

    2009-01-01

    Hepato-subcellular effect of Ang II and ethanol on the p42/44 MAP Kinase and MEK1/2 were investigated in the nucleus of rat hepatocytes. Hepatocytes were treated with ethanol (100 mM) for 24 hr and stimulated with angiotensin II (Ang II, 100 nM, 5 min). The levels of p42/44 MAPK and MEK1/2 were monitored in the nuclear fraction using antibodies. Ang II itself caused significant accumulation of phospho-p42/44 MAPK in the nucleus without any significant translocation of p42/44 MAPK protein there by suggesting activation of p42/44 MAPK in the nucleus. Ang II caused marked accumulation of phospho-MEK 1/2 in the nucleus without any significant accumulation of MEK1/2 protein. Ratio of phospho-MEK 1/2 to MEK 1/2 protein in the nucleus after Ang II treatment was 2.4 times greater than control suggesting phosphorylation of MEK 1/2 inside the nucleus. Ethanol had no effect on the protein level or the activation of p42/44 MAPK in the nucleus. Ethanol treatment potentiated nuclear activation of p42/44 MPAK by Ang II but not translocation of p42/44 MAPK protein. This was accompanied by potentiation of Ang II stimulated accumulation of phospho-MEK 1/2 in the nucleus by ethanol. MEK 1/2 inhibitor, U-0126 inhibited Ang II response or its potentiation by ethanol. These results suggest that Ang II mediated accumulation of phospho-p42/44 MAPK in the hepatocyte nucleus involves MEK 1/2 dependent activation and this effect is potentiated by ethanol. PMID:19560630

  5. Exit Strategies: S1P Signaling and T Cell Migration.

    Science.gov (United States)

    Baeyens, Audrey; Fang, Victoria; Chen, Cynthia; Schwab, Susan R

    2015-12-01

    Whereas the role of sphingosine 1-phosphate receptor 1 (S1PR1) in T cell egress and the regulation of S1P gradients between lymphoid organs and circulatory fluids in homeostasis are increasingly well understood, much remains to be learned about S1P signaling and distribution during an immune response. Recent data suggest that the role of S1PR1 in directing cells from tissues into circulatory fluids is reprised again and again, particularly in guiding activated T cells from non-lymphoid tissues into lymphatics. Conversely, S1P receptor 2 (S1PR2), which antagonizes migration towards chemokines, confines cells within tissues. Here we review the current understanding of the roles of S1P signaling in activated T cell migration. In this context, we outline open questions, particularly regarding the shape of S1P gradients in different tissues in homeostasis and inflammation, and discuss recent strategies to measure S1P. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Fluorescent investigation of the interactions between N-(p-chlorophenyl)-N'-(1-naphthyl) thiourea and serum albumin: Synchronous fluorescence determination of serum albumin

    International Nuclear Information System (INIS)

    Cui Fengling; Wang Junli; Cui Yanrui; Li Jianping

    2006-01-01

    The interactions between N-(p-chlorophenyl)-N'-(1-naphthyl) thiourea and serum albumin were investigated by fluorescence spectroscopy and UV absorption spectrum under physiological conditions. The results of spectroscopic measurements suggested that N-(p-chlorophenyl)-N'-(1-naphthyl) thiourea should have a strong ability to quench the intrinsic fluorescence of both bovine serum albumin and human serum albumin through static quenching procedure, and the hydrophobic interaction was the predominant intermolecular force stabilizing the complex. Thermodynamic parameter enthalpy changes (ΔH) and entropy changes (ΔS) were calculated according to the Vant'Hoff equation. The binding distances between N-(p-chlorophenyl)-N'-(1-naphthyl) thiourea and the proteins were evaluated on the basis of the theory of Foester energy transfer. In addition, the effects of other ions on the binding constants of complexes were also discussed. Synchronous fluorescence technology was successfully applied to the determination of serum albumins added to the CPNT solution

  7. Randomizing quantum states to Shatten p -norm for all p1

    International Nuclear Information System (INIS)

    Jeong, Kabgyun

    2014-01-01

    We formularize a method for randomizing quantum states with respect to the Shatten p-norms (p1) in trace class. In particular, this work includes the operator norm, p = ∞, and the trace norm, p = 1, simultaneously in a single statement via McDiarmid's inequality and a net construction

  8. Optimized efficiency in InP nanowire solar cells with accurate 1D analysis

    Science.gov (United States)

    Chen, Yang; Kivisaari, Pyry; Pistol, Mats-Erik; Anttu, Nicklas

    2018-01-01

    Semiconductor nanowire arrays are a promising candidate for next generation solar cells due to enhanced absorption and reduced material consumption. However, to optimize their performance, time consuming three-dimensional (3D) opto-electronics modeling is usually performed. Here, we develop an accurate one-dimensional (1D) modeling method for the analysis. The 1D modeling is about 400 times faster than 3D modeling and allows direct application of concepts from planar pn-junctions on the analysis of nanowire solar cells. We show that the superposition principle can break down in InP nanowires due to strong surface recombination in the depletion region, giving rise to an IV-behavior similar to that with low shunt resistance. Importantly, we find that the open-circuit voltage of nanowire solar cells is typically limited by contact leakage. Therefore, to increase the efficiency, we have investigated the effect of high-bandgap GaP carrier-selective contact segments at the top and bottom of the InP nanowire and we find that GaP contact segments improve the solar cell efficiency. Next, we discuss the merit of p-i-n and p-n junction concepts in nanowire solar cells. With GaP carrier selective top and bottom contact segments in the InP nanowire array, we find that a p-n junction design is superior to a p-i-n junction design. We predict a best efficiency of 25% for a surface recombination velocity of 4500 cm s-1, corresponding to a non-radiative lifetime of 1 ns in p-n junction cells. The developed 1D model can be used for general modeling of axial p-n and p-i-n junctions in semiconductor nanowires. This includes also LED applications and we expect faster progress in device modeling using our method.

  9. Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

    Science.gov (United States)

    Patmanathan, Sathya Narayanan; Johnson, Steven P; Lai, Sook Ling; Panja Bernam, Suthashini; Lopes, Victor; Wei, Wenbin; Ibrahim, Maha Hafez; Torta, Federico; Narayanaswamy, Pradeep; Wenk, Markus R; Herr, Deron R; Murray, Paul G; Yap, Lee Fah; Paterson, Ian C

    2016-05-10

    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.

  10. The three-loop splitting functions P{sup (2)}{sub qg} and P{sup (2,N{sub F})}{sub gg}

    Energy Technology Data Exchange (ETDEWEB)

    Ablinger, J.; Schneider, C. [Johannes Kepler Univ., Linz (Austria). Research Inst. for Symbolic Computation (RISC); Behring, A. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); RWTH Aachen Univ. (Germany). Inst. fuer Theoretische Teilchenphysik und Kosmologie; Bluemlein, J.; Freitas, A. de [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Von Manteuffel, A. [Michigan State Univ., East Lansing, MI (United States). Dept. of Physics and Astronomy

    2017-04-15

    We calculate the unpolarized twist-2 three-loop splitting functions P{sup (2)}{sub qg}(x) and P{sup (2,N{sub F})}{sub gg}(x) and the associated anomalous dimensions using massive three-loop operator matrix elements. While we calculate P{sup (2,N{sub F})}{sub gg}(x) directly, P{sup (2)}{sub qg}(x) is computed from 1200 even moments, without any structural prejudice, using a hierarchy of recurrences obtained for the corresponding operator matrix element. The largest recurrence to be solved is of order 12 and degree 191. We confirm results in the foregoing literature.

  11. 1.0 MeV irradiation of OHMIC, MS, MIS contacts to InP

    International Nuclear Information System (INIS)

    Warren, C.E.; Wagner, B.F.; Anderson, W.A.

    1986-01-01

    The radiation effects of 1.0 MeV electrons with a dose of 10/sup 15/cm/sup -2/ to MS and MIS Schottky diodes on InP have been compared to the radiation effects of MIS diodes on GaAs and Si. The radiation effects to ohmic contacts were also investigated. The metal for the diodes on the InP was gold. Au/Ti/Al was used for the GaAs diodes and Cr for the silicon diodes. Oxide layers on InP were grown by anodization in 0.1 N KOH. Oxides to GaAs and Si were grown thermally. Ohmic contacts to InP were formed using AuGe/Ni and AuSn alloys, followed by annealing in N/sub 2//H/sub 2/ (85%/15%). Metal Semiconductor diodes on InP were found to be at least sensitive to the irradiation. The InP MS and MIS diodes showed only small changes in the current voltage (I-V) characteristic, whereas the GaAs and Si devices showed a decrease in reverse current after irradiation. The ohmic contact resistance was increased by a factor of 2 to 5 after irradiation

  12. Endogenous n-3 Polyunsaturated Fatty Acids Delay Progression of Pancreatic Ductal Adenocarcinoma in Fat-1-p48Cre/+-LSL-KrasG12D/+ Mice

    Directory of Open Access Journals (Sweden)

    Altaf Mohammed

    2012-12-01

    Full Text Available Preclinical studies suggest that diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs may be beneficial for prevention of pancreatic cancer. Nutritional intervention studies are often complex, and there is no clear evidence, without potential confounding factors, on whether conversion of n-6 PUFAs to n-3 PUFAs in pancreatic tissues would provide protection. Experiments were designed using n-3 fatty acid desaturase (Fat-1 transgenic mice, which can convert n-6 PUFA to n-3 FAs endogenously, to determine the impact of n-3 PUFAs on pancreatic intraepithelial neoplasms (PanINs and their progression to pancreatic ductal adenocarcinoma (PDAC. Six-weekold female p48Cre/+-LSL-KrasG12D/+ andcompoundFat-1-p48Cre/+-LSL-KrasG12D/+ mice were fed (AIN-76A diets containing 10% safflower oil for 35 weeks. Pancreata were evaluated histopathologically for PanINs and PDAC. Results showed a dramatic reduction in incidence of PDAC (84%; P 85%; P < .05–0.01 in pancreas of compound transgenic mice than in those of p48Cre/+-LSL-KrasG12D/+ mice. Molecular analysis of the pancreas showed a significant down-regulation of proliferating cell nuclear antigen, cyclooxygenase-2, 5-lipoxygenase (5-LOX, 5-LOX-activating protein, Bcl-2, and cyclin D1 expression levels in Fat-1-p48Cre/+-LSL-KrasG12D/+ mice compared to p48Cre/+-LSL-KrasG12D/+ mice. These data highlight the promise of dietary n-3 FAs for chemoprevention of pancreatic cancer in high-risk individuals.

  13. Transcription factors Asg1p and Hal9p regulate pH homeostasis in Candida glabrata

    Directory of Open Access Journals (Sweden)

    Jing eWu

    2015-08-01

    Full Text Available Candida glabrata is an important microorganism used in commercial fermentation to produce pyruvate, but very little is known about its mechanisms for surviving acid stress in culture. In this study, it was shown that transcription factors Asg1p and Hal9p play essential roles in C. glabrata in the tolerance of acid stress, as the deletion of CgASG1 or CgHAL9 resulted in the inability to survive in an acidic environment. Cgasg1 and Cghal9 mutant strains are unable to maintain pH homeostasis, as evidenced by a decrease in intracellular pH and an increase in reactive oxygen species production, which results in metabolic disorders. The results showed that intracellular acidification was partly due to the diminished activity of the plasma membrane proton pump, CgPma1p. In addition, transcriptome sequencing revealed that Cgasg1 and Cghal9 mutant strains displayed a variety of changes in gene expression under acidic conditions, including genes in the MAPK signaling pathway, plasma membrane or cell wall organization, trehalose accumulation, and the RIM101 signaling pathway. Lastly, quantitative reverse-transcribed PCR and cellular localization showed that CgAsg1p and CgHal9p played independent roles in response to acid stress.

  14. Layered P2-Na 2/3 Co 1/2 Ti 1/2 O 2 as a high-performance cathode material for sodium-ion batteries

    Energy Technology Data Exchange (ETDEWEB)

    Sabi, Noha; Doubaji, Siham; Hashimoto, Kazuki; Komaba, Shinichi; Amine, Khalil; Solhy, Abderrahim; Manoun, Bouchaib; Bilal, Essaid; Saadoune, Ismael

    2017-02-01

    Layered oxides are regarded as promising cathode materials for sodium-ion batteries. We present Na2/3Co1/2Ti1/2O2 as a potential new cathode material for sodium-ion batteries. The crystal features and morphology of the pristine powder were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The cathode material is evaluated in galvanostatic charge-discharge and galvanostatic intermittent titration tests, as well as ex-situ X-ray diffraction analysis. Synthesized by a high-temperature solid state reaction, Na2/3Co1/2Ti1/2O2 crystallizes in P2-type structure with P6(3)/mmc space group. The material presents reversible electrochemical behavior and delivers a specific discharge capacity of 100 mAh g(-1) when tested in Na half cells between 2.0 and 4.2 V (vs. Na+/Na), with capacity retention of 98% after 50 cycles. Furthermore, the electrochemical cycling of this titanium-containing material evidenced a reduction of the potential jumps recorded in the NaxCoO2 parent phase, revealing a positive impact of Ti substitution for Co. The ex-situ XRD measurements confirmed the reversibility and stability of the material. No structural changes were observed in the XRD patterns, and the P2-type structure was stable during the charge/discharge process between 2.0 and 4.2 V vs. Na+/Na. These outcomes will contribute to the progress of developing low cost electrode materials for sodium-ion batteries. (C) 2017 Elsevier B.V. All rights reserved.

  15. Effect of orbital alignment on the forward and reverse electronic energy transfer Ca(4s5p 1P1)+Marrow-right-leftCa(4s5p 3P/sub J/)+M with rare gases

    International Nuclear Information System (INIS)

    Bussert, W.; Neuschaefer, D.; Leone, S.R.; Departments of Physics and Chemistry, University of Colorado, Boulder, Colorado 80309-0440)

    1987-01-01

    Effects of orbital alignment on the relative cross sections for electronic energy transfer are determined for the near resonant transfer between Ca(4s5p 1 P 1 ) and Ca(4s5p 3 P/sub J/) states with rare gas collision partners. The experiments are carried out by pulsed laser excitation in a crossed beam. The results for the forward direction, 1 P to 3 P, formulated in terms of the ratio of the maximum to minimum transfer probability are: 3 He 1.61 +- 0.05; He 1.60 +- 0.03; Ne 1.55 +- 0.10; Ar 1.52 +- 0.21; for Kr, transfer occurs, but no preference is distinguishable within 1 +- 0.2; Xe 1.44 +- 0.06. The results for He, Ne, and Ar indicate a clear preference in the transfer for the initially prepared molecular Pi state. For Xe the molecular Σ state is dominant. The energy transfer is also carried out in the reverse direction, 3 P 1 to 1 P, for He and Xe, obtaining 1.65 +- 0.10 and 1.94 +- 0.22, respectively. Analysis of the state preparation suggests that the reverse direction favors the asymptotic molecular Σ state for He and the molecular Pi state for Xe. These alignment results provide a first experimental determination of the dominant electronic states involved in a collisional energy transfer process

  16. CELULE FOTOVOLTAICE CU HETEROJONCŢIUNEA nCdS-pInP

    Directory of Open Access Journals (Sweden)

    Vasile BOTNARIUC

    2015-12-01

    Full Text Available Au fost studiate proprietăţile electrice şi fotoelectrice ale heterojoncţiunilor nCdS-pInP cu şi fără strat epitaxial inter-mediar poInP. S-a stabilit că la polarizări directe în mecanismul de transport al curentului predomină procesele de recom-binare în regiunea de sarcină spaţială. La polarizări inverse predomină procesele de tunelare. Prezenţa stratului epitaxial poInP depus repetat măreşte ISC până la 28,2 mA·cm-2, UCD până la 0,780 V, iar eficienţa conversiei energiei până la 15% la 300 K şi iluminare 100 mW/cm2. Fotosensibilitatea CF nCdS-poInP-pInP corespunde intervalului λ=550...950 nm cu un maximum plat localizat în intervalul λ=700...850 nm.HETEROJONCTION nCdS–pInP FOTOVOLTAIC CELLSElectrical and photoelectrical properties of nCdS-pInP hetero-junctions with and without intermediate poInP epitaxial layer were studied. It was established that the current flow mechanism at direct biases is determined mainly by the recombi-nation processes in the space charge region of the junction. At the reverse biases the tunneling processes are predominant. The presence of poInP layer leads to the photo-electrical parameters enhancing of hetero-junction: short circuit current increases up to 28,2 mA·cm -2, open circuit voltage up to 0,780V and the efficiency of solar energy conversion up to 15 % (at 300 K and illumination of 100mw/cm2. The photo-sensitivity of nCdS- poInP -pInP is in the wavelength region of λ= 550-950nm with a maximum localized to λ=700-850nm.

  17. Fine structure and ionization energy of the 1s2s2p 4P state of the helium negative ion He-.

    Science.gov (United States)

    Wang, Liming; Li, Chun; Yan, Zong-Chao; Drake, G W F

    2014-12-31

    The fine structure and ionization energy of the 1s2s2p (4)P state of the helium negative ion He(-) are calculated in Hylleraas coordinates, including relativistic and QED corrections up to O(α(4)mc(2)), O((μ/M)α(4)mc(2)), O(α(5)mc(2)), and O((μ/M)α(5)mc(2)). Higher order corrections are estimated for the ionization energy. A comparison is made with other calculations and experiments. We find that the present results for the fine structure splittings agree with experiment very well. However, the calculated ionization energy deviates from the experimental result by about 1 standard deviation. The estimated theoretical uncertainty in the ionization energy is much less than the experimental accuracy.

  18. Contribution to {pi}{sup +}p inelastic scattering at incoming pion energies near 1 GeV; Contribution a la diffusion inelastique {pi}{sup +}p pour des energies du {pi} incident voisines de 1 GeV

    Energy Technology Data Exchange (ETDEWEB)

    Deler, B [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1968-06-01

    Results on {pi}{sup +}p scattering at 810 and 1300 MeV incoming kinetic energy are presented. In the three-body final states ({pi}{sup +}p {yields} {pi}{sup +}{pi}{sup 0}p or {pi}{sup +}{pi}{sup +}n) the N{sup *}{sub 33} production is strongly dominant. At 1300 MeV one also observes the {rho}, N{sup *}{sub 1/2} {sub 3/2} and N{sup *}{sub 1/2} {sub 5/2} productions. The difficulty in correctly separating these channels demands trying a more general analysis, taking simultaneously into account several processes (N{sup *}{pi}, {rho}N,...). A generalized isobaric model is discussed. Assuming the interaction of particles by pairs, we can carry out a partial wave analysis of the three body final state reactions. The expansion of the differential cross section in spherical harmonics for data between 600 and 1460 MeV (compilation of data from different laboratories) leads to a simple discussion of the angular effects for different parts of the Dalitz plot. A partial wave analysis has been made below 1 GeV. The reaction p {pi}{sup +}{pi}{sup 0} is correctly explained by considering only the N{sup *}{sub 33} production. The different partial waves are in agreement with the elastic phase shift analysis, except for the wave SD1 (corresponding to the elastic wave S31) which is found to be small. Therefore, the S31 resonance appears weakly coupled to the N{sup *}{sub 33}-{pi} channel. (author) [French] Les resultats de la mesure de la diffusion {pi}{sup +}p pour des energies cinetiques du {pi} incident egales a 810 MeV et 1300 MeV sont presentes. Dans les reactions a trois corps, {pi}{sup +}p {yields} {pi}{sup +}{pi}{sup 0}p ou {pi}{sup +}{pi}{sup +}n, la production de l'isobare 3/2 3/2 est fortement dominante. A 1300 MeV, on observe egalement la production du {rho} et des isobares 1/2 3/2 et 1/2 5/2. L'impossibilite de separer correctement ces differentes productions demande de chercher a effectuer l'analyse des donnees sous une forme plus generale permettant de tenir compte

  19. Critical Parameters and Critical-Region (p,ρ ,T) Data of trans-1,1,1,3-Tetrafluorobut-2-ene [HFO-1354mzy(E)

    Science.gov (United States)

    Kimura, Takeru; Kayukawa, Yohei; Miyamoto, Hiroyuki; Saito, Kiyoshi

    2017-08-01

    This study presents the experimental measurement of the pρ T properties and critical parameters of a low GWP type refrigerant, trans-1,1,1,3-Tetrafluorobut-2-ene (HFO-1354mzy(E)). The sample purity of the substance was 99 area %. p ρ T property measurements and visual observations of the meniscus of HFO-1354mzy(E) were carried out using a metal-bellows volumometer with an optical cell. The critical temperature was determined by observation of the critical opalescence. The critical pressure and critical density were determined as the inflection point of the isothermal p ρ T property data at the critical temperature. For more precise clarification of the thermodynamic surface in the vicinity of the critical point, additional p ρ T property measurements were carried out on three isotherms in the supercritical region. The expanded uncertainties (k = 2) in the temperature, pressure, and density measurements were estimated to be less than 3 mK, 1.2 kPa, and 0.32 \\hbox {kg} \\cdot \\hbox {m}^{-3}, respectively. The expanded uncertainties of the critical parameters were estimated to be less than 13 mK, 1.4 kPa, and 2.3 \\hbox {kg} \\cdot \\hbox {m}^{-3}, respectively. These values are the first reported for HFO-1354mzy(E) and are necessary for the development of its equation of state in the near future.

  20. Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3.

    Science.gov (United States)

    Lee, Hui Min; Lo, Kwok-Wai; Wei, Wenbin; Tsao, Sai Wah; Chung, Grace Tin Yun; Ibrahim, Maha Hafez; Dawson, Christopher W; Murray, Paul G; Paterson, Ian C; Yap, Lee Fah

    2017-05-01

    Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1, and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is overexpressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  1. P2Y1 receptor antagonists mitigate oxygen and glucose deprivation‑induced astrocyte injury.

    Science.gov (United States)

    Guo, Hui; Liu, Zhong-Qiang; Zhou, Hui; Wang, Zhi-Ling; Tao, Yu-Hong; Tong, Yu

    2018-01-01

    The aim of the present study was to elucidate the effects of blocking the calcium signaling pathway of astrocytes (ASs) on oxygen and glucose deprivation (OGD)‑induced AS injury. The association between the changes in the concentrations of AS‑derived transmitter ATP and glutamic acid, and the changes in calcium signaling under the challenge of OGD were investigated. The cortical ASs of Sprague Dawley rats were cultured to establish the OGD models of ASs. The extracellular concentrations of ATP and glutamic acid in the normal group and the OGD group were detected, and the intracellular concentration of calcium ions (Ca2+) was detected. The effects of 2'‑deoxy‑N6‑methyl adenosine 3', 5'‑diphosphate diammonium salt (MRS2179), a P2Y1 receptor antagonist, on the release of calcium and glutamic acid of ASs under the condition of OGD were observed. The OGD challenge induced the release of glutamic acid and ATP by ASs in a time‑dependent manner, whereas elevation in the concentration of glutamic acid lagged behind that of the ATP and Ca2+. The concentration of Ca2+ inside ASs peaked 16 h after OGD, following which the concentration of Ca2+ was decreased. The effects of elevated release of glutamic acid by ASs when challenged by OGD may be blocked by MRS2179, a P2Y1 receptor antagonist. Furthermore, MRS2179 may significantly mitigate OGD‑induced AS injury and increase cell survival. The ASs of rats cultured in vitro expressed P2Y1 receptors, which may inhibit excessive elevation in the concentration of intracellular Ca2+. Avoidance of intracellular calcium overload and the excessive release of glutamic acid may be an important reason why MRS2179 mitigates OGD‑induced AS injury.

  2. [1,3-Bis(diphenyl-phosphino)pentane-κP,P']tetra-carbonyl-chromium(0).

    Science.gov (United States)

    Shawkataly, Omar Bin; Thangadurai, Daniel T; Pankhi, Mohd Aslam A; Shahinoor Dulal Islam, S M; Fun, Hoong-Kun

    2009-02-04

    In the title compound, [Cr(C(29)H(30)P(2))(CO)(4)], the Cr atom is octa-hedrally coordinated by four carbonyl ligands and one bidentate phosphine ligand, which is bounded as a chelate in a cis position. The average Cr-P and Cr-C bond lengths are 2.377 and 1.865 Å, respectively.

  3. Analysis of cellular responses to aflatoxin B{sub 1} in yeast expressing human cytochrome P450 1A2 using cDNA microarrays

    Energy Technology Data Exchange (ETDEWEB)

    Guo Yingying [Departmental of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Breeden, Linda L. [Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Fan, Wenhong [Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Zhao Lueping [Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Eaton, David L. [Departmental of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Zarbl, Helmut [Departmental of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States) and Fred Hutchinson Cancer Research Center, Seattle, WA (United States)]. E-mail: hzarbl@fhcrc.org

    2006-01-29

    Aflatoxin B1 (AFB{sub 1}) is a potent human hepatotoxin and hepatocarcinogen produced by the mold Aspergillus flavus. In human, AFB{sub 1} is bioactivated by cytochrome P450 (CYP450) enzymes, primarily CYP1A2, to the genotoxic epoxide that forms N{sup 7}-guanine DNA adducts. To characterize the transcriptional responses to genotoxic insults from AFB{sub 1}, a strain of Saccharomyces cerevisiae engineered to express human CYP1A2 was exposed to doses of AFB{sub 1} that resulted in minimal lethality, but substantial genotoxicity. Flow cytometric analysis demonstrated a dose and time dependent S phase delay under the same treatment conditions, indicating a checkpoint response to DNA damage. Replicate cDNA microarray analyses of AFB{sub 1} treated cells showed that about 200 genes were significantly affected by the exposure. The genes activated by AFB{sub 1}-treatment included RAD51, DUN1 and other members of the DNA damage response signature reported in a previous study with methylmethane sulfonate and ionizing radiation [A.P. Gasch, M. Huang, S. Metzner, D. Botstein, S.J. Elledge, P.O. Brown, Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p, Mol. Biol. Cell 12 (2001) 2987-3003]. However, unlike previous studies using highly cytotoxic doses, environmental stress response genes [A.P. Gasch, P.T. Spellman, C.M. Kao, O. Carmel-Harel, M.B. Eisen, G. Storz, D. Botstein, P.O. Brown, Genomic expression programs in the response of yeast cells to environmental changes, Mol. Biol. Cell 11 (2000) 4241-4257] were largely unaffected by our dosing regimen. About half of the transcripts affected are also known to be cell cycle regulated. The most strongly repressed transcripts were those encoding the histone genes and a group of genes that are cell cycle regulated and peak in M phase and early G1. These include most of the known daughter-specific genes. The rapid and coordinated repression of histones and M/G1-specific

  4. ZrCu2P2 and HfCu2P2 phosphides and their crystal structure

    International Nuclear Information System (INIS)

    Lomnitskaya, Ya.F.

    1986-01-01

    Isostructural ZrCu 2 P 2 and HfCu 2 P 2 compounds are prepared for the first time. X-ray diffraction analysis (of powder, DRON-2.0 diffractometer, FeKsub(α) radiation) was used to study crystal structure of HfCu 2 P 2 phosphide belonging to the CaAl 2 Si 2 structural type (sp. group P anti 3 m 1, R=0.095). Lattice parameters the compounds are as follows: for ZrCu 2 P 2 a=0.3810(1), c=0.6184(5); for HfCu 2 P 2 a=0.3799(1), c=0.6160(2) (nm). Atomic parameters in the HfCu 2 P 2 structure and interatomic distances are determined

  5. Continuous Ecosystem Stoichiometry (C:N:P) in a Large Spring-fed River Reveals Decoupled N and P Assimilatory Dynamics

    Science.gov (United States)

    Cohen, M. J.; Douglass, R. L.; Martin, J. B.; Thomas, R. G.; Heffernan, J. B.; Foster, C. R.

    2010-12-01

    Diel variation in solutes offers insight into lotic ecosystem processes. Diel variation in dissolved oxygen (DO) is the standard method to estimate aquatic primary production (C fixation). Recently, diel variation in nitrate concentration was used to infer rates and pathways of N processing. From coupled C and N measurements, stoichiometric ratios of nutrient assimilation can be obtained, and variation therein linked back to environmental drivers and ecological changes. Here we present data obtained using an in situ phosphate sensor (Cycle-P, WetLabs, Philomath OR) that permits coupled high frequency C, N and P measurements. We collected hourly samples over 3 two-week deployments in the Ichetucknee River, a large (Q ~ 10 m3 s-1), productive (GPP ~ 6 g C m-2 d-1), entirely spring-fed river in north Florida. We observed average soluble reactive P (SRP) concentrations of 44, 41 and 45 µg/L for Dec-09, Feb-10 and Apr-10, respectively, and marked diel variation that averaged 6.7±0.9 µg/L. Observed river concentrations were consistently at or below the flow-weighted average input concentration of the 6 main springs that feed the river (49 µg/L) suggesting net SRP removal over the 5 km reach. Removal from co-precipitation with calcite or Fe-oxides is unlikely since variation in Fe and Ca is smaller than, and out of phase with, P variation. Since internal stores are presumed to be at steady-state given conditions of constant discharge, the balance of P export likely occurs as organic matter. Based on discharge during each deployment, diel variation of P concentrations indicate system-wide assimilation of 1505 ± 423 g P d-1, or 8.0 ± 2.3 mg P m-2 d-1 over the 17 ha of benthic surface area. Contemporaneous measurements of DO and nitrate implied average ecosystem stoichiometry (C:N:P) of 267:14:1, consistent with production dominated by submerged aquatic macrophytes rather than algae and other microflora. Of particular interest is the observation that diel variation in

  6. Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

    Science.gov (United States)

    Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

    1989-03-15

    Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

  7. Sphingosine-1-phosphate (S1P) activates STAT3 to protect against de novo acute heart failure (AHF).

    Science.gov (United States)

    Deshpande, Gaurang P; Imamdin, Aqeela; Lecour, Sandrine; Opie, Lionel H

    2018-03-01

    Acute heart failure (AHF) is a burden disease, with high mortality and re-hospitalisations. Using an ex-vivo model of AHF, we have previously reported that sphingosine-1-phosphate (S1P) confers cardioprotection. However, the mechanisms remain to be elucidated. In the present study, we aimed to examine the role of the cardioprotective signal transducer and activator of transcription 3 (STAT3) in S1P mediated improved functional recovery in AHF. Isolated hearts from male Long-Evans rats were subjected to hypotensive AHF for 35 min followed by a recovery phase of 30 min (n ≥ 4/group). S1P (10 nM) was given during either the hypotensive or the recovery phase with/without an inhibitor of STAT3, AG490. Functional parameters were recorded throughout the experiment. Following an AHF insult, S1P, given during the recovery phase, improved the heart rate (HR) compared to the control (175.2 ± 30.7 vs. 71.6 ± 27.4 beats per minute (BPM); p S1P abolished the cardioprotective effect of S1P (42.3 ± 17.1 vs. 148.8 ± 26.4 BPM for S1P; p S1P protects in an ex-vivo rat heart model of AHF by activation of STAT3 and provide further evidence for the usage of S1P as a potential therapy in patients suffering from AHF. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Contribution to the study of {pi}N {yields} {pi}{sub 1}{pi}{sub 2}N reactions with creation of an intermediate N{sup *}{sub 3/2} {sub (1236)} isobar from 0.4 to 1.5 GeV; Contribution a l'etude des reactions {pi}N {yields} {pi}{sub 1}{pi}{sub 2}N avec creation d'un isobare intermediaire N{sup *}{sub 3/2} {sub (1236)} de 0.4 a 1.5 GeV

    Energy Technology Data Exchange (ETDEWEB)

    Merlo, J P [Commissariat a l' Energie Atomique, 91 - Saclay (France). Centre d' Etudes Nucleaires. Division de la Physique, Departement de Physique des Particules Elementaires

    1976-07-01

    The one pion production reaction {pi}{sup +}p {yields} {pi}{sup +}p{pi}{sup 0} has been studied up to 1.5 GeV. The {pi}{sup 0} angular distribution measured by counter techniques has been compared to bubble chamber data. Angular distributions are interpreted in the hypothesis of formation of the intermediate N{sup *}{sub 3/2}(1236) isobar. Angular distributions for isobar production and decay in one pion production reactions {pi}N {yields} {pi}{sub 1}N{sup *} (N{sup *} {yields} {pi}{sub 2}N], are calculated in chapter II. {pi}{sup +}p {yields} {pi}{sup +}p{pi}{sup 0} experimental results are reported and analyzed in chapter III. An estimation of the pion-isobar partial wave amplitudes in reaction {pi}{sup +}p {yields} {pi}{sup 0}N{sup *++}{sub 3/2}(1236) has been tempted. Comparison with {pi}{sup +}p phase shift analyses is made. Bubble chamber data for {pi}{sup -}p {yields} {pi}{sup -}{pi}{sup +}n channel are presented at the end of chapter III. (author) [French] La reaction de production d'un pion {pi}{sup +}p {yields} {pi}{sup +}p{pi}{sup 0} a ete etudiee jusqu'a 1.5 GeV. La distribution angulaire du {pi}{sup 0} mesuree par la technique des compteurs a ete comparee aux resultats de chambre a bulles. Les distributions angulaires sont interpretees dans l'hypothese de la formation de l'isobare N{sup *}{sub 3/2}(1236) intermediaire. Les distributions angulaires de production et de desintegration de l'isobare dans les reactions de production d'un pion, {pi}N {yields} {pi}{sub 1}N{sup *} (N{sup *} {yields} {pi}{sub 2}N], sont calculees au second chapitre. Les resultats experimentaux de la voie {pi}{sup +}p {yields} {pi}{sup +}p{pi}{sup 0} sont presentes et analyses au troisieme chapitre. Une evaluation des amplitudes d'ondes partielles de production de l'isobare N{sup *}{sub 3/2}(1236) dans la reaction {pi}{sup +}p {yields} {pi}{sup 0}N{sup *++}{sub 3/2}(1236) a ete tentee. Une comparaison est faite avec les analyses en dephasages de l'interaction {pi}{sup +}p. Les

  9. SGK1 (glucose transport), dishevelled2 (wnt signaling), LC3/p62 (autophagy) and p53 (apoptosis) proteins are unaltered in Lafora disease

    Energy Technology Data Exchange (ETDEWEB)

    Wang, P.; Israelian, L.; Xue, Y.; Song, S.; Attisano, L.; Minassian, B.

    2016-07-01

    Glycogen forms through the concerted actions of glycogen synthase (GS) which elongates glycogen strands, and glycogen branching enzyme (GBE). Lafora disease (LD) is a fatal neurodegenerative epilepsy that results from neuronal accumulation of hyperphosphorylated glycogen with excessively long strands (called polyglucosans). There is no GBE deficiency in LD. Instead, the disease is caused by loss-of-function mutations in the EPM2A or EPM2B genes, encoding, respectively, a phosphatase, laforin, and an E3 ubiquiting ligase, malin. A number of experimentally derived hypotheses have been published to explain LD, including: The SGK1 hypothesis - Phosphorylated SGK1 (pSGK1) raises cellular glucose uptake and levels, which would activate GS. Based on observing increased pSGK1 in LD mice it was proposed that raised pSGK1 leads to polyglucosan generation through GS hyperactivation. The Dishevelled2 hypothesis - Downregulating malin in cell culture was reported to increase levels of dishevelled2, which through the wnt/glycogen synthase kinase-3 pathway would likewise overactivate GS. The Autophagic defect hypothesis - Polyglucosans may be natural byproducts of normal glycogen metabolism. LD mice were reported to be autophagy-defective. LD would arise from failed autophagy leading to failed polyglucosan clearance. Finally, the p53 hypothesis - laforin and malin were reported to downregulate p53, their absence leading to increased p53, which would activate apoptosis, leading to the neurodegeneration of LD. In the present work we repeat key experiments that underlie these four hypotheses. We are unable to confirm increased pSGK1, dishevelled2, or p53 in LD mice, nor the reported autophagic defects. Our work does not support the above hypotheses in understanding this unique and severe form of epilepsy.

  10. SGK1 (glucose transport), dishevelled2 (wnt signaling), LC3/p62 (autophagy) and p53 (apoptosis) proteins are unaltered in Lafora disease

    International Nuclear Information System (INIS)

    Wang, P.; Israelian, L.; Xue, Y.; Song, S.; Attisano, L.; Minassian, B.

    2016-01-01

    Glycogen forms through the concerted actions of glycogen synthase (GS) which elongates glycogen strands, and glycogen branching enzyme (GBE). Lafora disease (LD) is a fatal neurodegenerative epilepsy that results from neuronal accumulation of hyperphosphorylated glycogen with excessively long strands (called polyglucosans). There is no GBE deficiency in LD. Instead, the disease is caused by loss-of-function mutations in the EPM2A or EPM2B genes, encoding, respectively, a phosphatase, laforin, and an E3 ubiquiting ligase, malin. A number of experimentally derived hypotheses have been published to explain LD, including: The SGK1 hypothesis - Phosphorylated SGK1 (pSGK1) raises cellular glucose uptake and levels, which would activate GS. Based on observing increased pSGK1 in LD mice it was proposed that raised pSGK1 leads to polyglucosan generation through GS hyperactivation. The Dishevelled2 hypothesis - Downregulating malin in cell culture was reported to increase levels of dishevelled2, which through the wnt/glycogen synthase kinase-3 pathway would likewise overactivate GS. The Autophagic defect hypothesis - Polyglucosans may be natural byproducts of normal glycogen metabolism. LD mice were reported to be autophagy-defective. LD would arise from failed autophagy leading to failed polyglucosan clearance. Finally, the p53 hypothesis - laforin and malin were reported to downregulate p53, their absence leading to increased p53, which would activate apoptosis, leading to the neurodegeneration of LD. In the present work we repeat key experiments that underlie these four hypotheses. We are unable to confirm increased pSGK1, dishevelled2, or p53 in LD mice, nor the reported autophagic defects. Our work does not support the above hypotheses in understanding this unique and severe form of epilepsy.

  11. Field effect of P fertilization on N$_{2}$ fixation rate of Ulex europaeus

    OpenAIRE

    Cavard , Xavier; Augusto , Laurent; Saur , Etienne; Trichet , Pierre

    2007-01-01

    European gorse (Ulex europaeus L.) N-2 fixation rate (% Ndfa) was studied in a maritime pine (Pinus pinaster Ait.) oligotrophic forest. Fertilization field trials were carried out on 5 sites with various inputs of phosphorus (0-240 kg P2O5. ha(-1)). Seven to ten years after pine planting, gorse were sampled to evaluate the effect of P fertilization on gorse % Ndfa, determined using the N-15 natural abundance method. One of the prerequisites of this method is the existence of a significant dif...

  12. Growth of epitaxial (Sr, Ba){sub n+1}Ru{sub n}O{sub 3n}P+{sub 1}films

    Energy Technology Data Exchange (ETDEWEB)

    Schlom, D.G.; Knapp, S.B.; Wozniak, S. [Department of Materials Science and Engineering, Penn State University, University Park, PA (United States); Zou, L.N.; Park, J.; Liu, Y. [Department of Physics, Penn State University, University Park, PA (United States); Hawley, M.E.; Brown, G.W. [Center for Materials Science, Los Alamos National Laboratory, Los Alamos, NM (United States); Dabkowski, A.; Dabkowska, H.A. [Institute of Materials Research, McMaster University, Hamilton, Ontario (Canada); Uecker, R.; Reiche, P. [Institute of Crystal Growth, Berlin (Germany)

    1997-12-01

    We have grown epitaxial (Sr,Ba){sub n+1}Ru{sub n}O{sub 3n+1} films, n = 1, 2 and {infinity}, by pulsed laser deposition (PLD) and controlled their orientation by choosing appropriate substrates. The growth conditions yielding phase-pure films have been mapped out. Resistivity versus temperature measurements show that both a-axis and c-axis films of Sr{sub 2}RuO{sub 4} are metallic, but not superconducting. The latter is probably due to the presence of low-level impurities that are difficult to avoid given the target preparation process involved in growing these films by PLD. (author)

  13. Structural insights into the p97-Ufd1-Npl4 complex

    Science.gov (United States)

    Pye, Valerie E.; Beuron, Fabienne; Keetch, Catherine A.; McKeown, Ciaran; Robinson, Carol V.; Meyer, Hemmo H.; Zhang, Xiaodong; Freemont, Paul S.

    2007-01-01

    p97/VCP (Cdc48 in yeast) is an essential and abundant member of the AAA+ family of ATPases and is involved in a number of diverse cellular pathways through interactions with different adaptor proteins. The two most characterized adaptors for p97 are p47 and the Ufd1 (ubiquitin fusion degradation 1)-Npl4 (nuclear protein localization 4) complex. p47 directs p97 to membrane fusion events and has been shown to be involved in protein degradation. The Ufd1-Npl4 complex directs p97 to an essential role in endoplasmic reticulum-associated degradation and an important role in mitotic spindle disassembly postmitosis. Here we describe the structural features of the Ufd1-Npl4 complex and its interaction with p97 with the aid of EM and other biophysical techniques. The Ufd1-Npl4 heterodimer has an elongated bilobed structure that is ≈80 × 30 Å in dimension. One Ufd1-Npl4 heterodimer is shown to interact with one p97 hexamer to form the p97-Ufd1-Npl4 complex. The Ufd1-Npl4 heterodimer emanates from one region on the periphery of the N-D1 plane of the p97 hexamer. Intriguingly, the p97-p47 and the p97-Ufd1-Npl4 complexes are significantly different in stoichiometry, symmetry, and quaternary arrangement, reflecting their specific actions and their ability to interact with additional cofactors that cooperate with p97 in diverse cellular pathways. PMID:17202270

  14. Distinct roles of two ceramide synthases, CaLag1p and CaLac1p, in the morphogenesis of Candida albicans

    DEFF Research Database (Denmark)

    Cheon, Seon Ah; Bal, Jyotiranjan; Song, Yunkyoung

    2012-01-01

    p) and Lac1p (CaLac1p) are functionally distinct. Lack of CaLag1p, but not CaLac1p, caused severe defects in the growth and hyphal morphogenesis of C. albicans. Deletion of CaLAG1 decreased expression of the hypha-specific HWP1 and ECE1 genes. Moreover, overexpression of CaLAG1 induced pseudohyphal...... growth in this organism under non-hypha-inducing conditions, suggesting that CaLag1p is necessary for relaying signals to induce hypha-specific gene expression. Analysis of ceramide and sphingolipid composition revealed that CaLag1p predominantly synthesizes ceramides with C24:0/C26:0 fatty acid moieties...

  15. A constitutional translocation t(1;17(p36.2;q11.2 in a neuroblastoma patient disrupts the human NBPF1 and ACCN1 genes.

    Directory of Open Access Journals (Sweden)

    Karl Vandepoele

    Full Text Available The human 1p36 region is deleted in many different types of tumors, and so it probably harbors one or more tumor suppressor genes. In a Belgian neuroblastoma patient, a constitutional balanced translocation t(1;17(p36.2;q11.2 may have led to the development of the tumor by disrupting or activating a gene. Here, we report the cloning of both translocation breakpoints and the identification of a novel gene that is disrupted by this translocation. This gene, named NBPF1 for Neuroblastoma BreakPoint Family member 1, belongs to a recently described gene family encoding highly similar proteins, the functions of which are unknown. The translocation truncates NBPF1 and gives rise to two chimeric transcripts of NBPF1 sequences fused to sequences derived from chromosome 17. On chromosome 17, the translocation disrupts one of the isoforms of ACCN1, a potential glioma tumor suppressor gene. Expression of the NBPF family in neuroblastoma cell lines is highly variable, but it is decreased in cell lines that have a deletion of chromosome 1p. More importantly, expression profiling of the NBPF1 gene showed that its expression is significantly lower in cell lines with heterozygous NBPF1 loss than in cell lines with a normal 1p chromosome. Meta-analysis of the expression of NBPF and ACCN1 in neuroblastoma tumors indicates a role for the NBPF genes and for ACCN1 in tumor aggressiveness. Additionally, DLD1 cells with inducible NBPF1 expression showed a marked decrease of clonal growth in a soft agar assay. The disruption of both NBPF1 and ACCN1 genes in this neuroblastoma patient indicates that these genes might suppress development of neuroblastoma and possibly other tumor types.

  16. (p,2p) study of high-momentum components at 2.1 GeV

    International Nuclear Information System (INIS)

    Treuhaft, R.N.

    1982-07-01

    A (p,2p) experiment designed to isolate interactions with small numbers of fast nuclear constituents is described. Special attention is paid to the experimental manifestation and description of a correlated pair of nucleons in the nucleus. Phase space calculations are presented for the proton-pair three-body final state and for final states with larger number of particles. The Two Armed Spectrometer System (TASS) is described in detail. The data suggest the possibility of isolating an interaction with one or two nucleons in the nucleus which may have momenta far in excess of those described in a Fermi gas model

  17. (p,2p) study of high-momentum components at 2. 1 GeV

    Energy Technology Data Exchange (ETDEWEB)

    Treuhaft, R.N.

    1982-07-01

    A (p,2p) experiment designed to isolate interactions with small numbers of fast nuclear constituents is described. Special attention is paid to the experimental manifestation and description of a correlated pair of nucleons in the nucleus. Phase space calculations are presented for the proton-pair three-body final state and for final states with larger number of particles. The Two Armed Spectrometer System (TASS) is described in detail. The data suggest the possibility of isolating an interaction with one or two nucleons in the nucleus which may have momenta far in excess of those described in a Fermi gas model.

  18. P N Shukla

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Earth System Science. P N Shukla. Articles written in Journal of Earth System Science. Volume 110 Issue 2 June 2001 pp 103-110. High Iridium concentration of alkaline rocks of Deccan and implications to K/T boundary · P N Shukla N Bhandari Anirban Das A D Shukla J S Ray · More Details ...

  19. (p,3He) reactions on 1p shell nuclei at 41 and 45 MeV

    International Nuclear Information System (INIS)

    Rapp, V.

    1982-01-01

    In the present thesis the (p, 3 He) reactions on target nuclei of the 1p shell were studied. The measurements were performed at the isochronous cyclotron of the KFA Juelich. Angular distribution at 41 and 45 MeV to residual nuclear states in 7 Li, 8 Be, 9 Be, 10 B, 11 B, 12 C, 13 C, and 14 N. were evaluated. (orig.) [de

  20. Acidic pH facilitates peripheral αβmeATP-mediated nociception in rats: differential roles of P2X, P2Y, ASIC and TRPV1 receptors in ATP-induced mechanical allodynia and thermal hyperalgesia.

    Science.gov (United States)

    Seo, Hyoung-Sig; Roh, Dae-Hyun; Kwon, Soon-Gu; Yoon, Seo-Yeon; Kang, Suk-Yun; Moon, Ji-Young; Choi, Sheu-Ran; Beitz, Alvin J; Lee, Jang-Hern

    2011-03-01

    Peripheral ischemia is commonly associated with an increase in tissue ATP concentration and a decrease in tissue pH. Although in vitro data suggest that low tissue pH can affect ATP-binding affinities to P2 receptors, the mechanistic relationship between ATP and low pH on peripheral nociception has not been fully examined. This study was designed to investigate the potential role of an acidified environment on intraplantar αβmeATP-induced peripheral pain responses in rats. The mechanical allodynia (MA) produced by injection of αβmeATP was significantly increased in animals that received the drug diluted in pH 4.0 saline compared to those that received the drug diluted in pH 7.0 saline. Moreover, animals injected with αβmeATP (100 nmol) in pH 4.0 saline developed thermal hyperalgesia (TH), which did not occur in animals treated with αβmeATP diluted in pH 7.0 saline. To elucidate which receptors were involved in this pH-related facilitation of αβmeATP-induced MA and TH, rats were pretreated with PPADS (P2 antagonist), TNP-ATP (P2X antagonist), MRS2179 (P2Y1 antagonist), AMG9810 (TRPV1 antagonist) or amiloride (ASIC blocker). Both PPADS and TNP-ATP dose-dependently blocked pH-facilitated MA, while TH was significantly reduced by pre-treatment with MRS2179 or AMG9810. Moreover, amiloride injection significantly reduced low pH-induced facilitation of αβmeATP-mediated MA, but not TH. These results demonstrate that low tissue pH facilitates ATP-mediated MA via the activation of P2X receptors and ASICs, whereas TH induced by ATP under low pH conditions is mediated by the P2Y1 receptor and TRPV1, but not ASIC. Thus distinct mechanisms are responsible for the development of MA and TH under conditions of tissue acidosis and increased ATP. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. In Situ Proteolysis for Crystallization of Membrane Bound Cytochrome P450 17A1 and 17A2 Proteins from Zebrafish.

    Science.gov (United States)

    Lei, Li; Egli, Martin

    2016-04-01

    Fish and human cytochrome P450 (P450) 17A1 catalyze both steroid 17α-hydroxylation and 17α,20-lyase reactions. Fish P450 17A2 catalyzes only 17α-hydroxylation. Both enzymes are microsomal-type P450s, integral membrane proteins that bind to the membrane through their N-terminal hydrophobic segment, the signal anchor sequence. The presence of this N-terminal region renders expression of full-length proteins challenging or impossible. For some proteins, variable truncation of the signal anchor sequence precludes expression or results in poor expression levels. To crystallize P450 17A1 and 17A2 in order to gain insight into their different activities, we used an alternative N-terminal sequence to boost expression together with in situ proteolysis. Key features of our approach to identify crystallizable P450 fragments were the use of an N-terminal leader sequence, a screen composed of 12 proteases to establish optimal cleavage, variations of protease concentration in combination with an SDS-PAGE assay, and analysis of the resulting fragments using Edman sequencing. Described in this unit are protocols for vector preparation, expression, purification, and in situ proteolytic crystallization of two membrane-bound P450 proteins. Copyright © 2016 John Wiley & Sons, Inc.

  2. [1,4-Bis(diphenylphosphanylbutane-κ2P,P′]chlorido(η5-indenylruthenium(II

    Directory of Open Access Journals (Sweden)

    Hui-Ling Sung

    2011-05-01

    Full Text Available Facile ligand substitution is observed when the ruthenium chloride complex [Ru(η5-C9H7Cl(PPh32] is treated with 1,4-bis(diphenylphosphanylbutane in refluxing toluene yielding the title compound, [Ru(C9H7Cl(C28H28P2]. The RuII atom has a typical piano-stool coordination, defined by the indenyl ligand, one Cl atom and two phosphanyl P atoms. The Ru—P bond lengths are 2.2502 (9 and 2.2968 (8 Å.

  3. Study of four-jet events and evidence for double parton interactions in p bar p collisions at √s =1.8 TeV

    International Nuclear Information System (INIS)

    Abe, F.; Albrow, M.; Amidei, D.; Anway-Wiese, C.; Apollinari, G.; Atac, M.; Auchincloss, P.; Azzi, P.; Baden, A.R.; Bacchetta, N.; Badgett, W.; Bailey, M.W.; Bamberger, A.; de Barbaro, P.; Barbaro-Galtieri, A.; Barnes, V.E.; Barnett, B.A.; Bauer, G.; Baumann, T.; Bedeschi, F.; Behrends, S.; Belforte, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Benlloch, J.; Bensinger, J.; Beretvas, A.; Berge, J.P.; Bertolucci, S.; Biery, K.; Bhadra, S.; Binkley, M.; Bisello, D.; Blair, R.; Blocker, C.; Bodek, A.; Bolognesi, V.; Booth, A.W.; Boswell, C.; Brandenburg, G.; Brown, D.; Buckley-Geer, E.; Budd, H.S.; Busetto, G.; Byon-Wagner, A.; Byrum, K.L.; Campagnari, C.; Campbell, M.; Caner, A.; Carey, R.; Carithers, W.; Carlsmith, D.; Carroll, J.T.; Cashmore, R.; Castro, A.; Cervelli, F.; Chadwick, K.; Chapman, J.; Chiarelli, G.; Chinowsky, W.; Cihangir, S.; Clark, A.G.; Cobal, M.; Connor, D.; Contreras, M.; Cooper, J.; Cordelli, M.; Crane, D.; Cunningham, J.D.; Day, C.; DeJongh, F.; Dell'Agnello, S.; Dell'Orso, M.; Demortier, L.; Denby, B.; Derwent, P.F.; Devlin, T.; DiBitonto, D.; Dickson, M.; Drucker, R.B.; Einsweiler, K.; Elias, J.E.; Ely, R.; Eno, S.; Errede, S.; Etchegoyen, A.; Farhat, B.; Frautschi, M.; Feldman, G.J.; Flaugher, B.; Foster, G.W.; Franklin, M.; Freeman, J.; Frisch, H.; Fuess, T.; Fukui, Y.; Garfinkel, A.F.; Gauthier, A.; Geer, S.; Gerdes, D.W.; Giannetti, P.; Giokaris, N.; Giromini, P.; Gladney, L.; Gold, M.; Gonzalez, J.; Goulianos, K.; Grassmann, H.; Grieco, G.M.; Grindley, R.; Grosso-Pilcher, C.; Haber, C.; Hahn, S.R.; Handler, R.; Hara, K.; Harral, B.; Harris, R.M.; Hauger, S.A.; Hauser, J.; Hawk, C.; Hessing, T.; Hollebeek, R.; Holloway, L.; Hong, S.; Houk, G.; Hu, P.; Hubbard, B.; Huffman, B.T.; Hughes, R.; Hurst, P.; Huth, J.; Hylen, J.; Incagli, M.; Ino, T.; Iso, H.; Jensen, H.; Jessop, C.P.; Johnson, R.P.; Joshi, U.; Kadel, R.W.; Kamon, T.; Kanda, S.; Kardelis, D.A.; Karliner, I.; Kearns, E.; Keeble, L.; Kephart, R.; Kesten, P.; Keup, R.

    1993-01-01

    Kinematic properties of four-jet events produced in p bar p collisions at √s =1.8 TeV have been studied using data with an integrated luminosity of 325 nb -1 collected using the Collider Detector at Fermilab during the 1988--1989 Fermilab Collider run. The individual jet p T spectra and the angles between each jet pair are compared to the predictions of leading-order quantum chromodynamics for the double gluon bremsstrahlung process and good agreement is observed. In addition, a search for double parton scattering has been undertaken using variables sensitive to the topology of four-jet events. A small double parton content provides the best description of the data. We find N DP /N DB =5.4 -2.0 +1.6 %, where N represents the number of events attributed to each process. We measure σ DP =63 -28 +32 nb for jets having p T >25 GeV/c in the pseudorapidity interval |η|<3.5

  4. A distributed incentive compatible pricing mechanism for P2P networks

    Science.gov (United States)

    Zhang, Jie; Zhao, Zheng; Xiong, Xiao; Shi, Qingwei

    2007-09-01

    Peer-to-Peer (P2P) systems are currently receiving considerable interest. However, as experience with P2P networks shows, the selfish behaviors of peers may lead to serious problems of P2P network, such as free-riding and white-washing. In order to solve these problems, there are increasing considerations on reputation system design in the study of P2P networks. Most of the existing works is concerning probabilistic estimation or social networks to evaluate the trustworthiness for a peer to others. However, these models can not be efficient all the time. In this paper, our aim is to provide a general mechanism that can maximize P2P networks social welfare in a way of Vickrey-Clarke-Groves family, while assuming every peer in P2P networks is rational and selfish, which means they only concern about their own outcome. This mechanism has some desirable properties using an O(n) algorithm: (1) incentive compatibility, every peer truly report its connection type; (2) individually rationality; and (3) fully decentralized, we design a multiple-principal multiple-agent model, concerning about the service provider and service requester individually.

  5. A high-sensitivity, fast-response, rapid-recovery p–n heterojunction photodiode based on rutile TiO{sub 2} nanorod array on p-Si(1 1 1)

    Energy Technology Data Exchange (ETDEWEB)

    Selman, Abbas M., E-mail: alabbasiabbas@yahoo.co.uk [Nano-Optoelectronics Research and Technology Laboratory (N.O.R.), School of Physics, Universiti Sains Malaysia, Penang 11800 (Malaysia); Department of Pharmacology and Toxicology, College of Pharmacy, University of Kufa, Najaf (Iraq); Hassan, Z.; Husham, M.; Ahmed, Naser M. [Nano-Optoelectronics Research and Technology Laboratory (N.O.R.), School of Physics, Universiti Sains Malaysia, Penang 11800 (Malaysia)

    2014-06-01

    The growth and characterization of a p–n heterojunction photodiode were studied. This photodiode was based on rutile TiO{sub 2} nanorods (NRs) grown on p-type (1 1 1)-oriented silicon substrate seeded with a TiO{sub 2} layer synthesized by radio-frequency (RF) reactive magnetron sputtering. Chemical bath deposition (CBD) was performed to grow rutile TiO{sub 2} NRs on Si substrate. The structural and optical properties of the sample were studied by X-ray diffraction (XRD) and field emission-scanning electron microscopy (FESEM) analyses. Results showed the tetragonal rutile structure of the synthesized TiO{sub 2} NRs. Optical properties were further examined by photoluminescence spectroscopy, and a high-intensity UV peak centered at around 392 nm compared with visible defect peaks centered at 527 and 707 nm was observed. Upon exposure to 395 nm light (2.3 mW/cm) at five-bias voltage, the device showed 2.9 × 10{sup 2} sensitivity. In addition, the internal gain of the photodiode was 3.92, and the photoresponse peak was 106 mA/W. Furthermore, the photocurrent was 3.06 × 10{sup −4} A. The response and the recovery times were calculated to be 10.4 and 11 ms, respectively, upon illumination to a pulse UV light (405 nm, 0.22 mW/cm{sup 2}) at five-bias voltage. All of these results demonstrate that this high-quality photodiode can be a promising candidate as a low-cost UV photodetector for commercially integrated photoelectronic applications.

  6. The color tuning of PS-b-P2VP lamellar films with changing the alkyl chain length of 1-iodoalkanes.

    Science.gov (United States)

    Shin, Sung-Eui; Kim, Su-Young; Shin, Dong-Myung

    2011-05-01

    Photonic crystals with tunability in the visible or near-infrared region have drawn increasing attention for controlling and processing light for the active components of future display. We prepared polystyrene-b-poly(2-vinyl pyridine) (PS-b-P2VP) lamellar films which is hydrophobic block-hydrophilic polyelectrolyte block polymer of 57 kg/mol-b-57 kg/mol. The lamellar stacks, which is alternating layer of hydrophilic and hydrophobic moiety of PS-b-P2VP, are obtained by exposing the spin coated film under chloroform vapor. The band gaps of the lamellar films interestingly varied after immersion into the quaternizing solvents containing 5 wt% of iodomethane, iodoethane, 1-iodobutane, 1-iodopentane, 1-iodohexane and 1-iodooctane solubilized in n-hexane. The iodoalkanes reacted with pyridine groups in PS-b-P2VP and generated the alkyl pyridinium salts readily. The degree of quaternization, alkyl chain length of iodoalkane and the salt water concentration affects the spacing of layer structure of PS-b-P2VP. The iodomethane and iodohexane produced similar band gaps and salt concentration dependence. These results are very much dependent on the hydrophobic-hydrophilic characters of PS-b-P2VP lamellar surface.

  7. Effects of electron and proton irradiations on n/p and p/n GaAs cells grown by MOCVD

    International Nuclear Information System (INIS)

    Weinberg, I.; Swartz, C.K.; Hart, R.E. Jr.

    1987-01-01

    State-of-the-art n/p and p/n heteroface GaAs cells, processed by metal organic chemical vapor deposition, were irradiated by 1 MeV electrons and 37 MeV protons and their performance determined as a function of fluence. It was found that the p/n cells were more radiation resistant than the n/p cells. The increased loss in the n/p cells was attributed to increases in series resistance and losses in the p-region resulting from the irradiation. The greater loss in fill factor observed for the n/p cells introduces the possibility that the presently observed superiority of the p/n cells may not be an intrinsic property of this configuration in GaAs

  8. Optical properties of InxGa1-xP/InP grown at high fluence Ga+ implantation on InP using focused ion beam

    International Nuclear Information System (INIS)

    Fang, Hsin-Chiao; Liu, Chuan-Pu; Dhara, Sandip

    2011-01-01

    Single-crystalline InP(1 0 0) substrate was implanted by 30 keV Ga + ions with fluences of 1 x 10 16 -1.5 x 10 17 cm -2 followed by post-annealing treatment at 750 o C to recover implantation-induced structural defects and activate dopants into the lattices. The optical property, composition, and microstructure of the Ga + -implanted InP were studied by Raman spectroscopy and transmission electron microscopy (TEM). Raman spectra show that the In x Ga 1-x P phase is formed at a critical fluence of 7 x 10 16 cm -2 . The newly grown phase was identified with the appearance of Ga rich TO InP and In rich TO GaP modes of a random alloy in the 1 bond-2 phonon mode configuration along with TEM structural identification.

  9. The impact of nonpolar lipids on the regulation of the steryl ester hydrolases Tgl1p and Yeh1p in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Klein, Isabella; Korber, Martina; Athenstaedt, Karin; Daum, Günther

    2017-12-01

    In the yeast Saccharomyces cerevisiae degradation of steryl esters is catalyzed by the steryl ester hydrolases Tgl1p, Yeh1p and Yeh2p. The two steryl ester hydrolases Tgl1p and Yeh1p localize to lipid droplets, a cell compartment storing steryl esters and triacylglycerols. In the present study we investigated regulatory aspects of these two hydrolytic enzymes, namely the gene expression level, protein amount, stability and enzyme activity of Tgl1p and Yeh1p in strains lacking both or only one of the two major nonpolar lipids, steryl esters and triacylglycerols. In a strain lacking both nonpolar lipids and consequently lipid droplets, Tgl1p as well as Yeh1p were present at low amount, became highly unstable compared to wild-type cells, and lost their enzymatic activity. Under these conditions both steryl ester hydrolases were retained in the endoplasmic reticulum. The lack of steryl esters alone was not sufficient to cause an altered intracellular localization of Tgl1p and Yeh1p. Surprisingly, the stability of Tgl1p and Yeh1p was markedly reduced in a strain lacking triacylglycerols, but their capacity to mobilize steryl esters remained unaffected. We also tested a possible cross-regulation of Tgl1p and Yeh1p by analyzing the behavior of each hydrolase in the absence of its counterpart steryl ester hydrolases. In summary, this study demonstrates a strong regulation of the two lipid droplet associated steryl ester hydrolases Tgl1p and Yeh1p due to the presence/absence of their host organelle. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Solvability of a (p, n-p-type multi-point boundary-value problem for higher-order differential equations

    Directory of Open Access Journals (Sweden)

    Yuji Liu

    2003-12-01

    Full Text Available In this article, we study the differential equation $$ (-1^{n-p} x^{(n}(t=f(t,x(t,x'(t,dots,x^{(n-1}(t, $$ subject to the multi-point boundary conditions $$displaylines{ x^{(i}(0=0 quad hbox{for }i=0,1,dots,p-1,cr x^{(i}(1=0 quad hbox{for }i=p+1,dots,n-1,cr sum_{i=1}^malpha_ix^{(p}(xi_i=0, }$$ where $1le ple n-1$. We establish sufficient conditions for the existence of at least one solution at resonance and another at non-resonance. The emphasis in this paper is that $f$ depends on all higher-order derivatives. Examples are given to illustrate the main results of this article.

  11. The seroprevalence of pandemic influenza H1N1 (2009 virus in China.

    Directory of Open Access Journals (Sweden)

    Cuiling Xu

    2011-04-01

    Full Text Available Mainland China experienced pandemic influenza H1N1 (2009 virus (pH1N1 with peak activity during November-December 2009. To understand the geographic extent, risk factors, and attack rate of pH1N1 infection in China we conducted a nationwide serological survey to determine the prevalence of antibodies to pH1N1.Stored serum samples (n = 2,379 collected during 2006-2008 were used to estimate baseline serum reactogenicity to pH1N1. In January 2010, we used a multistage-stratified random sampling method to select 50,111 subjects who met eligibility criteria and collected serum samples and administered a standardized questionnaire. Antibody response to pH1N1 was measured using haemagglutination inhibition (HI assay and the weighted seroprevalence was calculated using the Taylor series linearization method. Multivariable logistic regression analyses were used to examine risk factors for pH1N1 seropositivity. Baseline seroprevalence of pH1N1 antibody (HI titer ≥40 was 1.2%. The weighted seroprevalence of pH1N1 among the Chinese population was 21.5%(vaccinated: 62.0%; unvaccinated: 17.1%. Among unvaccinated participants, those aged 6-15 years (32.9% and 16-24 years (30.3% had higher seroprevalence compared with participants aged 25-59 years (10.7% and ≥60 years (9.9%, P<0.0001. Children in kindergarten and students had higher odds of seropositivity than children in family care (OR: 1.36 and 2.05, respectively. We estimated that 207.7 million individuals (15.9% experienced pH1N1 infection in China.The Chinese population had low pre-existing immunity to pH1N1 and experienced a relatively high attack rate in 2009 of this virus. We recommend routine control measures such as vaccination to reduce transmission and spread of seasonal and pandemic influenza viruses.

  12. Sphingosine-1-Phosphate (S1P)-Related Response of Human Conjunctival Fibroblasts After Filtration Surgery for Glaucoma.

    Science.gov (United States)

    Aoyama-Araki, Yuka; Honjo, Megumi; Uchida, Takatoshi; Yamagishi, Reiko; Kano, Kuniyuki; Aoki, Junken; Aihara, Makoto

    2017-04-01

    To investigate levels of sphingosine-1-phosphate (S1P) in aqueous fluid samples taken before and after filtration surgery and S1P-induced human conjunctival fibroblast (HCF) responses. Levels of S1P and its related sphingophospholipids in aqueous fluid obtained immediately before and after filtration surgery were determined by liquid chromatography-tandem mass spectrometry. HCFs were used for all in vitro experiments. The expression of five S1P receptor subtypes in HCFs was examined by quantitative real-time PCR. The effect of S1P and receptor-specific antagonists on HCF viability and cell migration was assessed by WST-1 assay and scratch migration assay, respectively. Differentiation to myofibroblasts and extracellular matrix production was evaluated by examining changes in F-actin, α-smooth muscle actin (αSMA), and collagen expression with immunocytochemistry, Western blotting, and collagen accumulation assay, respectively. No significant S1P levels in the aqueous fluid samples were detectable immediately before surgery, but postoperative levels of several lysophospholipids, including S1P, dehydro-S1P, and sphingosine, were significantly increased to bioactive concentrations in aqueous fluid in the blebs (P S1P receptor subtypes was detected in HCFs. Although S1P levels did not influence HCF proliferation, S1P enhanced cell migration, which could be inhibited by the S1P2 antagonist JTE 013. F-actin, αSMA, and collagen expression was significantly increased by S1P stimulation and was reduced by JTE 013. Bioactive S1P concentrations were present in the aqueous fluid at the end of filtration surgery. S1P activated HCFs via S1P2 receptors. These results revealed the potential of S1P2 antagonists in preventing scarring after glaucoma filtration surgery.

  13. SIRT1 mediates Sphk1/S1P-induced proliferation and migration of endothelial cells.

    Science.gov (United States)

    Gao, Zhan; Wang, Hua; Xiao, Feng-Jun; Shi, Xue-Feng; Zhang, Yi-Kun; Xu, Qin Qin; Zhang, Xiao-Yan; Ha, Xiao-Qin; Wang, Li-Sheng

    2016-05-01

    Angiogenesis is one of the most important components of embryonic organ formation and vessel growth after birth. Sphingosine kinase 1 (Sphk1) and S1P has been confirmed to participate in various cell signaling pathways and physiological processes including neovascularisation. However, the mechanisms that Sphk1/S1P regulates neovascularisation remain unclear. In this study, we elucidated that Sphk1/S1P upregulates sirtuin 1 (SIRT1), a NAD+ dependent deacetylases protease which exerts multiple cellular functions, to regulate the proliferation and migration of endothelial cells. By using CCK8 and Transwell assays, we demonstrated that Sphk1 and SIRT1 knockdown could significantly decrease proliferation and migration of HUVEC cells. Sphk1 inhibition results in SIRT1 downregulation which could be reversed by exogenous S1P in HUVEC cells. Treatment of HUVECs with S1P reverses the impaired proliferation and migration caused by SIRT1 knockdown. Furthermore, Sphk1 knockdown inhibits the phosphorylation of P38 MAPK, ERK and AKT. Treatment of HUVECs with PD98059, SB203580 and Wortmannin, which are the inhibitors of ERK, P38 MAPK and AKT respectively, resulted in decreased SIRT1 expression and reduced migration of HUVEC cells. Thus, we conclude that Sphk1/S1P induces SIRT1 upregulation through multiple pathways including P38 MAPK, ERK and AKT signals. This is the first report to disclose the existence and roles of Sphk1/S1P/SIRT1 axis in regulation of endothelial cell proliferation and migration, which may provide a theoretical basis for angiogenesis. Copyright © 2016. Published by Elsevier Ltd.

  14. YB1/p32, a nuclear Y-box binding protein 1, is a novel regulator of myoblast differentiation that interacts with Msx1 homeoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Song, Young Joon [Department of Biological Sciences, College of Natural Science, Inha University, 253 Yonghyun-dong, Nam-Gu, Incheon, Korea, 402-751 (Korea, Republic of); Lee, Hansol, E-mail: hlee@inha.ac.kr [Department of Biological Sciences, College of Natural Science, Inha University, 253 Yonghyun-dong, Nam-Gu, Incheon, Korea, 402-751 (Korea, Republic of)

    2010-02-15

    Precisely controlled cellular differentiation is essential for the proper development of vertebrate embryo and deregulated differentiation is a major cause of many human congenital diseases as well as cancer. Msx1 is a member of the homeoprotein family implicated in these processes, which inhibits the differentiation of skeletal muscle and other cell types, presumably by regulating transcription of target genes through interaction with other cellular factors. We presently show that YB1/p32, a nuclear Y-box binding protein 1, interacts with Msx1 homeoprotein and functions as a regulator of C2C12 myoblast differentiation. We demonstrate that YB1/p32 functionally interacts with Msx1 through its N-terminal region and colocalizes with Msx1 at the nuclear periphery. Moreover, we find that YB1/p32 is competent for inhibition of C2C12 myoblast differentiation, which is correlated with its activity as a negative regulator of MyoD gene expression and binding to the MyoD core enhancer region (CER). Furthermore, YB1/p32 cooperates with Msx1 in transcriptional repression and knocking down the expression of endogenous YB1 attenuates the effects of Msx1. Taken together, our study has uncovered a new function of YB1/p32, a regulator of skeletal muscle differentiation.

  15. YB1/p32, a nuclear Y-box binding protein 1, is a novel regulator of myoblast differentiation that interacts with Msx1 homeoprotein

    International Nuclear Information System (INIS)

    Song, Young Joon; Lee, Hansol

    2010-01-01

    Precisely controlled cellular differentiation is essential for the proper development of vertebrate embryo and deregulated differentiation is a major cause of many human congenital diseases as well as cancer. Msx1 is a member of the homeoprotein family implicated in these processes, which inhibits the differentiation of skeletal muscle and other cell types, presumably by regulating transcription of target genes through interaction with other cellular factors. We presently show that YB1/p32, a nuclear Y-box binding protein 1, interacts with Msx1 homeoprotein and functions as a regulator of C2C12 myoblast differentiation. We demonstrate that YB1/p32 functionally interacts with Msx1 through its N-terminal region and colocalizes with Msx1 at the nuclear periphery. Moreover, we find that YB1/p32 is competent for inhibition of C2C12 myoblast differentiation, which is correlated with its activity as a negative regulator of MyoD gene expression and binding to the MyoD core enhancer region (CER). Furthermore, YB1/p32 cooperates with Msx1 in transcriptional repression and knocking down the expression of endogenous YB1 attenuates the effects of Msx1. Taken together, our study has uncovered a new function of YB1/p32, a regulator of skeletal muscle differentiation.

  16. Search for Randall-Sundrum gravitons with 1 fb.sup.-1./sup. of data from p anti-p collisions at s**(1/2) = 1.96 TeV

    Czech Academy of Sciences Publication Activity Database

    Abazov, V. M.; Abbott, B.; Abolins, M.; Kupčo, Alexander; Lokajíček, Miloš

    2008-01-01

    Roč. 100, č. 9 (2008), 091802/1-091802/7 ISSN 0031-9007 R&D Projects: GA MŠk LC527; GA MŠk LA08047; GA MŠk 1P05LA257 Institutional research plan: CEZ:AV0Z10100502 Keywords : D0 * Tevatron Subject RIV: BF - Elementary Particles and High Energy Physics Impact factor: 7.180, year: 2008

  17. X(3872), IG(JPC) = 0+(1++), as the χc1(2P) charmonium

    Science.gov (United States)

    Achasov, N. N.; Rogozina, E. V.

    2015-09-01

    Contrary to almost standard opinion that the X(3872) resonance is the D∗0D¯0 + c.c. molecule or the qcq¯c¯ four-quark state, we discuss the scenario where the X(3872) resonance is the cc¯ = χc1(2P) charmonium which “sits on” the D∗0D¯0 threshold. We explain the shift of the mass of the X(3872) resonance with respect to the prediction of a potential model for the mass of the χc1(2P) charmonium by the contribution of the virtual D∗D¯ + c.c. intermediate states into the self energy of the X(3872) resonance. This allows us to estimate the coupling constant of the X(7872) resonance with the D∗0D¯0 channel, the branching ratio of the X(3872) → D∗0D¯0 + c.c. decay, and the branching ratio of the X(3872) decay into all non-D∗0D¯0 + c.c. states. We predict a significant number of unknown decays of X(3872) via two gluon: X(3872) →gluon gluon →hadrons. We suggest a physically clear program of experimental researches for verification of our assumption.

  18. Dimerization of nitrophorin 4 at low pH and comparison to the K1A mutant of nitrophorin 1.

    Science.gov (United States)

    Berry, Robert E; Yang, Fei; Shokhireva, Tatiana K; Amoia, Angela M; Garrett, Sarah A; Goren, Allena M; Korte, Stephanie R; Zhang, Hongjun; Weichsel, Andrzej; Montfort, William R; Walker, F Ann

    2015-01-20

    Nitrophorin 4, one of the four NO-carrying heme proteins from the salivary glands of Rhodnius prolixus, forms a homodimer at pH 5.0 with a Kd of ∼8 μM. This dimer begins to dissociate at pH 5.5 and is completely dissociated to monomer at pH 7.3, even at 3.7 mM. The dimer is significantly stabilized by binding NO to the heme and at pH 7.3 would require dilution to well below 0.2 mM to completely dissociate the NP4-NO homodimer. The primary techniques used for investigating the homodimer and the monomer-dimer equilibrium were size-exclusion fast protein liquid chromatography at pH 5.0 and (1)H{(15)N} heteronuclear single-quantum coherence spectroscopy as a function of pH and concentration. Preparation of site-directed mutants of NP4 (A1K, D30A, D30N, V36A/D129A/L130A, K38A, R39A, K125A, K125E, D132A, L133V, and K38Q/R39Q/K125Q) showed that the N-terminus, D30, D129, D132, at least one heme propionate, and, by association, likely also E32 and D35 are involved in the dimerization. The "closed loop" form of the A-B and G-H flexible loops of monomeric NP4, which predominates in crystal structures of the monomeric protein reported at pH 5.6 but not at pH 7.5 and which involves all of the residues listed above except D132, is required for dimer formation. Wild-type NP1 does not form a homodimer, but NP1(K1A) and native N-terminal NP1 form dimers in the presence of NO. The homodimer of NP1, however, is considerably less stable than that of NP4 in the absence of NO. This suggests that additional aspartate or glutamate residues present in the C-terminal region of NP4, but not NP1, are also involved in stabilizing the dimer.

  19. S1P and the birth of platelets

    Science.gov (United States)

    Galvani, Sylvain; Rafii, Shahin; Nachman, Ralph

    2012-01-01

    Recent work has highlighted the multitude of biological functions of sphingosine 1-phosphate (S1P), which include roles in hematopoietic cell trafficking, organization of immune organs, vascular development, and neuroinflammation. Indeed, a functional antagonist of S1P1 receptor, FTY720/Gilenya, has entered the clinic as a novel therapeutic for multiple sclerosis. In this issue of the JEM, Zhang et al. highlight yet another function of this lipid mediator: thrombopoiesis. The S1P1 receptor is required for the growth of proplatelet strings in the bloodstream and the shedding of platelets into the circulation. Notably, the sharp gradient of S1P between blood and the interstitial fluids seems to be essential to ensure the production of platelets, and S1P appears to cooperate with the CXCL12–CXCR4 axis. Pharmacologic modulation of the S1P1 receptor altered circulating platelet numbers acutely, suggesting a potential therapeutic strategy for controlling thrombocytopenic states. However, the S1P4 receptor may also regulate thrombopoiesis during stress-induced accelerated platelet production. This work reveals a novel physiological action of the S1P/S1P1 duet that could potentially be harnessed for clinical translation. PMID:23166370

  20. Mean life of the 2p4(1S)3s 2S state in fluorine

    International Nuclear Information System (INIS)

    Cheng, K.T.; Chen, M.H.

    1985-01-01

    In this work, we calculate the radiationless as well as the radiative decay rates for the 2p 4 ( 1 S)3s 2 S state. For comparison purposes, we also make similar calculations for the 2p 4 ( 1 D)4s 2 D state. Our calculation is based on the multi-configuration Dirac-Fock (MCDF) method. As spin-orbit interaction is built in, this method is capable of studying LS forbidden Auger transitions. Details of the Auger transition calculations have been given before. 9 refs