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Sample records for fr01oc10r pp 60967-60999

  1. Locally homogeneous pp-waves

    NASA Astrophysics Data System (ADS)

    Globke, Wolfgang; Leistner, Thomas

    2016-10-01

    We show that every n-dimensional locally homogeneous pp-wave is a plane wave, provided it is indecomposable and its curvature operator, when acting on 2-forms, has rank greater than one. As a consequence we obtain that indecomposable, Ricci-flat locally homogeneous pp-waves are plane waves. This generalises a classical result by Jordan, Ehlers and Kundt in dimension 4. Several examples show that our assumptions on indecomposability and the rank of the curvature are essential.

  2. Analysis of Vernier Scans during the PP2PP run in 2009 (pp at 100 GeV/beam)

    SciTech Connect

    Drees, A.

    2011-12-13

    At the end of RHIC's 2009 operation a dedicated run for the PP2PP experiment (part of the STAR experiment) took place from Jun 29 to Jul 06 2009. Polarized protons were accelerated to 100 GeV using ramp-file pp100-90pp2pp with a {beta}* = 22 m in IR6. Since only transverse polarization was required no rotator ramp was in use. The PP2PP experiment consists mainly of two Roman Pot detectors (one horizontal and one vertical) on either side of IR6 in the outgoing-beam arms between the Q3 and Q4 magnets. The yellow pots are in sector 5, the blue ones in sector 6. Roman Pot type detectors are installed inside the beampipe causing an accelerator safety concern. To address this concern there is a limit to the allowable total beam current in the machine while Roman Pots are enabled to move closer to the beam. This limit was set to a motion limit of 5 mm from the center of the beampipe and 50 {center_dot} 10{sup 11} beam current per ring. In order to reduce the background in the detectors, beams were scraped using the RHIC collimator system prior to moving the pots closer. This was typically repeated several times throughout a store since beam halo reforms over the course of hours.

  3. Differential regulation of single CFTR channels by PP2C, PP2A, and other phosphatases.

    PubMed

    Luo, J; Pato, M D; Riordan, J R; Hanrahan, J W

    1998-05-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel activity declines rapidly when excised from transfected Chinese hamster ovary (CHO) or human airway cells because of membrane-associated phosphatase activity. In the present study, we found that CFTR channels usually remained active in patches excised from baby hamster kidney (BHK) cells overexpressing CFTR. Those patches with stable channel activity were used to investigate the regulation of CFTR by exogenous protein phosphatases (PP). Adding PP2A, PP2C, or alkaline phosphatase to excised patches reduced CFTR channel activity by > 90% but did not abolish it completely. PP2B caused weak deactivation, whereas PP1 had no detectable effect on open probability (Po). Interestingly, the time course of deactivation by PP2C was identical to that of the spontaneous rundown observed in some patches after excision. PP2C and PP2A had distinct effects on channel gating Po declined during exposure to exogenous PP2C (and during spontaneous rundown, when it was observed) without any change in mean burst duration. By contrast, deactivation by exogenous PP2A was associated with a dramatic shortening of burst duration similar to that reported previously in patches from cardiac cells during deactivation of CFTR by endogenous phosphatases. Rundown of CFTR-mediated current across intact T84 epithelial cell monolayers was insensitive to toxic levels of the PP2A inhibitor calyculin A. These results demonstrate that exogenous PP2C is a potent regulator of CFTR activity, that its effects on single-channel gating are distinct from those of PP2A but similar to those of endogenous phosphatases in CHO, BHK, and T84 epithelial cells, and that multiple protein phosphatases may be required for complete deactivation of CFTR channels.

  4. Texturing of polypropylene (PP) with nanosecond lasers

    NASA Astrophysics Data System (ADS)

    Riveiro, A.; Soto, R.; del Val, J.; Comesaña, R.; Boutinguiza, M.; Quintero, F.; Lusquiños, F.; Pou, J.

    2016-06-01

    Polypropylene (PP) is a biocompatible and biostable polymer, showing good mechanical properties that has been recently introduced in the biomedical field for bone repairing applications; however, its poor surface properties due to its low surface energy limit their use in biomedical applications. In this work, we have studied the topographical modification of polypropylene (PP) laser textured with Nd:YVO4 nanosecond lasers emitting at λ = 1064 nm, 532 nm, and 355 nm. First, optical response of this material under these laser wavelengths was determined. The application of an absorbing coating was also studied. The influence of the laser processing parameters on the surface modification of PP was investigated by means of statistically designed experiments. Processing maps to tailor the roughness, and wettability, the main parameters affecting cell adhesion characteristics of implants, were also determined. Microhardness measurements were performed to discern the impact of laser treatment on the final mechanical properties of PP.

  5. The Popularity of P&P

    ERIC Educational Resources Information Center

    Ruffins, Paul

    2006-01-01

    "Principles and Practices" (P&P), a real estate pre-licensing class, is one of the most popular courses in adult education, because it can literally be the key to the dual American dreams: striking it rich and owning a home. One of the things that makes the P&P class unique is that it is taught in so many different venues. The…

  6. {Delta} isobars and (p,p') reactions

    SciTech Connect

    Sammarruca, F.; Stephenson, E. J.

    2001-09-01

    We explore the role of coupling to {Delta} isobars (in both the N{Delta} and {Delta}{Delta} channels) in medium modifications of the effective NN interaction that drives 200-MeV proton inelastic scattering. A comparison of the predictions to natural-parity (p,p') cross section and analyzing power data show that isobar degrees of freedom in the medium generate overly repulsive effective interactions. Furthermore, this model extension is unable to resolve difficulties observed earlier describing polarization transfer measurements in some high-spin, unnatural-parity (p,p') transitions.

  7. New boundaries for the "ppK-" production in p+p collisions

    NASA Astrophysics Data System (ADS)

    Epple, Eliane

    2014-11-01

    The HADES collaboration has searched for the anti-kaonic nuclear cluster "ppK-" in p+p collisions by its decay into pΛ. In the course of this analysis several cross checks had to be performed. This report discusses two examples thereof. In one test it was checked whether the presence of background events could introduce a bias on the applied partial wave analysis. The second item discussed here is the extraction of the total pK+Λ production cross section necessary to derive the absolute upper limit on the "ppK-" production cross section.

  8. Structure-Activity Relationship Studies of Fostriecin, Cytostatin, and Key Analogs, with PP1, PP2A, PP5, and (β12–β13)-Chimeras (PP1/PP2A and PP5/PP2A), Provide Further Insight into the Inhibitory Actions of Fostriecin Family Inhibitors

    PubMed Central

    Swingle, Mark R.; Amable, Lauren; Lawhorn, Brian G.; Buck, Suzanne B.; Burke, Christopher P.; Ratti, Pukar; Fischer, Kimberly L.; Boger, Dale L.

    2009-01-01

    Fostriecin and cytostatin are structurally related natural inhibitors of serine/threonine phosphatases, with promising antitumor activity. The total synthesis of these antitumor agents has enabled the production of structural analogs, which are useful to explore the biological significance of features contained in the parent compounds. Here, the inhibitory activity of fostriecin, cytostatin, and 10 key structural analogs were tested in side-by-side phosphatase assays to further characterize their inhibitory activity against PP1c (Ser/Thr protein phosphatase 1 catalytic subunit), PP2Ac (Ser/Thr protein phosphatase 2A catalytic subunit), PP5c (Ser/Thr protein phosphatase 5 catalytic subunit), and chimeras of PP1 (Ser/Thr protein phosphatase 1) and PP5 (Ser/Thr protein phosphatase 5), in which key residues predicted for inhibitor contact with PP2A (Ser/Thr protein phosphatase 2A) were introduced into PP1 and PP5 using site-directed mutagenesis. The data confirm the importance of the C9-phosphate and C11-alcohol for general inhibition and further demonstrate the importance of a predicted C3 interaction with a unique cysteine (Cys269) in the β12–β13 loop of PP2A. The data also indicate that additional features beyond the unsaturated lactone contribute to inhibitory potency and selectivity. Notably, a derivative of fostriecin lacking the entire lactone subunit demonstrated marked potency and selectivity for PP2A, while having substantially reduced and similar activity against PP1 and PP1/PP2A- PP5/PP2A-chimeras that have greatly increased sensitivity to both fostriecin and cytostatin. This suggests that other features [e.g., the (Z,Z,E)-triene] also contribute to inhibitory selectivity. When considered together with previous data, these studies suggest that, despite the high structural conservation of the catalytic site in PP1, PP2A and PP5, the development of highly selective catalytic inhibitors should be feasible. PMID:19592665

  9. Heavy quark production in pp collisions

    SciTech Connect

    McGaughey, P.L.; Quack, E.; Ruuskanen, P.V. |

    1995-07-01

    A systematic study of the inclusive single heavy quark and heavy-quark pair production cross sections in pp collisions is presented for RHIC and LHC energies. We compare with existing data when possible. The dependence of the rates on the renormalization and factorization scales is discussed. Predictions of the cross sections are given for two different sets of parton distribution functions.

  10. Regulation of PP2A by Sphingolipid Metabolism and Signaling

    PubMed Central

    Oaks, Joshua; Ogretmen, Besim

    2014-01-01

    Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that is a primary regulator of cellular proliferation through targeting of proliferative kinases, cell cycle regulators, and apoptosis inhibitors. It is through the regulation of these regulatory elements that gives PP2A tumor suppressor functions. In addition to mutations on the regulatory subunits, the phosphatase/tumor suppressing activity of PP2A is also inhibited in several cancer types due to overexpression or modification of the endogenous PP2A inhibitors such as SET/I2PP2A. This review focuses on the current literature regarding the interactions between the lipid signaling molecules, selectively sphingolipids, and the PP2A inhibitor SET for the regulation of PP2A, and the therapeutic potential of sphingolipids as PP2A activators for tumor suppression via targeting SET oncoprotein. PMID:25642418

  11. Structure investigations of PP-PA blends

    NASA Astrophysics Data System (ADS)

    Janicki, Jaroslaw; Wlochowicz, Andrzej; Slusarczyk, Czeslaw

    1997-02-01

    In the paper we have used the SAXS method in order to determine the supermolecular structure parameters, including the transition layer thickness, of polypropylene/polyamide-6 (PP/PA) blends. The transition layer thickness has been obtained by means of two methods elaborated by Koberstein and co-workers and by Ruland, respectively. Both these methods assume that changes of the electron density in the transition region can be described by a Gaussian function with a standard deviation (sigma) . The parameter (sigma) have been determined graphically from the appropriate plots. Then, the thickness of the phase boundary E was estimated as (root)12(sigma) . The investigated PP/PA blends are multiphase systems and the problem of determination of the boundary width is more complicated because the meaning of Porod's law must be considered with caution. This problem is discussed based on wide range of the investigated samples prepared over various pressure and crystallization temperature conditions.

  12. Leishmania donovani phosphoproteins pp41 and pp29 re-establishes host protective immune response in visceral leishmaniasis.

    PubMed

    Das, Pranati; Amit, Ajay; Singh, Shubhankar Kumar; Chaudhary, Rajesh; Dikhit, Manas Ranjan; Yadav, Anupam; Pandey, Krishna; Das, Vidya Nand Rabi; Sundram, Shanty; Das, P; Bimal, Sanjiva

    2015-02-01

    As phospho proteins are reported to be involved in virulence and survival, the ability of Leishmania to inhibit macrophage effector functions may result from a direct interference of leishmanial molecules with macrophage signal transduction pathways. Several such proteins such as pp63, pp41 and pp29 have also been identified as a Th1 stimulatory protein in the Leishmania donovani. In the present study, the immunogenicity of a cocktail of pp63+pp41+pp29 was assessed by estimation of serum antibody titre, nitric oxide(NO) production, estimation of Th1 cytokine(IFN-γ) as well as Th2 cytokines(IL-4), and determination of parasite load in L. donovani infected mice. In the group immunized with antigenic cocktail there was a sharp rise in antibody titer up to Day 20 which reduced considerably by Day 50. Groups of mice vaccinated with pp63, pp41, pp29 and the antigenic cocktail expressed 10-fold, 16-fold, 22-fold and 25-fold increase respectively in NO production by splenocytes. The animal groups immunized with pp63, pp41, pp29 and the antigenic cocktail showed reduced parasite load in the liver and spleen, as well as increased IFN-gamma production in the spleen. Furthermore immunized animals remained with a normal hematological profile, whereas L. donovani in unimmunized mice lead to significant anemia.

  13. PP: A Lisp Pretty Printing System.

    DTIC Science & Technology

    1984-12-01

    level :length :lines :array :radix :circle :case : gensym This function is like PRIN1 except that it does not force ,PRINT-ESCAPE, to be T. The...PRINT-CASE, and ,PRINT- GENSYM , respectively. (’llhe last four of these variables are not supported by release 5 of the I isp Machine System...variables. PP:SET-INTERACTIVE-CONTROL-VARIABLES &key :escape :base :pretty :level :length :lines :array :radix :circle :case : gensym This function specifies

  14. Nuclear trafficking of the human cytomegalovirus pp71 (ppUL82) tegument protein

    SciTech Connect

    Shen Weiping; Westgard, Elizabeth; Huang Liqun; Ward, Michael D.; Osborn, Jodi L.; Chau, Nha H.; Collins, Lindsay; Marcum, Benjamin; Koach, Margaret A.; Bibbs, Jennifer; Semmes, O. John; Kerry, Julie A.

    2008-06-20

    The human cytomegalovirus tegument protein pp71 localizes to the nucleus immediately upon infection, and functions to initiate viral gene expression. Analysis of a series of random insertion mutations revealed that sequences within the mid region (MR) of pp71 are important for localization to the nucleus. Fusion of MR sequences with eGFP revealed that amino acids 94 to 300 were sufficient to target proteins to the nucleus. Random substitution mutagenesis within this domain resulted in two double substitution mutants, pp71P203T/T223M and pp71T228M/L275Q, with a predominantly cytoplasmic localization. Disruption of nuclear targeting resulted in relocalization of the fusion proteins to a distinct perinuclear region. Using tandem mass spectrometry, we determined that threonine 223 can be phosphorylated. Mutation of this residue to a phosphomimetic amino acid resulted in abrogation of nuclear targeting. These results strongly suggest that the intracellular trafficking of pp71 is regulated by phosphorylation.

  15. Exclusive pp{yields}pp{pi}{sup +{pi}-} reaction: From the threshold to LHC

    SciTech Connect

    Lebiedowicz, P.; Szczurek, A.

    2010-02-01

    We evaluate differential distributions for the four-body pp{yields}pp{pi}{sup +{pi}-} (and pp{yields}pp{pi}{sup +{pi}-}) reaction which constitutes an irreducible background to three-body processes pp{yields}ppM, where M are a broad resonances in the {pi}{sup +{pi}-} channel, e.g., M={sigma}, {rho}{sup 0}, f{sub 0}(980), f{sub 2}(1275), f{sub 0}(1500). We include both double-diffractive contribution (both Pomeron and Reggeon exchanges) as well as pion-pion rescattering contribution. The first process dominates at higher energies and small pion-pion invariant masses while the second becomes important at lower energies and higher pion-pion invariant masses. The amplitude(s) is(are) calculated in the Regge approach. We compare our results with measured cross sections for the Intersecting Storage Ring and Fermi National Accelerator Laboratory experiments. We make predictions for future experiments at the anti-Proton ANnihilation at DArmstadt (PANDA), Relativistic Heavy Ion Collider, Tevatron, and LHC energies. Differential distributions in invariant two-pion mass, pion rapidities and transverse momenta of pions are presented. The two-dimensional distribution in (y{sub {pi}}{sup +},y{sub {pi}}{sup -}) is particularly interesting. The higher the incident energy, the higher preference for the same-hemisphere emission of pions. The processes considered constitute a sizeable contribution to the total nucleon-nucleon cross section as well as to pion inclusive cross section.

  16. Cytomegalovirus pp65 limits dissemination but is dispensable for persistence

    SciTech Connect

    Malouli, Daniel; Hansen, Scott G.; Nakayasu, Ernesto S.; Marshall, Emily E.; Hughes, Colette M.; Ventura, Abigail B.; Gilbride, Roxanne M.; Lewis, Matthew S.; Xu, Guangwu; Kreklywich, Craig; Whizin, Nathan; Fischer, Miranda; Legasse, Alfred W.; Viswanathan, Kasinath; Siess, Don; Camp, David G.; Axthelm, Michael K.; Kahl, Christoph; DeFilippis, Victor R.; Smith, Richard D.; Streblow, Daniel N.; Picker, Louis J.; Früh, Klaus

    2014-04-01

    The tegument phosphoprotein pp65 (UL83) is the most abundant virion protein in human cytomegalovirus (HCMV). Since pp65 is immunodominant in persistently infected individuals, subunit vaccines against HCMV often include pp65 as T cell stimulatory component. Although HCMV pp65 is non-essential for viral growth in vitro it is thought to have an important role in primary and persistent infection since pp65 displays multiple immunomodulatory functions. To determine whether pp65 is required for infection and to evaluate its role in natural and vaccination-induced immunity we generated a rhesus CMV lacking both homologues, pp65a (Rh111) and pp65b (Rh112). Lack of pp65 resulted in a slight growth defect in vitro and an increase of defective particle formation. However, most pp65-deleted virions in the supernatant were phenotypically normal and proteomics analysis revealed that the ratios of the remaining viral proteins were largely unchanged. RhCMV Δpp65ab was able to persistently infect CMV-negative rhesus macaques (RM) and to super-infect RM previously infected with CMV. To determine whether T cells against pp65 are essential for protection against CMV, we challenged Δpp65ab-infected animals with RhCMV ΔUS2-11, a viral recombinant that lacks inhibitors of MHC-I antigen presentation and is thus unable to overcome CMV-specific T cell immunity. Despite a complete lack of pp65-specific T cells, Δpp65ab protected against ΔUS2-11 challenge suggesting that pp65-specific T cells are not essential for T cell immunity against CMV. Using the same approach we further demonstrate that pp65b-specific T cells, induced by heterologous prime/boost vaccination, are not sufficient to protect against ΔUS2-11 challenge. Our data provides a new approach to test the efficacy of subunit vaccine candidates and suggest that pp65 vaccines are insufficient to induce a T cell response that recapitulates the protective effect of natural infection.

  17. Leading neutrons from polarized pp collisions

    SciTech Connect

    Kopeliovich, B. Z.; Potashnikova, I. K.; Schmidt, Ivan; Soffer, J.

    2008-10-13

    We calculate the cross section and single-spin azimuthal asymmetry, A{sub n}(t) for inclusive neutron production in pp collisions at forward rapidities relative to the polarized proton. Absorptive corrections to the pion pole generate a relative phase between the spin-flip and non-flip amplitudes, which leads to an appreciable spin asymmetry. However, the asymmetry observed recently in the PHENIX experiment at RHIC at very small |t|{approx}0.01 GeV{sup 2} cannot be explained by this mechanism.

  18. Collective phenomena in pp and ep scattering

    NASA Astrophysics Data System (ADS)

    Celiberto, Francesco Giovanni; Fiore, Roberto; Jenkovszky, László

    2017-03-01

    Bjorken scaling violation in deep inelastic electron-proton scattering (DIS) is related to the rise of hadronic cross sections by using the additive quark model. Of special interest is the connection between saturation in the low-x behavior of the DIS structure functions (SF) and possible slow-down of the pp cross section rise due to saturation effects. We also identify saturation effects in the DIS SF with phase transition that can be described by the Van der Waals equation of state.

  19. PP-O and PP-V, Monascus pigment homologues, production, and phylogenetic analysis in Penicillium purpurogenum.

    PubMed

    Arai, Teppei; Kojima, Ryo; Motegi, Yoshiki; Kato, Jun; Kasumi, Takafumi; Ogihara, Jun

    2015-12-01

    The production of pigments as secondary metabolites by microbes is known to vary by species and by physiological conditions within a single strain. The fungus strain Penicillium purpurogenum IAM15392 has been found to produce violet pigment (PP-V) and orange pigment (PP-O),Monascus azaphilone pigment homologues, when grown under specific culture conditions. In this study, we analysed PP-V and PP-O production capability in seven strains of P. purpurogenum in addition to strain IAM15392 under specific culture conditions. The pigment production pattern of five strains cultivated in PP-V production medium was similar to that of strain IAM15392, and all violet pigments produced by these five strains were confirmed to be PP-V. Strains that did not produce pigment were also identified. In addition, two strains cultivated in PP-O production medium produced a violet pigment identified as PP-V. The ribosomal DNA (rDNA) internal transcribed spacer (ITS) region sequences from the eight P. purpurogenum strains were sequenced and used to construct a neighbor-joining phylogenetic tree. PP-O and PP-V production of P. purpurogenum was shown to be related to phylogenetic placement based on rDNA ITS sequence. Based on these results, two hypotheses for the alteration of pigment production of P. purpurogenum in evolution were proposed.

  20. Development and characterization of antibacterial nanocomposite fiber based on PP/PET/nanosilver compatibilized with PP-g-MA

    NASA Astrophysics Data System (ADS)

    Barzegar, A.; Golshan Ebrahimi, N.

    2010-03-01

    The polypropylene (PP) /polyethylene terephthalate (PET) /Nanosilver (Ag) nanocomposite fibers were prepared for the achievement of permanent antibacterial activity to common synthetic textile. The fibers were melt-spun by co-extrusion of PP/PET with compatibilizer (PP-g-MA) as core and PP/Ag master-batches as sheath and vice versa then fiber formation was carried out through the spinneret. The effects of content PP-g-MA as compatibilizer were also investigated. The morphology and mechanical properties of uncompatibilized and compatibilized PP/PET fibers were comprehensively assessed utilizing scanning electron microscopy (SEM) and tensile test experiments. It was observed that the fibrillar distributed morphology achieved at 3.5 Wt% of PP-g-MA has a significant performance. The antibacterial activity of nanosilver in fibers was evaluated after certain contact time and calculated by percent reduction of two kinds of bacteria; Staphylococus aureus and Escherichia coli. The antibacterial efficacy of spun fibers was excellent when the masterbatch used as the sheath. The SEM micrograph of these fibers (PP/ PP-g-MA/PET)/(PP/Nanosilver) shows nearly good distribution of nanosilver particles with little aggregation. Mechanical and antibacterial properties data have also shown that the fiber has a significant performance when the master-batch used as the sheath.

  1. Psychosine induces the dephosphorylation of neurofilaments by deregulation of PP1 and PP2A phosphatases

    PubMed Central

    Cantuti-Castelvetri, Ludovico; Zhu, Hongling; Givogri, Maria I.; Chidavaenzi, Robstein L.; Lopez-Rosas, Aurora; Bongarzone, Ernesto R.

    2012-01-01

    Patients with Krabbe disease, a genetic demyelinating syndrome caused by deficiency of galactosyl-ceramidase and the resulting accumulation of galactosyl-sphingolipids, develop signs of a dying-back axonopathy compounded by a deficiency of large-caliber axons. Here, we show that axonal caliber in Twitcher mice, an animal model for Krabbe disease, is impaired in peripheral axons and is accompanied by a progressive reduction in the abundance and phosphorylation of the three neurofilament (NF) subunits. These changes correlate with an increase in the density of NFs per cross-sectional area in numerous mutant peripheral axons and abnormal increases in the activity of two serine/threonine phosphatases (PP1 and PP2A) in mutant tissue. Similarly, acutely isolated mutant cortical neurons show abnormal phosphorylation of NFs. Psychosine, the neurotoxin accumulated in Krabbe disease, was sufficient to induce abnormal dephosphorylation of NF subunits in a normal motor neuron cell line as well as in acutely isolated normal cortical neurons. This in vitro effect was mediated by PP1 and PP2A, which specifically dephosphorylated NFs. These results demonstrate that the reduced caliber observed in some axons in Krabbe disease involves abnormal dephosphorylation of NFs. We propose that a psychosine-driven pathogenic mechanism through deregulated phosphotransferase activities may be involved in this process. PMID:22326830

  2. The extended PP1 toolkit: designed to create specificity

    PubMed Central

    Bollen, Mathieu; Peti, Wolfgang; Ragusa, Michael J.; Beullens, Monique

    2011-01-01

    Protein Ser/Thr phosphatase-1 (PP1) catalyzes the majority of eukaryotic protein dephosphorylation reactions in a highly regulated and selective manner. Recent studies have identified an unusually diversified PP1 interactome with the properties of a regulatory toolkit. PP1-interacting proteins (PIPs) function as targeting subunits, substrates and/or inhibitors. As targeting subunits, PIPs contribute to substrate selection by bringing PP1 into the vicinity of specific substrates and by modulating substrate specificity via additional substrate docking sites or blocking substrate-binding channels. Many of the nearly 200 established mammalian PIPs are predicted to be intrinsically disordered, a property that facilitates their binding to a large surface area of PP1 via multiple docking motifs. These novel insights offer perspectives for the therapeutic targeting of PP1 by interfering with the binding of PIPs or substrates. PMID:20399103

  3. Effects of overlapping strings in pp collisions

    DOE PAGES

    Bierlich, Christian; Gustafson, Gösta; Lönnblad, Leif; ...

    2015-03-26

    In models for hadron collisions based on string hadronization, the strings are usually treated as independent, allowing no interaction between the confined colour fields. In studies of nucleus collisions it has been suggested that strings close in space can fuse to form "colour ropes." Such ropes are expected to give more strange particles and baryons, which also has been suggested as a signal for plasma formation. Overlapping strings can also be expected in pp collisions, where usually no phase transition is expected. In particular at the high LHC energies the expected density of strings is quite high. To investigate possiblemore » effects of rope formation, we present a model in which strings are allowed to combine into higher multiplets, giving rise to increased production of baryons and strangeness, or recombine into singlet structures and vanish. Also a crude model for strings recombining into junction structures is considered, again giving rise to increased baryon production. The models are implemented in the DIPSY MC event generator, using PYTHIA8 for hadronization, and comparison to pp minimum bias data, reveals improvement in the description of identified particle spectra.« less

  4. Effects of overlapping strings in pp collisions

    SciTech Connect

    Bierlich, Christian; Gustafson, Gösta; Lönnblad, Leif; Tarasov, Andrey

    2015-03-26

    In models for hadron collisions based on string hadronization, the strings are usually treated as independent, allowing no interaction between the confined colour fields. In studies of nucleus collisions it has been suggested that strings close in space can fuse to form "colour ropes." Such ropes are expected to give more strange particles and baryons, which also has been suggested as a signal for plasma formation. Overlapping strings can also be expected in pp collisions, where usually no phase transition is expected. In particular at the high LHC energies the expected density of strings is quite high. To investigate possible effects of rope formation, we present a model in which strings are allowed to combine into higher multiplets, giving rise to increased production of baryons and strangeness, or recombine into singlet structures and vanish. Also a crude model for strings recombining into junction structures is considered, again giving rise to increased baryon production. The models are implemented in the DIPSY MC event generator, using PYTHIA8 for hadronization, and comparison to pp minimum bias data, reveals improvement in the description of identified particle spectra.

  5. Strangeness production in AA and pp collisions

    NASA Astrophysics Data System (ADS)

    Castorina, Paolo; Satz, Helmut

    2016-07-01

    Boost-invariant hadron production in high-energy collisions occurs in causally disconnected regions of finite space-time size. As a result, globally conserved quantum numbers (charge, strangeness, baryon number) are conserved locally in spatially restricted correlation clusters. Their size is determined by two time scales: the equilibration time specifying the formation of a quark-gluon plasma, and the hadronization time, specifying the onset of confinement. The expected values for these scales provide the theoretical basis for the suppression observed for strangeness production in elementary interactions ( pp , e^+e^- below LHC energies. In contrast, the space-time superposition of individual collisions in high-energy heavy-ion interactions leads to higher energy densities, resulting in much later hadronization and hence much larger hadronization volumes. This largely removes the causality constraints and results in an ideal hadronic resonance gas in full chemical equilibrium. In the present paper, we determine the collision energies needed for that; we also estimate when pp collisions reach comparable hadronization volumes and thus determine when strangeness suppression should disappear there as well.

  6. Study of the decay mechanism for B→pp¯K and B→pp¯π

    NASA Astrophysics Data System (ADS)

    Belle Collaboration; Wei, J.-T.; Wang, M.-Z.; Adachi, I.; Aihara, H.; Aulchenko, V.; Aushev, T.; Bakich, A. M.; Balagura, V.; Barberio, E.; Bay, A.; Belous, K.; Bitenc, U.; Bondar, A.; Bozek, A.; Bračko, M.; Browder, T. E.; Chang, P.; Chao, Y.; Chen, A.; Chen, K.-F.; Cheon, B. G.; Chiang, C.-C.; Cho, I.-S.; Choi, Y.; Choi, Y. K.; Cole, S.; Danilov, M.; Dash, M.; Drutskoy, A.; Eidelman, S.; Fratina, S.; Gabyshev, N.; Golob, B.; Ha, H.; Haba, J.; Hara, T.; Hayasaka, K.; Hayashii, H.; Hazumi, M.; Heffernan, D.; Hokuue, T.; Hoshi, Y.; Hsiung, Y. B.; Hyun, H. J.; Iijima, T.; Ikado, K.; Inami, K.; Ishikawa, A.; Itoh, R.; Iwasaki, M.; Iwasaki, Y.; Kah, D. H.; Kang, J. H.; Katayama, N.; Kawai, H.; Kawasaki, T.; Kichimi, H.; Kim, Y. J.; Kinoshita, K.; Korpar, S.; Križan, P.; Krokovny, P.; Kumar, R.; Kuo, C. C.; Kuzmin, A.; Kwon, Y.-J.; Lee, J. S.; Lee, S. E.; Lesiak, T.; Lin, S.-W.; Liu, Y.; Liventsev, D.; Mandl, F.; Matsumoto, T.; Matyja, A.; McOnie, S.; Medvedeva, T.; Mitaroff, W.; Miyabayashi, K.; Miyake, H.; Miyata, H.; Miyazaki, Y.; Mizuk, R.; Nagasaka, Y.; Nakano, E.; Nakao, M.; Nishida, S.; Nitoh, O.; Ogawa, S.; Ohshima, T.; Okuno, S.; Olsen, S. L.; Ozaki, H.; Pakhlov, P.; Pakhlova, G.; Park, C. W.; Park, H.; Park, K. S.; Pestotnik, R.; Piilonen, L. E.; Sahoo, H.; Sakai, Y.; Schneider, O.; Schümann, J.; Seidl, R.; Senyo, K.; Sevior, M. E.; Shapkin, M.; Shibuya, H.; Shiu, J.-G.; Singh, J. B.; Sokolov, A.; Somov, A.; Stanič, S.; Starič, M.; Sumiyoshi, T.; Tajima, O.; Takasaki, F.; Tamai, K.; Tanaka, M.; Taylor, G. N.; Teramoto, Y.; Tian, X. C.; Tikhomirov, I.; Tsuboyama, T.; Uehara, S.; Ueno, K.; Uglov, T.; Unno, Y.; Uno, S.; Urquijo, P.; Varner, G.; Varvell, K. E.; Vervink, K.; Villa, S.; Vinokurova, A.; Wang, C. C.; Wang, C. H.; Wang, P.; Watanabe, Y.; Wedd, R.; Won, E.; Yamaguchi, A.; Yamashita, Y.; Yamauchi, M.; Zhang, C. C.; Zhang, Z. P.; Zhilich, V.; Zupanc, A.

    2008-01-01

    We study the characteristics of the low mass pp¯ enhancements near threshold in the three-body decays B→pp¯K and B→pp¯π. We observe that the proton polar angle distributions in the pp¯ helicity frame in the two decays have the opposite polarity, and measure the forward-backward asymmetries as a function of the pp¯ mass for the pp¯K mode. We also search for the intermediate two-body decays, B→p¯Δ and B→pΔ, and set upper limits on their branching fractions. These results are obtained from a 414 fb data sample that contains 449×10BB¯ events collected near the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy ee collider.

  7. /bar p/p collider physics

    SciTech Connect

    Green, D.

    1989-03-01

    This note encompasses a set of six lectures given at the summer school held at Campos Do Jordao in January of 1989 near Sao Paulo, Brazil. The intent of the lectures was to describe the physics of /bar p/p at CERN and Fermilab. Particular attention has been paid to making a self contained presentation to a prospective audience of graduate students. Since large Monte Carlo codes might not be available to all members of this audience, great reliance was placed on ''back of the envelope estimates.'' Emphasis was also placed on experimental data rather than theoretical speculation, since predictions for, for example, supersymmetric particle production are easily obtained by transcription of formulae already obtained. 9 refs., 67 figs., 2 tabs.

  8. {lambda}0 Polarization in Exclusive pp Reactions

    SciTech Connect

    Felix, J.

    2006-09-25

    Among all properties of baryons, the polarization they acquire when created from unpolarized p-nucleus collisions is the most recent discovered one; so far, the origin of this polarization remains unexplained in spite of the experimental evidences accumulated in the past thirty years. Up to these days, {lambda}0 is the most studied baryon for polarization, due to it is very easy to produce {lambda}0's at the energies of the principal high energy physics accelerators of the world. This article is a review of the experimental experience accumulated on the polarization of {lambda}0 in unpolarized exclusive pp collisions as function of xF, PT, and M({lambda}0K+) in the past fifteen years here at the Instituto de Fisica, Universidad de Guanajuato, inside Fermilab e690 and Brookhaven National Laboratory e766 collaborations.

  9. Setting the scale of the pp and pp total cross sections using AdS/QCD

    SciTech Connect

    Domokos, Sophia K.; Harvey, Jeffrey A.; Mann, Nelia

    2010-11-15

    This paper is an addendum to earlier work where we computed the Pomeron contribution to pp and pp scattering in AdS/QCD. Our model for pp scattering in the Regge regime depends on four parameters: the slope and intercept of the Pomeron trajectory {alpha}{sub c}{sup '}, {alpha}{sub c}(0), a mass scale M{sub d}, which determines a form factor entering into matrix elements of the energy-momentum tensor, and a coupling {lambda}{sub P} between the lightest spin-two glueball and the proton, which sets the overall scale of the total cross section. Here we perform a more detailed computation of {lambda}{sub P} in the Sakai-Sugimoto model by using the construction of nucleons as instantons of the dual 5D gauge theory and an effective 5D fermion description of these nucleons which has been successfully used to compute a variety of nucleon-meson couplings. We find {lambda}{sub P,SS{approx_equal}}6.38 GeV{sup -1}, which is in reasonable agreement with the value {lambda}{sub P,fit}=8.28 GeV{sup -1} determined by fitting single Pomeron exchange to data.

  10. Comparison of forward and backward pp pair knockout in 3He(e,e'pp)n

    DOE PAGES

    Baghdasaryan, H.; Weinstein, L. B.; Laget, J. M.; ...

    2012-06-21

    Measuring nucleon-nucleon Short Range Correlations (SRC) has been a goal of the nuclear physics community for many years. They are an important part of the nuclear wavefunction, accounting for almost all of the high-momentum strength. They are closely related to the EMC effect. While their overall probability has been measured, measuring their momentum distributions is more difficult. In order to determine the best configuration for studying SRC momentum distributions, we measured the 3He(e,e'pp)n reaction, looking at events with high momentum protons (pp > 0.35 GeV/c) and a low momentum neutron (pn < 0.2 GeV/c). We examined two angular configurations: eithermore » both protons emitted forward or one proton emitted forward and one backward (with respect to the momentum transfer, →q). Thus, the measured relative momentum distribution of the events with one forward and one backward proton was much closer to the calculated initial-state pp relative momentum distribution, indicating that this is the preferred configuration for measuring SRC.« less

  11. Isoliensinine induces dephosphorylation of NF-κB p65 subunit at Ser536 via a PP2A-dependent mechanism in hepatocellular carcinoma cells: roles of impairing PP2A/I2PP2A interaction

    PubMed Central

    Shu, Guangwen; Zhang, Lang; Jiang, Shanqing; Cheng, Zhuo; Wang, Guan; Huang, Xu; Yang, Xinzhou

    2016-01-01

    Our previous study discovered that isoliensinine (isolie) triggers hepatocellular carcinoma (HCC) cell apoptosis via inducing p65 dephosphorylation at Ser536 and inhibition of NF-κB. Here, we showed that isolie promoted p65/PP2A interaction in vitro and in vivo. Repression of PP2A activity or knockdown of the expression of PP2A-C (the catalytic subunit of PP2A) abrogated isolie-provoked p65 dephosphorylation. I2PP2A is an endogenous PP2A inhibitor. Isolie directly impaired PP2A/I2PP2A interaction. Knockdown of I2PP2A boosted p65/PP2A association and p65 dephosphorylation. Overexpression of I2PP2A restrained isolie-induced p65 dephosphorylation. Untransformed hepatocytes were insensitive to isolie-induced NF-κB inhibition and cell apoptosis. In these cells, basal levels of I2PP2A and p65 phosphorylation at Ser536 were lower than in HCC cells. These findings collectively indicated that isolie suppresses NF-κB in HCC cells through impairing PP2A/I2PP2A interaction and stimulating PP2A-dependent p65 dephosphorylation at Ser536. PMID:27244888

  12. Isoliensinine induces dephosphorylation of NF-kB p65 subunit at Ser536 via a PP2A-dependent mechanism in hepatocellular carcinoma cells: roles of impairing PP2A/I2PP2A interaction.

    PubMed

    Shu, Guangwen; Zhang, Lang; Jiang, Shanqing; Cheng, Zhuo; Wang, Guan; Huang, Xu; Yang, Xinzhou

    2016-06-28

    Our previous study discovered that isoliensinine (isolie) triggers hepatocellular carcinoma (HCC) cell apoptosis via inducing p65 dephosphorylation at Ser536 and inhibition of NF-κB. Here, we showed that isolie promoted p65/PP2A interaction in vitro and in vivo. Repression of PP2A activity or knockdown of the expression of PP2A-C (the catalytic subunit of PP2A) abrogated isolie-provoked p65 dephosphorylation. I2PP2A is an endogenous PP2A inhibitor. Isolie directly impaired PP2A/I2PP2A interaction. Knockdown of I2PP2A boosted p65/PP2A association and p65 dephosphorylation. Overexpression of I2PP2A restrained isolie-induced p65 dephosphorylation. Untransformed hepatocytes were insensitive to isolie-induced NF-κB inhibition and cell apoptosis. In these cells, basal levels of I2PP2A and p65 phosphorylation at Ser536 were lower than in HCC cells. These findings collectively indicated that isolie suppresses NF-κB in HCC cells through impairing PP2A/I2PP2A interaction and stimulating PP2A-dependent p65 dephosphorylation at Ser536.

  13. Properties of PP/MWCNT-COOH /PP composites made by melt mixing versus solution cast /melt mixing methods

    NASA Astrophysics Data System (ADS)

    Reinholds, I.; Roja, Z.; Zicans, J.; Merijs Meri, R.; Bitenieks, J.

    2015-03-01

    An approach on improvement of the properties of polypropylene / carbon nanotube (PP/CNT) composites is reported. PP blend compositions with carboxylic acid functionalized multi-walled carbon nanotubes (MWCNT-COOH) at filler content 1.0 wt.% were researched. One part of the composites was manufactured by direct thermoplastic mixing PP with the filler, but the other one was made from solution casted masterbatch with the following thermoplastic mixing. An increase of mechanical properties (Young's modulus, storage modulus and tensile strength), compared to an increase of glass transition temperature indicated a reinforcement effect of CNTs on PP matrix, determined from the tensile tests and differential mechanical analysis (DMA), while the elongation was reduced, compared to PP matrix. By differential scanning calorimetry (DSC) analysis, the effect of nanofiller on the reorganization of PP crystallites was observed. A noticeable enhanced effect on increase of the crystallization temperature was indicated for masterbatch manufactured composite. An increase of thermal stability was also observed, compared to pristine PP and the composite made by direct thermoplastic mixing PP with the filler.

  14. The PP2A inhibitor I2PP2A is essential for sister chromatid segregation in oocyte meiosis II.

    PubMed

    Chambon, Jean-Philippe; Touati, Sandra A; Berneau, Stéphane; Cladière, Damien; Hebras, Céline; Groeme, Rachel; McDougall, Alex; Wassmann, Katja

    2013-03-18

    Haploid gametes are generated through two consecutive meiotic divisions, with the segregation of chromosome pairs in meiosis I and sister chromatids in meiosis II. Separase-mediated stepwise removal of cohesion, first from chromosome arms and later from the centromere region, is a prerequisite for maintaining sister chromatids together until their separation in meiosis II [1]. In all model organisms, centromeric cohesin is protected from separase-dependent removal in meiosis I through the activity of PP2A-B56 phosphatase, which is recruited to centromeres by shugoshin/MEI-S332 (Sgo) [2-5]. How this protection of centromeric cohesin is removed in meiosis II is not entirely clear; we find that all the PP2A subunits remain colocalized with the cohesin subunit Rec8 at the centromere of metaphase II chromosomes. Here, we show that sister chromatid separation in oocytes depends on a PP2A inhibitor, namely I2PP2A. I2PP2A colocalizes with the PP2A enzyme at centromeres at metaphase II, independently of bipolar attachment. When I2PP2A is depleted, sister chromatids fail to segregate during meiosis II. Our findings demonstrate that in oocytes I2PP2A is essential for faithful sister chromatid segregation by mediating deprotection of centromeric cohesin in meiosis II.

  15. Expression of human cytomegalovirus pp150 gene in transgenic Vicia faba L. and immunogenicity of pp150 protein in mice.

    PubMed

    Yan, Hua; Yan, Huishen; Li, Guocai; Gong, Weijuan; Jiao, Hongmei; Chen, Hongju; Ji, Mingchun

    2010-03-01

    The pp150 gene of human cytomegalovirus (HCMV) was transferred into Vicia faba plants by Agrobacterium tumefaciens-mediated transformation. Three of five hygromycin resistant V. faba plants were identified as positive by PCR and dot-blot hybridization. The ELISA results indicated that pp150 protein from three plants of transformed V. faba leaves and seeds made up 0.005-0.015% of the total soluble protein. The results of detection by immunoblot and inhibition of immunofluorescent assay (IFA) showed that pp150 soluble protein had immunity activity. HCMV pp150-specific antibody (IgG, IgA) and IFN-gamma producing T cells were detected in 100% of the mice immunized with pp150 transgenic V. faba seeds by ELISA and intracellular staining and flow cytometry analysis, respectively. The transgenic V. faba plants will provide new material for the development of edible vaccination against HCMV infection.

  16. EMODnet Physical Parameters (EMODNet PP) Portal

    NASA Astrophysics Data System (ADS)

    Novellino, A.; Schaap, D.; Manzella, G. M. R.; Pouliquen, S.; Gorringe, P.

    2012-04-01

    In December 2007 the European Parliament and Council adopted a common text for the Marine Strategy Framework Directive which aims to achieve environmentally healthy marine waters by 2020. This Directive includes an initiative for an overarching European Marine Observation and Data Network (EMODNet). During the one-year consultation phase that followed the release of the EU Green Paper on a Future Maritime Policy for the European Union, stakeholders gave an overwhelming positive response. Facilitating access to high quality marine data will resolve difficulties and stimulate an expansion of value-added public and commercial services, lay the foundations for sound governance and reduce uncertainties on human impact on the planet as well as of forecasts relating to the future state of the marine environment. Better and linked marine data will have an immediate impact on the planning of environmental policy and mitigation measures, and will also facilitate impact assessments and scientific work. The overall objectives of the EMODnet Physical Parameters (EMODNet PP) preparatory action is to provide access to archived and near real-time data on physical conditions in Europe's seas and oceans by means of a dedicated Pilot Portal and to determine how well the data meet the needs of users from industry, public authorities and scientists. The latter implicates that it is also an objective to identify data gaps and arguments why these gaps should be filled in future monitoring. This project will contribute towards the definition of an operational European Marine Observation and Data Network (EMODnet). This is done done by: 1. providing through a portal: a. access to marine data from measurement stations and ferryboxes. Both near real-time and archived data of time series are to be made available. b. metadata for these data sets using EMODnet/INSPIRE standards. c. metadata maps and overviews for whole sea-basins showing the availability of data and monitoring intensity of that

  17. Intracellular uptake and behavior of two types zinc protoporphyrin (ZnPP) micelles, SMA-ZnPP and PEG-ZnPP as anticancer agents; unique intracellular disintegration of SMA micelles.

    PubMed

    Nakamura, Hideaki; Fang, Jun; Gahininath, Bharate; Tsukigawa, Kenji; Maeda, Hiroshi

    2011-11-07

    SMA-ZnPP and PEG-ZnPP are micellar drugs, encapsulating zinc protoporphyrin IX (ZnPP) with styrene maleic acid copolymer (SMA) and covalent conjugate of ZnPP with polyethylene glycol (PEG) respectively. Their intracellular uptake rate and subcellular localization were investigated. We found SMA-ZnPP showed higher and more efficient (about 2.5 times) intracellular uptake rate than PEG-ZnPP, although both SMA-ZnPP and PEG-ZnPP micelles were localized at endoplasmic reticulum (ER) and inhibited the target enzyme heme oxygenase 1 (HO-1) similarly. Both micellar ZnPP were taken up into the tumor cells by endocytosis. Furthermore SMA-ZnPP and PEG-ZnPP were examined for their drug releasing mechanisms. Liberation of ZnPP from the SMA micelle appears to depend on cellular amphiphilic components such as lecithin, while that for PEG-ZnPP depends on hydrolytic cleavage. These results indicate that these micelle formulations make water insoluble ZnPP to water soluble practical anticancer agents.

  18. ALA-induced PpIX fluorescence in epileptogenic tissue

    NASA Astrophysics Data System (ADS)

    Kleen, Jonathan K.; Valdes, Pablo A.; Harris, Brent T.; Holmes, Gregory L.; Paulsen, Keith D.; Roberts, David W.

    2011-03-01

    Astrogliotic tissue displays markedly increased levels of ALA-induced PpIX fluorescence, making it useful for fluorescence-guided resection in glioma surgery. In patients with temporal lobe epilepsy (TLE) and corresponding animal models, there are areas of astrogliosis that often co-localize with the epileptic focus, which can be resected to eliminate seizures in the majority of treated patients. If this epileptogenic tissue can exhibit PpIX fluorescence that is sufficiently localized, it could potentially help identify margins in epilepsy surgery. We tested the hypothesis that ALA-induced PpIX fluorescence could visually accentuate epileptogenic tissue, using an established animal model of chronic TLE. An acute dose of pilocarpine was used to induce chronic seizure activity in a rat. This rat and a normal control were given ALA, euthanized, and brains examined post-mortem for PpIX fluorescence and neuropathology. Preliminary evidence indicates increased PpIX fluorescence in areas associated with chronic epileptic changes and seizure generation in TLE, including the hippocampus and parahippocampal areas. In addition, strong PpIX fluorescence was clearly observed in layer II of the piriform cortex, a region known for epileptic reorganization and involvement in the generation of seizures in animal studies. We are further investigating whether ALA-induced PpIX fluorescence can consistently identify epileptogenic zones, which could warrant the extension of this technique to clinical studies for use as an adjuvant guidance technology in the resection of epileptic tissue.

  19. PP composites with Hybrid Nanofillers: NTC phenomenon

    NASA Astrophysics Data System (ADS)

    Sarlin, Juha; Immonen, Kirsi

    2010-06-01

    Electric conductive plastic composites have a wide potential for commercial applications, some examples are EMI shielding housings and components in automotive industry and in consumer electronics, equipments in health care sector and fuel cell components. A phenomenon in conductive composites, especially in composites with carbon based fillers, is change of thermal induced change in conductivity as a result of morphological transitions. Usually the observed changes are practically irreversible. The phenomenon may cause increasing resistivity, usually called as "positive temperature coefficient" (PTC) or decreasing resistivity, called "negative temperature coefficient (NTC), where the new morphology created by heat treatment is more favorable for electric conductivity compared to the original state. The existence of NTC is a sing of the lost potential in material design and processing. Therefore detailed information about the phenomenon gives us tools to develop high performance conductive materials. It this paper we discuss about NTC phenomenon observed in PP composites with CNT or in-situ synthesized CNT-PANi hybrid nanofiller with an amphiphilic dispersing agent. The goal of the paper is not to present a comprehensive model of this phenomenon; we present some experimental results which may be related to polymer-filler interactions. These details are a part of this complicated phenomenon.

  20. PP and PS interferometric images of near-seafloor sediments

    USGS Publications Warehouse

    Haines, S.S.

    2011-01-01

    I present interferometric processing examples from an ocean-bottom cable OBC dataset collected at a water depth of 800 m in the Gulf of Mexico. Virtual source and receiver gathers created through cross-correlation of full wavefields show clear PP reflections and PS conversions from near-seafloor layers of interest. Virtual gathers from wavefield-separated data show improved PP and PS arrivals. PP and PS brute stacks from the wavefield-separated data compare favorably with images from a non-interferometric processing flow. ?? 2011 Society of Exploration Geophysicists.

  1. Ambient Metrics for n-Dimensional pp-Waves

    NASA Astrophysics Data System (ADS)

    Leistner, Thomas; Nurowski, Pawel

    2010-06-01

    We provide an explicit formula for the Fefferman-Graham ambient metric of an n-dimensional conformal pp-wave in those cases where it exists. In even dimensions we calculate the obstruction explicitly. Furthermore, we describe all 4-dimensional pp-waves that are Bach-flat, and give a large class of Bach-flat examples which are conformally Cotton-flat, but not conformally Einstein. Finally, as an application, we use the obtained ambient metric to show that even-dimensional pp-waves have vanishing critical Q-curvature.

  2. Synthesis of PP-g-MA as compatibilizer for PP/PLA biocomposites: Thermal, mechanical and biodegradability properties

    NASA Astrophysics Data System (ADS)

    Ghozali, Muhammad; Rohmah, Elfi Nur

    2017-01-01

    A synthesis of polypropylene-graft-maleic anhydride (PP-g-MA) with benzoyl peroxide (BPO) as an initiator has been conducted in a stainless-steel reactor at 120°C for 1 hours. The composition of maleic anhydride (MA) was varied between 10-40 phr, whereas BPO was between 0.5-2.0 phr. The grafting degree (GD) was determined by calculating the MA monomer grafted into polypropylene (PP). Fourier Transform Infrared (FTIR) analysis was performed to study the functional group in the copolymer PP-g-MA. The result shows that the highest GD of 11.85% was obtained when the use of MA and BPO are 40 phr and 1 phr, respectively. PP/PLA biocomposites have been manufactured by adding polypropylene (PP), polylactic acid (PLA) and PP-g-MA as compatibilizer into rheomix at a temperature of 200-210°C with a stirring speed of 25 rpm for 7-10 minutes. PP/PLA biocomposites were varied at a ratio of 0/100, 20/80, 40/60, 60/40, 80/20 and 100/0. Fourier Transform Infrared (FTIR), Ultimate Testing Machine (UTM), Thermogravimetric Analysis (TGA) and biodegradation analysis were performed to determine the functional groups, thermal stability, tensile strength and the biodegradability level of PP/PLA biocomposites, respectively. Thermal and mechanical analysis results indicate that the addition of PLA into PP/PLA biocomposites can reduce the thermal stability and mechanical properties, however the biodegradability is increased.

  3. Protein phosphatase 2A family members (PP2A and PP6) associate with U1 snRNP and the spliceosome during pre-mRNA splicing

    PubMed Central

    Kamoun, Malek; Filali, Mohammed; Murray, Michael V.; Awasthi, Sita; Wadzinski, Brian E.

    2013-01-01

    Protein phosphorylation and dephosphorylation are both important for multiple steps in the splicing pathway. Members of the PP1 and PP2A subfamilies of phospho-serine/threonine phosphatases play essential but redundant roles in the second step of the splicing reaction. PP6, a member of the PP2A subfamily, is the mammalian homologue of yeast Sit4p and ppe1, which are involved in cell cycle regulation; however, the involvement of PP6 in the splicing pathway remains unclear. Here we show that PP2A family members physically associate with the spliceosome throughout the splicing reaction. PP2A holoenzyme and PP6 were found stably associated with U1 snRNP. Together our findings indicate that these phosphatases regulate splicing catalysis involving U1 snRNP and suggest an important evolutionary conserved role of PP2A family phosphatases in pre-mRNA splicing. PMID:24064353

  4. Surface treated polypropylene (PP) fibres for reinforced concrete

    SciTech Connect

    López-Buendía, Angel M.; Romero-Sánchez, María Dolores; Climent, Verónica

    2013-12-15

    Surface treatments on a polypropylene (PP) fibre have contributed to the improvement of fibre/concrete adhesion in fibre-reinforced concrete. The treatments to the PP fibre were characterized by contact angle measurements, ATR-IR and XPS to analyse chemical alterations. The surface topography and fibre/concrete interaction were analysed by several microscopic techniques, namely optical petrographic, and scanning electron microscopy. Treatment modified the surface chemistry and topography of the fibre by introducing sodium moieties and created additional fibre surface roughness. Modifications in the fibre surface led to an increase in the adhesion properties between the treated fibres and concrete and an improvement in the mechanical properties of the fibre-reinforced concrete composite as compared to the concrete containing untreated PP fibres. Compatibility with the concrete and increased roughness and mineral surface was also improved by nucleated portlandite and ettringite mineral association anchored on the alkaline PP fibre surface, which is induced during treatment.

  5. Mitotic exit: Determining the PP2A dephosphorylation program.

    PubMed

    Pereira, Gislene; Schiebel, Elmar

    2016-08-29

    In mitotic exit, proteins that were highly phosphorylated are sequentially targeted by the phosphatase PP2A-B55, but what underlies substrate selection is unclear. In this issue, Cundell et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201606033) identify the determinants of PP2A-B55's dephosphorylation program, thereby influencing spindle disassembly, nuclear envelope reformation, and cytokinesis.

  6. Mitotic exit: Determining the PP2A dephosphorylation program

    PubMed Central

    2016-01-01

    In mitotic exit, proteins that were highly phosphorylated are sequentially targeted by the phosphatase PP2A-B55, but what underlies substrate selection is unclear. In this issue, Cundell et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201606033) identify the determinants of PP2A-B55’s dephosphorylation program, thereby influencing spindle disassembly, nuclear envelope reformation, and cytokinesis. PMID:27551057

  7. High p{sub T} jet production in pp collisions

    SciTech Connect

    Eskola, K.J.; Wang, X.N.

    1995-07-01

    Production rates of large p{sub T} jets in pp collisions at RHIC and LHC energies are studied using the next-to-leading order calculation of S. D. Ellis, Z. Zunszt and D. Soper. The computed inclusive one-jet cross sections are compared against the CERN and Fermilab jet data from p{bar p} and pp collisions. The dependence of the results on the choice of the parton distributions and renormalization/factorization scales is investigated.

  8. Rac GTPase signaling through the PP5 protein phosphatase

    PubMed Central

    Gentile, Saverio; Darden, Thomas; Erxleben, Christian; Romeo, Charles; Russo, Angela; Martin, Negin; Rossie, Sandra; Armstrong, David L.

    2006-01-01

    We have investigated the Rac-dependent mechanism of KCNH2 channel stimulation by thyroid hormone in a rat pituitary cell line, GH4C1, with the patch-clamp technique. Here we present physiological evidence for the protein serine/threonine phosphatase, PP5, as an effector of Rac GTPase signaling. We also propose and test a specific molecular mechanism for PP5 stimulation by Rac-GTP. Inhibition of PP5 with the microbial toxin, okadaic acid, blocked channel stimulation by thyroid hormone and by Rac, but signaling was restored by expression of a toxin-insensitive mutant of PP5, Y451A, which we engineered. PP5 is unique among protein phosphatases in that it contains an N-terminal regulatory domain with three tetratricopeptide repeats (TPR) that inhibit its activity. Expression of the TPR domain coupled to GFP blocked channel stimulation by the thyroid hormone. We also show that the published structures of the PP5 TPR domain and the TPR domain of p67, the Rac-binding subunit of NADPH oxidase, superimpose over 92 α carbons. Mutation of the PP5 TPR domain at two predicted contact points with Rac-GTP prevents the TPR domain from functioning as a dominant negative and blocks the ability of Y451A to rescue signaling in the presence of okadaic acid. PP5 stimulation by Rac provides a unique molecular mechanism for the antagonism of Rho-dependent signaling through protein kinases in many cellular processes, including metastasis, immune cell chemotaxis, and neuronal development. PMID:16549782

  9. PP2A Regulates HDAC4 Nuclear Import

    PubMed Central

    Paroni, Gabriela; Cernotta, Nadia; Dello Russo, Claudio; Gallinari, Paola; Pallaoro, Michele; Foti, Carmela; Talamo, Fabio; Orsatti, Laura; Steinkühler, Christian

    2008-01-01

    Different signal-regulated serine/threonine kinases phosphorylate class II histone deacetylases (HDACs) to promote nuclear export, cytosolic accumulation, and activation of gene transcription. However, little is known about mechanisms operating in the opposite direction, which, possibly through phosphatases, should promote class II HDACs nuclear entry and subsequent gene repression. Here we show that HDAC4 forms a complex with the PP2A holoenzyme Cα, Aα, B/PR55α. In vitro and in vivo binding studies demonstrate that the N-terminus of HDAC4 interacts with the catalytic subunit of PP2A. HDAC4 is dephosphorylated by PP2A and experiments using okadaic acid or RNA interference have revealed that PP2A controls HDAC4 nuclear import. Moreover, we identified serine 298 as a putative phosphorylation site important for HDAC4 nuclear import. The HDAC4 mutant mimicking phosphorylation of serine 298 is defective in nuclear import. Mutation of serine 298 to alanine partially rescues the defect in HDAC4 nuclear import observed in cells with down-regulated PP2A. These observations suggest that PP2A, via the dephosphorylation of multiple serines including the 14-3-3 binding sites and serine 298, controls HDAC4 nuclear import. PMID:18045992

  10. Onset of radial flow in p+p collisions

    DOE PAGES

    Jiang, Kun; Zhu, Yinying; Liu, Weitao; ...

    2015-02-23

    It has been debated for decades whether hadrons emerging from p+p collisions exhibit collective expansion. The signal of the collective motion in p+p collisions is not as clear as in heavy-ion collisions because of the low multiplicity and large fluctuation in p+p collisions. Tsallis Blast-Wave (TBW) model is a thermodynamic approach, introduced to handle the overwhelming correlation and fluctuation in the hadronic processes. We have systematically studied the identified particle spectra in p+p collisions from RHIC to LHC using TBW and found no appreciable radial flow in p+p collisions below √s = 900 GeV. At LHC higher energy of 7more » TeV in p+p collisions, the radial flow velocity achieves an average of (β) = 0.320 ± 0.005. This flow velocity is comparable to that in peripheral (40-60%) Au+Au collisions at RHIC. In addition, breaking of the identified particle spectra mT scaling was also observed at LHC from a model independent test.« less

  11. Evidence for a J/{psi}pp Pauli strong coupling?

    SciTech Connect

    Barnes, T.; Li, X.; Roberts, W.

    2008-03-01

    The couplings of charmonia and charmonium hybrids (generically {psi}) to pp are of great interest in view of future plans to study these states using an antiproton storage ring at GSI. These low to moderate energy {psi}pp couplings are not well understood theoretically, and currently must be determined from experiment. In this paper we note that the two independent Dirac ({gamma}{sub {mu}}) and Pauli ({sigma}{sub {mu}}{sub {nu}}) pp couplings of the J/{psi} and {psi}{sup '} can be constrained by the angular distribution of e{sup +}e{sup -}{yields}(J/{psi},{psi}{sup '}){yields}pp on resonance. A comparison of our theoretical results to recent unpolarized data allows estimates of the pp couplings; in the better determined J/{psi} case the data is inconsistent with a pure Dirac ({gamma}{sub {mu}}) coupling, and can be explained by the presence of a {sigma}{sub {mu}}{sub {nu}} term. This Pauli coupling may significantly affect the cross section of the PANDA process pp{yields}{pi}{sup 0}J/{psi} near threshold. There is a phase ambiguity that makes it impossible to uniquely determine the magnitudes and relative phase of the Dirac and Pauli couplings from the unpolarized angular distributions alone; we show in detail how this can be resolved through a study of the polarized reactions.

  12. Synthesis of Highly Selective Submicromolar Microcystin‐Based Inhibitors of Protein Phosphatase (PP)2A over PP1

    PubMed Central

    Fontanillo, Miriam; Zemskov, Ivan; Häfner, Maximilian; Uhrig, Ulrike; Salvi, Francesca; Simon, Bernd; Wittmann, Valentin

    2016-01-01

    Abstract Research and therapeutic targeting of the phosphoserine/threonine phosphatases PP1 and PP2A is hindered by the lack of selective inhibitors. The microcystin (MC) natural toxins target both phosphatases with equal potency, and their complex synthesis has complicated structure–activity relationship studies in the past. We report herein the synthesis and biochemical evaluation of 11 MC analogues, which was accomplished through an efficient strategy combining solid‐ and solution‐phase approaches. Our approach led to the first MC analogue with submicromolar inhibitory potency that is strongly selective for PP2A over PP1 and does not require the complex lipophilic Adda group. Through mutational and structural analyses, we identified a new key element for binding, as well as reasons for the selectivity. This work gives unprecedented insight into how selectivity between these phosphatases can be achieved with MC analogues. PMID:27723199

  13. K restriction inhibits protein phosphatase 2B (PP2B) and suppression of PP2B decreases ROMK channel activity in the CCD

    PubMed Central

    Zhang, Yan; Lin, Dao-Hong; Wang, Zhi-Jian; Jin, Yan; Yang, Baofeng; Wang, Wen-Hui

    2009-01-01

    We used Western blot analysis to examine the effect of dietary K intake on the expression of serine/threonine protein phosphatase in the kidney. K restriction significantly decreased the expression of catalytic subunit of protein phosphatase (PP)2B but increased the expression of PP2B regulatory subunit in both rat and mouse kidney. However, K depletion did not affect the expression of PP1 and PP2A. Treatment of M-1 cells, mouse cortical collecting duct (CCD) cells, or 293T cells with glucose oxidase (GO), which generates superoxide anions through glucose metabolism, mimicked the effect of K restriction on PP2B expression and significantly decreased expression of PP2B catalytic subunits. However, GO treatment increased expression of regulatory subunit of PP2B and had no effect on expression of PP1, PP2A, and protein tyrosine phosphatase 1D. Moreover, deletion of gp91-containing NADPH oxidase abolished the effect of K depletion on PP2B. Thus superoxide anions or related products may mediate the inhibitory effect of K restriction on the expression of PP2B catalytic subunit. We also used patch-clamp technique to study the effect of inhibiting PP2B on renal outer medullary K (ROMK) channels in the CCD. Application of cyclosporin A or FK506, inhibitors of PP2B, significantly decreased ROMK channels, and the effect of PP2B inhibitors was abolished by blocking p38 mitogen-activated protein kinase (MAPK) and ERK. Furthermore, Western blot demonstrated that inhibition of PP2B with cyclosporin A or small interfering RNA increased the phosphorylation of ERK and p38 MAPK. We conclude that K restriction suppresses the expression of PP2B catalytic subunits and that inhibition of PP2B decreases ROMK channel activity through stimulation of MAPK in the CCD. PMID:18184875

  14. Site specificity of DSP-PP cleavage by BMP1.

    PubMed

    Yang, Robert T; Lim, Glendale L; Yee, Colin T; Fuller, Robert S; Ritchie, Helena H

    2014-08-01

    Bone morphogenic protein 1 (BMP1), a metalloproteinase, is known to cleave a wide variety of extracellular matrix proteins, suggesting that a consensus substrate cleavage amino acid sequence might exist. However, while such a consensus sequence has been proposed based on P4 to P4' (i.e. the four amino acids flanking either side of the BMP1 cleavage site; P4P3P2P1|P1'P2'P3'P4') sequence homologies between two BMP1 substrates, dentin matrix protein 1 and dentin sialoprotein phosphophoryn (DSP-PP) (i.e. xMQx|DDP), no direct testing has so far been attempted. Using an Sf9 cell expression system, we have been able to produce large amounts of uncleaved DSP-PP. Point mutations introduced into this recombinant DSP-PP were then tested for their effects on DSP-PP cleavage by either Sf9 endogenous tolloid-related protein 1 (TLR-1) or by its human homolog, BMP1. Here, we have measured DSP-PP cleavage efficiencies after modifications based on P4-P4' sequence comparisons with dentin matrix protein 1, as well as for prolysyl oxidase and chordin, two other BMP1 substrates. Our results demonstrate that any mutations within or outside of the DSP-PP P4 to P4' cleavage site can block, impair or accelerate DSP-PP cleavage, and suggest that its BMP1 cleavage site is highly conserved in order to regulate its cleavage efficiency, possibly with additional assistance from its conserved exosites. Thus, BMP1 cleavage cannot be based on a consensus substrate cleavage site.

  15. Overexpression of a novel Arabidopsis PP2C isoform, AtPP2CF1, enhances plant biomass production by increasing inflorescence stem growth.

    PubMed

    Sugimoto, Hiroki; Kondo, Satoshi; Tanaka, Tomoko; Imamura, Chie; Muramoto, Nobuhiko; Hattori, Etsuko; Ogawa, Ken'ichi; Mitsukawa, Norihiro; Ohto, Chikara

    2014-10-01

    In contrast to mammals, higher plants have evolved to express diverse protein phosphatase 2Cs (PP2Cs). Of all Arabidopsis thaliana PP2Cs, members of PP2C subfamily A, including ABI1, have been shown to be key negative regulators of abscisic acid (ABA) signalling pathways, which regulate plant growth and development as well as tolerance to adverse environmental conditions. However, little is known about the enzymatic and signalling roles of other PP2C subfamilies. Here, we report a novel Arabidopsis subfamily E PP2C gene, At3g05640, designated AtPP2CF1. AtPP2CF1 was dramatically expressed in response to exogenous ABA and was expressed in vascular tissues and guard cells, similar to most subfamily A PP2C genes. In vitro enzymatic activity assays showed that AtPP2CF1 possessed functional PP2C activity. However, yeast two-hybrid analysis revealed that AtPP2CF1 did not interact with PYR/PYL/RCAR receptors or three SnRK2 kinases, which are ABI1-interacting proteins. This was supported by homology-based structural modelling demonstrating that the putative active- and substrate-binding site of AtPP2CF1 differed from that of ABI1. Furthermore, while overexpression of ABI1 in plants induced an ABA-insensitive phenotype, Arabidopsis plants overexpressing AtPP2CF1 (AtPP2CF1oe) were weakly hypersensitive to ABA during seed germination and drought stress. Unexpectedly, AtPP2CF1oe plants also exhibited increased biomass yield, mainly due to accelerated growth of inflorescence stems through the activation of cell proliferation and expansion. Our results provide new insights into the physiological significance of AtPP2CF1 as a candidate gene for plant growth production and for potential application in the sustainable supply of plant biomass.

  16. Overexpression of a novel Arabidopsis PP2C isoform, AtPP2CF1, enhances plant biomass production by increasing inflorescence stem growth

    PubMed Central

    Sugimoto, Hiroki; Kondo, Satoshi; Tanaka, Tomoko; Imamura, Chie; Muramoto, Nobuhiko; Hattori, Etsuko; Ogawa, Ken’ichi; Mitsukawa, Norihiro; Ohto, Chikara

    2014-01-01

    In contrast to mammals, higher plants have evolved to express diverse protein phosphatase 2Cs (PP2Cs). Of all Arabidopsis thaliana PP2Cs, members of PP2C subfamily A, including ABI1, have been shown to be key negative regulators of abscisic acid (ABA) signalling pathways, which regulate plant growth and development as well as tolerance to adverse environmental conditions. However, little is known about the enzymatic and signalling roles of other PP2C subfamilies. Here, we report a novel Arabidopsis subfamily E PP2C gene, At3g05640, designated AtPP2CF1. AtPP2CF1 was dramatically expressed in response to exogenous ABA and was expressed in vascular tissues and guard cells, similar to most subfamily A PP2C genes. In vitro enzymatic activity assays showed that AtPP2CF1 possessed functional PP2C activity. However, yeast two-hybrid analysis revealed that AtPP2CF1 did not interact with PYR/PYL/RCAR receptors or three SnRK2 kinases, which are ABI1-interacting proteins. This was supported by homology-based structural modelling demonstrating that the putative active- and substrate-binding site of AtPP2CF1 differed from that of ABI1. Furthermore, while overexpression of ABI1 in plants induced an ABA-insensitive phenotype, Arabidopsis plants overexpressing AtPP2CF1 (AtPP2CF1oe) were weakly hypersensitive to ABA during seed germination and drought stress. Unexpectedly, AtPP2CF1oe plants also exhibited increased biomass yield, mainly due to accelerated growth of inflorescence stems through the activation of cell proliferation and expansion. Our results provide new insights into the physiological significance of AtPP2CF1 as a candidate gene for plant growth production and for potential application in the sustainable supply of plant biomass. PMID:25038254

  17. Auxin promotes the transition from chloronema to caulonema in moss protonema by positively regulating PpRSL1and PpRSL2 in Physcomitrella patens.

    PubMed

    Jang, Geupil; Dolan, Liam

    2011-10-01

    Protonemata are multicellular filamentous networks that develop following the germination of a haploid moss spore and comprise two different cell types - chloronema and caulonema. The ROOT HAIR DEFECTIVE SIX-LIKE1 (PpRSL1) and PpRSL2 basic helix-loop-helix transcription factors and auxin promote the development of caulonema in Physcomitrella patens but the mechanism by which these regulators interact during development is unknown. We characterized the role of auxin in regulating the function of PpRSL1 and PpRSL2 in the chloronema-to-caulonema transition during protonema development. Here, we showed that a gradient of cell identity developed along protonemal filaments; cells were chloronemal in proximal regions near the site of spore germination becoming progressively more caulonemal distally as filaments elongated. Auxin controlled this transition by positively regulating the expression of PpRSL1 and PpRSL2 genes. Auxin did not induce caulonemal development in Pprsl1 Pprsl2 double mutants that lack PpRSL1 and PpRSL2 gene activity while constitutive co-expression of PpRSL1 and PpRSL2 in the absence of auxin was sufficient to program constitutive caulonema development. Together, these data indicate that auxin positively regulates PpRSL1 and PpRSL2 whose expression is sufficient to promote caulonema differentiation in moss protonema.

  18. Overexpression of RelA/SpoT homologs, PpRSH2a and PpRSH2b, induces the growth suppression of the moss Physcomitrella patens.

    PubMed

    Sato, Michio; Takahashi, Tomohiro; Ochi, Kozo; Matsuura, Hideyuki; Nabeta, Kensuke; Takahashi, Kosaku

    2015-01-01

    Two genes encoding RelA/SpoT homologs, PpRSH2a and PpRSH2b, which are involved in the synthesis of bacterial alarmone guanosine 5'-diphosphate 3'-diphosphate (ppGpp) for the stringent response, were isolated from the moss, Physcomitrella patens. A complementary analysis of PpRSH2a and PpRSH2b in Escherichia coli showed that these genes had ppGpp biosynthetic activity. The recombinant PpRSH2a and PpRSH2b were also shown to synthesize ppGpp in vitro. Both proteins were localized to the chloroplasts of P. patens. Expression of the PpRSH genes was induced upon treatment with abscisic acid or abiotic stresses, such as dehydration and UV irradiation. Overexpression of PpRSH2a and PpRSH2b caused suppression of the growth in response to 1% (w/v) of glucose. The present study suggests the existence of a mechanism to regulate the growth of P. patens, which is governed by plant RSH in chloroplasts.

  19. Ectopic expression of inhibitors of protein phosphatase type 1 (PP1) can be used to analyze roles of PP1 in Drosophila development.

    PubMed Central

    Bennett, Daimark; Szöor, Balázs; Gross, Sascha; Vereshchagina, Natalia; Alphey, Luke

    2003-01-01

    We have identified two proteins that bind with high specificity to type 1 serine/threonine protein phosphatase (PP1) and have exploited their inhibitory properties to develop an efficient and flexible strategy for conditional inactivation of PP1 in vivo. We show that modest overexpression of Drosophila homologs of I-2 and NIPP1 (I-2Dm and NIPP1Dm) reduces the level of PP1 activity and phenotypically resembles known PP1 mutants. These phenotypes, which include lethality, abnormal mitotic figures, and defects in muscle development, are suppressed by coexpression of PP1, indicating that the effect is due specifically to loss of PP1 activity. Reactivation of I-2Dm:PP1c complexes suggests that inhibition of PP1 activity in vivo does not result in a compensating increase in synthesis of active PP1. PP1 mutants enhance the wing overgrowth phenotype caused by ectopic expression of the type II TGF beta superfamily signaling receptor Punt. Using I-2Dm, which has a less severe effect than NIPP1Dm, we show that lowering the level of PP1 activity specifically in cells overexpressing Punt is sufficient for wing overgrowth and that the interaction between PP1 and Punt requires the type I receptor Thick-veins (Tkv) but is not strongly sensitive to the level of the ligand, Decapentaplegic (Dpp), nor to that of the other type I receptors. This is consistent with a role for PP1 in antagonizing Punt by preventing phosphorylation of Tkv. These studies demonstrate that inhibitors of PP1 can be used in a tissue- and developmental-specific manner to examine the developmental roles of PP1. PMID:12750335

  20. Silencing I2PP2A Rescues Tau Pathologies and Memory Deficits through Rescuing PP2A and Inhibiting GSK-3β Signaling in Human Tau Transgenic Mice

    PubMed Central

    Zhang, Yao; Ma, Rong-Hong; Li, Xia-Chun; Zhang, Jia-Yu; Shi, Hai-Rong; Wei, Wei; Luo, Dan-Ju; Wang, Qun; Wang, Jian-Zhi; Liu, Gong-Ping

    2014-01-01

    Increase of inhibitor-2 of protein phosphatase-2A I2PP2A is associated with protein phosphatase-2A (PP2A) inhibition and tau hyperphosphorylation in Alzheimer’s disease (AD). Down-regulating I2PP2A attenuated amyloidogenesis and improved the cognitive functions in transgenic mice expressing amyloid precursor protein (tg2576). Here, we found that silencing I2PP2A by hippocampal infusion of Lenti - siI2PP2A down-regulated I2PP2A (~45%) with reduction of tau phosphorylation/accumulation, improvement of memory deficits, and dendritic plasticity in 12-month-old human tau transgenic mice. Silencing I2PP2A not only restored PP2A activity but also inhibited glycogen synthase kinase-3β (GSK-3β) with a significant activation of protein kinase A (PKA) and Akt. In HEK293/tau and N2a/tau cells, silencing I2PP2A by pSUPER - siI2PP2A also significantly reduced tau hyperphosphorylation with restoration of PP2A activity and inhibition of GSK-3β, demonstrated by the decreased GSK-3β total protein and mRNA levels, and the increased inhibitory phosphorylation of GSK-3β at serine-9. Furthermore, activation of PKA but not Akt mediated the inhibition of GSK-3β by I2PP2A silencing. We conclude that targeting I2PP2A can improve tau pathologies and memory deficits in human tau transgenic mice, and activation of PKA contributes to GSK-3β inhibition induced by silencing I2PP2A in vitro, suggesting that I2PP2A is a promising multiple target of AD. PMID:24987368

  1. Modern geothermal power: GeoPP with geothermal steam turbines

    NASA Astrophysics Data System (ADS)

    Tomarov, G. V.; Shipkov, A. A.

    2017-03-01

    The first part of the review presents information on the scale and specific features of geothermal energy development in various countries. The classification of geothermal power plant (GeoPP) process flow diagrams by a phase state of the primary heat source (a geothermal fluid), thermodynamic cycle, and applicable turbines is proposed. Features of geothermal plants using methods of flashing and steam separation in the process loop and a flowsheet and thermodynamic process of a geothermal fluid heat-to-power conversion in a GeoPP of the most widespread type using a double-flash separation are considered. It is shown that, for combined cycle power units, the specific power-to-consumption geothermal fluid ratio is 20-25% higher than that for traditional single-loop GeoPP. Information about basic chemical components and their concentration range for geothermal fluids of various formations around the world is presented. Three historic stages of improving geothermal energy technologies are determined, such as development of high-temperature geothermal resources (dry, superheated steam) and application of a two-phase wet-steam geothermal fluid in GeoPP power units with one or two expansion pressures and development of binary cycle GeoPPs. A current trend of more active use of binary power plants in GeoPP technological processes is noted. Design features of GeoPP's steam turbines and steam separating devices, determined by the use of low-potential geothermal saturated steam as a working medium, which is characterized by corrosion aggressiveness and a tendency to form deposits, are considered. Most promising Russian geothermal energy projects are determined. A list of today's most advanced geothermal turbine performance technologies is presented. By an example of a 25 MW steam turbine design, made by JSC Kaluga Turbine Works, advantages of the internal moisture separation with a special turbine-separator stage are shown.

  2. PP2C gamma: a human protein phosphatase with a unique acidic domain.

    PubMed

    Travis, S M; Welsh, M J

    1997-08-04

    We have cloned a novel cDNA from human skeletal muscle which encodes a protein phosphatase with a unique acidic domain. It is 34% identical to mammalian PP2C alpha and PP2C beta and we call it PP2C gamma. It more closely resembles PP2Cs from Paramecium tetraurelia and Schizosaccharomyces pombe than mammalian PP2Cs. Northern blot analysis shows that PP2C gamma is widely expressed, and is most abundant in testis, skeletal muscle, and heart. Like known PP2Cs, recombinant PP2C gamma requires Mg2+ or Mn2+ for activity. Unlike any other known phosphatase, PP2C gamma has a highly acidic domain: 75% of the 54 residues are glutamate or aspartate.

  3. Near-Threshold Production of ϕ Mesons in pp Collisions

    NASA Astrophysics Data System (ADS)

    Hartmann, M.; Maeda, Y.; Keshelashvili, I.; Koch, H. R.; Mikirtytchiants, S.; Barsov, S.; Borgs, W.; Büscher, M.; Dimitrov, V. I.; Dymov, S.; Hejny, V.; Kleber, V.; Koptev, V.; Kulessa, P.; Mersmann, T.; Merzliakov, S.; Mussgiller, A.; Nekipelov, M.; Nioradze, M.; Ohm, H.; Pysz, K.; Schleichert, R.; Stein, H. J.; Ströher, H.; Watzlawik, K.-H.; Wüstner, P.

    2006-06-01

    The pp→ppϕ reaction has been studied at the Cooler Synchrotron COSY-Jülich, using the internal beam and ANKE facility. Total cross sections have been determined at three excess energies γ near the production threshold. The differential cross section closest to threshold at γ=18.5MeV exhibits a clear S wave dominance as well as a noticeable effect due to the proton-proton final-state interaction. Taken together with data for ppω production, a significant enhancement of the ϕ/ω ratio of a factor 8 is found compared to predictions based on the Okubo-Zweig-Iizuka rule.

  4. pp wave big bangs: Matrix strings and shrinking fuzzy spheres

    SciTech Connect

    Das, Sumit R.; Michelson, Jeremy

    2005-10-15

    We find pp wave solutions in string theory with null-like linear dilatons. These provide toy models of big bang cosmologies. We formulate matrix string theory in these backgrounds. Near the big bang 'singularity', the string theory becomes strongly coupled but the Yang-Mills description of the matrix string is weakly coupled. The presence of a second length scale allows us to focus on a specific class of non-Abelian configurations, viz. fuzzy cylinders, for a suitable regime of parameters. We show that, for a class of pp waves, fuzzy cylinders which start out big at early times dynamically shrink into usual strings at sufficiently late times.

  5. Characterization of phosphatidylinositol phosphate kinases from the moss Physcomitrella patens: PpPIPK1 and PpPIPK2.

    PubMed

    Saavedra, Laura; Balbi, Virginia; Dove, Stephen K; Hiwatashi, Yuji; Mikami, Koji; Sommarin, Marianne

    2009-03-01

    Phosphoinositides (PIs) play a major role in eukaryotic cells, despite being a minor component of most membranes. This is the first report on PI metabolism in a bryophyte, the moss Physcomitrella patens. Moss PI composition is similar to that of other land plants growing under normal conditions. In contrast to the large number of PIPK genes present in flowering plants, the P. patens genome encodes only two type I/II PIPK genes, PpPIPK1 and PpPIPK2, which are very similar at both the nucleotide and protein product levels. However, the expression of the two genes is differentially regulated, and in vitro biochemical characterization shows that the resulting enzymes have different substrate specificities. PpPIPK1 uses PtdIns4P and PtdIns3P with similar preference and also metabolizes PtdIns(3,4)P(2) to produce PtdIns(3,4,5)P(3), a PI not yet detected in intact plant cells. PpPIPK2 prefers PtdIns as substrate and is much less active towards PtdIns4P and PtdIns3P. Thus, PpPIPK2 shows properties reminiscent of both PtdInsP-kinase and PtdIns-kinases. Moreover, a substitution of glutamic acid by alanine in the activation loop drastically reduced PpPIPK1 activity and altered the substrate specificity to PtdIns5P being the preferred substrate compared with PtdIns4P and PtdIns3P. These findings demonstrate that the substrate specificity of plant PIPKs is determined in a plant-specific manner, which provides new insights into the regulatory modes of PIPK activity in plants.

  6. Molecular mechanism of serine/threonine protein phosphatase 1 (PP1cα-PP1r7) in spermatogenesis of Toxocara canis.

    PubMed

    Ma, Guang Xu; Zhou, Rong Qiong; Song, Zhen Hui; Zhu, Hong Hong; Zhou, Zuo Yong; Zeng, Yuan Qin

    2015-09-01

    Toxocariasis is one of the most important, but neglected, zoonoses, which is mainly caused by Toxocara canis. To better understand the role of serine/threonine protein phosphatase 1 (PP1) in reproductive processes of male adult T. canis, differential expression analysis was used to reveal the profiles of PP1 catalytic subunit α (PP1cα) gene Tc-stp-1 and PP1 regulatory subunit 7 (PP1r7) gene TcM-1309. Indirect fluorescence immunocytochemistry was carried out to determine the subcellular distribution of PP1cα. Double-stranded RNA interference (RNAi) assays were employed to illustrate the function and mechanism of PP1cα in male adult reproduction. Real-time quantitative PCR (qPCR) showed transcriptional consistency of Tc-stp-1 and TcM-1309 in sperm-producing germline tissues and localization research showed cytoplasmic distribution of PP1cα in sf9 cells, which indicated relevant involvements of PP1cα and PP1r7 in spermatogenesis. Moreover, spatiotemporal transcriptional differences of Tc-stp-1 were determined by gene knockdown analysis, which revealed abnormal morphologies and blocked meiotic divisions of spermatocytes by phenotypic aberration scanning, thereby highlighting the crucial involvement of PP1cα in spermatogenesis. These results revealed a PP1cα-PP1r7 mechanism by which PP1 regulates kinetochore-microtubule interactions in spermatogenesis and provided important clues to identify novel drug or vaccine targets for toxocariasis control.

  7. Evidence for collectivity in pp collisions at the LHC

    NASA Astrophysics Data System (ADS)

    Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; König, A.; Krätschmer, I.; Liko, D.; Matsushita, T.; Mikulec, I.; Rabady, D.; Rad, N.; Rahbaran, B.; Rohringer, H.; Schieck, J.; Strauss, J.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; De Wolf, E. A.; Janssen, X.; Lauwers, J.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; Daci, N.; De Bruyn, I.; Deroover, K.; Heracleous, N.; Lowette, S.; Moortgat, S.; Moreels, L.; Olbrechts, A.; Python, Q.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Brun, H.; Caillol, C.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Léonard, A.; Luetic, J.; Maerschalk, T.; Marinov, A.; Randle-conde, A.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Yonamine, R.; Zenoni, F.; Zhang, F.; Cimmino, A.; Cornelis, T.; Dobur, D.; Fagot, A.; Garcia, G.; Gul, M.; Poyraz, D.; Salva, S.; Schöfbeck, R.; Sharma, A.; Tytgat, M.; Van Driessche, W.; Yazgan, E.; Zaganidis, N.; Bakhshiansohi, H.; Beluffi, C.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; De Visscher, S.; Delaere, C.; Delcourt, M.; Francois, B.; Giammanco, A.; Jafari, A.; Jez, P.; Komm, M.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Nuttens, C.; Piotrzkowski, K.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; Da Silveira, G. G.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Matos Figueiredo, D.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; Dogra, S.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Moon, C. S.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Chen, Y.; Cheng, T.; Jiang, C. H.; Leggat, D.; Liu, Z.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Zhang, H.; Zhao, J.; Ban, Y.; Chen, G.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; González Hernández, C. F.; Ruiz Alvarez, J. D.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Micanovic, S.; Sudic, L.; Susa, T.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M.; Carrera Jarrin, E.; Abdelalim, A. A.; El-khateeb, E.; Salama, E.; Calpas, B.; Kadastik, M.; Murumaa, M.; Perrini, L.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. 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M.; Stöver, M.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Barth, C.; Baus, C.; Berger, J.; Butz, E.; Chwalek, T.; Colombo, F.; De Boer, W.; Dierlamm, A.; Fink, S.; Friese, R.; Giffels, M.; Gilbert, A.; Goldenzweig, P.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Katkov, I.; Lobelle Pardo, P.; Maier, B.; Mildner, H.; Mozer, M. U.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Röcker, S.; Roscher, F.; Schröder, M.; Shvetsov, I.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Topsis-Giotis, I.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Tziaferi, E.; Evangelou, I.; Flouris, G.; Foudas, C.; Kokkas, P.; Loukas, N.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Filipovic, N.; Bencze, G.; Hajdu, C.; Hidas, P.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Makovec, A.; Molnar, J.; Szillasi, Z.; Bartók, M.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Bahinipati, S.; Choudhury, S.; Mal, P.; Mandal, K.; Nayak, A.; Sahoo, D. K.; Sahoo, N.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Chawla, R.; Bhawandeep, U.; Kalsi, A. K.; Kaur, A.; Kaur, M.; Kumar, R.; Mehta, A.; Mittal, M.; Singh, J. B.; Walia, G.; Kumar, Ashok; Bhardwaj, A.; Choudhary, B. C.; Garg, R. 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M.; Fahim, A.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Calabria, C.; Caputo, C.; Colaleo, A.; Creanza, D.; Cristella, L.; De Filippis, N.; De Palma, M.; Fiore, L.; Iaselli, G.; Maggi, G.; Maggi, M.; Miniello, G.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Ranieri, A.; Selvaggi, G.; Silvestris, L.; Venditti, R.; Verwilligen, P.; Abbiendi, G.; Battilana, C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Chhibra, S. S.; 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.; Rossi, A. M.; Rovelli, T.; Siroli, G. 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M.; Lanza, G.; Lista, L.; Meola, S.; Paolucci, P.; Sciacca, C.; Thyssen, F.; Azzi, P.; Bacchetta, N.; Benato, L.; Bisello, D.; Boletti, A.; Carlin, R.; Carvalho Antunes De Oliveira, A.; Checchia, P.; Dall'Osso, M.; De Castro Manzano, P.; Dorigo, T.; Dosselli, U.; Gasparini, F.; Gasparini, U.; Gozzelino, A.; Lacaprara, S.; Margoni, M.; Meneguzzo, A. T.; Pazzini, J.; Pozzobon, N.; Ronchese, P.; Simonetto, F.; Torassa, E.; Zanetti, M.; Zotto, P.; Zucchetta, A.; Zumerle, G.; Braghieri, A.; Magnani, A.; Montagna, P.; Ratti, S. P.; Re, V.; Riccardi, C.; Salvini, P.; Vai, I.; Vitulo, P.; Alunni Solestizi, L.; Bilei, G. M.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Leonardi, R.; Mantovani, G.; Menichelli, M.; Saha, A.; Santocchia, A.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Donato, S.; Fedi, G.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Martini, L.; Messineo, A.; Palla, F.; Rizzi, A.; Savoy-Navarro, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Cipriani, M.; D'imperio, G.; Del Re, D.; Diemoz, M.; Gelli, S.; Longo, E.; Margaroli, F.; Meridiani, P.; Organtini, G.; Paramatti, R.; Preiato, F.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bartosik, N.; Bellan, R.; Biino, C.; Cartiglia, N.; Cenna, F.; Costa, M.; Covarelli, R.; Degano, A.; Demaria, N.; Finco, L.; Kiani, B.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Monteil, E.; Obertino, M. M.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Ravera, F.; Romero, A.; Ruspa, M.; Sacchi, R.; Shchelina, K.; Sola, V.; Solano, A.; Staiano, A.; Traczyk, P.; Belforte, S.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; La Licata, C.; Schizzi, A.; Zanetti, A.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Lee, S.; Lee, S. W.; Oh, Y. D.; Sekmen, S.; Son, D. C.; Yang, Y. C.; Lee, A.; Kim, H.; Brochero Cifuentes, J. A.; Kim, T. J.; Cho, S.; Choi, S.; Go, Y.; Gyun, D.; Ha, S.; Hong, B.; Jo, Y.; Kim, Y.; Lee, B.; Lee, K.; Lee, K. S.; Lee, S.; Lim, J.; Park, S. K.; Roh, Y.; Almond, J.; Kim, J.; Lee, H.; Oh, S. B.; Radburn-Smith, B. C.; Seo, S. h.; Yang, U. K.; Yoo, H. D.; Yu, G. B.; Choi, M.; Kim, H.; Kim, J. H.; Lee, J. S. H.; Park, I. C.; Ryu, G.; Ryu, M. S.; Choi, Y.; Goh, J.; Hwang, C.; Lee, J.; Yu, I.; Dudenas, V.; Juodagalvis, A.; Vaitkus, J.; Ahmed, I.; Ibrahim, Z. A.; Komaragiri, J. R.; Md Ali, M. A. B.; Mohamad Idris, F.; Wan Abdullah, W. A. T.; Yusli, M. N.; Zolkapli, Z.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-De La Cruz, I.; Hernandez-Almada, A.; Lopez-Fernandez, R.; Magaña Villalba, R.; Mejia Guisao, J.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Oropeza Barrera, C.; Vazquez Valencia, F.; Carpinteyro, S.; Pedraza, I.; Salazar Ibarguen, H. A.; Uribe Estrada, C.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Khan, W. A.; Shah, M. A.; Shoaib, M.; Waqas, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Zalewski, P.; Bunkowski, K.; Byszuk, A.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Walczak, M.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Di Francesco, A.; Faccioli, P.; Ferreira Parracho, P. G.; Gallinaro, M.; Hollar, J.; Leonardo, N.; Lloret Iglesias, L.; Nemallapudi, M. V.; Rodrigues Antunes, J.; Seixas, J.; Toldaiev, O.; Vadruccio, D.; Varela, J.; Vischia, P.; Afanasiev, S.; Bunin, P.; Gavrilenko, M.; Golutvin, I.; Gorbunov, I.; Kamenev, A.; Karjavin, V.; Lanev, A.; Malakhov, A.; Matveev, V.; Moisenz, P.; Palichik, V.; Perelygin, V.; Shmatov, S.; Shulha, S.; Skatchkov, N.; Smirnov, V.; Voytishin, N.; Zarubin, A.; Chtchipounov, L.; Golovtsov, V.; Ivanov, Y.; Kim, V.; Kuznetsova, E.; Murzin, V.; Oreshkin, V.; Sulimov, V.; Vorobyev, A.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Karneyeu, A.; Kirsanov, M.; Krasnikov, N.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Pozdnyakov, I.; Safronov, G.; Spiridonov, A.; Toms, M.; Vlasov, E.; Zhokin, A.; Bylinkin, A.; Chadeeva, M.; Chistov, R.; Rusinov, V.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Leonidov, A.; Rusakov, S. V.; Terkulov, A.; Baskakov, A.; Belyaev, A.; Boos, E.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Klyukhin, V.; Kodolova, O.; Lokhtin, I.; Miagkov, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Snigirev, A.; Blinov, V.; Skovpen, Y.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Elumakhov, D.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Krychkine, V.; Petrov, V.; Ryutin, R.; Sobol, A.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Cirkovic, P.; Devetak, D.; Dordevic, M.; Milosevic, J.; Rekovic, V.; Alcaraz Maestre, J.; Barrio Luna, M.; Calvo, E.; Cerrada, M.; Chamizo Llatas, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; 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.; Navarro De Martino, E.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Soares, M. S.; de Trocóniz, J. F.; Missiroli, M.; Moran, D.; Cuevas, J.; Fernandez Menendez, J.; Gonzalez Caballero, I.; González Fernández, J. R.; Palencia Cortezon, E.; Sanchez Cruz, S.; Suárez Andrés, I.; Vizan Garcia, J. M.; Cabrillo, I. J.; Calderon, A.; Castiñeiras De Saa, J. R.; Curras, E.; Fernandez, M.; Garcia-Ferrero, J.; Gomez, G.; Lopez Virto, A.; Marco, J.; Martinez Rivero, C.; Matorras, F.; Piedra Gomez, J.; Rodrigo, T.; Ruiz-Jimeno, A.; Scodellaro, L.; Trevisani, N.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Auffray, E.; Auzinger, G.; Bachtis, M.; Baillon, P.; Ball, A. H.; Barney, D.; Bloch, P.; Bocci, A.; Bonato, A.; Botta, C.; Camporesi, T.; Castello, R.; Cepeda, M.; Cerminara, G.; D'Alfonso, M.; d'Enterria, D.; Dabrowski, A.; Daponte, V.; David, A.; De Gruttola, M.; De Roeck, A.; Di Marco, E.; Dobson, M.; Dorney, B.; du Pree, T.; Duggan, D.; Dünser, M.; Dupont, N.; Elliott-Peisert, A.; Fartoukh, S.; Franzoni, G.; Fulcher, J.; Funk, W.; Gigi, D.; Gill, K.; Girone, M.; Glege, F.; Gulhan, D.; Gundacker, S.; Guthoff, M.; Hammer, J.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Kieseler, J.; Kirschenmann, H.; Knünz, V.; Kornmayer, A.; Kortelainen, M. J.; Kousouris, K.; Krammer, M.; Lange, C.; Lecoq, P.; Lourenço, C.; Lucchini, M. T.; Malgeri, L.; Mannelli, M.; Martelli, A.; Meijers, F.; Merlin, J. A.; Mersi, S.; Meschi, E.; Moortgat, F.; Morovic, S.; Mulders, M.; Neugebauer, H.; Orfanelli, S.; Orsini, L.; Pape, L.; Perez, E.; Peruzzi, M.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Racz, A.; Reis, T.; Rolandi, G.; Rovere, M.; Ruan, M.; Sakulin, H.; Sauvan, J. B.; Schäfer, C.; Schwick, C.; Seidel, M.; Sharma, A.; Silva, P.; Sphicas, P.; Steggemann, J.; Stoye, M.; Takahashi, Y.; Tosi, M.; Treille, D.; Triossi, A.; Tsirou, A.; Veckalns, V.; Veres, G. I.; Wardle, N.; Zagozdzinska, A.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Rohe, T.; Bachmair, F.; Bäni, L.; Bianchini, L.; Casal, B.; Dissertori, G.; Dittmar, M.; Donegà, M.; Grab, C.; Heidegger, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Lecomte, P.; Lustermann, W.; Mangano, B.; Marionneau, M.; Martinez Ruiz del Arbol, P.; Masciovecchio, M.; Meinhard, M. T.; Meister, D.; Micheli, F.; Musella, P.; Nessi-Tedaldi, F.; Pandolfi, F.; Pata, J.; Pauss, F.; Perrin, G.; Perrozzi, L.; Quittnat, M.; Rossini, M.; Schönenberger, M.; Starodumov, A.; Tavolaro, V. R.; Theofilatos, K.; Wallny, R.; Aarrestad, T. K.; Amsler, C.; Caminada, L.; Canelli, M. F.; De Cosa, A.; Galloni, C.; Hinzmann, A.; Hreus, T.; Kilminster, B.; Ngadiuba, J.; Pinna, D.; Rauco, G.; Robmann, P.; Salerno, D.; Yang, Y.; Candelise, V.; Doan, T. H.; Jain, Sh.; Khurana, R.; Konyushikhin, M.; Kuo, C. M.; Lin, W.; Lu, Y. J.; Pozdnyakov, A.; Yu, S. S.; Kumar, Arun; Chang, P.; Chang, Y. H.; Chang, Y. W.; Chao, Y.; Chen, K. F.; Chen, P. H.; Dietz, C.; Fiori, F.; Hou, W.-S.; Hsiung, Y.; Liu, Y. F.; Lu, R.-S.; Miñano Moya, M.; Paganis, E.; Psallidas, A.; Tsai, J. f.; Tzeng, Y. M.; Asavapibhop, B.; Singh, G.; Srimanobhas, N.; Suwonjandee, N.; Cerci, S.; Damarseckin, S.; Demiroglu, Z. S.; Dozen, C.; Dumanoglu, I.; Girgis, S.; Gokbulut, G.; Guler, Y.; Gurpinar, E.; Hos, I.; Kangal, E. E.; Kara, O.; Kayis Topaksu, A.; Kiminsu, U.; Oglakci, M.; Onengut, G.; Ozdemir, K.; Sunar Cerci, D.; Tali, B.; Turkcapar, S.; Zorbakir, I. S.; Zorbilmez, C.; Bilin, B.; Bilmis, S.; Isildak, B.; Karapinar, G.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Kaya, M.; Kaya, O.; Yetkin, E. A.; Yetkin, T.; Cakir, A.; Cankocak, K.; Sen, S.; Grynyov, B.; Levchuk, L.; Sorokin, P.; Aggleton, R.; Ball, F.; Beck, L.; Brooke, J. J.; Burns, D.; Clement, E.; Cussans, D.; Flacher, H.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Sakuma, T.; Seif El Nasr-storey, S.; Smith, D.; Smith, V. J.; Barducci, D.; Belyaev, A.; Brew, C.; Brown, R. M.; Calligaris, L.; Cieri, D.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Williams, T.; Baber, M.; Bainbridge, R.; Buchmuller, O.; Bundock, A.; Burton, D.; Casasso, S.; Citron, M.; Colling, D.; Corpe, L.; Dauncey, P.; Davies, G.; De Wit, A.; Della Negra, M.; Di Maria, R.; Dunne, P.; Elwood, A.; Futyan, D.; Haddad, Y.; Hall, G.; Iles, G.; James, T.; Lane, R.; Laner, C.; Lucas, R.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mastrolorenzo, L.; Nash, J.; Nikitenko, A.; Pela, J.; Penning, B.; Pesaresi, M.; Raymond, D. M.; Richards, A.; Rose, A.; Seez, C.; Summers, S.; Tapper, A.; Uchida, K.; Vazquez Acosta, M.; Virdee, T.; Wright, J.; Zenz, S. C.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Leslie, D.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Borzou, A.; Call, K.; Dittmann, J.; Hatakeyama, K.; Liu, H.; Pastika, N.; Charaf, O.; Cooper, S. I.; Henderson, C.; Rumerio, P.; West, C.; Arcaro, D.; Avetisyan, A.; Bose, T.; Gastler, D.; Rankin, D.; Richardson, C.; Rohlf, J.; Sulak, L.; Zou, D.; Benelli, G.; Berry, E.; Cutts, D.; Garabedian, A.; Hakala, J.; Heintz, U.; Hogan, J. M.; Jesus, O.; Laird, E.; Landsberg, G.; Mao, Z.; Narain, M.; Piperov, S.; Sagir, S.; Spencer, E.; Syarif, R.; Breedon, R.; Breto, G.; Burns, D.; Calderon De La Barca Sanchez, M.; Chauhan, S.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Flores, C.; Funk, G.; Gardner, M.; Ko, W.; Lander, R.; Mclean, C.; Mulhearn, M.; Pellett, D.; Pilot, J.; Shalhout, S.; Smith, J.; Squires, M.; Stolp, D.; Tripathi, M.; Wilbur, S.; Yohay, R.; Cousins, R.; Everaerts, P.; Florent, A.; Hauser, J.; Ignatenko, M.; Saltzberg, D.; Takasugi, E.; Valuev, V.; Weber, M.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Hanson, G.; Heilman, J.; Jandir, P.; Kennedy, E.; Lacroix, F.; Long, O. R.; Olmedo Negrete, M.; Paneva, M. I.; Shrinivas, A.; Si, W.; Wei, H.; Wimpenny, S.; Yates, B. R.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; Derdzinski, M.; Gerosa, R.; Holzner, A.; Klein, D.; Krutelyov, V.; Letts, J.; Macneill, I.; Olivito, D.; Padhi, S.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Vartak, A.; Wasserbaech, S.; Welke, C.; Wood, J.; Würthwein, F.; Yagil, A.; Zevi Della Porta, G.; Bhandari, R.; Bradmiller-Feld, J.; Campagnari, C.; Dishaw, A.; Dutta, V.; Flowers, K.; Franco Sevilla, M.; Geffert, P.; George, C.; Golf, F.; Gouskos, L.; Gran, J.; Heller, R.; Incandela, J.; Mccoll, N.; Mullin, S. D.; Ovcharova, A.; Richman, J.; Stuart, D.; Suarez, I.; Yoo, J.; Anderson, D.; Apresyan, A.; Bendavid, J.; Bornheim, A.; Bunn, J.; Chen, Y.; Duarte, J.; Lawhorn, J. M.; Mott, A.; Newman, H. B.; Pena, C.; Spiropulu, M.; Vlimant, J. R.; Xie, S.; Zhu, R. Y.; Andrews, M. B.; Azzolini, V.; Ferguson, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; Mcdermott, K.; Mirman, N.; Nicolas Kaufman, G.; Patterson, J. R.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Zientek, M.; Winn, D.; Abdullin, S.; Albrow, M.; Apollinari, G.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Cremonesi, M.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Hare, D.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Linacre, J.; Lincoln, D.; Lipton, R.; Liu, T.; Lopes De Sá, R.; Lykken, J.; Maeshima, K.; Magini, N.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; Newman-Holmes, C.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Das, S.; Field, R. D.; Furic, I. K.; Konigsberg, J.; Korytov, A.; Ma, P.; Matchev, K.; Mei, H.; Milenovic, P.; Mitselmakher, G.; Rank, D.; Shchutska, L.; Sperka, D.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Ackert, A.; Adams, J. R.; Adams, T.; Askew, A.; Bein, S.; Diamond, B.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Khatiwada, A.; Prosper, H.; Santra, A.; Weinberg, M.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Bucinskaite, I.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Kurt, P.; O'Brien, C.; Sandoval Gonzalez, I. D.; Turner, P.; Varelas, N.; Wang, H.; Wu, Z.; Zakaria, M.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Anderson, I.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Osherson, M.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; Xin, Y.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Boren, S.; Bowen, J.; Bruner, C.; Castle, J.; Forthomme, L.; Kenny, R. P., III; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Sanders, S.; Stringer, R.; Tapia Takaki, J. D.; Wang, Q.; Ivanov, A.; Kaadze, K.; Khalil, S.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Gomez, J. A.; Hadley, N. J.; Jabeen, S.; Kellogg, R. G.; Kolberg, T.; Kunkle, J.; Lu, Y.; Mignerey, A. C.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Tonjes, M. B.; Tonwar, S. C.; Abercrombie, D.; Allen, B.; Apyan, A.; Barbieri, R.; Baty, A.; Bi, R.; Bierwagen, K.; Brandt, S.; Busza, W.; Cali, I. A.; Demiragli, Z.; Di Matteo, L.; Gomez Ceballos, G.; Goncharov, M.; Hsu, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Krajczar, K.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Sumorok, K.; Tatar, K.; Varma, M.; Velicanu, D.; Veverka, J.; Wang, J.; Wang, T. W.; Wyslouch, B.; Yang, M.; Zhukova, V.; Benvenuti, A. C.; Chatterjee, R. M.; Evans, A.; Finkel, A.; Gude, A.; Hansen, P.; Kalafut, S.; Kao, S. C.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bartek, R.; Bloom, K.; Claes, D. R.; Dominguez, A.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Kravchenko, I.; Malta Rodrigues, A.; Meier, F.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; George, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Kaisen, J.; Kharchilava, A.; Kumar, A.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Baumgartel, D.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira De Lima, R.; Trocino, D.; Wang, R.-J.; Wood, D.; Bhattacharya, S.; Hahn, K. A.; Kubik, A.; Kumar, A.; Low, J. F.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Hurtado Anampa, K.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Smith, G.; Taroni, S.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Brinson, J.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Hughes, R.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Winer, B. L.; Wulsin, H. W.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Lange, D.; Luo, J.; Marlow, D.; Medvedeva, T.; Mei, K.; Mooney, M.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Tully, C.; Zuranski, A.; Malik, S.; Barker, A.; Barnes, V. E.; Folgueras, S.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Jung, K.; Miller, D. H.; Neumeister, N.; Shi, X.; Sun, J.; Svyatkovskiy, A.; Wang, F.; Xie, W.; Xu, L.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Redjimi, R.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Betchart, B.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Agapitos, A.; Chou, J. P.; Contreras-Campana, E.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hidas, D.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Nash, K.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Juska, E.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Rose, A.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Cowden, C.; Damgov, J.; De Guio, F.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Delannoy, A. G.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Xia, F.; Clarke, C.; Harr, R.; Karchin, P. E.; Lamichhane, P.; Sturdy, J.; Belknap, D. A.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Ojalvo, I.; Perry, T.; Polese, G.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.

    2017-02-01

    Measurements of two- and multi-particle angular correlations in pp collisions at √{ s} = 5 , 7, and 13TeV are presented as a function of charged-particle multiplicity. The data, corresponding to integrated luminosities of 1.0pb-1 (5 TeV), 6.2pb-1 (7 TeV), and 0.7pb-1 (13 TeV), were collected using the CMS detector at the LHC. The second-order (v2) and third-order (v3) azimuthal anisotropy harmonics of unidentified charged particles, as well as v2 of KS0 and Λ / Λ ‾ particles, are extracted from long-range two-particle correlations as functions of particle multiplicity and transverse momentum. For high-multiplicity pp events, a mass ordering is observed for the v2 values of charged hadrons (mostly pions), KS0 , and Λ / Λ ‾, with lighter particle species exhibiting a stronger azimuthal anisotropy signal below pT ≈ 2GeV/ c. For 13 TeV data, the v2 signals are also extracted from four- and six-particle correlations for the first time in pp collisions, with comparable magnitude to those from two-particle correlations. These observations are similar to those seen in pPb and PbPb collisions, and support the interpretation of a collective origin for the observed long-range correlations in high-multiplicity pp collisions.

  8. The Hyperon {Lambda}(1405) in p+p reactions

    SciTech Connect

    Siebenson, Johannes

    2011-10-21

    We present an analysis of the hyperon {Lambda}(1405) for p+p reactions at 3.5 GeV kinetic beam energy. The data were taken with the High Acceptance Di-Electron Spectrometer (HADES). A {Lambda}(1405) signal could be reconstructed in both charged decay channels ({Lambda}(1405){yields}{Sigma}{sup {+-}}{pi}{sup {+-}}).

  9. Toughening of wood plastic composite based on X-PP

    NASA Astrophysics Data System (ADS)

    Meekum, U.; Khongrit, A.

    2016-03-01

    Wood plastic composite(WPC) based on crosslinked polypropylene(X-PP)/wood flour was explored. The peroxide/silane was used as crosslinking system. The sauna incubation under moisture saturated oven was applied to accelerate the competition of the siloxy/moisture networking reaction. There were three parts of the research work; design of experiment, toughening of WPC and the effect of peroxide, silane and PP copolymer on properties of the WPC, respectively. In this published work, the toughness improvement of the composite was focused. Ultra-high molecular weight polyethylene (UHMWPE) and Ethylene propylene diene terpolymer(EPDM) were employed to improve impact strength via blending with x-PP matrix. Composites were compounded into pellets by co-rotational twin screw extruder and test specimens were prepared by injection molding. Sauna incubation at 105°C for 12 hrs in oven chamber was performed to accelerate the final silane condensation crosslink reaction. MFI, impact strength, flexural properties and heat deflection temperature measurement were conducted. Impact strength, HDT and flexural modulus were improved with increasing UHMWPE content, and the optimal values around 5-10 phr of UHMWPE were achieved. Addition of EPDM elastomer to the matrix blends, reduced flexural strength and modulus but increased impact strength. While incorporation of EPDM into the PP/UHMWPE blends was exhibited much higher impact strength than that of the PP/UHMWPE binary blends. Silane crosslinked through sauna treatment improved the impact strength. HDT were also much risen for the crosslinked composite comparing with the non-crosslinked one.

  10. Genetic characterization of two fully sequenced multi-drug resistant plasmids pP10164-2 and pP10164-3 from Leclercia adecarboxylata

    PubMed Central

    Sun, Fengjun; Zhou, Dongsheng; Sun, Qiang; Luo, Wenbo; Tong, Yigang; Zhang, Defu; Wang, Qian; Feng, Wei; Chen, Weijun; Fan, Yahan; Xia, Peiyuan

    2016-01-01

    We previously reported the complete sequence of the resistance plasmid pP10164-NDM, harboring blaNDM (conferring carbapenem resistance) and bleMBL (conferring bleomycin resistance), which is recovered from a clinical Leclercia adecarboxylata isolate P10164 from China. This follow-up work disclosed that there were still two multidrug-resistant (MDR) plasmids pP10164-2 and pP10164-3 coexisting in this strain. pP10164-2 and pP10164-3 were completely sequenced and shown to carry a wealth of resistance genes, which encoded the resistance to at least 10 classes of antibiotics (β-lactams. macrolides, quinolones, aminoglycosides, tetracyclines, amphenicols, quaternary ammonium compounds, sulphonamides, trimethoprim, and rifampicin) and 7 kinds of heavy mental (mercury, silver, copper, nickel, chromate, arsenic, and tellurium). All of these antibiotic resistance genes are associated with mobile elements such as transposons, integrons, and insertion sequence-based transposable units, constituting a total of three novel MDR regions, two in pP10164-2 and the other one in pP10164-3. Coexistence of three resistance plasmids pP10164-NDM, pP10164-2 and pP10164-3 makes L. adecarboxylata P10164 tend to become extensively drug-resistant. PMID:27658354

  11. Polarized proton parameters for the 2015 PP-on-Aluminum setup in RHIC

    SciTech Connect

    Gardner, C. J.

    2015-10-02

    Values are given for RHIC circumference shifts due to snakes for various situations. Relevant parameters are tabulated for polarized protons (PP) in the booster and in AGS and RHIC for PP-on-Aluminum stores.

  12. Polarized proton parameters for the 2015 PP-on-Au setup in RHIC

    SciTech Connect

    Gardner, C. J.

    2015-08-25

    Values are given for RHIC circumference shifts due to snakes for various situations. Relevant parameters are tabulated for polarized protons (PP) in the booster and in AGS and RHIC for PP-on-Au stores.

  13. Visualization of the dynamic multimerization of human Cytomegalovirus pp65 in punctuate nuclear foci

    SciTech Connect

    Cui Zongqiang; Zhang Ke; Zhang Zhiping; Liu Yalan; Zhou Yafeng; Wei Hongping; Zhang Xian-En

    2009-09-30

    The phosphorylated protein pp65 of human Cytomegalovirus (HCMV) is the predominant virion protein and the major tegument constituent. It plays important roles in HCMV infection and virion assembly. Live cell imaging and fluorescence recovery after photobleaching (FRAP) analysis showed that HCMV pp65 accumulated dynamically in punctuate nuclear foci when transiently expressed in mammalian cells. Fluorescence resonance energy transfer (FRET) imaging disclosed that pp65 can self-interact in its localization foci. Yeast two-hybrid assay verified that pp65 is a self-associating protein, and the N-terminal amino acids 14-22 were determined to be essential for pp65 self-association. However, these amino acids were not related to pp65 localization in the specific nuclear foci. The interaction of pp65 and ppUL97 was also studied by FRET microscopy, and the result suggested that there is another signal sequence in pp65, being the ppUL97 phosphorylation site, that is responsible for localization of pp65 in nuclear foci. These results help to understand the function of pp65 in HCMV infection and virion morphogenesis.

  14. Improved murine glioma detection following modified diet and photobleaching of skin PpIX fluorescence

    NASA Astrophysics Data System (ADS)

    Gibbs, Summer L.; O'Hara, Julia A.; Hoopes, P. Jack; Pogue, Brian W.

    2007-02-01

    The Aminolevulinic Acid (ALA) - Protoporphyrin IX (PpIX) system is unique in the world of photosensitizers in that the prodrug ALA is enzymatically transformed via the tissue of interest into fluorescently detectable levels of PpIX. This system can be used to monitor cellular metabolism of tumor tissue for applications such as therapy monitoring. Detecting PpIX fluorescence noninvasively has proven difficult due to the high levels of PpIX produced in the skin compared to other tissue both with and without ALA administration. In the current study, methods to decrease skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration have been examined. Use of a purified diet is found to decrease both skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration, while addition of a broad spectrum antibiotic to the water shows little effect. Following ALA administration, improved brain tumor detection is seen when skin PpIX fluorescence is photobleached via blue light prior to transmission spectroscopic measurements of tumor bearing and control animals. Both of these methods to decrease skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration are shown to have a large effect on the ability to detect tumor tissue PpIX fluorescence noninvasively in vivo.

  15. Cloning and characterization of a novel mammalian PP2C isozyme.

    PubMed

    Tong, Y; Quirion, R; Shen, S H

    1998-12-25

    PP2C is a structurally diversified protein phosphatase family with a wide range of functions in cellular signal transduction. A novel PP2C subtype, designated PP2Cdelta, was identified from a rat cDNA clone, which encodes a protein of 392 amino acid residues. While PP2Cdelta shares approximately 30% sequence identity in its catalytic domain with the mammalian PP2C, it lacks a 90-residue carboxyl-terminal sequence conserved in mammalian PP2C. Northern blot analysis showed that PP2Cdelta is widely expressed in rat tissues. The transcription of the PP2Cdelta gene was activated in response to stress, such as the addition of ethanol to the culture medium or UV irradiation of cells. Recombinant PP2Cdelta purified from bacteria exhibited a potent Mn2+-dependent serine/threonine phosphatase activity. Unlike other members of the PP2C family, the activity of PP2Cdelta was inhibited, rather than stimulated, by Mg2+. Transfection with PP2Cdelta resulted in inhibition of cell growth, precluding generation of stable 293 or CHO transfectants. Using a modified tetracycline-regulated PP2Cdelta-GFP dicistronic expression cassette, it was revealed that overexpression of PP2Cdelta blocked cell cycle progression and arrested cells at early S phase, resulting in inhibition of DNA synthesis and leading to cell death. These results suggest that PP2Cdelta plays a role in regulation of cell cycle progression via dephosphorylation of its substrates whose appropriate phosphorylation states might be crucial for cell proliferation.

  16. Prompt photon production in p-p collisions

    SciTech Connect

    Cleymans, J.; Quack, E.; Redlich, K.

    1995-07-01

    A systematic study of the inclusive photon cross-section in p-p collisions is presented. The dependence of the {gamma} rates on the renormalization and factorization scales is discussed. A comparison is made with experimental data for centre-of-mass energies ranging from 23 GeV to 1.8 TeV. Predictions of the cross-sections are given for two different sets of structure functions for RHIC and LHC energies.

  17. Pathologic significance of SET/I2PP2A-mediated PP2A and non-PP2A pathways in polycystic ovary syndrome (PCOS).

    PubMed

    Jiang, Shi-Wen; Xu, Siliang; Chen, Haibin; Liu, Xiaoqiang; Tang, Zuoqing; Cui, Yugui; Liu, Jiayin

    2017-01-01

    SET (SE translocation, SET), a constitutive inhibitor of protein phosphatase 2A (PP2A), is a multifunctional oncoprotein involved in DNA replication, histone modification, nucleosome assembly, gene transcription and cell proliferation. It is widely expressed in human tissues including the gonadal system and brain. Intensive studies have shown that overexpressed SET plays an important role in the development of Alzheimer's disease (AD), and may also contribute to the malignant transformation of breast and ovarian cancers. Recent studies indicated that through interaction with PP2A, SET may upregulate androgen biosynthesis and contribute to hyperandrogenism in polycystic ovary syndrome (PCOS) patients. This review article summarizes data concerning the SET expression in ovaries from PCOS and normal women, and analyzes the role/regulatory mechanism of SET for androgen biosynthesis in PCOS, as well as the significance of this action in the development of PCOS. The potential value of SET-triggered pathway as a therapeutic target and the application of anti-SET reagents for treating hyperandrogenism in PCOS patients are also discussed.

  18. Repo-Man/PP1 regulates heterochromatin formation in interphase

    PubMed Central

    de Castro, Inês J.; Budzak, James; Di Giacinto, Maria L.; Ligammari, Lorena; Gokhan, Ezgi; Spanos, Christos; Moralli, Daniela; Richardson, Christine; de las Heras, Jose I.; Salatino, Silvia; Schirmer, Eric C.; Ullman, Katharine S.; Bickmore, Wendy A.; Green, Catherine; Rappsilber, Juri; Lamble, Sarah; Goldberg, Martin W.; Vinciotti, Veronica; Vagnarelli, Paola

    2017-01-01

    Repo-Man is a protein phosphatase 1 (PP1) targeting subunit that regulates mitotic progression and chromatin remodelling. After mitosis, Repo-Man/PP1 remains associated with chromatin but its function in interphase is not known. Here we show that Repo-Man, via Nup153, is enriched on condensed chromatin at the nuclear periphery and at the edge of the nucleopore basket. Repo-Man/PP1 regulates the formation of heterochromatin, dephosphorylates H3S28 and it is necessary and sufficient for heterochromatin protein 1 binding and H3K27me3 recruitment. Using a novel proteogenomic approach, we show that Repo-Man is enriched at subtelomeric regions together with H2AZ and H3.3 and that depletion of Repo-Man alters the peripheral localization of a subset of these regions and alleviates repression of some polycomb telomeric genes. This study shows a role for a mitotic phosphatase in the regulation of the epigenetic landscape and gene expression in interphase. PMID:28091603

  19. Thermal Degradation of Filler/PP Composite and Its Depression

    NASA Astrophysics Data System (ADS)

    Hosoi, Hiroshi; Funami, Fumiyasu; Yasuda, Naoki; Nomura, Manabu; Yui, Hiroshi; Ikuta, Nobuo

    To examine thermal degradation accelerated by filling inorganic particles in polypropylene (PP), the composites were made with three types of inorganic powders : talc, magnesium hydroxide, and mica. They were easily degraded with the fillers in this order in the thermal aging test. A commercial heat resistance agent, ‘Plenlizer MK-400’, was added while making the composites. The degradation resistance of the agent remarkably appeared in the reverse order. That is, thermal degradation was most depressed in talc-filled composite with the agent. In another experience, soxhlet extraction was carried out to the filler with an organic solvent, o-xylene, that was able to dissolve PP. A lot of inorganic ions were detected in the extractant. In particular, the detected amount of aluminum ion increased in the order of talc, magnesium hydroxide, and mica. This order was the same as the fillers indicated by the degree of degradation. Infrared analysis of the agent with inorganic ions in chloroform showed that the peaks due to the agent were much stronger with aluminum ion than those with iron ion. These results suggested that a cause of degradation was aluminum ion dispersed from particles to PP matrix during the molding.

  20. Polarization Processes of Nanocomposite Silicate-EVA and PP Materials

    NASA Astrophysics Data System (ADS)

    Montanari, Gian Carlo; Palmieri, Fabrizio; Testa, Luigi; Motori, Antonio; Saccani, Andrea; Patuelli, Francesca

    Recent works indicate that polypropylene (PP) and ethylene-vinylacetate (EVA) filled by nanosilicates may present low content of space charge and high electric strength. Investigations are being made to explain nanocomposite behaviour and characterize their electrical, thermal and mechanical properties. In this paper, the results of broad-band dielectric spectroscopy performed on EVA and PP filled by layered nanosized silicates are reported. Isochronal and isothermal curves of complex permittivity, as well as activation energies of the relaxation processes, are presented and discussed. Nanostructuration gives rise to substantial changes in the polarisation and dielectric loss behaviour. While the relaxation process of EVA, associated with glass transition of the material amorphous phase, results unchanged from base to nanostructured material, nanocomposites EVA and PP have shown the rise of a new process at higher temperatures respect to the typical host material processes, as well as a different distribution of relaxation processes. Changes in space charge accumulation in relation to the effectiveness of the purification process performed upon nanostructured materials are also reported: while the dispersion of the clean clays leads to a reduction of the space charge, especially at high fields, an unclean filler gives rise to significant homo-charge accumulation and interfacial polarisation phenomena.

  1. Associated charmonium production in low energy pp annihilation

    SciTech Connect

    Barnes, T.; Li, X.

    2007-03-01

    The QCD mechanisms underlying the exclusive strong decays and hadronic production amplitudes of charmonium remain poorly understood, despite decades of study and an increasingly detailed body of experimental information. One set of hadronic channels of special interest are those that include baryon-antibaryon states. These are being investigated experimentally at BES and CLEO-c in terms of their baryon resonance content, and are also of interest for the future PANDA experiment, in which charmonium and charmonium hybrids will be produced in pp annihilation in association with light mesons. In this paper we develop a simple initial-state light meson emission model of the near-threshold associated charmonium production processes pp{yields}{pi}{sup 0}{psi}, and evaluate the differential and total cross sections for these reactions in this model. (Here we consider the states {psi}={eta}{sub c}, J/{psi}, {psi}{sup '}, {chi}{sub 0} and {chi}{sub 1}.) The predicted near-threshold cross section for pp{yields}{pi}{sup 0}J/{psi} is found to be numerically similar to two previous theoretical estimates, and is roughly comparable to the (sparse) existing data for this process. The theoretical charmonium angular distributions predicted by this model are far from isotropic, which may be of interest for PANDA detector design studies.

  2. Generation IV PR and PP Methods and Applications

    SciTech Connect

    Bari,R.A.

    2008-10-13

    This paper presents an evaluation methodology for proliferation resistance and physical protection (PR&PP) of Generation IV nuclear energy systems (NESs). For a proposed NES design, the methodology defines a set of challenges, analyzes system response to these challenges, and assesses outcomes. The challenges to the NES are the threats posed by potential actors (proliferant States or sub-national adversaries). The characteristics of Generation IV systems, both technical and institutional, are used to evaluate the response of the system and determine its resistance against proliferation threats and robustness against sabotage and terrorism threats. The outcomes of the system response are expressed in terms of six measures for PR and three measures for PP, which are the high-level PR&PP characteristics of the NES. The methodology is organized to allow evaluations to be performed at the earliest stages of system design and to become more detailed and more representative as design progresses. Uncertainty of results are recognized and incorporated into the evaluation at all stages. The results are intended for three types of users: system designers, program policy makers, and external stakeholders. Particular current relevant activities will be discussed in this regard. The methodology has been illustrated in a series of demonstration and case studies and these will be summarized in the paper.

  3. Combining polyethylene and polypropylene: Enhanced performance with PE/iPP multiblock polymers.

    PubMed

    Eagan, James M; Xu, Jun; Di Girolamo, Rocco; Thurber, Christopher M; Macosko, Christopher W; LaPointe, Anne M; Bates, Frank S; Coates, Geoffrey W

    2017-02-24

    Polyethylene (PE) and isotactic polypropylene (iPP) constitute nearly two-thirds of the world's plastic. Despite their similar hydrocarbon makeup, the polymers are immiscible with one another. Thus, common grades of PE and iPP do not adhere or blend, creating challenges for recycling these materials. We synthesized PE/iPP multiblock copolymers using an isoselective alkene polymerization initiator. These polymers can weld common grades of commercial PE and iPP together, depending on the molecular weights and architecture of the block copolymers. Interfacial compatibilization of phase-separated PE and iPP with tetrablock copolymers enables morphological control, transforming brittle materials into mechanically tough blends.

  4. PP2A inhibition as a novel therapeutic target in castration-resistant prostate cancer.

    PubMed

    González-Alonso, Paula; Cristóbal, Ion; Manso, Rebeca; Madoz-Gúrpide, Juan; García-Foncillas, Jesús; Rojo, Federico

    2015-08-01

    Protein phosphatase 2A (PP2A) is a well-known tumor suppressor frequently inhibited in human cancer. Alterations affecting PP2A subunits together with the deregulation of endogenous PP2A inhibitors such as CIP2A and SET have been described as contributing mechanisms to inactivate PP2A in prostate cancer. Moreover, recent findings highlight that functional inactivation of PP2A could represent a key event in the acquisition of castration-resistant phenotype and a novel molecular target with high impact at both clinical and therapeutic levels in prostate cancer.

  5. Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone

    SciTech Connect

    Guo, Feng; Stanevich, Vitali; Wlodarchak, Nathan; Sengupta, Rituparna; Jiang, Li; Satyshur, Kenneth A.; Xing, Yongna

    2013-10-08

    Proper activation of protein phosphatase 2A (PP2A) catalytic subunit is central for the complex PP2A regulation and is crucial for broad aspects of cellular function. The crystal structure of PP2A bound to PP2A phosphatase activator (PTPA) and ATPγS reveals that PTPA makes broad contacts with the structural elements surrounding the PP2A active site and the adenine moiety of ATP. PTPA-binding stabilizes the protein fold of apo-PP2A required for activation, and orients ATP phosphoryl groups to bind directly to the PP2A active site. This allows ATP to modulate the metal-binding preferences of the PP2A active site and utilize the PP2A active site for ATP hydrolysis. In vitro, ATP selectively and drastically enhances binding of endogenous catalytic metal ions, which requires ATP hydrolysis and is crucial for acquisition of pSer/Thr-specific phosphatase activity. Furthermore, both PP2A- and ATP-binding are required for PTPA function in cell proliferation and survival. Our results suggest novel mechanisms of PTPA in PP2A activation with structural economy and a unique ATP-binding pocket that could potentially serve as a specific therapeutic target.

  6. Molecular mutagenesis of ppGpp: turning a RelA activator into an inhibitor

    PubMed Central

    Beljantseva, Jelena; Kudrin, Pavel; Jimmy, Steffi; Ehn, Marcel; Pohl, Radek; Varik, Vallo; Tozawa, Yuzuru; Shingler, Victoria; Tenson, Tanel; Rejman, Dominik; Hauryliuk, Vasili

    2017-01-01

    The alarmone nucleotide (p)ppGpp is a key regulator of bacterial metabolism, growth, stress tolerance and virulence, making (p)ppGpp-mediated signaling a promising target for development of antibacterials. Although ppGpp itself is an activator of the ribosome-associated ppGpp synthetase RelA, several ppGpp mimics have been developed as RelA inhibitors. However promising, the currently available ppGpp mimics are relatively inefficient, with IC50 in the sub-mM range. In an attempt to identify a potent and specific inhibitor of RelA capable of abrogating (p)ppGpp production in live bacterial cells, we have tested a targeted nucleotide library using a biochemical test system comprised of purified Escherichia coli components. While none of the compounds fulfilled this aim, the screen has yielded several potentially useful molecular tools for biochemical and structural work. PMID:28157202

  7. "PP2C7s", Genes Most Highly Elaborated in Photosynthetic Organisms, Reveal the Bacterial Origin and Stepwise Evolution of PPM/PP2C Protein Phosphatases.

    PubMed

    Kerk, David; Silver, Dylan; Uhrig, R Glen; Moorhead, Greg B G

    2015-01-01

    Mg+2/Mn+2-dependent type 2C protein phosphatases (PP2Cs) are ubiquitous in eukaryotes, mediating diverse cellular signaling processes through metal ion catalyzed dephosphorylation of target proteins. We have identified a distinct PP2C sequence class ("PP2C7s") which is nearly universally distributed in Eukaryotes, and therefore apparently ancient. PP2C7s are by far most prominent and diverse in plants and green algae. Combining phylogenetic analysis, subcellular localization predictions, and a distillation of publically available gene expression data, we have traced the evolutionary trajectory of this gene family in photosynthetic eukaryotes, demonstrating two major sequence assemblages featuring a succession of increasingly derived sub-clades. These display predominant expression moving from an ancestral pattern in photosynthetic tissues toward non-photosynthetic, specialized and reproductive structures. Gene co-expression network composition strongly suggests a shifting pattern of PP2C7 gene functions, including possible regulation of starch metabolism for one homologue set in Arabidopsis and rice. Distinct plant PP2C7 sub-clades demonstrate novel amino terminal protein sequences upon motif analysis, consistent with a shifting pattern of regulation of protein function. More broadly, neither the major events in PP2C sequence evolution, nor the origin of the diversity of metal binding characteristics currently observed in different PP2C lineages, are clearly understood. Identification of the PP2C7 sequence clade has allowed us to provide a better understanding of both of these issues. Phylogenetic analysis and sequence comparisons using Hidden Markov Models strongly suggest that PP2Cs originated in Bacteria (Group II PP2C sequences), entered Eukaryotes through the ancestral mitochondrial endosymbiosis, elaborated in Eukaryotes, then re-entered Bacteria through an inter-domain gene transfer, ultimately producing bacterial Group I PP2C sequences. A key evolutionary

  8. "PP2C7s", Genes Most Highly Elaborated in Photosynthetic Organisms, Reveal the Bacterial Origin and Stepwise Evolution of PPM/PP2C Protein Phosphatases

    PubMed Central

    Kerk, David; Silver, Dylan; Uhrig, R. Glen; Moorhead, Greg B. G.

    2015-01-01

    Mg+2/Mn+2-dependent type 2C protein phosphatases (PP2Cs) are ubiquitous in eukaryotes, mediating diverse cellular signaling processes through metal ion catalyzed dephosphorylation of target proteins. We have identified a distinct PP2C sequence class (“PP2C7s”) which is nearly universally distributed in Eukaryotes, and therefore apparently ancient. PP2C7s are by far most prominent and diverse in plants and green algae. Combining phylogenetic analysis, subcellular localization predictions, and a distillation of publically available gene expression data, we have traced the evolutionary trajectory of this gene family in photosynthetic eukaryotes, demonstrating two major sequence assemblages featuring a succession of increasingly derived sub-clades. These display predominant expression moving from an ancestral pattern in photosynthetic tissues toward non-photosynthetic, specialized and reproductive structures. Gene co-expression network composition strongly suggests a shifting pattern of PP2C7 gene functions, including possible regulation of starch metabolism for one homologue set in Arabidopsis and rice. Distinct plant PP2C7 sub-clades demonstrate novel amino terminal protein sequences upon motif analysis, consistent with a shifting pattern of regulation of protein function. More broadly, neither the major events in PP2C sequence evolution, nor the origin of the diversity of metal binding characteristics currently observed in different PP2C lineages, are clearly understood. Identification of the PP2C7 sequence clade has allowed us to provide a better understanding of both of these issues. Phylogenetic analysis and sequence comparisons using Hidden Markov Models strongly suggest that PP2Cs originated in Bacteria (Group II PP2C sequences), entered Eukaryotes through the ancestral mitochondrial endosymbiosis, elaborated in Eukaryotes, then re-entered Bacteria through an inter-domain gene transfer, ultimately producing bacterial Group I PP2C sequences. A key

  9. Basal Levels of (p)ppGpp in Enterococcus faecalis: the Magic beyond the Stringent Response

    PubMed Central

    Gaca, Anthony O.; Kajfasz, Jessica K.; Miller, James H.; Liu, Kuanqing; Wang, Jue D.; Abranches, Jacqueline; Lemos, José A.

    2013-01-01

    ABSTRACT The stringent response (SR), mediated by the alarmone (p)ppGpp, is a conserved bacterial adaptation system controlling broad metabolic alterations necessary for survival under adverse conditions. In Enterococcus faecalis, production of (p)ppGpp is controlled by the bifunctional protein RSH (for “Rel SpoT homologue”; also known as RelA) and by the monofunctional synthetase RelQ. Previous characterization of E. faecalis strains lacking rsh, relQ, or both revealed that RSH is responsible for activation of the SR and that alterations in (p)ppGpp production negatively impact bacterial stress survival and virulence. Despite its well-characterized role as the effector of the SR, the significance of (p)ppGpp during balanced growth remains poorly understood. Microarrays of E. faecalis strains producing different basal amounts of (p)ppGpp identified several genes and pathways regulated by modest changes in (p)ppGpp. Notably, expression of numerous genes involved in energy generation were induced in the ∆rsh ∆relQ [(p)ppGpp0] strain, suggesting that a lack of basal (p)ppGpp places the cell in a “transcriptionally relaxed” state. Alterations in the fermentation profile and increased production of H2O2 in the (p)ppGpp0 strain substantiate the observed transcriptional changes. We confirm that, similar to what is seen in Bacillus subtilis, (p)ppGpp directly inhibits the activity of enzymes involved in GTP biosynthesis, and complete loss of (p)ppGpp leads to dysregulation of GTP homeostasis. Finally, we show that the association of (p)ppGpp with antibiotic survival does not relate to the SR but rather relates to basal (p)ppGpp pools. Collectively, this study highlights the critical but still underappreciated role of basal (p)ppGpp pools under balanced growth conditions. PMID:24065631

  10. Substrate analysis of Arabidopsis PP2C-type protein phosphatases.

    PubMed

    Umbrasaite, Julija; Schweighofer, Alois; Meskiene, Irute

    2011-01-01

    Protein phosphorylation by protein kinases can be reversed by the action of protein phosphatases. In plants, the Ser/Thr-specific phosphatases dominate among the protein phosphatase families with the type 2C protein phosphatases (PP2Cs) being the most abundant among them. PP2Cs are monomeric enzymes that require metal cations for their activity and are insensitive to known phosphatase inhibitors. PP2Cs were shown to counteract the mitogen-activated protein kinase (MAP kinase/MAPK) activities in plants and to regulate developmental and stress signaling pathways. Studies of PP2C activities can be performed in vitro using recombinant proteins. The potential substrates of PP2Cs can be tested for dephosphorylation by the phosphatase in vitro. We have found that the stress-induced PP2Cs from alfalfa and Arabidopsis interact with stress-activated MAPKs in yeast two-hybrid (Y2H) screens. Consequently, recombinant MAPKs were employed as substrates for dephosphorylation by selected PP2Cs from different family clusters. The members of the PP2C phosphatase family demonstrated specificity toward the substrate already in vitro, supporting the notion that protein phosphatases are specific enzymes. The PP2C from Arabidopsis thaliana cluster B, Arabidopsis PP2C-type phosphatase (AP2C1), and its homolog from Medicago sativa, Medicago PP2C-type phosphatase (MP2C), were able to dephosphorylate and inactivate MAPKs, whereas the ABSCISIC ACID (ABA)-INSENSITIVE 2 (ABI2) and HOMOLOGY TO ABI1 (HAB1) PP2Cs from the distinct Arabidopsis cluster A were not able to do so. The method described here can be used for the determination of PP2C protein activity and for studying the effect of mutations introduced into their catalytic domains.

  11. Inclusive Jet Production in pp¯ Collisions

    NASA Astrophysics Data System (ADS)

    Abbott, B.; Abdesselam, A.; Abolins, M.; Abramov, V.; Acharya, B. S.; Adams, D. L.; Adams, M.; Alves, G. A.; Amos, N.; Anderson, E. W.; Baarmand, M. M.; Babintsev, V. V.; Babukhadia, L.; Bacon, T. C.; Baden, A.; Baldin, B.; Balm, P. W.; Banerjee, S.; Barberis, E.; Baringer, P.; Bartlett, J. F.; Bassler, U.; Bauer, D.; Bean, A.; Begel, M.; Belyaev, A.; Beri, S. B.; Bernardi, G.; Bertram, I.; Besson, A.; Beuselinck, R.; Bezzubov, V. A.; Bhat, P. C.; Bhatnagar, V.; Bhattacharjee, M.; Blazey, G.; Blessing, S.; Boehnlein, A.; Bojko, N. I.; Borcherding, F.; Brandt, A.; Breedon, R.; Briskin, G.; Brock, R.; Brooijmans, G.; Bross, A.; Buchholz, D.; Buehler, M.; Buescher, V.; Burtovoi, V. S.; Butler, J. M.; Canelli, F.; Carvalho, W.; Casey, D.; Casilum, Z.; Castilla-Valdez, H.; Chakraborty, D.; Chan, K. M.; Chekulaev, S. V.; Cho, D. K.; Choi, S.; Chopra, S.; Christenson, J. H.; Chung, M.; Claes, D.; Clark, A. R.; Cochran, J.; Coney, L.; Connolly, B.; Cooper, W. E.; Coppage, D.; Cummings, M. A.; Cutts, D.; Davis, G. A.; Davis, K.; de, K.; del Signore, K.; Demarteau, M.; Demina, R.; Demine, P.; Denisov, D.; Denisov, S. P.; Desai, S.; Diehl, H. T.; Diesburg, M.; di Loreto, G.; Doulas, S.; Draper, P.; Ducros, Y.; Dudko, L. V.; Duensing, S.; Duflot, L.; Dugad, S. R.; Dyshkant, A.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Engelmann, R.; Eno, S.; Eppley, G.; Ermolov, P.; Eroshin, O. V.; Estrada, J.; Evans, H.; Evdokimov, V. N.; Fahland, T.; Feher, S.; Fein, D.; Ferbel, T.; Fisk, H. E.; Fisyak, Y.; Flattum, E.; Fleuret, F.; Fortner, M.; Frame, K. C.; Fuess, S.; Gallas, E.; Galyaev, A. N.; Gao, M.; Gavrilov, V.; Genik, R. J.; Genser, K.; Gerber, C. E.; Gershtein, Y.; Gilmartin, R.; Ginther, G.; Gómez, B.; Gómez, G.; Goncharov, P. I.; González Solís, J. L.; Gordon, H.; Goss, L. T.; Gounder, K.; Goussiou, A.; Graf, N.; Graham, G.; Grannis, P. D.; Green, J. A.; Greenlee, H.; Grinstein, S.; Groer, L.; Grünendahl, S.; Gupta, A.; Gurzhiev, S. N.; Gutierrez, G.; Gutierrez, P.; Hadley, N. J.; Haggerty, H.; Hagopian, S.; Hagopian, V.; Hahn, K. S.; Hall, R. E.; Hanlet, P.; Hansen, S.; Hauptman, J. M.; Hays, C.; Hebert, C.; Hedin, D.; Heinson, A. P.; Heintz, U.; Heuring, T.; Hirosky, R.; Hobbs, J. D.; Hoeneisen, B.; Hoftun, J. S.; Hou, S.; Huang, Y.; Illingworth, R.; Ito, A. S.; Jaffré, M.; Jerger, S. A.; Jesik, R.; Johns, K.; Johnson, M.; Jonckheere, A.; Jones, M.; Jöstlein, H.; Juste, A.; Kahn, S.; Kajfasz, E.; Karmanov, D.; Karmgard, D.; Kim, S. K.; Klima, B.; Klopfenstein, C.; Knuteson, B.; Ko, W.; Kohli, J. M.; Kostritskiy, A. V.; Kotcher, J.; Kotwal, A. V.; Kozelov, A. V.; Kozlovsky, E. A.; Krane, J.; Krishnaswamy, M. R.; Krzywdzinski, S.; Kubantsev, M.; Kuleshov, S.; Kulik, Y.; Kunori, S.; Kuznetsov, V. E.; Landsberg, G.; Leflat, A.; Leggett, C.; Lehner, F.; Li, J.; Li, Q. Z.; Lima, J. G.; Lincoln, D.; Linn, S. L.; Linnemann, J.; Lipton, R.; Lucotte, A.; Lueking, L.; Lundstedt, C.; Luo, C.; Maciel, A. K.; Madaras, R. J.; Manankov, V.; Mao, H. S.; Marshall, T.; Martin, M. I.; Martin, R. D.; Mauritz, K. M.; May, B.; Mayorov, A. A.; McCarthy, R.; McDonald, J.; McMahon, T.; Melanson, H. L.; Meng, X. C.; Merkin, M.; Merritt, K. W.; Miao, C.; Miettinen, H.; Mihalcea, D.; Mishra, C. S.; Mokhov, N.; Mondal, N. K.; Montgomery, H. E.; Moore, R. W.; Mostafa, M.; da Motta, H.; Nagy, E.; Nang, F.; Narain, M.; Narasimham, V. S.; Neal, H. A.; Negret, J. P.; Negroni, S.; Norman, D.; Nunnemann, T.; Oesch, L.; Oguri, V.; Olivier, B.; Oshima, N.; Padley, P.; Pan, L. J.; Papageorgiou, K.; Para, A.; Parashar, N.; Partridge, R.; Parua, N.; Paterno, M.; Patwa, A.; Pawlik, B.; Perkins, J.; Peters, M.; Peters, O.; Pétroff, P.; Piegaia, R.; Piekarz, H.; Pope, B. G.; Popkov, E.; Prosper, H. B.; Protopopescu, S.; Qian, J.; Quintas, P. Z.; Raja, R.; Rajagopalan, S.; Ramberg, E.; Rapidis, P. A.; Reay, N. W.; Reucroft, S.; Rha, J.; Ridel, M.; Rijssenbeek, M.; Rockwell, T.; Roco, M.; Rubinov, P.; Ruchti, R.; Rutherfoord, J.; Santoro, A.; Sawyer, L.; Schamberger, R. D.; Schellman, H.; Schwartzman, A.; Sen, N.; Shabalina, E.; Shivpuri, R. K.; Shpakov, D.; Shupe, M.; Sidwell, R. A.; Simak, V.; Singh, H.; Singh, J. B.; Sirotenko, V.; Slattery, P.; Smith, E.; Smith, R. P.; Snihur, R.; Snow, G. R.; Snow, J.; Snyder, S.; Solomon, J.; Sorín, V.; Sosebee, M.; Sotnikova, N.; Soustruznik, K.; Souza, M.; Stanton, N. R.; Steinbrück, G.; Stephens, R. W.; Stichelbaut, F.; Stoker, D.; Stolin, V.; Stoyanova, D. A.; Strauss, M.; Strovink, M.; Stutte, L.; Sznajder, A.; Taylor, W.; Tentindo-Repond, S.; Thompson, J.; Toback, D.; Tripathi, S. M.; Trippe, T. G.; Turcot, A. S.; Tuts, P. M.; van Gemmeren, P.; Vaniev, V.; van Kooten, R.; Varelas, N.; Volkov, A. A.; Vorobiev, A. P.; Wahl, H. D.; Wang, H.; Wang, Z.-M.; Warchol, J.; Watts, G.; Wayne, M.; Weerts, H.; White, A.; White, J. T.; Whiteson, D.; Wightman, J. A.; Wijngaarden, D. A.; Willis, S.; Wimpenny, S. J.; Wirjawan, J. V.; Womersley, J.; Wood, D. R.; Yamada, R.; Yamin, P.; Yasuda, T.; Yip, K.; Youssef, S.; Yu, J.; Yu, Z.; Zanabria, M.; Zheng, H.; Zhou, Z.; Zielinski, M.; Zieminska, D.; Zieminski, A.; Zutshi, V.; Zverev, E. G.; Zylberstejn, A.

    2001-02-01

    We report a new measurement of the pseudorapidity ( η) and transverse-energy ( ET) dependence of the inclusive jet production cross section in pp¯ collisions at s = 1.8 TeV using 95 pb-1 of data collected with the D0 detector at the Fermilab Tevatron. The differential cross section d2σ/\\(dETdη\\) is presented up to \\|η\\| = 3, significantly extending previous measurements. The results are in good overall agreement with next-to-leading order predictions from QCD and indicate a preference for certain parton distribution functions.

  12. Double Parton Interactions in pp and pA Collisions

    NASA Astrophysics Data System (ADS)

    Treleani, Daniele; Calucci, Giorgio; Salvini, Simona

    2016-11-01

    As a consequence of the increasingly large flux of partons at small x, Double Parton Interactions (DPI) play an increasingly important role at high energies. A detail understanding of DPI dynamics is therefore mandatory, for a reliable subtraction of the background in the search of new physics. On the other hand, DPI are an interesting topic of research by themselves, as DPI probe the hadron structure in a rather different way, as compared with the large pt processes usually considered. In this note we will make a short illustration of some of the main features characterizing DPI in pp and in pA collisions.

  13. RHIC FY15 pp Run RHIC and AGS polarization analysis

    SciTech Connect

    Huang, H.; Adams, P.

    2016-02-20

    The polarization information is important for the spin physics program in Relativistic Heavy Ion Collider (RHIC). There are discrepancies between AGS and RHIC polarization measurements. First, the face value of AGS polarization is higher than RHIC ones in general. Second, the measured polarization profile (described by the profile ratio R) is stronger in AGS than in RHIC. This note analyzes the polarization data from FY15 pp run period. The results show that the differences between AGS and RHIC polarization measurements are reasonable, but the R value difference is puzzling. The difference between blue and yellow ring is worth of spin simulation to explain.

  14. An altered form of pp60/sup c-src/ is expressed primarily in the central nervous system

    SciTech Connect

    Le Beau, J.M.; Wiestler, O.D.; Walter, G.

    1987-11-01

    The expression of two forms of pp60/sup c-scr/, pp60 and pp60/sup +/, was measured in the central nervous system (CNS) and the peripheral nervous system. Both forms were expressed in the CNS, whereas only pp60 was primarily detected in the peripheral nervous system. Our findings suggest that pp60/sup +/ may play a role in events important to the CNS.

  15. Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase type 5 (PP5)

    NASA Technical Reports Server (NTRS)

    Swingle, Mark R.; Ciszak, Ewa M.; Honkanen, Richard E.

    2004-01-01

    Serine/threonine protein phosphatase-5 (PP5) is a member of the PPP-gene family of protein phosphatases that is widely expressed in mammalian tissues and is highly conserved among eukaryotes. PP5 associates with several proteins that affect signal transduction networks, including the glucocorticoid receptor (GR)-heat shock protein-90 (Hsp90)-heterocomplex, the CDC16 and CDC27 subunits of the anaphase-promoting complex, elF2alpha kinase, the A subunit of PP2A, the G12-alpha / G13-alpha subunits of heterotrimeric G proteins and DNA-PK. The catalytic domain of PP5 (PP5c) shares 35-45% sequence identity with the catalytic domains of other PPP-phosphatases, including protein phosphatase-1 (PP1), -2A (PP2A), -2B / calcineurin (PP2B), -4 (PP4), -6 (PP6), and -7 (PP7). Like PP1, PP2A and PP4, PP5 is also sensitive to inhibition by okadaic acid, microcystin, cantharidin, tautomycin, and calyculin A. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 angstroms. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp(sup 271)-M(sub 1):M(sub 2)-W(sup 1)-His(sup 304)-Asp(sup 274) catalytic motif. The structure of PP5c provides a possible structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

  16. Molecular Mimicry Regulates ABA Signaling by SnRK2 Kinases and PP2C Phosphatases

    SciTech Connect

    Soon, Fen-Fen; Ng, Ley-Moy; Zhou, X. Edward; West, Graham M.; Kovach, Amanda; Tan, M.H. Eileen; Suino-Powell, Kelly M.; He, Yuanzheng; Xu, Yong; Chalmers, Michael J.; Brunzelle, Joseph S.; Zhang, Huiming; Yang, Huaiyu; Jiang, Hualiang; Li, Jun; Yong, Eu-Leong; Cutler, Sean; Zhu, Jian-Kang; Griffin, Patrick R.; Melcher, Karsten; Xu, H. Eric

    2014-10-02

    Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites.

  17. Molecular Mimicry Regulates ABA Signaling by SnRK2 Kinases and PP2C Phosphatases

    PubMed Central

    Soon, Fen-Fen; Ng, Ley-Moy; Zhou, X. Edward; West, Graham M.; Kovach, Amanda; Tan, M. H. Eileen; Suino-Powell, Kelly M.; He, Yuanzheng; Xu, Yong; Chalmers, Michael J.; Brunzelle, Joseph S.; Zhang, Huiming; Yang, Huaiyu; Jiang, Hualiang; Li, Jun; Yong, Eu-Leong; Cutler, Sean; Zhu, Jian-Kang; Griffin, Patrick R.; Melcher, Karsten; Xu, H. Eric

    2013-01-01

    Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites. PMID:22116026

  18. ppGpp couples transcription to DNA repair in E. coli.

    PubMed

    Kamarthapu, Venu; Epshtein, Vitaly; Benjamin, Bradley; Proshkin, Sergey; Mironov, Alexander; Cashel, Michael; Nudler, Evgeny

    2016-05-20

    The small molecule alarmone (p)ppGpp mediates bacterial adaptation to nutrient deprivation by altering the initiation properties of RNA polymerase (RNAP). ppGpp is generated in Escherichia coli by two related enzymes, RelA and SpoT. We show that ppGpp is robustly, but transiently, induced in response to DNA damage and is required for efficient nucleotide excision DNA repair (NER). This explains why relA-spoT-deficient cells are sensitive to diverse genotoxic agents and ultraviolet radiation, whereas ppGpp induction renders them more resistant to such challenges. The mechanism of DNA protection by ppGpp involves promotion of UvrD-mediated RNAP backtracking. By rendering RNAP backtracking-prone, ppGpp couples transcription to DNA repair and prompts transitions between repair and recovery states.

  19. Study of Processing and Mechanical Behavior of Pp/clay Nanocomposites Prepared by Melt Blending

    NASA Astrophysics Data System (ADS)

    Shirazi, Sareh Mosleh; Janghorban, Kamal

    In this research, the melt blending technique was used to prepare various polypropylene (PP) based nanocomposites containing 1,3,5,7 wt% montmorillonite (MMT). A commercial organoclay (denoted K-10) served as the filler for PP matrix and the polypropylene grafted maleic anhydride (PP-g-MA) was used as compatibalizer. The morphology of the nanocomposites was studied by X-ray diffraction (XRD), results of which showed that the nanocomposites are best described as intercalated-exfoliated systems. PP/MMT nanocomposites showed good thermal stability in the TGA analysis. Introducion of 3% MMT in the nanocomposites increased the onset temperature of the degradation by 27.5 °C compared to that of pure PP. Test results showed that PP/clay nanocomposites had an enhanced tensile strength, hardness and decreased wear rates.

  20. Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases.

    PubMed

    Soon, Fen-Fen; Ng, Ley-Moy; Zhou, X Edward; West, Graham M; Kovach, Amanda; Tan, M H Eileen; Suino-Powell, Kelly M; He, Yuanzheng; Xu, Yong; Chalmers, Michael J; Brunzelle, Joseph S; Zhang, Huiming; Yang, Huaiyu; Jiang, Hualiang; Li, Jun; Yong, Eu-Leong; Cutler, Sean; Zhu, Jian-Kang; Griffin, Patrick R; Melcher, Karsten; Xu, H Eric

    2012-01-06

    Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites.

  1. Recent functional insights into the role of (p)ppGpp in bacterial physiology

    PubMed Central

    Hauryliuk, Vasili; Atkinson, Gemma C.; Murakami, Katsuhiko S.; Tenson, Tanel; Gerdes, Kenn

    2015-01-01

    The alarmone (p)ppGpp is involved in regulating growth and several different stress responses in bacteria. In recent years, substantial progress has been made in our understanding of the molecular mechanisms of (p)ppGpp metabolism and (p)ppGpp-mediated regulation. In this Review, we summarize these recent insights, with a focus on the molecular mechanisms governing the activity of the RelA/SpoT Homologue (RSH) proteins, which are key players that regulate the cellular leves of (p)ppGpp, the structural basis of transcriptional regulation by (p)ppGpp and the role of (p)ppGpp in GTP metabolism and in the emergence of bacterial persisters. PMID:25853779

  2. PR55α, a Regulatory Subunit of PP2A, Specifically Regulates PP2A-mediated β-Catenin Dephosphorylation

    PubMed Central

    Zhang, Wen; Yang, Jun; Liu, Yajuan; Chen, Xi; Yu, Tianxin; Jia, Jianhang; Liu, Chunming

    2009-01-01

    A central question in Wnt signaling is the regulation of β-catenin phosphorylation and degradation. Multiple kinases, including CKIα and GSK3, are involved in β-catenin phosphorylation. Protein phosphatases such as PP2A and PP1 have been implicated in the regulation of β-catenin. However, which phosphatase dephosphorylates β-catenin in vivo and how the specificity of β-catenin dephosphorylation is regulated are not clear. In this study, we show that PP2A regulates β-catenin phosphorylation and degradation in vivo. We demonstrate that PP2A is required for Wnt/β-catenin signaling in Drosophila. Moreover, we have identified PR55α as the regulatory subunit of PP2A that controls β-catenin phosphorylation and degradation. PR55α, but not the catalytic subunit, PP2Ac, directly interacts with β-catenin. RNA interference knockdown of PR55α elevates β-catenin phosphorylation and decreases Wnt signaling, whereas overexpressing PR55α enhances Wnt signaling. Taken together, our results suggest that PR55α specifically regulates PP2A-mediated β-catenin dephosphorylation and plays an essential role in Wnt signaling. PMID:19556239

  3. Internal meson dominance for pp-bar annihilation

    SciTech Connect

    Brix, G.; Genz, H.; Tatur, S.

    1989-04-01

    The previously considered /sup 3/S/sub 1/ internal fusion model of pp-bar..-->..YY-bar, YY-bar /sup */, and Y/sup */Y-bar/sup */ (Y denotes hyperon) at low energies is modified and thereby extended to also include pp-bar..-->..nn-bar and ..delta../sup ++/Delta-bar/sup - -/. It is assumed that the same nonperturbative mechanism that mixes the different qq-bar pairs within the neutral, nonstrange mesons is also responsible for the scattering, annihilation, and creation of qq-bar pairs within the baryon-antibaryon system. More specifically, we assume that processes qq-bar..-->..QQ-bar within the baryon-antibaryon system with q = d or u and Q = d, u, or s quarks is mediated by fusion of the qq-bar to a pseudoscalar or vector meson that also within the system decays into QQ-bar. The /sup 1/S/sub 0/ pseudoscalar-meson model disagrees with experiment whereas the /sup 3/S/sub 1/ vector-meson fusion model is in reasonable agreement with it. As compared to the previously considered /sup 3/S/sub 1/ internal fusion model the main change is an extension of the approximate agreement to the nonstrange final-state baryons. This is achieved since strange baryons in the model are only produced via the small ..omega..-phi mixing.

  4. Targeting of PP2C in budding yeast.

    PubMed

    Ota, Irene M; Mapes, James

    2007-01-01

    Type 2C Ser/Thr phosphatases or PP2Cs are monomeric metal-requiring protein phosphatases that are present in prokaryotes and eukaryotes. In the yeast Saccharomyces cerevisiae, there are seven PP2Cs called PTCs (phosphatase 2C). Molecular genetic studies have implicated PTCs in many different functions, including RNA splicing, the unfolded protein response, mitogen-activated protein kinase (MAPK) pathway, and cell-cycle regulation. We have shown that three PTCs (Ptc1, Ptc2, and Ptc3), regulate the stress-activated high-osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathway. Proteomics studies have provided additional possible functions for these phosphatases by identifying interacting proteins. These studies have also provided the possible means by which these phosphatases are targeted to their substrates. For example, Nbp2-Ptc1 was identified as an interacting pair in yeast two-hybrid studies, and Nbp2 was found together with Ptc1 and HOG pathway kinases. We have shown that Nbp2 is an adapter in this pathway, mediating interaction between Ptc1 and the Pbs2 MAP/ERK kinase in the HOG pathway.

  5. N* production from pp and p-barp collisions

    SciTech Connect

    Wu Jiajun; Cao Xu; Molina, R.; Oset, E.; Zou, B. S.

    2011-10-21

    With an effective Lagrangian approach, we give a full analysis on the NN{yields}NN{pi}{pi} and pp{yields}pn{pi}{sup +} reactions for proton beam energy from 1 to 1.5 GeV. The results are very consistent with the experiment data from CELSIUS, KEK, COSY, and so on. Based on these results, we consider the N-barN{yields}N-barN{pi}{pi} and p-barp{yields}p-barn{pi}{sup +} for proton beam energy up to 4 GeV. Compare to the pp collisions, there are many benefits to study N* resonances in these two reactions. And for the high proton beam energy up to 15 GeV, we consider some new resonances with hidden charm which are definitely beyond three constituent quarks model in the p-barp{yields}p-barpJ/{psi} and p-barp{yields}p-barp{eta}{sub c}, where there are very nice places to find these new N{sub cc}-bar*. The predicted results about p-barp collisions can be looked for at the forthcoming PANDA/FAIR experiments.

  6. 5-ALA/PpIX fluorescence detection of gastrointestinal neoplasia

    NASA Astrophysics Data System (ADS)

    Borisova, Ekaterina G.; Vladimirov, Borislav; Terziev, Ivan; Ivanova, Radina; Avramov, Latchezar

    2009-07-01

    In the recent study delta-ALA/PpIX is used as fluorescent marker for dysplasia and tumor detection in esophagus, stomach and colon. ALA is administered per os six to eight (depending on the lesion location) hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built for the LED to use the light guide of standard video-endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. The fluorescence detected from tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to re-absorption of oxy-hemoglobin in this spectral area. Endogenous and exogenous fluorescence spectra are used to develop simple but effective algorithm, based on dimensionless ratio of the signals at 560 and 635 nm, for differentiation of normal/abnormal gastrointestinal tissues. Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

  7. A PP6-type phosphatase holoenzyme directly regulates PIN phosphorylation and auxin efflux in Arabidopsis.

    PubMed

    Dai, Mingqiu; Zhang, Chen; Kania, Urszula; Chen, Fang; Xue, Qin; McCray, Tyra; Li, Gang; Qin, Genji; Wakeley, Michelle; Terzaghi, William; Wan, Jianmin; Zhao, Yunde; Xu, Jian; Friml, Jirí; Deng, Xing Wang; Wang, Haiyang

    2012-06-01

    The directional transport of the phytohormone auxin depends on the phosphorylation status and polar localization of PIN-FORMED (PIN) auxin efflux proteins. While PINIOD (PID) kinase is directly involved in the phosphorylation of PIN proteins, the phosphatase holoenzyme complexes that dephosphorylate PIN proteins remain elusive. Here, we demonstrate that mutations simultaneously disrupting the function of Arabidopsis thaliana FyPP1 (for Phytochrome-associated serine/threonine protein phosphatase1) and FyPP3, two homologous genes encoding the catalytic subunits of protein phosphatase6 (PP6), cause elevated accumulation of phosphorylated PIN proteins, correlating with a basal-to-apical shift in subcellular PIN localization. The changes in PIN polarity result in increased root basipetal auxin transport and severe defects, including shorter roots, fewer lateral roots, defective columella cells, root meristem collapse, abnormal cotyledons (small, cup-shaped, or fused cotyledons), and altered leaf venation. Our molecular, biochemical, and genetic data support the notion that FyPP1/3, SAL (for SAPS DOMAIN-LIKE), and PP2AA proteins (RCN1 [for ROOTS CURL IN NAPHTHYLPHTHALAMIC ACID1] or PP2AA1, PP2AA2, and PP2AA3) physically interact to form a novel PP6-type heterotrimeric holoenzyme complex. We also show that FyPP1/3, SAL, and PP2AA interact with a subset of PIN proteins and that for SAL the strength of the interaction depends on the PIN phosphorylation status. Thus, an Arabidopsis PP6-type phosphatase holoenzyme acts antagonistically with PID to direct auxin transport polarity and plant development by directly regulating PIN phosphorylation.

  8. Updating Boer-Mulders functions from unpolarized pd and pp Drell-Yan data

    SciTech Connect

    Lu Zhun; Schmidt, Ivan

    2010-02-01

    We extract the Boer-Mulders functions for the proton by combining the unpolarized pd and pp Drell-Yan data measured by the E866/NuSea Collaboration by the assumption that the cos2{phi} asymmetry is from the Boer-Mulders functions. Using the extracted Boer-Mulders functions, we present the predictions for the cos2{phi} asymmetries in future pp experiments at J-PARC and pp experiments at PANDA and PAX.

  9. ToF-SIMS imaging of PE/PP polymer using multivariate analysis

    NASA Astrophysics Data System (ADS)

    Miyasaka, Toyomitsu; Ikemoto, Takashi; Kohno, Teiichiro

    2008-12-01

    The distribution of polyethylene (PE) and polypropylene (PP) in PE/PP blended-polymer film was determined by applying principal components analysis (PCA) and multivariate curve resolution (MCR) to time-of-flight secondary ion mass spectroscopy (ToF-SIMS) imaging, together with preprocessing by pixel binning, normalization, and autoscaling to increase image contrast by reducing topographic and charge-distribution effects. The PE/PP distribution was confirmed by MVA conducted on the image data over static limit. The MCR score with normalized-autoscaling was found to give the PE/PP distribution distinctly.

  10. Differential regulation by ppGpp versus pppGpp in Escherichia coli.

    PubMed

    Mechold, Undine; Potrykus, Katarzyna; Murphy, Helen; Murakami, Katsuhiko S; Cashel, Michael

    2013-07-01

    Both ppGpp and pppGpp are thought to function collectively as second messengers for many complex cellular responses to nutritional stress throughout biology. There are few indications that their regulatory effects might be different; however, this question has been largely unexplored for lack of an ability to experimentally manipulate the relative abundance of ppGpp and pppGpp. Here, we achieve preferential accumulation of either ppGpp or pppGpp with Escherichia coli strains through induction of different Streptococcal (p)ppGpp synthetase fragments. In addition, expression of E. coli GppA, a pppGpp 5'-gamma phosphate hydrolase that converts pppGpp to ppGpp, is manipulated to fine tune differential accumulation of ppGpp and pppGpp. In vivo and in vitro experiments show that pppGpp is less potent than ppGpp with respect to regulation of growth rate, RNA/DNA ratios, ribosomal RNA P1 promoter transcription inhibition, threonine operon promoter activation and RpoS induction. To provide further insights into regulation by (p)ppGpp, we have also determined crystal structures of E. coli RNA polymerase-σ(70) holoenzyme with ppGpp and pppGpp. We find that both nucleotides bind to a site at the interface between β' and ω subunits.

  11. Protein phosphatase 2C (PP2C) function in higher plants.

    PubMed

    Rodriguez, P L

    1998-12-01

    In the past few years, molecular cloning studies have revealed the primary structure of plant protein serine/threonine phosphatases. Two structurally distinct families, the PP1/PP2A family and the PP2C family, are present in plants as well as in animals. This review will focus on the plant PP2C family of protein phosphatases. Biochemical and molecular genetic studies in Arabidopsis have identified PP2C enzymes as key players in plant signal transduction processes. For instance, the ABI1/ABI2 PP2Cs are central components in abscisic acid (ABA) signal transduction. Arabidopsis mutants containing a single amino acid exchange in ABI1 or ABI2 show a reduced response to ABA. Another member of the PP2C family, kinase-associated protein phosphatase (KAPP), appears to be an important element in some receptor-like kinase (RLK) signalling pathways. Finally, an alfalfa PP2C acts as a negative regulator of a plant mitogen-activated protein kinase (MAPK) pathway. Thus, the plant PP2Cs function as regulators of various signal transduction pathways.

  12. Characterization and interstrain transfer of prophage pp3 of Pseudomonas aeruginosa

    PubMed Central

    Li, Gang; Lu, Shuguang; Shen, Mengyu; Le, Shuai; Shen, Wei; Tan, Yinling; Wang, Jing; Zhao, Xia; Zhao, Yan; Gong, Yali; Yang, Yuhui; Zhu, Hongbin; Hu, Fuquan

    2017-01-01

    Prophages are major contributors to horizontal gene transfer and drive the evolution and diversification of bacteria. Here, we describe the characterization of a prophage element designated pp3 in the clinical Pseudomonas aeruginosa isolate PA1. pp3 spontaneously excises from the PA1 genome and circularizes at a very high frequency of 25%. pp3 is likely to be a defective prophage due to its inability to form plaques on P. aeruginosa indicator strains, and no phage particles could be detected in PA1 supernatants. The pp3-encoded integrase is essential for excision by mediating site-specific recombination at the 26-bp attachment sequence. Using a filter mating experiment, we demonstrated that pp3 can transfer into P. aeruginosa recipient strains that do not possess this element naturally. Upon transfer, pp3 integrates into the same attachment site as in PA1 and maintains the ability to excise and circularize. Furthermore, pp3 significantly promotes biofilm formation in the recipient. Sequence alignment reveals that the 26-bp attachment site recognized by pp3 is conserved in all P. aeruginosa strains sequenced to date, making it possible that pp3 could be extensively disseminated in P. aeruginosa. This work improves our understanding of the ways in which prophages influence bacterial behavior and evolution. PMID:28346467

  13. The Structural Basis for Tight Control of PP2A Methylation and Function by LCMT-1

    SciTech Connect

    V Stanevich; L Jiang; K Satyshur; Y Li; P Jeffrey; Z Li; P Menden; M Semmelhack; Y Xing

    2011-12-31

    Proper formation of protein phosphatase 2A (PP2A) holoenzymes is essential for the fitness of all eukaryotic cells. Carboxyl methylation of the PP2A catalytic subunit plays a critical role in regulating holoenzyme assembly; methylation is catalyzed by PP2A-specific methyltransferase LCMT-1, an enzyme required for cell survival. We determined crystal structures of human LCMT-1 in isolation and in complex with PP2A stabilized by a cofactor mimic. The structures show that the LCMT-1 active-site pocket recognizes the carboxyl terminus of PP2A, and, interestingly, the PP2A active site makes extensive contacts to LCMT-1. We demonstrated that activation of the PP2A active site stimulates methylation, suggesting a mechanism for efficient conversion of activated PP2A into substrate-specific holoenzymes, thus minimizing unregulated phosphatase activity or formation of inactive holoenzymes. A dominant-negative LCMT-1 mutant attenuates the cell cycle without causing cell death, likely by inhibiting uncontrolled phosphatase activity. Our studies suggested mechanisms of LCMT-1 in tight control of PP2A function, important for the cell cycle and cell survival.

  14. The Structural Basis for Tight Control of PP2A Methylation and Function by LCMT-1

    SciTech Connect

    Stanevich, Vitali; Jiang, Li; Satyshur, Kenneth A.; Li, Yongfeng; Jeffrey, Philip D.; Li, Zhu; Menden, Patrick; Semmelhack, Martin F.; Xing, Yongna

    2012-05-29

    Proper formation of protein phosphatase 2A (PP2A) holoenzymes is essential for the fitness of all eukaryotic cells. Carboxyl methylation of the PP2A catalytic subunit plays a critical role in regulating holoenzyme assembly; methylation is catalyzed by PP2A-specific methyltransferase LCMT-1, an enzyme required for cell survival. We determined crystal structures of human LCMT-1 in isolation and in complex with PP2A stabilized by a cofactor mimic. The structures show that the LCMT-1 active-site pocket recognizes the carboxyl terminus of PP2A, and, interestingly, the PP2A active site makes extensive contacts to LCMT-1. We demonstrated that activation of the PP2A active site stimulates methylation, suggesting a mechanism for efficient conversion of activated PP2A into substrate-specific holoenzymes, thus minimizing unregulated phosphatase activity or formation of inactive holoenzymes. A dominant-negative LCMT-1 mutant attenuates the cell cycle without causing cell death, likely by inhibiting uncontrolled phosphatase activity. Our studies suggested mechanisms of LCMT-1 in tight control of PP2A function, important for the cell cycle and cell survival.

  15. The spectroscopy analyses of PpIX by ultrasound irradiation and its sonotoxicity in vitro.

    PubMed

    Wang, Pan; Wang, Xiaobing; Zhang, Kun; Gao, Kaili; Song, Ming; Liu, Quanhong

    2013-07-01

    Protoporphyrin IX (PpIX) has been used as a sensitizer in photodynamic therapy (PDT) as well as in sonodynamic therapy (SDT). The photo-bleaching of PpIX has been well investigated in many experimental systems and some photo-products have also been identified in PDT. But until now, little information has been reported about the sono-damage of PpIX in SDT. So, the present study was to investigate changes of PpIX properties before and after different ultrasound treatment, and the potential interactions between PpIX, ultrasound and the irradiated cells. In cell-free system, the absorption and fluorescence spectra of PpIX in different solutions were measured by ultraviolet spectrometer and fluorescence spectrophotometer, respectively. The terephthalic acid dosimetry was applied to evaluate the efficiency of ultrasound cavitation by monitoring hydroxyl radical (OH) production on the thermolysis of H2O in the ultrasound field. In in vitro study, confocal microscopy was applied to detect the sub-cellular localization of PpIX in S180 cells before and after ultrasound exposure. Flow cytometry was used to detect the reactive oxygen species (ROS) generation during PpIX-SDT. MTT assay was performed to evaluate the cell viability of S180 cells after SDT treatment with or without ROS scavengers. The results show that PpIX displayed different spectral patterns in different solutions. PpIX was decomposed by ultrasound exposure as measured by the decreased absorption and fluorescence peak values in RPMI-1640 medium. In addition, the decomposition of PpIX was found to be simultaneously accompanied by OH production with increasing output power from ultrasound generator. PpIX at 1μg/ml significantly enhanced the ultrasound induced cavitation as measured by OH generation, and which was greatly eliminated by NaN3, histidine, mannitol, EDTA and catalase, but not by SOD. The in vitro study indicates more PpIX entered into S180 cells after ultrasound exposure. And, the extra-cellular Pp

  16. pp{yields}p{Lambda}K{sup +} reaction in search for the K{sup -}pp state - quest for a kaonic nuclei

    SciTech Connect

    Suzuki, Ken; Kienle, Paul; Maggiora, Marco; Yamazaki, Toshimitsu

    2011-10-21

    The dibaryonic kaonic nuclear bound state, K{sup -}pp is searched by studying an exclusive p+p{yields}p+{Lambda}+K{sup +} process at several beam energies. A signature of the K{sup -}pp is explored in a p+p{yields}X({identical_to}K{sup -}pp)+K{sup +} reaction that follows a decay of the X into p+{Lambda}. We found in a missing-mass {Delta}M(K{sup +}) spectrum and a {Lambda}p invariant-mass M({Lambda}p) spectrum of DISTO data at 2.85 GeV a resonance with M = 2267 MeV/c{sup 2} and {Gamma} = 118 MeV. Those events are found to be associated with a mono energetic kaon. We investigate this resonance as a candidate of the K{sup -}pp further also with a different beam energies.

  17. Rheological and thermal properties of PP-based WPC

    NASA Astrophysics Data System (ADS)

    Mazzanti, V.; Mollica, F.; El Kissi, N.

    2014-05-01

    Wood Plastic Composite (WPC) has attracted great interest in outdoor building products for the reduced cost and the possibility of using recycled materials. Nevertheless the material shows two problems: the large viscosity due to the presence of high concentrations of filler and the degradation of cellulose during processing The aim of this work was to investigate the rheological and thermal properties of WPC. The material used for the experiments was a commercial PP-based WPC compound, with different concentrations of natural fibers (30, 50, 70% wt.). The thermal properties were studied to check for degradation of natural fibers during the subsequent rheological tests. Analyzing the storage and loss moduli and the complex viscosity curves obtained using a parallel plate rheometer it was possible to observe some features related to the viscoelastic nature of the composite.

  18. VII Workshop Italiano sulla fisica pp a LHC

    NASA Astrophysics Data System (ADS)

    LHCpp2016 è la settima edizione dell'incontro nazionale sulla fisica p-p a LHC. Questa serie di incontri è nata a Pisa nel 2003 con lo scopo di stimolare lo scambio di idee tra le comunità sperimentali di ATLAS, CMS e LHCB e la comunità teorica. Caratteristica fondamentale di questi incontri è la preparazione di larga parte dei talk in collaborazione tra i vari esperimenti e la comunità teorica. Largo spazio nella preparazione e presentazione dei talk viene dato ai giovani ricercatori. In questa settima edizione, che si tiene di nuovo a Pisa, vogliamo concentrare l'attenzione sulle potenzialità di scoperta offerte dai dati raccolti durante il runII di LHC.

  19. {phi} meson production in pp annihilation at rest

    SciTech Connect

    Srisuphaphon, S.; Yan, Y.; Gutsche, Thomas; Lyubovitskij, Valery E.

    2011-10-01

    Apparent channel-dependent violations of the Okubo-Zwieg-Iizuka (OZI) rule in nucleon-antinucleon annihilation reactions in the presence of an intrinsic strangeness component in the nucleon are discussed. Admixture of ss quark pairs in the nucleon wave function enables the direct coupling to the {phi}-meson in the annihilation channel without violating the OZI rule. Three forms are considered in this work for the strangeness content of the proton wave function, namely, the uud cluster with a ss sea-quark component, kaon-hyperon clusters based on a simple chiral quark model, and the pentaquark picture uudss. Nonrelativistic quark model calculations reveal that the strangeness magnetic moment {mu}{sub s} and the strangeness contribution to the proton spin {sigma}{sub s} from the first two models are consistent with recent experimental data, where {mu}{sub s} and {sigma}{sub s} are negative. For the third model, the uuds subsystem with the configurations [31]{sub FS}[211]{sub F}[22]{sub S} and [31]{sub FS}[31]{sub F}[22]{sub S} leads to negative values of {mu}{sub s} and {sigma}{sub s}. With effective quark line diagrams incorporating the {sup 3}P{sub 0} model, we give estimates for the branching ratios of the annihilation reactions at rest pp{yields}{phi}X (X={pi}{sup 0}, {eta}, {rho}{sup 0}, {omega}). Results for the branching ratios of {phi}X production from atomic pp s-wave states are for the first and third model found to be strongly channel dependent, in good agreement with measured rates.

  20. Cytotoxicity of PP(Arg)2- and PP(Ala)2(Arg)2-based photodynamic therapy and early stage of apoptosis induction in human breast cancers in vitro.

    PubMed

    Nowak-Stępniowska, Agata; Wiktorska, Katarzyna; Małecki, Maciej; Milczarek, Małgorzata; Lubelska, Katarzyna; Padzik-Graczyk, Alfreda

    2012-01-01

    Mitochondria are cell energetic centers where ATP is produced. They also play a very important role in the PDT as intracellular sites of photosensitizer localization. Photosensitizers gathering in mitochondria (like porphyrin derivatives used in this work) are more effective in tumor cell destruction. Moreover, it was assumed that di-amino acid substituents attached to porphyrin ring will strengthen the effectivity of interaction with membrane receptors of examined cells. MTT assay was performed to investigate the influence of PP(Arg)(2) and PP(Ala)(2)(Arg)(2)-based PDT on breast cancer cell viability for 24 h, 48 h and 120 h after cell irradiation. Then the influence of PP(Ala)(2)(Arg)(2)- and PP(Arg)(2)-mediated PDT on early mitochondrial apoptosis induction via measurements of the transmembrane mitochondrial potential changes was examined. Results showed that lower energy doses and maximal nontoxic photosensitizer doses of PP(Ala)(2)(Arg)(2) and PP(Arg)(2) applied in PDT can imply apoptotic cell death. It was confirmed that modification of the protoporphyrin IX by attaching two alanine substituents raised the efficiency of photodynamic therapy.

  1. Suggested Involvement of PP1/PP2A Activity and De Novo Gene Expression in Anhydrobiotic Survival in a Tardigrade, Hypsibius dujardini, by Chemical Genetic Approach.

    PubMed

    Kondo, Koyuki; Kubo, Takeo; Kunieda, Takekazu

    2015-01-01

    Upon desiccation, some tardigrades enter an ametabolic dehydrated state called anhydrobiosis and can survive a desiccated environment in this state. For successful transition to anhydrobiosis, some anhydrobiotic tardigrades require pre-incubation under high humidity conditions, a process called preconditioning, prior to exposure to severe desiccation. Although tardigrades are thought to prepare for transition to anhydrobiosis during preconditioning, the molecular mechanisms governing such processes remain unknown. In this study, we used chemical genetic approaches to elucidate the regulatory mechanisms of anhydrobiosis in the anhydrobiotic tardigrade, Hypsibius dujardini. We first demonstrated that inhibition of transcription or translation drastically impaired anhydrobiotic survival, suggesting that de novo gene expression is required for successful transition to anhydrobiosis in this tardigrade. We then screened 81 chemicals and identified 5 chemicals that significantly impaired anhydrobiotic survival after severe desiccation, in contrast to little or no effect on survival after high humidity exposure only. In particular, cantharidic acid, a selective inhibitor of protein phosphatase (PP) 1 and PP2A, exhibited the most profound inhibitory effects. Another PP1/PP2A inhibitor, okadaic acid, also significantly and specifically impaired anhydrobiotic survival, suggesting that PP1/PP2A activity plays an important role for anhydrobiosis in this species. This is, to our knowledge, the first report of the required activities of signaling molecules for desiccation tolerance in tardigrades. The identified inhibitory chemicals could provide novel clues to elucidate the regulatory mechanisms underlying anhydrobiosis in tardigrades.

  2. Suggested Involvement of PP1/PP2A Activity and De Novo Gene Expression in Anhydrobiotic Survival in a Tardigrade, Hypsibius dujardini, by Chemical Genetic Approach

    PubMed Central

    Kondo, Koyuki; Kubo, Takeo; Kunieda, Takekazu

    2015-01-01

    Upon desiccation, some tardigrades enter an ametabolic dehydrated state called anhydrobiosis and can survive a desiccated environment in this state. For successful transition to anhydrobiosis, some anhydrobiotic tardigrades require pre-incubation under high humidity conditions, a process called preconditioning, prior to exposure to severe desiccation. Although tardigrades are thought to prepare for transition to anhydrobiosis during preconditioning, the molecular mechanisms governing such processes remain unknown. In this study, we used chemical genetic approaches to elucidate the regulatory mechanisms of anhydrobiosis in the anhydrobiotic tardigrade, Hypsibius dujardini. We first demonstrated that inhibition of transcription or translation drastically impaired anhydrobiotic survival, suggesting that de novo gene expression is required for successful transition to anhydrobiosis in this tardigrade. We then screened 81 chemicals and identified 5 chemicals that significantly impaired anhydrobiotic survival after severe desiccation, in contrast to little or no effect on survival after high humidity exposure only. In particular, cantharidic acid, a selective inhibitor of protein phosphatase (PP) 1 and PP2A, exhibited the most profound inhibitory effects. Another PP1/PP2A inhibitor, okadaic acid, also significantly and specifically impaired anhydrobiotic survival, suggesting that PP1/PP2A activity plays an important role for anhydrobiosis in this species. This is, to our knowledge, the first report of the required activities of signaling molecules for desiccation tolerance in tardigrades. The identified inhibitory chemicals could provide novel clues to elucidate the regulatory mechanisms underlying anhydrobiosis in tardigrades. PMID:26690982

  3. Evidence for CP violation in B+ → ppK+ decays.

    PubMed

    Aaij, R; Adeva, B; Adinolfi, M; Affolder, A; 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; Anderson, J; Andreassen, R; Andreotti, M; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Badalov, A; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M-O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Borsato, M; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brodzicka, J; Brook, N H; Brown, H; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Calabrese, R; Calvi, M; Calvo Gomez, M; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cenci, R; Charles, M; Charpentier, Ph; Chefdeville, M; Chen, S; Cheung, S-F; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coco, V; Cogan, J; Cogneras, E; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Corvo, M; Counts, I; Couturier, B; Cowan, G A; Craik, D C; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; Dalseno, J; David, P; David, P N Y; Davis, A; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Donleavy, S; Dordei, F; Dorigo, M; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dreimanis, K; Dujany, G; Dupertuis, F; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Ely, S; Esen, S; Evans, H-M; Evans, T; Falabella, A; Färber, C; Farinelli, C; Farley, N; Farry, S; Fay, Rf; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Fu, J; Furfaro, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; García Pardiñas, J; Garofoli, J; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gavardi, L; Gavrilov, G; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianelle, A; Giani', S; Gibson, V; Giubega, L; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gotti, C; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Griffith, P; Grillo, L; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hamilton, B; Hampson, T; Han, X; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; He, J; Head, T; Heijne, V; Hennessy, K; Henrard, P; Henry, L; Hernando Morata, J A; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hoballah, M; Hombach, C; Hulsbergen, W; Hunt, P; Hussain, N; Hutchcroft, D; Hynds, D; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jalocha, J; Jans, E; Jaton, P; Jawahery, A; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kaballo, M; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Karodia, S; Kelsey, M; Kenyon, I R; Ketel, T; Khanji, B; Khurewathanakul, C; Klaver, S; Klimaszewski, K; Kochebina, O; Kolpin, M; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kurek, K; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanfranchi, G; Langenbruch, C; Langhans, B; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Likhomanenko, T; Liles, M; Lindner, R; Linn, C; Lionetto, F; Liu, B; Lohn, S; Longstaff, I; Lopes, J H; Lopez-March, N; Lowdon, P; Lu, H; Lucchesi, D; Luo, H; Lupato, A; Luppi, E; Lupton, O; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Malinin, A; Manca, G; Mancinelli, G; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marino, P; Märki, R; Marks, J; Martellotti, G; Martens, A; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Mazurov, A; McCann, M; McCarthy, J; McNab, A; McNulty, R; McSkelly, B; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M-N; Moggi, N; Molina Rodriguez, J; Monteil, S; Morandin, M; Morawski, P; Mordà, A; Morello, M J; Moron, J; Morris, A-B; Mountain, R; Muheim, F; Müller, K; Mussini, M; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Novoselov, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Onderwater, G; Orlandea, M; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palombo, F; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Pappalardo, L L; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrignani, C; Pazos Alvarez, A; Pearce, A; Pellegrino, A; Pepe Altarelli, M; Perazzini, S; Perez Trigo, E; Perret, P; Perrin-Terrin, M; Pescatore, L; Pesen, E; Petridis, K; Petrolini, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Pistone, A; Playfer, S; Plo Casasus, M; Polci, F; Poluektov, A; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Price, E; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rachwal, B; Rademacker, J H; Rakotomiaramanana, B; Rama, M; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Reichert, S; Reid, M M; Dos Reis, A C; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Rodrigues, A B; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rotondo, M; Rouvinet, J; Ruf, T; Ruffini, F; Ruiz, H; Ruiz Valls, P; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salustino Guimaraes, V; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrie, M; Savrina, D; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Sepp, I; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Shires, A; Silva Coutinho, R; Simi, G; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, N A; Smith, E; Smith, E; Smith, J; Smith, M; Snoek, H; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Steinkamp, O; Stenyakin, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Stracka, S; Straticiuc, M; Straumann, U; Stroili, R; Subbiah, V K; Sun, L; Sutcliffe, W; Swientek, K; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szilard, D; Szumlak, T; T'Jampens, S; Teklishyn, M; Tellarini, G; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vagnoni, V; Valenti, G; Vallier, A; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vieites Diaz, M; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; de Vries, J A; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Websdale, D; Whitehead, M; Wicht, J; Wiedner, D; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wimberley, J; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, Z; Xu, Z; Yang, Z; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

    2014-10-03

    Three-body B+ → ppK+ and B(+) → ppπ(+) decays are studied using a data sample corresponding to an integrated luminosity of 3.0 fb(-1) collected by the LHCb experiment in proton-proton collisions at center-of-mass energies of 7 and 8 TeV. Evidence of CP violation in the B(+) → ppK(+) decay is found in regions of the phase space, representing the first measurement of this kind for a final state containing baryons. Measurements of the forward-backward asymmetry of the light meson in the pp rest frame yield A(FB)(ppK(+),m(pp)<2.85 GeV/c(2)) = 0.495 ± 0.012 (stat) ± 0.007 (syst) and A(FB)(ppπ(+),m(pp) <2.85 GeV/c(2)) = -0.409 ± 0.033 (stat) ± 0.006 (syst). In addition, the branching fraction of the decay B(+) → Λ(1520)p is measured to be B(B(+) → Λ(1520)p) = (3.15 ± 0.48 (stat) ± 0.07 (syst) ± 0.26 (BF)) × 10(-7), where BF denotes the uncertainty on secondary branching fractions.

  4. AbetaPP/APLP2 family of Kunitz serine proteinase inhibitors regulate cerebral thrombosis.

    PubMed

    Xu, Feng; Previti, Mary Lou; Nieman, Marvin T; Davis, Judianne; Schmaier, Alvin H; Van Nostrand, William E

    2009-04-29

    The amyloid beta-protein precursor (AbetaPP) is best recognized as the precursor to the Abeta peptide that accumulates in the brains of patients with Alzheimer's disease, but less is known about its physiological functions. Isoforms of AbetaPP that contain a Kunitz-type serine proteinase inhibitor (KPI) domain are expressed in brain and, outside the CNS, in circulating blood platelets. Recently, we showed that KPI-containing forms of AbetaPP regulates cerebral thrombosis in vivo (Xu et al., 2005, 2007). Amyloid precursor like protein-2 (APLP2), a closely related homolog to AbetaPP, also possesses a highly conserved KPI domain. Virtually nothing is known of its function. Here, we show that APLP2 also regulates cerebral thrombosis risk. Recombinant purified KPI domains of AbetaPP and APLP2 both inhibit the plasma clotting in vitro. In a carotid artery thrombosis model, both AbetaPP(-/-) and APLP2(-/-) mice exhibit similar significantly shorter times to vessel occlusion compared with wild-type mice indicating a prothrombotic phenotype. Similarly, in an experimental model of intracerebral hemorrhage, both AbetaPP(-/-) and APLP2(-/-) mice produce significantly smaller hematomas with reduced brain hemoglobin content compared with wild-type mice. Together, these results indicate that AbetaPP and APLP2 share overlapping anticoagulant functions with regard to regulating thrombosis after cerebral vascular injury.

  5. Molecular Mechanism and Evolution of Guanylate Kinase Regulation by (p)ppGpp

    SciTech Connect

    Liu, Kuanqing; Myers, Angela R.; Pisithkul, Tippapha; Claas, Kathy R.; Satyshur, Kenneth A.; Amador-Noguez, Daniel; Keck, James L.; Wang, Jue D.

    2015-02-01

    The nucleotide (p)ppGpp mediates bacterial stress responses, but its targets and underlying mechanisms of action vary among bacterial species and remain incompletely understood. Here, we characterize the molecular interaction between (p)ppGpp and guanylate kinase (GMK), revealing the importance of this interaction in adaptation to starvation. Combining structural and kinetic analyses, we show that (p)ppGpp binds the GMK active site and competitively inhibits the enzyme. The (p)ppGpp-GMK interaction prevents the conversion of GMP to GDP, resulting in GMP accumulation upon amino acid downshift. Abolishing this interaction leads to excess (p)ppGpp and defective adaptation to amino acid starvation. A survey of GMKs from phylogenetically diverse bacteria shows that the (p)ppGpp-GMK interaction is conserved in members of Firmicutes, Actinobacteria, and Deinococcus-Thermus, but not in Proteobacteria, where (p)ppGpp regulates RNA polymerase (RNAP). We propose that GMK is an ancestral (p)ppGpp target and RNAP evolved more recently as a direct target in Proteobacteria.

  6. Evaluation of PpIX formation in Cervical Intraepithelial Neoplasia I (CIN) using widefield fluorescence images

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Fortunato, Thereza C.; Lombardi, Welington; da Silva, Eduardo V.; Vollet Filho, José D.; Kurachi, Cristina; Pratavieira, Sebastião.; Bagnato, Vanderlei S.

    2016-03-01

    Optical techniques has been described as auxiliary technology for screening of neoplasia because shows the potential for tissues differentiation in real-time and it is a noninvasive detection and safe. However, only endogenous fluorophores presents the lesion may be insufficient and needed of the administration of the fluorophores synthesized, such as, precursor molecule of protoporphyrin IX (PpIX) induced by 5- aminolevulinic acid and your derivatives. Topical application of methylaminolevulinate (MAL), induces formation of the endogenous photosensitizer, PpIX in tissues where carcinogenesis has begun. The PpIX tend to accumulate in premalignant and malignant tissues and the illumination with light with appropriate wavelength beginning to excitation of PpIX fluorescence, which helps to localize PpIX-rich areas and identify potentially malignant tissues. The aim of the study is to evaluate the production of PpIX in the cervix with CIN I through of the fluorescence images captured after 1 hour of cream application. It was possible to visualize PpIX fluorescence in cervix and it was possible to observe the selectivity in fluorescence in squamous-columnar junction, which a pre-cancerous condition (CIN) and usually is localized. Through the image processing it was possible to quantify the increase of red fluorescence. For the CIN I the increase of red fluorescence was approximately of 4 times indicating a good PpIX formation.

  7. From the Biology of PP2A to the PADs for Therapy of Hematologic Malignancies

    PubMed Central

    Ciccone, Maria; Calin, George A.; Perrotti, Danilo

    2015-01-01

    Over the past decades, an emerging role of phosphatases in the pathogenesis of hematologic malignancies and solid tumors has been established. The tumor-suppressor protein phosphatase 2A (PP2A) belongs to the serine–threonine phosphatases family and accounts for the majority of serine–threonine phosphatase activity in eukaryotic cells. Numerous studies have shown that inhibition of PP2A expression and/or function may contribute to leukemogenesis in several hematological malignancies. Likewise, overexpression or aberrant expression of physiologic PP2A inhibitory molecules (e.g., SET and its associated SETBP1 and CIP2A) may turn off PP2A function and participate to leukemic progression. The discovery of PP2A as tumor suppressor has prompted the evaluation of the safety and the efficacy of new compounds, which can restore PP2A activity in leukemic cells. Although further studies are needed to better understand how PP2A acts in the intricate phosphatases/kinases cancer network, the results reviewed herein strongly support the development on new PP2A-activating drugs and the immediate introduction of those available into clinical protocols for leukemia patients refractory or resistant to current available therapies. PMID:25763353

  8. Modulation of cell spreading and migration by pp125FAK phosphorylation.

    PubMed Central

    Sankar, S.; Mahooti-Brooks, N.; Hu, G.; Madri, J. A.

    1995-01-01

    We provide evidence for both matrix-dependent and pp60v-src tyrosine kinase-dependent modulation of cell migration via tyrosine phosphorylation of pp125FAK, a focal adhesion kinase, thought to be involved in integrin-mediated signaling. Enhanced pp125FAK tyrosine phosphorylation and cell spreading was associated with decreased migration. Cells plated on type I collagen were less spread and exhibited lower levels of pp125FAK tyrosine phosphorylation and faster migration rates compared with cells on fibronectin that were well spread, which exhibited enhanced levels of pp125FAK tyrosine phosphorylation and slower migration rates. Inside-out signaling via expression of pp60v-src or its kinase-negative mutant caused a decrease in cell migration by changing the extent of pp125FAK tyrosine phosphorylation to above or below the levels obtained with control cells plated on fibronectin. Hence, pp125FAK tyrosine phosphorylation appears to play a role in the signaling cascade pathway involved in regulation of extracellular matrix-modulated, integrin-mediated cell migration. Images Figure 1 Figure 2 Figure 3 PMID:7677174

  9. Noninvasive murine glioma detection improved following photobleaching of skin PpIX fluorescence

    NASA Astrophysics Data System (ADS)

    Gibbs-Strauss, Summer L.; Davis, Scott C.; O'Hara, Julia A.; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

    2008-02-01

    Aminolevulinic Acid (ALA) is a prodrug which can be administered to cells, animals or patients after which it is transformed via the Heme synthesis pathway into the fluorescent molecule Protoporphyrin IX (PpIX). PpIX has been shown to be useful as both a photosensitizer for photodynamic therapy (PDT) and as a fluorescence imaging contrast agent. The ALA-PpIX system not only provides contrast for fluorescence imaging but also gives information about the metabolic activity of the imaged tissue and thus could be useful for monitoring cancer therapy. In the current study skin photobleaching was examined to determine if PpIX fluorescence contrast in malignant brain tumors could be better visualized noninvasively. Red light photobleaching decreased skin PpIX fluorescence and increased the ability to noninvasively quantify PpIX fluorescence in murine gliomas, as in vivo measurements of mean PpIX fluorescence more closely matched ex vivo quantification following skin photobleaching. Three doses of blue light photobleaching (4 J/cm2, 8 J/cm2 and 12 J/cm2) were tested and determined to give similar levels of skin photobleaching as well as a similar window of decreased skin PpIX fluorescence for noninvasive fluorescence imaging following the photobleaching dose administration.

  10. Synaptic NMDA receptor stimulation activates PP1 by inhibiting its phosphorylation by Cdk5

    PubMed Central

    Hou, Hailong; Sun, Lu; Siddoway, Benjamin A.; Petralia, Ronald S.; Yang, Hongtian; Gu, Hua; Nairn, Angus C.

    2013-01-01

    The serine/threonine protein phosphatase protein phosphatase 1 (PP1) is known to play an important role in learning and memory by mediating local and downstream aspects of synaptic signaling, but how PP1 activity is controlled in different forms of synaptic plasticity remains unknown. We find that synaptic N-methyl-d-aspartate (NMDA) receptor stimulation in neurons leads to activation of PP1 through a mechanism involving inhibitory phosphorylation at Thr320 by Cdk5. Synaptic stimulation led to proteasome-dependent degradation of the Cdk5 regulator p35, inactivation of Cdk5, and increased auto-dephosphorylation of Thr320 of PP1. We also found that neither inhibitor-1 nor calcineurin were involved in the control of PP1 activity in response to synaptic NMDA receptor stimulation. Rather, the PP1 regulatory protein, inhibitor-2, formed a complex with PP1 that was controlled by synaptic stimulation. Finally, we found that inhibitor-2 was critical for the induction of long-term depression in primary neurons. Our work fills a major gap regarding the regulation of PP1 in synaptic plasticity. PMID:24189275

  11. Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells

    PubMed Central

    Rusin, Scott F.; Schlosser, Kate A.; Adamo, Mark E.; Kettenbach, Arminja N.

    2017-01-01

    Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry–based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c–dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2–dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity. PMID:26462736

  12. Additional diterpenes from Physcomitrella patens synthesized by copalyl diphosphate/kaurene synthase (PpCPS/KS).

    PubMed

    Zhan, Xin; Bach, Søren Spanner; Hansen, Nikolaj Lervad; Lunde, Christina; Simonsen, Henrik Toft

    2015-11-01

    The bifunctional diterpene synthase, copalyl diphosphate/kaurene synthase from the moss Physcomitrella patens (PpCPS/KS), catalyses the formation of at least four diterpenes, including ent-beyerene, ent-sandaracopimaradiene, ent-kaur-16-ene, and 16-hydroxy-ent-kaurene. The enzymatic activity has been confirmed through generation of a targeted PpCPS/KS knock-out mutant in P. patens via homologous recombination, through transient expression of PpCPS/KS in Nicotiana benthamiana, and expression of PpCPS/KS in E. coli. GC-MS analysis of the knock-out mutant shows that it lacks the diterpenoids, supporting that all are products of PpCPS/KS as observed in N. benthamiana and E. coli. These results provide additional knowledge of the mechanism of this bifunctional diterpene synthase, and are in line with proposed reaction mechanisms in kaurene biosynthesis.

  13. The Molecular Chaperone Hsp70 Activates Protein Phosphatase 5 (PP5) by Binding the Tetratricopeptide Repeat (TPR) Domain*

    PubMed Central

    Connarn, Jamie N.; Assimon, Victoria A.; Reed, Rebecca A.; Tse, Eric; Southworth, Daniel R.; Zuiderweg, Erik R. P.; Gestwicki, Jason E.; Sun, Duxin

    2014-01-01

    Protein phosphatase 5 (PP5) is auto-inhibited by intramolecular interactions with its tetratricopeptide repeat (TPR) domain. Hsp90 has been shown to bind PP5 to activate its phosphatase activity. However, the functional implications of binding Hsp70 to PP5 are not yet clear. In this study, we find that both Hsp90 and Hsp70 bind to PP5 using a luciferase fragment complementation assay. A fluorescence polarization assay shows that Hsp90 (MEEVD motif) binds to the TPR domain of PP5 almost 3-fold higher affinity than Hsp70 (IEEVD motif). However, Hsp70 binding to PP5 stimulates higher phosphatase activity of PP5 than the binding of Hsp90. We find that PP5 forms a stable 1:1 complex with Hsp70, but the interaction appears asymmetric with Hsp90, with one PP5 binding the dimer. Solution NMR studies reveal that Hsc70 and PP5 proteins are dynamically independent in complex, tethered by a disordered region that connects the Hsc70 core and the IEEVD-TPR contact area. This tethered binding is expected to allow PP5 to carry out multi-site dephosphorylation of Hsp70-bound clients with a range of sizes and shapes. Together, these results demonstrate that Hsp70 recruits PP5 and activates its phosphatase activity which suggests dual roles for PP5 that might link chaperone systems with signaling pathways in cancer and development. PMID:24327656

  14. Measurement of the ratio of differential cross sections σ(pp̄→Z+b jet)/σ(pp̄→Z+jet) in pp̄ collisions at √s=1.96 TeV

    SciTech Connect

    Abazov, V. M.; Abbott, B.; Acharya, B. S.; Adams, M.; Adams, T.; Alexeev, G. D.; Alkhazov, G.; Alton, A.; Askew, A.; Atkins, S.; Augsten, K.; Avila, C.; Badaud, F.; Bagby, L.; Baldin, B.; Bandurin, D. V.; Banerjee, S.; Barberis, E.; Baringer, P.; Bartlett, J. F.; Bassler, U.; Bazterra, V.; Bean, A.; Begalli, M.; Bellantoni, L.; Beri, S. B.; Bernardi, G.; Bernhard, R.; Bertram, I.; Besançon, M.; Beuselinck, R.; Bhat, P. C.; Bhatia, S.; Bhatnagar, V.; Blazey, G.; Blessing, S.; Bloom, K.; Boehnlein, A.; Boline, D.; Boos, E. E.; Borissov, G.; Brandt, A.; Brandt, O.; Brock, R.; Bross, A.; Brown, D.; Brown, J.; Bu, X. B.; Buehler, M.; Buescher, V.; Bunichev, V.; Burdin, S.; Buszello, C. P.; Camacho-Pérez, E.; Casey, B. C. K.; Castilla-Valdez, H.; Caughron, S.; Chakrabarti, S.; Chakraborty, D.; Chan, K. M.; Chandra, A.; Chapon, E.; Chen, G.; Cho, S. W.; Choi, S.; Choudhary, B.; Cihangir, S.; Claes, D.; Clutter, J.; Cooke, M.; Cooper, W. E.; Corcoran, M.; Couderc, F.; Cousinou, M.-C.; Cutts, D.; Das, A.; Davies, G.; de Jong, S. J.; De La Cruz-Burelo, E.; Déliot, F.; Demina, R.; Denisov, D.; Denisov, S. P.; Desai, S.; Deterre, C.; DeVaughan, K.; Diehl, H. T.; Diesburg, M.; Ding, P. F.; Dominguez, A.; Dubey, A.; Dudko, L. V.; Duggan, D.; Duperrin, A.; Dutt, S.; Dyshkant, A.; Eads, M.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Enari, Y.; Evans, H.; Evdokimov, V. N.; Facini, G.; Feng, L.; Ferbel, T.; Fiedler, F.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Fortner, M.; Fox, H.; Fuess, S.; Garcia-Bellido, A.; García-González, J. A.; García-Guerra, G. A.; Gavrilov, V.; Geng, W.; Gerber, C. E.; Gershtein, Y.; Ginther, G.; Golovanov, G.; Grannis, P. D.; Greder, S.; Greenlee, H.; Grenier, G.; Gris, Ph.; Grivaz, J.-F.; Grohsjean, A.; Grünendahl, S.; Grünewald, M. W.; Guillemin, T.; Gutierrez, G.; Gutierrez, P.; Haley, J.; Han, L.; Harder, K.; Harel, A.; Hauptman, J. M.; Hays, J.; Head, T.; Hebbeker, T.; Hedin, D.; Hegab, H.; Heinson, A. P.; Heintz, U.; Hensel, C.; Heredia-De La Cruz, I.; Herner, K.; Hesketh, G.; Hildreth, M. D.; Hirosky, R.; Hoang, T.; Hobbs, J. D.; Hoeneisen, B.; Hogan, J.; Hohlfeld, M.; Howley, I.; Hubacek, Z.; Hynek, V.; Iashvili, I.; Ilchenko, Y.; Illingworth, R.; Ito, A. S.; Jabeen, S.; Jaffré, M.; Jayasinghe, A.; Jeong, M. S.; Jesik, R.; Jiang, P.; Johns, K.; Johnson, E.; Johnson, M.; Jonckheere, A.; Jonsson, P.; Joshi, J.; Jung, A. W.; Juste, A.; Kajfasz, E.; Karmanov, D.; Kasper, P. A.; Katsanos, I.; Kehoe, R.; Kermiche, S.; Khalatyan, N.; Khanov, A.; Kharchilava, A.; Kharzheev, Y. N.; Kiselevich, I.; Kohli, J. M.; Kozelov, A. V.; Kraus, J.; Kumar, A.; Kupco, A.; Kurča, T.; Kuzmin, V. A.; Lammers, S.; Landsberg, G.; Lebrun, P.; Lee, H. S.; Lee, S. W.; Lee, W. M.; Lei, X.; Lellouch, J.; Li, D.; Li, H.; Li, L.; Li, Q. Z.; Lim, J. K.; Lincoln, D.; Linnemann, J.; Lipaev, V. V.; Lipton, R.; Liu, H.; Liu, Y.; Lobodenko, A.; Lokajicek, M.; Lopes de Sa, R.; Luna-Garcia, R.; Lyon, A. L.; Maciel, A. K. A.; Magaña-Villalba, R.; Malik, S.; Malyshev, V. L.; Maravin, Y.; Martínez-Ortega, J.; McCarthy, R.; McGivern, C. L.; Meijer, M. M.; Melnitchouk, A.; Menezes, D.; Mercadante, P. G.; Merkin, M.; Meyer, A.; Meyer, J.; Miconi, F.; Mondal, N. K.; Mulhearn, M.; Nagy, E.; Naimuddin, M.; Narain, M.; Nayyar, R.; Neal, H. A.; Negret, J. P.; Neustroev, P.; Nguyen, H. T.; Nunnemann, T.; Orduna, J.; Osman, N.; Osta, J.; Padilla, M.; Pal, A.; Parashar, N.; Parihar, V.; Park, S. K.; Partridge, R.; Parua, N.; Patwa, A.; Penning, B.; Perfilov, M.; Peters, Y.; Petridis, K.; Petrillo, G.; Pétroff, P.; Pleier, M.-A.; Podesta-Lerma, P. L. M.; Podstavkov, V. M.; Popov, A. V.; Prewitt, M.; Price, D.; Prokopenko, N.; Qian, J.; Quadt, A.; Quinn, B.; Rangel, M. S.; Ranjan, K.; Ratoff, P. N.; Razumov, I.; Renkel, P.; Ripp-Baudot, I.; Rizatdinova, F.; Rominsky, M.; Ross, A.; Royon, C.; Rubinov, P.; Ruchti, R.; Sajot, G.; Salcido, P.; Sánchez-Hernández, A.; Sanders, M. P.; Santos, A. S.; Savage, G.; Sawyer, L.; Scanlon, T.; Schamberger, R. D.; Scheglov, Y.; Schellman, H.; Schwanenberger, C.; Schwienhorst, R.; Sekaric, J.; Severini, H.; Shabalina, E.; Shary, V.; Shaw, S.; Shchukin, A. A.; Shivpuri, R. K.; Simak, V.; Skubic, P.; Slattery, P.; Smirnov, D.; Smith, K. J.; Snow, G. R.; Snow, J.; Snyder, S.; Söldner-Rembold, S.; Sonnenschein, L.; Soustruznik, K.; Stark, J.; Stoyanova, D. A.; Strauss, M.; Suter, L.; Svoisky, P.; Titov, M.; Tokmenin, V. V.; Tsai, Y.-T.; Tsybychev, D.; Tuchming, B.; Tully, C.; Uvarov, L.; Uvarov, S.; Uzunyan, S.; Van Kooten, R.; van Leeuwen, W. M.; Varelas, N.; Varnes, E. W.; Vasilyev, I. A.; Verdier, P.; Verkheev, A. Y.; Vertogradov, L. S.; Verzocchi, M.; Vesterinen, M.; Vilanova, D.; Vokac, P.; Wahl, H. D.; Wang, M. H. L. S.; Warchol, J.; Watts, G.; Wayne, M.; Weichert, J.; Welty-Rieger, L.; White, A.

    2013-05-28

    We measure the ratio of cross sections, σ(pp̄→Z+b jet)/σ(pp̄→Z+jet), for associated production of a Z boson with at least one jet. The ratio is also measured as a function of the Z boson transverse momentum, jet transverse momentum, jet pseudorapidity, and the azimuthal angle between the Z boson with respect to the highest pT b tagged jet. These measurements use data collected by the D0 experiment in Run II of Fermilab’s Tevatron pp̄ Collider at a center-of-mass energy of 1.96 TeV, and correspond to an integrated luminosity of 9.7 fb⁻¹. The results are compared to predictions from next-to-leading order calculations and various Monte Carlo event generators.

  15. Measurement of the ratio of differential cross sections σ(pp̄→Z+b jet)/σ(pp̄→Z+jet) in pp̄ collisions at √s=1.96 TeV

    DOE PAGES

    Abazov, V. M.; Abbott, B.; Acharya, B. S.; ...

    2013-05-28

    We measure the ratio of cross sections, σ(pp̄→Z+b jet)/σ(pp̄→Z+jet), for associated production of a Z boson with at least one jet. The ratio is also measured as a function of the Z boson transverse momentum, jet transverse momentum, jet pseudorapidity, and the azimuthal angle between the Z boson with respect to the highest pT b tagged jet. These measurements use data collected by the D0 experiment in Run II of Fermilab’s Tevatron pp̄ Collider at a center-of-mass energy of 1.96 TeV, and correspond to an integrated luminosity of 9.7 fb⁻¹. The results are compared to predictions from next-to-leading order calculationsmore » and various Monte Carlo event generators.« less

  16. Molecular cloning, expression and single nucleotide polymorphisms of protein phosphatase 1 (PP1) in mandarin fish (Siniperca chuatsi).

    PubMed

    Cheng, Xiao-Yan; He, Shan; Liang, Xu-Fang; Song, Yi; Yuan, Xiao-Chen; Li, Ling; Wen, Zheng-Yong; Cai, Wen-Jing; Tao, Ya-Xiong

    2015-11-01

    In the wild, mandarin fish (Siniperca chuatsi) only feed on live prey fish, refusing dead prey. When reared in ponds, training will result in some mandarin fish accepting artificial diets. However, little is currently known about the molecular mechanism of the individual difference. Serine/threonine protein phosphatase 1 (PP1) is a suppressor of learning and long-term memory (LTM) in mammals. In the present study, the relationship between PP1 and the individual difference in acceptance of artificial diets in mandarin fish was investigated. The complete CDS (coding sequence) of four PP1 isoforms (PP1caa, PP1cab, PP1cb and PP1cc) were cloned in mandarin fish. The amino acid sequences of these PP1 isoforms are highly conserved in different species. The mRNA expressions of PP1caa and PP1cb in brain of artificial diet feeders were significantly higher than those in nonfeeders, suggesting the deficiency in the maintenance of long-term memory of its natural food habit (live prey fish). The SNP loci in PP1caa and PP1cb were also found to be associated with the individual difference in acceptance of artificial diets in mandarin fish. These SNPs of PP1caa and PP1cb genes could be useful markers for gene-associated breeding of mandarin fish, which could accept artificial diets. In conclusion, different mRNA expression and SNPs of PP1caa and PP1cb genes in feeders and nonfeeders of artificial diets might contribute to understanding the molecular mechanism of individual difference in acceptance of artificial diets in mandarin fish.

  17. 78 FR 19194 - P&P Computers, 2531 West Maryland Avenue, Tampa, FL 33629; Order Denying Export Privileges

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-29

    ... Bureau of Industry and Security P&P Computers, 2531 West Maryland Avenue, Tampa, FL 33629; Order Denying... Division, P&P Computers (``P&P'') was convicted of violating the International Emergency Economic Powers... IEEPA and the Iranian Transactions Regulations by exporting computer and related equipment from...

  18. Drosophila Uri, a PP1α binding protein, is essential for viability, maintenance of DNA integrity and normal transcriptional activity

    PubMed Central

    Kirchner, Jasmin; Vissi, Emese; Gross, Sascha; Szoor, Balazs; Rudenko, Andrey; Alphey, Luke; White-Cooper, Helen

    2008-01-01

    Background Protein phosphatase 1 (PP1) is involved in diverse cellular processes, and is targeted to substrates via interaction with many different protein binding partners. PP1 catalytic subunits (PP1c) fall into PP1α and PP1β subfamilies based on sequence analysis, however very few PP1c binding proteins have been demonstrated to discriminate between PP1α and PP1β. Results URI (unconventional prefoldin RPB5 interactor) is a conserved molecular chaperone implicated in a variety of cellular processes, including the transcriptional response to nutrient signalling and maintenance of DNA integrity. We show that Drosophila Uri binds PP1α with much higher affinity than PP1β, and that this ability to discriminate between PP1c forms is conserved to humans. Most Uri is cytoplasmic, however we found some protein associated with active RNAPII on chromatin. We generated a uri loss of function allele, and show that uri is essential for viability in Drosophila. uri mutants have transcriptional defects, reduced cell viability and differentiation in the germline, and accumulate DNA damage in their nuclei. Conclusion Uri is the first PP1α specific binding protein to be described in Drosophila. Uri protein plays a role in transcriptional regulation. Activity of uri is required to maintain DNA integrity and cell survival in normal development. PMID:18412953

  19. Fabrication of borassus fruit lignocellulose fiber/PP composites and comparison with jute, sisal and coir fibers.

    PubMed

    Sudhakara, P; Jagadeesh, Dani; Wang, YiQi; Prasad, C Venkata; Devi, A P Kamala; Balakrishnan, G; Kim, B S; Song, J I

    2013-10-15

    Novel composites based on borassus fruit fine fiber (BFF) and polypropylene (PP) were fabricated with variable fiber composition (5, 10, 15 and 20 wt%) by injection molding. Maleated PP (MAPP) was also used as compatibilizer at 5 wt% for effective fiber-matrix adhesion. FTIR analysis confirms the evidence of a chemical bonding between the fiber and polymeric matrix through esterification in presence of MAPP. The tensile and flexural properties were found to increase with 15 and 10 wt% fiber loadings respectively, and decreased thereafter. Coir, jute and sisal fiber composites were also fabricated with 15 wt% fiber loading under the same conditions as used for BFF/PP composites. It was found that the mechanical properties of BFF (15 wt%)/PP composites were equivalent to jute/PP, sisal/PP and superior to coir/PP composites. Jute/PP and sisal/PP composites showed higher water absorption than BFF/PP and coir/PP composites. These results have demonstrated that the BFF/PP composites can also be an alternative material for composites applications.

  20. 75 FR 78705 - Issuance of Exposure Drafts on Implementation Guidance on the Accounting for the Disposal of G-PP...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-16

    ... G-PP&E and Implementation Guidance for Estimating the Historical Cost of G-PP&E AGENCY: Federal... Historical Cost of G- PP&E. The Exposure Drafts are available on the FASAB home page http://www.fasab.gov... From the Federal Register Online via the Government Publishing Office FEDERAL ACCOUNTING...

  1. Mechanical and thermal properties of polypropylene (PP) composites filled with modified shell waste.

    PubMed

    Yao, Z T; Chen, T; Li, H Y; Xia, M S; Ye, Y; Zheng, H

    2013-11-15

    Shell waste, with its high content of calcium carbonate (CaCO3) plus organic matrix, has a potential to be used as a bio-filler. In this work, shell waste was modified by furfural and then incorporated to reinforce polypropylene (PP). The shell waste and modified powder were characterized by means of X-ray diffraction (XRD), scanning electron microscopy equipped with an energy dispersive spectrometer (SEM-EDS), X-ray photoelectronic spectroscopy (XPS), and Fourier transformed infrared spectroscopy (FTIR). The mechanical and thermal properties of neat PP and PP composites were investigated as well. Thermal gravimetric (TG) analyses confirmed the reinforcing role of modified powder in PP composites. The mechanical properties studied showed that adding modified powder could significantly increase the impact strength, elongation at break point and flexural modulus of composites. The maximum incorporation content could reach 15 wt.% with a good balance between toughness and stiffness of PP composites. Differential scanning calorimetry (DSC) results showed that the modified powder could act as a nucleating agent and thus increase the crystallization temperature of PP. Polarized optical microscopy (POM) observation also indicated that the introduction of modified powder could promote the heterogeneous nucleation of PP matrix.

  2. Catalytic mechanism and allosteric regulation of an oligomeric (p)ppGpp synthetase by an alarmone

    PubMed Central

    Steinchen, Wieland; Schuhmacher, Jan S.; Altegoer, Florian; Fage, Christopher D.; Srinivasan, Vasundara; Linne, Uwe; Marahiel, Mohamed A.; Bange, Gert

    2015-01-01

    Nucleotide-based second messengers serve in the response of living organisms to environmental changes. In bacteria and plant chloroplasts, guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) [collectively named “(p)ppGpp”] act as alarmones that globally reprogram cellular physiology during various stress conditions. Enzymes of the RelA/SpoT homology (RSH) family synthesize (p)ppGpp by transferring pyrophosphate from ATP to GDP or GTP. Little is known about the catalytic mechanism and regulation of alarmone synthesis. It also is unclear whether ppGpp and pppGpp execute different functions. Here, we unravel the mechanism and allosteric regulation of the highly cooperative alarmone synthetase small alarmone synthetase 1 (SAS1) from Bacillus subtilis. We determine that the catalytic pathway of (p)ppGpp synthesis involves a sequentially ordered substrate binding, activation of ATP in a strained conformation, and transfer of pyrophosphate through a nucleophilic substitution (SN2) reaction. We show that pppGpp—but not ppGpp—positively regulates SAS1 at an allosteric site. Although the physiological significance remains to be elucidated, we establish the structural and mechanistic basis for a biological activity in which ppGpp and pppGpp execute different functional roles. PMID:26460002

  3. Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia

    PubMed Central

    Gutierrez, Alejandro; Pan, Li; Groen, Richard W.J.; Baleydier, Frederic; Kentsis, Alex; Marineau, Jason; Grebliunaite, Ruta; Kozakewich, Elena; Reed, Casie; Pflumio, Francoise; Poglio, Sandrine; Uzan, Benjamin; Clemons, Paul; VerPlank, Lynn; An, Frank; Burbank, Jason; Norton, Stephanie; Tolliday, Nicola; Steen, Hanno; Weng, Andrew P.; Yuan, Huipin; Bradner, James E.; Mitsiades, Constantine; Look, A. Thomas; Aster, Jon C.

    2014-01-01

    T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that is frequently associated with activating mutations in NOTCH1 and dysregulation of MYC. Here, we performed 2 complementary screens to identify FDA-approved drugs and drug-like small molecules with activity against T-ALL. We developed a zebrafish system to screen small molecules for toxic activity toward MYC-overexpressing thymocytes and used a human T-ALL cell line to screen for small molecules that synergize with Notch inhibitors. We identified the antipsychotic drug perphenazine in both screens due to its ability to induce apoptosis in fish, mouse, and human T-ALL cells. Using ligand-affinity chromatography coupled with mass spectrometry, we identified protein phosphatase 2A (PP2A) as a perphenazine target. T-ALL cell lines treated with perphenazine exhibited rapid dephosphorylation of multiple PP2A substrates and subsequent apoptosis. Moreover, shRNA knockdown of specific PP2A subunits attenuated perphenazine activity, indicating that PP2A mediates the drug’s antileukemic activity. Finally, human T-ALLs treated with perphenazine exhibited suppressed cell growth and dephosphorylation of PP2A targets in vitro and in vivo. Our findings provide a mechanistic explanation for the recurring identification of phenothiazines as a class of drugs with anticancer effects. Furthermore, these data suggest that pharmacologic PP2A activation in T-ALL and other cancers driven by hyperphosphorylated PP2A substrates has therapeutic potential. PMID:24401270

  4. Greatwall dephosphorylation and inactivation upon mitotic exit is triggered by PP1.

    PubMed

    Ma, Sheng; Vigneron, Suzanne; Robert, Perle; Strub, Jean Marc; Cianferani, Sara; Castro, Anna; Lorca, Thierry

    2016-04-01

    Entry into mitosis is induced by the activation of cyclin-B-Cdk1 and Greatwall (Gwl; also known as MASTL in mammals) kinases. Cyclin-B-Cdk1 phosphorylates mitotic substrates, whereas Gwl activation promotes the phosphorylation of the small proteins Arpp19 and ENSA. Phosphorylated Arpp19 and/or ENSA bind to and inhibit PP2A comprising the B55 subunit (PP2A-B55; B55 is also known as PPP2R2A), the phosphatase responsible for cyclin-B-Cdk1 substrate dephosphorylation, allowing the stable phosphorylation of mitotic proteins. Upon mitotic exit, cyclin-B-Cdk1 and Gwl kinases are inactivated, and mitotic substrates are dephosphorylated. Here, we have identified protein phosphatase-1 (PP1) as the phosphatase involved in the dephosphorylation of the activating site (Ser875) of Gwl. Depletion of PP1 from meioticXenopusegg extracts maintains phosphorylation of Ser875, as well as the full activity of this kinase, resulting in a block of meiotic and mitotic exit. By contrast, preventing the reactivation of PP2A-B55 through the addition of a hyperactive Gwl mutant (GwlK72M) mainly affected Gwl dephosphorylation on Thr194, resulting in partial inactivation of Gwl and in the incomplete exit from mitosis or meiosis. We also show that when PP2A-B55 is fully reactivated by depleting Arpp19, this protein phosphatase is able to dephosphorylate both activating sites, even in the absence of PP1.

  5. A Phytophthora infestans RXLR effector targets plant PP1c isoforms that promote late blight disease

    PubMed Central

    Boevink, Petra C.; Wang, Xiaodan; McLellan, Hazel; He, Qin; Naqvi, Shaista; Armstrong, Miles R.; Zhang, Wei; Hein, Ingo; Gilroy, Eleanor M.; Tian, Zhendong; Birch, Paul R. J.

    2016-01-01

    Plant pathogens deliver effectors to alter host processes. Knowledge of how effectors target and manipulate host proteins is critical to understand crop disease. Here, we show that in planta expression of the RXLR effector Pi04314 enhances leaf colonization by Phytophthora infestans via activity in the host nucleus and attenuates induction of jasmonic and salicylic acid-responsive genes. Pi04314 interacts with three host protein phosphatase 1 catalytic (PP1c) isoforms, causing their re-localization from the nucleolus to the nucleoplasm. Re-localization of PP1c-1 also occurs during infection and is dependent on an R/KVxF motif in the effector. Silencing the PP1c isoforms or overexpression of a phosphatase-dead PP1c-1 mutant attenuates infection, demonstrating that host PP1c activity is required for disease. Moreover, expression of PP1c–1mut abolishes enhanced leaf colonization mediated by in planta Pi04314 expression. We argue that PP1c isoforms are susceptibility factors forming holoenzymes with Pi04314 to promote late blight disease. PMID:26822079

  6. Characterization of pp85; A target of oncogenes and growth factor receptors

    SciTech Connect

    Cohen, B.; Liu, Y.; Schaffhausen, B.S. ); Druker, B.; Roberts, T.M. )

    1990-06-01

    An 85,000-molecular-weight polypeptide (85 K polypeptide) has previously been identified as a common substrate for tyrosine phosphorylation upon polyomavirus middle T transformation or upon platelet-derived growth factor stimulation of 3T3 cells. In each case, pp85 has an associated phosphatidylinositol kinase activity.The tissue distribution of pp85 was determined by middle T blotting experiments; the highest levels were found in brain, lung, and spleen tissues. High-resolution examination of 85 K by isoelectric focusing demonstrated that there are at least 10 different forms. These were resolved into two families, 85 K and 86 K; the ratio of the two families changed in different cells. Similar forms were found for pp85 associated with pp60{sup v-{ital src}}. Individual species within each family differed by phosphorylation. This paper reports that analysis of pp85 and pp86 by immunoprecipitation with anti-phosphotyrosine antibody showed increasing phosphorylation in response to middle T or pp60{sup v-{ital src}} transformation.

  7. Group A PP2Cs evolved in land plants as key regulators of intrinsic desiccation tolerance.

    PubMed

    Komatsu, Kenji; Suzuki, Norihiro; Kuwamura, Mayuri; Nishikawa, Yuri; Nakatani, Mao; Ohtawa, Hitomi; Takezawa, Daisuke; Seki, Motoaki; Tanaka, Maho; Taji, Teruaki; Hayashi, Takahisa; Sakata, Yoichi

    2013-01-01

    Vegetative desiccation tolerance is common in bryophytes, although this character has been lost in most vascular plants. The moss Physcomitrella patens survives complete desiccation if treated with abscisic acid (ABA). Group A protein phosphatases type 2C (PP2C) are negative regulators of abscisic acid signalling. Here we show that the elimination of Group A PP2C is sufficient to ensure P. patens survival to full desiccation, without ABA treatment, although its growth is severely hindered. Microarray analysis shows that the Group A PP2C-regulated genes exclusively overlap with genes exhibiting a high level of ABA induction. Group A PP2C disruption weakly affects ABA-activated kinase activity, indicating Group A PP2C action downstream of these kinases in the moss. We propose that Group A PP2C emerged in land plants to repress desiccation tolerance mechanisms, possibly facilitating plants propagation on land, whereas ABA releases the intrinsic desiccation tolerance from Group A PP2C regulation.

  8. A PP2C-1 Allele Underlying a Quantitative Trait Locus Enhances Soybean 100-Seed Weight.

    PubMed

    Lu, Xiang; Xiong, Qing; Cheng, Tong; Li, Qing-Tian; Liu, Xin-Lei; Bi, Ying-Dong; Li, Wei; Zhang, Wan-Ke; Ma, Biao; Lai, Yong-Cai; Du, Wei-Guang; Man, Wei-Qun; Chen, Shou-Yi; Zhang, Jin-Song

    2017-03-28

    Cultivated soybeans may lose some useful genetic locus during domestication. Introgression of genes from wild soybeans may broaden the genetic background and improve soybean agronomic traits. Here, through whole-genome sequencing of an RIL population derived from a cross between a wild soybean ZYD7 and a cultivated soybean HN44, and mapping of QTLs for seed weight, we discover that a phosphatase 2C-1 (PP2C-1) allele from wild soybean ZYD7 contributes to the increase of seed weight/size in transgenic plants. The PP2C-1 may achieve this function by enhancing cell size of integument and activating a subset of seed trait-related genes. The PP2C-1 was further found to associate with a transcription factor GmBZR1 and facilitate accumulation of dephosphorylated GmBZR1. In contrast, a PP2C-2 allele with variations of a few amino acids at N-terminus does not exhibit this function. Moreover, the GmBZR1 can promote seed weight/size in transgenic plants. Through analysis of cultivated soybean accessions, we find that 40% of the examined accessions do not have the PP2C-1 allele, suggesting that these accessions can be improved through introduction of the PP2C-1 allele. Our study identifies an elite allele PP2C-1, which can enhance seed weight/size. Manipulation of the allele by molecule-assisted breeding may increase production in soybean and other legumes/crops.

  9. Ongoing advances in quantitative PpIX fluorescence guided intracranial tumor resection (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Olson, Jonathan D.; Kanick, Stephen C.; Bravo, Jaime J.; Roberts, David W.; Paulsen, Keith D.

    2016-03-01

    Aminolevulinc-acid induced protoporphyrin IX (ALA-PpIX) is being investigated as a biomarker to guide neurosurgical resection of brain tumors. ALA-PpIX fluorescence can be observed visually in the surgical field; however, raw fluorescence emissions can be distorted by factors other than the fluorophore concentration. Specifically, fluorescence emissions are mixed with autofluorescence and attenuated by background absorption and scattering properties of the tissue. Recent work at Dartmouth has developed advanced fluorescence detection approaches that return quantitative assessments of PpIX concentration, which are independent of background optical properties. The quantitative fluorescence imaging (qFI) approach has increased sensitivity to residual disease within the resection cavity at the end of surgery that was not visible to the naked eye through the operating microscope. This presentation outlines clinical observations made during an ongoing investigation of ALA-PpIX based guidance of tumor resection. PpIX fluorescence measurements made in a wide-field hyperspectral imaging approach are co-registered with point-assessment using a fiber optic probe. Data show variations in the measured PpIX accumulation among different clinical tumor grades (i.e. high grade glioma, low grade glioma), types (i.e. primary tumors. metastases) and normal structures of interest (e.g. normal cortex, hippocampus). These results highlight the contrast enhancement and underscore the potential clinical benefit offered from quantitative measurements of PpIX concentration during resection of intracranial tumors.

  10. Distinct roles of ppGpp and DksA in Legionella pneumophila differentiation

    PubMed Central

    Dalebroux, Zachary D.; Yagi, Brian F.; Sahr, Tobias; Buchrieser, Carmen; Swanson, Michele S.

    2010-01-01

    SUMMARY To transit between hosts, intracellular Legionella pneumophila transform into a motile, infectious, transmissive state. Here we exploit the pathogen’s life cycle to examine how guanosine tetraphosphate (ppGpp) and DksA cooperate to govern bacterial differentiation. Transcriptional profiling revealed that during transmission alarmone accumulation increases the mRNA for flagellar and Type IV-secretion components, secreted host effectors, and regulators, and decreases transcripts for translation, membrane modification and ATP synthesis machinery. DksA is critical for differentiation, since mutants are defective for stationary phase survival, flagellar gene activation, lysosome avoidance, and macrophage cytotoxicity. The roles of ppGpp and DksA depend on the context. For macrophage transmission, ppGpp is essential, whereas DksA is dispensable, indicating ppGpp can act autonomously. In broth, DksA promotes differentiation when ppGpp levels increase, or during fatty acid stress, as judged by flaA expression and evasion of degradation by macrophages. For flagella morphogenesis, DksA is required for basal fliA (σ28) promoter activity. When alarmone levels increase, DksA cooperates with ppGpp to generate a pulse of Class II rod RNA or to amplify the Class III sigma factor and Class IV flagellin RNAs. Thus, DksA responds to the level of ppGpp and other stress signals to coordinate L. pneumophila differentiation. PMID:20199605

  11. A Phytophthora infestans RXLR effector targets plant PP1c isoforms that promote late blight disease.

    PubMed

    Boevink, Petra C; Wang, Xiaodan; McLellan, Hazel; He, Qin; Naqvi, Shaista; Armstrong, Miles R; Zhang, Wei; Hein, Ingo; Gilroy, Eleanor M; Tian, Zhendong; Birch, Paul R J

    2016-01-29

    Plant pathogens deliver effectors to alter host processes. Knowledge of how effectors target and manipulate host proteins is critical to understand crop disease. Here, we show that in planta expression of the RXLR effector Pi04314 enhances leaf colonization by Phytophthora infestans via activity in the host nucleus and attenuates induction of jasmonic and salicylic acid-responsive genes. Pi04314 interacts with three host protein phosphatase 1 catalytic (PP1c) isoforms, causing their re-localization from the nucleolus to the nucleoplasm. Re-localization of PP1c-1 also occurs during infection and is dependent on an R/KVxF motif in the effector. Silencing the PP1c isoforms or overexpression of a phosphatase-dead PP1c-1 mutant attenuates infection, demonstrating that host PP1c activity is required for disease. Moreover, expression of PP1c-1mut abolishes enhanced leaf colonization mediated by in planta Pi04314 expression. We argue that PP1c isoforms are susceptibility factors forming holoenzymes with Pi04314 to promote late blight disease.

  12. PP: A graphics post-processor for the EQ6 reaction path code

    SciTech Connect

    Stockman, H.W.

    1994-09-01

    The PP code is a graphics post-processor and plotting program for EQ6, a popular reaction-path code. PP runs on personal computers, allocates memory dynamically, and can handle very large reaction path runs. Plots of simple variable groups, such as fluid and solid phase composition, can be obtained with as few as two keystrokes. Navigation through the list of reaction path variables is simple and efficient. Graphics files can be exported for inclusion in word processing documents and spreadsheets, and experimental data may be imported and superposed on the reaction path runs. The EQ6 thermodynamic database can be searched from within PP, to simplify interpretation of complex plots.

  13. Imaging the proton via hard exclusive production in diffractive pp scattering

    SciTech Connect

    Charles Hyde; Leonid Frankfurt; Mark Strikman; Christian Weiss

    2007-05-21

    We discuss the prospects for probing Generalized Parton Distributions (GPDs) via exclusive production of a high-mass system (H = heavy quarkonium, di-photon, di-jet, Higgs boson) in diffractive pp scattering, pp -> p + H + p. In such processes the interplay of hard and soft interactions gives rise to a diffraction pattern in the final-state proton transverse momenta, which is sensitive to the transverse spatial distribution of partons in the colliding protons. We comment on the plans for diffractive pp measurements at RHIC and LHC. Such studies could complement future measurements of GPDs in hard exclusive ep scattering (JLab, COMPASS, EIC).

  14. Is the Z0 observed in pp collisions a composite object?

    NASA Astrophysics Data System (ADS)

    Renard, F. M.

    1983-12-01

    If the Z0 boson is made of colored subconstituents it can be produced in pp (and pp) collisions through the subprocess gluon + gluon --> Z0 + gluon. The rate is estimated from the Z0 - γ mixing parameter and found comparable to that of the Drell-Yan process. Events with a large pTZ0 and a large pT balancing gluon should be observed at the pp collider. Address after October 1, 1983: Dêpartment de Physique Mathématique, USTL, 34060 Montpellier Cedex, France.

  15. Energy calibration of tagged photons by the d(γ,π-pp) reaction

    NASA Astrophysics Data System (ADS)

    Han, Yun-Cheng; Nobuyuki, Chiga; Yu, Fujii; Kenta, Futatsukawa; Osamu, Hashimoto; Kentaro, Hirose; Takatsugu, Ishikawa; Hiroki, Kanda; Masashi, Kaneta; Daisuke, Kawama; Yue, Ma; Kazushige, Maeda; Tomofumi, Maruta; Nayuta, Maruyama; Akihiko, Matsumura; Youhei, Miyagi; Koji, Miwa; Satoshi, Nakamura N.; Hajime, Shimizu; Koutarou, Shirotori; Koutaku, Suzuki; Tadaaki, Tamae; Hirokazu, Tamura; Kyo, Tsukada; Wang, Tie-Shan; Hirohito, Yamazaki

    2010-01-01

    The energy of tagged photons, which were provided from the internal photon tagging system of the Laboratory of Nuclear Science, Tohoku University, has been calibrated using the d(γ,π-pp) reaction. Charged pions and protons in the final state were detected with the Neutral Kaon Spectrometer (NKS2). Photon energies were obtained from the reaction of d(γ,π-pp). The derived photon energy was consistent with the design of the tagger system and the previous measurement using electron-positron pair production. The consistency demonstrates the performance of NKS2 and the capability of the photon energy calibration using d(γ,π-pp).

  16. Expressional regulation of PpDAM5 and PpDAM6, peach (Prunus persica) dormancy-associated MADS-box genes, by low temperature and dormancy-breaking reagent treatment.

    PubMed

    Yamane, Hisayo; Ooka, Tomomi; Jotatsu, Hiroaki; Hosaka, Yukari; Sasaki, Ryuta; Tao, Ryutaro

    2011-06-01

    The present study investigated the expressional regulation of PpDAM5 and PpDAM6, two of the six peach (Prunus persica) dormancy-associated MADS-box genes, in relation to lateral bud endodormancy. PpDAM5 and PpDAM6 were originally identified as homologues of Arabidopsis SHORT VEGETATIVE PHASE/AGAMOUS-LIKE 24 identified in the EVERGROWING locus of peach. Furthermore, PpDAM5 and PpDAM6 have recently been suggested to be involved in terminal bud dormancy. In this study, seasonal expression analyses using leaves, stems, and lateral buds of high-chill and low-chill peaches in field conditions indicated that both genes were up-regulated during the endodormancy period and down-regulated with endodormancy release. Controlled environment experiments showed that the expression of both PpDAM5 and PpDAM6 were up-regulated by ambient cool temperatures in autumn, while they were down-regulated by the prolonged period of cold temperatures in winter. A negative correlation between expression levels of PpDAM5 and PpDAM6 and bud burst percentage was found in the prolonged cold temperature treatment. Application of the dormancy-breaking reagent cyanamide to endo/ecodormant lateral buds induced early bud break and down-regulation of PpDAM5 and PpDAM6 expression at the same time. These results collectively suggest that PpDAM5 and PpDAM6 may function in the chilling requirement of peach lateral buds through growth-inhibiting functions for bud break.

  17. The PP2PP experiment at RHIC: silicon detectors installed in Roman Pots for forward proton detection close to the beam

    NASA Astrophysics Data System (ADS)

    Bültmann, S.; Chen, W.; Chiang, I. H.; Chrien, R. E.; Drees, A.; Gill, R. L.; Guryn, W.; Landgraf, J.; Li, Z.; Ljubicic, T. A.; Lynn, D.; Pearson, C.; Pile, P.; Radeka, V.; Rusek, A.; Sakitt, M.; Scheetz, R.; Tepikian, S.; Chwastowski, J.; Pawlik, B.; Haguenauer, M.; Bogdanov, A. A.; Nurushev, S. B.; Runtzo, M. F.; Strikhanov, M. N.; Alekseev, I. G.; Kanavets, V. P.; Koroleva, L. I.; Morozov, B. V.; Svirida, D. N.; Khodinov, A.; Rijssenbeek, M.; Tang, C.; Whitehead, L.; Yeung, S.; De, K.; Guler, N.; Li, J.; Öztürk, N.; Sandacz, A.

    2004-12-01

    The PP2PP experiment is one of five experiments at the Relativistic Heavy Ion Collider (RHIC) at the Brookhaven National Laboratory, Long Island, New York. It is designed to measure the elastic scattering of protons at √{s} = 50-500 GeV. The detector consists of silicon strip detectors mounted in Roman Pots and installed in the RHIC ring 60 m from the interaction region. During the engineering run of 2002 and physics run of 2003 the detectors were inserted as close as 15 mm from the proton beam. An overview of the experiment and details of the detector design and performance will be presented.

  18. Intrinsic fluctuations of the proton saturation momentum scale in high multiplicity p+p collisions

    SciTech Connect

    McLerran, Larry; Tribedy, Prithwish

    2015-11-02

    High multiplicity events in p+p collisions are studied using the theory of the Color Glass Condensate. Here, we show that intrinsic fluctuations of the proton saturation momentum scale are needed in addition to the sub-nucleonic color charge fluctuations to explain the very high multiplicity tail of distributions in p+p collisions. It is presumed that the origin of such intrinsic fluctuations is non-perturbative in nature. Classical Yang Mills simulations using the IP-Glasma model are performed to make quantitative estimations. Furthermore, we find that fluctuations as large as O(1) of the average values of the saturation momentum scale can lead to rare high multiplicity events seen in p+p data at RHIC and LHC energies. Using the available data on multiplicity distributions we try to constrain the distribution of the proton saturation momentum scale and make predictions for the multiplicity distribution in 13 TeV p+p collisions.

  19. Facile Method to Fabricate Highly Thermally Conductive Graphite/PP Composite with Network Structures.

    PubMed

    Feng, Changping; Ni, Haiying; Chen, Jun; Yang, Wei

    2016-08-03

    Thermally conductive polymer composites have aroused significant academic and industrial interest for several decades. Herein, we report a novel fabrication method of graphite/polypropylene (PP) composites with high thermal conductivity in which graphite flakes construct a continuous thermally conductive network. The thermal conductivity coefficient of the graphite/PP composites is markedly improved to be 5.4 W/mK at a graphite loading of 21.2 vol %. Such a great improvement of the thermal conductivity is ascribed to the occurrence of orientations of crystalline graphite flakes with large particles around PP resin particles and the formation of a perfect thermally conductive network. The model of Hashin-Shtrikman (HS) is adopted to interpret the outstanding thermally conductive property of the graphite/PP composites. This work provides a guideline for the easy fabrication of thermally conductive composites with network structures.

  20. Structural relationship between a bacterial developmental protein and eukaryotic PP2C protein phosphatases.

    PubMed

    Adler, E; Donella-Deana, A; Arigoni, F; Pinna, L A; Stragler, P

    1997-01-01

    Bacillus subtilis SpoIIE is a Ser protein phosphatase whose action on the phosphoprotein SpoIIAA triggers the cell type-specific activation of a sporulation transcription factor. Here we report that SpoIIE displays sequence similarity to the PP2C family of eukaryotic Ser/Thr protein phosphatases, and that residues common to these proteins are required for the function of both SpoIIE and TPD1, a yeast PP2C. These findings suggest that SpoIIE and the PP2C protein phosphatases are structurally related, and reveal a striking formal similarity between the SpoIIAA regulatory circuit and that of mammalian mitochondrial pyruvate dehydrogenase. This similarity may reflect an evolutionarily conserved mechanism of biological regulation based on the interplay of His protein kinase-like Ser kinases and PP2C-like protein phosphatases.

  1. Recognition of a PP2C interaction motif in several plant protein kinases.

    PubMed

    Chakraborty, Niranjan; Ohta, Masaru; Zhu, Jian-Kang

    2007-01-01

    Protein phosphatase 2Cs (PP2Cs) constitute a major class of phosphatases in plants. PP2Cs play important roles in many signaling pathways by countering the action of specific protein kinases. In addition to their role in several environmental stress-related signal transduction pathways, they are also involved in plant metabolism. Protein phosphatases often physically associate with their protein kinase counterparts. One approach to understanding PP2C function is to identify their interacting protein kinases. We describe a yeast two-hybrid assay system used in our lab to determine the interaction between members of the PP2C family and protein kinases in the SOS2 family. This chapter and the cited articles describing related work might be of help in discovering interactions between other protein phosphatases and kinases.

  2. All roads lead to PP2A: Exploiting the therapeutic potential of this phosphatase

    PubMed Central

    Sangodkar, Jaya; Farrington, Caroline; McClinch, Kimberly; Galsky, Matthew D.; Kastrinsky, David B.; Narla, Goutham

    2015-01-01

    Protein phosphatase 2A is a serine/threonine phosphatase involved in the regulation of many cellular processes. A confirmed tumor suppressor protein, PP2A is genetically altered or functionally inactivated in many cancers highlighting a need for its therapeutic reactivation. In this review we will discuss recent literature on PP2A: the elucidation of its structure and the functions of its subunits, and the identification of molecular lesions and post-translational modifications leading to its dysregulation in cancer. A final section will discuss the proteins and small molecules that modulate PP2A and how these might be used to target dysregulated forms of PP2A to treat cancers and other diseases. PMID:26507691

  3. Regulation of the phosphatase PP2B by protein–protein interactions

    PubMed Central

    Nygren, Patrick J.; Scott, John D.

    2016-01-01

    Protein dephosphorylation is important for regulating cellular signaling in a variety of contexts. Protein phosphatase-2B (PP2B), or calcineurin, is a widely expressed serine/threonine phosphatase that acts on a large cross section of potential protein substrates when activated by increased levels of intracellular calcium in concert with calmodulin. PxIxIT and LxVP targeting motifs are important for maintaining specificity in response to elevated calcium. In the present study, we describe the mechanism of PP2B activation, discuss its targeting by conserved binding motifs and review recent advances in the understanding of an A-kinase anchoring protein 79/PP2B/protein kinase A complex’s role in synaptic long-term depression. Finally, we discuss potential for targeting PP2B anchoring motifs for therapeutic benefit. PMID:27911714

  4. Remarks on B-physics with interactions of pp and e sup + e sup minus

    SciTech Connect

    Fridman, A. Paris-6 Univ., 75 Paris-7 Univ., 75 ); Snyder, A. )

    1990-08-01

    We compare the B-physics that could be studied with pp or e{sup +}e{sup {minus}} interactions. The pp colliders at cm energies of 16 TeV (LHC) and 40 TeV (SSC) as well as asymmetric e{sup +}e{sup {minus}} colliders at the {Upsilon}(4S) cm energy are considered. In the case of pp interactions, we discuss the B production using pp colliders and a p beam with an external fixed target. For this preliminary comparison we explore the possibility of searching CP violation in the B{sub d}{sup 0}, {bar B}{sub d}{sup 0} {yields} J/{psi}K{sub s}{sup 0}, {pi}{sup +}{pi}{sup {minus}} decays. 25 refs., 4 figs.

  5. DETAIL OF THE EXTERIOR OF PP44L (VIEWING PORTAL), ALTITUDE CHAMBER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF THE EXTERIOR OF PP44L (VIEWING PORTAL), ALTITUDE CHAMBER L, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Altitude Chambers, First Street, between Avenue D and Avenue E, Cape Canaveral, Brevard County, FL

  6. DETAIL OF THE EXTERIOR OF PP45L (PATCHBOARD), ALTITUDE CHAMBER L, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF THE EXTERIOR OF PP45L (PATCHBOARD), ALTITUDE CHAMBER L, FACING EAST - Cape Canaveral Air Force Station, Launch Complex 39, Altitude Chambers, First Street, between Avenue D and Avenue E, Cape Canaveral, Brevard County, FL

  7. DETAIL OF THE INTERIOR OF PP45L (PATCHBOARD), ALTITUDE CHAMBER L, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF THE INTERIOR OF PP45L (PATCHBOARD), ALTITUDE CHAMBER L, FACING WEST - Cape Canaveral Air Force Station, Launch Complex 39, Altitude Chambers, First Street, between Avenue D and Avenue E, Cape Canaveral, Brevard County, FL

  8. Spectroscopic observation of SN 2017pp by NUTS (NOT Un-biased Transient Survey)

    NASA Astrophysics Data System (ADS)

    Pastorello, A.; Elias-Rosa, N.; Benetti, S.; Cappellaro, E.; Terreran, G.; Tomasella, L.; Tronsgaard, R.

    2017-01-01

    The Nordic Optical Telescope (NOT) Unbiased Transient Survey (NUTS; ATel #8992) reports the spectroscopic classification of SN 2017pp in PGC 1378162. The candidate was discovered by F. Ciabattari, E. Mazzoni, S. Donati (ISSP; http://italiansupernovae.org).

  9. Investigating hadronic resonances in pp interactions with HADES

    NASA Astrophysics Data System (ADS)

    Przygoda, Witold

    2015-06-01

    In this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e- were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e- channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.

  10. PpRab1, a Rab GTPase from maritime pine is differentially expressed during embryogenesis.

    PubMed

    Gonçalves, Sónia; Cairney, John; Rodríguez, María Pérez; Cánovas, Francisco; Oliveira, Margarida; Miguel, Célia

    2007-09-01

    Rab-related small GTP-binding proteins are known to be involved in the regulation of the vesicular transport system in eukaryotic cells. We report the characterization of a previously isolated full-length cDNA PpRab1 from Pinus pinaster. Amino acid sequence analysis revealed the presence of G1-G5 conserved domains of the GTPase Ras superfamily and a double cysteine motif in the C-terminal, characteristic of Rab proteins. The PpRab1 protein shows high sequence similarity to several Rab1 GTP-binding proteins in plants. Phylogenetic analysis showed that, within the Ras superfamily, PpRab1 is more closely related to the Rab family and within this, PpRab1 protein was found to cluster with Arabidopsis subfamily AtRABE, whose members are known to regulate ER-to-Golgi membrane trafficking steps. PpRab1 transcripts were expressed at constitutively high levels for the initial stages of zygotic embryo development, and then their relative abundance decreased as embryo matures. The PpRab1 transcript is not embryo-specific as it was found in roots, cotyledons and hypocotyls. An increase in PpRab1 expression level was observed when seeds are germinated and collected at successive time points of development. In situ RT-PCR analysis revealed an expression signal in early zygotic embryos. In view of the proposed roles of Rab1 GTP-binding protein, the possible function of the protein encoded by PpRab1 in embryogenesis is discussed.

  11. Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats

    NASA Astrophysics Data System (ADS)

    Lucroy, Michael D.; Edwards, Benjamin F.; Peavy, George M.; Krasieva, Tatiana B.; Griffey, Stephen M.; Madewell, Bruce R.

    1998-07-01

    Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIX), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIX production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, of 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than those dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.

  12. Placental Protein 13 (PP13) – A Placental Immunoregulatory Galectin Protecting Pregnancy

    PubMed Central

    Than, Nándor Gábor; Balogh, Andrea; Romero, Roberto; Kárpáti, Éva; Erez, Offer; Szilágyi, András; Kovalszky, Ilona; Sammar, Marei; Gizurarson, Sveinbjorn; Matkó, János; Závodszky, Péter; Papp, Zoltán; Meiri, Hamutal

    2014-01-01

    Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a “jelly-roll” fold, carbohydrate-recognition domain and sugar-binding preference resembling other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ, suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low concentrations in first trimester maternal sera are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure

  13. The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121

    SciTech Connect

    Peng, Yi; Zhou, Yajuan; Cheng, Long; Hu, Desheng; Zhou, Xiaoyi; Wang, Zhaohua; Xie, Conghua; Zhou, Fuxiang

    2015-09-11

    Here we explored the potential effect of PP121, a novel dual inhibitor of tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We showed that PP121 exerted potent cytotoxic effect in primary (patient-derived) and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly through activating caspase-3-dependnent apoptosis. PP121 was, however, non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of rapamycin) activation in esophageal cancer cells, which was restored by introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, we showed that PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude mice, and significantly improved mice survival. Further, the immunohistochemistry (IHC) and Western blot assays analyzing xenografted tumors showed that PP121 inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly through concurrently inhibiting Akt-mTOR and NFκB signalings. - Highlights: • PP121 is cytotoxic against primary and established esophageal cancer cells. • PP121 induces caspase-3-dependnent apoptosis in esophageal cancer cells. • PP121 blocks Akt-mTOR activation in esophageal cancer cells. • PP121 inhibits NFκB activation, independent of Akt-mTOR blockage. • PP121 inhibits Eca-109 xenograft growth and Akt-mTOR/NFκB activation in vivo.

  14. The "K-pp" System Investigated with a Coupled-Channel Complex Scaling Method

    NASA Astrophysics Data System (ADS)

    Doté, Akinobu

    Nuclear systems with anti-kaons (kaonic nuclei) are expected to have exotic nature such as formation of a dense state, due to the strong attraction between an anti-kaon and a nucleon. In this article, the current theoretical studies of the most essential kaonic nucleus "K-pp" are reviewed and our study of "K-pp" based on a coupled-channel Complex Scaling Method is reported. With a new version of our chiral SU(3)-based potential constrained by a precise measurement of kaonic hydrogen atom (SIDDHARTA experiment), the "K-pp" state is found to be rather shallowly bound: BK - pp = 15-22 MeV and Γ M = 20-50 MeV. The "K-pp" seems to have another pole, and it might possibly have so-called a double-pole structure, similarly to the Λ (1405). Recent results of the K-pp search experiments (J-PARC E15 and E27) are discussed in comparison with several new theoretical studies.

  15. The catalytic role of the M2 metal ion in PP2Cα.

    PubMed

    Pan, Chang; Tang, Jun-yi; Xu, Yun-fei; Xiao, Peng; Liu, Hong-da; Wang, Hao-an; Wang, Wen-bo; Meng, Fan-guo; Yu, Xiao; Sun, Jin-peng

    2015-02-24

    PP2C family phosphatases (the type 2C family of protein phosphatases; or metal-dependent phosphatase, PPM) constitute an important class of signaling enzymes that regulate many fundamental life activities. All PP2C family members have a conserved binuclear metal ion active center that is essential for their catalysis. However, the catalytic role of each metal ion during catalysis remains elusive. In this study, we discovered that mutations in the structurally buried D38 residue of PP2Cα (PPM1A) redefined the water-mediated hydrogen network in the active site and selectively disrupted M2 metal ion binding. Using the D38A and D38K mutations of PP2Cα as specific tools in combination with enzymology analysis, our results demonstrated that the M2 metal ion determines the rate-limiting step of substrate hydrolysis, participates in dianion substrate binding and stabilizes the leaving group after P-O bond cleavage. The newly characterized catalytic role of the M2 metal ion in this family not only provides insight into how the binuclear metal centers of the PP2C phosphatases are organized for efficient catalysis but also helps increase our understanding of the function and substrate specificity of PP2C family members.

  16. PP2C family members play key roles in regulation of cell survival and apoptosis.

    PubMed

    Tamura, Shinri; Toriumi, Shinnosuke; Saito, Jun-Ichi; Awano, Kenjiro; Kudo, Tada-Aki; Kobayashi, Takayasu

    2006-07-01

    Although unlimited proliferation of cancer cells is supported by multiple signaling pathways involved in the regulation of proliferation, survival, and apoptosis, the molecular mechanisms coordinating these different pathways to promote the proliferation and survival of cancer cells have remained unclear. SAPK and integrin-ILK signaling pathways play key roles in the promotion of apoptosis and cell proliferation/survival, respectively. Studies of TNFalpha- and H2O2-induced apoptosis revealed that ASK1, a component of the SAPK system, mediates the TNFalpha and H2O2 signaling of apoptosis. ASK1 is activated by autophosphorylation of a specific threonine residue (T845) following TNFalpha stimulation. Our recent studies indicate that PP2Cepsilon, a member of the PP2C family, associates with and inactivates ASK1 by dephosphorylating T845. In contrast, PP2Cdelta/ILKAP, a second PP2C family member, activates ASK1 by enhancing cellular phosphorylation of T845. PP2Cdelta/ILKAP also forms a complex with ILK1 to inhibit the GSK3beta-mediated integrin-ILK1 signaling in vivo, inhibiting cell cycle progression. These observations raise the possibility that PP2Cdelta/ILKAP acts to control the cross-talk between integrin-induced and TNFalpha-induced signaling pathways, inhibiting the former and stimulating the latter, thereby inhibiting proliferation and survival and promoting the apoptosis of cancer cells.

  17. The catalytic role of the M2 metal ion in PP2Cα

    NASA Astrophysics Data System (ADS)

    Pan, Chang; Tang, Jun-Yi; Xu, Yun-Fei; Xiao, Peng; Liu, Hong-Da; Wang, Hao-An; Wang, Wen-Bo; Meng, Fan-Guo; Yu, Xiao; Sun, Jin-Peng

    2015-02-01

    PP2C family phosphatases (the type 2C family of protein phosphatases; or metal-dependent phosphatase, PPM) constitute an important class of signaling enzymes that regulate many fundamental life activities. All PP2C family members have a conserved binuclear metal ion active center that is essential for their catalysis. However, the catalytic role of each metal ion during catalysis remains elusive. In this study, we discovered that mutations in the structurally buried D38 residue of PP2Cα (PPM1A) redefined the water-mediated hydrogen network in the active site and selectively disrupted M2 metal ion binding. Using the D38A and D38K mutations of PP2Cα as specific tools in combination with enzymology analysis, our results demonstrated that the M2 metal ion determines the rate-limiting step of substrate hydrolysis, participates in dianion substrate binding and stabilizes the leaving group after P-O bond cleavage. The newly characterized catalytic role of the M2 metal ion in this family not only provides insight into how the binuclear metal centers of the PP2C phosphatases are organized for efficient catalysis but also helps increase our understanding of the function and substrate specificity of PP2C family members.

  18. A subset of RAB proteins modulates PP2A phosphatase activity.

    PubMed

    Sacco, Francesca; Mattioni, Anna; Boldt, Karsten; Panni, Simona; Santonico, Elena; Castagnoli, Luisa; Ueffing, Marius; Cesareni, Gianni

    2016-09-09

    Protein phosphatase 2A (PP2A) is one of the most abundant serine-threonine phosphatases in mammalian cells. PP2A is a hetero-trimeric holoenzyme participating in a variety of physiological processes whose deregulation is often associated to cancer. The specificity and activity of this phosphatase is tightly modulated by a family of regulatory B subunits that dock the catalytic subunit to the substrates. Here we characterize a novel and unconventional molecular mechanism controlling the activity of the tumor suppressor PP2A. By applying a mass spectrometry-based interactomics approach, we identified novel PP2A interacting proteins. Unexpectedly we found that a significant number of RAB proteins associate with the PP2A scaffold subunit (PPP2R1A), but not with the catalytic subunit (PPP2CA). Such interactions occur in vitro and in vivo in specific subcellular compartments. Notably we demonstrated that one of these RAB proteins, RAB9, competes with the catalytic subunit PPP2CA in binding to PPP2R1A. This competitive association has an important role in controlling the PP2A catalytic activity, which is compromised in several solid tumors and leukemias.

  19. New KF-PP-SVM classification method for EEG in brain-computer interfaces.

    PubMed

    Yang, Banghua; Han, Zhijun; Zan, Peng; Wang, Qian

    2014-01-01

    Classification methods are a crucial direction in the current study of brain-computer interfaces (BCIs). To improve the classification accuracy for electroencephalogram (EEG) signals, a novel KF-PP-SVM (kernel fisher, posterior probability, and support vector machine) classification method is developed. Its detailed process entails the use of common spatial patterns to obtain features, based on which the within-class scatter is calculated. Then the scatter is added into the kernel function of a radial basis function to construct a new kernel function. This new kernel is integrated into the SVM to obtain a new classification model. Finally, the output of SVM is calculated based on posterior probability and the final recognition result is obtained. To evaluate the effectiveness of the proposed KF-PP-SVM method, EEG data collected from laboratory are processed with four different classification schemes (KF-PP-SVM, KF-SVM, PP-SVM, and SVM). The results showed that the overall average improvements arising from the use of the KF-PP-SVM scheme as opposed to KF-SVM, PP-SVM and SVM schemes are 2.49%, 5.83 % and 6.49 % respectively.

  20. PpRT1: the first complete gypsy-like retrotransposon isolated in Pinus pinaster.

    PubMed

    Rocheta, Margarida; Cordeiro, Jorge; Oliveira, M; Miguel, Célia

    2007-02-01

    We have isolated and characterized a complete retrotransposon sequence, named PpRT1, from the genome of Pinus pinaster. PpRT1 is 5,966 bp long and is closely related to IFG7 gypsy retrotransposon from Pinus radiata. The long terminal repeats (LTRs) have 333 bp each and show a 5.4% sequence divergence between them. In addition to the characteristic polypurine tract (PPT) and the primer binding site (PBS), PpRT1 carries internal regions with homology to retroviral genes gag and pol. The pol region contains sequence motifs related to the enzymes protease, reverse transcriptase, RNAseH and integrase in the same typical order known for Ty3/gypsy-like retrotransposons. PpRT1 was extended from an EST database sequence indicating that its transcription is occurring in pine tissues. Southern blot analyses indicate however, that PpRT1 is present in a unique or a low number of copies in the P. pinaster genome. The differences in nucleotide sequence found between PpRT1 and IFG7 may explain the strikingly different copy number in the two pine species genome. Based on the homologies observed when comparing LTR region among different gypsy elements we propose that the highly conserved LTR regions may be useful to amplify other retrotransposon sequences of the same or close retrotransposon family.

  1. Regulation of σ factor competition by the alarmone ppGpp

    PubMed Central

    Jishage, Miki; Kvint, Kristian; Shingler, Victoria; Nyström, Thomas

    2002-01-01

    Many regulons controlled by alternative σ factors, including σS and σ32, are poorly induced in cells lacking the alarmone ppGpp. We show that ppGpp is not absolutely required for the activity of σS-dependent promoters because underproduction of σ70, specific mutations in rpoD (rpoD40 and rpoD35), or overproduction of Rsd (anti-σ70) restored expression from σS-dependent promoters in vivo in the absence of ppGpp accumulation. An in vitro transcription/competition assay with reconstituted RNA polymerase showed that addition of ppGpp reduces the ability of wild-type σ70 to compete with σ32 for core binding and the mutant σ70 proteins, encoded by rpoD40 and rpoD35, compete less efficiently than wild-type σ70. Similarly, an in vivo competition assay showed that the ability of both σ32 and σS to compete with σ70 is diminished in cells lacking ppGpp. Consistently, the fraction of σS and σ32 bound to core was drastically reduced in ppGpp-deficient cells. Thus, the stringent response encompasses a mechanism that alters the relative competitiveness of σ factors in accordance with cellular demands during physiological stress. PMID:12023304

  2. The melt-recrystallization behavior of highly oriented α-iPP fibers embedded in a HIPS matrix.

    PubMed

    Ye, Liwei; Li, Huihui; Qiu, Zhaobin; Yan, Shouke

    2015-03-21

    The melt-recrystallization behavior of α-iPP fibers embedded in an amorphous HIPS matrix has been studied by means of optical microscopy. The amorphous HIPS serving as a supporter of iPP fibers does not become involved in the nucleation and crystallization process of the molten highly oriented iPP fibers. It also does not provide any birefringence under the optical microscope with crossed polarizers. This enables the study of orientation-induced β-iPP crystallization through a control of the melting status of the fibers. Through melting the fibers at different temperatures above 175 °C and subsequent recrystallization, some β-iPP crystals were always produced. The content of the β-iPP crystal depends strongly on the melting temperature and melting time of the iPP fibers. It was confirmed that melting the iPP fibers at relatively lower temperature, e.g. 176 °C, less amount of β-iPP crystals were observed. The content of β-iPP crystal enhances first with increasing melting temperature and then decreases with further increase of the fiber melting temperature. The β-iPP crystallization is found to be most favorable upon melting the fibers at 178 °C for 2 min. This demonstrates the requirement of a certain chain or chain segment orientation for generating β-iPP crystallization on the one hand, while higher orientation of the iPP chains or chain segments encourages the growth of iPP crystals in the α-form on the other hand. This has been further confirmed by varying the melting time of the fiber at different temperatures, since relaxation of the iPP molecular chains at a fixed temperature is time dependent. Moreover, the complete transformation of α-iPP fibers in some local places into β-iPP crystals implies that the αβ-transition may not be required for the orientation-induced β-iPP crystallization.

  3. Many Means to a Common End: the Intricacies of (p)ppGpp Metabolism and Its Control of Bacterial Homeostasis

    PubMed Central

    Gaca, Anthony O.; Colomer-Winter, Cristina

    2015-01-01

    In nearly all bacterial species examined so far, amino acid starvation triggers the rapid accumulation of the nucleotide second messenger (p)ppGpp, the effector of the stringent response. While for years the enzymes involved in (p)ppGpp metabolism and the significance of (p)ppGpp accumulation to stress survival were considered well defined, a recent surge of interest in the field has uncovered an unanticipated level of diversity in how bacteria metabolize and utilize (p)ppGpp to rapidly synchronize a variety of biological processes important for growth and stress survival. In addition to the classic activation of the stringent response, it has become evident that (p)ppGpp exerts differential effects on cell physiology in an incremental manner rather than simply acting as a biphasic switch that controls growth or stasis. Of particular interest is the intimate relationship of (p)ppGpp with persister cell formation and virulence, which has spurred the pursuit of (p)ppGpp inhibitors as a means to control recalcitrant infections. Here, we present an overview of the enzymes responsible for (p)ppGpp metabolism, elaborate on the intricacies that link basal production of (p)ppGpp to bacterial homeostasis, and discuss the implications of targeting (p)ppGpp synthesis as a means to disrupt long-term bacterial survival strategies. PMID:25605304

  4. From QCD-based hard-scattering to nonextensive statistical mechanical descriptions of transverse momentum spectra in high-energy pp and pp¯ collisions

    DOE PAGES

    Wong, Cheuk-Yin; Wilk, Grzegorz; Cirto, Leonardo J. L.; ...

    2015-06-22

    Transverse spectra of both jets and hadrons obtained in high-energymore » $pp$ and $$p\\bar p $$ collisions at central rapidity exhibit power-law behavior of $$1/p_T^n$$ at high $$p_T$$. The power index $n$ is 4-5 for jet production and is slightly greater for hadron production. Furthermore, the hadron spectra spanning over 14 orders of magnitude down to the lowest $$p_T$$ region in $pp$ collisions at LHC can be adequately described by a single nonextensive statistical mechanical distribution that is widely used in other branches of science. This suggests indirectly the dominance of the hard-scattering process over essentially the whole $$p_T$$ region at central rapidity in $pp$ collisions at LHC. We show here direct evidences of such a dominance of the hard-scattering process by investigating the power index of UA1 jet spectra over an extended $$p_T$$ region and the two-particle correlation data of the STAR and PHENIX Collaborations in high-energy $pp$ and $$p \\bar p$$ collisions at central rapidity. We then study how the showering of the hard-scattering product partons alters the power index of the hadron spectra and leads to a hadron distribution that can be cast into a single-particle non-extensive statistical mechanical distribution. Lastly, because of such a connection, the non-extensive statistical mechanical distribution can be considered as a lowest-order approximation of the hard-scattering of partons followed by the subsequent process of parton showering that turns the jets into hadrons, in high energy $pp$ and $$p\\bar p$$ collisions.« less

  5. Site Specificity of Cleavage of DSP-PP by BMP1

    PubMed Central

    Yang, Robert T.; Lim, Glendale L.; Yee, Colin T.; Fuller, Robert S.; Ritchie, Helena H.

    2015-01-01

    Bone morphogenic protein 1 (BMP1), a metalloproteinase, is known to cleave a wide variety of extracellular matrix proteins, suggesting that a consensus substrate cleavage amino acid sequence might exist. However, while such a consensus sequence has been proposed based on P4 to P4′ (i.e., the four amino acids flanking either side of the BMP1 cleavage site; P4P3P2P1|P1′P2′P3′P4′) sequence homologies between two BMP1 substrates, dentin matrix protein 1 and dentin sialoprotein phosphophoryn (DSP-PP) (i.e., xMQx | DDP), no direct testing has so far been attempted. Using an Sf9 cell expression system, we have been able to produce large amounts of uncleaved DSP-PP,. Point mutations introduced into this recombinant DSP-PP were then tested for their affects on DSP-PP cleavage by either Sf9 endogenous tolloid-related protein 1 (TLR-1) or by its human homolog, BMP1. Here we have measured DSP-PP cleavage efficiencies after modifications based on P4-P4′ sequence comparisons with dentin matrix protein 1, as well as for prolysyl oxidase and chordin, two other BMP1 substrates. Our results demonstrate that any mutations within or outside of the DSP-PP P4 to P4′ cleavage site can block, impair or accelerate DSP-PP cleavage, and suggest that its BMP1 cleavage site is highly conserved in order to regulate its cleavage efficiency, possibly with additional assistance from its conserved exosites. Thus, BMP1 cleavage cannot be based on a consensus substrate cleavage site. PMID:25158199

  6. Role of (p)ppGpp in Viability and Biofilm Formation of Actinobacillus pleuropneumoniae S8

    PubMed Central

    Li, Gang; Xie, Fang; Zhang, Yanhe; Bossé, Janine T.; Langford, Paul R.; Wang, Chunlai

    2015-01-01

    Actinobacillus pleuropneumoniae is a Gram-negative bacterium and the cause of porcine pleuropneumonia. When the bacterium encounters nutritional starvation, the relA-dependent (p)ppGpp-mediated stringent response is activated. The modified nucleotides guanosine 5’-diphosphate 3’-diphosphate (ppGpp) and guanosine 5’-triphosphate 3’-diphosphate (pppGpp) are known to be signaling molecules in other prokaryotes. Here, to investigate the role of (p)ppGpp in A. pleuropneumoniae, we created a mutant A. pleuropneumoniae strain, S8ΔrelA, which lacks the (p)ppGpp-synthesizing enzyme RelA, and investigated its phenotype in vitro. S8ΔrelA did not survive after stationary phase (starvation condition) and grew exclusively as non-extended cells. Compared to the wild-type (WT) strain, the S8ΔrelA mutant had an increased ability to form a biofilm. Transcriptional profiles of early stationary phase cultures revealed that a total of 405 bacterial genes were differentially expressed (including 380 up-regulated and 25 down-regulated genes) in S8ΔrelA as compared with the WT strain. Most of the up-regulated genes are involved in ribosomal structure and biogenesis, amino acid transport and metabolism, translation cell wall/membrane/envelope biogenesis. The data indicate that (p)ppGpp coordinates the growth, viability, morphology, biofilm formation and metabolic ability of A. pleuropneumoniae in starvation conditions. Furthermore, S8ΔrelA could not use certain sugars nor produce urease which has been associated with the virulence of A. pleuropneumoniae, suggesting that (p)ppGpp may directly or indirectly affect the pathogenesis of A. pleuropneumoniae during the infection process. In summary, (p)ppGpp signaling represents an essential component of the regulatory network governing stress adaptation and virulence in A. pleuropneumoniae. PMID:26509499

  7. Overexpression of the PP2A-C5 gene confers increased salt tolerance in Arabidopsis thaliana

    PubMed Central

    Hu, Rongbin; Zhu, Yinfeng; Shen, Guoxin; Zhang, Hong

    2017-01-01

    ABSTRACT Protein phosphatase 2A (PP2A) was shown to play important roles in biotic and abiotic stress signaling pathways in plants. PP2A is made of 3 subunits: a scaffolding subunit A, a regulatory subunit B, and a catalytic subunit C. It is believed that the B subunit recognizes specific substrates and the C subunit directly acts on the selected substrates, whereas the A subunit brings a B subunit and a C subunit together to form a specific PP2A holoenzyme. Because there are multiple isoforms for each PP2A subunit, there could be hundreds of novel PP2A holoenzymes in plants. For an example, there are 3 A subunits, 17 B subunits, and 5 C subunits in Arabidopsis, which could form 255 different PP2A holoenzymes. Understanding the roles of these PP2A holoenzymes in various signaling pathways is a challenging task. In a recent study,1 we discovered that PP2A-C5, the catalytic subunit 5 of PP2A, plays an important role in salt tolerance in Arabidopsis. We found that a knockout mutant of PP2A-C5 (i.e. pp2a-c5–1) was very sensitive to salt treatments, whereas PP2A-C5-overexpressing plants were more tolerant to salt stresses. Genetic analyses between pp2a-c5–1 and Salt-Overly-Sensitive (SOS) mutants indicated that PP2A-C5 does not function in the same pathway as SOS genes. Using yeast 2-hybrid analysis, we found that PP2A-C5 interacts with several vacuolar membrane bound chloride channel proteins. We hypothesize that these vacuolar chloride channel proteins might be PP2A-C5's substrates in vivo, and the action of PP2A-C5 on these channel proteins could increase or activate their activities, thereby result in accumulation of the chloride and sodium contents in vacuoles, leading to increased salt tolerance in plants. PMID:28045581

  8. Mechanism of PP2A-mediated IKKβ dephosphorylation: a systems biological approach

    PubMed Central

    Witt, Johannes; Barisic, Sandra; Schumann, Eva; Allgöwer, Frank; Sawodny, Oliver; Sauter, Thomas; Kulms, Dagmar

    2009-01-01

    Background Biological effects of nuclear factor-κB (NFκB) can differ tremendously depending on the cellular context. For example, NFκB induced by interleukin-1 (IL-1) is converted from an inhibitor of death receptor induced apoptosis into a promoter of ultraviolet-B radiation (UVB)-induced apoptosis. This conversion requires prolonged NFκB activation and is facilitated by IL-1 + UVB-induced abrogation of the negative feedback loop for NFκB, involving a lack of inhibitor of κB (IκBα) protein reappearance. Permanent activation of the upstream kinase IKKβ results from UVB-induced inhibition of the catalytic subunit of Ser-Thr phosphatase PP2A (PP2Ac), leading to immediate phosphorylation and degradation of newly synthesized IκBα. Results To investigate the mechanism underlying the general PP2A-mediated tuning of IKKβ phosphorylation upon IL-1 stimulation, we have developed a strictly reduced mathematical model based on ordinary differential equations which includes the essential processes concerning the IL-1 receptor, IKKβ and PP2A. Combining experimental and modelling approaches we demonstrate that constitutively active, but not post-stimulation activated PP2A, tunes out IKKβ phosphorylation thus allowing for IκBα resynthesis in response to IL-1. Identifiability analysis and determination of confidence intervals reveal that the model allows reliable predictions regarding the dynamics of PP2A deactivation and IKKβ phosphorylation. Additionally, scenario analysis is used to scrutinize several hypotheses regarding the mode of UVB-induced PP2Ac inhibition. The model suggests that down regulation of PP2Ac activity, which results in prevention of IκBα reappearance, is not a direct UVB action but requires instrumentality. Conclusion The model developed here can be used as a reliable building block of larger NFκB models and offers comprehensive simplification potential for future modeling of NFκB signaling. It gives more insight into the newly discovered

  9. Molecular cloning, expression and functional analysis of three subunits of protein phosphatase 2A (PP2A) from black tiger shrimps (Penaeus monodon).

    PubMed

    Zhao, Chao; Wang, Yan; Fu, Mingjun; Yang, Keng; Qiu, Lihua

    2017-02-01

    Protein phosphatase 2A (PP2A) is a cellular serine-threonine (Ser/Thr) phosphatase that plays a crucial role in regulating most cellular functions. In the present study, the full-length cDNAs of three subunits of PmPP2A (PmPP2A-A, PP2A-B and PP2A-C) were cloned from Penaeus monodon, which are the first available for shrimps. Sequence analysis showed that PmPP2A-A, PmPP2A-B and PmPP2A-C encoded polypeptides of 591, 443, and 324 amino acids, respectively. The mRNAs of three subunits of PmPP2A were expressed constitutively in all tissues examined, and predominantly in the ovaries. In ovarian maturation stages, the three subunits of PmPP2A were continuously but differentially expressed. Dopamine and 5-hydroxytryptamine injection experiments were conducted to study the expression profile of three subunits of PmPP2A, and the results indicated that PmPP2A played a negative regulatory role in the process of ovarian maturation. In addition, the recombinant proteins of three subunits of PmPP2A were successfully obtained, and the phosphatase activity of PmPP2A was tested in vitro. The results of this study will advance our understanding about the molecular mechanisms of PmPP2A in Penaeus monodon.

  10. PP6 controls T cell development and homeostasis by negatively regulating distal TCR signaling.

    PubMed

    Ye, Jian; Shi, Hao; Shen, Ye; Peng, Chao; Liu, Yan; Li, Chenyu; Deng, Kejing; Geng, Jianguo; Xu, Tian; Zhuang, Yuan; Zheng, Biao; Tao, Wufan

    2015-02-15

    T cell development and homeostasis are both regulated by TCR signals. Protein phosphorylation and dephosphorylation, which are catalyzed by protein kinases and phosphatases, respectively, serve as important switches controlling multiple downstream pathways triggered by TCR recognition of Ags. It has been well documented that protein tyrosine phosphatases are involved in negative regulation of proximal TCR signaling. However, how TCR signals are terminated or attenuated in the distal TCR signaling pathways is largely unknown. We investigated the function of Ser/Thr protein phosphatase (PP) 6 in TCR signaling. T cell lineage-specific ablation of PP6 in mice resulted in enhanced thymic positive and negative selection, and preferential expansion of fetal-derived, IL-17-producing Vγ6Vδ1(+) T cells. Both PP6-deficient peripheral CD4(+) helper and CD8(+) cytolytic cells could not maintain a naive state and became fast-proliferating and short-lived effector cells. PP6 deficiency led to profound hyperactivation of multiple distal TCR signaling molecules, including MAPKs, AKT, and NF-κB. Our studies demonstrate that PP6 acts as a critical negative regulator, not only controlling both αβ and γδ lineage development, but also maintaining naive T cell homeostasis by preventing their premature activation before Ag stimulation.

  11. Release property and antioxidant effectiveness of tocopherol-incorporated LDPE/PP blend films.

    PubMed

    Zhu, X; Lee, D S; Yam, K L

    2012-01-01

    Low-density polyethylene (LDPE)/polypropylene (PP) blend films in various blending ratios containing 3000 mg  kg⁻¹ of tocopherol were manufactured by an extrusion process. Tocopherol release properties were characterised and correlated with antioxidant effectiveness in retarding the oxidation of linoleic acid contacting the films at 40°C. The conditions without tocopherol (control) and with instant tocopherol addition corresponding to the amount included in the films were also prepared and compared with the film-contacting solutions. The effect of tocopherol inclusion and the blending ratio on their physical properties was also examined. A wide range of tocopherol diffusivity in 6.6 × 10⁻¹⁶-4.6 × 10⁻¹⁴m² s⁻¹ were obtained by blend films. As PP content increases, the diffusivity decreased sharply at the beginning and levelled off later. The slower release of tocopherol in LDPE/PP blend films corresponding to lower tocopherol diffusivity retained the higher tocopherol concentration in the linoleic acid system providing better antioxidant effectiveness of the extended induction period in oxidation. The tocopherol inclusion reduced tensile strength and transparency significantly in an affordable range with higher tensile strength given by a higher PP ratio. LDPE/PP blending can be a useful tool to modulate the release profile of tocopherol and thus the antioxidant effectiveness of the tocopherol-incorporated antioxidant packaging film.

  12. PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells

    PubMed Central

    Rogers, Samuel; Fey, Dirk; McCloy, Rachael A.; Parker, Benjamin L.; Mitchell, Nicholas J.; Payne, Richard J.; Daly, Roger J.; James, David E.; Caldon, C. Elizabeth; Watkins, D. Neil; Croucher, David R.; Burgess, Andrew

    2016-01-01

    ABSTRACT Entry into mitosis is driven by the phosphorylation of thousands of substrates, under the master control of Cdk1. During entry into mitosis, Cdk1, in collaboration with MASTL kinase, represses the activity of the major mitotic protein phosphatases, PP1 and PP2A, thereby ensuring mitotic substrates remain phosphorylated. For cells to complete and exit mitosis, these phosphorylation events must be removed, and hence, phosphatase activity must be reactivated. This reactivation of phosphatase activity presumably requires the inhibition of MASTL; however, it is not currently understood what deactivates MASTL and how this is achieved. In this study, we identified that PP1 is associated with, and capable of partially dephosphorylating and deactivating, MASTL during mitotic exit. Using mathematical modelling, we were able to confirm that deactivation of MASTL is essential for mitotic exit. Furthermore, small decreases in Cdk1 activity during metaphase are sufficient to initiate the reactivation of PP1, which in turn partially deactivates MASTL to release inhibition of PP2A and, hence, create a feedback loop. This feedback loop drives complete deactivation of MASTL, ensuring a strong switch-like activation of phosphatase activity during mitotic exit. PMID:26872783

  13. PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells.

    PubMed

    Rogers, Samuel; Fey, Dirk; McCloy, Rachael A; Parker, Benjamin L; Mitchell, Nicholas J; Payne, Richard J; Daly, Roger J; James, David E; Caldon, C Elizabeth; Watkins, D Neil; Croucher, David R; Burgess, Andrew

    2016-04-01

    Entry into mitosis is driven by the phosphorylation of thousands of substrates, under the master control of Cdk1. During entry into mitosis, Cdk1, in collaboration with MASTL kinase, represses the activity of the major mitotic protein phosphatases, PP1 and PP2A, thereby ensuring mitotic substrates remain phosphorylated. For cells to complete and exit mitosis, these phosphorylation events must be removed, and hence, phosphatase activity must be reactivated. This reactivation of phosphatase activity presumably requires the inhibition of MASTL; however, it is not currently understood what deactivates MASTL and how this is achieved. In this study, we identified that PP1 is associated with, and capable of partially dephosphorylating and deactivating, MASTL during mitotic exit. Using mathematical modelling, we were able to confirm that deactivation of MASTL is essential for mitotic exit. Furthermore, small decreases in Cdk1 activity during metaphase are sufficient to initiate the reactivation of PP1, which in turn partially deactivates MASTL to release inhibition of PP2A and, hence, create a feedback loop. This feedback loop drives complete deactivation of MASTL, ensuring a strong switch-like activation of phosphatase activity during mitotic exit.

  14. PP2A phosphatase acts upon SAS-5 to ensure centriole formation in C. elegans embryos.

    PubMed

    Kitagawa, Daiju; Flückiger, Isabelle; Polanowska, Jolanta; Keller, Debora; Reboul, Jérôme; Gönczy, Pierre

    2011-04-19

    Centrosome duplication occurs once per cell cycle and ensures that the two resulting centrosomes assemble a bipolar mitotic spindle. Centriole formation is fundamental for centrosome duplication. In Caenorhabditis elegans, the evolutionarily conserved proteins SPD-2, ZYG-1, SAS-6, SAS-5, and SAS-4 are essential for centriole formation, but how they function is not fully understood. Here, we demonstrate that Protein Phosphatase 2A (PP2A) is also critical for centriole formation in C. elegans embryos. We find that PP2A subunits genetically and physically interact with the SAS-5/SAS-6 complex. Furthermore, we show that PP2A-mediated dephosphorylation promotes centriolar targeting of SAS-5 and ensures SAS-6 delivery to the site of centriole assembly. We find that PP2A is similarly needed for the presence of HsSAS-6 at centrioles and for centriole formation in human cells. These findings lead us to propose that PP2A-mediated loading of SAS-6 proteins is critical at the onset of centriole formation.

  15. Phosphorylation of PP1 Regulator Sds22 by PLK1 Ensures Accurate Chromosome Segregation.

    PubMed

    Duan, Hequan; Wang, Chunli; Wang, Ming; Gao, Xinjiao; Yan, Maomao; Akram, Saima; Peng, Wei; Zou, Hanfa; Wang, Dong; Zhou, Jiajia; Chu, Youjun; Dou, Zhen; Barrett, Gregory; Green, Hadiyah-Nichole; Wang, Fangjun; Tian, Ruijun; He, Ping; Wang, Wenwen; Liu, Xing; Yao, Xuebiao

    2016-09-30

    During cell division, accurate chromosome segregation is tightly regulated by Polo-like kinase 1 (PLK1) and opposing activities of Aurora B kinase and protein phosphatase 1 (PP1). However, the regulatory mechanisms underlying the aforementioned hierarchical signaling cascade during mitotic chromosome segregation have remained elusive. Sds22 is a conserved regulator of PP1 activity, but how it regulates PP1 activity in space and time during mitosis remains elusive. Here we show that Sds22 is a novel and cognate substrate of PLK1 in mitosis, and the phosphorylation of Sds22 by PLK1 elicited an inhibition of PP1-mediated dephosphorylation of Aurora B at threonine 232 (Thr(232)) in a dose-dependent manner. Overexpression of a phosphomimetic mutant of Sds22 causes a dramatic increase in mitotic delay, whereas overexpression of a non-phosphorylatable mutant of Sds22 results in mitotic arrest. Mechanistically, the phosphorylation of Sds22 by PLK1 strengthens the binding of Sds22 to PP1 and inhibits the dephosphorylation of Thr(232) of Aurora B to ensure a robust, error-free metaphase-anaphase transition. These findings delineate a conserved signaling hierarchy that orchestrates dynamic protein phosphorylation and dephosphorylation of critical mitotic regulators during chromosome segregation to guard chromosome stability.

  16. The therapeutic effects of SET/I2PP2A inhibitors on canine melanoma.

    PubMed

    Enjoji, Shuhei; Yabe, Ryotaro; Fujiwara, Nobuyuki; Tsuji, Shunya; Vitek, Michael P; Mizuno, Takuya; Nakagawa, Takayuki; Usui, Tatsuya; Ohama, Takashi; Sato, Koichi

    2015-11-01

    Canine melanoma is one of the most important diseases in small animal medicine. Protein phosphatase 2A (PP2A), a well conserved serine/threonine phosphatase, plays a critical role as a tumor suppressor. SET/I2PP2A is an endogenous inhibitor for PP2A, which directly binds to PP2A and suppresses its phosphatase activity. Elevated SET protein levels have been reported to exacerbate human tumor progression. The role of SET in canine melanoma, however, has not been understood. Here, we investigated the potential therapeutic role for SET inhibitors in canine melanoma. The expression of SET protein was observed in 6 canine melanoma cell lines. We used CMeC-1 cells (primary origin) and CMeC-2 cells (metastatic origin) to generate cell lines stably expressing SET-targeting shRNAs. Knockdown of SET expression in CMeC-2, but not in CMeC-1, leads to decreased cell proliferation, invasion and colony formation. Phosphorylation level of p70 S6 kinase was decreased by SET knockdown in CMeC-2, suggesting the involvement of mTOR (mammalian target of rapamycin)/p70 S6 kinase signaling. The SET inhibitors, OP449 and FTY720, more effectively killed CMeC-2 than CMeC-1. We observed PP2A activation in CMeC-2 treated with OP449 and FTY720. These results demonstrated the potential therapeutic application of SET inhibitors for canine melanoma.

  17. {lambda}{sup 0} Polarization in Exclusive pp Reactions From the FNAL e690 Experiment

    SciTech Connect

    Felix, J.; Berisso, M. C.; Christian, D. C.; Gottschalk, E. E.; Gutierrez, G.; Wang, M. H. L. S.; Wehmann, A.; Gara, A.; Hartouni, E. P.; Knapp, B. C.; Kreisler, M. N.; Lee, S.; Markianos, K.; Moreno, G.; Reyes, M. A.; Wesson, D.

    2009-04-20

    It is an experimental evidence that all baryons are created polarized from unpolarized p-nucleus collisions. So far, the origin of this polarization remains unexplained in spite of the experimental evidences accumulated in the past thirty years. Up to these days, {lambda}{sup 0} is the most studied baryon for polarization, for it is copiously produced in p--nucleus collisions at the energies of the principal high energy physics accelerators of the world. This paper is an overview of the experimental evidences accumulated on the polarization of {lambda}{sup 0} from unpolarized exclusive pp collisions as function of x{sub F}, P{sub T}, and M({lambda}{sup 0}K{sup +}) in the past fifteen years inside Fermilab e690 experiment, in the particular reactions pp{yields}p{lambda}{sup 0}K{sup 0}{pi}{sup +}, pp{yields}pp{lambda}{sup 0}{lambda}{sup -0}, pp{yields}p{lambda}{sup 0}K{sup +}, produced at 800 GeV.

  18. Identified particle production in pp collisions at = 7 and 13 TeV measured with ALICE

    NASA Astrophysics Data System (ADS)

    Derradi de Souza, R.; ALICE Collaboration

    2017-01-01

    Proton-proton (pp) collisions have been used extensively as a reference for the study of interactions of larger colliding systems at the LHC. Recent measurements performed in high-multiplicity pp and proton-lead (p-Pb) collisions have shown features that are reminiscent of those observed in lead-lead (Pb-Pb) collisions. In this context, the study of identified particle spectra and yields as a function of multiplicity is a key tool for the understanding of similarities and differences between small and large systems. We report on the production of pions, kaons, protons, , Λ, Ξ, Ω and K *0 as a function of multiplicity in pp collisions at = 7 TeV measured with the ALICE experiment. The work presented here represents the most comprehensive set of results on identified particle production in pp collisions at the LHC. Spectral shapes, studied both for individual particles and via particle ratios as a function of p T, exhibit an evolution with charged particle multiplicity that is similar to the one observed in larger systems. In addition, results on the production of light flavour hadrons in pp collisions at = 13 TeV, the highest centre-of-mass energy ever reached in the laboratory, are also presented and compared with previous, lower energy results.

  19. Sperm development and motility are regulated by PP1 phosphatases in Caenorhabditis elegans.

    PubMed

    Wu, Jui-ching; Go, Aiza C; Samson, Mark; Cintra, Thais; Mirsoian, Susan; Wu, Tammy F; Jow, Margaret M; Routman, Eric J; Chu, Diana S

    2012-01-01

    Sperm from different species have evolved distinctive motility structures, including tubulin-based flagella in mammals and major sperm protein (MSP)-based pseudopods in nematodes. Despite such divergence, we show that sperm-specific PP1 phosphatases, which are required for male fertility in mouse, function in multiple processes in the development and motility of Caenorhabditis elegans amoeboid sperm. We used live-imaging analysis to show the PP1 phosphatases GSP-3 and GSP-4 (GSP-3/4) are required to partition chromosomes during sperm meiosis. Postmeiosis, tracking fluorescently labeled sperm revealed that both male and hermaphrodite sperm lacking GSP-3/4 are immotile. Genetic and in vitro activation assays show lack of GSP-3/4 causes defects in pseudopod development and the rate of pseudopodial treadmilling. Further, GSP-3/4 are required for the localization dynamics of MSP. GSP-3/4 shift localization in concert with MSP from fibrous bodies that sequester MSP at the base of the pseudopod, where directed MSP disassembly facilitates pseudopod contraction. Consistent with a role for GSP-3/4 as a spatial regulator of MSP disassembly, MSP is mislocalized in sperm lacking GSP-3/4. Although a requirement for PP1 phosphatases in nematode and mammalian sperm suggests evolutionary conservation, we show PP1s have independently evolved sperm-specific paralogs in separate lineages. Thus PP1 phosphatases are highly adaptable and employed across a broad range of sexually reproducing species to regulate male fertility.

  20. Dual Regulation of the Mitotic Exit Network (MEN) by PP2A-Cdc55 Phosphatase

    PubMed Central

    Baro, Barbara; Hernáez, María Luisa; Gil, Concha; Queralt, Ethel

    2013-01-01

    Exit from mitosis in budding yeast is triggered by activation of the key mitotic phosphatase Cdc14. At anaphase onset, the protease separase and Zds1 promote the downregulation of PP2ACdc55 phosphatase, which facilitates Cdk1-dependent phosphorylation of Net1 and provides the first wave of Cdc14 activity. Once Cdk1 activity starts to decline, the mitotic exit network (MEN) is activated to achieve full Cdc14 activation. Here we describe how the PP2ACdc55 phosphatase could act as a functional link between FEAR and MEN due to its action on Bfa1 and Mob1. We demonstrate that PP2ACdc55 regulates MEN activation by facilitating Cdc5- and Cdk1-dependent phosphorylation of Bfa1 and Mob1, respectively. Downregulation of PP2ACdc55 initiates MEN activity up to Cdc15 by Bfa1 inactivation. Surprisingly, the premature Bfa1 inactivation observed does not entail premature MEN activation, since an additional Cdk1-Clb2 inhibitory signal acting towards Dbf2-Mob1 activity restrains MEN activity until anaphase. In conclusion, we propose a clear picture of how PP2ACdc55 functions affect the regulation of various MEN components, contributing to mitotic exit. PMID:24339788

  1. Cationic bactericidal peptide 1018 does not specifically target the stringent response alarmone (p)ppGpp

    PubMed Central

    Andresen, Liis; Tenson, Tanel; Hauryliuk, Vasili

    2016-01-01

    The bacterial stringent response is a key regulator of bacterial virulence, biofilm formation and antibiotic tolerance, and is a promising target for the development of new antibacterial compounds. The intracellular nucleotide (p)ppGpp acts as a messenger orchestrating the stringent response. A synthetic peptide 1018 was recently proposed to specifically disrupt biofilms by inhibiting the stringent response via direct interaction with (p)ppGpp (de la Fuente-Núñez et al. (2014) PLoS Pathogens). We have interrogated the specificity of the proposed molecular mechanism. When inhibition of Pseudomonas aeruginosa planktonic and biofilm growth is tested simultaneously in the same assay, peptides 1018 and the control peptide 8101 generated by an inversion of the amino acid sequence of 1018 are equally potent, and, importantly, do not display a preferential activity against biofilm. 1018 inhibits planktonic growth of Escherichia coli equally efficiently either when the alleged target, (p)ppGpp, is essential (MOPS media lacking amino acid L-valine), or dispensable for growth (MOPS media supplemented with L-valine). Genetic disruption of the genes relA and spoT responsible for (p)ppGpp synthesis moderately sensitizes – rather than protects – E. coli to 1018. We suggest that the antimicrobial activity of 1018 does not rely on specific recognition of the stringent response messenger (p)ppGpp. PMID:27819280

  2. A PP6-Type Phosphatase Holoenzyme Directly Regulates PIN Phosphorylation and Auxin Efflux in Arabidopsis[C][W

    PubMed Central

    Dai, Mingqiu; Zhang, Chen; Kania, Urszula; Chen, Fang; Xue, Qin; Mccray, Tyra; Li, Gang; Qin, Genji; Wakeley, Michelle; Terzaghi, William; Wan, Jianmin; Zhao, Yunde; Xu, Jian; Friml, Jiří; Deng, Xing Wang; Wang, Haiyang

    2012-01-01

    The directional transport of the phytohormone auxin depends on the phosphorylation status and polar localization of PIN-FORMED (PIN) auxin efflux proteins. While PINIOD (PID) kinase is directly involved in the phosphorylation of PIN proteins, the phosphatase holoenzyme complexes that dephosphorylate PIN proteins remain elusive. Here, we demonstrate that mutations simultaneously disrupting the function of Arabidopsis thaliana FyPP1 (for Phytochrome-associated serine/threonine protein phosphatase1) and FyPP3, two homologous genes encoding the catalytic subunits of protein phosphatase6 (PP6), cause elevated accumulation of phosphorylated PIN proteins, correlating with a basal-to-apical shift in subcellular PIN localization. The changes in PIN polarity result in increased root basipetal auxin transport and severe defects, including shorter roots, fewer lateral roots, defective columella cells, root meristem collapse, abnormal cotyledons (small, cup-shaped, or fused cotyledons), and altered leaf venation. Our molecular, biochemical, and genetic data support the notion that FyPP1/3, SAL (for SAPS DOMAIN-LIKE), and PP2AA proteins (RCN1 [for ROOTS CURL IN NAPHTHYLPHTHALAMIC ACID1] or PP2AA1, PP2AA2, and PP2AA3) physically interact to form a novel PP6-type heterotrimeric holoenzyme complex. We also show that FyPP1/3, SAL, and PP2AA interact with a subset of PIN proteins and that for SAL the strength of the interaction depends on the PIN phosphorylation status. Thus, an Arabidopsis PP6-type phosphatase holoenzyme acts antagonistically with PID to direct auxin transport polarity and plant development by directly regulating PIN phosphorylation. PMID:22715043

  3. Preparation of EPR/silica filler by a co-irradiation method forming PP/EPR/silica nanocomposites

    NASA Astrophysics Data System (ADS)

    Qian, Jun; Dang, Shuaiying; Huang, Zhijuan; Xu, Yongshen

    2012-01-01

    This paper presents a novel approach to prepare ethylene-propylene rubber (EPR)/silica filler by co-irradiation method forming polypropylene (PP)/EPR/silica nanocomposites. The grafting of maleic anhydride (MAH) on EPR was first studied by co-irradiation in the micro-suspension without any chemical initiator, and the effects of MAH concentration and the total co-irradiation dose on the graft degree of MAH were investigated. Then PP/EPR/silica nanocomposites were successfully prepared by blending of PP matrix and EPR/silica filler, which was obtained by co-irradiation using a mixture of EPR/MAH microsuspension in xylene and tetraethoxysilane/KH560 sol in formic acid. FTIR and SEM results showed that the reactions between MAH on EPR chains and KH560 surrounding silica particles were adopted to form the EPR/silica filler with strong bonding and well silica dispersion. Mechanical properties of PP/EPR/silica nanocomposites with different silica contents and the comparisons with PP, PP/EPR and PP/silica films were studied. The rigid silica particles were trapped in EPR shell and well dispersed in PP/EPR/silica nanocomposites with good compatibility and strong interfacial adhesion, achieving overall improvements in stiffness, strength and toughness compared with pure PP.

  4. Fabrication of PP-g-PEGMA-g-heparin and its hemocompatibility: From protein adsorption to anticoagulant tendency

    NASA Astrophysics Data System (ADS)

    Jin, Jing; Jiang, Wei; shi, Qiang; Zhao, Jie; Yin, Jinghua; Stagnaro, Paola

    2012-05-01

    We described a two-step process to fabricate the heparinized polypropylene (PP) film using cyanuric chloride (CC) as a trifunctional reagent and poly (ethylene glycol) methacrylate (PEGMA) as a spacer. The modified PP films were characterized by attenuated total reflectance FT-IR and X-ray photoelectron spectroscopy; the content of PEGMA and heparin were determined by gravimetric method and a toluidine blue assay, respectively. For the PP-g-PEGMA films, it was found that small size protein BSA tended to adsorb on the surface of low molecular weight monomer grafted PP, whereas big spindle-shaped fibrinogen tended to adsorb on the surface of high molecular weight monomer grafted PP. We gave a definition of anti-protein adsorptive factor r with two model proteins, albumin and fibrinogen. The results by platelet adhesion and plasma recalcification time (PRT) experiments indicated that the factor r could be used to quantitatively evaluate the anticoagulant tendency of PP-g-PEGMA modified films. For the PP-g-PEGMA-g-heparin modified films, the surface was proved to have a high bioactivity by the adsorption of AT III assay and very low platelet adhesion. It indicated that immobilization of heparin on the PP film with PEGMA as a spacer was an effective way to improve the hemocompatibility of PP.

  5. GridPP - Preparing for LHC Run 2 and the Wider Context

    NASA Astrophysics Data System (ADS)

    Coles, Jeremy

    2015-12-01

    This paper elaborates upon the operational status and directions within the UK Computing for Particle Physics (GridPP) project as it approaches LHC Run 2. It details the pressures that have been gradually reshaping the deployed hardware and middleware environments at GridPP sites - from the increasing adoption of larger multicore nodes to the move towards alternative batch systems and cloud alternatives - as well as changes being driven by funding considerations. The paper highlights work being done with non-LHC communities and describes some of the early outcomes of adopting a generic DIRAC based job submission and management framework. The paper presents results from an analysis of how GridPP effort is distributed across various deployment and operations tasks and how this may be used to target further improvements in efficiency.

  6. The prospective pediatric continuous renal replacement therapy (ppCRRT) registry: a critical appraisal.

    PubMed

    Sutherland, Scott M; Goldstein, Stuart L; Alexander, Steven R

    2014-11-01

    Continuous renal replacement therapy (CRRT), which provides gradual, predictable clearance and fluid removal, is commonly used to manage acute kidney injury (AKI) and fluid overload in critically ill children. The Prospective Pediatric CRRT (ppCRRT) Registry, founded in 2001 and comprising 13 pediatric centers in the United States, represents the largest cohort of children receiving CRRT to date. Data from the ppCRRT has been used to describe pediatric CRRT demographics and epidemiology, improve technical aspects of CRRT provision for children, and identify novel or underappreciated risk factors affecting survival. Whereas the registry has successfully answered many questions, a number of questions remain unanswered and new ones have arisen. This article describes the ppCRRT Registry, including its major findings, the lessons learned, and the limitations inherent in its design. Additionally, using the registry as a framework, areas of future study are identified and potential methodologies examined.

  7. C-terminal truncation of GSK-3β enhances its dephosphorylation by PP2A.

    PubMed

    Jin, Nana; Wu, Yue; Xu, Wen; Gong, Cheng-Xin; Iqbal, Khalid; Liu, Fei

    2017-03-07

    Glycogen synthase kinase-3β (GSK-3β) is the major tau kinase. Its phosphorylation at Ser9 suppresses the activity. In Alzheimer's disease (AD) brain, GSK-3β is truncated at the C-terminus by over-activated calpain I, leading to an increase in its activity. However, the effect of truncation on its phosphorylation is unknown. We found here that in AD brain and in cultured cells, C-terminally truncated GSK-3β is less phosphorylated at Ser9 than the full-length enzyme. The truncation promotes GSK-3β nuclear translocation and enhances its interaction with protein phosphatase 2A (PP2A), leading to dephosphorylation. Thus, the truncation of GSK-3β may enhance its activity through Ser9 dephosphorylation by PP2A. Our findings shed new light onto the role of calpain - GSK-3β - PP2A in tau pathogenesis of AD. This article is protected by copyright. All rights reserved.

  8. Catalytic mechanism and kinase interactions of ABA-signaling PP2C phosphatases.

    PubMed

    Zhou, X Edward; Soon, Fen-Fen; Ng, Ley-Moy; Kovach, Amanda; Suino-Powell, Kelly M; Li, Jun; Yong, Eu-Leong; Zhu, Jian-Kang; Xu, H Eric; Melcher, Karsten

    2012-05-01

    Abscisic acid (ABA) is an essential hormone that controls plant growth, development and responses to abiotic stresses. ABA signaling is mediated by type 2C protein phosphatases (PP2Cs), including HAB1 and ABI2, which inhibit stress-activated SnRK2 kinases and whose activity is regulated by ABA and ABA receptors. Based on biochemical data and our previously determined crystal structures of ABI2 and the SnRK2.6-HAB1 complex, we present the catalytic mechanism of PP2C and provide new insight into PP2C-SnRK2 interactions and possible roles of other SnRK2 kinases in ABA signaling.

  9. Tensor Correlations Measured in 3He(e,e'pp)n

    SciTech Connect

    Baghdasaryan, H; Weinstein, L B; Adhikari, K P; Aghasyan, K P; Amarian, M; Anghinolfi, M; Avakian, H; Ball, J; Battaglieri, M; Bedlinskiy, I; Berman, B L; Biselli, A S; Bookwalter, C; Briscoe, W J; Brooks, W K; Boltmann, S; Burkert, V D; Carman, D S; Crede, V; D'Angelo, A; Daniel, A; Dashyan, N; DeVita, R; DeSanctis, E; Deur, A; Dey, B; Dickson, R; Djalali, C; Dodge, G E; Doughty, D; Dupre, R; Egiyan, H; El Alaoui, A; El Fassi, L; Eugenio, P; Fegan, S; Gabrielyan, M Y; Gilfoyle, G P; Giovanetti, K L; Gohn, W; Gothe, R W; Griffioen, K A; Guidal, M; Guo, L; Gyurjyan, V; Hakobyan, H; Hanretty, C; Hyde, C E; Hicks, K; Holtrop, M; Ilieva, Y; Ireland, D G; Joo, K; Keller, D; Khandaker, M; Khetarpal, P; Kim, A; Kim, W; Klein, A; Klein, F J; Konczykowski, P; Kubarovsky, V; Kuhn, S E; Kuleshov, S V; Kuznetsov, V; Kvaltine, N D; Livingston, K; Lu, H Y; MacGregor, I.J.D.; Markov, N; Mayer, M; McAndrew, J; McKinnon, B; Meyer, C A; Mikhailov, K; Mokeev, V; Moreno, B; Moriya, K; Morrison, B; Moutarde, H; Munevar, E; Nadel-Turonski, P; Nepali, C; Niccolai, S; Niculescu, G; Niculescu, I; Osipenko, M; Ostrovidov, A I; Paremuzyan, R; Park, K; Park, S; Pasyuk, E; Anefalos Pereira, S; Pisano, S; Pogorelko, O; Pozdniakov, S; Price, J W; Procureur, S; Protopopescu, D; Ricco, G; Ripani, M; Rosner, G; Rossi, P; Sabatie, F; Salgado, C; Schumacher, R A; Seraydaryan, H; Smith, G D; Sober, D I; Sokhan, D; Stepanyan, S S; Stepanyan, S; Stoler, P; Strauch, S; Taiuti, M; Tang, W; Taylor, C E; Tedeschi, D J; Ungaro, M; Vineyard, M F; Voutier, E; Watts, D P; Weygand, D P; Wood, M H; Zhao, B; Zhao, Z W

    2010-11-01

    We have measured the 3He(e,e'pp)n reaction at an incident energy of 4.7 GeV over a wide kinematic range. We identified spectator correlated pp and pn nucleon pairs by using kinematic cuts and measured their relative and total momentum distributions. This is the first measurement of the ratio of pp to pn pairs as a function of pair total momentum ptot. For pair relative momenta between 0.3 and 0.5 GeV/c, the ratio is very small at low ptot and rises to approximately 0.5 at large ptot. This shows the dominance of tensor over central correlations at this relative momentum.

  10. Completeness of general pp-wave spacetimes and their impulsive limit

    NASA Astrophysics Data System (ADS)

    Sämann, Clemens; Steinbauer, Roland; Švarc, Robert

    2016-11-01

    We investigate geodesic completeness in the full family of pp-wave (or Brinkmann) spacetimes in their extended and impulsive forms. This class of geometries contains the recently studied gyratonic pp-waves, modelling the exterior field of a spinning beam of null particles, as well as N-fronted waves with parallel rays, which generalize classical pp-waves by allowing for a general wave surface. The problem of geodesic completeness reduces to the question of completeness of trajectories on a Riemannian manifold under an external force field. Building upon respective recent results, we derive completeness criteria in terms of the spatial asymptotics of the profile function in the extended case. In the impulsive case, we use a fixed-point argument to show that, irrespective of the behaviour of the profile function, all geometries in the class are complete.

  11. Quantitative comparison of measurement methods for the evaluation of micro- and nanostructures written with 2PP

    NASA Astrophysics Data System (ADS)

    Harnisch, Emely Marie; König, Niels; Schmitt, Robert

    2016-04-01

    Two-Photon Polymerization (2PP) has become an established process for fabricating individual micro-and nanostructures nearly in the last two decades. Its high degree of freedom opened up novel possibilities for a large range of applications like functional structures for cell growth, photonic crystals, nanoantennas, diffractive optical elements and lab-on-a-chip structures (just to name a few). Since the measurement of structures written with 2PP is always very time consuming, we present a comparison between white light interferometry (WLI) and confocal microscopy (CM) which were used for measuring structures written with 2PP. By performing a GageRR analysis with both metrology devices, we calculated the process tolerance one has to accept when measuring these structures with WLI or CM.

  12. Effects of layer-multiplying and interface on the content of β-transcrystallization in PP

    SciTech Connect

    Lei, Fan; Li, Jiang E-mail: nic7702@scu.edu.cn; Guo, Shaoyun E-mail: nic7702@scu.edu.cn

    2015-05-22

    The alternating multilayered polypropylene (PP layer)/β-nucleating agent filled-polypropylene (β-PP layer) were prepared through layer-multiplying extrusion combined with an assembly of layer-multiplying elements (LM Es). The content of β-crystal was firstly evaluated by differential scanning calorimetry (DSC), which indicated that the relative amount of the β-crystal increased from 38.67% to 81.22% with the increase of layer numbers from 2-layer to 128-layer. It was well consistent with the results of X-ray diffraction (XRD). The morphology observation of β-crystal by polarizing microscope (POM) revealed that the closely packed nuclei in the interface could induce numerous β-transcrystallization in pure PP layer due to the confinement effect. The non-isothermal crystallization kinetic analysis via Mozhishen’s methods manifested that the crystallization rate was greatly enhanced by the augment of the layered interface.

  13. PNUTS/PP1 Regulates RNAPII-Mediated Gene Expression and Is Necessary for Developmental Growth

    PubMed Central

    Ciurciu, Anita; Duncalf, Louise; Jonchere, Vincent; Lansdale, Nick; Vasieva, Olga; Glenday, Peter; Rudenko, Andreii; Vissi, Emese; Cobbe, Neville; Alphey, Luke; Bennett, Daimark

    2013-01-01

    In multicellular organisms, tight regulation of gene expression ensures appropriate tissue and organismal growth throughout development. Reversible phosphorylation of the RNA Polymerase II (RNAPII) C-terminal domain (CTD) is critical for the regulation of gene expression states, but how phosphorylation is actively modified in a developmental context remains poorly understood. Protein phosphatase 1 (PP1) is one of several enzymes that has been reported to dephosphorylate the RNAPII CTD. However, PP1's contribution to transcriptional regulation during animal development and the mechanisms by which its activity is targeted to RNAPII have not been fully elucidated. Here we show that the Drosophila orthologue of the PP1 Nuclear Targeting Subunit (dPNUTS) is essential for organismal development and is cell autonomously required for growth of developing tissues. The function of dPNUTS in tissue development depends on its binding to PP1, which we show is targeted by dPNUTS to RNAPII at many active sites of transcription on chromosomes. Loss of dPNUTS function or specific disruption of its ability to bind PP1 results in hyperphosphorylation of the RNAPII CTD in whole animal extracts and on chromosomes. Consistent with dPNUTS being a global transcriptional regulator, we find that loss of dPNUTS function affects the expression of the majority of genes in developing 1st instar larvae, including those that promote proliferative growth. Together, these findings shed light on the in vivo role of the PNUTS-PP1 holoenzyme and its contribution to the control of gene expression during early Drosophila development. PMID:24204300

  14. Cloning and expression analysis of PpSUT2 encoding a sucrose transporter in pear.

    PubMed

    Tang, J; Lin, J; Zhang, B L; Wang, Z H; Li, X G; Chang, Y H

    2014-10-31

    A 1794-bp cDNA fragment was amplified from mRNA isolated from pear (Pyrus pyrifolia NaKai. Cuiguan) leaves by using primers based on the sequences generated during the analysis of the pear transcriptome. The 597-amino acid sequence encoded by the cDNA was compared with the sequences in GenBank, and it was found to be similar to that of members of the sucrose-proton co-transporter family. The hydrophobic protein, which was predicted to have 11 transmembrane domains, was designated as PpSUT2. Real-time fluorescent quantitative polymerase chain reaction analysis indicated the accumulation of PpSUT2 mRNA throughout the plant, with the highest levels in the buds. Analysis of the expression of PpSUT2 during fruit development showed that the abundance of its transcripts increased at the end of April and then decreased to the lowest level at the end of July. Subcellular localization studies with the pCXDG vector as a probe demonstrated that PpSUT2 localized to cell membranes. An expression vector was constructed by inserting the PpSUT2 cDNA into pET32(a), and the vector was expressed in Escherichia coli (strain BL21) after induction with 1 mM isopropyl b-d-1-thiogalactopyranoside at 25°C. Analysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis identified the induction of a 71-kDa protein. Further analysis indicated that PpSUT2 might be not directly involved in sucrose transport, instead, functioning as a sucrose sensor on the cytoplasmic membrane.

  15. PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells

    PubMed Central

    Neviani, Paolo; Harb, Jason G.; Oaks, Joshua J.; Santhanam, Ramasamy; Walker, Christopher J.; Ellis, Justin J.; Ferenchak, Gregory; Dorrance, Adrienne M.; Paisie, Carolyn A.; Eiring, Anna M.; Ma, Yihui; Mao, Hsiaoyin C.; Zhang, Bin; Wunderlich, Mark; May, Philippa C.; Sun, Chaode; Saddoughi, Sahar A.; Bielawski, Jacek; Blum, William; Klisovic, Rebecca B.; Solt, Janelle A.; Byrd, John C.; Volinia, Stefano; Cortes, Jorge; Huettner, Claudia S.; Koschmieder, Steffen; Holyoake, Tessa L.; Devine, Steven; Caligiuri, Michael A.; Croce, Carlo M.; Garzon, Ramiro; Ogretmen, Besim; Arlinghaus, Ralph B.; Chen, Ching-Shih; Bittman, Robert; Hokland, Peter; Roy, Denis-Claude; Milojkovic, Dragana; Apperley, Jane; Goldman, John M.; Reid, Alistair; Mulloy, James C.; Bhatia, Ravi; Marcucci, Guido; Perrotti, Danilo

    2013-01-01

    The success of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML) depends on the requirement for BCR-ABL1 kinase activity in CML progenitors. However, CML quiescent HSCs are TKI resistant and represent a BCR-ABL1 kinase–independent disease reservoir. Here we have shown that persistence of leukemic HSCs in BM requires inhibition of the tumor suppressor protein phosphatase 2A (PP2A) and expression — but not activity — of the BCR-ABL1 oncogene. Examination of HSCs from CML patients and healthy individuals revealed that PP2A activity was suppressed in CML compared with normal HSCs. TKI-resistant CML quiescent HSCs showed increased levels of BCR-ABL1, but very low kinase activity. BCR-ABL1 expression, but not kinase function, was required for recruitment of JAK2, activation of a JAK2/β-catenin survival/self-renewal pathway, and inhibition of PP2A. PP2A-activating drugs (PADs) markedly reduced survival and self-renewal of CML quiescent HSCs, but not normal quiescent HSCs, through BCR-ABL1 kinase–independent and PP2A-mediated inhibition of JAK2 and β-catenin. This led to suppression of human leukemic, but not normal, HSC/progenitor survival in BM xenografts and interference with long-term maintenance of BCR-ABL1–positive HSCs in serial transplantation assays. Targeting the JAK2/PP2A/β-catenin network in quiescent HSCs with PADs (e.g., FTY720) has the potential to treat TKI-refractory CML and relieve lifelong patient dependence on TKIs. PMID:23999433

  16. [Preparation of microencapsulated red phosphorus and its flame-retardant application in PP composites].

    PubMed

    Jiang, Wen-Jun; Li, Zhe-Zhao; Zhang, Chun-Xiang; Fang, Jin; Yang, Xu-Jie; Lu, Lu-De; Pu, Long-Juan

    2010-05-01

    In the present study, the melamine-formaldehyde prepolymer (MFP) was first synthesized at pH 8-8.5 under about 80 degrees C with melamine, formaldehyde, triethanolamine and methanol as the starting materials. Subsequently, the microencapsulated red phosphorus (MRP) was successfully prepared by in-situ polymerization at pH 5.5 under 65 degrees C, using MFP and red phosphorus (RP) powders as raw materials, and potassium persulphate (KPS) as catalyst. The obtained products were detected by differential scan calorimetry (DSC), scanning electron microscope (SEM), Fourier transform infrared (FTIR) and X-ray photo-electron spectroscopy (XPS). It was found that KPS is useful in enhancing the reaction activity of MFP, which can make RP be well encapsulated by melamine-formaldehyde resin (MF) and reduce the reaction time. The DSC, SEM and XPS results show that it won't get well-encapsulated MRP only under acidic condition and without any KPS. When a proper quantity of KPS is employed, the RP particles can be almost completely-encapsulated by MF and the peak temperature of oxidation reaction for MRP is 480 degrees C, which is much higher than that of RP, extending the applications for MRP. The FTIR spectrum demonstrates that the coating material on the surface of RP accurately is MF, in agreement with the reference. Polyproplene (PP) composites with different formulations were prepared by melt extrusion. It was shown that the flame-retardant efficiencies are very low when the PP composites only contain MRP or MH. However, the flame-retardant property can obviously improve if MRP and MH are both used in the PP composites. When PP : MRP: MH = 100 (phr) : 15 (phr) : 50 (phr), the limited oxygen index of the MRP/MH/PP composite is 26%, and vertical firing ranks UL-94 V-0. In addition, the possible flame-retardant mechanism of the PP composites has also been discussed, and further verified by FTIR and Raman spectroscopy.

  17. Absence of intraepidermal glycosyltransferase ppGalNac-T3 expression in familial tumoral calcinosis.

    PubMed

    Topaz, Orit; Bergman, Reuven; Mandel, Ulla; Maor, Gila; Goldberg, Ruth; Richard, Gabriele; Sprecher, Eli

    2005-06-01

    Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder characterized by progressive, tumor-like calcifications in the dermis and subcutaneous tissues. The disease is associated with primary hyperphosphatemia due to increased renal tubular reabsorption of phosphate. We recently identified mutations in GALNT3 as the proximal cause of this metabolic disorder. GALNT3 encodes the glycosyltransferase UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 3 (ppGalNAc-T3), which initiates mucin-type O-glycosylation and thus takes part in posttranslational modification and formation of mucin-type glycoproteins. A number of studies have previously described the histopathological and ultrastructural features of lesional skin in HFTC, but little is currently known about the morphology of the normal-appearing non-lesional skin. We obtained biopsies of uninvolved skin from two HFTC patients carrying a known splice site mutation in GALNT3. Light and electron microscopic examination of a biopsy of one of the two patients did not reveal abnormal findings in the epidermis or dermis. However, immunohistochemical studies of frozen skin sections of biopsies of the two patients using monoclonal antibodies directed against three ppGalNac isoforms revealed the complete absence of immunostaining for ppGalNAc-T3 while the staining pattern for ppGalNAc-T2 and -T6 was identical in skin biopsies obtained from HFTC patients and healthy control individuals. Our data provide for the first time evidence for ppGalNAc-T3 deficiency in the skin of HFTC patients and suggest that immunostaining of skin biopsy samples for ppGal-Nac-T3 might be a useful tool for the diagnosis of HFTC.

  18. Measurement of Solar pp-neutrino flux with Borexino: results and implications

    NASA Astrophysics Data System (ADS)

    Smirnov, O. Yu; Agostini, M.; Appel, S.; Bellini, G.; Benziger, J.; Bick, D.; Bonfini, G.; Bravo, D.; Caccianiga, B.; Calaprice, F.; Caminata, A.; Cavalcante, P.; Chepurnov, A.; D'Angelo, D.; Davini, S.; Derbin, A.; Di Noto, L.; Drachnev, I.; Etenko, A.; Fomenko, K.; Franco, D.; Gabriele, F.; Galbiati, C.; Ghiano, C.; Giammarchi, M.; Goeger-Neff, M.; Goretti, A.; Gromov, M.; Hagner, C.; Hungerford, E.; Ianni, Aldo; Ianni, Andrea; Jedrzejczak, K.; Kaiser, M.; Kobychev, V.; Korablev, D.; Korga, G.; Kryn, D.; Laubenstein, M.; Lehnert, B.; Litvinovich, E.; Lombardi, F.; Lombardi, P.; Ludhova, L.; Lukyanchenko, G.; Machulin, O.; Manecki, S.; Maneschg, W.; Marcocci, S.; Meroni, E.; Meyer, M.; Miramonti, L.; Misiaszek, M.; Montuschi, M.; Mosteiro, P.; Muratova, V.; Neumair, B.; Oberauer, L.; Obolensky, M.; Ortica, F.; Pallavicini, M.; Papp, L.; Perasso, L.; Pocar, A.; Ranucci, G.; Razeto, A.; Re, A.; Romani, A.; Roncin, R.; Rossi, N.; Schönert, S.; Semenov, D.; Simgen, H.; Skorokhvatov, M.; Sotnikov, A.; Sukhotin, S.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Thurn, J.; Toropova, M.; Unzhakov, E.; Vishneva, A.; Vogelaar, R. B.; von Feilitzsch, F.; Wang, H.; Weinz, S.; Winter, J.; Wojcik, M.; Wurm, M.; Yokley, Z.; Zaimidoroga, O.; Zavatarelli, S.; Zuber, K.; Zuzel, G.

    2016-02-01

    Measurement of the Solar pp-neutrino flux completed the measurement of Solar neutrino fluxes from the pp-chain of reactions in Borexino experiment. The result is in agreement with the prediction of the Standard Solar Model and the MSW/LMA oscillation scenario. A comparison of the total neutrino flux from the Sun with Solar luminosity in photons provides a test of the stability of the Sun on the 105 years time scale, and sets a strong limit on the power production by the unknown energy sources in the Sun.

  19. Two-Nucleon Momentum Distributions Measured in 3He(e,e'pp)n

    SciTech Connect

    R.A. Niyazov; L.B. Weinstein; et al

    2004-02-01

    We have measured the 3He(e,e'pp)n reaction at 2.2 GeV over a wide kinematic range. The kinetic energy distribution for ''fast'' nucleons (p > 250 MeV/c) peaks where two nucleons each have 20% or less, and the third nucleon has most of the transferred energy. These fast pp and pn pairs are back-to-back with little momentum along the three-momentum transfer, indicating that they are spectators. Experimental and theoretical evidence indicates that we have measured distorted two-nucleon momentum distributions by striking the third nucleon and detecting the spectator correlated pair.

  20. The protein phosphatase 2C (PP2C) superfamily: detection of bacterial homologues.

    PubMed

    Bork, P; Brown, N P; Hegyi, H; Schultz, J

    1996-07-01

    A thorough sequence analysis of the various members of the eukaryotic protein serine/threonine phosphatase 2C (PP2C) family revealed the conservation of 11 motifs. These motifs could be identified in numerous other sequences, including fungal adenylate cyclases that are predicted to contain a functionally active PP2C domain, and a family of prokaryotic serine/threonine phosphatases including SpoIIE. Phylogenetic analysis of all the proteins indicates a widespread sequence family for which a considerable number of isoenzymes can be inferred.

  1. Search for the decay B ¯0→Λc+p ¯pp ¯

    NASA Astrophysics Data System (ADS)

    Lees, J. P.; Poireau, V.; Tisserand, V.; Grauges, E.; Palano, A.; Eigen, G.; Stugu, B.; Brown, D. N.; Kerth, L. T.; Kolomensky, Yu. G.; Lee, M. J.; Lynch, G.; Koch, H.; 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.; Yushkov, A. N.; Kirkby, D.; Lankford, A. J.; Mandelkern, M.; Dey, B.; Gary, J. W.; Long, O.; Campagnari, C.; Franco Sevilla, M.; Hong, T. M.; Kovalskyi, D.; Richman, J. D.; West, C. A.; Eisner, A. M.; Lockman, W. S.; Schumm, B. A.; Seiden, A.; Chao, D. S.; Cheng, C. H.; Echenard, B.; Flood, K. T.; Hitlin, D. G.; Ongmongkolkul, P.; Porter, F. C.; Andreassen, R.; Huard, Z.; Meadows, B. T.; Pushpawela, B. G.; Sokoloff, M. D.; Sun, L.; Bloom, P. C.; Ford, W. T.; Gaz, A.; Nauenberg, U.; Smith, J. G.; Wagner, S. R.; Ayad, R.; Toki, W. H.; Spaan, B.; Schwierz, R.; Bernard, D.; Verderi, M.; Playfer, S.; Bettoni, D.; Bozzi, C.; Calabrese, R.; Cibinetto, G.; Fioravanti, E.; Garzia, I.; Luppi, E.; Piemontese, L.; Santoro, V.; Baldini-Ferroli, R.; Calcaterra, A.; de Sangro, R.; Finocchiaro, G.; Martellotti, S.; Patteri, P.; Peruzzi, I. M.; Piccolo, M.; Rama, M.; Zallo, A.; Contri, R.; Guido, E.; Lo Vetere, M.; Monge, M. R.; Passaggio, S.; Patrignani, C.; Robutti, E.; Bhuyan, B.; Prasad, V.; Morii, M.; Adametz, A.; Uwer, U.; Lacker, H. M.; Dauncey, P. D.; Mallik, U.; Chen, C.; Cochran, J.; Meyer, W. T.; 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.; Prencipe, E.; Schubert, K. R.; Barlow, R. J.; Lafferty, G. D.; Behn, E.; Cenci, R.; Hamilton, B.; Jawahery, A.; Roberts, D. A.; Cowan, R.; Dujmic, D.; Sciolla, G.; Cheaib, R.; Patel, P. M.; Robertson, S. H.; Biassoni, P.; Neri, N.; Palombo, F.; Cremaldi, L.; Godang, R.; Sonnek, P.; Summers, D. J.; Simard, M.; Taras, P.; de Nardo, G.; Monorchio, D.; Onorato, G.; Sciacca, C.; Martinelli, M.; Raven, G.; Jessop, C. P.; Losecco, J. M.; Honscheid, K.; Kass, R.; Brau, J.; Frey, R.; Sinev, N. B.; Strom, D.; Torrence, E.; Ahmed, H.; 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.; Sitt, S.; Biasini, M.; Manoni, E.; Pacetti, S.; Rossi, A.; Angelini, C.; Batignani, G.; Bettarini, S.; Carpinelli, M.; Casarosa, G.; Cervelli, A.; Forti, F.; Giorgi, M. A.; Lusiani, A.; Oberhof, B.; Paoloni, E.; Perez, A.; Rizzo, G.; Walsh, J. J.; Lopes Pegna, D.; Olsen, J.; Smith, A. J. S.; Faccini, R.; Ferrarotto, F.; Ferroni, F.; Gaspero, M.; Li Gioi, L.; Piredda, G.; Bünger, C.; Grünberg, O.; Hartmann, T.; Leddig, T.; Schröder, H.; Voß, C.; Waldi, R.; Adye, T.; Olaiya, E. O.; Wilson, F. F.; Emery, S.; Hamel de Monchenault, G.; Vasseur, G.; Yèche, Ch.; Anulli, F.; Aston, D.; Bard, D. J.; Benitez, J. F.; Cartaro, C.; Convery, M. R.; Dorfan, J.; Dubois-Felsmann, G. P.; Dunwoodie, W.; Ebert, M.; Field, R. C.; Fulsom, B. G.; Gabareen, A. M.; Graham, M. T.; Hast, C.; Innes, W. R.; Kim, P.; Kocian, M. L.; Leith, D. W. G. S.; Lewis, P.; Lindemann, D.; Lindquist, B.; Luitz, S.; Luth, V.; Lynch, H. L.; Macfarlane, D. B.; Muller, D. R.; Neal, H.; Nelson, S.; 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.; Wagner, A. P.; Wang, W. F.; Wisniewski, W. J.; Wittgen, M.; Wright, D. H.; Wulsin, H. W.; Ziegler, V.; Park, W.; Purohit, M. V.; White, R. M.; Wilson, J. R.; Randle-Conde, A.; Sekula, S. J.; Bellis, M.; Burchat, P. R.; Miyashita, T. S.; 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.; Zambito, S.; Lanceri, L.; Vitale, L.; Martinez-Vidal, F.; Oyanguren, A.; Villanueva-Perez, P.; Albert, J.; Banerjee, Sw.; Bernlochner, F. U.; Choi, H. H. F.; King, G. J.; 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.; Wu, S. L.; Babar Collaboration

    2014-04-01

    We report a search for the decay B ¯0→Λc+p ¯pp ¯. Using a data sample of 471×106 BB ¯ pairs collected with the BABAR detector at the PEP-II2 storage ring at SLAC, we find no events and set an upper limit on the branching fraction B(B ¯0→Λc+p ¯pp ¯)×B(Λ/c+→pK-π+)0.050<2.8×10-6 at 90% C.L., where we have normalized B(Λc+→pK-π+) to the world average value.

  2. Regulation of protein phosphatase 2A (PP2A) tumor suppressor function by PME-1.

    PubMed

    Kaur, Amanpreet; Westermarck, Jukka

    2016-12-15

    Protein phosphatase 2A (PP2A) plays a major role in maintaining cellular signaling homeostasis by dephosphorylation of a variety of signaling proteins and acts as a tumor suppressor. Protein phosphatase methylesterase-1 (PME-1) negatively regulates PP2A activity by highly complex mechanisms that are reviewed here. Importantly, recent studies have shown that PME-1 promotes oncogenic MAPK/ERK and AKT pathway activities in various cancer types. In human glioma, high PME-1 expression correlates with tumor progression and kinase inhibitor resistance. We discuss the emerging cancer-associated function of PME-1 and its potential clinical relevance.

  3. Real-time spectroscopy of solar pp-neutrinos using 150Nd

    NASA Astrophysics Data System (ADS)

    Zuber, K.

    2012-03-01

    The potential real-time spectroscopy of solar pp-neutrinos using 150Nd as target is investigated. The threshold of 196 keV would be the lowest of all solar neutrino experiments running so far. Experimental rates and parameters are discussed, about 906 SNU can be expected from pp-neutrinos and another 574 SNU from 7Be. Furthermore, it is investigated whether charged current reactions might cause a new background component for future double beta decay experiments based on a large amount of 150Nd.

  4. Off-shell effects for the reaction pp{yields}{pi}d at high energies

    SciTech Connect

    Lee, T.S.H.; Locher, M.P.; Lu, Y.

    1995-08-01

    The reaction pp {yields} {pi}d is studied in a relativistic meson rescattering model. For 1.3 < T{sub p} < 2.4 GeV, the differential cross section and the asymmetry are calculated and compared to experiment. The model introduces simple form factors for the leading {pi}N partial waves, which depend on the virtuality of the exchanged {pi} and {rho} mesons. All remaining input is derived from experimental constraints. The data can be described by energy-independent form factors. The asymmetries are sensitive to pp distortion factors and further details of the model. A paper describing our results was published.

  5. DSP-PP Precursor Protein Cleavage by Tolloid-Related-1 Protein and by Bone Morphogenetic Protein-1

    PubMed Central

    Ritchie, Helena H.; Yee, Colin T.; Tang, Xu-na; Dong, Zhihong; Fuller, Robert S.

    2012-01-01

    Dentin sialoprotein (DSP) and phosphophoryn (PP), acidic proteins critical to dentin mineralization, are translated from a single transcript as a DSP-PP precursor that undergoes specific proteolytic processing to generate DSP and PP. The cleavage mechanism continues to be controversial, in part because of the difficulty of obtaining DSP-PP from mammalian cells and dentin matrix. We have infected Sf9 cells with a recombinant baculovirus to produce large amounts of secreted DSP-PP240, a variant form of rat DSP-PP. Mass spectrometric analysis shows that DSP-PP240 secreted by Sf9 cells undergoes specific cleavage at the site predicted from the N-terminal sequence of PP extracted from dentin matrix: SMQG447↓D448DPN. DSP-PP240 is cleaved after secretion by a zinc-dependent activity secreted by Sf9 cells, generating DSP430 and PP240 products that are stable in the medium. DSP-PP processing activity is constitutively secreted by Sf9 cells, but secretion is diminished 3 days after infection. Using primers corresponding to the highly conserved catalytic domain of Drosophila melanogaster tolloid (a mammalian BMP1 homolog), we isolated a partial cDNA for a Spodopotera frugiperda tolloid-related-1 protein (TLR1) that is 78% identical to Drosophila TLR1 but only 65% identical to Drosophila tolloid. Tlr1 mRNA decreased rapidly in Sf9 cells after baculovirus infection and was undetectable 4d after infection, paralleling the observed decrease in secretion of the DSP-PP240 processing activity after infection. Human BMP1 is more similar to Sf9 and Drosophila TLR1 than to tolloid, and Sf9 TLR1 is more similar to BMP1 than to other mammalian homologs. Recombinant human BMP1 correctly processed baculovirus-expressed DSP-PP240 in a dose-dependent manner. Together, these data suggest that the physiologically accurate cleavage of mammalian DSP-PP240 in the Sf9 cell system represents the action of a conserved processing enzyme and support the proposed role of BMP1 in processing DSP-PP in

  6. DSP-PP precursor protein cleavage by tolloid-related-1 protein and by bone morphogenetic protein-1.

    PubMed

    Ritchie, Helena H; Yee, Colin T; Tang, Xu-Na; Dong, Zhihong; Fuller, Robert S

    2012-01-01

    Dentin sialoprotein (DSP) and phosphophoryn (PP), acidic proteins critical to dentin mineralization, are translated from a single transcript as a DSP-PP precursor that undergoes specific proteolytic processing to generate DSP and PP. The cleavage mechanism continues to be controversial, in part because of the difficulty of obtaining DSP-PP from mammalian cells and dentin matrix. We have infected Sf9 cells with a recombinant baculovirus to produce large amounts of secreted DSP-PP(240), a variant form of rat DSP-PP. Mass spectrometric analysis shows that DSP-PP(240) secreted by Sf9 cells undergoes specific cleavage at the site predicted from the N-terminal sequence of PP extracted from dentin matrix: SMQG(447)↓D(448)DPN. DSP-PP(240) is cleaved after secretion by a zinc-dependent activity secreted by Sf9 cells, generating DSP(430) and PP(240) products that are stable in the medium. DSP-PP processing activity is constitutively secreted by Sf9 cells, but secretion is diminished 3 days after infection. Using primers corresponding to the highly conserved catalytic domain of Drosophila melanogaster tolloid (a mammalian BMP1 homolog), we isolated a partial cDNA for a Spodopotera frugiperda tolloid-related-1 protein (TLR1) that is 78% identical to Drosophila TLR1 but only 65% identical to Drosophila tolloid. Tlr1 mRNA decreased rapidly in Sf9 cells after baculovirus infection and was undetectable 4d after infection, paralleling the observed decrease in secretion of the DSP-PP(240) processing activity after infection. Human BMP1 is more similar to Sf9 and Drosophila TLR1 than to tolloid, and Sf9 TLR1 is more similar to BMP1 than to other mammalian homologs. Recombinant human BMP1 correctly processed baculovirus-expressed DSP-PP(240) in a dose-dependent manner. Together, these data suggest that the physiologically accurate cleavage of mammalian DSP-PP(240) in the Sf9 cell system represents the action of a conserved processing enzyme and support the proposed role of BMP1 in

  7. DksA and (p)ppGpp have unique and overlapping contributions to Haemophilus ducreyi pathogenesis in humans.

    PubMed

    Holley, Concerta L; Zhang, Xinjun; Fortney, Kate R; Ellinger, Sheila; Johnson, Paula; Baker, Beth; Liu, Yunlong; Janowicz, Diane M; Katz, Barry P; Munson, Robert S; Spinola, Stanley M

    2015-08-01

    The (p)ppGpp-mediated stringent response is important for bacterial survival in nutrient limiting conditions. For maximal effect, (p)ppGpp interacts with the cofactor DksA, which stabilizes (p)ppGpp's interaction with RNA polymerase. We previously demonstrated that (p)ppGpp was required for the virulence of Haemophilus ducreyi in humans. Here, we constructed an H. ducreyi dksA mutant and showed it was also partially attenuated for pustule formation in human volunteers. To understand the roles of (p)ppGpp and DksA in gene regulation in H. ducreyi, we defined genes potentially altered by (p)ppGpp and DksA deficiency using transcriptome sequencing (RNA-seq). In bacteria collected at stationary phase, lack of (p)ppGpp and DksA altered expression of 28% and 17% of H. ducreyi open reading frames, respectively, including genes involved in transcription, translation, and metabolism. There was significant overlap in genes differentially expressed in the (p)ppGpp mutant relative to the dksA mutant. Loss of (p)ppGpp or DksA resulted in the dysregulation of several known virulence determinants. Deletion of dksA downregulated lspB and rendered the organism less resistant to phagocytosis and increased its sensitivity to oxidative stress. Both mutants had reduced ability to attach to human foreskin fibroblasts; the defect correlated with reduced expression of the Flp adhesin proteins in the (p)ppGpp mutant but not in the dksA mutant, suggesting that DksA regulates the expression of an unknown cofactor(s) required for Flp-mediated adherence. We conclude that both (p)ppGpp and DksA serve as major regulators of H. ducreyi gene expression in stationary phase and have both overlapping and unique contributions to pathogenesis.

  8. The E3 Ubiquitin Ligase- and Protein Phosphatase 2A (PP2A)-binding Domains of the Alpha4 Protein Are Both Required for Alpha4 to Inhibit PP2A Degradation

    SciTech Connect

    LeNoue-Newton, Michele; Watkins, Guy R.; Zou, Ping; Germane, Katherine L.; McCorvey, Lisa R.; Wadzinski, Brian E.; Spiller, Benjamin W.

    2012-04-30

    Protein phosphatase 2A (PP2A) is regulated through a variety of mechanisms, including post-translational modifications and association with regulatory proteins. Alpha4 is one such regulatory protein that binds the PP2A catalytic subunit (PP2Ac) and protects it from polyubiquitination and degradation. Alpha4 is a multidomain protein with a C-terminal domain that binds Mid1, a putative E3 ubiquitin ligase, and an N-terminal domain containing the PP2Ac-binding site. In this work, we present the structure of the N-terminal domain of mammalian Alpha4 determined by x-ray crystallography and use double electron-electron resonance spectroscopy to show that it is a flexible tetratricopeptide repeat-like protein. Structurally, Alpha4 differs from its yeast homolog, Tap42, in two important ways: (1) the position of the helix containing the PP2Ac-binding residues is in a more open conformation, showing flexibility in this region; and (2) Alpha4 contains a ubiquitin-interacting motif. The effects of wild-type and mutant Alpha4 on PP2Ac ubiquitination and stability were examined in mammalian cells by performing tandem ubiquitin-binding entity precipitations and cycloheximide chase experiments. Our results reveal that both the C-terminal Mid1-binding domain and the PP2Ac-binding determinants are required for Alpha4-mediated protection of PP2Ac from polyubiquitination and degradation.

  9. Phosphorylation of eIF2α triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma.

    PubMed

    Wengrod, Jordan; Wang, Ding; Weiss, Sarah; Zhong, Hua; Osman, Iman; Gardner, Lawrence B

    2015-03-10

    Amino acid deprivation promotes the inhibition of the kinase complex mTORC1 (mammalian target of rapamycin complex 1) and activation of the kinase GCN2 (general control nonrepressed 2). Signaling pathways downstream of both kinases have been thought to independently induce autophagy. We showed that these two amino acid-sensing systems are linked. We showed that pharmacological inhibition of mTORC1 led to activation of GCN2 and phosphorylation of the eukaryotic initiation factor 2α (eIF2α) in a mechanism dependent on the catalytic subunit of protein phosphatase 6 (PP6C). Autophagy induced by pharmacological inhibition of mTORC1 required PP6C, GCN2, and eIF2α phosphorylation. Although some of the PP6C mutants found in melanoma did not form a strong complex with PP6 regulatory subunits and were rapidly degraded, these mutants paradoxically stabilized PP6C encoded by the wild-type allele and increased eIF2α phosphorylation. Furthermore, these PP6C mutations were associated with increased autophagy in vitro and in human melanoma samples. Thus, these data showed that GCN2 activation and phosphorylation of eIF2α in response to mTORC1 inhibition are necessary for autophagy. Additionally, we described a role for PP6C in this process and provided a mechanism for PP6C mutations associated with melanoma.

  10. The magic spot: identification of the binding site for ppGpp on E. coli RNA polymerase

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite more than 40 years of study of the global regulatory nucleotide ppGpp ("magic spot") in Escherichia coli, its target site on RNA polymerase (RNAP), and therefore its mechanism of action, is unknown. We report here a binding site for ppGpp on E. coli RNAP, identified by crosslinking, protease...

  11. Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers

    PubMed Central

    Williams, Byron C; Filter, Joshua J; Blake-Hodek, Kristina A; Wadzinski, Brian E; Fuda, Nicholas J; Shalloway, David; Goldberg, Michael L

    2014-01-01

    During M phase, Endosulfine (Endos) family proteins are phosphorylated by Greatwall kinase (Gwl), and the resultant pEndos inhibits the phosphatase PP2A-B55, which would otherwise prematurely reverse many CDK-driven phosphorylations. We show here that PP2A-B55 is the enzyme responsible for dephosphorylating pEndos during M phase exit. The kinetic parameters for PP2A-B55’s action on pEndos are orders of magnitude lower than those for CDK-phosphorylated substrates, suggesting a simple model for PP2A-B55 regulation that we call inhibition by unfair competition. As the name suggests, during M phase PP2A-B55’s attention is diverted to pEndos, which binds much more avidly and is dephosphorylated more slowly than other substrates. When Gwl is inactivated during the M phase-to-interphase transition, the dynamic balance changes: pEndos dephosphorylated by PP2A-B55 cannot be replaced, so the phosphatase can refocus its attention on CDK-phosphorylated substrates. This mechanism explains simultaneously how PP2A-B55 and Gwl together regulate pEndos, and how pEndos controls PP2A-B55. DOI: http://dx.doi.org/10.7554/eLife.01695.001 PMID:24618897

  12. Intrinsic fluctuations of the proton saturation momentum scale in high multiplicity p+p collisions

    DOE PAGES

    McLerran, Larry; Tribedy, Prithwish

    2015-11-02

    High multiplicity events in p+p collisions are studied using the theory of the Color Glass Condensate. Here, we show that intrinsic fluctuations of the proton saturation momentum scale are needed in addition to the sub-nucleonic color charge fluctuations to explain the very high multiplicity tail of distributions in p+p collisions. It is presumed that the origin of such intrinsic fluctuations is non-perturbative in nature. Classical Yang Mills simulations using the IP-Glasma model are performed to make quantitative estimations. Furthermore, we find that fluctuations as large as O(1) of the average values of the saturation momentum scale can lead to raremore » high multiplicity events seen in p+p data at RHIC and LHC energies. Using the available data on multiplicity distributions we try to constrain the distribution of the proton saturation momentum scale and make predictions for the multiplicity distribution in 13 TeV p+p collisions.« less

  13. First Trimester Maternal Serum PP13 in the Risk Assessment for Preeclampsia

    PubMed Central

    ROMERO, Roberto; KUSANOVIC, Juan Pedro; THAN, Nandor Gabor; EREZ, Offer; GOTSCH, Francesca; ESPINOZA, Jimmy; EDWIN, Samuel; CHEFETZ, Ilana; GOMEZ, Ricardo; NIEN, Jyh Kae; SAMMAR, Marei; PINELES, Beth; HASSAN, Sonia S.; MEIRI, Hamutal; TAL, Yossi; KUHNREICH, Ido; PAPP, Zoltan; CUCKLE, Howard S.

    2008-01-01

    Objective To determine whether first trimester maternal serum Placental Protein 13 (PP13) concentrations can be used in the risk assessment for preeclampsia. Study Design This case-control study included 50 patients with preeclampsia and 250 patients with normal pregnancies. Samples were collected between 8-13 weeks of gestation. Serum PP13 concentrations were measured by ELISA and expressed as medians and multiples of the median (MoM) for gestational age. Sensitivity and specificity were derived from receiver operating characteristic curve analysis. Results 1) Serum PP13 concentration in the first trimester was significantly lower in patients who developed preterm and early-onset preeclampsia than in those with normal pregnancies; and 2) At 80% specificity, a cutoff of 0.39 MoM had a sensitivity of 100% for early-onset preeclampsia and 85% for preterm preeclampsia. Conclusion Maternal serum first trimester PP13 appears to be a reasonable marker for risk assessment, but a weak marker for severe preeclampsia at term, and ineffective for identifying mild preeclampsia at term. PMID:18539259

  14. Collectivity of (non-)strange hadrons in high-multiplicity pp with CMS

    NASA Astrophysics Data System (ADS)

    Stephans, George S. F.; CMS collaboration

    2017-01-01

    Observation of an enhanced long-range, near-side, two-particle correlation (known as the “Ridge”) in high-multiplicity pp and pPb collisions opened up new opportunities of exploring QCD dynamics in small collision systems. The CMS detector at the LHC has excellent capabilities of reconstructing weakly decaying strange hadrons such as , Λ and Ξ. Studies of strange hadron production and correlations in small colliding systems provide additional insights into the physical origin of the observed collective phenomena. New results for pT spectra and long-range two-particle correlations for charged particles and identified strange hadrons in high-multiplicity pp and pPb collisions are presented. The data at various collision energies for pp and pPb collisions are compared to those obtained for PbPb at similar multiplicities. Multi-particle cumulants for pp and pPb events are studied in order to more fully explore the collective nature of the long-range correlations.

  15. Degradation of trichloroethylene by methanol-growth cultures of Methylosinus trichosporium OB3b PP358

    SciTech Connect

    Fitch, M.W.; Georgiou, G.; Speitel, G.E. Jr.

    1996-03-01

    Methylosinus trichosporium OB3b is a methanotrophic bacteria which rapidly degrades chlorinated solvents including trichloroethylene. This report focuses on continuous growth of Methylosinus trichosporium PP358 and the influence of growth conditions on TCE degradation and transformation capacity. 20 refs., 2 tabs.

  16. PP1-mediated moesin dephosphorylation couples polar relaxation to mitotic exit.

    PubMed

    Kunda, Patricia; Rodrigues, Nelio T L; Moeendarbary, Emadaldin; Liu, Tao; Ivetic, Aleksandar; Charras, Guillaume; Baum, Buzz

    2012-02-07

    Animal cells undergo dramatic actin-dependent changes in shape as they progress through mitosis; they round up upon mitotic entry and elongate during chromosome segregation before dividing into two [1-3]. Moesin, the sole Drosophila ERM-family protein [4], plays a critical role in this process, through the construction of a stiff, rounded metaphase cortex [5-7]. At mitotic exit, this rigid cortex must be dismantled to allow for anaphase elongation and cytokinesis through the loss of the active pool of phospho-Thr559moesin from cell poles. Here, in an RNA interference (RNAi) screen for phosphatases involved in the temporal and spatial control of moesin, we identify PP1-87B RNAi as having elevated p-moesin levels and reduced cortical compliance. In mitosis, RNAi-induced depletion of PP1-87B or depletion of a conserved noncatalytic PP1 phosphatase subunit Sds22 leads to defects in p-moesin clearance from cell poles at anaphase, a delay in anaphase elongation, together with defects in bipolar anaphase relaxation and cytokinesis. Importantly, similar cortical defects are seen at anaphase following the expression of a constitutively active, phosphomimetic version of moesin. These data reveal a new role for the PP1-87B/Sds22 phosphatase, an important regulator of the metaphase-anaphase transition, in coupling moesin-dependent cell shape changes to mitotic exit.

  17. The Arabidopsis Protein Phosphatase PP2C38 Negatively Regulates the Central Immune Kinase BIK1.

    PubMed

    Couto, Daniel; Niebergall, Roda; Liang, Xiangxiu; Bücherl, Christoph A; Sklenar, Jan; Macho, Alberto P; Ntoukakis, Vardis; Derbyshire, Paul; Altenbach, Denise; Maclean, Dan; Robatzek, Silke; Uhrig, Joachim; Menke, Frank; Zhou, Jian-Min; Zipfel, Cyril

    2016-08-01

    Plants recognize pathogen-associated molecular patterns (PAMPs) via cell surface-localized pattern recognition receptors (PRRs), leading to PRR-triggered immunity (PTI). The Arabidopsis cytoplasmic kinase BIK1 is a downstream substrate of several PRR complexes. How plant PTI is negatively regulated is not fully understood. Here, we identify the protein phosphatase PP2C38 as a negative regulator of BIK1 activity and BIK1-mediated immunity. PP2C38 dynamically associates with BIK1, as well as with the PRRs FLS2 and EFR, but not with the co-receptor BAK1. PP2C38 regulates PAMP-induced BIK1 phosphorylation and impairs the phosphorylation of the NADPH oxidase RBOHD by BIK1, leading to reduced oxidative burst and stomatal immunity. Upon PAMP perception, PP2C38 is phosphorylated on serine 77 and dissociates from the FLS2/EFR-BIK1 complexes, enabling full BIK1 activation. Together with our recent work on the control of BIK1 turnover, this study reveals another important regulatory mechanism of this central immune component.

  18. The Arabidopsis Protein Phosphatase PP2C38 Negatively Regulates the Central Immune Kinase BIK1

    PubMed Central

    Liang, Xiangxiu; Bücherl, Christoph A.; Sklenar, Jan; Macho, Alberto P.; Ntoukakis, Vardis; Derbyshire, Paul; Altenbach, Denise; Robatzek, Silke; Uhrig, Joachim; Menke, Frank; Zhou, Jian-Min

    2016-01-01

    Plants recognize pathogen-associated molecular patterns (PAMPs) via cell surface-localized pattern recognition receptors (PRRs), leading to PRR-triggered immunity (PTI). The Arabidopsis cytoplasmic kinase BIK1 is a downstream substrate of several PRR complexes. How plant PTI is negatively regulated is not fully understood. Here, we identify the protein phosphatase PP2C38 as a negative regulator of BIK1 activity and BIK1-mediated immunity. PP2C38 dynamically associates with BIK1, as well as with the PRRs FLS2 and EFR, but not with the co-receptor BAK1. PP2C38 regulates PAMP-induced BIK1 phosphorylation and impairs the phosphorylation of the NADPH oxidase RBOHD by BIK1, leading to reduced oxidative burst and stomatal immunity. Upon PAMP perception, PP2C38 is phosphorylated on serine 77 and dissociates from the FLS2/EFR-BIK1 complexes, enabling full BIK1 activation. Together with our recent work on the control of BIK1 turnover, this study reveals another important regulatory mechanism of this central immune component. PMID:27494702

  19. A functional genomic analysis of Arabidopsis thaliana PP2C clade D

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the reference dicot plant Arabidopsis thaliana, the PP2C family of P-protein phosphatases includes the products of 80 genes that have been separated into 10 multi-protein clades plus six singletons. Clade D includes the products of nine genes distributed among 3 chromosomes (PPD1, At3g12620; PPD2...

  20. Designed abscisic acid analogs as antagonists of PYL-PP2C receptor interactions.

    PubMed

    Takeuchi, Jun; Okamoto, Masanori; Akiyama, Tomonori; Muto, Takuya; Yajima, Shunsuke; Sue, Masayuki; Seo, Mitsunori; Kanno, Yuri; Kamo, Tsunashi; Endo, Akira; Nambara, Eiji; Hirai, Nobuhiro; Ohnishi, Toshiyuki; Cutler, Sean R; Todoroki, Yasushi

    2014-06-01

    The plant stress hormone abscisic acid (ABA) is critical for several abiotic stress responses. ABA signaling is normally repressed by group-A protein phosphatases 2C (PP2Cs), but stress-induced ABA binds Arabidopsis PYR/PYL/RCAR (PYL) receptors, which then bind and inhibit PP2Cs. X-ray structures of several receptor-ABA complexes revealed a tunnel above ABA's 3' ring CH that opens at the PP2C binding interface. Here, ABA analogs with sufficiently long 3' alkyl chains were predicted to traverse this tunnel and block PYL-PP2C interactions. To test this, a series of 3'-alkylsulfanyl ABAs were synthesized with different alkyl chain lengths. Physiological, biochemical and structural analyses revealed that a six-carbon alkyl substitution produced a potent ABA antagonist that was sufficiently active to block multiple stress-induced ABA responses in vivo. This study provides a new approach for the design of ABA analogs, and the results validated structure-based design for this target class.

  1. Anti-biofilm activity of Pseudoalteromonas flavipulchra SktPp1 against Serratia marcescens SMJ-11

    NASA Astrophysics Data System (ADS)

    Iqbal, Faiq; Usup, Gires; Ahmad, Asmat

    2015-09-01

    This study aimed to examine the anti-biofilm activity of Pseudoalteromonas flavipulchra SktPp1 crude extract against the biofilm producer, Serratia marcescens. The crude extract of P. flavipulchra SktPp1 was extracted with ethyl acetate. The sub-minimum inhibitory concentration (MIC), 0.1 mg/ml, has been used in this study. The anti-biofilm activity of P. flavipulchra SktPp1 crude extract was assessed against the biofilm of S. marcescens using the crystal violet assay. The growth curve has been used as the indicator of the effect of crude extracts to bacterial growth. The sub-MIC crude extract was tested against two of S. marcescens virulence factors, including the swarming ability and production of prodigiosin using the swarming assay and prodigiosin assay. The growth curves of S. marcescens indicated that the sub-MIC concentration of crude extract did not affect the growth of S. marcescens. The production of prodigiosin was reduced by 44%. The diameter of the swarming area was reduced from 8.7 cm to 0.8 cm. The sub-MIC crude extract inhibits 26.9% of the biofilm production in S. marcescens. This crude extract lost its activity at 50°C and above. In conclusion, crude extract of P. flavipulchra SktPp1 has the ability to inhibit S. marcescens SMJ-11 biofilm formation.

  2. Detecting W/Z pairs and Higgs at high energy pp colliders: Main experimental issues

    SciTech Connect

    Alverson, G.; Bengtsson, H.U.; Hauptman, J.; Hedin, D.; Herrero, M.J.; Wang, E.; Linn, S.; Young, C.; Milliken, B.; Paige, F.

    1987-03-01

    The main detection issues implied by the search for W and Z/sup 0/ pairs and Higgs in a high energy pp collider context are discussed here. It includes: precise electron identification, missing energy measurement, multilepton recognition, sophisticated jet pattern recognition, and pile-up. The study uses, as much as possible, a ''realistic simulation of life.''

  3. Search for the kaonic bound state ppK- in pp→ pK +Λ

    NASA Astrophysics Data System (ADS)

    Münzer, Robert; Epple, Eliane; Fabbietti, Laura

    2015-08-01

    The investigation of the kaon-nucleon interaction has been intensified in the last years due to new measurements of the Λ(1405) resonance and indications on the existence of the ppK- bound state. Such results are heavily discussed, since they can lead to new knowledge about the -Nucleon interaction. In the last years, the reaction p+p →p+ K+ + Λ has been measured at the GSI Helmholtzcentre in Darmstadt with the FOPI and the HADES spectrometers at beam energies of 3.1 GeV and 3.5 GeV, respectively. New analyses methods have been developed to understand quantitatively all the processes contributing to the pK+Λ final state. At the FOPI experiment a set of around 1.000 events and in the HADES experiment around 22.000 events of the exclusive reaction p+p →p+ K+ + Λ could be extracted. These reconstructed exclusive events were analyzed within the Bonn Gatchina Partial Wave Analysis (BG-PWA) framework, which provides a coherent description of the data including several resonant and non-resonant production channels. The results have shown that the inclusion of interferences between different channels has to be considered in the analysis. Based on the description of the data with the Partial Wave Analysis an upper limit on the cross-section for the production of the ppK- could be determined.

  4. Study on structure and hydrophobicity of PP/EVA co-blending membrane: Quenching rate

    NASA Astrophysics Data System (ADS)

    Tang, Na; Li, Zhao; Hua, Xinxin

    2017-03-01

    Isotactic polypropylene (iPP)/ethylene vinyl acetate (EVA) co-blending hydrophobic microporous membranes for vacuum membrane distillation (VMD) were prepared via thermally induced phase separation (TIPS). In the process of preparation, quenching rate has a great influence on the membrane morphology.

  5. Measurement of the. pi. d. -->. pp reaction at T/sub. pi. / = 65 MeV

    SciTech Connect

    Ottermann, C.R.; Boschitz, E.T.; Gyles, W.; List, W.; Tacik, R.; Mango, S.; Konter, J.A.; van den Brandt, B.; Smith, G.R.

    1986-05-01

    The vector analyzing power iT/sub 11/ has been measured for the ..pi..d..-->..pp reaction at an incident pion energy of 65 MeV, using a vector polarized deuteron target. The data are compared with predictions from coupled channels, Faddeev, and perturbation theory calculations.

  6. PP2A and GSK-3beta act antagonistically to regulate active zone development.

    PubMed

    Viquez, Natasha M; Füger, Petra; Valakh, Vera; Daniels, Richard W; Rasse, Tobias M; DiAntonio, Aaron

    2009-09-16

    The synapse is composed of an active zone apposed to a postsynaptic cluster of neurotransmitter receptors. Each Drosophila neuromuscular junction comprises hundreds of such individual release sites apposed to clusters of glutamate receptors. Here, we show that protein phosphatase 2A (PP2A) is required for the development of structurally normal active zones opposite glutamate receptors. When PP2A is inhibited presynaptically, many glutamate receptor clusters are unapposed to Bruchpilot (Brp), an active zone protein required for normal transmitter release. These unapposed receptors are not due to presynaptic retraction of synaptic boutons, since other presynaptic components are still apposed to the entire postsynaptic specialization. Instead, these data suggest that Brp localization is regulated at the level of individual release sites. Live imaging of glutamate receptors demonstrates that this disruption to active zone development is accompanied by abnormal postsynaptic development, with decreased formation of glutamate receptor clusters. Remarkably, inhibition of the serine-threonine kinase GSK-3beta completely suppresses the active zone defect, as well as other synaptic morphology phenotypes associated with inhibition of PP2A. These data suggest that PP2A and GSK-3beta function antagonistically to control active zone development, providing a potential mechanism for regulating synaptic efficacy at a single release site.

  7. CHARGED PARTICLE PRODUCTION AT HIGH RAPIDITY IN p+p COLLISIONS AT RHIC.

    SciTech Connect

    DEBBE,R.

    2006-05-30

    This report describes the recent analysis of identified charged particle production at high rapidity performed on data collected from p+p collisions at RHIC ({radical}s = 200 GeV). The extracted invariant cross-sections compare well to NLO pQCD calculations. However, a puzzling high yield of protons at high rapidity and p{sub T} has been found.

  8. DETAIL OF THE INTERIOR OF PP37L (VIEWING PORTAL), AND A ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF THE INTERIOR OF PP37L (VIEWING PORTAL), AND A FLUORESCENT LIGHT, ALTITUDE CHAMBER L, FACING SOUTH - Cape Canaveral Air Force Station, Launch Complex 39, Altitude Chambers, First Street, between Avenue D and Avenue E, Cape Canaveral, Brevard County, FL

  9. On the angular and energy distribution of solar neutrons generated in P-P reactions

    NASA Technical Reports Server (NTRS)

    Efimov, Y. E.; Kocharov, G. E.

    1985-01-01

    The problem of high energy neutron generation in P-P reactions in the solar atmosphere is reconsidered. It is shown that the angular distribution of emitted neutrons is anisotropic and the energy spectrum of neutrons depends on the angle of neutron emission.

  10. PP2A: The Achilles Heal in MDS with 5q Deletion.

    PubMed

    Sallman, David A; Wei, Sheng; List, Alan

    2014-01-01

    Myelodysplastic syndromes (MDS) represent a hematologically diverse group of myeloid neoplasms, however, one subtype characterized by an isolated deletion of chromosome 5q [del(5q)] is pathologically and clinically distinct. Patients with del(5q) MDS share biological features that account for the profound hypoplastic anemia and unique sensitivity to treatment with lenalidomide. Ineffective erythropoiesis in del(5q) MDS arises from allelic deletion of the ribosomal processing S-14 (RPS14) gene, which leads to MDM2 sequestration with consequent p53 activation and erythroid cell death. Since its approval in 2005, lenalidomide has changed the natural course of the disease. Patients who achieve transfusion independence and/or a cytogenetic response with lenalidomide have a decreased risk of progression to acute myeloid leukemia and an improved overall survival compared to non-responders. Elucidation of the mechanisms of action of lenalidomide in del(5q) MDS has advanced therapeutic strategies for this disease. The selective cytotoxicity of lenalidomide in del(5q) clones derives from inhibition of a haplodeficient phosphatase whose catalytic domain is encoded within the common deleted region on chromosome 5q, i.e., protein phosphatase 2A (PP2Acα). PP2A is a highly conserved, dual specificity phosphatase that plays an essential role in regulation of the G2/M checkpoint. Inhibition of PP2Acα results in cell-cycle arrest and apoptosis in del(5q) cells. Targeted knockdown of PP2Acα using siRNA is sufficient to sensitize non-del(5q) clones to lenalidomide. Through its inhibitory effect on PP2A, lenalidomide stabilizes MDM2 to restore p53 degradation in erythroid precursors, with subsequent arrest in G2/M. Unfortunately, the majority of patients with del(5q) MDS develop resistance to lenalidomide over time associated with PP2Acα over-expression. Targeted inhibition of PP2A with a more potent inhibitor has emerged as an attractive therapeutic approach for patients with del

  11. Direct and Indirect Targeting of PP2A by Conserved Bacterial Type-III Effector Proteins

    PubMed Central

    Jin, Lin; Ham, Jong Hyun; Hage, Rosemary; Zhao, Wanying; Soto-Hernández, Jaricelis; Lee, Sang Yeol; Paek, Seung-Mann; Kim, Min Gab; Boone, Charles; Coplin, David L.; Mackey, David

    2016-01-01

    Bacterial AvrE-family Type-III effector proteins (T3Es) contribute significantly to the virulence of plant-pathogenic species of Pseudomonas, Pantoea, Ralstonia, Erwinia, Dickeya and Pectobacterium, with hosts ranging from monocots to dicots. However, the mode of action of AvrE-family T3Es remains enigmatic, due in large part to their toxicity when expressed in plant or yeast cells. To search for targets of WtsE, an AvrE-family T3E from the maize pathogen Pantoea stewartii subsp. stewartii, we employed a yeast-two-hybrid screen with non-lethal fragments of WtsE and a synthetic genetic array with full-length WtsE. Together these screens indicate that WtsE targets maize protein phosphatase 2A (PP2A) heterotrimeric enzyme complexes via direct interaction with B’ regulatory subunits. AvrE1, another AvrE-family T3E from Pseudomonas syringae pv. tomato strain DC3000 (Pto DC3000), associates with specific PP2A B’ subunit proteins from its susceptible host Arabidopsis that are homologous to the maize B’ subunits shown to interact with WtsE. Additionally, AvrE1 was observed to associate with the WtsE-interacting maize proteins, indicating that PP2A B’ subunits are likely conserved targets of AvrE-family T3Es. Notably, the ability of AvrE1 to promote bacterial growth and/or suppress callose deposition was compromised in Arabidopsis plants with mutations of PP2A genes. Also, chemical inhibition of PP2A activity blocked the virulence activity of both WtsE and AvrE1 in planta. The function of HopM1, a Pto DC3000 T3E that is functionally redundant to AvrE1, was also impaired in specific PP2A mutant lines, although no direct interaction with B’ subunits was observed. These results indicate that sub-component specific PP2A complexes are targeted by bacterial T3Es, including direct targeting by members of the widely conserved AvrE-family. PMID:27191168

  12. Measurement of associated W + charm production in pp collisions at = 7 TeV

    NASA Astrophysics Data System (ADS)

    Chatrchyan, S.; Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Bergauer, T.; Dragicevic, M.; Erö, J.; Fabjan, C.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Kiesenhofer, W.; Knünz, V.; Krammer, M.; Krätschmer, I.; Liko, D.; Mikulec, I.; Rabady, D.; Rahbaran, B.; Rohringer, C.; 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.; Mucibello, L.; Ochesanu, S.; Roland, B.; Rougny, R.; Staykova, Z.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Blekman, F.; Blyweert, S.; D'Hondt, J.; Kalogeropoulos, A.; Keaveney, J.; Maes, M.; Olbrechts, A.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Villella, I.; Caillol, C.; Clerbaux, B.; De Lentdecker, G.; Favart, L.; Gay, A. P. R.; Hreus, T.; Léonard, A.; Marage, P. E.; 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.; Dildick, S.; Garcia, G.; Klein, B.; Lellouch, J.; Marinov, A.; Mccartin, J.; Ocampo Rios, A. A.; Ryckbosch, D.; Sigamani, M.; Strobbe, N.; Thyssen, F.; Tytgat, M.; Walsh, S.; 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.; Lemaitre, V.; Liao, J.; Militaru, O.; Nuttens, C.; Pagano, D.; Pin, A.; Piotrzkowski, K.; Popov, A.; Selvaggi, M.; Vidal Marono, M.; Vizan Garcia, J. M.; Beliy, N.; Caebergs, T.; Daubie, E.; Hammad, G. H.; Alves, G. A.; Correa Martins, M.; Martins, T.; Pol, M. E.; Souza, M. H. G.; Aldá, W. L.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Malbouisson, H.; Malek, M.; Matos Figueiredo, D.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Bernardes, C. A.; Dias, F. A.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Lagana, C.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Genchev, V.; Iaydjiev, P.; Piperov, S.; Rodozov, M.; Sultanov, G.; Vutova, M.; Dimitrov, A.; Hadjiiska, R.; Kozhuharov, V.; Litov, L.; Pavlov, B.; Petkov, P.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Jiang, C. H.; Liang, D.; Liang, S.; Meng, X.; 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.; Carrillo Montoya, C. A.; Chaparro Sierra, L. F.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Plestina, R.; Polic, D.; Puljak, I.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Kadija, K.; Luetic, J.; Mekterovic, D.; Morovic, S.; Tikvica, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Finger, M.; Finger, M.; Abdelalim, A. A.; Assran, Y.; Elgammal, S.; Ellithi Kamel, A.; Mahmoud, M. A.; Radi, A.; Kadastik, M.; Müntel, M.; Murumaa, M.; Raidal, M.; Rebane, L.; 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.; Ferri, F.; Ganjour, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Malcles, J.; Millischer, L.; Nayak, A.; Rander, J.; Rosowsky, A.; Titov, M.; Baffioni, S.; Beaudette, F.; Benhabib, L.; Bluj, M.; Busson, P.; Charlot, C.; Daci, N.; Dahms, T.; Dalchenko, M.; Dobrzynski, L.; Florent, A.; Granier de Cassagnac, R.; Haguenauer, M.; Miné, P.; Mironov, C.; Naranjo, I. N.; Nguyen, M.; Ochando, C.; Paganini, P.; Sabes, D.; Salerno, R.; Sirois, Y.; Veelken, C.; Zabi, A.; Agram, J.-L.; Andrea, J.; Bloch, D.; Brom, J.-M.; Chabert, E. C.; Collard, C.; Conte, E.; Drouhin, F.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Goetzmann, C.; Juillot, P.; Le Bihan, A.-C.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Beaupere, N.; Boudoul, G.; Brochet, S.; 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.; Sgandurra, L.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Xiao, H.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Bontenackels, M.; Calpas, B.; Edelhoff, M.; Feld, L.; Heracleous, N.; Hindrichs, O.; Klein, K.; Ostapchuk, A.; Perieanu, A.; Raupach, F.; Sammet, J.; Schael, S.; Sprenger, D.; Weber, H.; Wittmer, B.; Zhukov, V.; Ata, M.; Caudron, J.; 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.; Olschewski, M.; Padeken, K.; Papacz, P.; Pieta, H.; Reithler, H.; Schmitz, S. A.; Sonnenschein, L.; Steggemann, J.; Teyssier, D.; Thüer, S.; Weber, M.; Cherepanov, V.; Erdogan, Y.; Flügge, G.; Geenen, H.; Geisler, M.; Haj Ahmad, W.; 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.; Flucke, G.; Geiser, A.; Glushkov, I.; Grebenyuk, A.; Gunnellini, P.; Habib, S.; Hauk, J.; Hellwig, G.; Horton, D.; Jung, H.; Kasemann, M.; Katsas, P.; Kleinwort, C.; Kluge, H.; Krämer, M.; Krücker, D.; Kuznetsova, E.; Lange, W.; Leonard, J.; Lipka, K.; Lohmann, W.; Lutz, B.; Mankel, R.; Marfin, I.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mnich, J.; Mussgiller, A.; Naumann-Emme, S.; Novgorodova, O.; Nowak, F.; Olzem, J.; Perrey, H.; Petrukhin, A.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Ribeiro Cipriano, P. M.; Riedl, C.; Ron, E.; Sahin, M. Ö.; Salfeld-Nebgen, J.; Schmidt, R.; Schoerner-Sadenius, T.; Sen, N.; Stein, M.; Walsh, R.; Wissing, C.; Aldaya Martin, M.; Blobel, V.; Enderle, H.; Erfle, J.; Garutti, E.; Gebbert, U.; Görner, M.; Gosselink, M.; Haller, J.; Heine, K.; Höing, R. S.; Kaussen, G.; Kirschenmann, H.; Klanner, R.; Kogler, R.; Lange, J.; Marchesini, I.; Peiffer, T.; Pietsch, N.; Rathjens, D.; Sander, C.; Schettler, H.; Schleper, P.; Schlieckau, E.; Schmidt, A.; Schröder, M.; Schum, T.; Seidel, M.; Sibille, J.; Sola, V.; Stadie, H.; Steinbrück, G.; Thomsen, J.; 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.; Guthoff, M.; Hartmann, F.; Hauth, T.; Held, H.; Hoffmann, K. H.; Husemann, U.; Katkov, I.; Komaragiri, J. R.; Kornmayer, A.; Lobelle Pardo, P.; Martschei, D.; Müller, Th.; Niegel, M.; Nürnberg, A.; Oberst, O.; Ott, J.; Quast, G.; Rabbertz, K.; Ratnikov, F.; Röcker, S.; Schilling, F.-P.; Schott, G.; Simonis, H. J.; Stober, F. M.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weiler, T.; Zeise, M.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Kesisoglou, S.; Kyriakis, A.; Loukas, D.; Markou, A.; Markou, C.; Ntomari, E.; Topsis-giotis, I.; Gouskos, L.; 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.; Molnar, J.; Palinkas, J.; Szillasi, Z.; Karancsi, J.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Swain, S. K.; Beri, S. B.; Bhatnagar, V.; Dhingra, N.; Gupta, R.; Kaur, M.; Mehta, M. Z.; Mittal, M.; Nishu, N.; Sharma, A.; Singh, J. B.; Kumar, Ashok; Kumar, Arun; Ahuja, S.; Bhardwaj, A.; Choudhary, B. C.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Saxena, P.; Sharma, V.; Shivpuri, R. K.; 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.; Singh, A. P.; Abdulsalam, A.; Dutta, D.; Kailas, S.; Kumar, V.; Mohanty, A. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Chatterjee, R. M.; 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.; Banerjee, S.; Dugad, S.; Arfaei, H.; Bakhshiansohi, H.; Etesami, S. M.; Fahim, A.; Jafari, A.; Khakzad, M.; Mohammadi Najafabadi, M.; Paktinat Mehdiabadi, S.; Safarzadeh, B.; Zeinali, 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.; Marangelli, B.; My, S.; Nuzzo, S.; Pacifico, N.; Pompili, A.; Pugliese, G.; 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.; Meneghelli, M.; Montanari, A.; Navarria, F. L.; Odorici, F.; Perrotta, A.; Primavera, F.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Travaglini, R.; Albergo, S.; Chiorboli, M.; Costa, S.; Giordano, F.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Frosali, S.; Gallo, E.; Gonzi, S.; Gori, V.; Lenzi, P.; Meschini, M.; Paoletti, S.; Sguazzoni, G.; Tropiano, A.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Fabbricatore, P.; Ferretti, R.; Ferro, F.; Vetere, M. Lo; Musenich, R.; Robutti, E.; Tosi, S.; Benaglia, A.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Ghezzi, A.; Govoni, P.; Lucchini, M. T.; Malvezzi, S.; Manzoni, R. A.; Martelli, A.; Menasce, D.; Moroni, L.; Paganoni, M.; Pedrini, D.; Ragazzi, S.; Redaelli, N.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; De Cosa, A.; Fabozzi, F.; Iorio, A. O. M.; Lista, L.; Meola, S.; Merola, M.; Paolucci, P.; Azzi, P.; Bacchetta, N.; Bisello, D.; Branca, A.; Carlin, R.; Checchia, P.; Dorigo, T.; Dosselli, U.; Galanti, M.; Gasparini, F.; Gasparini, U.; Giubilato, P.; Gonella, F.; Gozzelino, A.; Kanishchev, K.; Lacaprara, S.; Lazzizzera, I.; Margoni, M.; Meneguzzo, A. T.; Montecassiano, F.; Pazzini, J.; Pegoraro, M.; Pozzobon, N.; Ronchese, P.; Simonetto, F.; Torassa, E.; Tosi, M.; Vanini, S.; Zotto, P.; Zucchetta, A.; Zumerle, G.; Gabusi, M.; Ratti, S. P.; Riccardi, C.; Vitulo, P.; Biasini, M.; Bilei, G. M.; Fanò, L.; Lariccia, P.; Mantovani, G.; Menichelli, M.; Nappi, A.; 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.; D'Agnolo, R. T.; Dell'Orso, R.; Fiori, F.; Foà, L.; Giassi, A.; Grippo, M. T.; Kraan, A.; 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.; Del Re, D.; Diemoz, M.; Grassi, M.; Longo, E.; Margaroli, F.; Meridiani, P.; Micheli, F.; Nourbakhsh, S.; Organtini, G.; Paramatti, R.; Rahatlou, S.; Rovelli, C.; Soffi, L.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bellan, R.; Biino, C.; Cartiglia, N.; Casasso, S.; Costa, M.; Degano, A.; Demaria, N.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Musich, M.; Obertino, M. M.; Pastrone, N.; Pelliccioni, M.; 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.; Penzo, A.; Schizzi, A.; Zanetti, A.; Chang, S.; Kim, T. Y.; Nam, S. K.; Kim, D. H.; Kim, G. N.; Kim, J. E.; Kong, D. J.; Lee, S.; Oh, Y. D.; Park, H.; Son, D. C.; Kim, J. Y.; Kim, Zero J.; Song, S.; Choi, S.; Gyun, D.; Hong, B.; Jo, M.; Kim, H.; Kim, T. J.; Lee, K. S.; Park, S. K.; Roh, Y.; Choi, M.; Kim, J. H.; Park, C.; Park, I. C.; Park, S.; Ryu, G.; Choi, Y.; Choi, Y. K.; Goh, J.; Kim, M. S.; Kwon, E.; Lee, B.; Lee, J.; Lee, S.; Seo, H.; Yu, I.; Grigelionis, I.; Juodagalvis, A.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-de La Cruz, I.; Lopez-Fernandez, R.; Martínez-Ortega, J.; Sanchez-Hernandez, A.; Villasenor-Cendejas, L. M.; Carrillo Moreno, S.; Vazquez Valencia, F.; Salazar Ibarguen, H. A.; Casimiro Linares, E.; Morelos Pineda, A.; Reyes-Santos, M. A.; Krofcheck, D.; Butler, P. H.; Doesburg, R.; Reucroft, S.; Silverwood, H.; Ahmad, M.; Asghar, M. I.; Butt, J.; Hoorani, H. R.; Khalid, S.; Khan, W. A.; Khurshid, T.; Qazi, S.; Shah, M. A.; Shoaib, M.; Bialkowska, H.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Wrochna, G.; Zalewski, P.; Brona, G.; Bunkowski, K.; Cwiok, M.; Dominik, W.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Wolszczak, W.; Almeida, N.; 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.; Bunin, P.; Gavrilenko, M.; Golutvin, I.; Gorbunov, I.; Kamenev, A.; Karjavin, V.; Konoplyanikov, V.; Lanev, A.; Malakhov, A.; Matveev, V.; Moisenz, P.; Palichik, V.; Perelygin, V.; Shmatov, S.; Skatchkov, N.; Smirnov, V.; Zarubin, A.; Evstyukhin, S.; 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.; Erofeeva, M.; 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.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Klyukhin, V.; Kodolova, O.; Lokhtin, I.; Markina, A.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Snigirev, A.; 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.; Djordjevic, M.; Ekmedzic, M.; Krpic, D.; Milosevic, J.; Aguilar-Benitez, M.; Alcaraz Maestre, J.; Battilana, C.; Calvo, E.; Cerrada, M.; Chamizo Llatas, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Domínguez Vázquez, D.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Ferrando, A.; 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.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Santaolalla, J.; Soares, M. S.; Willmott, C.; Albajar, C.; de Trocóniz, J. 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A.; Colafranceschi, S.; D'Alfonso, M.; d'Enterria, D.; Dabrowski, A.; David, A.; De Guio, F.; De Roeck, A.; De Visscher, S.; Di Guida, S.; Dobson, M.; Dupont-Sagorin, N.; Elliott-Peisert, A.; Eugster, J.; Funk, W.; Georgiou, G.; Giffels, M.; Gigi, D.; Gill, K.; Giordano, D.; Girone, M.; Giunta, M.; Glege, F.; Gomez-Reino Garrido, R.; Gowdy, S.; Guida, R.; Hammer, J.; Hansen, M.; Harris, P.; Hartl, C.; Hinzmann, A.; Innocente, V.; Janot, P.; Karavakis, E.; Kousouris, K.; Krajczar, K.; Lecoq, P.; Lee, Y.-J.; Lourenço, C.; Magini, N.; Malgeri, L.; Mannelli, M.; Masetti, L.; Meijers, F.; Mersi, S.; Meschi, E.; Moser, R.; Mulders, M.; Musella, P.; Nesvold, E.; Orsini, L.; Palencia Cortezon, E.; Perez, E.; Perrozzi, L.; Petrilli, A.; Pfeiffer, A.; Pierini, M.; Pimiä, M.; Piparo, D.; Plagge, M.; Quertenmont, L.; Racz, A.; Reece, W.; Rojo, J.; Rolandi, G.; Rovere, M.; Sakulin, H.; Santanastasio, F.; Schäfer, C.; Schwick, C.; Segoni, I.; Sekmen, S.; Sharma, A.; Siegrist, P.; Silva, P.; Simon, M.; Sphicas, P.; Spiga, D.; Stoye, M.; Tsirou, A.; Veres, G. I.; Vlimant, J. R.; Wöhri, H. K.; Worm, S. D.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Gabathuler, K.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; König, S.; 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.; Freudenreich, K.; Grab, C.; Hits, D.; Lecomte, P.; Lustermann, W.; Mangano, B.; Marini, A. C.; Martinez Ruiz del Arbol, P.; Meister, D.; Mohr, N.; Moortgat, F.; Nägeli, C.; Nef, P.; Nessi-Tedaldi, F.; Pandolfi, F.; Pape, L.; Pauss, F.; Peruzzi, M.; Ronga, F. J.; Rossini, M.; Sala, L.; Sanchez, A. K.; Starodumov, A.; Stieger, B.; Takahashi, M.; Tauscher, L.; Thea, A.; Theofilatos, K.; Treille, D.; Urscheler, C.; Wallny, R.; Weber, H. A.; Amsler, C.; Chiochia, V.; Favaro, C.; Ivova Rikova, M.; Kilminster, B.; Millan Mejias, B.; Robmann, P.; Snoek, H.; Taroni, S.; Verzetti, M.; Yang, Y.; Cardaci, M.; Chen, K. H.; Ferro, C.; Kuo, C. M.; Li, S. W.; Lin, W.; Lu, Y. J.; Volpe, R.; Yu, S. S.; Bartalini, P.; Chang, P.; Chang, Y. H.; Chang, Y. W.; Chao, Y.; Chen, K. F.; Dietz, C.; Grundler, U.; Hou, W.-S.; Hsiung, Y.; Kao, K. Y.; Lei, Y. J.; Lu, R.-S.; Majumder, D.; Petrakou, E.; Shi, X.; Shiu, J. G.; Tzeng, Y. M.; Wang, M.; Asavapibhop, B.; 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.; Aliev, T.; Bilin, B.; Bilmis, S.; Deniz, M.; Gamsizkan, H.; Guler, A. M.; Karapinar, G.; Ocalan, K.; Ozpineci, A.; Serin, M.; Sever, R.; Surat, U. E.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Isildak, B.; Kaya, M.; Kaya, O.; Ozkorucuklu, S.; Sonmez, N.; Bahtiyar, H.; Barlas, E.; Cankocak, K.; Günaydin, Y. O.; 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.; Kreczko, L.; Lucas, C.; Meng, Z.; Metson, S.; Newbold, D. M.; Nirunpong, K.; Paramesvaran, S.; Poll, A.; Senkin, S.; Smith, V. J.; Williams, T.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Ilic, J.; Olaiya, E.; Petyt, D.; Radburn-Smith, B. C.; ShepherdThemistocleous, C. H.; Tomalin, I. R.; Womersley, W. J.; Bainbridge, R.; Buchmuller, O.; Burton, D.; Colling, D.; Cripps, N.; Cutajar, M.; Dauncey, P.; Davies, G.; Della Negra, M.; Ferguson, W.; Fulcher, J.; Futyan, D.; Gilbert, A.; Guneratne Bryer, A.; Hall, G.; Hatherell, Z.; Hays, J.; Iles, G.; Jarvis, M.; Karapostoli, G.; Kenzie, M.; Lane, R.; Lucas, R.; Lyons, L.; Magnan, A.-M.; Marrouche, J.; Mathias, B.; Nandi, R.; Nash, J.; Nikitenko, A.; Pela, J.; Pesaresi, M.; Petridis, K.; Pioppi, M.; Raymond, D. M.; Rogerson, S.; Rose, A.; Seez, C.; Sharp, P.; Sparrow, A.; Tapper, A.; Vazquez Acosta, M.; Virdee, T.; Wakefield, S.; Wardle, N.; Chadwick, M.; 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.; Heister, A.; Lawson, P.; Lazic, D.; Rohlf, J.; Sperka, D.; John, J. St.; Sulak, L.; Alimena, J.; Bhattacharya, S.; Christopher, G.; Cutts, D.; Demiragli, Z.; Ferapontov, A.; Garabedian, A.; Heintz, U.; Jabeen, S.; Kukartsev, G.; Laird, E.; Landsberg, G.; Luk, M.; Narain, M.; Segala, M.; Sinthuprasith, T.; Speer, T.; 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.; Houtz, R.; Ko, W.; Kopecky, A.; Lander, R.; Miceli, T.; Pellett, D.; Pilot, J.; Ricci-Tam, F.; Rutherford, B.; Searle, M.; Smith, J.; Squires, M.; Tripathi, M.; Wilbur, S.; Yohay, R.; Andreev, V.; Cline, D.; Cousins, R.; Erhan, S.; Everaerts, P.; Farrell, C.; Felcini, M.; Hauser, J.; Ignatenko, M.; Jarvis, C.; Rakness, G.; Schlein, P.; Takasugi, E.; Traczyk, P.; Valuev, V.; Weber, M.; Babb, J.; Clare, R.; Ellison, J.; Gary, J. W.; Hanson, G.; Heilman, J.; Jandir, P.; Liu, H.; Long, O. R.; Luthra, A.; Malberti, M.; Nguyen, H.; Shrinivas, A.; Sturdy, J.; Sumowidagdo, S.; Wilken, R.; Wimpenny, S.; Andrews, W.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; Evans, D.; Holzner, A.; Kelley, R.; Lebourgeois, M.; Letts, J.; Macneill, I.; Padhi, S.; Palmer, C.; Petrucciani, G.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Sudano, E.; Tadel, M.; Tu, Y.; Vartak, A.; Wasserbaech, S.; Würthwein, F.; Yagil, A.; Yoo, J.; Barge, D.; Campagnari, C.; Danielson, T.; Flowers, K.; Geffert, P.; George, C.; Golf, F.; Incandela, J.; Justus, C.; Kovalskyi, D.; Krutelyov, V.; Lowette, S.; Magaña Villalba, R.; Mccoll, N.; Pavlunin, V.; Richman, J.; Rossin, R.; Stuart, D.; To, W.; West, C.; Apresyan, A.; Bornheim, A.; Bunn, J.; Chen, Y.; Di Marco, E.; Duarte, J.; Kcira, D.; Ma, Y.; Mott, A.; Newman, H. B.; Pena, C.; Rogan, C.; Spiropulu, M.; Timciuc, V.; Veverka, J.; Wilkinson, R.; Xie, S.; Zhu, R. Y.; Azzolini, V.; Calamba, A.; Carroll, R.; Ferguson, T.; Iiyama, Y.; Jang, D. W.; Liu, Y. F.; Paulini, M.; Russ, J.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Drell, B. R.; 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.; Eggert, N.; Gibbons, L. K.; Hopkins, W.; Khukhunaishvili, A.; Kreis, B.; Mirman, N.; Nicolas Kaufman, G.; Patterson, J. R.; Ryd, A.; Salvati, E.; 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.; Chetluru, V.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gao, Y.; Gottschalk, E.; Gray, L.; Green, D.; Gutsche, O.; Hare, D.; Harris, R. M.; Hirschauer, J.; Hooberman, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Kaadze, K.; Klima, B.; Kunori, S.; Kwan, S.; Linacre, J.; Lincoln, D.; Lipton, R.; Lykken, J.; Maeshima, K.; Marraffino, J. M.; Martinez Outschoorn, V. I.; Maruyama, S.; Mason, D.; McBride, P.; Mishra, K.; Mrenna, S.; Musienko, Y.; Newman-Holmes, C.; O'Dell, V.; Prokofyev, O.; Ratnikova, N.; Sexton-Kennedy, E.; Sharma, S.; Spalding, W. J.; Spiegel, L.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vidal, R.; Whitmore, J.; Wu, W.; Yang, F.; Yun, J. C.; Acosta, D.; Avery, P.; Bourilkov, D.; Chen, M.; Cheng, T.; Das, S.; De Gruttola, M.; Di Giovanni, G. P.; Dobur, D.; Drozdetskiy, A.; Field, R. D.; Fisher, M.; Fu, Y.; Furic, I. K.; Hugon, J.; Kim, B.; Konigsberg, J.; Korytov, A.; Kropivnitskaya, A.; Kypreos, T.; Low, J. F.; Matchev, K.; Milenovic, P.; Mitselmakher, G.; Muniz, L.; Remington, R.; Rinkevicius, A.; Skhirtladze, N.; Snowball, M.; Yelton, J.; Zakaria, M.; Gaultney, V.; Hewamanage, S.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Adams, T.; Askew, A.; Bochenek, J.; Chen, J.; Diamond, B.; Haas, J.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Prosper, H.; Veeraraghavan, V.; Weinberg, M.; Baarmand, M. M.; Dorney, B.; Hohlmann, M.; Kalakhety, H.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Bazterra, V. E.; Betts, R. R.; Bucinskaite, I.; Callner, J.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Khalatyan, S.; Kurt, P.; Lacroix, F.; Moon, D. H.; O'Brien, C.; Silkworth, C.; Strom, D.; Turner, P.; Varelas, N.; Akgun, U.; Albayrak, E. A.; Bilki, B.; Clarida, W.; Dilsiz, K.; Duru, F.; Griffiths, S.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Newsom, C. R.; Ogul, H.; Onel, Y.; Ozok, F.; Sen, S.; Tan, P.; Tiras, E.; Wetzel, J.; Yetkin, T.; Yi, K.; Barnett, B. A.; Blumenfeld, B.; Bolognesi, S.; Giurgiu, G.; Gritsan, A. V.; Hu, G.; Maksimovic, P.; Martin, C.; Swartz, M.; Whitbeck, A.; Baringer, P.; Bean, A.; Benelli, G.; Kenny, R. P.; Murray, M.; Noonan, D.; Sanders, S.; Stringer, R.; Wood, J. S.; Barfuss, A. F.; Chakaberia, I.; Ivanov, A.; Khalil, S.; Makouski, M.; Maravin, Y.; Saini, L. K.; Shrestha, S.; Svintradze, I.; Gronberg, J.; Lange, D.; Rebassoo, F.; Wright, D.; Baden, 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.; Peterman, A.; Skuja, A.; Temple, J.; Tonjes, M. B.; Tonwar, S. C.; Apyan, A.; Bauer, G.; Busza, W.; Cali, I. A.; Chan, M.; Di Matteo, L.; Dutta, V.; Gomez Ceballos, G.; Goncharov, M.; Gulhan, D.; Kim, Y.; Klute, M.; Lai, Y. S.; Levin, A.; Luckey, P. D.; Ma, T.; Nahn, S.; Paus, C.; Ralph, D.; Roland, C.; Roland, G.; Stephans, G. S. F.; Stöckli, F.; Sumorok, K.; Velicanu, D.; Wolf, R.; Wyslouch, B.; Yang, M.; Yilmaz, Y.; Yoon, A. S.; Zanetti, M.; Zhukova, V.; Dahmes, B.; De Benedetti, A.; Franzoni, G.; Gude, A.; Haupt, J.; Kao, S. C.; Klapoetke, K.; Kubota, Y.; Mans, J.; Pastika, N.; Rusack, R.; Sasseville, M.; Singovsky, A.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Cremaldi, L. M.; Kroeger, R.; Oliveros, S.; Perera, L.; Rahmat, R.; Sanders, D. A.; Summers, D.; Avdeeva, E.; Bloom, K.; Bose, S.; Claes, D. R.; Dominguez, A.; Eads, M.; Gonzalez Suarez, R.; Keller, J.; Kravchenko, I.; Lazo-Flores, J.; Malik, S.; Meier, F.; Snow, G. R.; Dolen, J.; Godshalk, A.; Iashvili, I.; Jain, S.; Kharchilava, A.; Kumar, A.; Rappoccio, S.; Wan, Z.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Haley, J.; Massironi, A.; Nash, D.; Orimoto, T.; Trocino, D.; Wood, D.; Zhang, J.; Anastassov, A.; Hahn, K. A.; Kubik, A.; Lusito, L.; Mucia, N.; Odell, N.; Pollack, B.; Pozdnyakov, A.; Schmitt, M.; Stoynev, S.; Sung, K.; Velasco, M.; Won, S.; Berry, D.; Brinkerhoff, A.; Chan, K. M.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kolb, J.; Lannon, K.; Luo, W.; Lynch, S.; Marinelli, N.; Morse, D. M.; Pearson, T.; Planer, M.; Ruchti, R.; Slaunwhite, J.; Valls, N.; Wayne, M.; Wolf, M.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Hill, C.; Hughes, R.; Kotov, K.; Ling, T. Y.; Puigh, D.; Rodenburg, M.; Smith, G.; Vuosalo, C.; Winer, B. L.; Wolfe, H.; Berry, E.; Elmer, P.; Halyo, V.; Hebda, P.; Hegeman, J.; Hunt, A.; Jindal, P.; Koay, S. A.; Lujan, P.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Piroué, P.; Quan, X.; Raval, A.; Saka, H.; Stickland, D.; Tully, C.; Werner, J. S.; Zenz, S. C.; Zuranski, A.; Brownson, E.; Lopez, A.; Mendez, H.; Ramirez Vargas, J. E.; Alagoz, E.; Benedetti, D.; Bolla, G.; Bortoletto, D.; De Mattia, M.; Everett, A.; Hu, Z.; Jones, M.; Jung, K.; Koybasi, O.; Kress, M.; Leonardo, N.; Lopes Pegna, D.; Maroussov, V.; Merkel, P.; Miller, D. H.; Neumeister, N.; Shipsey, I.; Silvers, D.; Svyatkovskiy, A.; Wang, F.; Xie, W.; Xu, L.; Yoo, H. D.; Zablocki, J.; Zheng, Y.; Parashar, N.; 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.; Miner, D. C.; Petrillo, G.; Vishnevskiy, D.; Zielinski, M.; Bhatti, A.; Ciesielski, R.; Demortier, L.; Goulianos, K.; Lungu, G.; Malik, S.; 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.; Lath, A.; Panwalkar, S.; Park, M.; Patel, R.; Rekovic, V.; Robles, J.; Salur, S.; Schnetzer, S.; Seitz, C.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Cerizza, G.; Hollingsworth, M.; Rose, K.; Spanier, S.; Yang, Z. C.; York, A.; Bouhali, O.; Eusebi, R.; Flanagan, W.; Gilmore, J.; Kamon, T.; Khotilovich, V.; Montalvo, R.; Osipenkov, I.; Pakhotin, Y.; Perloff, A.; Roe, J.; Safonov, A.; Sakuma, T.; Suarez, I.; Tatarinov, A.; Toback, D.; Akchurin, N.; Cowden, C.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Kovitanggoon, K.; 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.; Lin, C.; Neu, C.; Wood, J.; Gollapinni, S.; Harr, R.; Karchin, P. E.; Kottachchi Kankanamge Don, C.; Lamichhane, P.; Sakharov, A.; Belknap, D. A.; Borrello, L.; Carlsmith, D.; Cepeda, M.; Dasu, S.; Duric, S.; Friis, E.; Grothe, M.; Hall-Wilton, R.; Herndon, M.; Hervé, A.; Klabbers, P.; Klukas, J.; Lanaro, A.; Loveless, R.; Mohapatra, A.; Mozer, M. U.; Ojalvo, I.; Perry, T.; Pierro, G. A.; Polese, G.; Ross, I.; Sarangi, T.; Savin, A.; Smith, W. H.; Swanson, J.

    2014-02-01

    Measurements are presented of the associated production of a W boson and a charm-quark jet (W + c) in pp collisions at a center-of-mass energy of 7 TeV. The analysis is conducted with a data sample corresponding to a total integrated luminosity of 5 fb-1, collected by the CMS detector at the LHC. W boson candidates are identified by their decay into a charged lepton (muon or electron) and a neutrino. The W + c measurements are performed for charm-quark jets in the kinematic region > 25 GeV, |ηjet| < 2 .5, for two different thresholds for the transverse momentum of the lepton from the W-boson decay, and in the pseudorapidity range |ηℓ| < 2 .1. Hadronic and inclusive semileptonic decays of charm hadrons are used to measure the following total cross sections: σ(pp → W + c + X) × (W → ℓν) = 107 .7 ± 3 .3 (stat .) ± 6 .9 (syst .) pb ( > 25 GeV) and σ(pp → W + c + X)×(W → ℓν) = 84 .1 ± 2 .0 (stat .) ± 4 .9 (syst .) pb ( > 35 GeV), and the cross section ratios σ(pp → W+ + + X) /σ(pp → W- + c + X) = 0 .954 ± 0 .025 (stat .) ± 0 .004 (syst .) ( > 25 GeV) and σ(pp → W+ + + X) /σ(pp → W- + c + X) = 0 .938 ± 0 .019 (stat .) ± 0 .006 (syst .) ( > 35 GeV). Cross sections and cross section ratios are also measured differentially with respect to the absolute value of the pseudorapidity of the lepton from the W-boson decay. These are the first measurements from the LHC directly sensitive to the strange quark and antiquark content of the proton. Results are compared with theoretical predictions and are consistent with the predictions based on global fits of parton distribution functions. [Figure not available: see fulltext.

  13. The upcycling of post-industrial PP/PET waste streams through in-situ microfibrillar preparation

    SciTech Connect

    Delva, Laurens Ragaert, Kim Cardon, Ludwig

    2015-12-17

    Post-industrial plastic waste streams can be re-used as secondary material streams for polymer processing by extrusion or injection moulding. One of the major commercially available waste stream contains polypropylene (PP) contaminated with polyesters (mostly polyethylene tereftalate - PET). An important practical hurdle for the direct implementation of this waste stream is the immiscibility of PP and PET in the melt, which leads to segregation within the polymer structure and adversely affects the reproducibility and mechanical properties of the manufactured parts. It has been indicated in literature that the creation of PET microfibrils in the PP matrix could undo these drawbacks and upcycle the PP/PET combination. Within the current research, a commercially available virgin PP/PET was evaluated for the microfibrillar preparation. The mechanical (tensile and impact) properties, thermal properties and morphology of the composites were characterized at different stages of the microfibrillar preparation.

  14. Subsurface PpIX imaging in vivo with ultrasound-guided tomographic spectroscopy: reconstruction vs. born-normalized data

    NASA Astrophysics Data System (ADS)

    Flynn, Brendan P.; D'Souza, Alisha V.; Kanick, Stephen C.; Maytin, Edward; Hasan, Tayyaba; Pogue, Brian W.

    2013-03-01

    Aminolevulinic acid (ALA)-induced Protoporphyrin IX (PpIX)-based photodynamic therapy (PDT) is an effective treatment for skin cancers including basal cell carcinoma (BCC). Topically applied ALA promotes PpIX production preferentially in tumors, and many strategies have been developed to increase PpIX distribution and PDT treatment efficacy at depths > 1mm is not fully understood. While surface imaging techniques provide useful diagnosis, dosimetry, and efficacy information for superficial tumors, these methods cannot interrogate deeper tumors to provide in situ insight into spatial PpIX distributions. We have developed an ultrasound-guided, white-light-informed, tomographics spectroscopy system for the spatial measurement of subsurface PpIX. Detailed imaging system specifications, methodology, and optical-phantom-based characterization will be presented separately. Here we evaluate preliminary in vivo results using both full tomographic reconstruction and by plotting individual tomographic source-detector pair data against US images.

  15. Importance of the ammonia assimilation by Penicillium purpurogenum in amino derivative Monascus pigment, PP-V, production.

    PubMed

    Arai, Teppei; Koganei, Kasumi; Umemura, Sara; Kojima, Ryo; Kato, Jun; Kasumi, Takafumi; Ogihara, Jun

    2013-03-28

    A fungal strain, Penicillium purpurogenum IAM 15392, produced the azaphilone Monascus pigment homolog when cultured in a medium composed of soluble starch, ammonium nitrate, yeast extract, and citrate buffer, pH 5.0. One of the typical features of violet pigment PP-V [(10Z)-12- carboxyl-monascorubramine] is that pyranoid oxygen is replaced with nitrogen. In this study, we found that glutamine synthetase (glnB) and glutamate dehydrogenase (gdh1) genes were expressed in the culture conditions conducive to PP-V production. Gln and Glu both support PP-V biosynthesis, but PP-V biosynthesis was much more efficient with Gln. We determined that synthesis of Gln by glutamine synthetase from ammonium is important for PP-V production.

  16. The upcycling of post-industrial PP/PET waste streams through in-situ microfibrillar preparation

    NASA Astrophysics Data System (ADS)

    Delva, Laurens; Ragaert, Kim; Cardon, Ludwig

    2015-12-01

    Post-industrial plastic waste streams can be re-used as secondary material streams for polymer processing by extrusion or injection moulding. One of the major commercially available waste stream contains polypropylene (PP) contaminated with polyesters (mostly polyethylene tereftalate - PET). An important practical hurdle for the direct implementation of this waste stream is the immiscibility of PP and PET in the melt, which leads to segregation within the polymer structure and adversely affects the reproducibility and mechanical properties of the manufactured parts. It has been indicated in literature that the creation of PET microfibrils in the PP matrix could undo these drawbacks and upcycle the PP/PET combination. Within the current research, a commercially available virgin PP/PET was evaluated for the microfibrillar preparation. The mechanical (tensile and impact) properties, thermal properties and morphology of the composites were characterized at different stages of the microfibrillar preparation.

  17. PP2A targeting by viral proteins: a widespread biological strategy from DNA/RNA tumor viruses to HIV-1.

    PubMed

    Guergnon, Julien; Godet, Angélique N; Galioot, Amandine; Falanga, Pierre Barthélémy; Colle, Jean-Hervé; Cayla, Xavier; Garcia, Alphonse

    2011-11-01

    Protein phosphatase 2A (PP2A) is a large family of holoenzymes that comprises 1% of total cellular proteins and accounts for the majority of Ser/Thr phosphatase activity in eukaryotic cells. Although initially viewed as constitutive housekeeping enzymes, it is now well established that PP2A proteins represent a family of highly and sophistically regulated phosphatases. The past decade, multiple complementary studies have improved our knowledge about structural and functional regulation of PP2A holoenzymes. In this regard, after summarizing major cellular regulation, this review will mainly focus on discussing a particulate biological strategy, used by various viruses, which is based on the targeting of PP2A enzymes by viral proteins in order to specifically deregulate, for their own benefit, cellular pathways of their hosts. The impact of such PP2A targeting for research in human diseases, and in further therapeutic developments, is also discussed.

  18. A role for protein phosphatase PP1γ in SMN complex formation and subnuclear localization to Cajal bodies.

    PubMed

    Renvoisé, Benoît; Quérol, Gwendoline; Verrier, Eloi Rémi; Burlet, Philippe; Lefebvre, Suzie

    2012-06-15

    The spinal muscular atrophy (SMA) gene product SMN forms with gem-associated protein 2-8 (Gemin2-8) and unrip (also known as STRAP) the ubiquitous survival motor neuron (SMN) complex, which is required for the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs), their nuclear import and their localization to subnuclear domain Cajal bodies (CBs). The concentration of the SMN complex and snRNPs in CBs is reduced upon SMN deficiency in SMA cells. Subcellular localization of the SMN complex is regulated in a phosphorylation-dependent manner and the precise mechanisms remain poorly understood. Using co-immunoprecipitation in HeLa cell extracts and in vitro protein binding assays, we show here that the SMN complex and its component Gemin8 interact directly with protein phosphatase PP1γ. Overexpression of Gemin8 in cells increases the number of CBs and results in targeting of PP1γ to CBs. Moreover, depletion of PP1γ by RNA interference enhances the localization of the SMN complex and snRNPs to CBs. Consequently, the interaction between SMN and Gemin8 increases in cytoplasmic and nuclear extracts of PP1γ-depleted cells. Two-dimensional protein gel electrophoresis revealed that SMN is hyperphosphorylated in nuclear extracts of PP1γ-depleted cells and expression of PP1γ restores these isoforms. Notably, SMN deficiency in SMA leads to the aberrant subcellular localization of Gemin8 and PP1γ in the atrophic skeletal muscles, suggesting that the function of PP1γ is likely to be affected in disease. Our findings reveal a role of PP1γ in the formation of the SMN complex and the maintenance of CB integrity. Finally, we propose Gemin8 interaction with PP1γ as a target for therapeutic intervention in SMA.

  19. Activation of the pp60c-src kinase by middle T antigen binding or by dephosphorylation.

    PubMed Central

    Courtneidge, S A

    1985-01-01

    The transforming protein of polyoma virus, middle T antigen, associates with the protein tyrosine kinase pp60c-src, and analysis of mutants of middle T suggests that this complex plays an important role in transformation by polyoma. It has recently been reported that pp60c-src from polyoma virus-transformed cells has enhanced tyrosine kinase activity in vitro. The data presented here confirm these findings and show that the enhanced kinase activity of pp60c-src is due to an increase in the Vmax of the enzyme. Sucrose density gradient analysis demonstrates that only the form of pp60c-src which is bound to middle T antigen is activated. The difference in enzyme activity between pp60c-src from normal and middle T-transformed cells is more marked when the enzyme is prepared from lysates containing the phosphotyrosine protein phosphatase inhibitor, sodium orthovanadate. pp60c-src from middle T transformed cells is unaffected, but pp60c-src from normal cells has reduced kinase activity if dephosphorylation is prevented. The kinase activity of pp60c-src thus appears to be regulated by its degree of phosphorylation at tyrosine, and data are presented which support this hypothesis. pp60c-src is the first example of a protein tyrosine kinase whose activity is inhibited by phosphorylation at tyrosine. Middle T antigen may increase the kinase activity of pp60c-src by preventing phosphorylation at this regulatory site. Images Fig. 4. Fig. 7. Fig. 8. PMID:2411538

  20. MS_RHII-RSD, a Dual-Function RNase HII-(p)ppGpp Synthetase from Mycobacterium smegmatis

    PubMed Central

    Murdeshwar, Maya S.

    2012-01-01

    In the noninfectious soil saprophyte Mycobacterium smegmatis, intracellular levels of the stress alarmones guanosine tetraphosphate and guanosine pentaphosphate, together termed (p)ppGpp, are regulated by the enzyme RelMsm. This enzyme consists of a single, bifunctional polypeptide chain that is capable of both synthesizing and hydrolyzing (p)ppGpp. The relMsm knockout strain of M. smegmatis (ΔrelMsm) is expected to show a (p)ppGpp null [(p)ppGpp0] phenotype. Contrary to this expectation, the strain is capable of synthesizing (p)ppGpp in vivo. In this study, we identify and functionally characterize the open reading frame (ORF), MSMEG_5849, that encodes a second functional (p)ppGpp synthetase in M. smegmatis. In addition to (p)ppGpp synthesis, the 567-amino-acid-long protein encoded by this gene is capable of hydrolyzing RNA·DNA hybrids and bears similarity to the conventional RNase HII enzymes. We have classified this protein as actRelMsm in accordance with the recent nomenclature proposed and have named it MS_RHII-RSD, indicating the two enzymatic activities present [RHII, RNase HII domain, originally identified as domain of unknown function 429 (DUF429), and RSD, RelA_SpoT nucleotidyl transferase domain, the SYNTH domain responsible for (p)ppGpp synthesis activity]. MS_RHII-RSD is expressed and is constitutively active in vivo and behaves like a monofunctional (p)ppGpp synthetase in vitro. The occurrence of the RNase HII and (p)ppGpp synthetase domains together on the same polypeptide chain is suggestive of an in vivo role for this novel protein as a link connecting the essential life processes of DNA replication, repair, and transcription to the highly conserved stress survival pathway, the stringent response. PMID:22636779

  1. A novel protein phosphatase 2A (PP2A) is involved in the transformation of human protozoan parasite Trypanosoma cruzi.

    PubMed Central

    González, Jorge; Cornejo, Alberto; Santos, Marcia R M; Cordero, Esteban M; Gutiérrez, Bessy; Porcile, Patricio; Mortara, Renato A; Sagua, Hernán; Da Silveira, José Franco; Araya, Jorge E

    2003-01-01

    Here we provide evidence for a critical role of PP2As (protein phosphatase 2As) in the transformation of Trypanosoma cruzi. In axenic medium at pH 5.0, trypomastigotes rapidly transform into amastigotes, a process blocked by okadaic acid, a potent PP2A inhibitor, at concentrations as low as 0.1 microM. 1-Norokadaone, an inactive okadaic acid analogue, did not affect the transformation. Electron microscopy studies indicated that okadaic acid-treated trypomastigotes had not undergone ultrastructural modifications, reinforcing the idea that PP2A inhibits transformation. Using a microcystin-Sepharose affinity column we purified the native T. cruzi PP2A. The enzyme displayed activity against 32P-labelled phosphorylase a that was inhibited in a dose-dependent manner by okadaic acid. The protein was also submitted to MS and, from the peptides obtained, degenerate primers were used to clone a novel T. cruzi PP2A enzyme by PCR. The isolated gene encodes a protein of 303 amino acids, termed TcPP2A, which displayed a high degree of homology (86%) with the catalytic subunit of Trypanosoma brucei PP2A. Northern-blot analysis revealed the presence of a major 2.1-kb mRNA hybridizing in all T. cruzi developmental stages. Southern-blot analysis suggested that the TcPP2A gene is present in low copy number in the T. cruzi genome. These results are consistent with the mapping of PP2A genes in two chromosomal bands by pulsed-field gel electrophoresis and chromoblot hybridization. Our studies suggest that in T. cruzi PP2A is important for the complete transformation of trypomastigotes into amastigotes during the life cycle of this protozoan parasite. PMID:12737627

  2. Influence of PP-g-MA compatibilizer characteristics on mechanical properties of glass fiber reinforced polypropylene composites

    NASA Astrophysics Data System (ADS)

    Guan, Zhuo

    Glass fiber (GF) reinforced polypropylene (PP) has become a common composite material used for various applications. Previous reports indicated that grafting ratio and molecular weight (MW) of znaleic anhydride grafted polypropylene (PP-g-MA) are the two most significant factors affecting the mechanical properties of PP/PP-g-MA/GF composites, but the combined effect of these two factors remains controversial. The study of the importance of MA grafting ratio and MW is continued in this work using PPIPP-g MA/GF composites containing various grades and concentrations of PP-g MA compatibilizer. First, MFR and FT1R analyses were performed to characterize the physical and chemical properties- of each PP-g-MA resin. Then, premixed PP and PP-g-MA blend were compounded with GF via twin screw extrusion, with the compounds injection molded into tensile, flexural and Izod impact specimens (all ASTM standard) for mechanical properties testing. Generally speaking, at a given GF content, higher compatibilizer concentrations led to higher tensile, flexural and notched Izod impact strength up to an optimum MA concentrations above which these properties tended to level off PP-g-MA resins with higher grafting ratio were more efficient compatibilizers as indicated by improved tensile, flexural and impact properties at lower PP-g-MA contents. In addition, MW was expected to affect properties as well, with too high and too 16w MW values leading to reduced reinforcement. While the optimum MW values for tensile and impact strength were still not clear based on present results, the estimated optimum weight average MW for maximum flexural strength was 90,000 +/- 1,400 g/mol.

  3. Diversity in guanosine 3',5'-bisdiphosphate (ppGpp) sensitivity among guanylate kinases of bacteria and plants.

    PubMed

    Nomura, Yuhta; Izumi, Atsushi; Fukunaga, Yoshinori; Kusumi, Kensuke; Iba, Koh; Watanabe, Seiya; Nakahira, Yoichi; Weber, Andreas P M; Nozawa, Akira; Tozawa, Yuzuru

    2014-05-30

    The guanosine 3',5'-bisdiphosphate (ppGpp) signaling system is shared by bacteria and plant chloroplasts, but its role in plants has remained unclear. Here we show that guanylate kinase (GK), a key enzyme in guanine nucleotide biosynthesis that catalyzes the conversion of GMP to GDP, is a target of regulation by ppGpp in chloroplasts of rice, pea, and Arabidopsis. Plants have two distinct types of GK that are localized to organelles (GKpm) or to the cytosol (GKc), with both enzymes being essential for growth and development. We found that the activity of rice GKpm in vitro was inhibited by ppGpp with a Ki of 2.8 μM relative to the substrate GMP, whereas the Km of this enzyme for GMP was 73 μM. The IC50 of ppGpp for GKpm was ∼10 μM. In contrast, the activity of rice GKc was insensitive to ppGpp, as was that of GK from bakers' yeast, which is also a cytosolic enzyme. These observations suggest that ppGpp plays a pivotal role in the regulation of GTP biosynthesis in chloroplasts through specific inhibition of GKpm activity, with the regulation of GTP biosynthesis in chloroplasts thus being independent of that in the cytosol. We also found that GKs of Escherichia coli and Synechococcus elongatus PCC 7942 are insensitive to ppGpp, in contrast to the ppGpp sensitivity of the Bacillus subtilis enzyme. Our biochemical characterization of GK enzymes has thus revealed a novel target of ppGpp in chloroplasts and has uncovered diversity among bacterial GKs with regard to regulation by ppGpp.

  4. Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function.

    PubMed

    Katayama, Kazuhiro; Yamaguchi, Miho; Noguchi, Kohji; Sugimoto, Yoshikazu

    2014-04-01

    P-glycoprotein (P-gp)/ABCB1 is a key molecule of multidrug resistance in cancer. Protein phosphatase (PP) 2A, regulatory subunit B, gamma (PPP2R3C), which is a regulatory subunit of PP2A and PP5, was identified as a binding candidate to P-gp. Immunoprecipitation-western blotting revealed that PP5 and PPP2R3C were coprecipitated with P-gp, while PP2A was not. PP5/PPP2R3C dephosphorylated protein kinase A/protein kinase C-phosphorylation of P-gp. Knockdown of PP5 and/or PPP2R3C increased P-gp expression and lowered the sensitivity to vincristine and doxorubicin. Consequently, our results indicate that PP5/PPP2R3C negatively regulates P-gp expression and function.

  5. Measurement of the slope parameter for the {eta}{yields}3{pi}{sup 0} decay in the pp{yields}pp{eta} reaction

    SciTech Connect

    Bashkanov, M.; Clement, H.; Meier, R.; Skorodko, T.; Wagner, G. J.; Bogoslawsky, D.; Ivanov, G.; Jiganov, E.; Kuznetsov, A.; Morosov, B.; Petukhov, Y.; Povtorejko, A.; Tikhomirov, V.; Calen, H.; Ekstroem, C.; Fransson, K.; Kupsc, A.; Marciniewski, P.; Ruber, R. J. M. Y.; Capellaro, F.

    2007-10-15

    The CELSIUS-WASA setup is used to measure the 3{pi}{sup 0} decay of {eta} mesons produced in pp interactions with beam kinetic energies of 1.36 and 1.45 GeV. The efficiency-corrected Dalitz plot and density distributions for this decay are shown, together with a fit of the quadratic slope parameter {alpha} yielding {alpha}=-0.026{+-}0.010(stat){+-}0.010(syst). This value is compared to recent experimental results and theoretical predictions.

  6. Synthetic growth phenotypes of E.coli lacking ppGpp and transketolase A (tktA) are due to ppGpp-mediated transcriptional regulation of tktB

    PubMed Central

    Harinarayanan, Rajendran; Murphy, Helen; Cashel, Michael

    2008-01-01

    Summary Many physiological adjustments to nutrient changes involve ppGpp. Recent attempts to deduce ppGpp regulatory effects using proteomics or gene profiling can rigorously identify proteins or transcripts, but the functional significance is often unclear. Using a random screen for synthetic lethals we found a ppGpp-dependent functional pathway that operates through transketolase-B (TktB), and which is “buffered” in wildtype strain by the presence of an isozyme, transketolase-A (TktA). Transketolase activity is required in cells to make erythrose-4-phosphate, a precursor of aromatic amino acids and vitamins. By studying tktB-dependent nutritional requirements as well as measuring activities using PtalA-tktB′-lacZ transcriptional reporter fusion we show positive transcriptional regulation of the talA-tktB operon by ppGpp. Our results show the existence of RpoS-dependent and independent modes of positive regulation by ppGpp. Both routes of activation are magnified by elevating ppGpp levels with a spoT mutation (spoT-R39A) defective in hydrolase but not synthetase activity or with the stringent suppressor mutations rpoB-A532Δ or rpoB-T563P in the absence of ppGpp. PMID:18532980

  7. Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C.

    PubMed

    Chattopadhyay, Debasish; Swingle, Mark R; Salter, Edward A; Wood, Eric; D'Arcy, Brandon; Zivanov, Catherine; Abney, Kevin; Musiyenko, Alla; Rusin, Scott F; Kettenbach, Arminja; Yet, Larry; Schroeder, Chad E; Golden, Jennifer E; Dunham, Wade H; Gingras, Anne-Claude; Banerjee, Surajit; Forbes, David; Wierzbicki, Andrzej; Honkanen, Richard E

    2016-06-01

    Cantharidin is a natural toxin and an active constituent in a traditional Chinese medicine used to treat tumors. Cantharidin acts as a semi-selective inhibitor of PPP-family ser/thr protein phosphatases. Despite sharing a common catalytic mechanism and marked structural similarity with PP1C, PP2AC and PP5C, human PP4C was found to be insensitive to the inhibitory activity of cantharidin. To explore the molecular basis for this selectivity, we synthesized and tested novel C5/C6-derivatives designed from quantum-based modeling of the interactions revealed in the co-crystal structures of PP5C in complex with cantharidin. Structure-activity relationship studies and analysis of high-resolution (1.25Å) PP5C-inhibitor co-crystal structures reveal close contacts between the inhibitor bridgehead oxygen and both a catalytic metal ion and a non-catalytic phenylalanine residue, the latter of which is substituted by tryptophan in PP4C. Quantum chemistry calculations predicted that steric clashes with the bulkier tryptophan side chain in PP4C would force all cantharidin-based inhibitors into an unfavorable binding mode, disrupting the strong coordination of active site metal ions observed in the PP5C co-crystal structures, thereby rendering PP4C insensitive to the inhibitors. This prediction was confirmed by inhibition studies employing native human PP4C. Mutation of PP5C (F446W) and PP1C (F257W), to mimic the PP4C active site, resulted in markedly suppressed sensitivity to cantharidin. These observations provide insight into the structural basis for the natural selectivity of cantharidin and provide an avenue for PP4C deselection. The novel crystal structures also provide insight into interactions that provide increased selectivity of the C5/C6 modifications for PP5C versus other PPP-family phosphatases.

  8. Cytoplasmic Retention of Protein Phosphatase 2A Inhibitor 2 (I2PP2A) Induces Alzheimer-like Abnormal Hyperphosphorylation of Tau*

    PubMed Central

    Arif, Mohammad; Wei, Jianshe; Zhang, Qi; Liu, Fei; Basurto-Islas, Gustavo; Grundke-Iqbal, Inge; Iqbal, Khalid

    2014-01-01

    Abnormal hyperphosphorylation of Tau leads to the formation of neurofibrillary tangles, a hallmark of Alzheimer disease (AD), and related tauopathies. The phosphorylation of Tau is regulated by protein phosphatase 2A (PP2A), which in turn is modulated by endogenous inhibitor 2 (I2PP2A). In AD brain, I2PP2A is translocated from neuronal nucleus to cytoplasm, where it inhibits PP2A activity and promotes abnormal phosphorylation of Tau. Here we describe the identification of a potential nuclear localization signal (NLS) in the C-terminal region of I2PP2A containing a conserved basic motif, 179RKR181, which is sufficient for directing its nuclear localization. The current study further presents an inducible cell model (Tet-Off system) of AD-type abnormal hyperphosphorylation of Tau by expressing I2PP2A in which the NLS was inactivated by 179RKR181 → AAA along with 168KR169 → AA mutations. In this model, the mutant NLS (mNLS)-I2PP2A (I2PP2AAA-AAA) was retained in the cell cytoplasm, where it physically interacted with PP2A and inhibited its activity. Inhibition of PP2A was associated with the abnormal hyperphosphorylation of Tau, which resulted in microtubule network instability and neurite outgrowth impairment. Expression of mNLS-I2PP2A activated CAMKII and GSK-3β, which are Tau kinases regulated by PP2A. The immunoprecipitation experiments showed the direct interaction of I2PP2A with PP2A and GSK-3β but not with CAMKII. Thus, the cell model provides insights into the nature of the potential NLS and the mechanistic relationship between I2PP2A-induced inhibition of PP2A and hyperphosphorylation of Tau that can be utilized to develop drugs preventing Tau pathology. PMID:25128526

  9. Shugoshin-1 balances Aurora B kinase activity via PP2A to promote chromosome bi-orientation.

    PubMed

    Meppelink, Amanda; Kabeche, Lilian; Vromans, Martijn J M; Compton, Duane A; Lens, Susanne M A

    2015-04-28

    Correction of faulty kinetochore-microtubule attachments is essential for faithful chromosome segregation and dictated by the opposing activities of Aurora B kinase and PP1 and PP2A phosphatases. How kinase and phosphatase activities are appropriately balanced is less clear. Here, we show that a centromeric pool of PP2A-B56 counteracts Aurora B T-loop phosphorylation and is recruited to centromeres through Shugoshin-1 (Sgo1). In non-transformed RPE-1 cells, Aurora B, Sgo1, and PP2A-B56 are enriched on centromeres and levels diminish as chromosomes establish bi-oriented attachments. Elevating Sgo1 levels at centromeres recruits excess PP2A-B56, and this counteracts Aurora B kinase activity, undermining efficient correction of kinetochore-microtubule attachment errors. Conversely, Sgo1-depleted cells display reduced centromeric localization of Aurora B, whereas the remaining kinase is hyperactive due to concomitant reduction of centromeric PP2A-B56. Our data suggest that Sgo1 can tune the stability of kinetochore-microtubule attachments through recruitment of PP2A-B56 that balances Aurora B activity at the centromere.

  10. A pp32-retinoblastoma protein complex modulates androgen receptor-mediated transcription and associates with components of the splicing machinery

    SciTech Connect

    Adegbola, Onikepe; Pasternack, Gary R. . E-mail: gpastern@jhmi.edu

    2005-08-26

    We have previously shown pp32 and the retinoblastoma protein interact. pp32 and the retinoblastoma protein are nuclear receptor transcriptional coregulators: the retinoblastoma protein is a coactivator for androgen receptor, the major regulator of prostate cancer growth, while pp32, which is highly expressed in prostate cancer, is a corepressor of the estrogen receptor. We now show pp32 increases androgen receptor-mediated transcription and the retinoblastoma protein modulates this activity. Using affinity purification and mass spectrometry, we identify members of the pp32-retinoblastoma protein complex as PSF and nonO/p54nrb, proteins implicated in coordinate regulation of nuclear receptor-mediated transcription and splicing. We show that the pp32-retinoblastoma protein complex is modulated during TPA-induced K562 differentiation. Present evidence suggests that nuclear receptors assemble multiprotein complexes to coordinately regulate transcription and mRNA processing. Our results suggest that pp32 and the retinoblastoma protein may be part of a multiprotein complex that coordinately regulates nuclear receptor-mediated transcription and mRNA processing.

  11. PP2C phosphatase activity is coupled to cAMP-mediated pathway in rat parotid acinar cells.

    PubMed

    Yokoyama, N; Kobayashi, T; Tamura, S; Sugiya, H

    1995-07-01

    A 26 kDa particulate protein is phosphorylated during stimulation of amylase secretion by a beta-adrenergic agonist in the rat parotid gland. Previous study has shown that PP2C phosphatase is involved in dephosphorylation of this 26 kDa protein [Yokoyama, N. et al. (1994) Biochem. Biophys. Res. Commun. 200, 497-503]. In this study, immunotransblot analysis using anti-PP2C phosphatase antibody showed that PP2C phosphatase was found prominently in the cystolic fractions and less in secretory granule membranes. When cells were stimulated by isoproterenol, cytosolic PP2C phosphatase activity increased to 145% at 5 min and returned to basal level at 30 min. Forskolin increased PP2C phosphatase activity. H89 inhibited increase of PP2C phosphatase activity following beta-adrenergic stimulation. These results suggest that PP2C phosphatase activity is regulated by cAMP-mediated signaling following beta-adrenergic stimulation and participates in dephosphorylation of this 26 kDa protein.

  12. PP2A methylation controls sensitivity and resistance to β-amyloid-induced cognitive and electrophysiological impairments.

    PubMed

    Nicholls, Russell E; Sontag, Jean-Marie; Zhang, Hong; Staniszewski, Agnieszka; Yan, Shijun; Kim, Carla Y; Yim, Michael; Woodruff, Caitlin M; Arning, Erland; Wasek, Brandi; Yin, Deqi; Bottiglieri, Teodoro; Sontag, Estelle; Kandel, Eric R; Arancio, Ottavio

    2016-03-22

    Elevated levels of the β-amyloid peptide (Aβ) are thought to contribute to cognitive and behavioral impairments observed in Alzheimer's disease (AD). Protein phosphatase 2A (PP2A) participates in multiple molecular pathways implicated in AD, and its expression and activity are reduced in postmortem brains of AD patients. PP2A is regulated by protein methylation, and impaired PP2A methylation is thought to contribute to increased AD risk in hyperhomocysteinemic individuals. To examine further the link between PP2A and AD, we generated transgenic mice that overexpress the PP2A methylesterase, protein phosphatase methylesterase-1 (PME-1), or the PP2A methyltransferase, leucine carboxyl methyltransferase-1 (LCMT-1), and examined the sensitivity of these animals to behavioral and electrophysiological impairments caused by exogenous Aβ exposure. We found that PME-1 overexpression enhanced these impairments, whereas LCMT-1 overexpression protected against Aβ-induced impairments. Neither transgene affected Aβ production or the electrophysiological response to low concentrations of Aβ, suggesting that these manipulations selectively affect the pathological response to elevated Aβ levels. Together these data identify a molecular mechanism linking PP2A to the development of AD-related cognitive impairments that might be therapeutically exploited to target selectively the pathological effects caused by elevated Aβ levels in AD patients.

  13. PP2A methylation controls sensitivity and resistance to β-amyloid–induced cognitive and electrophysiological impairments

    PubMed Central

    Nicholls, Russell E.; Sontag, Jean-Marie; Zhang, Hong; Staniszewski, Agnieszka; Yan, Shijun; Kim, Carla Y.; Yim, Michael; Woodruff, Caitlin M.; Arning, Erland; Wasek, Brandi; Yin, Deqi; Bottiglieri, Teodoro; Sontag, Estelle; Kandel, Eric R.; Arancio, Ottavio

    2016-01-01

    Elevated levels of the β-amyloid peptide (Aβ) are thought to contribute to cognitive and behavioral impairments observed in Alzheimer’s disease (AD). Protein phosphatase 2A (PP2A) participates in multiple molecular pathways implicated in AD, and its expression and activity are reduced in postmortem brains of AD patients. PP2A is regulated by protein methylation, and impaired PP2A methylation is thought to contribute to increased AD risk in hyperhomocysteinemic individuals. To examine further the link between PP2A and AD, we generated transgenic mice that overexpress the PP2A methylesterase, protein phosphatase methylesterase-1 (PME-1), or the PP2A methyltransferase, leucine carboxyl methyltransferase-1 (LCMT-1), and examined the sensitivity of these animals to behavioral and electrophysiological impairments caused by exogenous Aβ exposure. We found that PME-1 overexpression enhanced these impairments, whereas LCMT-1 overexpression protected against Aβ-induced impairments. Neither transgene affected Aβ production or the electrophysiological response to low concentrations of Aβ, suggesting that these manipulations selectively affect the pathological response to elevated Aβ levels. Together these data identify a molecular mechanism linking PP2A to the development of AD-related cognitive impairments that might be therapeutically exploited to target selectively the pathological effects caused by elevated Aβ levels in AD patients. PMID:26951658

  14. SCF E3 ligase PP2-B11 plays a positive role in response to salt stress in Arabidopsis

    PubMed Central

    Jia, Fengjuan; Wang, Chunyan; Huang, Jinguang; Yang, Guodong; Wu, Changai; Zheng, Chengchao

    2015-01-01

    Skp1–Cullin–F-box (SCF) E3 ligases are essential to the post-translational regulation of many important factors involved in cellular signal transduction. In this study, we identified an F-box protein from Arabidopsis thaliana, AtPP2-B11, which was remarkably induced with increased duration of salt treatment in terms of both transcript and protein levels. Transgenic Arabidopsis plants overexpressing AtPP2-B11 exhibited obvious tolerance to high salinity, whereas the RNA interference line was more sensitive to salt stress than wild-type plants. Isobaric tag for relative and absolute quantification analysis revealed that 4311 differentially expressed proteins were regulated by AtPP2-B11 under salt stress. AtPP2-B11 could upregulate the expression of annexin1 (AnnAt1) and function as a molecular link between salt stress and reactive oxygen species accumulation in Arabidopsis. Moreover, AtPP2-B11 influenced the expression of Na+ homeostasis genes under salt stress, and the AtPP2-B11 overexpressing lines exhibited lower Na+ accumulation. These results suggest that AtPP2-B11 functions as a positive regulator in response to salt stress in Arabidopsis. PMID:26041321

  15. (p)ppGpp, a Small Nucleotide Regulator, Directs the Metabolic Fate of Glucose in Vibrio cholerae*

    PubMed Central

    Oh, Young Taek; Lee, Kang-Mu; Bari, Wasimul; Raskin, David M.; Yoon, Sang Sun

    2015-01-01

    When V. cholerae encounters nutritional stress, it activates (p)ppGpp-mediated stringent response. The genes relA and relV are involved in the production of (p)ppGpp, whereas the spoT gene encodes an enzyme that hydrolyzes it. Herein, we show that the bacterial capability to produce (p)ppGpp plays an essential role in glucose metabolism. The V. cholerae mutants defective in (p)ppGpp production (i.e. ΔrelAΔrelV and ΔrelAΔrelVΔspoT mutants) lost their viability because of uncontrolled production of organic acids, when grown with extra glucose. In contrast, the ΔrelAΔspoT mutant, a (p)ppGpp overproducer strain, exhibited better growth in the presence of the same glucose concentration. An RNA sequencing analysis demonstrated that transcriptions of genes consisting of an operon for acetoin biosynthesis were markedly elevated in N16961, a seventh pandemic O1 strain, but not in its (p)ppGpp0 mutant during glucose-stimulated growth. Transposon insertion in acetoin biosynthesis gene cluster resulted in glucose-induced loss of viability of the ΔrelAΔspoT mutant, further suggesting the crucial role of acetoin production in balanced growth under glucose-rich environments. Additional deletion of the aphA gene, encoding a negative regulator for acetoin production, failed to rescue the (p)ppGpp0 mutant from the defective glucose-mediated growth, suggesting that (p)ppGpp-mediated acetoin production occurs independent of the presence of AphA. Overall, our results reveal that (p)ppGpp, in addition to its well known role as a stringent response mediator, positively regulates acetoin production that contributes to the successful glucose metabolism and consequently the proliferation of V. cholerae cells under a glucose-rich environment, a condition that may mimic the human intestine. PMID:25882848

  16. Search for electroweak production of single top quarks in pp¯ collisions

    NASA Astrophysics Data System (ADS)

    Abbott, B.; Abolins, M.; Abramov, V.; Acharya, B. S.; Adams, D. L.; Adams, M.; Alves, G. A.; Amos, N.; Anderson, E. W.; Baarmand, M. M.; Babintsev, V. V.; Babukhadia, L.; Baden, A.; Baldin, B.; Balm, P. W.; Banerjee, S.; Bantly, J.; Barberis, E.; Baringer, P.; Bartlett, J. F.; Bassler, U.; Bean, A.; Begel, M.; Belyaev, A.; Beri, S. B.; Bernardi, G.; Bertram, I.; Besson, A.; Bezzubov, V. A.; Bhat, P. C.; Bhatnagar, V.; Bhattacharjee, M.; Blazey, G.; Blessing, S.; Boehnlein, A.; Bojko, N. I.; Boos, E. E.; Borcherding, F.; Brandt, A.; Breedon, R.; Briskin, G.; Brock, R.; Brooijmans, G.; Bross, A.; Buchholz, D.; Buehler, M.; Buescher, V.; Burtovoi, V. S.; Butler, J. M.; Canelli, F.; Carvalho, W.; Casey, D.; Casilum, Z.; Castilla-Valdez, H.; Chakraborty, D.; Chan, K. M.; Chekulaev, S. V.; Cho, D. K.; Choi, S.; Chopra, S.; Christenson, J. H.; Chung, M.; Claes, D.; Clark, A. R.; Cochran, J.; Coney, L.; Connolly, B.; Cooper, W. E.; Coppage, D.; Cummings, M. A.; Cutts, D.; Dahl, O. I.; Davis, G. A.; Davis, K.; de, K.; del Signore, K.; Demarteau, M.; Demina, R.; Demine, P.; Denisov, D.; Denisov, S. P.; Desai, S.; Diehl, H. T.; Diesburg, M.; di Loreto, G.; Doulas, S.; Draper, P.; Ducros, Y.; Dudko, L. V.; Duensing, S.; Dugad, S. R.; Dyshkant, A.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Engelmann, R.; Eno, S.; Eppley, G.; Ermolov, P.; Eroshin, O. V.; Estrada, J.; Evans, H.; Evdokimov, V. N.; Fahland, T.; Feher, S.; Fein, D.; Ferbel, T.; Fisk, H. E.; Fisyak, Y.; Flattum, E.; Fleuret, F.; Fortner, M.; Frame, K. C.; Fuess, S.; Gallas, E.; Galyaev, A. N.; Gartung, P.; Gavrilov, V.; Genik, R. J.; Genser, K.; Gerber, C. E.; Gershtein, Y.; Gibbard, B.; Gilmartin, R.; Ginther, G.; Gómez, B.; Gómez, G.; Goncharov, P. I.; González Solís, J. L.; Gordon, H.; Goss, L. T.; Gounder, K.; Goussiou, A.; Graf, N.; Graham, G.; Grannis, P. D.; Green, J. A.; Greenlee, H.; Grinstein, S.; Groer, L.; Grudberg, P.; Grünendahl, S.; Gupta, A.; Gurzhiev, S. N.; Gutierrez, G.; Gutierrez, P.; Hadley, N. J.; Haggerty, H.; Hagopian, S.; Hagopian, V.; Hahn, K. S.; Hall, R. E.; Hanlet, P.; Hansen, S.; Hauptman, J. M.; Hays, C.; Hebert, C.; Hedin, D.; Heinson, A. P.; Heintz, U.; Heuring, T.; Hirosky, R.; Hobbs, J. D.; Hoeneisen, B.; Hoftun, J. S.; Hou, S.; Huang, Y.; Ito, A. S.; Jerger, S. A.; Jesik, R.; Johns, K.; Johnson, M.; Jonckheere, A.; Jones, M.; Jöstlein, H.; Juste, A.; Kahn, S.; Kajfasz, E.; Karmanov, D.; Karmgard, D.; Kehoe, R.; Kim, S. K.; Klima, B.; Klopfenstein, C.; Knuteson, B.; Ko, W.; Kohli, J. M.; Kostritskiy, A. V.; Kotcher, J.; Kotwal, A. V.; Kozelov, A. V.; Kozlovsky, E. A.; Krane, J.; Krishnaswamy, M. R.; Krzywdzinski, S.; Kubantsev, M.; Kuleshov, S.; Kulik, Y.; Kunori, S.; Kuznetsov, V. E.; Landsberg, G.; Leflat, A.; Lehner, F.; Li, J.; Li, Q. Z.; Lima, J. G.; Lincoln, D.; Linn, S. L.; Linnemann, J.; Lipton, R.; Lucotte, A.; Lueking, L.; Lundstedt, C.; Maciel, A. K.; Madaras, R. J.; Manankov, V.; Mao, H. S.; Marshall, T.; Martin, M. I.; Martin, R. D.; Mauritz, K. M.; May, B.; Mayorov, A. A.; McCarthy, R.; McDonald, J.; McMahon, T.; Melanson, H. L.; Meng, X. C.; Merkin, M.; Merritt, K. W.; Miao, C.; Miettinen, H.; Mihalcea, D.; Mincer, A.; Mishra, C. S.; Mokhov, N.; Mondal, N. K.; Montgomery, H. E.; Moore, R. W.; Mostafa, M.; da Motta, H.; Nagy, E.; Nang, F.; Narain, M.; Narasimham, V. S.; Neal, H. A.; Negret, J. P.; Negroni, S.; Norman, D.; Oesch, L.; Oguri, V.; Olivier, B.; Oshima, N.; Padley, P.; Pan, L. J.; Para, A.; Parashar, N.; Partridge, R.; Parua, N.; Paterno, M.; Patwa, A.; Pawlik, B.; Perkins, J.; Peters, M.; Peters, O.; Piegaia, R.; Piekarz, H.; Pope, B. G.; Popkov, E.; Prosper, H. B.; Protopopescu, S.; Qian, J.; Quintas, P. Z.; Raja, R.; Rajagopalan, S.; Ramberg, E.; Rapidis, P. A.; Reay, N. W.; Reucroft, S.; Rha, J.; Rijssenbeek, M.; Rockwell, T.; Roco, M.; Rubinov, P.; Ruchti, R.; Rutherfoord, J.; Santoro, A.; Sawyer, L.; Schamberger, R. D.; Schellman, H.; Schwartzman, A.; Sculli, J.; Sen, N.; Shabalina, E.; Shankar, H. C.; Shivpuri, R. K.; Shpakov, D.; Shupe, M.; Sidwell, R. A.; Simak, V.; Singh, H.; Singh, J. B.; Sirotenko, V.; Slattery, P.; Smith, E.; Smith, R. P.; Snihur, R.; Snow, G. R.; Snow, J.; Snyder, S.; Solomon, J.; Sorín, V.; Sosebee, M.; Sotnikova, N.; Soustruznik, K.; Souza, M.; Stanton, N. R.; Steinbrück, G.; Stephens, R. W.; Stevenson, M. L.; Stichelbaut, F.; Stoker, D.; Stolin, V.; Stoyanova, D. A.; Strauss, M.; Streets, K.; Strovink, M.; Stutte, L.; Sznajder, A.; Taylor, W.; Tentindo-Repond, S.; Thompson, J.; Toback, D.; Tripathi, S. M.; Trippe, T. G.; Turcot, A. S.; Tuts, P. M.; van Gemmeren, P.; Vaniev, V.; van Kooten, R.; Varelas, N.; Volkov, A. A.; Vorobiev, A. P.; Wahl, H. D.; Wang, H.; Wang, Z.-M.; Warchol, J.; Watts, G.; Wayne, M.; Weerts, H.; White, A.; White, J. T.; Whiteson, D.; Wightman, J. A.; Wijngaarden, D. A.; Willis, S.; Wimpenny, S. J.; Wirjawan, J. V.; Womersley, J.; Wood, D. R.; Yamada, R.; Yamin, P.; Yasuda, T.; Yip, K.; Youssef, S.; Yu, J.; Yu, Z.; Zanabria, M.; Zheng, H.; Zhou, Z.; Zhu, Z. H.; Zielinski, M.; Zieminska, D.; Zieminski, A.; Zutshi, V.; Zverev, E. G.; Zylberstejn, A.

    2001-02-01

    We present a search for electroweak production of single top quarks in the electron+jets and muon+jets decay channels. The measurements use ~90 pb-1 of data from Run 1 of the Fermilab Tevatron collider, collected at 1.8 TeV with the DØ detector between 1992 and 1995. We use events that include a tagging muon, implying the presence of a b jet, to set an upper limit at the 95% confidence level on the cross section for the s-channel process pp¯-->tb+X of 39 pb. The upper limit for the t-channel process pp¯-->tqb+X is 58 pb.

  17. Charmonium production in pp, pPb and PbPb with CMS

    NASA Astrophysics Data System (ADS)

    Lee, Songkyo; CMS collaboration

    2017-01-01

    We report on the analysis of charmonia in pp, pPb and PbPb collisions with the CMS experiment with various observables. The cross section for coherent J/ψ photoproduction is measured in ultra-peripheral PbPb collisions at 2.76 TeV. The ratio of prompt J/ψ yields at forward (proton-going direction) and backward (Pb-going direction) is studied as a function of p T, rapidity, and the event activity in pPb collisions at 5.02 TeV. The nuclear modification factor of prompt J/ψ in PbPb collisions at 2.76 TeV is presented as a function of centrality, p T, and rapidity. Finally, the production yields of ψ(2S) and J/ψ in pp and PbPb collisions have been compared.

  18. Regulators of PP2C phosphatase activity function as abscisic acid sensors.

    PubMed

    Ma, Yue; Szostkiewicz, Izabela; Korte, Arthur; Moes, Danièle; Yang, Yi; Christmann, Alexander; Grill, Erwin

    2009-05-22

    The plant hormone abscisic acid (ABA) acts as a developmental signal and as an integrator of environmental cues such as drought and cold. Key players in ABA signal transduction include the type 2C protein phosphatases (PP2Cs) ABI1 and ABI2, which act by negatively regulating ABA responses. In this study, we identify interactors of ABI1 and ABI2 which we have named regulatory components of ABA receptor (RCARs). In Arabidopsis, RCARs belong to a family with 14 members that share structural similarity with class 10 pathogen-related proteins. RCAR1 was shown to bind ABA, to mediate ABA-dependent inactivation of ABI1 or ABI2 in vitro, and to antagonize PP2C action in planta. Other RCARs also mediated ABA-dependent regulation of ABI1 and ABI2, consistent with a combinatorial assembly of receptor complexes.

  19. Influence of porous PTFE/LDPE/PP composite electret in skin ultrastructure

    NASA Astrophysics Data System (ADS)

    Jiang, J.; Liang, Y. Y.; Cui, L. L.; Hou, X. M.; Tang, Y.; Ye, X. T.; Yang, Y. J.; Song, M. H.

    2008-12-01

    Corona charging and heat melting method were used to prepare porous PTFE electret and porous PTFE/LDPE/PP composite electret, respectively. After 0.5, 1, 1.5, 3 and 4 hour's action of fluorescein sodium (FINa) and -300V porous PTFE/LDPE/PP composite electret on the excised abdominal skin of rat, the skin structure was studied by means of scanning electron microscopy, transmission electron microscopy and confocal laser scanning microscopy, respectively, to probe the mechanism of electret on transdermal drug delivery. The results indicated that negative electret could increase the transdermal delivery of FINa due to its effect on changing the organized structure of stratum corneum, enlarging the hair follicles, which may be the mechanism of electret in enhancing transdermal drug delivery.

  20. The microsortation of post-consumer HDPE/PP mixtures using near-critical carbon dioxide

    SciTech Connect

    Karmana, E.; Eiler, B.; Mainiero, D.

    1996-12-31

    The microsortation of mixed polyolefins was accomplished using near-critical carbon dioxide as a float-sink medium. A slowly turning U-shaped, helical or large-diameter pitched blade impeller was required to agitate the mixed plastics, however. This slight agitation allowed these irregular, jagged chips to either float or sink without being hindered by the neighboring chips. A post-consumer flake mixture of 85%HDPE/15%PP was sorted into HDPE and PP streams of 99+% purity. A discounted cash flow economic analysis of a 900 kg/hr polyolefin microsortation plant indicated that the value of sorted plastics must be $0.03-$0.04/lb greater than the clean, dry, mixed feed to achieve a reasonable rate of return. 14 refs., 3 figs., 1 tab.

  1. Energy dependence of the transverse momentum distributions of charged particles in pp collisions measured by ALICE.

    PubMed

    Abelev, B; Adam, J; Adamová, D; Adare, A M; Aggarwal, M M; Aglieri Rinella, G; Agnello, M; Agocs, A G; Agostinelli, A; Ahammed, Z; Ahmad, N; Ahmad Masoodi, A; Ahmed, I; Ahn, S A; Ahn, S U; Aimo, I; Aiola, S; Ajaz, M; Akindinov, A; Aleksandrov, D; Alessandro, B; Alexandre, D; Alici, A; Alkin, A; Alme, J; Alt, T; Altini, V; Altinpinar, S; Altsybeev, I; Alves Garcia Prado, C; Andrei, C; Andronic, A; Anguelov, V; Anielski, J; Antičić, T; Antinori, F; Antonioli, P; Aphecetche, L; Appelshäuser, H; Arbor, N; Arcelli, S; Armesto, N; Arnaldi, R; Aronsson, T; Arsene, I C; Arslandok, M; Augustinus, A; Averbeck, R; Awes, T C; Äystö, J; Azmi, M D; Bach, M; Badalà, A; Baek, Y W; Bailhache, R; Bala, R; Baldisseri, A; Baltasar Dos Santos Pedrosa, F; Bán, J; Baral, R C; Barbera, R; Barile, F; Barnaföldi, G G; Barnby, L S; Barret, V; Bartke, J; Basile, M; Bastid, N; Basu, S; Bathen, B; Batigne, G; Batyunya, B; Batzing, P C; Baumann, C; Bearden, I G; Beck, H; Bedda, C; Behera, N K; Belikov, I; Bellini, F; 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Dupieux, P; Dutta Majumdar, A K; D Erasmo, G; Elia, D; Emschermann, D; Engel, H; Erazmus, B; Erdal, H A; Eschweiler, D; Espagnon, B; Estienne, M; Esumi, S; Evans, D; Evdokimov, S; Eyyubova, G; Fabris, D; Faivre, J; Falchieri, D; Fantoni, A; Fasel, M; Fehlker, D; Feldkamp, L; Felea, D; Feliciello, A; Feofilov, G; Fernández Téllez, A; Ferreiro, E G; Ferretti, A; Festanti, A; Figiel, J; Figueredo, M A S; Filchagin, S; Finogeev, D; Fionda, F M; Fiore, E M; Floratos, E; Floris, M; Foertsch, S; Foka, P; Fokin, S; Fragiacomo, E; Francescon, A; Frankenfeld, U; Fuchs, U; Furget, C; Fusco Girard, M; Gaardhøje, J J; Gagliardi, M; Gago, A; Gallio, M; Gangadharan, D R; Ganoti, P; Garabatos, C; Garcia-Solis, E; Gargiulo, C; Garishvili, I; Gerhard, J; Germain, M; Gheata, A; Gheata, M; Ghidini, B; Ghosh, P; Gianotti, P; Giubellino, P; Gladysz-Dziadus, E; Glässel, P; Goerlich, L; Gomez, R; González-Zamora, P; Gorbunov, S; Gotovac, S; Graczykowski, L K; Grajcarek, R; Grelli, A; Grigoras, C; Grigoras, A; Grigoriev, V; Grigoryan, A; Grigoryan, S; Grinyov, B; Grion, N; Grosse-Oetringhaus, J F; Grossiord, J-Y; Grosso, R; Guber, F; Guernane, R; Guerzoni, B; Guilbaud, M; Gulbrandsen, K; Gulkanyan, H; Gunji, T; Gupta, A; Gupta, R; Khan, K H; Haake, R; Haaland, Ø; Hadjidakis, C; Haiduc, M; Hamagaki, H; Hamar, G; Hanratty, L D; Hansen, A; Harris, J W; Harton, A; Hatzifotiadou, D; Hayashi, S; Hayrapetyan, A; Heckel, S T; Heide, M; Helstrup, H; Herghelegiu, A; Herrera Corral, G; Herrmann, N; Hess, B A; Hetland, K F; Hicks, B; Hippolyte, B; Hori, Y; Hristov, P; Hřivnáčová, I; Huang, M; Humanic, T J; Hutter, D; Hwang, D S; Ichou, R; Ilkaev, R; Ilkiv, I; Inaba, M; Incani, E; Innocenti, G M; Ionita, C; Ippolitov, M; Irfan, M; Ivanov, V; Ivanov, M; Ivanytskyi, O; Jachołkowski, A; Jahnke, C; Jang, H J; Janik, M A; Jayarathna, P H S Y; Jena, S; Jimenez Bustamante, R T; Jones, P G; Jung, H; Jusko, A; Kalcher, S; Kaliňák, P; Kalliokoski, T; Kalweit, A; Kang, J H; Kaplin, V; Kar, S; Karasu Uysal, A; Karavichev, O; Karavicheva, T; Karpechev, E; Kazantsev, A; Kebschull, U; Keidel, R; Ketzer, B; Khan, S A; Khan, M M; Khan, P; Khanzadeev, A; Kharlov, Y; Kileng, B; Kim, S; Kim, D W; Kim, D J; Kim, B; Kim, T; Kim, M; Kim, M; Kim, J S; Kirsch, S; Kisel, I; Kiselev, S; Kisiel, A; Kiss, G; Klay, J L; Klein, J; Klein-Bösing, C; Kluge, A; Knichel, M L; Knospe, A G; Köhler, M K; Kollegger, T; Kolojvari, A; Kondratiev, V; Kondratyeva, N; Konevskikh, A; Kovalenko, V; Kowalski, M; Kox, S; Koyithatta Meethaleveedu, G; Kral, J; Králik, I; Kramer, F; Kravčáková, A; Krelina, M; Kretz, M; Krivda, M; Krizek, F; Krus, M; Kryshen, E; Krzewicki, M; Kucera, V; Kucheriaev, Y; Kugathasan, T; Kuhn, C; Kuijer, P G; Kulakov, I; Kumar, J; Kurashvili, P; Kurepin, A B; Kurepin, A; Kuryakin, A; Kushpil, S; Kushpil, V; Kweon, M J; Kwon, Y; Ladrón de Guevara, P; Lagana Fernandes, C; Lakomov, I; Langoy, R; Lara, C; Lardeux, A; La Pointe, S L; La Rocca, P; Lea, R; Lechman, M; Lee, S C; Lee, G R; Legrand, I; Lehnert, J; Lemmon, R C; Lenhardt, M; Lenti, V; León Monzón, I; Lévai, P; Li, S; Lien, J; Lietava, R; Lindal, S; Lindenstruth, V; Lippmann, C; Lisa, M A; Ljunggren, H M; Lodato, D F; Loenne, P I; Loggins, V R; Loginov, V; Lohner, D; Loizides, C; Loo, K K; Lopez, X; López Torres, E; Løvhøiden, G; Lu, X-G; Luettig, P; Lunardon, M; Luo, J; Luparello, G; Luzzi, C; Jacobs, P M; Ma, R; Maevskaya, A; Mager, M; Mahapatra, D P; Maire, A; Malaev, M; Maldonado Cervantes, I; Malinina, L; Mal'Kevich, D; Malzacher, P; Mamonov, A; Manceau, L; Manko, V; Manso, F; Manzari, V; Marchisone, M; Mareš, J; Margagliotti, G V; Margotti, A; Marín, A; Markert, C; Marquard, M; Martashvili, I; Martin, N A; Martinengo, P; Martínez, M I; Martínez García, G; Martin Blanco, J; Martynov, Y; Mas, A; Masciocchi, S; Masera, M; Masoni, A; Massacrier, L; Mastroserio, A; Matyja, A; Mazer, J; Mazumder, R; Mazzoni, M A; Meddi, F; Menchaca-Rocha, A; Mercado Pérez, J; Meres, M; Miake, Y; Mikhaylov, K; Milano, L; Milosevic, J; Mischke, A; Mishra, A N; Miśkowiec, D; Mitu, C; Mlynarz, J; Mohanty, B; Molnar, L; Montaño Zetina, L; Monteno, M; Montes, E; Moon, T; Morando, M; Moreira De Godoy, D A; Moretto, S; Morreale, A; Morsch, A; Muccifora, V; Mudnic, E; Muhuri, S; Mukherjee, M; Müller, H; Munhoz, M G; Murray, S; Musa, L; Nandi, B K; Nania, R; Nappi, E; Nattrass, C; Nayak, T K; Nazarenko, S; Nedosekin, A; Nicassio, M; Niculescu, M; Nielsen, B S; Nikolaev, S; Nikulin, S; Nikulin, V; Nilsen, B S; Nilsson, M S; Noferini, F; Nomokonov, P; Nooren, G; Nyanin, A; Nyatha, A; Nystrand, J; Oeschler, H; Oh, S K; Oh, S; Olah, L; Oleniacz, J; Oliveira Da Silva, A C; Onderwaater, J; Oppedisano, C; Ortiz Velasquez, A; Oskarsson, A; Otwinowski, J; Oyama, K; Pachmayer, Y; Pachr, M; Pagano, P; Paić, G; Painke, F; Pajares, C; Pal, S K; Palaha, A; Palmeri, A; Papikyan, V; Pappalardo, G S; Park, W J; Passfeld, A; Patalakha, D I; Paticchio, V; Paul, B; Pawlak, T; Peitzmann, T; Pereira Da Costa, H; Pereira De Oliveira Filho, E; Peresunko, D; Pérez Lara, C E; Perrino, D; Peryt, W; Pesci, A; Pestov, Y; Petráček, V; Petran, M; Petris, M; Petrov, P; Petrovici, M; Petta, C; Piano, S; Pikna, M; Pillot, P; Pinazza, O; Pinsky, L; Pitz, N; Piyarathna, D B; Planinic, M; Płoskoń, M; Pluta, J; Pochybova, S; Podesta-Lerma, P L M; Poghosyan, M G; Polichtchouk, B; Poljak, N; Pop, A; Porteboeuf-Houssais, S; Pospíšil, V; Potukuchi, B; Prasad, S K; Preghenella, R; Prino, F; Pruneau, C A; Pshenichnov, I; Puddu, G; Punin, V; Putschke, J; Qvigstad, H; Rachevski, A; Rademakers, A; Rak, J; Rakotozafindrabe, A; Ramello, L; Raniwala, S; Raniwala, R; Räsänen, S S; Rascanu, B T; Rathee, D; Rauch, W; Rauf, A W; Razazi, V; Read, K F; Real, J S; Redlich, K; Reed, R J; Rehman, A; Reichelt, P; Reicher, M; Reidt, F; Renfordt, R; Reolon, A R; Reshetin, A; Rettig, F; Revol, J-P; Reygers, K; Riccati, L; Ricci, R A; Richert, T; Richter, M; Riedler, P; Riegler, W; Riggi, F; Rivetti, A; Rodríguez Cahuantzi, M; Rodriguez Manso, A; Røed, K; Rogochaya, E; Rohni, S; Rohr, D; Röhrich, D; Romita, R; Ronchetti, F; Rosnet, P; Rossegger, S; Rossi, A; Roy, P; Roy, C; Rubio Montero, A J; Rui, R; Russo, R; Ryabinkin, E; Rybicki, A; Sadovsky, S; Šafařík, K; Sahoo, R; Sahu, P K; Saini, J; Sakaguchi, H; Sakai, S; Sakata, D; Salgado, C A; Salzwedel, J; Sambyal, S; Samsonov, V; Sanchez Castro, X; Šándor, L; Sandoval, A; Sano, M; Santagati, G; Santoro, R; Sarkar, D; Scapparone, E; Scarlassara, F; Scharenberg, R P; Schiaua, C; Schicker, R; Schmidt, C; Schmidt, H R; Schuchmann, S; Schukraft, J; Schulc, M; Schuster, T; Schutz, Y; Schwarz, K; Schweda, K; Scioli, G; Scomparin, E; Scott, R; Scott, P A; Segato, G; Selyuzhenkov, I; Seo, J; Serci, S; Serradilla, E; Sevcenco, A; Shabetai, A; Shabratova, G; Shahoyan, R; Sharma, S; Sharma, N; Shigaki, K; Shtejer, K; Sibiriak, Y; Siddhanta, S; Siemiarczuk, T; Silvermyr, D; Silvestre, C; Simatovic, G; Singaraju, R; Singh, R; Singha, S; Singhal, V; Sinha, B C; Sinha, T; Sitar, B; Sitta, M; Skaali, T B; Skjerdal, K; Smakal, R; Smirnov, N; Snellings, R J M; Søgaard, C; Soltz, R; Song, M; Song, J; Soos, C; Soramel, F; Spacek, M; Sputowska, I; Spyropoulou-Stassinaki, M; Srivastava, B K; Stachel, J; Stan, I; Stefanek, G; Steinpreis, M; Stenlund, E; Steyn, G; Stiller, J H; Stocco, D; Stolpovskiy, M; Strmen, P; Suaide, A A P; Subieta Vásquez, M A; Sugitate, T; Suire, C; Suleymanov, M; Sultanov, R; Šumbera, M; Susa, T; Symons, T J M; Szanto de Toledo, A; Szarka, I; Szczepankiewicz, A; Szymański, M; Takahashi, J; Tangaro, M A; Tapia Takaki, J D; Tarantola Peloni, A; Tarazona Martinez, A; Tauro, A; Tejeda Muñoz, G; Telesca, A; Terrevoli, C; Ter Minasyan, A; Thäder, J; Thomas, D; Tieulent, R; Timmins, A R; Toia, A; Torii, H; Trubnikov, V; Trzaska, W H; Tsuji, T; Tumkin, A; Turrisi, R; Tveter, T S; Ulery, J; Ullaland, K; Ulrich, J; Uras, A; Urciuoli, G M; Usai, G L; Vajzer, M; Vala, M; Valencia Palomo, L; Vande Vyvre, P; Vannucci, L; Van Hoorne, J W; van Leeuwen, M; Vargas, A; Varma, R; Vasileiou, M; Vasiliev, A; Vechernin, V; Veldhoen, M; Venaruzzo, M; Vercellin, E; Vergara, S; Vernet, R; Verweij, M; Vickovic, L; Viesti, G; Viinikainen, J; Vilakazi, Z; Villalobos Baillie, O; Vinogradov, A; Vinogradov, L; Vinogradov, Y; Virgili, T; Viyogi, Y P; Vodopyanov, A; Völkl, M A; Voloshin, S; Voloshin, K; Volpe, G; von Haller, B; Vorobyev, I; Vranic, D; Vrláková, J; Vulpescu, B; Vyushin, A; Wagner, B; Wagner, V; Wagner, J; Wang, Y; Wang, Y; Wang, M; Watanabe, D; Watanabe, K; Weber, M; Wessels, J P; Westerhoff, U; Wiechula, J; Wikne, J; Wilde, M; Wilk, G; Wilkinson, J; Williams, M C S; Windelband, B; Winn, M; Xiang, C; Yaldo, C G; Yamaguchi, Y; Yang, H; Yang, P; Yang, S; Yano, S; Yasnopolskiy, S; Yi, J; Yin, Z; Yoo, I-K; Yushmanov, I; Zaccolo, V; Zach, C; Zampolli, C; Zaporozhets, S; Zarochentsev, A; Závada, P; Zaviyalov, N; Zbroszczyk, H; Zelnicek, P; Zgura, I S; Zhalov, M; Zhang, F; Zhang, Y; Zhang, H; Zhang, X; Zhou, D; Zhou, Y; Zhou, F; Zhu, X; Zhu, J; Zhu, J; Zhu, H; Zichichi, A; Zimmermann, M B; Zimmermann, A; Zinovjev, G; Zoccarato, Y; Zynovyev, M; Zyzak, M

    Differential cross sections of charged particles in inelastic pp collisions as a function of pT have been measured at [Formula: see text] at the LHC. The pT spectra are compared to NLO-pQCD calculations. Though the differential cross section for an individual [Formula: see text] cannot be described by NLO-pQCD, the relative increase of cross section with [Formula: see text] is in agreement with NLO-pQCD. Based on these measurements and observations, procedures are discussed to construct pp reference spectra at [Formula: see text] up to pT=50 GeV/c as required for the calculation of the nuclear modification factor in nucleus-nucleus and proton-nucleus collisions.

  2. Extraction of {gamma} from charmless hadronic B {yields} PP decays using SU(3) flavor symmetry

    SciTech Connect

    Suprun, Denis A.

    2006-07-11

    The decays of B mesons to a pair of charmless pseudoscalar mesons (PP decays) have been analyzed within the framework of flavor SU(3) symmetry and quark-diagrammatic topological approach. Flavor symmetry breaking is taken into account in tree (T) amplitudes through ratios of decay constants fK and f{pi}; exact SU(3) is assumed elsewhere. Acceptable fits to B {yields} PP branching ratios and CP asymmetries are obtained with tree, color-suppressed and QCD penguin amplitudes. Singlet penguin amplitude was introduced to describe decay amplitudes of the modes with {eta} and {eta}' mesons in the final state. Electroweak penguin amplitudes were expressed in terms of the corresponding tree-level diagrams. Values of the weak phase {gamma} were found to be consistent with the current indirect bounds from other analyses of CKM parameters.

  3. RESEARCH NOTE FROM COLLABORATION: GridPP: development of the UK computing Grid for particle physics

    NASA Astrophysics Data System (ADS)

    Grid PP Collaboration; Faulkner, P. J. W.; Lowe, L. S.; Tan, C. L. A.; Watkins, P. M.; Bailey, D. S.; Barrass, T. A.; Brook, N. H.; Croft, R. J. H.; Kelly, M. P.; Mackay, C. K.; Metson, S.; Maroney, O. J. E.; Newbold, D. M.; Wilson, F. F.; Hobson, P. R.; Khan, A.; Kyberd, P.; Nebrensky, J. J.; Bly, M.; Brew, C.; Burke, S.; Byrom, R.; Coles, J.; Cornwall, L. A.; Djaoui, A.; Field, L.; Fisher, S. M.; Folkes, G. T.; Geddes, N. I.; Gordon, J. C.; Hicks, S. J. C.; Jensen, J. G.; Johnson, G.; Kant, D.; Kelsey, D. P.; Kuznetsov, G.; Leake, J.; Middleton, R. P.; Patrick, G. N.; Prassas, G.; Saunders, B. J.; Ross, D.; Sansum, R. A.; Shah, T.; Strong, B.; Synge, O.; Tam, R.; Thorpe, M.; Traylen, S.; Wheeler, J. F.; White, N. G. H.; Wilson, A. J.; Antcheva, I.; Artiaga, E.; Beringer, J.; Bird, I. G.; Casey, J.; Cass, A. J.; Chytracek, R.; Gallas Torreira, M. V.; Generowicz, J.; Girone, M.; Govi, G.; Harris, F.; Heikkurinen, M.; Horvath, A.; Knezo, E.; Litmaath, M.; Lubeck, M.; Moscicki, J.; Neilson, I.; Poinsignon, E.; Pokorski, W.; Ribon, A.; Sekera, Z.; Smith, D. H.; Tomlin, W. L.; van Eldik, J. E.; Wojcieszuk, J.; Brochu, F. M.; Das, S.; Harrison, K.; Hayes, M.; Hill, J. C.; Lester, C. G.; Palmer, M. J.; Parker, M. A.; Nelson, M.; Whalley, M. R.; Glover, E. W. N.; Anderson, P.; Clark, P. J.; Earl, A. D.; Holt, A.; Jackson, A.; Joo, B.; Kenway, R. D.; Maynard, C. M.; Perry, J.; Smith, L.; Thorn, S.; Trew, A. S.; Bell, W. H.; Burgon-Lyon, M.; Cameron, D. G.; Doyle, A. T.; Flavell, A.; Hanlon, S. J.; Martin, D. J.; McCance, G.; Millar, A. P.; Nicholson, C.; Paterson, S. K.; Pickford, A.; Soler, P.; Speirs, F.; St. Denis, R.; Thompson, A. S.; Britton, D.; Cameron, W.; Colling, D.; Davies, G.; Dornan, P.; Egede, U.; Georgiou, K.; Lewis, P.; MacEvoy, B.; Marr, S.; Martyniak, J.; Tallini, H.; Wakefield, S.; Walker, R.; Bertram, I. A.; Bouhova-Thacker, E.; Evans, D.; Henderson, R. C. W.; Jones, R. W. L.; Love, P.; Downing, S.; George, M. P.; Irving, A. C.; McNeile, C.; Sroczynski, Z.; Tobin, M.; Washbrook, A. J.; Barlow, R. J.; Dallison, S.; Fairey, G.; Forti, A.; Hughes-Jones, R. E.; Jones, M. A. S.; Kaushal, S.; Marshall, R.; McNab, A.; Salih, S.; Werner, J. C.; Bartsch, V.; Cioffi, C.; Gronbech, P.; Harnew, N.; Harris, J. F.; Huffman, B. T.; Leslie, M.; McArthur, I.; Newman, R.; Soroko, A.; Stokes-Rees, I.; Stonjek, S.; Tseng, J.; Waters, D.; Wilkinson, G.; Arter, T. R.; Cordenonsi, R. A.; Datta, A. S.; Hartin, T.; Lloyd, S. L.; Martin, A. J.; Pearce, S. E.; Williams, C. J.; Gardner, M.; George, S.; Green, B. J.; Johal, S.; Rybkine, G.; Strong, J. A.; Teixeira-Dias, P.; Hodgson, P.; Robinson, M.; Tovey, D. R.; Spooner, N. J. C.; Allton, C. R.; Armour, W.; Clarke, P.; Mealor, P.; Waters, D.; Waugh, B.; West, B.

    2006-01-01

    The GridPP Collaboration is building a UK computing Grid for particle physics, as part of the international effort towards computing for the Large Hadron Collider. The project, funded by the UK Particle Physics and Astronomy Research Council (PPARC), began in September 2001 and completed its first phase 3 years later. GridPP is a collaboration of approximately 100 researchers in 19 UK university particle physics groups, the Council for the Central Laboratory of the Research Councils and CERN, reflecting the strategic importance of the project. In collaboration with other European and US efforts, the first phase of the project demonstrated the feasibility of developing, deploying and operating a Grid-based computing system to meet the UK needs of the Large Hadron Collider experiments. This note describes the work undertaken to achieve this goal.

  4. IK-guided PP2A suppresses Aurora B activity in the interphase of tumor cells.

    PubMed

    Lee, Sunyi; Jeong, Ae Lee; Park, Jeong Su; Han, Sora; Jang, Chang-Young; Kim, Keun Il; Kim, Yonghwan; Park, Jong Hoon; Lim, Jong-Seok; Lee, Myung Sok; Yang, Young

    2016-09-01

    Aurora B activation is triggered at the mitotic entry and required for proper microtubule-kinetochore attachment at mitotic phase. Therefore, Aurora B should be in inactive form in interphase to prevent aberrant cell cycle progression. However, it is unclear how the inactivation of Aurora B is sustained during interphase. In this study, we find that IK depletion-induced mitotic arrest leads to G2 arrest by Aurora B inhibition, indicating that IK depletion enhances Aurora B activation before mitotic entry. IK binds to Aurora B, and colocalizes on the nuclear foci during interphase. Our data further show that IK inhibits Aurora B activation through recruiting PP2A into IK and Aurora B complex. It is thus believed that IK, as a scaffold protein, guides PP2A into Aurora B to suppress its activity in interphase until mitotic entry.

  5. Color reconnection: a fundamental ingredient of the hadronisation in p-p collisions

    NASA Astrophysics Data System (ADS)

    Cuautle, E.; Iga, S.; Ortiz, A.; Paić, G.

    2016-07-01

    At the LHC very interesting similarities among different colliding systems (p-p, p-Pb and Pb-Pb) where observed in the multiplicity evolution of the transverse momentum spectra. This has prompted a number of analyses that have explained the results in terms of collective hydrodynamic flow. The explanation in terms of hydrodynamics has recognized problems with the smallness of the interaction volume in the systems created in p-p and p- Pb collisions. On the other hand, some event generators based on QCD produce a reasonable qualitative, and sometimes quantitative, agreement with the data. Those results can be achieved introducing in the hadronisation model the so-called color reconnection which produces flowlike patterns via boosted strings. In this work we present the behavior of the various color reconnection (CR) schemes compared to those without the CR case for different center-of-mass energies at the LHC (0.9, 7 and 13 TeV).

  6. Phase Inversion of EPDM/PP Blends: Effect of Viscosity Ratio

    NASA Astrophysics Data System (ADS)

    Machado, Ana Vera; Antunes, Carla Filipa; van Duin, Martin

    2011-07-01

    EPDM/PP blends and TPVs with and without crosslinking, respectively, were prepared, in a batch mixer, using three different EPDM rubbers. EPDM/PP based TPVs were dynamic vulcanised using the resol/SnCl2 system. Samples were collected along the time in order to get information on the morphology evolution and crosslinking density during dynamic vulcanisation. The morphology was studied by SEM and the crosslink density by gel content. In the case of low viscosity EPDMs, crosslinking of the EPDM phase was retarded due to its low crosslinking efficiency. This delay on crosslinking reaction enables the observation of the various stages of the morphological mechanism that takes place during dynamic vulcanisation. It could be observed that phase inversion takes place via lamellar mechanism. More detailed insight on phase inversion mechanism during dynamic vulcanisation was accomplished.

  7. Assessment of ALA-induced PpIX production in porcine skin pretreated with microneedles.

    PubMed

    Rodrigues, Phamilla Gracielli Sousa; Campos de Menezes, Priscila Fernanda; Fujita, Alessandra Keiko Lima; Escobar, André; Barboza de Nardi, Andrigo; Kurachi, Cristina; Bagnato, Vanderlei S

    2015-09-01

    Photodynamic therapy (PDT) is used for skin treatments of premalignant and cancer lesions and recognized as a non-invasive technique that combines tissue photosensitization and subsequent exposure to light to induce cell death. However, it is limited to the treatment of superficial lesions, mainly due to the low cream penetration. Therefore, the improvement of transdermal distribution of aminolevulinic acid (ALA) is needed. In this study, the kinetics and homogeneity of production of ALA-induced PpIX after the skin pre-treatment with microneedles rollers of 0.5, 1.0 and 1.5 mm length were investigated. An improvement in homogeneity and production of PpIX was shown in a porcine model. Widefield fluorescence imaging three hours after the topical application of ALA-cream in the combined treatment with microeedles rollers.

  8. Study of ω-meson production in pp collisions at ANKE

    NASA Astrophysics Data System (ADS)

    Barsov, S.; Büscher, M.; Hartmann, M.; Hejny, V.; Kacharava, A.; Keshelashvili, I.; Khoukaz, A.; Koptev, V.; Kulessa, P.; Kulikov, A.; Lehmann, I.; Leontyev, V.; Macharashvili, G.; Maeda, Y.; Mersmann, T.; Merzliakov, S.; Mikirtytchyants, S.; Mussgiller, A.; Oellers, D.; Ohm, H.; Rathmann, F.; Schleichert, R.; Seyfarth, H.; Ströher, H.; Trusov, S.; Valdau, Yu.; Wüstner, P.; Yaschenko, S.; Wilkin, C.

    2007-01-01

    The production of ω-mesons in the ppppω reaction has been investigated with the COSY-ANKE spectrometer for excess energies of 60 and 92MeV by detecting the two final protons and reconstructing their missing mass. The large physical background was subtracted using an event-by-event transformation of the proton momenta between the two energies. Differential distributions and total cross-sections were obtained after careful studies of possible systematic uncertainties in the overall ANKE acceptance. The results are compared with the predictions of theoretical models. Combined with data on the φ-meson, a more refined estimate is made of the Okubo-Zweig-Iizuka rule violation in the φ/ω production ratio.

  9. Use of Differential Scanning Calorimetry (DSC) in the Characterization of EPDM/PP Blends

    NASA Astrophysics Data System (ADS)

    Stelescu, Maria Daniela; Airinei, Anton; Grigoras, Cristian; Niculescu-Aron, Ileana-Gabriela

    2010-12-01

    New polyolefinic thermoplastic elastomers based on the ethylene-propylene-diene monomer (EPDM) and polypropylene (PP) containing an EPDM elastomer of the last generation (Nordel NDR 47130), obtained by polymerization in the gaseous phase with metallocene catalysis, were prepared and characterized. The melting and crystallization behavior of these blends was investigated by differential scanning calorimetry. It is observed that the melting temperature, crystallization temperature, and crystallinity degree increase with an increase of PP loading. The influence of the blend composition on the physico-mechanical characteristics was discussed using statistical processing of the experimental data. Two compatibilizing procedures were utilized to improve the physico-mechanical characteristics of the samples: an addition method using different compatibilizing agents and dynamical vulcanization with three types of crosslinking systems. Significant improvements of the tensile strength and tear strength were noted by dynamic crosslinking, and the best results were obtained using a crosslinking system based on phenolic resin and tin chloride.

  10. Mechanical, thermal, rheological and morphological behaviour of irradiated PP/HA composites

    NASA Astrophysics Data System (ADS)

    Ramírez, C.; Albano, C.; Karam, A.; Domínguez, N.; Sánchez, Y.; González, G.

    2005-07-01

    Hydroxyapatite (HA) reinforced polypropylene (PP) composites are being developed as bone graft materials. In this research, the effect of γ irradiation on mechanical, rheological, thermal and morphological behaviour of PP-HA composites was studied. The melt flow index of polymer increased markedly when it was exposed to radiation. This is indicative of chain scission reaction as the predominant process. During the tensile testing, the composites exhibited brittle behaviour, showing no fluency point. Elongation at break showed a tendency to decrease with the increase in radiation dose while stress at break did not show significant variation with radiation dose. High HA content (>20%) and radiation dose (25 kGy) had significant influence on thermal stability.

  11. Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac

    PubMed Central

    Tao, Min; Liu, Lu; Shen, Meng; Zhi, Qiaoming; Gong, Fei-Ran; Zhou, Binhua P.; Wu, Yadi; Liu, Haiyan; Chen, Kai; Shen, Bairong; Wu, Meng-Yao; Shou, Liu-Mei; Li, Wei

    2016-01-01

    ABSTRACT Previous studies have indicated that inflammatory stimulation represses protein phosphatase 2A (PP2A), a well-known tumor suppressor. However, whether PP2A repression participates in pancreatic cancer progression has not been verified. We used lipopolysaccharide (LPS) and macrophage-conditioned medium (MCM) to establish in vitro inflammation models, and investigated whether inflammatory stimuli affect pancreatic cancer cell growth and invasion PP2A catalytic subunit (PP2Ac)-dependently. Via nude mouse models of orthotopic tumor xenografts and dibutyltin dichloride (DBTC)-induced chronic pancreatitis, we evaluated the effect of an inflammatory microenvironment on PP2Ac expression in vivo. We cloned the PP2Acα and PP2Acβ isoform promoters to investigate the PP2Ac transcriptional regulation mechanisms. MCM accelerated pancreatic cancer cell growth; MCM and LPS promoted cell invasion. DBTC promoted xenograft growth and metastasis, induced tumor-associated macrophage infiltration, promoted angiogenesis, activated the nuclear factor-κB (NF-κB) pathway, and repressed PP2Ac expression. In vitro, LPS and MCM downregulated PP2Ac mRNA and protein. PP2Acα overexpression attenuated JNK, ERK, PKC, and IKK phosphorylation, and impaired LPS/MCM-stimulated cell invasion and MCM-promoted cell growth. LPS and MCM activated the NF-κB pathway in vitro. LPS and MCM induced IKK and IκB phosphorylation, leading to p65/RelA nuclear translocation and transcriptional activation. Overexpression of the dominant negative forms of IKKα attenuated LPS and MCM downregulation of PP2Ac, suggesting inflammatory stimuli repress PP2Ac expression NF-κB pathway–dependently. Luciferase reporter gene assay verified that LPS and MCM downregulated PP2Ac transcription through an NF-κB–dependent pathway. Our study presents a new mechanism in inflammation-driven cancer progression through NF-κB pathway–dependent PP2Ac repression. PMID:26761431

  12. Changes in Carboxy Methylation and Tyrosine Phosphorylation of Protein Phosphatase PP2A Are Associated with Epididymal Sperm Maturation and Motility

    PubMed Central

    Dudiki, Tejasvi; Kadunganattil, Suraj; Ferrara, John K.; Kline, Douglas W.; Vijayaraghavan, Srinivasan

    2015-01-01

    Mammalian sperm contain the serine/threonine phosphatases PP1γ2 and PP2A. The role of sperm PP1γ2 is relatively well studied. Here we confirm the presence of PP2A in sperm and show that it undergoes marked changes in methylation (leucine 309), tyrosine phosphorylation (tyrosine 307) and catalytic activity during epididymal sperm maturation. Spermatozoa isolated from proximal caput, distal caput and caudal regions of the epididymis contain equal immuno-reactive amounts of PP2A. Using demethyl sensitive antibodies we show that PP2A is methylated at its carboxy terminus in sperm from the distal caput and caudal regions but not in sperm from the proximal caput region of the epididymis. The methylation status of PP2A was confirmed by isolation of PP2A with microcystin agarose followed by alkali treatment, which causes hydrolysis of protein carboxy methyl esters. Tyrosine phosphorylation of sperm PP2A varied inversely with methylation. That is, PP2A was tyrosine phosphorylated when it was demethylated but not when methylated. PP2A demethylation and its reciprocal tyrosine phosphorylation were also affected by treatment of sperm with L-homocysteine and adenosine, which are known to elevate intracellular S-adenosylhomocysteine, a feedback inhibitor of methyltransferases. Catalytic activity of PP2A declined during epididymal sperm maturation. Inhibition of PP2A by okadaic acid or by incubation of caudal epididymal spermatozoa with L-homocysteine and adenosine resulted in increase of sperm motility parameters including percent motility, velocity, and lateral head amplitude. Demethylation or pharmacological inhibition of PP2A also leads to an increase in phosphorylation of glycogen synthase kinase-3 (GSK3). Our results show for the first time that changes in PP2A activity due to methylation and tyrosine phosphorylation occur in sperm and that these changes may play an important role in the regulation of sperm function. PMID:26569399

  13. The protein phosphatase 2C clade A protein OsPP2C51 positively regulates seed germination by directly inactivating OsbZIP10.

    PubMed

    Bhatnagar, Nikita; Min, Myung-Ki; Choi, Eun-Hye; Kim, Namhyo; Moon, Seok-Jun; Yoon, Insun; Kwon, Taekryoun; Jung, Ki-Hong; Kim, Beom-Gi

    2017-03-01

    Protein phosphatase 2C clade A members are major signaling components in the ABA-dependent signaling cascade that regulates seed germination. To elucidate the role of PP2CA genes in germination of rice seed, we selected OsPP2C51, which shows highly specific expression in the embryo compared with other protein phosphatases based on microarray data. GUS histochemical assay confirmed that OsPP2C51 is expressed in the seed embryo and that this expression pattern is unique compared with those of other OsPP2CA genes. Data obtained from germination assays and alpha-amylase assays of OsPP2C51 knockout and overexpression lines suggest that OsPP2C51 positively regulates seed germination in rice. The expression of alpha-amylase synthesizing genes was high in OsPP2C51 overexpressing plants, suggesting that elevated levels of OsPP2C51 might enhance gene expression related to higher rates of seed germination. Analysis of protein interactions between ABA signaling components showed that OsPP2C51 interacts with OsPYL/RCAR5 in an ABA-dependent manner. Furthermore, interactions were observed between OsPP2C51 and SAPK2, and between OsPP2C51 and OsbZIP10 and we found out that OsPP2C51 can dephosphorylates OsbZIP10. These findings suggest the existence of a new branch in ABA signaling pathway consisting of OsPYL/RCAR-OsPP2C-bZIP apart from the previously reported OsPYL/RCAR-OsPP2C-SAPK-bZIP. Overall, our result suggests that OsPP2C51 is a positive regulator of seed germination by directly suppressing active phosphorylated OsbZIP10.

  14. Injection molding of iPP samples in controlled conditions and resulting morphology

    SciTech Connect

    Sessa, Nino De Santis, Felice Pantani, Roberto

    2015-12-17

    Injection molded parts are driven down in size and weight especially for electronic applications. In this work, an investigation was carried out on the process of injection molding of thin iPP samples and on the morphology of these parts. Melt flow in the mold cavity was analyzed and described with a mathematical model. Influence of mold temperature and injection pressure was analyzed. Samples orientation was studied using optical microscopy.

  15. Computing posterior probabilities for score-based alignments using ppALIGN.

    PubMed

    Wolfsheimer, Stefan; Hartmann, Alexander; Rabus, Ralf; Nuel, Gregory

    2012-05-16

    Score-based pairwise alignments are widely used in bioinformatics in particular with molecular database search tools, such as the BLAST family. Due to sophisticated heuristics, such algorithms are usually fast but the underlying scoring model unfortunately lacks a statistical description of the reliability of the reported alignments. In particular, close to gaps, in low-score or low-complexity regions, a huge number of alternative alignments arise which results in a decrease of the certainty of the alignment. ppALIGN is a software package that uses hidden Markov Model techniques to compute position-wise reliability of score-based pairwise alignments of DNA or protein sequences. The design of the model allows for a direct connection between the scoring function and the parameters of the probabilistic model. For this reason it is suitable to analyze the outcomes of popular score based aligners and search tools without having to choose a complicated set of parameters. By contrast, our program only requires the classical score parameters (the scoring function and gap costs). The package comes along with a library written in C++, a standalone program for user defined alignments (ppALIGN) and another program (ppBLAST) which can process a complete result set of BLAST. The main algorithms essentially exhibit a linear time complexity (in the alignment lengths), and they are hence suitable for on-line computations. We have also included alternative decoding algorithms to provide alternative alignments. ppALIGN is a fast program/library that helps detect and quantify questionable regions in pairwise alignments. Due to its structure, the input/output interface it can to be connected to other post-processing tools. Empirically, we illustrate its usefulness in terms of correctly predicted reliable regions for sequences generated using the ROSE model for sequence evolution, and identify sensor-specific regions in the denitrifying betaproteobacterium Aromatoleum aromaticum.

  16. Phase ambiguity of the threshold amplitude in pp->pppi{sup 0}

    SciTech Connect

    Ramachandran, G.; Padmanabha, G.; Thomas, Sujith

    2010-06-15

    Measurements of spin observables in pp->p-vectorp-vectorpi{sup 0} are suggested to remove the phase ambiguity of the threshold amplitude. The suggested measurements complement the Indiana University Cyclotron Facility data on p-vectorp-vector->pppi{sup 0} to completely determine all the 12 partial wave amplitudes taken into consideration by Meyer et al. [Phys. Rev. C 63, 064002 (2001)] and Deepak et al. [Phys. Rev. C 72, 024004 (2005)].

  17. Whole-Genome Sequence of Rummeliibacillus stabekisii Strain PP9 Isolated from Antarctic Soil

    PubMed Central

    da Mota, Fábio Faria; Vollú, Renata Estebanez; Jurelevicius, Diogo

    2016-01-01

    The whole genome of Rummeliibacillus stabekisii PP9, isolated from a soil sample from Antarctica, consists of a circular chromosome of 3,412,092 bp and a circular plasmid of 8,647 bp, with 3,244 protein-coding genes, 12 copies of the 16S-23S-5S rRNA operon, 101 tRNA genes, and 6 noncoding RNAs (ncRNAs). PMID:27231360

  18. P(P bar)P elastic scattering and cosmic ray data

    NASA Technical Reports Server (NTRS)

    FAZAL-E-ALEEM; Saleem, M.

    1985-01-01

    It is shown that the total cross section for pp elastic scattering at cosmic ray energies, as well as the total cross section, the slope parameter b(s,t) and the differential cross section for small momentum transfer at ISR and collider energies for p(p)p elastic scattering can be simultaneously fitted by using a simple Regge pole model. The results of this theory is discussed in detail.

  19. Dijet azimuthal decorrelations in pp collisions at √s=7 TeV.

    PubMed

    Khachatryan, V; Sirunyan, A M; Tumasyan, A; Adam, W; Bergauer, T; Dragicevic, M; Erö, J; Fabjan, C; Friedl, M; Frühwirth, R; Ghete, V M; Hammer, J; Hänsel, S; Hartl, C; Hoch, M; Hörmann, N; Hrubec, J; Jeitler, M; Kasieczka, G; Kiesenhofer, W; Krammer, M; Liko, D; Mikulec, I; Pernicka, M; Rohringer, H; Schöfbeck, R; Strauss, J; Taurok, A; Teischinger, F; Wagner, P; Waltenberger, W; Walzel, G; Widl, E; Wulz, C-E; Mossolov, V; Shumeiko, N; Suarez Gonzalez, J; Benucci, L; Cerny, K; De Wolf, E A; Janssen, X; Maes, T; Mucibello, L; Ochesanu, S; Roland, B; Rougny, R; Selvaggi, M; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Beauceron, S; Blekman, F; Blyweert, S; D'Hondt, J; Devroede, O; Gonzalez Suarez, R; Kalogeropoulos, A; Maes, J; Maes, M; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Onsem, G P; Villella, I; Charaf, O; Clerbaux, B; De Lentdecker, G; Dero, V; Gay, A P R; Hammad, G H; Hreus, T; Marage, P E; Thomas, L; Vander Velde, C; Vanlaer, P; Wickens, J; Adler, V; Costantini, S; Grunewald, M; Klein, B; Marinov, A; Mccartin, J; Ryckbosch, D; Thyssen, F; Tytgat, M; Vanelderen, L; Verwilligen, P; Walsh, S; Zaganidis, N; Basegmez, S; Bruno, G; Caudron, J; Ceard, L; De Favereau De Jeneret, J; Delaere, C; Demin, P; Favart, D; Giammanco, A; Grégoire, G; Hollar, J; Lemaitre, V; Liao, J; Militaru, O; Ovyn, S; Pagano, D; Pin, A; Piotrzkowski, K; Schul, N; Beliy, N; Caebergs, T; Daubie, E; Alves, G A; De Jesus Damiao, D; Pol, M E; Souza, M H G; Carvalho, W; Da Costa, E M; De Oliveira Martins, C; Fonseca De Souza, S; Mundim, L; Nogima, H; Oguri, V; Prado Da Silva, W L; Santoro, A; Silva Do Amaral, S M; Sznajder, A; Dias, F A; Dias, M A F; Fernandez Perez Tomei, T R; Gregores, E M; Marinho, F; Novaes, S F; Padula, Sandra S; Darmenov, N; Dimitrov, L; Genchev, V; Iaydjiev, P; Piperov, S; Rodozov, M; Stoykova, S; Sultanov, G; Tcholakov, V; Trayanov, R; Vankov, I; Dyulendarova, M; Hadjiiska, R; Kozhuharov, V; Litov, L; Marinova, E; Mateev, M; Pavlov, B; Petkov, P; Bian, J G; Chen, G M; 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Koay, S A; Kovalskyi, D; Krutelyov, V; Lowette, S; McColl, N; Pavlunin, V; Rebassoo, F; Ribnik, J; Richman, J; Rossin, R; Stuart, D; To, W; Vlimant, J R; Bornheim, A; Bunn, J; Chen, Y; Gataullin, M; Kcira, D; Litvine, V; Ma, Y; Mott, A; Newman, H B; Rogan, C; Timciuc, V; Traczyk, P; Veverka, J; Wilkinson, R; Yang, Y; Zhu, R Y; Akgun, B; Carroll, R; Ferguson, T; Iiyama, Y; Jang, D W; Jun, S Y; Liu, Y F; Paulini, M; Russ, J; Terentyev, N; Vogel, H; Vorobiev, I; Cumalat, J P; Dinardo, M E; Drell, B R; Edelmaier, C J; Ford, W T; Gaz, A; Heyburn, B; Luiggi Lopez, E; Nauenberg, U; Smith, J G; Stenson, K; Ulmer, K A; Wagner, S R; Zang, S L; Agostino, L; Alexander, J; Chatterjee, A; Das, S; Eggert, N; Fields, L J; Gibbons, L K; Heltsley, B; Hopkins, W; Khukhunaishvili, A; Kreis, B; Kuznetsov, V; Kaufman, G Nicolas; Patterson, J R; Puigh, D; Riley, D; Ryd, A; Shi, X; Sun, W; Teo, W D; Thom, J; Thompson, J; Vaughan, J; Weng, Y; Winstrom, L; Wittich, P; Biselli, A; Cirino, G; Winn, D; Abdullin, S; Albrow, M; Anderson, J; Apollinari, G; Atac, M; Bakken, J A; Banerjee, S; Bauerdick, L A T; Beretvas, A; Berryhill, J; Bhat, P C; Bloch, I; Borcherding, F; Burkett, K; Butler, J N; Chetluru, V; Cheung, H W K; Chlebana, F; Cihangir, S; Demarteau, M; Eartly, D P; Elvira, V D; Esen, S; Fisk, I; Freeman, J; Gao, Y; Gottschalk, E; Green, D; Gunthoti, K; Gutsche, O; Hahn, A; Hanlon, J; Harris, R M; Hirschauer, J; Hooberman, B; James, E; Jensen, H; Johnson, M; Joshi, U; Khatiwada, R; Kilminster, B; Klima, B; Kousouris, K; Kunori, S; Kwan, S; Leonidopoulos, C; Limon, P; Lipton, R; Lykken, J; Maeshima, K; Marraffino, J M; Mason, D; McBride, P; McCauley, T; Miao, T; Mishra, K; Mrenna, S; Musienko, Y; Newman-Holmes, C; O'Dell, V; Popescu, S; Pordes, R; Prokofyev, O; Saoulidou, N; Sexton-Kennedy, E; Sharma, S; Soha, A; Spalding, W J; Spiegel, L; Tan, P; Taylor, L; Tkaczyk, S; Uplegger, L; Vaandering, E W; Vidal, R; Whitmore, J; Wu, W; Yang, F; Yumiceva, F; Yun, J C; Acosta, D; Avery, P; Bourilkov, D; Chen, M; Di Giovanni, G P; Dobur, D; Drozdetskiy, A; Field, R D; Fisher, M; Fu, Y; Furic, I K; Gartner, J; Goldberg, S; Kim, B; Klimenko, S; Konigsberg, J; Korytov, A; Kropivnitskaya, A; Kypreos, T; Matchev, K; Mitselmakher, G; Muniz, L; Pakhotin, Y; Prescott, C; Remington, R; Schmitt, M; Scurlock, B; Sellers, P; Skhirtladze, N; Wang, D; Yelton, J; Zakaria, M; Ceron, C; Gaultney, V; Kramer, L; Lebolo, L M; Linn, S; Markowitz, P; Martinez, G; Rodriguez, J L; Adams, T; Askew, A; Bandurin, D; Bochenek, J; Chen, J; Diamond, B; Gleyzer, S V; Haas, J; Hagopian, S; Hagopian, V; Jenkins, M; Johnson, K F; Prosper, H; Quertenmont, L; Sekmen, S; Veeraraghavan, V; Baarmand, M M; Dorney, B; Guragain, S; Hohlmann, M; Kalakhety, H; Ralich, R; Vodopiyanov, I; Adams, M R; Anghel, I M; Apanasevich, L; Bai, Y; Bazterra, V E; Betts, R R; Callner, J; Cavanaugh, R; Dragoiu, C; Garcia-Solis, E J; Gauthier, L; Gerber, C E; Hofman, D J; Khalatyan, S; Lacroix, F; Malek, M; O'Brien, C; Silvestre, C; Smoron, A; Strom, D; Varelas, N; Akgun, U; Albayrak, E A; Bilki, B; Cankocak, K; Clarida, W; Duru, F; Lae, C K; McCliment, E; Merlo, J-P; Mermerkaya, H; Mestvirishvili, A; Moeller, A; Nachtman, J; Newsom, C R; Norbeck, E; Olson, J; Onel, Y; Ozok, F; Sen, S; Wetzel, J; Yetkin, T; Yi, K; Barnett, B A; Blumenfeld, B; Bonato, A; Eskew, C; Fehling, D; Giurgiu, G; Gritsan, A V; Guo, Z J; Hu, G; Maksimovic, P; Rappoccio, S; Swartz, M; Tran, N V; Whitbeck, A; Baringer, P; Bean, A; Benelli, G; Grachov, O; Murray, M; Noonan, D; Radicci, V; Sanders, S; Wood, J S; Zhukova, V; Bolton, T; Chakaberia, I; Ivanov, A; Makouski, M; Maravin, Y; Shrestha, S; Svintradze, I; Wan, Z; Gronberg, J; Lange, D; Wright, D; Baden, A; Boutemeur, M; Eno, S C; Ferencek, D; Gomez, J A; Hadley, N J; Kellogg, R G; Kirn, M; Lu, Y; Mignerey, A C; Rossato, K; Rumerio, P; Santanastasio, F; Skuja, A; Temple, J; Tonjes, M B; Tonwar, S C; Twedt, E; Alver, B; Bauer, G; Bendavid, J; Busza, W; Butz, E; Cali, I A; Chan, M; Dutta, V; Everaerts, P; Gomez Ceballos, G; Goncharov, M; Hahn, K A; Harris, P; Kim, Y; Klute, M; Lee, Y-J; Li, W; Loizides, C; Luckey, P D; Ma, T; Nahn, S; Paus, C; Ralph, D; Roland, C; Roland, G; Rudolph, M; Stephans, G S F; Sumorok, K; Sung, K; Wenger, E A; Xie, S; Yang, M; Yilmaz, Y; Yoon, A S; Zanetti, M; Cole, P; Cooper, S I; Cushman, P; Dahmes, B; De Benedetti, A; Dudero, P R; Franzoni, G; Haupt, J; Klapoetke, K; Kubota, Y; Mans, J; Rekovic, V; Rusack, R; Sasseville, M; Singovsky, A; Cremaldi, L M; Godang, R; Kroeger, R; Perera, L; Rahmat, R; Sanders, D A; Summers, D; Bloom, K; Bose, S; Butt, J; Claes, D R; Dominguez, A; Eads, M; Keller, J; Kelly, T; Kravchenko, I; Lazo-Flores, J; Lundstedt, C; Malbouisson, H; Malik, S; Snow, G R; Baur, U; Godshalk, A; Iashvili, I; Jain, S; Kharchilava, A; Kumar, A; Shipkowski, S P; Smith, K; Alverson, G; Barberis, E; Baumgartel, D; Boeriu, O; Chasco, M; Reucroft, S; Swain, J; Wood, D; Zhang, J; Anastassov, A; Kubik, A; Odell, N; Ofierzynski, R A; Pollack, B; Pozdnyakov, A; Schmitt, M; Stoynev, S; Velasco, M; Won, S; Antonelli, L; Berry, D; Hildreth, M; Jessop, C; Karmgard, D J; Kolb, J; Kolberg, T; Lannon, K; Luo, W; Lynch, S; Marinelli, N; Morse, D M; Pearson, T; Ruchti, R; Slaunwhite, J; Valls, N; Warchol, J; Wayne, M; Ziegler, J; Bylsma, B; Durkin, L S; Gu, J; Hill, C; Killewald, P; Kotov, K; Ling, T Y; Rodenburg, M; Williams, G; Adam, N; Berry, E; Elmer, P; Gerbaudo, D; Halyo, V; Hebda, P; Hunt, A; Jones, J; Laird, E; Lopes Pegna, D; Marlow, D; Medvedeva, T; Mooney, M; Olsen, J; Piroué, P; Quan, X; Saka, H; Stickland, D; Tully, C; Werner, J S; Zuranski, A; Acosta, J G; Huang, X T; Lopez, A; Mendez, H; Oliveros, S; Ramirez Vargas, J E; Zatserklyaniy, A; Alagoz, E; Barnes, V E; Bolla, G; Borrello, L; Bortoletto, D; Everett, A; Garfinkel, A F; Gecse, Z; Gutay, L; Hu, Z; Jones, M; Koybasi, O; Laasanen, A T; Leonardo, N; Liu, C; Maroussov, V; Merkel, P; Miller, D H; Neumeister, N; Shipsey, I; Silvers, D; Svyatkovskiy, A; Yoo, H D; Zablocki, J; Zheng, Y; Jindal, P; Parashar, N; Boulahouache, C; Cuplov, V; Ecklund, K M; Geurts, F J M; Liu, J H; Padley, B P; Redjimi, R; Roberts, J; Zabel, J; Betchart, B; Bodek, A; Chung, Y S; Covarelli, R; de Barbaro, P; Demina, R; Eshaq, Y; Flacher, H; Garcia-Bellido, A; Goldenzweig, P; Gotra, Y; Han, J; Harel, A; Miner, D C; Orbaker, D; Petrillo, G; Vishnevskiy, D; Zielinski, M; Bhatti, A; Ciesielski, R; Demortier, L; Goulianos, K; Lungu, G; Mesropian, C; Yan, M; Atramentov, O; Barker, A; Duggan, D; Gershtein, Y; Gray, R; Halkiadakis, E; Hidas, D; Hits, D; Lath, A; Panwalkar, S; Patel, R; Richards, A; Rose, K; Schnetzer, S; Somalwar, S; Stone, R; Thomas, S; Cerizza, G; Hollingsworth, M; Spanier, S; Yang, Z C; York, A; Asaadi, J; Eusebi, R; Gilmore, J; Gurrola, A; Kamon, T; Khotilovich, V; Montalvo, R; Nguyen, C N; Osipenkov, I; Pivarski, J; Safonov, A; Sengupta, S; Tatarinov, A; Toback, D; Weinberger, M; Akchurin, N; Bardak, C; Damgov, J; Jeong, C; Kovitanggoon, K; Lee, S W; Mane, P; Roh, Y; Sill, A; Volobouev, I; Wigmans, R; Yazgan, E; Appelt, E; Brownson, E; Engh, D; Florez, C; Gabella, W; Johns, W; Kurt, P; Maguire, C; Melo, A; Sheldon, P; Velkovska, J; Arenton, M W; Balazs, M; Boutle, S; Buehler, M; Conetti, S; Cox, B; Francis, B; Hirosky, R; Ledovskoy, A; Lin, C; Neu, C; Yohay, R; Gollapinni, S; Harr, R; Karchin, P E; Lamichhane, P; Mattson, M; Milstène, C; Sakharov, A; Anderson, M; Bachtis, M; Bellinger, J N; Carlsmith, D; Dasu, S; Efron, J; Gray, L; Grogg, K S; Grothe, M; Hall-Wilton, R; Herndon, M; Klabbers, P; Klukas, J; Lanaro, A; Lazaridis, C; Leonard, J; Loveless, R; Mohapatra, A; Reeder, D; Ross, I; Savin, A; Smith, W H; Swanson, J; Weinberg, M

    2011-03-25

    Measurements of dijet azimuthal decorrelations in pp collisions at √s=7 TeV using the CMS detector at the CERN LHC are presented. The analysis is based on an inclusive dijet event sample corresponding to an integrated luminosity of 2.9 pb⁻¹. The results are compared to predictions from perturbative QCD calculations and various Monte Carlo event generators. The dijet azimuthal distributions are found to be sensitive to initial-state gluon radiation.

  20. Dijet Azimuthal Decorrelations in pp Collisions at sqrt(s) = 7 TeV

    SciTech Connect

    Khachatryan, Vardan; et al.

    2011-03-01

    Measurements of dijet azimuthal decorrelations in pp collisions at sqrt(s) = 7 TeV using the CMS detector at the CERN LHC are presented. The analysis is based on an inclusive dijet event sample corresponding to an integrated luminosity of 2.9 inverse picobarns. The results are compared to predictions from perturbative QCD calculations and various Monte Carlo event generators. The dijet azimuthal distributions are found to be sensitive to initial-state gluon radiation.

  1. Bose-Einstein correlations in pp and PbPb collisions with ALICE at the LHC

    ScienceCinema

    None

    2016-07-12

    We report on the results of identical pion femtoscopy at the LHC. The Bose-Einstein correlation analysis was performed on the large-statistics ALICE p+p at sqrt{s}= 0.9 TeV and 7 TeV datasets collected during 2010 LHC running and the first Pb+Pb dataset at sqrt{s_NN}= 2.76 TeV. Detailed pion femtoscopy studies in heavy-ion collisions have shown that emission region sizes ("HBT radii") decrease with increasing pair momentum, which is understood as a manifestation of the collective behavior of matter. 3D radii were also found to universally scale with event multiplicity. In p+p collisions at 7 TeV one measures multiplicities which are comparable with those registered in peripheral AuAu and CuCu collisions at RHIC, so direct comparisons and tests of scaling laws are now possible. We show the results of double-differential 3D pion HBT analysis, as a function of multiplicity and pair momentum. The results for two collision energies are compared to results obtained in the heavy-ion collisions at similar multiplicity and p+p collisions at lower energy. We identify the relevant scaling variables for the femtoscopic radii and discuss the similarities and differences to results from heavy-ions. The observed trends give insight into the soft particle production mechanism in p+p collisions and suggest that a self-interacting collective system may be created in sufficiently high multiplicity events. First results for the central Pb+Pb collisions are also shown. A significant increase of the reaction zone volume and lifetime in comparison to RHIC is observed. Signatures of collective hydrodynamics-like behavior of the system are also apparent, and are compared to model predictions.

  2. Exotic baryon searches in 800 GeV/c pp {yields} pX

    SciTech Connect

    Reyes, M. A.; Felix, J.; Lopez, E.; Moreno, G.; Perez, I. O.; Sosa, M.; Christian, D. C.; Gottschalk, E. E.; Gutierrez, G.; Wang, M. H. L. S.; Wehmann, A.; Hartouni, E. P.; Knapp, B. C.; Kreisler, M. N.

    2006-02-11

    We report the results of the search for the pentaquark candidates {theta}(1540) and {xi}(1862) using data from Fermilab experiment E690 in the reaction pp {yields} pX at 800 GeV/c. We find no evidence for narrow baryon resonances near 1862 MeV decaying to {xi}{pi}. Also, we find no evidence of a narrow resonance near 1540 MeV decaying to pK{sub s}{sup 0}.

  3. Analysis techniques for the {Lambda}(1405) in p+p reactions

    SciTech Connect

    Siebenson, Johannes

    2010-12-28

    We present an analysis of the {Lambda}(1405){yields}{Sigma}{sup {+-}}{pi}{sup {+-}} decay in p+p reactions at 3.5 GeV kinetic beam energy. The data were taken with the High Acceptance Di-Electron Spectrometer (HADES). The extraction of the {Lambda}(1405) signal was achieved by an effective background suppression combined with a quantitatively precise determination and identification of the remaining background sources. The different techniques, used for this analysis, are presented in this work.

  4. A comparative study of thermal and mechanical stabilities of gamma irradiated PMMA, PP and PVC

    NASA Astrophysics Data System (ADS)

    Güven, O.; Uzun, C.

    1993-10-01

    In this comparative study it has been tried to find a correlation between the thermal and mechanical stabilities of some γ-irradiated polymers. Among various mechanical properties evaluated, the best correlation was found between the toughness (energy to break point) and the time required for 10% weight loss (isothermally). Among three polymers irradiated up to 100 kGy in the form of thin films, the best fit was observed to be for PMMA while PVC and PP has shown poorer correlation.

  5. Bose-Einstein correlations in pp and PbPb collisions with ALICE at the LHC

    SciTech Connect

    2011-02-15

    We report on the results of identical pion femtoscopy at the LHC. The Bose-Einstein correlation analysis was performed on the large-statistics ALICE p+p at sqrt{s}= 0.9 TeV and 7 TeV datasets collected during 2010 LHC running and the first Pb+Pb dataset at sqrt{s_NN}= 2.76 TeV. Detailed pion femtoscopy studies in heavy-ion collisions have shown that emission region sizes ("HBT radii") decrease with increasing pair momentum, which is understood as a manifestation of the collective behavior of matter. 3D radii were also found to universally scale with event multiplicity. In p+p collisions at 7 TeV one measures multiplicities which are comparable with those registered in peripheral AuAu and CuCu collisions at RHIC, so direct comparisons and tests of scaling laws are now possible. We show the results of double-differential 3D pion HBT analysis, as a function of multiplicity and pair momentum. The results for two collision energies are compared to results obtained in the heavy-ion collisions at similar multiplicity and p+p collisions at lower energy. We identify the relevant scaling variables for the femtoscopic radii and discuss the similarities and differences to results from heavy-ions. The observed trends give insight into the soft particle production mechanism in p+p collisions and suggest that a self-interacting collective system may be created in sufficiently high multiplicity events. First results for the central Pb+Pb collisions are also shown. A significant increase of the reaction zone volume and lifetime in comparison to RHIC is observed. Signatures of collective hydrodynamics-like behavior of the system are also apparent, and are compared to model predictions.

  6. Direct experimental reconstruction of the pp elastic scattering matrix at 579 MeV

    SciTech Connect

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

    1981-04-20

    We have made, for the first time, a direct reconstruction of the pp elastic scattering matrix at 579 MeV from a series of experiments performed with a polarized beam line. Fifteen observables consisting of the polarization, two-spin correlation and transfer parameters, and three-spin parameters were measured at seven angles between 66/sup 0/ and 90/sup 0/ center of mass. The experimental results and reconstructed amplitudes are presented and compared to a phase-shift analysis.

  7. Global Regulation by (p)ppGpp and CodY in Streptococcus mutans▿ †

    PubMed Central

    Lemos, José A.; Nascimento, Marcelle M.; Lin, Vanessa K.; Abranches, Jacqueline; Burne, Robert A.

    2008-01-01

    The RelA, RelP, and RelQ enzymes are responsible for the production of the alarmone (p)ppGpp in Streptococcus mutans. A strain lacking all three synthetases (ΔrelAPQ) does not grow in minimal medium lacking the branched-chain amino acids (BCAA) leucine or valine but grows well if isoleucine is also omitted. Here, we investigated whether there was a correlation between growth in the absence of leucine and valine with (p)ppGpp pools and the activation of CodY. By using a combination of single, double, and triple mutants lacking the (p)ppGpp synthetase enzymes, we demonstrated that the ability to grow in the absence of leucine or valine required basal levels of (p)ppGpp production by RelP and RelQ. The introduction of a codY mutation into the ΔrelAPQ strain fully restored growth in medium lacking leucine or valine, revealing that the growth-defective phenotype of ΔrelAPQ was directly linked to CodY. Lowering GTP levels through the addition of decoyinine did not alleviate CodY repression or affect the expression of genes involved in BCAA biosynthesis, suggesting that S. mutans CodY is not activated by GTP. The results of phenotypic studies revealed that the codY mutant had a reduced capacity to form biofilms and that its growth was more sensitive to low pH, showing a role for CodY in two key virulence properties of S. mutans. Microarray results revealed the extent of the CodY regulon. Notably, the identification of putative CodY-binding boxes upstream of genes that were downregulated in the codY mutant indicates that CodY may also function as a transcriptional activator in S. mutans. PMID:18539745

  8. Measurement of the forward energy flow in pp collisions at [Formula: see text].

    PubMed

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Bursche, A; Buytaert, J; Cadeddu, S; Callot, O; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carranza-Mejia, H; Carson, L; Carvalho Akiba, K; Casse, G; Cattaneo, M; Cauet, Ch; Charles, M; Charpentier, Ph; Chen, P; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coca, C; Coco, V; Cogan, J; Cogneras, E; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Corti, G; Couturier, B; Cowan, G A; Craik, D C; Cunliffe, S; Currie, R; D'Ambrosio, C; David, P; David, P N Y; De Bonis, I; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Simone, P; Decamp, D; Deckenhoff, M; Degaudenzi, H; Del Buono, L; Deplano, C; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dickens, J; Dijkstra, H; Diniz Batista, P; Dogaru, M; Domingo Bonal, F; Donleavy, S; Dordei, F; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dupertuis, F; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; van Eijk, D; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Elsby, D; Falabella, A; Färber, C; Fardell, G; Farinelli, C; Farry, S; Fave, V; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fitzpatrick, C; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Furcas, S; Gallas Torreira, A; Galli, D; Gandelman, M; Gandini, P; Gao, Y; Garnier, J-C; Garofoli, J; Garosi, P; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gibson, V; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gordon, H; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hampson, T; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; Harrison, P F; Hartmann, T; He, J; Heijne, V; Hennessy, K; Henrard, P; Hernando Morata, J A; van Herwijnen, E; Hicks, E; Hill, D; Hoballah, M; Hopchev, P; Hulsbergen, W; Hunt, P; Huse, T; Hussain, N; Hutchcroft, D; Hynds, D; Iakovenko, V; Ilten, P; Imong, J; Jacobsson, R; Jaeger, A; Jahjah Hussein, M; Jans, E; Jansen, F; Jaton, P; Jean-Marie, B; Jing, F; John, M; Johnson, D; Jones, C R; Jost, B; Kaballo, M; Kandybei, S; Karacson, M; Karbach, T M; Kenyon, I R; Kerzel, U; Ketel, T; Keune, A; Khanji, B; Kim, Y M; Kochebina, O; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucharczyk, M; Kudryavtsev, V; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanciotti, E; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Leroy, O; Li, Y; Li Gioi, L; Liles, M; Lindner, R; Linn, C; Liu, B; Liu, G; von Loeben, J; Lopes, J H; Lopez Asamar, E; Lopez-March, N; Lu, H; Luisier, J; Luo, H; Mac Raighne, A; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Manca, G; Mancinelli, G; Mangiafave, N; Marconi, U; Märki, R; Marks, J; Martellotti, G; Martens, A; Martin, L; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martins Tostes, D; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Matveev, M; Maurice, E; Mazurov, A; McCarthy, J; McGregor, G; McNulty, R; Meier, F; Meissner, M; Merk, M; Merkel, J; Milanes, D A; Minard, M-N; Molina Rodriguez, J; Monteil, S; Moran, D; Morawski, P; Mountain, R; Mous, I; Muheim, F; Müller, K; Muresan, R; Muryn, B; Muster, B; Mylroie-Smith, J; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neufeld, N; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Nomerotski, A; Novoselov, A; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Orlandea, M; Otalora Goicochea, J M; Owen, P; Pal, B K; Palano, A; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrick, G N; Patrignani, C; Pavel-Nicorescu, C; Pazos Alvarez, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perego, D L; Perez Trigo, E; Pérez-Calero Yzquierdo, A; Perret, P; Perrin-Terrin, M; Pessina, G; Petridis, K; Petrolini, A; Phan, A; Picatoste Olloqui, E; Pie Valls, B; Pietrzyk, B; Pilař, T; Pinci, D; Playfer, S; Plo Casasus, M; Polci, F; Polok, G; Poluektov, A; Polycarpo, E; Popov, D; Popovici, B; Potterat, C; Powell, A; Prisciandaro, J; Pugatch, V; Puig Navarro, A; Qian, W; Rademacker, J H; Rakotomiaramanana, B; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Redford, S; Reid, M M; Dos Reis, A C; Ricciardi, S; Richards, A; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Rodrigues, E; Rodriguez Perez, P; Rogers, G J; Roiser, S; Romanovsky, V; Romero Vidal, A; Rouvinet, J; Ruf, T; Ruiz, H; Sabatino, G; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salzmann, C; Sanmartin Sedes, B; Sannino, M; Santacesaria, R; Santamarina Rios, C; Santinelli, R; Santovetti, E; Sapunov, M; Sarti, A; Satriano, C; Satta, A; Savrie, M; Savrina, D; Schaack, P; Schiller, M; Schindler, H; Schleich, S; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Senderowska, K; Sepp, I; Serra, N; Serrano, J; Seyfert, P; Shapkin, M; Shapoval, I; Shatalov, P; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, O; Shevchenko, V; Shires, A; Silva Coutinho, R; Skwarnicki, T; Smith, N A; Smith, E; Smith, M; Sobczak, K; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Stagni, F; Stahl, S; Steinkamp, O; Stoica, S; Stone, S; Storaci, B; Straticiuc, M; Straumann, U; Subbiah, V K; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szumlak, T; T'Jampens, S; Teklishyn, M; Teodorescu, E; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Urner, D; Uwer, U; Vagnoni, V; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Videau, I; Vieira, D; Vilasis-Cardona, X; Visniakov, J; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; Waldi, R; Wallace, R; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Webber, A D; Websdale, D; Whitehead, M; Wicht, J; Wiedner, D; Wiggers, L; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wishahi, J; Witek, M; Witzeling, W; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, F; Xing, Z; Yang, Z; Young, R; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, F; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

    The energy flow created in pp collisions at [Formula: see text] is studied within the pseudorapidity range 1.9<η<4.9 with data collected by the LHCb experiment. The measurements are performed for inclusive minimum-bias interactions, hard scattering processes and events with an enhanced or suppressed diffractive contribution. The results are compared to predictions given by Pythia-based and cosmic-ray event generators, which provide different models of soft hadronic interactions.

  9. On the potential role of the Collins effect in A_N in pp --> pion X

    SciTech Connect

    Anselmino, Mauro; Boglione, Mariaelena; D'Alesio, Umberto; Leader, Elliot; Melis, Stefano; Murgia, Francesco; Prokudin, Alexey

    2013-10-01

    Transverse single spin asymmetries in pp --> pion X processes, while on a quite firm ground experimentally, are still a much debated phenomenological issue. We consider them in a transverse momentum dependent factorization scheme. After revisiting a previous result, we give new estimates of the Collins contribution by adopting the latest information on the Collins and transversity functions, as extracted from SIDIS and e+e- data.

  10. Generalized parton distributions and rapidity gap survival in exclusive diffractive pp scattering

    SciTech Connect

    Frankfurt, L.; Hyde, C. E.; Strikman, M.; Weiss, C.

    2007-03-01

    We study rapidity gap survival (RGS) in the production of high-mass systems (H=dijet, heavy quarkonium, Higgs boson) in double-gap exclusive diffractive pp scattering, pp{yields}p+(gap)+H+(gap)+p. Our approach is based on the idea that hard and soft interactions are approximately independent because they proceed over widely different time and distance scales. We implement this idea in a partonic description of proton structure, which allows for a model-independent treatment of the interplay of hard and soft interactions. The high-mass system is produced in a hard scattering process with exchange of two gluons between the protons, whose amplitude is calculable in terms of the gluon generalized parton distribution (GPD), measured in exclusive ep scattering. The hard scattering process is modified by soft spectator interactions, which we calculate neglecting correlations between hard and soft interactions (independent interaction approximation). We obtain an analytic expression for the RGS probability in terms of the phenomenological pp elastic scattering amplitude, without reference to the eikonal approximation. Contributions from inelastic intermediate states are suppressed. The onset of the black-disk limit in pp scattering at TeV energies strongly suppresses diffraction at small impact parameters and is the main factor in determining the RGS probability. Correlations between hard and soft interactions (e.g. due to scattering from the long-range pion field of the proton or due to possible short-range transverse correlations between partons) further decrease the RGS probability. We also investigate the dependence of the diffractive cross section on the transverse momenta of the final-state protons ('diffraction pattern'). By measuring this dependence one can perform detailed tests of the interplay of hard and soft interactions and even extract information about the gluon GPD in the proton. Such studies appear to be feasible with the planned forward detectors at the

  11. Bio-composites fabricated by sandwiching sisal fibers with polypropylene (PP)

    NASA Astrophysics Data System (ADS)

    Sosiati, H.; Nahyudin, A.; Fauzi, I.; Wijayanti, D. A.; Triyana, K.

    2016-04-01

    Sisal fibers reinforced polypropylene (PP) composites were successfully fabricated using sandwiching sisal fibers with PP sheets. The ratio of fiber and polymer matrix was 50:50 (wt. %). Untreated short and long sisal fibers, and alkali treated short sisal fibers in 6% NaOH at 100°C for 1 and 3 h were used as reinforcement or fillers. A small amount (3 wt. %) of maleic anhydride grafted polypropylene (MAPP) was added as a coupling agent. Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were used to characterize the surface morphology and chemical composition of the fibers, respectively. Flexural test of sisal/PP composites was done according to ASTM D 790-02. The results showed that flexural strength of untreated long fiber reinforced composite is much higher than that of the untreated and alkali treated short fibers reinforced composites with and without the addition of MAPP. Alkalization related to fiber surface modification, fiber length/fiber orientation and a composite fabrication technique are important factors in contributing to the fiber distribution within the matrix, the bonding between the fiber and the matrix and the enhancement of flexural strength of the bio-composite.

  12. Nanoparticles dispersion in processing functionalised PP/TiO2 nanocomposites: distribution and properties

    NASA Astrophysics Data System (ADS)

    El-Dessouky, Hassan M.; Lawrence, Carl A.

    2011-03-01

    Future innovations in textiles and fibrous materials are likely to demand fibres with enhanced multifunctionality. The fibres can be functionalized by dispersing nanoadditives into the polymer during melt compounding/spinning. TiO2 nanoparticles have the potential to improve UV resistance, antistatic, as well as impart self-cleaning by photocatalysis and thereby de-odour and antimicrobial effects. In this study, a micro-lab twin-screw extruder was used to produce samples of polypropylene (PP) nanocomposite monofilaments, doped with nano titanium oxide (TiO2)/manganese oxide (MnO) compound having size ranging from 60 to 200 nm. As a control sample, PP filaments without additives were also extruded. Three samples were produced containing different concentrations (wt%) of the TiO2 compound, i.e. 0.95, 1.24 and 1.79%. Nano metal-oxide distribution in the as-spun and drawn nanocomposite filaments was analysed. Although, there are small clusters of the nanoparticles, the characterizing techniques showed good dispersion and distribution of the modified TiO2 along and across the processed filaments. From UV spectroscopy and TGA, a significant enhancement of polypropylene UV protection and thermal stability were observed: PP with higher percentage of TiO2 absorbed UV wavelength of 387 nm and thermally decomposed at 320.16 °C accompanied by 95% weight loss.

  13. Predicting minimum-bias trigger-associated dijet correlations in p-p collisions

    NASA Astrophysics Data System (ADS)

    Trainor, Thomas A.

    2015-08-01

    A method is derived to predict the structure of dijet-related hard components of trigger-associated (TA) hadron correlations from p-p collisions based on measured fragmentation functions (FFs) from {e}+-{e}- or p-\\bar{p} collisions and a minimum-bias (MB) jet or scattered-parton spectrum from p-\\bar{p} collisions. The method is based on the probability chain rule and Bayes’ theorem and relates a trigger-parton-associated-fragment system from reconstructed dijets to a trigger-hadron-associated hadron system from p-p data. The method is tested in this study by comparisons of FF TA structure with preliminary p-p TA data but can also be applied to p-A, d-A and A-A collisions over a range of energies. Quantitative comparisons of measured TA correlations with FF-derived predictions may confirm a quantum chromodynamics MB dijet mechanism for certain spectrum and correlation structures whose origins are currently questioned and have been attributed by some to collective expansion (flows).

  14. DSC study of the isothermal crystallization of iPP-CNF nanocomposites

    NASA Astrophysics Data System (ADS)

    Chipara, Dorina M.; Chipara, Mircea

    2013-03-01

    Nanocomposite materials have been obtained by dispersing vapor grown carbon nanofibers (VGCNFs) with diameters ranging between 60 and 100 nm and lengths between 30,000 and 100,000 nm supplied by Pyrograf Products, Inc (PR-24AG) within a polymer matrix - isotactic polypropylene (iPP) - type Marlex HLN-120-01 with density 0.906 g/cm3 and melt flow rate at 230 oC of 12 g/10 min, supplied by Philips Sumika Polypropylene Company. VGCNFs have been purified and disentangled by reflux in dichloromethane and deionized water followed by vacuum filtering (for 24 h) and drying at 110 oC for 24h. The nanocomposites were obtained by melt mixing at 180 oC for 9 minutes with a speed of 65 rpm followed by an additional mixing at 90 rpm for 5 minutes, using a HAAKE Rheomix, Nanocomposites loaded with various amounts of VGCNFs (0%, 1%, 2.5%, 5%, 7.5%, 10%, 15%, and 20% wt.) have been prepared and investigated by TA DSC Q-500. Isothermal crystallization was investigated in detail and analyzed by using an expression derived from the Avrami equation. The effect of the filler on the isothermal crystallization of iPP is discussed in detail. The research is focused on the effect of VGCNF on the degree of crystallization of iPP, crystallization rate, and dimensionality of the crystallization process. This research has been supported by National Science Foundation under DMR. Contract grant number 0934157.

  15. Study of J/ψ→pp̄ and J/ψ→nn̄

    DOE PAGES

    Ablikim, M.; Achasov, M. N.; Ambrose, D. J.; ...

    2012-08-31

    The decays J/ψ→pp̄ and J/ψ→nn̄ have been investigated with a sample of 225.2×10⁶ J/ψ events collected with the BESIII detector at the BEPCII e⁺e⁻ collider. The branching fractions are determined to be B(J/ψ→pp̄)=(2.112±0.004±0.031)×10⁻³ and B(J/ψ→nn̄)=(2.07±0.01±0.17)×10⁻³. Distributions of the angle θ between the proton or antineutron and the beam direction are well described by the form 1+αcos²θ, and we find α=0.595±0.012±0.015 for J/ψ→pp̄ and α=0.50±0.04±0.21 for J/ψ→nn̄. Our branching-fraction results suggest a large phase angle between the strong and electromagnetic amplitudes describing the J/ψ→NN¯¯¯ decay.

  16. The HAB1 PP2C is inhibited by ABA-dependent PYL10 interaction.

    PubMed

    Li, Juan; Shi, Chaowei; Sun, Demeng; He, Yao; Lai, Chaohua; Lv, Pei; Xiong, Ying; Zhang, Longhua; Wu, Fangming; Tian, Changlin

    2015-06-05

    PYL10 is a monomeric abscisic acid (ABA) receptor that inhibits protein phosphatase 2C (PP2C) activity in Arabidopsis thaliana. Previous studies reported that the PP2C phosphatase inhibition by PYL10 was ABA-independent. Here, systematic PYL10 biochemical studies demonstrated that PYL10 activity was ABA-dependent, and the previously reported studies was interfered by the presence of BSA in the commercial kit. To investigate dynamic mechanism of how ABA binding to PYL10 induces PP2C phosphatase inhibiting activity, solution NMR relaxation analysis of apo-PYL10 and PYL10/ABA were conducted following backbone resonance assignments. Reduced spectrum density mapping of the backbone relaxation data revealed that PYL10 was more flexible in ABA bound form than apo-PYL10, indicating an increased conformational entropy upon ligand binding. Moreover, to illustrate conformation exchanges of PYL10 upon ABA binding, NMR line shape analysis was performed with increasing concentrations of ABA, and the results indicated that PYL10 backbone conformational changes occur at different time scales.

  17. Molecular evolution of a sex determination protein. FEM-2 (pp2c) in Caenorhabditis.

    PubMed

    Hansen, D; Pilgrim, D

    1998-07-01

    Somatic sex determination in Caenorhabditis elegans involves a signal transduction pathway linking a membrane receptor to a transcription factor. The fem-2 gene is central to this pathway, producing a protein phosphatase (FEM-2) of the type 2C (PP2C). FEM-2 contains a long amino terminus that is absent in canonical PP2C enzymes. The function of this domain is difficult to predict, since it shows no sequence similarity to any other known proteins or motifs. Here we report the cloning of the fem-2 homologue from Caenorhabditis briggsae (Cb-fem-2). The sequence identity is much higher than that observed for other C. briggsae homologues of C. elegans sex determination proteins. However, this level is not uniform across the entire lengths of the proteins; it is much lower in the amino termini. Thus, the two domains of the same protein are evolving at different rates, suggesting that they have different functional constraints. Consistent with this, Cb-FEM-2 is able to replace some, but not all, of the Ce-FEM-2 in vivo function. We show that removal of the amino terminus from Ce-FEM-2 has no effect on its in vitro phosphatase activity, or its ability to replace the in vivo function of a yeast PP2C enzyme, but that it is necessary for proper FEM-2 function in worms. This demonstrates that the amino terminus is not an extended catalytic domain or a direct negative regulator of phosphatase activity.

  18. Role of PP2C-mediated ABA signaling in the moss Physcomitrella patens.

    PubMed

    Sakata, Yoichi; Komatsu, Kenji; Taji, Teruaki; Tanaka, Shigeo

    2009-09-01

    Plant hormone abscisic acid (ABA) is found in a wide range of land plants, from mosses to angiosperms. However, our knowledge concerning the function of ABA is limited to some angiosperm plant species. We have shown that the basal land plant Physcomitrella patens and the model plant Arabidopsis thaliana share a conserved abscisic acid (ABA) signaling pathway mediated through ABI1-related type 2C protein phosphatases (PP2Cs). Ectopic expression of Arabidopsis abi1-1, a dominant allele of ABI1 that functions as a negative regulator of ABA signaling, or targeted disruption of Physcomitrella ABI1-related gene (PpABI1A) resulted in altered ABA sensitivity and abiotic stress tolerance of Physcomitrella, as demonstrated by osmostress and freezing stress. Moreover, transgenic Physcomitrella overexpressing abi1-1 showed altered morphogenesis. These transgenic plants had longer stem lengths compared to the wild type, and continuous growth of archegonia (female organ) with few sporophytes under non-stress conditions. Our results suggest that PP2C-mediated ABA signaling is involved in both the abiotic stress responses and developmental regulation of Physcomitrella.

  19. Deep-Elastic pp Scattering at Lhc from LOW-x Gluons

    NASA Astrophysics Data System (ADS)

    Islam, M. M.; Kašpar, J.; Luddy, R. J.

    Deep-elastic pp scattering at c.m. energy 14 TeV at LHC in the momentum transfer range 4 GeV2 ≲ |t| ≲ 10 GeV2 is planned to be measured by the TOTEM group. We study this process in a model where the deep-elastic scattering is due to a single hard collision of a valence quark from one proton with a valence quark from the other proton. The hard collision originates from the low-x gluon cloud around one valence quark interacting with that of the other. The low-x gluon cloud can be identified as color glass condensate and has size ≃0.3 F. Our prediction is that pp dσ/dt in the large |t| region decreases smoothly as momentum transfer increases. This is in contrast to the prediction of pp dσ/dt with visible oscillations and smaller cross sections by a large number of other models.

  20. Testing the WWγ coupling of the standard model at pp¯ colliders

    NASA Astrophysics Data System (ADS)

    C´s, Jose; Hagiwara, Kaoru; Herzog, Franz

    1986-12-01

    The measurement of the magnetic moment μ W of the weak boson W is crucial to test the non-abelian gauge theory of the electroweak interaction formulated by Glashow, Salam and Weinberg. We propose methods to measure μ W at hadron colliders via the processes pp¯→W - γX; W - → ¢ℓ v and pp¯→W -X; W - → γℓ v. T he helicity amplitudes of the parton sub-process factorizesa`la Mikaelian in lowest order of the fine structure constant α, leading to peculiar angular distributions among the initial and final state particles. We make extensive numerical studies at the Tevatron collider energy √ s = 2TeV of these distributions applying experimentally feasible cuts. Furthermore we investigate the main background pp¯→W - jetX; W → ¢ ℓ v where the jet fakes a single isolated photon. The effect of the finite W-width is discussed and found to be small. The sensitivity of our results to higher order QCD corrections is considered qualitatively but remains unknown quantitatively.

  1. PP2A Inhibitor PME-1 Drives Kinase Inhibitor Resistance in Glioma Cells.

    PubMed

    Kaur, Amanpreet; Denisova, Oxana V; Qiao, Xi; Jumppanen, Mikael; Peuhu, Emilia; Ahmed, Shafiq U; Raheem, Olayinka; Haapasalo, Hannu; Eriksson, John; Chalmers, Anthony J; Laakkonen, Pirjo; Westermarck, Jukka

    2016-12-01

    Glioblastoma multiforme lacks effective therapy options. Although deregulated kinase pathways are drivers of malignant progression in glioblastoma multiforme, glioma cells exhibit intrinsic resistance toward many kinase inhibitors, and the molecular basis of this resistance remains poorly understood. Here, we show that overexpression of the protein phosphatase 2A (PP2A) inhibitor protein PME-1 drives resistance of glioma cells to various multikinase inhibitors. The PME-1-elicited resistance was dependent on specific PP2A complexes and was mediated by a decrease in cytoplasmic HDAC4 activity. Importantly, both PME-1 and HDAC4 associated with human glioma progression, supporting clinical relevance of the identified mechanism. Synthetic lethality induced by both PME-1 and HDAC4 inhibition was dependent on the coexpression of proapoptotic protein BAD. Thus, PME-1-mediated PP2A inhibition is a novel mechanistic explanation for multikinase inhibitor resistance in glioma cells. Clinically, these results may inform patient stratification strategies for future clinical trials with selected kinase inhibitors in glioblastoma multiforme. Cancer Res; 76(23); 7001-11. ©2016 AACR.

  2. Isospin mixing reveals 30P(p, γ)31S resonance influencing nova nucleosynthesis

    DOE PAGES

    Bennett, M. B.; Wrede, C.; Brown, B. A.; ...

    2016-03-08

    Here, the thermonuclear 30P(p, γ)31S reaction rate is critical for modeling the final elemental and isotopic abundances of ONe nova nucleosynthesis, which affect the calibration of proposed nova thermometers and the identification of presolar nova grains, respectively. Unfortunately, the rate of this reaction is essentially unconstrained experimentally, because the strengths of key 31S proton capture resonance states are not known, largely due to uncertainties in their spins and parities. Using the β decay of 31Cl, we have observed the β-delayed γ decay of a 31S state at Ex = 6390.2(7) keV, with a 30P(p, γ)31S resonance energy of Er =more » 259.3(8) keV, in the middle of the 30P(p, γ)31S Gamow window for peak nova temperatures. This state exhibits isospin mixing with the nearby isobaric analog state at Ex = 6279.0(6) keV, giving it an unambiguous spin and parity of 3/2+ and making it an important l = 0 resonance for proton capture on 30P.« less

  3. γ-Secretase Catalyzes Sequential Cleavages of the AβPP Transmembrane Domain

    PubMed Central

    Xu, Xuemin

    2009-01-01

    The biogenesis of the amyloid-β peptide (Aβ) is a central issue in Alzheimer's disease (AD) research. Aβ is produced by β- and γ-secretases from the amyloid-β protein precursor (AβPP). These proteases are targets for the development of therapeutic compounds to downregulate Aβ production. γ-secretase has received more attention 1) because it generates the C-terminus of Aβ, which is important in the pathogenesis of AD because the longer Aβ species are more amyloidogenic, and 2) because it cleaves AβPP within its transmembrane domain. In the understanding the mechanism of γ-secretase cleavage, three major cleavage sites have been identified, namely, γ-cleavage site at Aβ40/42, ζ-cleavage site at Aβ46, and ε-cleavage site at Aβ49. Moreover, the novel finding that some of the known γ-secretase inhibitors inhibit the formation of secreted Aβ40 and Aβ42, but cause an intracellular accumulation of long Aβ46, provided information extremely important for the development of strategies aimed at the design of γ-secretase inhibitors to prevent and treat AD. In addition, it has been established that the C-terminus of Aβ is generated by a series of sequential cleavages: first, ε-cleavage, followed by ζ-cleavage and finally by γ-cleavage, commencing from the membrane boundary to the middle of the AβPP membrane domain. PMID:19221413

  4. Influence of flavour absorption on oxygen permeation through LDPE, PP, PC and PET plastics food packaging.

    PubMed

    van Willige, R W G; Linssen, J P H; Meinders, M B J; van der Stege, H J; Voragen, A G J

    2002-03-01

    The effect of flavour absorption on the oxygen permeability of low-density polyethylene (LDPE), polypropylene (PP), polycarbonate (PC) and polyethylene terephthalate (PET) was studied using an isostatic continuous flow system. Polymer samples were exposed to a model solution containing limonene, hexyl acetate, nonanone and decanal at 40 degrees C. After exposure, one part of each sample was analysed for absorbed flavour compounds using a Large Volume Injection GC Ultrasonic 'in vial' extraction method, and from the other part, oxygen permeability was measured in a permeation cell at 25 degrees C. After 8 h of exposure, LDPE and PP samples showed a significant linear (R2 = 0.82 and 0.99) increase in oxygen permeability of 21 and 130%, respectively. Owing to swelling of the polymer samples resulting from flavour absorption, the structure of the polymeric network changed (i.e. opened) and consequently increased oxygen permeability. The oxygen permeability of exposed PC showed a significant linear (R2 = 0.78) decrease of 11% after 21 days. PC obviously did not swell like LDPE or PP. Therefore, it was suggested that absorbed flavour compounds occupied or blocked 'microcavities' through which normally oxygen is transported. Absorption of flavour compounds by PET did not affect the oxygen permeability of PET significantly.

  5. (p)ppGpp-dependent and -independent pathways for salt tolerance in Escherichia coli.

    PubMed

    Tarusawa, Takefusa; Ito, Shion; Goto, Simon; Ushida, Chisato; Muto, Akira; Himeno, Hyouta

    2016-07-01

    Addition of some kinds of translation inhibitors targeting the ribosome such as kasugamycin to the culture medium as well as removal of a ribosome maturation factor or a ribosomal protein provides Escherichia coli cells with tolerance to high salt stress. Here, we found that another kind of translation inhibitor, serine hydroxamate (SHX), which induces amino acid starvation leading to (p)ppGpp production, also has a similar effect, but via a different pathway. Unlike kasugamycin, SHX was not effective in (p)ppGpp-null mutant cells. SHX and depletion of RsgA, a ribosome maturation factor, had an additive effect on salt tolerance, while kasugamycin or depletion of RsgA did not. These results indicate the presence of two distinct pathways, (p)ppGpp-dependent and -independent pathways, for salt tolerance of E. coli cell. Both pathways operate even in the absence of σ(S), an alternative sigma factor involved in the stationary phase or stress response. Hastened activation of the exocytoplasmic stress-specific sigma factor, σ(E), after salt shock was observed in the cells treated with SHX, as has been observed in the cells treated with a translation inhibitor or depleted of a ribosome maturation factor.

  6. The bacterial alarmone (p)ppGpp is required for virulence and controls cell size and survival of Pseudomonas syringae on plants

    PubMed Central

    Chatnaparat, Tiyakhon; Li, Zhong; Korban, Schuyler S.; Zhao, Youfu

    2016-01-01

    Summary The stringent response, mediated by second messenger (p)ppGpp, results in swift and massive transcriptional reprogramming under nutrient limited conditions. In this study, the role of (p)ppGpp on virulence of P. syringae pv. syringae B728a (PssB728a) was investigated. The virulence of the relA/spoT (ppGpp0) double mutant was completely impaired on bean, and bacterial growth was significantly reduced, suggesting that (p)ppGpp is required for full virulence of P. syringae. Expression of T3SS and other virulence genes was reduced in ppGpp0 mutants. In addition, ppGpp deficiency resulted in loss of swarming motility, reduction of pyoverdine production, increased sensitivity to oxidative stress and antibiotic tolerance, as well as reduced ability to utilize γ-amino butyric acid. Increased levels of ppGpp resulted in reduced cell size of PssB728a when grown in a minimal medium and on plant surfaces, while most ppGpp0 mutant cells were not viable on plant surfaces 24 h after spray inoculation, suggesting that ppGpp-mediated stringent response temporarily limits cell growth, and might control cell survival on plants by limiting their growth. These results demonstrated that ppGpp-mediated stringent response plays a central role in P. syringae virulence and survival, and indicated that ppGpp serves as a global signal for regulating various virulence traits in PssB728a. PMID:25626964

  7. Protein phosphatase 4 (PP4) functions as a critical regulator in tumor necrosis factor (TNF)-α-induced hepatic insulin resistance.

    PubMed

    Zhao, Hongye; Huang, Xiuqing; Jiao, Juan; Zhang, Hangxiang; Liu, Jin; Qin, Weiwei; Meng, Xiangyu; Shen, Tao; Lin, Yajun; Chu, Jiaojiao; Li, Jian

    2015-12-15

    Protein phosphatase 4 (PP4) was shown to participate in multiple cellular processes, including DNA damage response, cell cycle and embryo development. Recent studies demonstrated a looming role of PP4 in glucose metabolism. However, whether PP4 is involved in hepatic insulin resistance remains poorly understood. The objective of this study was to estimate the role of PP4 in tumor necrosis factor (TNF)-α-induced hepatic insulin resistance. db/db mice and TNF-α-treated C57BL/6J mice were used as hepatic insulin resistance animal models. In vitro models were established in both HepG2 cells and primary hepatocytes by TNF-α treatment. We found that increased expression and activity of PP4 occurred in the livers of db/db mice and TNF-α-induced hepatic insulin resistance both in vitro and in vivo. Actually, PP4 silencing and suppression of PP4 activity ameliorated TNF-α-induced hepatic insulin resistance, whereas over-expression of PP4 caused insulin resistance. We then further investigated the prodiabetic mechanism of PP4 in TNF-α-induced insulin resistance. We found that PP4 formed a complex with IRS-1 to promote phosphorylation of IRS-1 on serine 307 via JNK activation and reduce the expression of IRS-1. Thus, PP4 is an important regulator in inflammatory related insulin resistance.

  8. PP2A impaired activity is a common event in acute myeloid leukemia and its activation by forskolin has a potent anti-leukemic effect.

    PubMed

    Cristóbal, I; Garcia-Orti, L; Cirauqui, C; Alonso, M M; Calasanz, M J; Odero, M D

    2011-04-01

    Protein phosphatase 2A (PP2A) is a human tumor suppressor that inhibits cellular transformation by regulating the activity of several signaling proteins critical for malignant cell behavior. PP2A has been described as a potential therapeutic target in chronic myeloid leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia and B-cell chronic lymphocytic leukemia. Here, we show that PP2A inactivation is a recurrent event in acute myeloid leukemia (AML), and that restoration of PP2A phosphatase activity by treatment with forskolin in AML cells blocks proliferation, induces caspase-dependent apoptosis and affects AKT and ERK1/2 activity. Moreover, treatment with forskolin had an additive effect with Idarubicin and Ara-c, drugs used in standard induction therapy in AML patients. Analysis at protein level of the PP2A activation status in a series of patients with AML at diagnosis showed PP2A hyperphosphorylation in 78% of cases (29/37). In addition, we found that either deregulated expression of the endogenous PP2A inhibitors SET or CIP2A, overexpression of SETBP1, or downregulation of some PP2A subunits, might be contributing to PP2A inhibition in AML. In conclusion, our results show that PP2A inhibition is a common event in AML cells and that PP2A activators, such as forskolin or FTY720, could represent potential novel therapeutic targets in AML.

  9. Placental protein 13 (PP13/galectin-13) undergoes lipid raft-associated subcellular redistribution in the syncytiotrophoblast in preterm preeclampsia and HELLP syndrome

    PubMed Central

    Balogh, Andrea; Pozsgay, Judit; Matkó, János; Dong, Zhong; Kim, Chong Jai; Várkonyi, Tibor; Sammar, Marei; Rigó, Jánow; Meiri, Hamutal; Romero, Roberto; Papp, Zoltán; Than, Nandor Gábor

    2012-01-01

    Objective To investigate placental protein 13 (PP13) localization in relation to cytoskeleton and lipid rafts in preeclampsia and HELLP syndrome. Study Design Placental cryosections from patients with preeclampsia and HELLP, and controls were stained for PP13, actin, PLAP (lipid raft marker), and CD71 (nonraft marker). BeWo cells exposed to stress conditions were stained for PP13 and actin. Protein localization were investigated by confocal microscopy, PP13 concentrations by ELISA. Results PP13-actin colocalization was increased in syncytiotrophoblast juxtamembrane regions in term/preterm preeclampsia and HELLP. PP13-CD71 colocalization was decreased and PP13-PLAP proximity was increased in preterm but not term preeclampsia and HELLP. PP13-release from BeWo cells was inhibited by cytoskeleton disruption, and augmented by Ca2+-influx and ischemic stress. Conclusion The actin cytoskeleton, probably in connection with lipid rafts, controls trophoblastic “nonclassical” PP13 export. PP13 is released from the syncytiotrophoblast in preterm preeclampsia and HELLP, mimicked in BeWo cells by ischemic stress, suggesting PP13 is a placental alarmin. PMID:21596368

  10. PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects

    PubMed Central

    Zazo, Sandra; Arpí, Oriol; Menéndez, Silvia; Manso, Rebeca; Lluch, Ana; Eroles, Pilar; Rovira, Ana; Albanell, Joan; García-Foncillas, Jesús; Madoz-Gúrpide, Juan; Rojo, Federico

    2015-01-01

    The protein phosphatase 2A (PP2A) is a key tumor suppressor which has emerged as a novel molecular target in some human cancers. Here, we show that PP2A inhibition is a common event in breast cancer and identified PP2A phosphorylation and deregulation SET and CIP2A as molecular contributing mechanisms to inactivate PP2A. Interestingly, restoration of PP2A activity after FTY720 treatment reduced cell growth, induced apoptosis and decreased AKT and ERK activation. Moreover, FTY720 led to PP2A activation then enhancing doxorubicin-induced antitumor effects both in vitro and in vivo. PP2A inhibition (CPscore: PP2A phosphorylation and/or CIP2A overexpression) was detected in 27% of cases (62/230), and associated with grade (p = 0.017), relapse (p < 0.001), negative estrogen (p < 0.001) and progesterone receptor expression (p < 0.001), HER2-positive tumors (p = 0.049), Ki-67 expression (p < 0.001), and higher AKT (p < 0.001) and ERK (p < 0.001) phosphorylation. Moreover, PP2A inhibition determined shorter overall (p = 0.006) and event-free survival (p = 0.003), and multivariate analysis confirmed its independent prognostic impact. Altogether, our results indicate that PP2A is frequently inactivated in breast cancer and determines worse outcome, and its restoration using PP2A activators represents an alternative therapeutic strategy in this disease. PMID:25726524

  11. PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects.

    PubMed

    Rincón, Raúl; Cristóbal, Ion; Zazo, Sandra; Arpí, Oriol; Menéndez, Silvia; Manso, Rebeca; Lluch, Ana; Eroles, Pilar; Rovira, Ana; Albanell, Joan; García-Foncillas, Jesús; Madoz-Gúrpide, Juan; Rojo, Federico

    2015-02-28

    The protein phosphatase 2A (PP2A) is a key tumor suppressor which has emerged as a novel molecular target in some human cancers. Here, we show that PP2A inhibition is a common event in breast cancer and identified PP2A phosphorylation and deregulation SET and CIP2A as molecular contributing mechanisms to inactivate PP2A. Interestingly, restoration of PP2A activity after FTY720 treatment reduced cell growth, induced apoptosis and decreased AKT and ERK activation. Moreover, FTY720 led to PP2A activation then enhancing doxorubicin-induced antitumor effects both in vitro and in vivo. PP2A inhibition (CPscore: PP2A phosphorylation and/or CIP2A overexpression) was detected in 27% of cases (62/230), and associated with grade (p = 0.017), relapse (p < 0.001), negative estrogen (p < 0.001) and progesterone receptor expression (p < 0.001), HER2-positive tumors (p = 0.049), Ki-67 expression (p < 0.001), and higher AKT (p < 0.001) and ERK (p < 0.001) phosphorylation. Moreover, PP2A inhibition determined shorter overall (p = 0.006) and event-free survival (p = 0.003), and multivariate analysis confirmed its independent prognostic impact. Altogether, our results indicate that PP2A is frequently inactivated in breast cancer and determines worse outcome, and its restoration using PP2A activators represents an alternative therapeutic strategy in this disease.

  12. Adaptation of HepG2 cells to a steady-state reduction in the content of protein phosphatase 6 (PP6) catalytic subunit.

    PubMed

    Boylan, Joan M; Salomon, Arthur R; Tantravahi, Umadevi; Gruppuso, Philip A

    2015-07-15

    Protein phosphatase 6 (PP6) is a ubiquitous Ser/Thr phosphatase involved in an array of cellular processes. To assess the potential of PP6 as a therapeutic target in liver disorders, we attenuated expression of the PP6 catalytic subunit in HepG2 cells using lentiviral-transduced shRNA. Two PP6 knock-down (PP6KD) cell lines (90% reduction of PP6-C protein content) were studied in depth. Both proliferated at a rate similar to control cells. However, flow cytometry indicated G2/M cell cycle arrest that was accounted for by a shift of the cells from a diploid to tetraploid state. PP6KD cells did not show an increase in apoptosis, nor did they exhibit reduced viability in the presence of bleomycin or taxol. Gene expression analysis by microarray showed attenuated anti-inflammatory signaling. Genes associated with DNA replication were downregulated. Mass spectrometry-based phosphoproteomic analysis yielded 80 phosphopeptides representing 56 proteins that were significantly affected by a stable reduction in PP6-C. Proteins involved in DNA replication, DNA damage repair and pre-mRNA splicing were overrepresented among these. PP6KD cells showed intact mTOR signaling. Our studies demonstrated involvement of PP6 in a diverse set of biological pathways and an adaptive response that may limit the effectiveness of targeting PP6 in liver disorders.

  13. Single Anomalous Production of the Fourth SM Family Leptons at Future e+e-, ep and pp Colliders

    SciTech Connect

    Ciftci, A. K.; Ciftci, R.; Karadeniz, H.; Sultansoy, S.; Yildiz, H. Duran

    2007-04-23

    Possible single productions of fourth SM family charged and neutral leptons via anomalous interactions at the future e+e-, ep, and pp colliders are studied. Signatures of such anomalous processes are argued at above colliders comparatively.

  14. Molecular cloning and characterization of a novel human protein phosphatase 2C cDNA (PP2C epsilon*).

    PubMed

    Jin, Feng; Ji, Chaoneng; Liu, Lingfeng; Dai, Jianfeng; Gu, Shaohua; Sun, Xianfei; Xie, Yi; Mao, Yumin

    2004-09-01

    We have isolated a novel cDNA from the human fetal brain cDNA library with homology to the Mg2+ -dependent serine/threonine protein phosphatase 2C (PP2C) family. The cDNA is 3055 bp in length, and the predicted coding region encodes a 360-amino-acid protein, which shows 99% identity to the PP2C epsilon from rat and mouse. Then we term it human PP2C epsilon gene. The gene is mapped to chromosome 3q26.1 and contains 4 exons. RT-PCR analysis shows that the PP2C epsilon is widely expressed in human tissues and the expression levels in heart, placenta, lung, liver, kidney, and pancreas are relatively high.

  15. Drosophila DPP2C1, a novel member of the protein phosphatase 2C (PP2C) family.

    PubMed

    Dick, T; Bahri, S M; Chia, W

    1997-10-15

    We report the molecular cloning, chromosome mapping and developmental transcription pattern of a putative serine/threonine protein phosphatase 2C (PP2C), DPP2C1, from Drosophila melanogaster. The 6-kb transcript of this first Drosophila PP2C gene encodes a 1428-aa deduced protein. The DPP2C1 protein contains a approximately 330-aa PP2C-like catalytic domain flanked by extensive N- and C-terminal sequences showing no similarities to other PP2Cs. The dpp2c1 gene maps to 4E1-2 on the X chromosome, 1.5 kb upstream of the ddlc1 gene. Northern blot analyses showed that dpp2c1 transcription is developmentally regulated, accumulating maximally during early (0-6 h) and late (12-24 h) embryogensis. The presented molecular characterisation provides the basis for a genetic dissection of DPP2C1 function.

  16. Single Anomalous Production of the Fourth SM Family Quarks at Future e+e-, ep, and pp Colliders

    SciTech Connect

    Ciftci, A. K.; Ciftci, R.; Sultansoy, S.; Yildiz, H. Duran

    2007-04-23

    Possible single productions of fourth SM family u4 and d4 quarks via anomalous interactions at the e+e-, ep, and pp colliders are investigated. Signatures of such anomalous processes are discussed at above colliders comparatively.

  17. Tensor hypercontracted ppRPA: Reducing the cost of the particle-particle random phase approximation from O(r 6) to O(r 4)

    NASA Astrophysics Data System (ADS)

    Shenvi, Neil; van Aggelen, Helen; Yang, Yang; Yang, Weitao

    2014-07-01

    In recent years, interest in the random-phase approximation (RPA) has grown rapidly. At the same time, tensor hypercontraction has emerged as an intriguing method to reduce the computational cost of electronic structure algorithms. In this paper, we combine the particle-particle random phase approximation with tensor hypercontraction to produce the tensor-hypercontracted particle-particle RPA (THC-ppRPA) algorithm. Unlike previous implementations of ppRPA which scale as O(r6), the THC-ppRPA algorithm scales asymptotically as only O(r4), albeit with a much larger prefactor than the traditional algorithm. We apply THC-ppRPA to several model systems and show that it yields the same results as traditional ppRPA to within mH accuracy. Our method opens the door to the development of post-Kohn Sham functionals based on ppRPA without the excessive asymptotic cost of traditional ppRPA implementations.

  18. Investigating the frequency dependence of mantle Q by stacking P and PP spectra

    NASA Astrophysics Data System (ADS)

    Warren, Linda M.; Shearer, Peter M.

    2000-11-01

    Using seismograms from globally distributed, shallow earthquakes between 1988 and 1998, we compute spectra for P arrivals from epicentral distances of 40° to 80° and PP arrivals from 80° to 160°. Selecting records with estimated signal-to-noise ratios greater than 2, we find 17,836 P and 14,721 PP spectra. We correct each spectrum for the known instrument response and for an ω-2 source model that accounts for varying event sizes. Next, we stack the logarithms of the P and PP spectra in bins of similar source-receiver range. The stacked log spectra, denoted as log(DP') and log(DPP'), appear stable between about 0.16 and 0.86 Hz, with noise and/or bias affecting the results at higher frequencies. Assuming that source spectral differences are randomly distributed, then for shallow events, when the PP range is twice the P range, the average residual source spectrum may be estimated as 2 log(DP')-log(DPP'), and the average P wave attenuation spectrum may be estimated as log(DPP') - log(DP'). The residual source spectral estimates exhibit a smooth additional falloff as ω-0.15±0.05 between 0.16 and 0.86 Hz, indicating that ω-2.15±0.05 is an appropriate average source model for shallow events. The attenuation spectra show little distance dependence over this band and have a P wave t¯* value of ˜0.5 s. We use t¯* measurements from individual P and PP spectra to invert for a frequency-independent Q model and find that the upper mantle is nearly 5 times as attenuating as the lower mantle. Frequency dependence in Qα is difficult to resolve directly in these data but, as previous researchers have noted, is required to reconcile these values with long-period Q estimates. Using Q model QL6 [Durek and Ekström, 1996] as a long-period constraint, we experiment with fitting our stacked log spectra with an absorption band model. We find that the upper corner frequency f2 in the absorption band must be depth-dependent to account for the lack of a strong distance

  19. GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA.

    PubMed Central

    Liu, Qing-Rong; Zhang, Ping-Wu; Lin, Zhicheng; Li, Qi-Fu; Woods, Amina S; Troncoso, Juan; Uhl, George R

    2004-01-01

    The activities of PP1 (protein phosphatase 1), a principal cellular phosphatase that reverses serine/threonine protein phosphorylation, can be altered by inhibitors whose activities are themselves regulated by phosphorylation. We now describe a novel PKC (protein kinase C)-dependent PP1 inhibitor, namely GBPI (gut and brain phosphatase inhibitor). The shorter mRNA that encodes this protein, GBPI-1, is expressed in brain, stomach, small intestine, colon and kidney, whereas a longer GBPI-2 splice variant mRNA is found in testis. Human GBPI-1 mRNA encodes a 145-amino-acid, 16.5 kDa protein with pI 7.92. GBPI contains a consensus PP1-binding motif at residues 21-25 and consensus sites for phosphorylation by enzymes, including PKC, PKA (protein kinase A or cAMP-dependent protein kinase) and casein kinase II. Recombinant GBPI-1-fusion protein inhibits PP1 activity with IC50=3 nM after phosphorylation by PKC. Phospho-GBPI can even enhance PP2A activity by >50% at submicromolar concentrations. Non-phosphorylated GBPI-1 is inactive in both assays. Each of the mutations in amino acids located in potential PP1-binding sequences, K21E+K22E and W25A, decrease the ability of GBPI-1 to inhibit PP1. Mutations in the potential PKC phosphoacceptor site T58E also dramatically decrease the ability of GBPI-1 to inhibit PP1. Interestingly, when PKC-phosphorylated GBPI-1 is further phosphorylated by PKA, it no longer inhibits PP1. Thus, GBPI-1 is well positioned to integrate PKC and PKA modulation of PP1 to regulate differentially protein phosphorylation patterns in brain and gut. GBPI, its closest family member CPI (PKC-potentiated PP1 inhibitor) and two other family members, kinase-enhanced phosphatase inhibitor and phosphatase holoenzyme inhibitor, probably modulate integrated control of protein phosphorylation states in these and other tissues. PMID:12974676

  20. Enhancement and optimization of PpIX-based photodynamic therapy of skin cancer: translational studies from bench to clinic

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Anand, Sanjay; Baran, Christine; Honari, Golara; Lohser, Sara; Kyei, Angela; Bailin, Philip; Pogue, Brian W.

    2009-02-01

    Nonmelanoma skin carcinomas are the most common of all human cancers. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) has been used to treat these tumors, but has shown variable results. We are pursuing a multifaceted approach toward optimizing tumor responsiveness. First, a new paradigm is being developed in which tumors are pretreated with differentiation-inducing agents, e.g. methotrexate or Vitamin D, to enhance synthesis of protoporphyrin IX (PpIX) and improve tumor cell killing upon exposure to 635 nm light. This principle was first elucidated in cell culture studies, and has now been shown to hold true for murine skin tumors, and for a human subcutaneous tumor model (A431 cells injected in nude mice). Clinical trials to test methotrexate and Vitamin D as augmenting agents for ALA-PDT of nonmelanoma skin cancer are being designed. Second, better methods to measure PpIX in patients' skin tumors in real time are being developed. In a clinical study to measure PpIX in patients with dysplastic skin lesions, in vivo fluorescence dosimetry was used to measure the accumulation of PpIX over time, and revealed that intralesional PpIX may reach clinically-useful levels earlier than previously thought for the treatment of actinic keratoses. In a second clinical study to examine depth of PpIX production in nonmelanoma skin cancer, the depth of PpIX within BCC tumors was found at relatively deep levels (>1 mm) in some tumor nests, but not in others. Production of PpIX in deep squamous cell carcinoma was very low. In summary, molecular approaches such as differentiation therapy to enhance ALA-PDT for individual patients may ultimately be needed to help to improve skin cancer responses to this modality.

  1. Adaptation of HepG2 cells to a steady-state reduction in the content of protein phosphatase 6 (PP6) catalytic subunit

    SciTech Connect

    Boylan, Joan M.; Salomon, Arthur R.; Tantravahi, Umadevi; Gruppuso, Philip A.

    2015-07-15

    Protein phosphatase 6 (PP6) is a ubiquitous Ser/Thr phosphatase involved in an array of cellular processes. To assess the potential of PP6 as a therapeutic target in liver disorders, we attenuated expression of the PP6 catalytic subunit in HepG2 cells using lentiviral-transduced shRNA. Two PP6 knock-down (PP6KD) cell lines (90% reduction of PP6-C protein content) were studied in depth. Both proliferated at a rate similar to control cells. However, flow cytometry indicated G2/M cell cycle arrest that was accounted for by a shift of the cells from a diploid to tetraploid state. PP6KD cells did not show an increase in apoptosis, nor did they exhibit reduced viability in the presence of bleomycin or taxol. Gene expression analysis by microarray showed attenuated anti-inflammatory signaling. Genes associated with DNA replication were downregulated. Mass spectrometry-based phosphoproteomic analysis yielded 80 phosphopeptides representing 56 proteins that were significantly affected by a stable reduction in PP6-C. Proteins involved in DNA replication, DNA damage repair and pre-mRNA splicing were overrepresented among these. PP6KD cells showed intact mTOR signaling. Our studies demonstrated involvement of PP6 in a diverse set of biological pathways and an adaptive response that may limit the effectiveness of targeting PP6 in liver disorders. - Highlights: • Lentiviral-transduced shRNA was used to generate a stable knockdown of PP6 in HepG2 cells. • Cells adapted to reduced PP6; cell proliferation was unaffected, and cell survival was normal. • However, PP6 knockdown was associated with a transition to a tetraploid state. • Genomic profiling showed downregulated anti-inflammatory signaling and DNA replication. • Phosphoproteomic profiling showed changes in proteins associated with DNA replication and repair.

  2. Orchestrated Action of PP2A Antagonizes Atg13 Phosphorylation and Promotes Autophagy after the Inactivation of TORC1

    PubMed Central

    Kondo, Akihiro; Kaneko, Atsuki; Koike, Naoki; Ushimaru, Takashi

    2016-01-01

    Target of rapamycin complex 1 (TORC1) phosphorylates autophagy-related Atg13 and represses autophagy under nutrient-rich conditions. However, when TORC1 becomes inactive upon nutrient depletion or treatment with the TORC1 inhibitor rapamycin, Atg13 dephosphorylation occurs rapidly, and autophagy is induced. At present, the phosphatases involved in Atg13 dephosphorylation remain unknown. Here, we show that two protein phosphatase 2A (PP2A) phosphatases, PP2A-Cdc55 and PP2A-Rts1, which are activated by inactivation of TORC1, are required for sufficient Atg13 dephosphorylation and autophagy induction after TORC1 inactivation in budding yeast. After rapamycin treatment, dephosphorylation of Atg13, activation of Atg1 kinase, pre-autophagosomal structure (PAS) formation and autophagy induction are all impaired in PP2A-deleted cells. Conversely, overexpression of non-phosphorylatable Atg13 suppressed defects in autophagy in PP2A mutant. This study revealed that the orchestrated action of PP2A antagonizes Atg13 phosphorylation and promotes autophagy after the inactivation of TORC1. PMID:27973551

  3. Two Higgs doublet model with vectorlike leptons and contributions to pp → W W and H → W W

    DOE PAGES

    Dermíšek, Radovan; Lunghi, Enrico; Shin, Seodong

    2016-02-18

    In this paper, we study a two Higgs doublet model extended by vectorlike leptons mixing with one family of standard model leptons. Generated flavor violating couplings between heavy and light leptons can dramatically alter the decay patterns of heavier Higgs bosons. We focus on pp → H → ν4νμ → W μνμ, where ν4 is a new neutral lepton, and study possible effects of this process on the measurements of pp → W W and H → W W since it leads to the same final states. We discuss predictions for contributions to pp → W W and H →WWmore » and their correlations from the region of the parameter space that satisfies all available constraints including precision electroweak observables and from pair production of vectorlike leptons. Large contributions, close to current limits, favor small tan β region of the parameter space. We find that, as a result of adopted cuts in experimental analyses, the contribution to pp → W W can be an order of magnitude larger than the contribution to H → W W . Thus, future precise measurements of pp → W W will further constrain the parameters of the model. Also, we also consider possible contributions to pp → W W from the heavy Higgs decays into a new charged lepton e4 (H → e4μ → W μνμ), exotic SM Higgs decays, and pair production of vectorlike leptons.« less

  4. Avian pancreatic polypeptide fragments refold to native aPP conformation when combined in solution: a CD and VCD study.

    PubMed

    Copps, Jeffrey; Murphy, Richard F; Lovas, Sándor

    2006-09-01

    An equimolar mixture of avian pancreatic polypeptide (aPP) fragments aPP(1-11)-NH2 and Ac-aPP(12-36) had an electronic circular dichroism (ECD) spectrum that was similar to that of whole aPP in H2O and even more so in 30% (v/v) trifluoroethanol (TFE) in 15 mM Na2HPO4, but was different from the sum of the spectra of the individual fragments. The vibrational circular dichroism (VCD) spectrum of the combined fragments in 30% (v/v) TFE in 15 mM Na2HPO4 in D2O was also similar to that of the intact aPP and unlike the sum of the VCD spectra of the fragments. The interaction of these fragments is thus sufficient to support the conformation of whole aPP. This study demonstrates that VCD, in combination with ECD, is useful for the study of protein-protein interactions.

  5. Novel Ser/Thr Protein Phosphatase 5 (PP5) Regulated Targets during DNA Damage Identified by Proteomics Analysis

    SciTech Connect

    Ham, Bryan M.; Jayachandran, Hemalatha; Yang, Feng; Jaitly, Navdeep; Polpitiya, Ashoka D.; Monroe, Matthew E.; Wang, Ling; Zhao, Rui; Purvine, Samuel O.; Livesay, Eric A.; Camp, David G.; Rossie, Sandra S.; Smith, Richard D.

    2010-02-05

    The DNA damage response is a global phosphorylation signaling cascade process involved in sensing the damaged DNA condition and coordinating responses to cope with and repair the perturbed cellular state. We utilized a label-free liquid chromatography-mass spectrometry approach to evaluate changes in protein phosphorylation associated with PP5 activity during the DNA damage response. Biological replicate analyses of bleomycin-treated HeLa cells expressing either WT-PP5 or mutant inactive PP5 lead to the identification of six potential target proteins of PP5 action. Four of these putative targets are known to be involved in DNA damage responses. Using phospho-site specific antibodies, we confirmed that phosphorylation of one target, ribosomal protein S6, was selectively decreased in cells overexpressing catalytically inactive PP5. Our findings also suggest that PP5 may play a role in controlling translation and in regulating substrates for proline-directed kinases, such as MAP kinases and cyclin-dependent protein kinases that are involved in response to DNA damage.

  6. Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56.

    PubMed

    Wang, Jiao; Okkeri, Juha; Pavic, Karolina; Wang, Zhizhi; Kauko, Otto; Halonen, Tuuli; Sarek, Grzegorz; Ojala, Päivi M; Rao, Zihe; Xu, Wenqing; Westermarck, Jukka

    2017-03-01

    Protein phosphatase 2A (PP2A) is a critical human tumor suppressor. Cancerous inhibitor of PP2A (CIP2A) supports the activity of several critical cancer drivers (Akt, MYC, E2F1) and promotes malignancy in most cancer types via PP2A inhibition. However, the 3D structure of CIP2A has not been solved, and it remains enigmatic how it interacts with PP2A. Here, we show by yeast two-hybrid assays, and subsequent validation experiments, that CIP2A forms homodimers. The homodimerization of CIP2A is confirmed by solving the crystal structure of an N-terminal CIP2A fragment (amino acids 1-560) at 3.0 Å resolution, and by subsequent structure-based mutational analyses of the dimerization interface. We further describe that the CIP2A dimer interacts with the PP2A subunits B56α and B56γ. CIP2A binds to the B56 proteins via a conserved N-terminal region, and dimerization promotes B56 binding. Intriguingly, inhibition of either CIP2A dimerization or B56α/γ expression destabilizes CIP2A, indicating opportunities for controlled degradation. These results provide the first structure-function analysis of the interaction of CIP2A with PP2A/B56 and have direct implications for its targeting in cancer therapy.

  7. Strong binding and shrinkage of single and double nuclear systems (K−pp, K−ppn, K−K−p and K−K−pp) predicted by Faddeev-Yakubovsky calculations

    PubMed Central

    MAEDA, Shuji; AKAISHI, Yoshinori; YAMAZAKI, Toshimitsu

    2013-01-01

    Non-relativistic Faddeev and Faddeev-Yakubovsky calculations were made for K−pp, K−ppn, K−K−p and K−K−pp kaonic nuclear clusters, where the quasi bound states were treated as bound states by employing real separable potential models for the K−-K− and the K−-nucleon interactions as well as for the nucleon-nucleon interaction. The binding energies and spatial shrinkages of these states, obtained for various values of the interaction, were found to increase rapidly with the interaction strength. Their behaviors are shown in a reference diagram, where possible changes by varying the interaction in the dense nuclear medium are given. Using the Λ(1405) ansatz with a PDG mass of 1405 MeV/c2 for K−p, the following ground-state binding energies together with the wave functions were obtained: 51.5 MeV (K−pp), 69 MeV (K−ppn), 30.4 MeV (K−K−p) and 93 MeV (K−K−pp), which are in good agreement with previous results of variational calculation based on the Akaishi-Yamazaki coupled-channel potential. The K−K−pp state has a significantly increased density where the two nucleons are located very close to each other, in spite of the inner NN repulsion. Relativistic corrections on the calculated non-relativistic results indicate substantial lowering of the bound-state masses, especially of K−K−pp, toward the kaon condensation regime. The fact that the recently observed binding energy of K−pp is much larger (by a factor of 2) than the originally predicted one may infer an enhancement of the interaction in dense nuclei by about 25% possibly due to chiral symmetry restoration. In this respect some qualitative accounts are given based on “clearing QCD vacuum” model of Brown, Kubodera and Rho. PMID:24213206

  8. Cyclic cis-locked phospho-dipeptides reduce entry of AβPP into amyloidogenic processing pathway

    PubMed Central

    Fisher, Carolyn L.; Resnick, Ross J.; De, Soumya; Acevedo, Lucila A.; Lu, Kun Ping; Schroeder, Frank C.; Nicholson, Linda K.

    2016-01-01

    The cis/trans isomerization of X-Pro peptide bonds in proteins in some instances acts as a molecular switch in biological pathways. Our prior work suggests that the cis isomer of the phospho-Thr668-Pro669 motif, located in the cytoplasmic domain of the amyloid-β precursor protein (AβPP), is correlated with an increase in amyloidogenic processing of AβPP and production of amyloid beta (Aβ), the neurotoxic peptide fragment in Alzheimer’s disease (AD). We designed a 100% cis-locked cyclic dipeptide composed of cyclized phospho-Thr-Pro (pCDP) as a mimic for this putative pathological conformation, and three phosphate-blocked derivatives (pCDP-diBzl, pCDP-Bzl, and pCDP-diPOM). Two H4 neuroglioma cell lines were established as AD cell models for use in testing these compounds: H4-AβPP695 for stable overexpression of wild-type AβPP695, and H4-BACE1 for stable overexpression of β-site AβPP Cleaving Enzyme-1 (BACE1). The level of the secreted AβPP fragment resulting from BACE1 activity, sAβPPβ, served as a key proxy for amyloidogenic processing, since cleavage of AβPP by BACE1 is a requisite first step in Aβ production. Of the compounds tested, pCDP-diBzl decreased sAβPPβ levels in both cell lines, while pCDP-diPOM decreased sAβPPβ levels in only H4-BACE1 cells, all with similar dose-dependences and patterns of proteolytic AβPP fragments. Enzymatic assays showed that none of the pCDP derivatives directly inhibit BACE1 catalytic activity. These results suggest a model in which pCDP-diBzl and pCDP-diPOM act at a common point to inhibit entry of AβPP into the amyloidogenic AβPP processing pathway but through different targets, and provide important insights for the development of novel AD therapeutics. Keywords: Amyloid beta-Protein Precursor, Alzheimer’s Disease, cyclic dipeptides, diketopiperazine, phosphorylated Thr668. PMID:27662285

  9. Genome-wide characterization of vibrio phage ϕpp2 with unique arrangements of the mob-like genes

    PubMed Central

    2012-01-01

    Background Vibrio parahaemolyticus is associated with gastroenteritis, wound infections, and septicemia in human and animals. Phages can control the population of the pathogen. So far, the only one reported genome among giant vibriophages is KVP40: 244,835 bp with 26% coding regions that have T4 homologs. Putative homing endonucleases (HE) were found in Vibrio phage KVP40 bearing one segD and Vibrio cholerae phage ICP1 carrying one mobC/E and one segG. Results A newly isolated Vibrio phage ϕpp2, which was specific to the hosts of V. parahaemolyticus and V. alginolyticus, featured a long nonenveloped head of ~90 × 150 nm and tail of ~110 nm. The phage can survive at 50°C for more than one hour. The genome of the phage ϕpp2 was sequenced to be 246,421 bp, which is 1587 bp larger than KVP40. 383 protein-encoding genes (PEGs) and 30 tRNAs were found in the phage ϕpp2. Between the genomes of ϕpp2 and KVP40, 254 genes including 29 PEGs for viral structure were of high similarity, whereas 17 PEGs of KVP40 and 21 PEGs of ϕpp2 were unmatched. In both genomes, the capsid and tail genes have been identified, as well as the extensive representation of the DNA replication, recombination, and repair enzymes. In addition to the three giant indels of 1098, 1143 and 3330 nt, ϕpp2 possessed unique proteins involved in potassium channel, gp2 (DNA end protector), tRNA nucleotidyltransferase, and mob-type HEs, which were not reported in KVP40. The ϕpp2 PEG274, with strong promoters and translational initiation, was identified to be a mobE type, flanked by NrdA and NrdB/C homologs. Coincidently, several pairs of HE-flanking homologs with empty center were found in the phages of Vibrio phages ϕpp2 and KVP40, as well as in Aeromonas phages (Aeh1 and Ae65), and cyanophage P-SSM2. Conclusions Vibrio phage ϕpp2 was characterized by morphology, growth, and genomics with three giant indels and different types of HEs. The gene analysis on the required elements for transcription

  10. Cyclic cis-Locked Phospho-Dipeptides Reduce Entry of AβPP into Amyloidogenic Processing Pathway.

    PubMed

    Fisher, Carolyn L; Resnick, Ross J; De, Soumya; Acevedo, Lucila A; Lu, Kun Ping; Schroeder, Frank C; Nicholson, Linda K

    2017-01-01

    The cis/trans isomerization of X-Pro peptide bonds in proteins in some instances acts as a molecular switch in biological pathways. Our prior work suggests that the cis isomer of the phospho-Thr668-Pro669 motif, located in the cytoplasmic domain of the amyloid-β protein precursor (AβPP), is correlated with an increase in amyloidogenic processing of AβPP and production of amyloid-beta (Aβ), the neurotoxic peptide fragment in Alzheimer's disease (AD). We designed a 100% cis-locked cyclic dipeptide composed of cyclized phospho-Thr-Pro (pCDP) as a mimic for this putative pathological conformation, and three phosphate-blocked derivatives (pCDP-diBzl, pCDP-Bzl, and pCDP-diPOM). Two H4 neuroglioma cell lines were established as AD cell models for use in testing these compounds: H4-AβPP695 for stable overexpression of wild-type AβPP695, and H4-BACE1 for stable overexpression of β-site AβPP cleaving enzyme-1 (BACE1). The level of the secreted AβPP fragment resulting from BACE1 activity, sAβPPβ, served as a key proxy for amyloidogenic processing, since cleavage of AβPP by BACE1 is a requisite first step in Aβ production. Of the compounds tested, pCDP-diBzl decreased sAβPPβ levels in both cell lines, while pCDP-diPOM decreased sAβPPβ levels in only H4-BACE1 cells, all with similar dose-dependences and patterns of proteolytic AβPP fragments. Enzymatic assays showed that none of the pCDP derivatives directly inhibit BACE1 catalytic activity. These results suggest a model in which pCDP-diBzl and pCDP-diPOM act at a common point to inhibit entry of AβPP into the amyloidogenic AβPP processing pathway but through different targets, and provide important insights for the development of novel AD therapeutics.

  11. Brachypodium distachyon BdPP2CA6 Interacts with BdPYLs and BdSnRK2 and Positively Regulates Salt Tolerance in Transgenic Arabidopsis

    PubMed Central

    Zhang, Fan; Wei, Qiuhui; Shi, Jiaochun; Jin, Xia; He, Yuan; Zhang, Yang; Luo, Qingchen; Wang, Yuesheng; Chang, Junli; Yang, Guangxiao; He, Guangyuan

    2017-01-01

    The phytohormone abscisic acid (ABA) is essential in plant responding to biotic and abiotic stresses. Although ABA signaling model is well established in Arabidopsis, ABA receptor PYL family and clade A PP2C subfamily are not yet characterized in monocot model plant Brachypodium distachyon. In this study, we identified 12 PYLs and 8 clade A PP2Cs from B. distachyon genome and successfully cloned 12 PYLs and 7 clade A PP2Cs. Bioinformatic and expression analyses showed that most of the identified genes respond to several signal molecules and abiotic stresses. Protein–protein interaction analysis revealed that many BdPYLs and BdPP2CAs participate in the classic ABA-PYL-PP2C-SnRK2 signaling pathway. A clade A PP2C, designated BdPP2CA6, interacted with BdPYL11 in the absence of ABA and localized in nucleus. Most clade A PP2C members from Arabidopsis showed negatively regulation in ABA signaling pathway, whereas BdPP2CA6-overexpression transgenic Arabidopsis showed ABA hypersensitive phenotype, resulting in enhanced stomatal closure and salinity tolerance. Our results indicate that BdPP2CA6 positively regulates ABA and stress signal pathway in transgenic Arabidopsis plant seedlings. PMID:28293246

  12. Brachypodium distachyon BdPP2CA6 Interacts with BdPYLs and BdSnRK2 and Positively Regulates Salt Tolerance in Transgenic Arabidopsis.

    PubMed

    Zhang, Fan; Wei, Qiuhui; Shi, Jiaochun; Jin, Xia; He, Yuan; Zhang, Yang; Luo, Qingchen; Wang, Yuesheng; Chang, Junli; Yang, Guangxiao; He, Guangyuan

    2017-01-01

    The phytohormone abscisic acid (ABA) is essential in plant responding to biotic and abiotic stresses. Although ABA signaling model is well established in Arabidopsis, ABA receptor PYL family and clade A PP2C subfamily are not yet characterized in monocot model plant Brachypodium distachyon. In this study, we identified 12 PYLs and 8 clade A PP2Cs from B. distachyon genome and successfully cloned 12 PYLs and 7 clade A PP2Cs. Bioinformatic and expression analyses showed that most of the identified genes respond to several signal molecules and abiotic stresses. Protein-protein interaction analysis revealed that many BdPYLs and BdPP2CAs participate in the classic ABA-PYL-PP2C-SnRK2 signaling pathway. A clade A PP2C, designated BdPP2CA6, interacted with BdPYL11 in the absence of ABA and localized in nucleus. Most clade A PP2C members from Arabidopsis showed negatively regulation in ABA signaling pathway, whereas BdPP2CA6-overexpression transgenic Arabidopsis showed ABA hypersensitive phenotype, resulting in enhanced stomatal closure and salinity tolerance. Our results indicate that BdPP2CA6 positively regulates ABA and stress signal pathway in transgenic Arabidopsis plant seedlings.

  13. Tissue- and environmental response-specific expression of 10 PP2C transcripts in Mesembryanthemum crystallinum.

    PubMed

    Miyazaki, S; Koga, R; Bohnert, H J; Fukuhara, T

    1999-03-01

    Ten transcripts (Mpc1-10) homologous to protein phosphatases of the 2C family have been isolated from the halophyte Mesembryanthemum crystallinum (common ice plant). Transcripts range in size from 1.6 to 2.6 kb, and encode proteins whose catalytic domains are between 24% and 62% identical to that of the Arabidopsis PP2C, ABI1. Transcript expression is tissue specific. Two isoforms are present only in roots (Mpc1 and Mpc5), three in young leaves (Mpc6, 8 and 9), two in old leaves (Mpc6 and Mpc8), and two in post-flowering leaves (Mpc8 and Mpc9). Mpc2 is strongly expressed in roots and also in seeds, meristematic tissues and mature flowers. Mpc3 is specific for leaf meristems, and Mpc4 is found in root and leaf meristems. Mpc7 is restricted to meristematic tissues. Mpc10 is only present in mature flowers. Mpc2 (in roots and leaves), Mpc5 (in roots) and Mpc8 (weakly in leaves) are induced by salinity stress and drought conditions with different kinetics in different tissues, but other Mpcs are downregulated by stress. Cold stress (4 degrees C) leads to a decline in Mpc5 and Mp6, but low temperature provoked a long-term (days) increase in Mpc2 levels in leaves and a transient increase (less than 24 h) in roots. Four full-length transcripts have been obtained. In each case, after over-expression in E. coli, the isolated proteins exhibited (Mg2+-dependent, okadeic acid-insensitive) protein phosphatase activity, although activity against 32P-phosphocasein varied among different PP2Cs. Determination of tissue developmental and stress response specificity of PP2C will facilitate functional studies of signal-transducing enzymes in this halophytic organism.

  14. Mechanistic study of protein phosphatase-1 (PP1), a catalytically promiscuous enzyme.

    PubMed

    McWhirter, Claire; Lund, Elizabeth A; Tanifum, Eric A; Feng, Guoqiang; Sheikh, Qaiser I; Hengge, Alvan C; Williams, Nicholas H

    2008-10-15

    The reaction catalyzed by the protein phosphatase-1 (PP1) has been examined by linear free energy relationships and kinetic isotope effects. With the substrate 4-nitrophenyl phosphate (4NPP), the reaction exhibits a bell-shaped pH-rate profile for kcat/KM indicative of catalysis by both acidic and basic residues, with kinetic pKa values of 6.0 and 7.2. The enzymatic hydrolysis of a series of aryl monoester substrates yields a Brønsted beta(lg) of -0.32, considerably less negative than that of the uncatalyzed hydrolysis of monoester dianions (-1.23). Kinetic isotope effects in the leaving group with the substrate 4NPP are (18)(V/K) bridge = 1.0170 and (15)(V/K) = 1.0010, which, compared against other enzymatic KIEs with and without general acid catalysis, are consistent with a loose transition state with partial neutralization of the leaving group. PP1 also efficiently catalyzes the hydrolysis of 4-nitrophenyl methylphosphonate (4NPMP). The enzymatic hydrolysis of a series of aryl methylphosphonate substrates yields a Brønsted beta(lg) of -0.30, smaller than the alkaline hydrolysis (-0.69) and similar to the beta(lg) measured for monoester substrates, indicative of similar transition states. The KIEs and the beta(lg) data point to a transition state for the alkaline hydrolysis of 4NPMP that is similar to that of diesters with the same leaving group. For the enzymatic reaction of 4NPMP, the KIEs are indicative of a transition state that is somewhat looser than the alkaline hydrolysis reaction and similar to the PP1-catalyzed monoester reaction. The data cumulatively point to enzymatic transition states for aryl phosphate monoester and aryl methylphosphonate hydrolysis reactions that are much more similar to one another than the nonenzymatic hydrolysis reactions of the two substrates.

  15. Dietary vitamin E and pulmonary biochemical and morphological alterations of rats exposed to 0. 1 ppM ozone

    SciTech Connect

    Chow, C.K.; Plopper, C.G.; Chiu, M.; Dungworth, D.L.

    1981-04-01

    Three groups of 28 1-month-old male Sprague-Dawley rats each were fed a basal vitamin E-deficient diet and supplemented with either 0, 11, or 110 ppM vitamin E for 38 days, and were then exposed to 0 or 0.1 ppM ozone continuously for 7 days. Following ozone exposure, the level of reduced glutathione (GSH) and activities of GSH peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase (G-6-PD), and lactate dehydrogenase (LDH), but not of malic dehydrogenase, were significantly elevated in the lungs of rats fed the vitamin E deficient diet. The level of GSH and activities of GSH peroxidase and G-6-PD were also significantly increased in the lungs of the animal group fed the 11 ppM vitamin E diet, while none of the biochemical measurements made was significantly altered by ozone in the 110-ppM vitamin E diet fed rats. Scanning electron microscope examination revealed that five out of six rats on the vitamin E-deficient diet and four out of six from the 11-ppM vitamin E diet had detectable lesions following ozone exposure, as compared with only one of the six exposed animals from the 110-ppM vitamin E diet. The lesion was restricted to bronchiolar epithelium and alveoli immediately adjacent to the bronchiole-alveolar duct junction. None of the control animals had detectable lesions. The results suggest that exposure to ozone at 0.1-ppM level can produce detectable pulmonary damage, and that dietary vitamin E alters pulmonary susceptibility to ozone exposure.

  16. Observation and study of the baryonic B-meson decays B→D(*)pp̄(π)(π)

    DOE PAGES

    del Amo Sanchez, P.; Lees, J. P.; Poireau, V.; ...

    2012-05-30

    We present results for B-meson decay modes involving a charm meson, protons, and pions using 455×10⁶ BB¯¯¯ pairs recorded by the BaBar detector at the SLAC PEP-II asymmetric-energy e⁺e⁻ collider. The branching fractions are measured for the following ten decays: B¯¯¯⁰→D⁰pp̄, B¯¯¯⁰→D*⁰pp̄, B¯¯¯⁰→D⁺pp̄π⁻, B¯¯¯⁰→D*⁺pp̄π⁻, B⁻→D⁰pp̄π⁻, B⁻→D*⁰pp̄π⁻, B¯¯¯⁰→D⁰pp̄π⁻π⁺, B¯¯¯⁰→D*⁰pp̄π⁻π⁺, B⁻→D⁺pp̄π⁻π⁻, and B⁻→D*⁺pp̄π⁻π⁻. The four B⁻ and the two five-body B¯¯¯⁰ modes are observed for the first time. The four-body modes are enhanced compared to the three- and the five-body modes. In the three-body modes, the M(pp̄) and M(D(*)⁰p) invariant-mass distributions show enhancements near threshold values. In the four-body mode B¯¯¯⁰→D⁺pp̄π⁻, themore » M(pπ⁻) distribution shows a narrow structure of unknown origin near 1.5 GeV/c². The distributions for the five-body modes, in contrast to the others, are similar to the expectations from uniform phase-space predictions.« less

  17. Observation and study of the baryonic B-meson decays B→D(*)pp̄(π)(π)

    SciTech Connect

    del Amo Sanchez, P.; Lees, J. P.; Poireau, V.; Prencipe, E.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Battaglia, M.; Brown, D. N.; Hooberman, B.; Kerth, L. T.; Kolomensky, Yu. G.; Lynch, G.; Osipenkov, I. L.; Tanabe, T.; Hawkes, C. M.; Watson, A. T.; Koch, H.; Schroeder, T.; Asgeirsson, D. J.; Hearty, C.; Mattison, T. S.; McKenna, J. A.; Khan, A.; Randle-Conde, A.; Blinov, V. E.; Buzykaev, A. R.; Druzhinin, V. P.; Golubev, V. B.; Onuchin, A. P.; Serednyakov, S. I.; Skovpen, Yu. I.; Solodov, E. P.; Todyshev, K. Yu.; Yushkov, A. N.; Bondioli, M.; Curry, S.; Kirkby, D.; Lankford, A. J.; Mandelkern, M.; Martin, E. C.; Stoker, D. P.; Atmacan, H.; Gary, J. W.; Liu, F.; Long, O.; Vitug, G. M.; Campagnari, C.; Flanigan, J. M.; Hong, T. M.; Kovalskyi, D.; Richman, J. D.; West, C.; Eisner, A. M.; Heusch, C. A.; Kroseberg, J.; Lockman, W. S.; Martinez, A. J.; Schalk, T.; Schumm, B. A.; Seiden, A.; Winstrom, L. O.; Cheng, C. H.; Doll, D. A.; Echenard, B.; Hitlin, D. G.; Ongmongkolkul, P.; Porter, F. C.; Rakitin, A. Y.; Andreassen, R.; Dubrovin, M. S.; Mancinelli, G.; Meadows, B. T.; Sokoloff, M. D.; Bloom, P. C.; Ford, W. T.; Gaz, A.; Nagel, M.; Nauenberg, U.; Smith, J. G.; Wagner, S. R.; Ayad, R.; Toki, W. H.; Jasper, H.; Karbach, T. M.; Merkel, J.; Petzold, A.; Spaan, B.; Wacker, K.; Kobel, M. J.; Schubert, K. R.; Schwierz, R.; Bernard, D.; Verderi, M.; Clark, P. J.; Playfer, S.; Watson, J. E.; Andreotti, M.; Bettoni, D.; Bozzi, C.; Calabrese, R.; Cecchi, A.; Cibinetto, G.; Fioravanti, E.; Franchini, P.; Luppi, E.; Munerato, M.; Negrini, M.; Petrella, A.; Piemontese, L.; Baldini-Ferroli, R.; Calcaterra, A.; de Sangro, R.; Finocchiaro, G.; Nicolaci, M.; Pacetti, S.; Patteri, P.; Peruzzi, I. M.; Piccolo, M.; Rama, M.; Zallo, A.; Contri, R.; Guido, E.; Lo Vetere, M.; Monge, M. R.; Passaggio, S.; Patrignani, C.; Robutti, E.; Tosi, S.; Bhuyan, B.; Prasad, V.; Lee, C. L.; Morii, M.; Adametz, A.; Marks, J.; Uwer, U.; Bernlochner, F. U.; Ebert, M.; Lacker, H. M.; Lueck, T.; Volk, A.; Dauncey, P. D.; Tibbetts, M.; Behera, P. K.; Mallik, U.; Chen, C.; Cochran, J.; Crawley, H. B.; Dong, L.; Meyer, W. T.; Prell, S.; Rosenberg, E. I.; Rubin, A. E.; Gritsan, A. V.; Guo, Z. J.; Arnaud, N.; Davier, M.; Derkach, D.; Firmino da Costa, J.; Grosdidier, G.; Le Diberder, F.; Lutz, A. M.; Malaescu, B.; Perez, A.; Roudeau, P.; Schune, M. H.; Serrano, J.; Sordini, V.; Stocchi, A.; Wang, L.; Wormser, G.; Lange, D. J.; Wright, D. M.; Bingham, I.; Chavez, C. A.; Coleman, J. P.; Fry, J. R.; Gabathuler, E.; Gamet, R.; Hutchcroft, D. E.; Payne, D. J.; Touramanis, C.; Bevan, A. J.; Di Lodovico, F.; Sacco, R.; Sigamani, M.; Cowan, G.; Paramesvaran, S.; Wren, A. C.; Brown, D. N.; Davis, C. L.; Denig, A. G.; Fritsch, M.; Gradl, W.; Hafner, A.; Alwyn, K. E.; Bailey, D.; Barlow, R. J.; Jackson, G.; Lafferty, G. D.; Anderson, J.; Cenci, R.; Jawahery, A.; Roberts, D. A.; Simi, G.; Tuggle, J. M.; Dallapiccola, C.; Salvati, E.; Cowan, R.; Dujmic, D.; Sciolla, G.; Zhao, M.; Lindemann, D.; Patel, P. M.; Robertson, S. H.; Schram, M.; Biassoni, P.; Lazzaro, A.; Lombardo, V.; Palombo, F.; Stracka, S.; Cremaldi, L.; Godang, R.; Kroeger, R.; Sonnek, P.; Summers, D. J.; Nguyen, X.; Simard, M.; Taras, P.; De Nardo, G.; Monorchio, D.; Onorato, G.; Sciacca, C.; Raven, G.; Snoek, H. L.; Jessop, C. P.; Knoepfel, K. J.; LoSecco, J. M.; Wang, W. F.; Corwin, L. A.; Honscheid, K.; Kass, R.; Morris, J. P.; Blount, N. L.; Brau, J.; Frey, R.; Igonkina, O.; Kolb, J. A.; Rahmat, R.; Sinev, N. B.; Strom, D.; Strube, J.; Torrence, E.; Castelli, G.; Feltresi, E.; Gagliardi, N.; Margoni, M.; Morandin, M.; Posocco, M.; Rotondo, M.; Simonetto, F.; Stroili, R.; Ben-Haim, E.; Bonneaud, G. R.; Briand, H.; Calderini, G.; Chauveau, J.; Hamon, O.; Leruste, Ph.; Marchiori, G.; Ocariz, J.; Prendki, J.; Sitt, S.; Biasini, M.; Manoni, E.; Rossi, A.; Angelini, C.; Batignani, G.; Bettarini, S.; Carpinelli, M.; Casarosa, G.; Cervelli, A.; Forti, F.; Giorgi, M. A.; Lusiani, A.; Neri, N.; Paoloni, E.; Rizzo, G.; Walsh, J. J.; Lopes Pegna, D.; Lu, C.; Olsen, J.; Smith, A. J. S.; Telnov, A. V.; Anulli, F.; Baracchini, E.; Cavoto, G.; Faccini, R.; Ferrarotto, F.; Ferroni, F.; Gaspero, M.; Li Gioi, L.; Mazzoni, M. A.; Piredda, G.; Renga, F.; Hartmann, T.; Leddig, T.; Schröder, H.; Waldi, R.; Adye, T.; Franek, B.; Olaiya, E. O.; Wilson, F. F.; Emery, S.; Hamel de Monchenault, G.; Vasseur, G.; Yèche, Ch.; Zito, M.; Allen, M. T.; Aston, D.; Bard, D. J.; Bartoldus, R.; Benitez, J. F.; Cartaro, C.; Convery, M. R.; Dorfan, J.; Dubois-Felsmann, G. P.; Dunwoodie, W.; Field, R. C.; Franco Sevilla, M.; Fulsom, B. G.; Gabareen, A. M.; Graham, M. T.; Grenier, P.; Hast, C.; Innes, W. R.; Kelsey, M. H.; Kim, H.; Kim, P.; Kocian, M. L.; Leith, D. W. G. S.; Li, S.; Lindquist, B.; Luitz, S.; Luth, V.; Lynch, H. L.; MacFarlane, D. B.; Marsiske, H.; Muller, D. R.; Neal, H.; Nelson, S.; O’Grady, C. P.; Ofte, I.; Perl, M.; Pulliam, T.; Ratcliff, B. N.; Roodman, A.; Salnikov, A. A.; Santoro, V.; Schindler, R. H.; Schwiening, J.; Snyder, A.; Su, D.; Sullivan, M. K.; Sun, S.; Suzuki, K.; Thompson, J. M.; Va’vra, J.; Wagner, A. P.; Weaver, M.; West, C. A.; Wisniewski, W. J.; Wittgen, M.; Wright, D. H.; Wulsin, H. W.; Yarritu, A. K.; Young, C. C.; Ziegler, V.; Chen, X. R.; Park, W.; Purohit, M. V.; White, R. M.; Wilson, J. R.; Sekula, S. J.; Bellis, M.; Burchat, P. R.; Edwards, A. J.; Miyashita, T. S.; Ahmed, S.; Alam, M. S.; Ernst, J. A.; Pan, B.; Saeed, M. A.; Zain, S. B.; Guttman, N.; Soffer, A.; Lund, P.; Spanier, S. M.; Eckmann, R.; Ritchie, J. L.; Ruland, A. M.; Schilling, C. J.; Schwitters, R. F.; Wray, B. C.; Izen, J. M.; Lou, X. C.; Bianchi, F.; Gamba, D.; Pelliccioni, M.; Bomben, M.; Lanceri, L.; Vitale, L.; Lopez-March, N.; Martinez-Vidal, F.; Milanes, D. A.; Oyanguren, A.; Albert, J.; Banerjee, Sw.; Choi, H. H. F.; Hamano, K.; King, G. J.; Kowalewski, R.; Lewczuk, M. J.; Nugent, I. M.; Roney, J. M.; Sobie, R. J.; Gershon, T. J.; Harrison, P. F.; Latham, T. E.; Puccio, E. M. T.; Band, H. R.; Dasu, S.; Flood, K. T.; Pan, Y.; Prepost, R.; Vuosalo, C. O.; Wu, S. L.

    2012-05-30

    We present results for B-meson decay modes involving a charm meson, protons, and pions using 455×10⁶ BB¯¯¯ pairs recorded by the BaBar detector at the SLAC PEP-II asymmetric-energy e⁺e⁻ collider. The branching fractions are measured for the following ten decays: B¯¯¯⁰→D⁰pp̄, B¯¯¯⁰→D*⁰pp̄, B¯¯¯⁰→D⁺pp̄π⁻, B¯¯¯⁰→D*⁺pp̄π⁻, B⁻→D⁰pp̄π⁻, B⁻→D*⁰pp̄π⁻, B¯¯¯⁰→D⁰pp̄π⁻π⁺, B¯¯¯⁰→D*⁰pp̄π⁻π⁺, B⁻→D⁺pp̄π⁻π⁻, and B⁻→D*⁺pp̄π⁻π⁻. The four B⁻ and the two five-body B¯¯¯⁰ modes are observed for the first time. The four-body modes are enhanced compared to the three- and the five-body modes. In the three-body modes, the M(pp̄) and M(D(*)⁰p) invariant-mass distributions show enhancements near threshold values. In the four-body mode B¯¯¯⁰→D⁺pp̄π⁻, the M(pπ⁻) distribution shows a narrow structure of unknown origin near 1.5 GeV/c². The distributions for the five-body modes, in contrast to the others, are similar to the expectations from uniform phase-space predictions.

  18. Mutational analysis of the pumpkin (Cucurbita maxima) phloem exudate lectin, PP2 reveals Ser-104 is crucial for carbohydrate binding.

    PubMed

    Bobbili, Kishore Babu; Bandari, Shyam; Grobe, Kay; Swamy, Musti J

    2014-07-18

    The pumpkin phloem lectin (PP2) is an RNA-binding, defense-related, chitooligosaccharide-specific, homodimeric lectin of Mr 48 kDa expressed at high concentrations in the sieve elements and companion cells of pumpkin (Cucurbita maxima). In the present study, PP2 was expressed in the methylotrophic yeast Pichia pastoris with the Saccharomyces α-factor sequence to direct the recombinant protein into the secretory pathway as a prerequisite for unimpaired folding and posttranslational glycosylation of recombinant PP2. Previous computational modeling and ligand docking studies predicted a putative chitooligosaccharide-binding site on the PP2 surface, which was divided into three subsites, with two amino acid residues in each subsite identified as possible candidates for interaction with chitooligosaccharides (CHOs). In this work, mutational analysis and hemagglutination assays were employed to verify the role of the predicted residues in the carbohydrate binding activity of the protein. The results obtained revealed that mutation of Ser-104 to Ala (S104A) at subsite-2 resulted in about 90% loss of agglutination activity of the protein, indicating that Ser-104 is crucial for the binding of CHOs to PP2. Also, L100A (at subsite-1) and K200A (at subsite-3) independently decreased the lectin activity by about 40%, indicating that these two residues also contribute significantly to sugar binding by PP2. Together, these findings confirm that all the three subsites contribute to varying degrees toward PP2-carbohydrate interaction, and confirm the validity of the computational model, as proposed earlier.

  19. Testable SUSY spectra from GUTs at a 100 TeV pp collider

    NASA Astrophysics Data System (ADS)

    Antusch, Stefan; Sluka, Constantin

    2016-10-01

    Grand Unified Theories (GUTs) are attractive candidates for more fundamental elementary particle theories. They cannot only unify the Standard Model (SM) interactions but also different types of SM fermions, in particular quarks and leptons, in joint representations of the GUT gauge group. We discuss how comparing predictive supersymmetric GUT models with the experimental results for quark and charged lepton masses leads to constraints on the SUSY spectrum. We show an example from a recent analysis where the resulting superpartner masses where found just beyond the reach of LHC Run 1, but fully within the reach of a 100 TeV pp collider.

  20. A comparative study on two characteristic parametrizations for high energy pp and overlinepp total cross sections

    NASA Astrophysics Data System (ADS)

    Bueno, A.; Velasco, J.

    1996-02-01

    Available high energy data for both pp and overlinepp total cross sections ( f GeV < s < 1.8 TeV ) are described by means of two well-known distinct parametrizations, characteristic of theoretical (“Regge-like” expression) and experimental (“Froissart-Martin-like” expression) practices, respectively. Both are compared from the statistical point of view. For the whole set of present data statistical analysis ( χ2/d.o.f.) seems to favour a “Froissart-like” ((ln s) γ≈2 ) rise of the total cross section rather than a “Regge-like” ( sɛ) one.

  1. Absolute np and pp cross section determinations aimed at improving the standard for cross section measurements

    SciTech Connect

    Laptev, Alexander B; Haight, Robert C; Tovesson, Fredrik; Arndt, Richard A; Briscoe, William J; Paris, Mark W; Strakovsky, Igor I; Workman, Ron L

    2010-01-01

    Purpose of present research is a keeping improvement of the standard for cross section measurements of neutron-induced reactions. The cross sections for np and pp scattering below 1000 MeV are determined based on partial-wave analyses (PW As) of nucleon-nucleon scattering data. These cross sections are compared with the most recent ENDF/B-V11.0 and JENDL-4.0 data files, and the Nijmegen PWA. Also a comparison of evaluated data with recent experimental data was made to check a quality of evaluation. Excellent agreement was found between the new experimental data and our PWA predictions.

  2. Absolute np and pp Cross Section Determinations Aimed At Improving The Standard For Cross Section Measurements

    SciTech Connect

    Laptev, A. B.; Haight, R. C.; Tovesson, F.; Arndt, R. A.; Briscoe, W. J.; Paris, M. W.; Strakovsky, I. I.; Workman, R. L.

    2011-06-01

    Purpose of present research is a keeping improvement of the standard for cross section measurements of neutron-induced reactions. The cross sections for np and pp scattering below 1 GeV are determined based on partial-wave analyses (PWAs) of nucleon-nucleon scattering data. These cross sections are compared with the most recent ENDF/B-VII.0 and JENDL-4.0 data files, and the Nijmegen PWA. Also a comparison of evaluated data with recent experimental data was made to check a quality of evaluation. Excellent agreement was found between the new experimental data and our PWA predictions.

  3. Proton source size measurements in the eA {yields} e{prime}ppX reaction

    SciTech Connect

    Aleksey Stavinskiy; Konstantin Mikhaylov; R. Lednicky; Alexander Vlassov; Et. Al.

    2004-06-01

    Two-proton correlations at small relative momentum q were studied in the eA({sup 3}He, {sup 4}He, C, Fe) {yields} e{prime}ppX reaction at E{sub 0} = 4.46 GeV using the CLAS detector at Jefferson Lab. The enhancement of the correlation function at small q was found to be in accordance with theoretical expectation. Emission region sizes were extracted and proved to be dependent on A and proton momentum. The size of the two-proton emission region on the lightest possible nucleus, He, was measured for the first time.

  4. J/ψ polarization in pp collisions at √s=7 TeV.

    PubMed

    Abelev, B; Abrahantes Quintana, A; Adamová, D; Adare, A M; Aggarwal, M M; Aglieri Rinella, G; Agocs, A G; Agostinelli, A; Aguilar Salazar, S; Ahammed, Z; Ahmad, N; Ahmad Masoodi, A; Ahn, S U; Akindinov, A; Aleksandrov, D; Alessandro, B; AlfaroMolina, R; Alici, A; Alkin, A; Almaráz Aviña, E; Alt, T; Altini, V; Altinpinar, S; Altsybeev, I; Andrei, C; Andronic, A; Anguelov, V; Anson, C; Antičić, T; Antinori, F; Antonioli, P; Aphecetche, L; Appelshäuser, H; Arbor, N; Arcelli, S; Arend, A; Armesto, N; Arnaldi, R; Aronsson, T; Arsene, I C; Arslandok, M; Asryan, A; Augustinus, A; Averbeck, R; Awes, T C; Aystö, J; Azmi, M D; Bach, M; Badalà, A; Baek, Y W; Bailhache, R; Bala, R; Baldini Ferroli, R; Baldisseri, A; Baldit, A; Baltasar Dos Santos Pedrosa, F; Bán, J; Baral, R C; Barbera, R; Barile, F; Barnaföldi, G G; Barnby, L S; Barret, V; Bartke, J; Basile, M; Bastid, N; Bathen, B; Batigne, G; Batyunya, B; Baumann, C; Bearden, I G; Beck, H; Belikov, I; Bellini, F; Bellwied, R; Belmont-Moreno, E; Beole, S; Berceanu, I; Bercuci, A; Berdnikov, Y; Berenyi, D; Bergmann, C; Berzano, D; Betev, L; Bhasin, A; Bhati, A K; Bianchi, N; Bianchi, L; Bianchin, C; Bielčík, J; Bielčíková, J; Bilandzic, A; Blanco, F; Blanco, F; Blau, D; Blume, C; Boccioli, M; Bock, N; Bogdanov, A; Bøggild, H; Bogolyubsky, M; Boldizsár, L; Bombara, M; Book, J; Borel, H; Borissov, A; Bortolin, C; Bose, S; Bossú, F; Botje, M; Böttger, S; Boyer, B; Braun-Munzinger, P; Bregant, M; Breitner, T; Broz, M; Brun, R; Bruna, E; Bruno, G E; Budnikov, D; Buesching, H; Bufalino, S; Bugaiev, K; Busch, O; Buthelezi, Z; Caffarri, D; Cai, X; Caines, H; Calvo Villar, E; Camerini, P; Canoa Roman, V; Cara Romeo, G; Carena, W; Carena, F; Carlin Filho, N; Carminati, F; Carrillo Montoya, C A; Casanova Díaz, A; Caselle, M; Castillo Castellanos, J; Castillo Hernandez, J F; Casula, E A R; Catanescu, V; Cavicchioli, C; Cepila, J; Cerello, P; Chang, B; Chapeland, S; Charvet, J L; Chattopadhyay, S; Chattopadhyay, S; Cherney, M; Cheshkov, C; 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Dönigus, B; Dordic, O; Driga, O; Dubey, A K; Ducroux, L; Dupieux, P; Dutta Majumdar, M R; Dutta Majumdar, A K; Elia, D; Emschermann, D; Engel, H; Erdal, H A; Espagnon, B; Estienne, M; Esumi, S; Evans, D; Eyyubova, G; Fabris, D; Faivre, J; Falchieri, D; Fantoni, A; Fasel, M; Fearick, R; Fedunov, A; Fehlker, D; Feldkamp, L; Felea, D; Feofilov, G; Fernández Téllez, A; Ferreiro, E G; Ferretti, A; Ferretti, R; Figiel, J; Figueredo, M A S; Filchagin, S; Fini, R; Finogeev, D; Fionda, F M; Fiore, E M; Floris, M; Foertsch, S; Foka, P; Fokin, S; Fragiacomo, E; Fragkiadakis, M; Frankenfeld, U; Fuchs, U; Furget, C; Fusco Girard, M; Gaardhøje, J J; Gagliardi, M; Gago, A; Gallio, M; Gangadharan, D R; Ganoti, P; Garabatos, C; Garcia-Solis, E; Garishvili, I; Gerhard, J; Germain, M; Geuna, C; Gheata, A; Gheata, M; Ghidini, B; Ghosh, P; Gianotti, P; Girard, M R; Giubellino, P; Gladysz-Dziadus, E; Glässel, P; Gomez, R; González-Trueba, L H; González-Zamora, P; Gorbunov, S; Goswami, A; Gotovac, S; Grabski, V; Graczykowski, L K; Grajcarek, R; Grelli, A; Grigoras, A; Grigoras, C; Grigoriev, V; Grigoryan, S; Grigoryan, A; Grinyov, B; Grion, N; Gros, P; Grosse-Oetringhaus, J F; Grossiord, J-Y; Grosso, R; Guber, F; Guernane, R; Guerra Gutierrez, C; Guerzoni, B; Guilbaud, M; Gulbrandsen, K; Gunji, T; Gupta, A; Gupta, R; Gutbrod, H; Haaland, Ø; Hadjidakis, C; Haiduc, M; Hamagaki, H; Hamar, G; Han, B H; Hanratty, L D; Hansen, A; Harmanova, Z; Harris, J W; Hartig, M; Hasegan, D; Hatzifotiadou, D; Hayrapetyan, A; Heide, M; Helstrup, H; Herghelegiu, A; Herrera Corral, G; Herrmann, N; Hetland, K F; Hicks, B; Hille, P T; Hippolyte, B; Horaguchi, T; Hori, Y; Hristov, P; Hřivnáčová, I; Huang, M; Huber, S; Humanic, T J; Hwang, D S; Ichou, R; Ilkaev, R; Ilkiv, I; Inaba, M; Incani, E; Innocenti, P G; Innocenti, G M; Ippolitov, M; Irfan, M; Ivan, C; Ivanov, A; Ivanov, M; Ivanov, V; Ivanytskyi, O; Jachołkowski, A; Jacobs, P M; Jancurová, L; Jangal, S; Janik, M A; Janik, R; Jayarathna, P H S Y; Jena, S; Jimenez Bustamante, R T; Jirden, L; Jones, P G; Jung, H; Jung, W; Jusko, A; Kaidalov, A B; Kakoyan, V; Kalcher, S; Kaliňák, P; Kalisky, M; Kalliokoski, T; Kalweit, A; Kanaki, K; Kang, J H; Kaplin, V; Karasu Uysal, A; Karavichev, O; Karavicheva, T; Karpechev, E; Kazantsev, A; Kebschull, U; Keidel, R; Khan, M M; Khan, S A; Khan, P; Khanzadeev, A; Kharlov, Y; Kileng, B; Kim, S; Kim, D W; Kim, J H; Kim, J S; Kim, M; Kim, S H; Kim, T; Kim, B; Kim, D J; Kirsch, S; Kisel, I; Kiselev, S; Kisiel, A; Klay, J L; Klein, J; Klein-Bösing, C; Kliemant, M; Kluge, A; Knichel, M L; Koch, K; Köhler, M K; Kolojvari, A; Kondratiev, V; Kondratyeva, N; Konevskikh, A; Kottachchi Kankanamge Don, C; Kour, R; Kowalski, M; Kox, S; Koyithatta Meethaleveedu, G; Kral, J; Králik, I; Kramer, F; Kraus, I; Krawutschke, T; Kretz, M; Krivda, M; Krizek, F; Krus, M; Kryshen, E; Krzewicki, M; Kucheriaev, Y; Kuhn, C; Kuijer, P G; Kurashvili, P; Kurepin, A B; Kurepin, A; Kuryakin, A; Kushpil, V; Kushpil, S; Kvaerno, H; Kweon, M J; Kwon, Y; Ladrón de Guevara, P; Lakomov, I; Langoy, R; Lara, C; Lardeux, A; La Rocca, P; Larsen, D T; Lazzeroni, C; Lea, R; Le Bornec, Y; Lee, S C; Lee, K S; Lefèvre, F; Lehnert, J; Leistam, L; Lenhardt, M; Lenti, V; León, H; León Monzón, I; León Vargas, H; Lévai, P; Li, X; Lien, J; Lietava, R; Lindal, S; Lindenstruth, V; Lippmann, C; Lisa, M A; Liu, L; Loenne, P I; Loggins, V R; Loginov, V; Lohn, S; Lohner, D; Loizides, C; Loo, K K; Lopez, X; López Torres, E; Løvhøiden, G; Lu, X-G; Luettig, P; Lunardon, M; Luo, J; Luparello, G; Luquin, L; Luzzi, C; Ma, R; Ma, K; Madagodahettige-Don, D M; Maevskaya, A; Mager, M; Mahapatra, D P; Maire, A; Malaev, M; Maldonado Cervantes, I; Malinina, L; Mal'Kevich, D; Malzacher, P; Mamonov, A; Manceau, L; Mangotra, L; Manko, V; Manso, F; Manzari, V; Mao, Y; Marchisone, M; Mareš, J; Margagliotti, G V; Margotti, A; Marín, A; Markert, C; Martashvili, I; Martinengo, P; Martínez, M I; Martínez Davalos, A; Martínez García, G; Martynov, Y; Mas, A; Masciocchi, S; Masera, M; Masoni, A; Massacrier, L; Mastromarco, M; Mastroserio, A; Matthews, Z L; Matyja, A; Mayani, D; Mayer, C; Mazzoni, M A; Meddi, F; Menchaca-Rocha, A; Mercado Pérez, J; Meres, M; Miake, Y; Michalon, A; Midori, J; Milano, L; Milosevic, J; Mischke, A; Mishra, A N; Miśkowiec, D; Mitu, C; Mlynarz, J; Mohanty, A K; Mohanty, B; Molnar, L; Montaño Zetina, L; Monteno, M; Montes, E; Moon, T; Morando, M; Moreira De Godoy, D A; Moretto, S; Morsch, A; Muccifora, V; Mudnic, E; Muhuri, S; Müller, H; Munhoz, M G; Musa, L; Musso, A; Nandi, B K; Nania, R; Nappi, E; Nattrass, C; Naumov, N P; Navin, S; Nayak, T K; Nazarenko, S; Nazarov, G; Nedosekin, A; Nicassio, M; Nielsen, B S; Niida, T; Nikolaev, S; Nikolic, V; Nikulin, V; Nikulin, S; Nilsen, B S; Nilsson, M S; Noferini, F; Nomokonov, P; Nooren, G; Novitzky, N; Nyanin, A; Nyatha, A; Nygaard, C; Nystrand, J; Obayashi, H; Ochirov, A; Oeschler, H; Oh, S K; Oleniacz, J; Oppedisano, C; Ortiz Velasquez, A; Ortona, G; Oskarsson, A; Ostrowski, P; Otterlund, I; Otwinowski, J; Øvrebekk, G; Oyama, K; Ozawa, K; Pachmayer, Y; Pachr, M; Padilla, F; Pagano, P; Paić, G; Painke, F; Pajares, C; Pal, S; Pal, S K; Palaha, A; Palmeri, A; Papikyan, V; Pappalardo, G S; Park, W J; Passfeld, A; Pastirčák, B; Patalakha, D I; Paticchio, V; Pavlinov, A; Pawlak, T; Peitzmann, T; Perales, M; Pereira De Oliveira Filho, E; Peresunko, D; Pérez Lara, C E; Perez Lezama, E; Perini, D; Perrino, D; Peryt, W; Pesci, A; Peskov, V; Pestov, Y; Petráček, V; Petran, M; Petris, M; Petrov, P; Petrovici, M; Petta, C; Piano, S; Piccotti, A; Pikna, M; Pillot, P; Pinazza, O; Pinsky, L; Pitz, N; Piuz, F; Piyarathna, D B; Płoskoń, M; Pluta, J; Pocheptsov, T; Pochybova, S; Podesta-Lerma, P L M; Poghosyan, M G; Polák, K; Polichtchouk, B; Pop, A; Porteboeuf-Houssais, S; Pospíšil, V; Potukuchi, B; Prasad, S K; Preghenella, R; Prino, F; Pruneau, C A; Pshenichnov, I; Puddu, G; Pulvirenti, A; Punin, V; Putiš, M; Putschke, J; Quercigh, E; Qvigstad, H; Rachevski, A; Rademakers, A; Radomski, S; Räihä, T S; Rak, J; Rakotozafindrabe, A; Ramello, L; Ramírez Reyes, A; Raniwala, S; Raniwala, R; Räsänen, S S; Rascanu, B T; Rathee, D; Read, K F; Real, J S; Redlich, K; Reichelt, P; Reicher, M; Renfordt, R; Reolon, A R; Reshetin, A; Rettig, F; Revol, J-P; Reygers, K; Ricaud, H; Riccati, L; Ricci, R A; Richter, M; Riedler, P; Riegler, W; Riggi, F; Rodríguez Cahuantzi, M; Rohr, D; Röhrich, D; Romita, R; Ronchetti, F; Rosnet, P; Rossegger, S; Rossi, A; Roukoutakis, F; Roy, C; Roy, P; Rubio Montero, A J; Rui, R; Ryabinkin, E; Rybicki, A; Sadovsky, S; Safařík, K; Sahu, P K; Saini, J; Sakaguchi, H; Sakai, S; Sakata, D; Salgado, C A; Sambyal, S; Samsonov, V; Sanchez Castro, X; Sándor, L; Sandoval, A; Sano, M; Sano, S; Santo, R; Santoro, R; Sarkamo, J; Scapparone, E; Scarlassara, F; Scharenberg, R P; Schiaua, C; Schicker, R; Schmidt, H R; Schmidt, C; Schreiner, S; Schuchmann, S; Schukraft, J; Schutz, Y; Schwarz, K; Schweda, K; Scioli, G; Scomparin, E; Scott, R; Scott, P A; Segato, G; Selyuzhenkov, I; Senyukov, S; Seo, J; Serci, S; Serradilla, E; 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Trzaska, W H; Tsuji, T; Tumkin, A; Turrisi, R; Tveter, T S; Ulery, J; Ullaland, K; Ulrich, J; Uras, A; Urbán, J; Urciuoli, G M; Usai, G L; Vajzer, M; Vala, M; Valencia Palomo, L; Vallero, S; van der Kolk, N; Vande Vyvre, P; van Leeuwen, M; Vannucci, L; Vargas, A; Varma, R; Vasileiou, M; Vasiliev, A; Vechernin, V; Veldhoen, M; Venaruzzo, M; Vercellin, E; Vergara, S; Vernekohl, D C; Vernet, R; Verweij, M; Vickovic, L; Viesti, G; Vikhlyantsev, O; Vilakazi, Z; Villalobos Baillie, O; Vinogradov, A; Vinogradov, L; Vinogradov, Y; Virgili, T; Viyogi, Y P; Vodopyanov, A; Voloshin, K; Voloshin, S; Volpe, G; von Haller, B; Vranic, D; Vrláková, J; Vulpescu, B; Vyushin, A; Wagner, V; Wagner, B; Wan, R; Wang, Y; Wang, D; Wang, Y; Wang, M; Watanabe, K; Wessels, J P; Westerhoff, U; Wiechula, J; Wikne, J; Wilde, M; Wilk, G; Wilk, A; Williams, M C S; Windelband, B; Xaplanteris Karampatsos, L; Yang, H; Yano, S; Yasnopolskiy, S; Yi, J; Yin, Z; Yokoyama, H; Yoo, I-K; Yoon, J; Yu, W; Yuan, X; Yushmanov, I; Zach, C; Zampolli, C; Zaporozhets, S; Zarochentsev, A; Závada, P; Zaviyalov, N; Zbroszczyk, H; Zelnicek, P; Zgura, I; Zhalov, M; Zhang, X; Zhou, F; Zhou, D; Zhou, Y; Zhu, X; Zichichi, A; Zimmermann, A; Zinovjev, G; Zoccarato, Y; Zynovyev, M

    2012-02-24

    The ALICE Collaboration has studied J/ψ production in pp collisions at √s=7 TeV at the LHC through its muon pair decay. The polar and azimuthal angle distributions of the decay muons were measured, and results on the J/ψ polarization parameters λ(θ) and λ(φ) were obtained. The study was performed in the kinematic region 2.5

  5. The energy dependence of the pp {yields} K{sup +}n{Sigma}{sup +} reaction

    SciTech Connect

    Valdau, Yu.

    2011-10-24

    The energy dependence of the total cross section for the pp {yields} K{sup +}n{Sigma}{sup +} reaction has been investigated at the magnetic spectrometer COSY-ANKE. Signals from the production of the {Sigma}{sup +} hyperon were searched for in three simultaneously measured spectra. The values obtained for the total production cross section {sigma}({Sigma}{sup +}) are slightly below those of {sigma}({Sigma}{sup 0}) at the same excess energies. They follow a phase space dependence and do not show any evidence for strong threshold effects or a significant n{Sigma}{sup +} final state interaction.

  6. Measurement of J/ψ polarization in pp collisions at [Formula: see text].

    PubMed

    Aaij, R; Abellan Beteta, C; Adeva, B; Adinolfi, M; Adrover, C; Affolder, A; Ajaltouni, Z; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; Anderlini, L; Anderson, J; Andreassen, R; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Bachmann, S; Back, J J; Baesso, C; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Bauer, Th; Bay, A; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Benayoun, M; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M-O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brook, N H; Brown, H; Burducea, I; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Callot, O; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carranza-Mejia, H; Carson, L; Carvalho Akiba, K; Casse, G; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Charles, M; Charpentier, Ph; Chen, P; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coca, C; Coco, V; Cogan, J; Cogneras, E; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Couturier, B; Cowan, G A; Craik, D C; Cunliffe, S; Currie, R; D'Ambrosio, C; David, P; David, P N Y; Davis, A; De Bonis, I; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Dogaru, M; Donleavy, S; Dordei, F; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dupertuis, F; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; van Eijk, D; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Elsby, D; Falabella, A; Färber, C; Fardell, G; Farinelli, C; Farry, S; Fave, V; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fitzpatrick, C; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Furcas, S; Furfaro, E; Gallas Torreira, A; Galli, D; Gandelman, M; Gandini, P; Gao, Y; Garofoli, J; Garosi, P; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gibson, V; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gordon, H; Gotti, C; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hampson, T; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; Hartmann, T; He, J; Heijne, V; Hennessy, K; Henrard, P; Hernando Morata, J A; van Herwijnen, E; Hicheur, A; Hicks, E; Hill, D; Hoballah, M; Hombach, C; Hopchev, P; Hulsbergen, W; Hunt, P; Huse, T; Hussain, N; Hutchcroft, D; Hynds, D; Iakovenko, V; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jans, E; Jaton, P; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Kaballo, M; Kandybei, S; Karacson, M; Karbach, T M; Kenyon, I R; Kerzel, U; Ketel, T; Keune, A; Khanji, B; Kochebina, O; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucharczyk, M; Kudryavtsev, V; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanciotti, E; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Li Gioi, L; Liles, M; Lindner, R; Linn, C; Liu, B; Liu, G; Lohn, S; Longstaff, I; Lopes, J H; Lopez Asamar, E; Lopez-March, N; Lu, H; Lucchesi, D; Luisier, J; Luo, H; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Manca, G; Mancinelli, G; Marconi, U; Märki, R; Marks, J; Martellotti, G; Martens, A; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martins Tostes, D; Martynov, A; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Maurice, E; Mazurov, A; McCarthy, J; McNab, A; McNulty, R; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M-N; Molina Rodriguez, J; Monteil, S; Moran, D; Morawski, P; Morello, M J; Mountain, R; Mous, I; Muheim, F; Müller, K; Muresan, R; Muryn, B; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neufeld, N; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Nomerotski, A; Novoselov, A; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Orlandea, M; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrick, G N; Patrignani, C; Pavel-Nicorescu, C; Pazos Alvarez, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perego, D L; Perez Trigo, E; Pérez-Calero Yzquierdo, A; Perret, P; Perrin-Terrin, M; Petridis, K; Petrolini, A; Phan, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Playfer, S; Plo Casasus, M; Polci, F; Polok, G; Poluektov, A; Polycarpo, E; Popov, D; Popovici, B; Potterat, C; Powell, A; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rademacker, J H; Rakotomiaramanana, B; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Redford, S; Reid, M M; Dos Reis, A C; Ricciardi, S; Richards, A; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rouvinet, J; Ruf, T; Ruffini, F; Ruiz, H; Ruiz Valls, P; Sabatino, G; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salzmann, C; Sanmartin Sedes, B; Sannino, M; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sapunov, M; Sarti, A; Satriano, C; Satta, A; Savrie, M; Savrina, D; Schaack, P; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Senderowska, K; Sepp, I; Serra, N; Serrano, J; Seyfert, P; Shapkin, M; Shapoval, I; Shatalov, P; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, O; Shevchenko, V; Shires, A; Silva Coutinho, R; Skwarnicki, T; Smith, N A; Smith, E; Smith, M; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Stagni, F; Stahl, S; Steinkamp, O; Stoica, S; Stone, S; Storaci, B; Straticiuc, M; Straumann, U; Subbiah, V K; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szumlak, T; T'Jampens, S; Teklishyn, M; Teodorescu, E; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Urner, D; Uwer, U; Vagnoni, V; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; Waldi, R; Wallace, R; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Webber, A D; Websdale, D; Whitehead, M; Wicht, J; Wiechczynski, J; Wiedner, D; Wiggers, L; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wishahi, J; Witek, M; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, Z; Yang, Z; Young, R; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, F; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

    An angular analysis of the decay J/ψ→μ(+)μ(-) is performed to measure the polarization of prompt J/ψ mesons produced in pp collisions at [Formula: see text]. The dataset corresponds to an integrated luminosity of 0.37 fb(-1) collected with the LHCb detector. The measurement is presented as a function of transverse momentum, pT, and rapidity, y, of the J/ψ meson, in the kinematic region 2

  7. QCD CORRECTIONS TO DILEPTON PRODUCTION NEAR PARTONIC THRESHOLD IN PP SCATTERING.

    SciTech Connect

    SHIMIZU, H.; STERMAN, G.; VOGELSANG, W.; YOKOYA, H.

    2005-10-02

    We present a recent study of the QCD corrections to dilepton production near partonic threshold in transversely polarized {bar p}p scattering, We analyze the role of the higher-order perturbative QCD corrections in terms of the available fixed-order contributions as well as of all-order soft-gluon resummations for the kinematical regime of proposed experiments at GSI-FAIR. We find that perturbative corrections are large for both unpolarized and polarized cross sections, but that the spin asymmetries are stable. The role of the far infrared region of the momentum integral in the resummed exponent and the effect of the NNLL resummation are briefly discussed.

  8. Production of Λ -hyperons in inelastic p+p interactions at 158 {GeV}/c

    NASA Astrophysics Data System (ADS)

    Aduszkiewicz, A.; Ali, Y.; Andronov, E.; Antićić, T.; Antoniou, N.; Baatar, B.; Bay, F.; Blondel, A.; Bogomilov, M.; Brandin, A.; Bravar, A.; Brzychczyk, J.; Bunyatov, S. A.; Busygina, O.; Christakoglou, P.; Ćirković, M.; Czopowicz, T.; Damyanova, A.; Davis, N.; Dembinski, H.; Deveaux, M.; Diakonos, F.; Di Luise, S.; Dominik, W.; Dumarchez, J.; Dynowski, K.; Engel, R.; Ereditato, A.; Feofilov, G. A.; Fodor, Z.; Garibov, A.; Gaździcki, M.; Golubeva, M.; Grebieszkow, K.; Grzeszczuk, A.; Guber, F.; Haesler, A.; Hasegawa, T.; Hervé, A. E.; Hierholzer, M.; Igolkin, S.; Ivashkin, A.; Johnson, S. R.; Kadija, K.; Kapoyannis, A.; Kaptur, E.; Kisiel, J.; Kobayashi, T.; Kolesnikov, V. I.; Kolev, D.; Kondratiev, V. P.; Korzenev, A.; Kowalik, K.; Kowalski, S.; Koziel, M.; Krasnoperov, A.; Kuich, M.; Kurepin, A.; Larsen, D.; László, A.; Lewicki, M.; Lyubushkin, V. V.; Maćkowiak-Pawłowska, M.; Maksiak, B.; Malakhov, A. I.; Manić, D.; Marcinek, A.; Marino, A. D.; Marton, K.; Mathes, H.-J.; Matulewicz, T.; Matveev, V.; Melkumov, G. L.; Messerly, B.; Mills, G. B.; Morozov, S.; Mrówczyński, S.; Nagai, Y.; Nakadaira, T.; Naskręt, M.; Nirkko, M.; Nishikawa, K.; Panagiotou, A. D.; Paolone, V.; Pavin, M.; Petukhov, O.; Pistillo, C.; Płaneta, R.; Popov, B. A.; Posiadała, M.; Puławski, S.; Puzović, J.; Rauch, W.; Ravonel, M.; Redij, A.; Renfordt, R.; Richter-Wąs, E.; Robert, A.; Röhrich, D.; Rondio, E.; Roth, M.; Rubbia, A.; Rumberger, B. T.; Rustamov, A.; Rybczynski, M.; Sadovsky, A.; Sakashita, K.; Schmidt, K.; Sekiguchi, T.; Selyuzhenkov, I.; Seryakov, A.; Seyboth, P.; Sgalaberna, D.; Shibata, M.; Słodkowski, M.; Staszel, P.; Stefanek, G.; Stepaniak, J.; Ströbele, H.; Šuša, T.; Szuba, M.; Tada, M.; Taranenko, A.; Tefelski, D.; Tereshchenko, V.; Tsenov, R.; Turko, L.; Ulrich, R.; Unger, M.; Vassiliou, M.; Veberič, D.; Vechernin, V. V.; Vesztergombi, G.; Vinogradov, L.; Wilczek, A.; Włodarczyk, Z.; Wojtaszek-Szwarc, A.; Wyszyński, O.; Zambelli, L.; Zimmerman, E. D.

    2016-04-01

    Inclusive production of Λ -hyperons was measured with the large acceptance NA61/SHINE spectrometer at the CERN SPS in inelastic p+p interactions at beam momentum of 158 {GeV}/c. Spectra of transverse momentum and transverse mass as well as distributions of rapidity and x_{_F} are presented. The mean multiplicity was estimated to be 0.120 {± } 0.006(stat.){± }0.010(sys.). The results are compared with previous measurements and predictions of the Epos, Ur qmd and Fritiof models.

  9. Identification of the Adenovirus E4orf4 Protein Binding Site on the B55α and Cdc55 Regulatory Subunits of PP2A: Implications for PP2A Function, Tumor Cell Killing and Viral Replication

    PubMed Central

    Mui, Melissa Z.; Kucharski, Michael; Miron, Marie-Joëlle; Hur, Woosuk Steve; Berghuis, Albert M.; Blanchette, Paola; Branton, Philip E.

    2013-01-01

    Adenovirus E4orf4 protein induces the death of human cancer cells and Saccharomyces cerevisiae. Binding of E4orf4 to the B/B55/Cdc55 regulatory subunit of protein phosphatase 2A (PP2A) is required, and such binding inhibits PP2AB55 activity leading to dose-dependent cell death. We found that E4orf4 binds across the putative substrate binding groove predicted from the crystal structure of B55α such that the substrate p107 can no longer interact with PP2AB55α. We propose that E4orf4 inhibits PP2AB55 activity by preventing access of substrates and that at high E4orf4 levels this inhibition results in cell death through the failure to dephosphorylate substrates required for cell cycle progression. However, E4orf4 is expressed at much lower and less toxic levels during a normal adenovirus infection. We suggest that in this context E4orf4 largely serves to recruit novel substrates such as ASF/SF2/SRSF1 to PP2AB55 to enhance adenovirus replication. Thus E4orf4 toxicity probably represents an artifact of overexpression and does not reflect the evolutionary function of this viral product. PMID:24244166

  10. Photoperiod-dependent regulation of cell growth by PpCCA1a and PpCCA1b genes encoding single-myb clock proteins in the moss Physcomitrella patens.

    PubMed

    Okada, Ryo; Satbhai, Santosh B; Aoki, Setsuyuki

    2009-10-01

    The PpCCA1a and PpCCA1b genes of the moss Physcomitrella patens are functional homologs of the Arabidopsis thaliana circadian clock genes CCA1/LHY. We made use of disruptant lines for PpCCA1a and/or PpCCA1b to elucidate the physiological significance of these genes in the growth of moss protonemal tissue under alternating day/night cycles. Protonemal cells of the double disruptant line, carrying neither of the two genes, grew faster than those of the wild-type plant (WT) in long days (LD), whereas no difference in the growth rate was detected between them in short days (SD). The double disruptant line also showed day length-dependent phenotypic changes in the PpCCA1b promoter activity: the diurnal profile of bioluminescence from the P(CCA1b)::LUC+ reporter strain was more significantly affected in LD than in SD. These observations are the first demonstration of a physiological function of the circadian clock in non-angiosperm land plants, and are consistent with recent findings that the clock controls hypocotyl elongation of A. thaliana in a photoperiod-dependent manner.

  11. Generalized Dalitz plot analysis of the near-threshold pp{yields}ppK{sup +}K{sup -} reaction in view of the K{sup +}K{sup -} final state interaction

    SciTech Connect

    Silarski, M.; Czyzykiewicz, R.; Gil, D.; Jarczyk, L.; Kamys, B.; Smyrski, J.; Zielinski, M.; Zdebik, J.; Moskal, P.; Czerwinski, E.; Klaja, J.; Klaja, P.; Krzemien, W.; Grzonka, D.; Oelert, W.; Ritman, J.; Sefzick, T.; Wolke, M.; Wuestner, P.; Khoukaz, A.

    2009-10-15

    The excitation function for the pp{yields}ppK{sup +}K{sup -} reaction revealed a significant enhancement close to threshold that may plausibly be assigned to the influence of the pK{sup -} and K{sup +}K{sup -} final-state interactions. In an improved reanalysis of COSY-11 data for the pp{yields}ppK{sup +}K{sup -} reaction at excess energies of Q=10 and 28 MeV, including the proton-K{sup -} interaction, the enhancement is confirmed. Invariant mass distributions for the two- and three-particle subsystems allow us to test at low excess energies the ansatz and parameters for the description of the interaction in the ppK{sup +}K{sup -} system as derived from the COSY-ANKE data. Finally, based for the first time on the low-energy K{sup +}K{sup -} invariant mass distributions and the generalized Dalitz plot analysis, we estimate the scattering length for the K{sup +}K{sup -} interaction to be |Re(a{sub K{sup +}}{sub K{sup -}})|=0.5{sub -0.5}{sup +4.0} fm and Im(a{sub K{sup +}}{sub K{sup -}})=3.0{+-}3.0 fm.

  12. Primary over-expression of AβPP in muscle does not lead to the development of inclusion body myositis in a new lineage of the MCK-AβPP transgenic mouse.

    PubMed

    Luo, Yue-Bei; Johnsen, Russell D; Griffiths, Lisa; Needham, Merrilee; Fabian, Victoria A; Fletcher, Sue; Wilton, Steve D; Mastaglia, Frank L

    2013-12-01

    The aim of this study is to determine whether primary over-expression of AβPP in skeletal muscle results in the development of features of inclusion body myositis (IBM) in a new lineage of the MCK-AβPP transgenic mouse. Quantitative histological, immunohistochemical and western blotting studies were performed on muscles from 3 to 18 month old transgenic and wild-type C57BL6/SJL mice. Electron microscopy was also performed on muscle sections from selected animals. Although western blotting confirmed that there was over-expression of full length AβPP in transgenic mouse muscles, deposition of amyloid-β and fibrillar amyloid could not be demonstrated histochemically or with electron microscopy. Additionally, other changes typical of IBM such as rimmed vacuoles, cytochrome C oxidase-deficient fibres, upregulation of MHC antigens, lymphocytic inflammatory infiltration and T cell fibre invasion were absent. The most prominent finding in both transgenic and wild-type animals was the presence of tubular aggregates which was age-related and largely restricted to male animals. Expression of full length AβPP in this MCK-AβPP mouse lineage did not reach the levels required for immunodetection or deposition of amyloid-β as in the original transgenic strains, and was not associated with the development of pathological features of IBM. These negative results emphasise the potential pitfalls of re-deriving transgenic mouse strains in different laboratories.

  13. Regulation of polo-like kinase 1 by DNA damage and PP2A/B55α

    PubMed Central

    Wang, Ling; Guo, Qingyuan; Fisher, Laura A; Liu, Dongxu; Peng, Aimin

    2015-01-01

    In addition to governing mitotic progression, Plk1 also suppresses the activation of the G2 DNA damage checkpoint and promotes checkpoint recovery. Previous studies have shown that checkpoint activation after DNA damage requires inhibition of Plk1, but the underlying mechanism of Plk1 regulation was unknown. In this study we show that the specific phosphatase activity toward Plk1 Thr-210 in interphase Xenopus egg extracts is predominantly PP2A-dependent, and this phosphatase activity is upregulated by DNA damage. Consistently, PP2A associates with Plk1 and the association increases after DNA damage. We further revealed that B55α, a targeting subunit of PP2A and putative tumor suppressor, mediates PP2A/Plk1 association and Plk1 dephosphorylation. B55α and PP2A association is greatly strengthened after DNA damage in an ATM/ATR and checkpoint kinase-dependent manner. Collectively, we report a phosphatase-dependent mechanism that responds to DNA damage and regulates Plk1 and checkpoint recovery. PMID:25483054

  14. Off-energy-shell p-p scattering at sub-Coulomb energies via the Trojan horse method

    NASA Astrophysics Data System (ADS)

    Tumino, A.; Spitaleri, C.; Mukhamedzhanov, A.; Rapisarda, G. G.; Campajola, L.; Cherubini, S.; Crucillá, V.; Elekes, Z.; Fülöp, Z.; Gialanella, L.; Gulino, M.; Gyürky, G.; Kiss, G.; Cognata, M. La; Lamia, L.; Ordine, A.; Pizzone, R. G.; Romano, S.; Sergi, M. L.; Somorjai, E.

    2008-12-01

    Two-proton scattering at sub-Coulomb energies has been measured indirectly via the Trojan horse method applied to the p+d→p+p+n reaction to investigate off-energy shell effects for scattering processes. The three-body experiment was performed at 5 and 4.7 MeV corresponding to a p-p relative energy ranging from 80 to 670 keV. The free p-p cross section exhibits a deep minimum right within this relative energy region due to Coulomb plus nuclear destructive interference. No minimum occurs instead in the Trojan horse p-p cross section, which was extracted by employing a simple plane-wave impulse approximation. A detailed formalism was developed to build up the expression of the theoretical half-off-shell p-p cross section. Its behavior agrees with the Trojan horse data and in turn formally fits the n-n, n-p, and nuclear p-p cross sections given the fact that in its expression the Coulomb amplitude is negligible with respect to the nuclear one. These results confirm the Trojan horse suppression of the Coulomb amplitude for scattering due to the off-shell character of the process.

  15. Inhibition of Pten deficient Castration Resistant Prostate Cancer by Targeting of the SET - PP2A Signaling axis.

    PubMed

    Hu, Xiaoyong; Garcia, Consuelo; Fazli, Ladan; Gleave, Martin; Vitek, Michael P; Jansen, Marilyn; Christensen, Dale; Mulholland, David J

    2015-11-13

    The PP2A signaling axis regulates multiple oncogenic drivers of castration resistant prostate cancer (CRPC). We show that targeting the endogenous PP2A regulator, SET (I2PP2A), is a viable strategy to inhibit prostate cancers that are resistant to androgen deprivation therapy. Our data is corroborated by analysis of prostate cancer patient cohorts showing significant elevation of SET transcripts. Tissue microarray analysis reveals that elevated SET expression correlates with clinical cancer grading, duration of neoadjuvant hormone therapy (NHT) and time to biochemical recurrence. Using prostate regeneration assays, we show that in vivo SET overexpression is sufficient to induce hyperplasia and prostatic intraepithelial neoplasia. Knockdown of SET induced significant reductions in tumorgenesis both in murine and human xenograft models. To further validate SET as a therapeutic target, we conducted in vitro and in vivo treatments using OP449 - a recently characterized PP2A-activating drug (PAD). OP449 elicits robust anti-cancer effects inhibiting growth in a panel of enzalutamide resistant prostate cancer cell lines. Using the Pten conditional deletion mouse model of prostate cancer, OP449 potently inhibited PI3K-Akt signaling and impeded CRPC progression. Collectively, our data supports a critical role for the SET-PP2A signaling axis in CRPC progression and hormone resistant disease.

  16. Study of e+e-→pp ¯π0 in the vicinity of the ψ(3770)

    NASA Astrophysics Data System (ADS)

    Ablikim, M.; Achasov, M. N.; Ai, X. C.; Albayrak, O.; Albrecht, M.; Ambrose, D. J.; An, F. F.; An, Q.; Bai, J. Z.; Baldini Ferroli, R.; Ban, Y.; Bennett, J. V.; Bertani, M.; Bian, J. M.; Boger, E.; Bondarenko, O.; Boyko, I.; Braun, S.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, X.; Chen, X. R.; Chen, Y. B.; Cheng, H. P.; Chu, X. K.; Chu, Y. P.; Cronin-Hennessy, D.; Dai, H. L.; Dai, J. P.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; Ding, W. M.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Fan, J. Z.; Fang, J.; Fang, S. S.; Fang, Y.; Fava, L.; Feng, C. Q.; Fu, C. D.; Fuks, O.; Gao, Q.; Gao, Y.; Geng, C.; Goetzen, K.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, T.; Guo, Y. P.; Han, Y. L.; Harris, F. A.; He, K. L.; He, M.; He, Z. Y.; Held, T.; Heng, Y. K.; Hou, Z. L.; Hu, C.; Hu, H. M.; Hu, J. F.; Hu, T.; Huang, G. M.; Huang, G. S.; Huang, H. P.; Huang, J. S.; Huang, L.; Huang, X. T.; Huang, Y.; Hussain, T.; Ji, C. S.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, L. L.; Jiang, L. W.; Jiang, X. S.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Johansson, T.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Kloss, B.; Kopf, B.; Kornicer, M.; Kühn, W.; Kupsc, A.; Lai, W.; Lange, J. S.; Lara, M.; Larin, P.; Leyhe, M.; Li, C. H.; Li, Cheng; Li, Cui; Li, D.; Li, D. M.; Li, F.; Li, G.; Li, H. B.; Li, J. C.; Li, K.; Li, K.; Li, Lei; Li, P. R.; Li, Q. J.; Li, T.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Lin, D. X.; Liu, B. J.; Liu, C. L.; Liu, C. X.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. H.; Liu, H. M.; Liu, J.; Liu, J. P.; Liu, K.; Liu, K. Y.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H.; Lou, X. C.; Lu, G. R.; Lu, H. J.; Lu, H. L.; Lu, J. G.; Lu, X. R.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lv, M.; Ma, F. C.; Ma, H. L.; Ma, Q. M.; Ma, S.; Ma, T.; Ma, X. Y.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, Y. J.; Mao, Z. P.; Messchendorp, J. G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Moeini, H.; Morales Morales, C.; Moriya, K.; Muchnoi, N. Yu.; Muramatsu, H.; Nefedov, Y.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Ping, J. L.; Ping, R. G.; Poling, R.; Q., N.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, L. Q.; Qin, X. S.; Qin, Y.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Ripka, M.; Rong, G.; Ruan, X. D.; Sarantsev, A.; Schoenning, K.; Schumann, S.; Shan, W.; Shao, M.; Shen, C. P.; Shen, X. Y.; Sheng, H. Y.; Shepherd, M. R.; Song, W. M.; Song, X. Y.; Spataro, S.; Spruck, B.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Tapan, I.; Thorndike, E. H.; Toth, D.; Ullrich, M.; Uman, I.; Varner, G. S.; Wang, B.; Wang, D.; Wang, D. Y.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, Q. J.; Wang, S. G.; Wang, W.; Wang, X. F.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. H.; Wang, Z. Y.; Wei, D. H.; Wei, J. B.; Weidenkaff, P.; Wen, S. P.; Werner, M.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, N.; Wu, Z.; Xia, L. G.; Xia, Y.; Xiao, D.; Xiao, Z. J.; Xie, Y. G.; Xiu, Q. L.; Xu, G. F.; Xu, L.; Xu, Q. J.; Xu, Q. N.; Xu, X. P.; Xue, Z.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, Y. H.; Yang, H. X.; Yang, L.; Yang, Y.; Yang, Y. X.; Ye, H.; Ye, M.; Ye, M. H.; Yu, B. X.; Yu, C. X.; Yu, H. W.; Yu, J. S.; Yu, S. P.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zallo, A.; Zang, S. L.; Zeng, Y.; Zhang, B. X.; Zhang, B. Y.; Zhang, C.; Zhang, C. B.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J. J.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, S. H.; Zhang, X. J.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. H.; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, Q. W.; Zhao, S. J.; Zhao, T. C.; Zhao, X. H.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, Li; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhu, K.; Zhu, K. J.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zou, B. S.; Zou, J. H.; Besiii Collaboration

    2014-08-01

    The process e+e-→pp ¯π0 has been studied by analyzing data collected at √s =3.773 GeV, at √s =3.650 GeV, and during a ψ(3770) line shape scan with the BESIII detector at the BEPCII collider. The Born cross section of pp ¯π0 in the vicinity of the ψ(3770) is measured, and the Born cross section of ψ(3770)→pp ¯π0 is extracted considering interference between resonant and continuum production amplitudes. Two solutions with the same probability and a significance of 1.5σ are found. The solutions for the Born cross section of ψ(3770)→pp ¯π0 are 33.8±1.8±2.1 pb and 0.06-0.04-0.01+0.10+0.01 pb (<0.22 pb at a 90% confidence level). Using the estimated cross section and a constant decay amplitude approximation, the cross section σ(pp ¯→ψ(3770)π0) is calculated for the kinematic situation of the planned P ¯ANDA experiment. The maximum cross section corresponding to the two solutions is expected to be less than 0.79 nb at 90% confidence level and 122±10 nb at a center-of-mass energy of 5.26 GeV.

  17. The molecular basis of ABA-independent inhibition of PP2Cs by a subclass of PYL proteins.

    PubMed

    Hao, Qi; Yin, Ping; Li, Wenqi; Wang, Li; Yan, Chuangye; Lin, Zhaohu; Wu, Jim Zhen; Wang, Jiawei; Yan, S Frank; Yan, Nieng

    2011-06-10

    PYR1/PYL/RCAR proteins (PYLs) are confirmed abscisic acid (ABA) receptors, which inhibit protein phosphatase 2C (PP2C) upon binding to ABA. Arabidopsis thaliana has 14 PYLs, yet their functional distinction remains unclear. Here, we report systematic biochemical characterization of PYLs. A subclass of PYLs, represented by PYL10, inhibited PP2C in the absence of any ligand. Crystal structures of PYL10, both in the free form and in the HAB1 (PP2C)-bound state, revealed the structural basis for its constitutive activity. Structural-guided biochemical analyses revealed that ABA-independent inhibition of PP2C requires the PYLs to exist in a monomeric state. In addition, the residues guarding the entrance to the ligand-binding pocket of these PYLs should be bulky and hydrophobic. Based on these principles, we were able to generate monomeric PYL2 variants that gained constitutive inhibitory effect on PP2Cs. These findings provide an important framework for understanding the complex regulation of ABA signaling by PYL proteins.

  18. Identification of isoforms of the exocytosis-sensitive phosphoprotein PP63/parafusin in Paramecium tetraurelia and demonstration of phosphoglucomutase activity.

    PubMed Central

    Hauser, K; Kissmehl, R; Linder, J; Schultz, J E; Lottspeich, F; Plattner, H

    1997-01-01

    PP63 (parafusin) is a 63 kDa phosphoprotein which is very rapidly (within 80 ms) dephosphorylated (to P63) during triggered trichocyst exocytosis; this occurs selectively in exocytosis-competent Paramecium tetraurelia strains. In the present work, two cDNAs coding for PP63/parafusin have been isolated, one of which is a new isoform. These isoforms are 99.6% identical and are derived from two different genes. Similarity searches revealed 43-51% identity of the deduced amino acid sequences with known phosphoglucomutases from yeast and mammals. The sequences of two proteolytic peptides obtained from PP63/parafusin isolated from Paramecium are identical to parts of the amino acid sequence deduced from the major cDNA. The major cDNA was mutated from the macronuclear ciliate genetic code into the universal genetic code and expressed in Escherichia coli. The recombinant protein shows the same biochemical and immunological characteristics as the (P)P63/parafusin originally isolated from Paramecium. It has the same specific phosphoglucomutase activity as phosphoglucomutase from chicken muscle. We also show that recombinant P63-1 parafusin 1 is a substrate of an endogenous casein kinase from Paramecium, as is the originally isolated P63/parafusin. Polyclonal antibodies against recombinant P63-1/parafusin 1 were raised which recognized phosphoglucomutases from different sources. Thus we show that PP63/parafusin and phosphoglucomutase in Paramecium are identical. PMID:9173895

  19. Study of e+e-→pp¯π0 in the vicinity of the ψ(3770)

    DOE PAGES

    Ablikim, M.; Achasov, M.  N.; Ai, X.  C.; ...

    2014-08-22

    The process e+e-→pp¯π0 has been studied by analyzing data collected at √s=3.773 GeV, at s√=3.650 GeV, and during a ψ(3770) line shape scan with the BESIII detector at the BEPCII collider. The Born cross section of pp¯π0 in the vicinity of the ψ(3770) is measured, and the Born cross section of ψ(3770)→pp¯π0 is extracted considering interference between resonant and continuum production amplitudes. Two solutions with the same probability and a significance of 1.5σ are found. The solutions for the Born cross section of ψ(3770)→pp¯π0 are 33.8±1.8±2.1 pb and 0.06+0.10-0.04+0.01-0.01 pb (<0.22 pb at a 90% confidence level). Using the estimatedmore » cross section and a constant decay amplitude approximation, the cross section σ(pp¯→ψ(3770)π0) is calculated for the kinematic situation of the planned P¯ANDA experiment. The maximum cross section corresponding to the two solutions is expected to be less than 0.79 nb at 90% confidence level and 122±10 nb at a center-of-mass energy of 5.26 GeV.« less

  20. AQP2 is a substrate for endogenous PP2B activity within an inner medullary AKAP-signaling complex.

    PubMed

    Jo, I; Ward, D T; Baum, M A; Scott, J D; Coghlan, V M; Hammond, T G; Harris, H W

    2001-11-01

    We have demonstrated that inner medullary collecting duct (IMCD) heavy endosomes purified from rat kidney IMCD contain the type II protein kinase A (PKA) regulatory subunit (RII), protein phosphatase (PP)2B, PKCzeta, and an RII-binding protein (relative molecular mass ~90 kDa) representing a putative A kinase anchoring protein (AKAP). Affinity chromatography of detergent-solubilized endosomes on cAMP-agarose permits recovery of a protein complex consisting of the 90-kDa AKAP, RII, PP2B, and PKCzeta. With the use of small-particle flow cytometry, RII and PKCzeta were localized to an identical population of endosomes, suggesting that these proteins are components of an endosomal multiprotein complex. (32)P-labeled aquaporin-2 (AQP2) present in these PKA-phosphorylated endosomes was dephosphorylated in vitro by either addition of exogenous PP2B or by an endogenous endosomal phosphatase that was inhibited by the PP2B inhibitors EDTA and the cyclophilin-cyclosporin A complex. We conclude that IMCD heavy endosomes possess an AKAP multiprotein-signaling complex similar to that described previously in hippocampal neurons. This signaling complex potentially mediates the phosphorylation of AQP2 to regulate its trafficking into the IMCD apical membrane. In addition, the PP2B component of the AKAP-signaling complex could also dephosphorylate AQP2 in vivo.

  1. Determination of polyparameter linear free energy relationship (pp-LFER) substance descriptors for established and alternative flame retardants.

    PubMed

    Stenzel, Angelika; Goss, Kai-Uwe; Endo, Satoshi

    2013-02-05

    Polyparameter linear free energy relationships (pp-LFERs) can predict partition coefficients for a multitude of environmental and biological phases with high accuracy. In this work, the pp-LFER substance descriptors of 40 established and alternative flame retardants (e.g., polybrominated diphenyl ethers, hexabromocyclododecane, bromobenzenes, trialkyl phosphates) were determined experimentally. In total, 251 data for gas-chromatographic (GC) retention times and liquid/liquid partition coefficients (K) were measured and used to calibrate the pp-LFER substance descriptors. Substance descriptors were validated through a comparison between predicted and experimental log K for the systems octanol/water (K(ow)), water/air (K(wa)), organic carbon/water (K(oc)) and liposome/water (K(lipw)), revealing a high reliability of pp-LFER predictions based on our descriptors. For instance, the difference between predicted and experimental log K(ow) was <0.3 log units for 17 out of 21 compounds for which experimental values were available. Moreover, we found an indication that the H-bond acceptor value (B) depends on the solvent for some compounds. Thus, for predicting environmentally relevant partition coefficients it is important to determine B values using measurements in aqueous systems. The pp-LFER descriptors calibrated in this study can be used to predict partition coefficients for which experimental data are unavailable, and the predicted values can serve as references for further experimental measurements.

  2. Inhibition of Pten deficient Castration Resistant Prostate Cancer by Targeting of the SET - PP2A Signaling axis

    PubMed Central

    Hu, Xiaoyong; Garcia, Consuelo; Fazli, Ladan; Gleave, Martin; Vitek, Michael P.; Jansen, Marilyn; Christensen, Dale; Mulholland, David J

    2015-01-01

    The PP2A signaling axis regulates multiple oncogenic drivers of castration resistant prostate cancer (CRPC). We show that targeting the endogenous PP2A regulator, SET (I2PP2A), is a viable strategy to inhibit prostate cancers that are resistant to androgen deprivation therapy. Our data is corroborated by analysis of prostate cancer patient cohorts showing significant elevation of SET transcripts. Tissue microarray analysis reveals that elevated SET expression correlates with clinical cancer grading, duration of neoadjuvant hormone therapy (NHT) and time to biochemical recurrence. Using prostate regeneration assays, we show that in vivo SET overexpression is sufficient to induce hyperplasia and prostatic intraepithelial neoplasia. Knockdown of SET induced significant reductions in tumorgenesis both in murine and human xenograft models. To further validate SET as a therapeutic target, we conducted in vitro and in vivo treatments using OP449 - a recently characterized PP2A-activating drug (PAD). OP449 elicits robust anti-cancer effects inhibiting growth in a panel of enzalutamide resistant prostate cancer cell lines. Using the Pten conditional deletion mouse model of prostate cancer, OP449 potently inhibited PI3K-Akt signaling and impeded CRPC progression. Collectively, our data supports a critical role for the SET-PP2A signaling axis in CRPC progression and hormone resistant disease. PMID:26563471

  3. Resveratrol Intervenes in the Cholesterol- and Isoprenoid-Mediated Amyloidogenic Processing of AβPP in Familial Alzheimer's Disease.

    PubMed

    Sathya, Mohan; Moorthi, Ponnusamy; Premkumar, Palanisamy; Kandasamy, Mahesh; Jayachandran, Kesavan Swaminathan; Anusuyadevi, Muthuswamy

    2017-12-03

    Deterioration of cholesterol metabolism has recently been a frontier subject of investigation in the field of Alzheimer's disease (AD). Though amyloid-β protein precursor (AβPP) primes the pathological cascade, changes in cholesterol levels and its intermediates, geranyl geranyl pyrophosphate and farnesyl pyrophosphate, is expected to have a different consequence on AβPP processing and amyloid-β (Aβ) generation. However, the use of statins (HMG-COA reductase inhibitor) has been widely implicated in slowing down the pathogenic progression of AD, while the epidemiological reports on its biological effect remains controversial. Considering this fact, the choice of drug that could maintain cholesterol homeostasis without altering its biosynthesis may yield a better therapeutic efficacy on AD. Thus, the present study focused on determining the influence of cholesterol and isoprenoids on amyloidogenic-cleavage of AβPP, in addition to resveratrol as a potent therapeutic drug in CHO-APPswe cell lines. High levels of cholesterol were found to enhance the maturation of AβPP and altered the expression and subcellular localization of ADAM10, BACE1, and PS1 thereby promoting Aβ generation, whereas high isoprenoids increased both maturation as well as amyloidogenic-cleavage of AβPP, which was evident through β-CTF production. Interestingly, the therapeutic efficacy of resveratrol maintained cholesterol homeostasis and reduced the amyloidogenic burden through its ability to enhance SIRT1 expression and thereby regulating differential expression of AD determinants.

  4. Phosphotransferase-dependent accumulation of (p)ppGpp in response to glutamine deprivation in Caulobacter crescentus

    PubMed Central

    Ronneau, Séverin; Petit, Kenny; De Bolle, Xavier; Hallez, Régis

    2016-01-01

    The alarmone (p)ppGpp is commonly used by bacteria to quickly respond to nutrient starvation. Although (p)ppGpp synthetases such as SpoT have been extensively studied, little is known about the molecular mechanisms stimulating alarmone synthesis upon starvation. Here, we describe an essential role of the nitrogen-related phosphotransferase system (PTSNtr) in controlling (p)ppGpp accumulation in Caulobacter crescentus. We show that cells sense nitrogen starvation by way of detecting glutamine deprivation using the first enzyme (EINtr) of PTSNtr. Decreasing intracellular glutamine concentration triggers phosphorylation of EINtr and its downstream components HPr and EIIANtr. Once phosphorylated, both HPr∼P and EIIANtr∼P stimulate (p)ppGpp accumulation by modulating SpoT activities. This burst of second messenger primarily impacts the non-replicative phase of the cell cycle by extending the G1 phase. This work highlights a new role for bacterial PTS systems in stimulating (p)ppGpp accumulation in response to metabolic cues and in controlling cell cycle progression and cell growth. PMID:27109061

  5. Investigation into the effect of space charges on the surface erosion of synthetic and natural organoclay nanofilled PP films

    NASA Astrophysics Data System (ADS)

    Dhara, Rohitha; Rab, Md. A.; Basappa, Prathap

    2014-08-01

    Literature indicates space charge formation in the polypropylene (PP) films when subjected to Partial Discharges (PD). The space charge thus formed also alters the PD characteristics in turn altering the PD resistance. The main focus of this work is to investigate the effect of space charge formed during the PD aging process on the main field with minimal space charge redistribution times. AC Ramp voltage that constantly increases with time at a rate of 667 V/s was applied across the samples for 20 second duration. PP films with natural organo clay nanofillers (0 (wt/v) % referred to as PP+N0% (base polymer) and 2 (wt/v) % referred to as PP+N2%), and synthetic organo clay nanofillers (2 (wt/v) % referred to as PP+S2%) were considered for experimentation. Results indicate that with the inclusion of the either natural or synthetic organo clay nanoparticles, with in the percolation threshold limit of nanofiller concentration, the final electric stress is reduced thus enhancing the resistance to surface PDs.

  6. Oxygen Availability for Porphyrin Biosynthesis Enzymes Determines the Production of Protoporphyrin IX (PpIX) during Hypoxia

    PubMed Central

    Otsuka, Shimpei; Matsumoto, Kentaro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun-ichiro

    2015-01-01

    5-Aminolevulinic acid (ALA), a precursor of porphyrin, is specifically converted to the fluorescent substance protoporphyrin IX (PpIX) in tumors to be used as a prodrug for photodynamic therapy and diagnosis. Hypoxia, a common feature of solid tumors, decreases the efficacy of ALA-based photodynamic therapy and diagnosis. This decrease results from the excretion of porphyrin precursor coproporphyrinogen III (CPgenIII), an intermediate in the biosynthesis of PpIX. However, the mechanism of CPgenIII excretion during hypoxia remains unclear. In this study, we revealed the importance of mitochondrial respiration for the production of PpIX during hypoxia. Porphyrin concentrations were estimated in human gastric cancer cell lines by HPLC. Expression levels of porphyrin biosynthesis genes were measured by qRT-PCR and immunoblotting. Blockage of porphyrin biosynthesis was an oxygen-dependent phenomenon resulting from decreased PpIX production in mitochondria under hypoxic conditions. PpIX production was increased by the inhibition of mitochondrial respiration complexes, which indicates that the enzymes of porphyrin biosynthesis compete with respiration complexes for molecular oxygen. Our results indicate that targeting the respiration complexes is a rationale for enhancing the effect of ALA-mediated treatment and diagnosis. PMID:26717566

  7. Strange Particle Production in $p+p$ Collisions at $\\sqrt{s}$= 200GeV

    SciTech Connect

    Abelev, B.I.; Adams, J.; Aggarwal, M.M.; Ahammed, Z.; Amonett,J.; Anderson, B.D.; Anderson, M.; Arkhipkin, D.; Averichev, G.S.; Bai,Y.; Balewski, J.; Barannikova, O.; Barnby, L.S.; Baudot, J.; Bekele, S.; Belaga, V.V.; Bellingeri-Laurikainen, A.; Bellwied, R.; Benedosso, F.; Bhardwaj, S.; Bhasin, A.; Bhati, A.K.; Bichsel, H.; Bielcik, J.; Bielcikova, J.; Bland, L.C.; Blyth, S.-L.; Bonner, B.E.; Botje, M.; Bouchet, J.; Brandin, A.V.; Bravar, A.; Bystersky, M.; Cadman, R.V.; Cai,X.Z.; Caines, H.; Calderon de la Barca Sanchez, M.; Castillo, J.; Catu,O.; Cebra, D.; Chajecki, Z.; Chaloupka, P.; Chattopadhyay, S.; Chen,H.F.; Chen, J.H.; Cheng, J.; Cherney, M.; Chikanian, A.; Christie, W.; Coffin, J.P.; Cormier, T.M.; Cosentino, M.R.; Cramer, J.G.; Crawford,H.J.; Das, D.; Das, S.; Daugherity, M.; de Moura, M.M.; Dedovich, T.G.; DePhillips, M.; Derevschikov, A.A.; Didenko, L.; Dietel, T.; Djawotho,P.; Dogra, S.M.; Dong, W.J.; Dong, X.; Draper, J.E.; Du, F.; Dunin, V.B.; Dunlop, J.C.; Dutta Mazumdar, M.R.; Eckardt, V.; Edwards, W.R.; Efimov,L.G.; Emelianov, V.; Engelage, J.; Eppley, G.; Erazmus, B.; Estienne, M.; Fachini, P.; Fatemi, R.; Fedorisin, J.; Filimonov, K.; Filip, P.; Finch,E.; Fine, V.; Fisyak, Y.; Fu, J.; Gagliardi, C.A.; Gaillard, L.; Ganti,M.S.; Ghazikhanian, V.; Ghosh, P.; Gonzalez, J.S.; Gorbunov, Y.G.; Gos,H.; Grebenyuk, O.; Grosnick, D.; Guertin, S.M.; Guimaraes, K.S.F.F.; Guo,Y.; Gupta,N.; Gutierrez, T.D.; Haag, B.; Hallman, T.J.; Hamed, A.; Harris, J.W.; He, W.; Heinz, M.; Henry, T.W.; Hepplemann, S.; Hippolyte,B.; Hirsch, A.; Hjort, E.; Hoffman, A.M.; Hoffmann, G.W.; Horner, M.J.; Huang, H.Z.; Huang, S.L.; Hughes, E.W.; Humanic, T.J.; Igo, G.; Jacobs,P.; Jacobs, W.W.; Jakl, P.; Jia, F.; Jiang, H.; Jones, P.G.; Judd, E.G.; Kabana, S.; Kang, K.; Kapitan, J.; Kaplan, M.; Keane, D.; Kechechyan, A.; Khodyrev, V.Yu.; Kim, B.C.; Kiryluk, J.; Kisiel, A.; Kislov, E.M.; Klein,S.R.; Kocoloski, A.; Koetke, D.D.; et al.

    2006-07-31

    We present strange particle spectra and yields measured atmid-rapidity in sqrt text s=200 GeV proton-proton (p+p) collisions atRHIC. We find that the previously observed universal transverse mass(mathrm mT \\equiv\\sqrt mathrm p_T 2+\\mathrm m2) scaling of hadronproduction in p+p collisions seems to break down at higher \\mt and thatthere is a difference in the shape of the \\mt spectrum between baryonsand mesons. We observe mid-rapidity anti-baryon to baryon ratios nearunity for Lambda and Xi baryons and no dependence of the ratio ontransverse momentum, indicating that our data do not yet reach thequark-jet dominated region. We show the dependence of the mean transversemomentum (\\mpt) on measured charged particle multiplicity and on particlemass and infer that these trends are consistent with gluon-jet dominatedparticle production. The data are compared to previous measurements fromCERN-SPS, ISR and FNAL experiments and to Leading Order (LO) and Next toLeading order (NLO) string fragmentation model predictions. We infer fromthese comparisons that the spectral shapes and particle yields from $p+p$collisions at RHIC energies have large contributions from gluon jetsrather than quark jets.

  8. PP1-Dependent Formin Bnr1 Dephosphorylation and Delocalization from a Cell Division Site.

    PubMed

    Orii, Minami; Kono, Keiko; Wen, Hsin-I; Nakanishi, Makoto

    2016-01-01

    Cell cycle ends with cytokinesis that is the physical separation of a cell into two daughter cells. For faithful cytokinesis, cells integrate multiple processes, such as actomyosin ring formation, contraction and plasma membrane closure, into coherent responses. Linear actin assembly by formins is essential for formation and maintenance of actomyosin ring. Although budding yeast's two formins, Bni1 and Bnr1, are known to switch their subcellular localization at the division site prior to cytokinesis, the underlying mechanisms were not completely understood. Here, we provide evidence showing that Bnr1 is dephosphorylated concomitant with its release from the division site. Impaired PP1/Glc7 activity delayed Bnr1 release and dephosphorylation, Bni1 recruitment and actomyosin ring formation at the division site. These results suggest the involvement of Glc7 in this regulation. Further, we identified Ref2 as the PP1 regulatory subunit responsible for this regulation. Taken together, Glc7 and Ref2 may have a role in actomyosin ring formation by modulating the localization of formins during cytokinesis.

  9. PP1-Dependent Formin Bnr1 Dephosphorylation and Delocalization from a Cell Division Site

    PubMed Central

    Orii, Minami; Kono, Keiko; Wen, Hsin-I; Nakanishi, Makoto

    2016-01-01

    Cell cycle ends with cytokinesis that is the physical separation of a cell into two daughter cells. For faithful cytokinesis, cells integrate multiple processes, such as actomyosin ring formation, contraction and plasma membrane closure, into coherent responses. Linear actin assembly by formins is essential for formation and maintenance of actomyosin ring. Although budding yeast’s two formins, Bni1 and Bnr1, are known to switch their subcellular localization at the division site prior to cytokinesis, the underlying mechanisms were not completely understood. Here, we provide evidence showing that Bnr1 is dephosphorylated concomitant with its release from the division site. Impaired PP1/Glc7 activity delayed Bnr1 release and dephosphorylation, Bni1 recruitment and actomyosin ring formation at the division site. These results suggest the involvement of Glc7 in this regulation. Further, we identified Ref2 as the PP1 regulatory subunit responsible for this regulation. Taken together, Glc7 and Ref2 may have a role in actomyosin ring formation by modulating the localization of formins during cytokinesis. PMID:26771880

  10. A quark model of {bar {Lambda}}{Lambda} production in {bar p}p interactions

    SciTech Connect

    Alberg, M.A. |; Henley, E.M.; Wilets, L.; Kunz, P.D.

    1993-12-31

    A quark model which includes both scalar and vector contributions to the reaction mechanism (SV quark model) is used in a DWBA calculation of {anti {Lambda}}{Lambda} production in {bar p}p interactions. Total and differential cross-sections, polarizations, depolarizations, and spin-correlation coefficients are computed for laboratory momenta from threshold to 1695 MeV/c. The free parameters of the calculation are the scalar and vector strengths, a quark cluster size parameter, and the parameters of the unknown {anti {Lambda}}{Lambda} potentials. Good agreement with experiment is found for constructive interference of the scalar and vector terms, and for {anti {Lambda}}{Lambda} potentials which differ from those suggested by several authors on the basis of SU(3) arguments. The fit to the data is better than that obtained by other quark models, which use only scalar or vector annihilation terms. The agreement with experiment is also better than that found in meson-exchange models. The recent suggestion [1] that measurement of the depolarization parameter D{sub nn} can be used to discriminate between meson-exchange and quark models is examined in detail. We conclude that a measurement of D{sub nn} will provide a test of which of these models, as presently constructed, is the more appropriate description of strangeness production in the {bar p}p {yields} {anti {Lambda}}{Lambda} reaction.

  11. Evolutionary Analysis of the B56 Gene Family of PP2A Regulatory Subunits

    PubMed Central

    Sommer, Lauren M.; Cho, Hyuk; Choudhary, Madhusudan; Seeling, Joni M.

    2015-01-01

    Protein phosphatase 2A (PP2A) is an abundant serine/threonine phosphatase that functions as a tumor suppressor in numerous cell-cell signaling pathways, including Wnt, myc, and ras. The B56 subunit of PP2A regulates its activity, and is encoded by five genes in humans. B56 proteins share a central core domain, but have divergent amino- and carboxy-termini, which are thought to provide isoform specificity. We performed phylogenetic analyses to better understand the evolution of the B56 gene family. We found that B56 was present as a single gene in eukaryotes prior to the divergence of animals, fungi, protists, and plants, and that B56 gene duplication prior to the divergence of protostomes and deuterostomes led to the origin of two B56 subfamilies, B56αβε and B56γδ. Further duplications led to three B56αβε genes and two B56γδ in vertebrates. Several nonvertebrate B56 gene names are based on distinct vertebrate isoform names, and would best be renamed. B56 subfamily genes lack significant divergence within primitive chordates, but each became distinct in complex vertebrates. Two vertebrate lineages have undergone B56 gene loss, Xenopus and Aves. In Xenopus, B56δ function may be compensated for by an alternatively spliced transcript, B56δ/γ, encoding a B56δ-like amino-terminal region and a B56γ core. PMID:25950761

  12. Influence of different components in a TPV PP/EPDM based with low hardness

    NASA Astrophysics Data System (ADS)

    Gheller, J.; Jacobi, M. M.

    2014-05-01

    Thermoplastic vulcanizates (TPVs) are a class of polymeric material obtained by dynamic vulcanization of an elastomer in a melted thermoplastic matrix. This work intend to evaluate different variables in the production of low hardness TPVs made of polypropylene (PP) and ethylene propylene rubber (EPDM), as well the optimization of the variables looking for TPVs with improved performance. In the Study I the influence of PP crystallinity were evaluated, in the Study II the effects of different amounts of dicumyl peroxide (DCP) were evaluated and in the Study III the amount of the phenolic resin were evaluated. This extended abstract presents, in a more detailed way, the results considering the curative phenolic resin content (Study III). The others results and discussions are briefly described in the results and discussions section. The compounds were obtained in a closed mixing chamber and their processability properties, swelling, hardness and tensile strength were evaluated. With the results obtained were possible to evaluate the influence of different ingredients in the TPVs properties. The results were discussed and presented looking for a better understanding of the influence of this variable in the final product, as well the correlation between then.

  13. Inclusive photon production at forward rapidities in pp collisions at LHC energies with the ALICE experiment

    NASA Astrophysics Data System (ADS)

    Sudipan Dethe ALICE Collaboration

    2016-04-01

    Measurements of multiplicity and pseudorapidity distributions of particles produced in pp collisions are important for the study of particle production mechanisms and to obtain baseline distributions to be compared with those from heavy-ion collisions. The inclusive photon measurements (dominated by π0 decays) are complementary to the charged particle measurements. The present work focuses on the forward rapidity region with comparisons to different models such as PYTHIA and PHOJET. We report the measurements of multiplicity and pseudorapidity distributions of inclusive photons using the ALICE Photon Multiplicity Detector (PMD) at forward rapidities (2.3 < η < 3.9) in pp collisions at = 0.9, 2.76 and 7 TeV. It is observed that the photon multiplicity distributions are well described by negative binomial distributions (NBD). Multiplicity distributions are studied in terms of KNO variables for each energy. It is shown that the increase in the average photon multiplicity as a function of beam energy is compatible with both a logarithmic and power law dependence. The results are compared to different model predictions. These models reproduce experimental results at lower energy while they are not accurate at higher energies.

  14. The toxofilin-actin-PP2C complex of Toxoplasma: identification of interacting domains.

    PubMed

    Jan, Gaelle; Delorme, Violaine; David, Violaine; Revenu, Celine; Rebollo, Angelita; Cayla, Xavier; Tardieux, Isabelle

    2007-02-01

    Toxofilin is a 27 kDa protein isolated from the human protozoan parasite Toxoplasma gondii, which causes toxoplasmosis. Toxofilin binds to G-actin, and in vitro studies have shown that it controls elongation of actin filaments by sequestering actin monomers. Toxofilin affinity for G-actin is controlled by the phosphorylation status of its Ser53, which depends on the activities of a casein kinase II and a type 2C serine/threonine phosphatase (PP2C). To get insights into the functional properties of toxofilin, we undertook a structure-function analysis of the protein using a combination of biochemical techniques. We identified a domain that was sufficient to sequester G-actin and that contains three peptide sequences selectively binding to G-actin. Two of these sequences are similar to sequences present in several G- and F-actin-binding proteins, while the third appears to be specific to toxofilin. Additionally, we identified two toxofilin domains that interact with PP2C, one of which contains the Ser53 substrate. In addition to characterizing the interacting domains of toxofilin with its partners, the present study also provides information on an in vivo-based approach to selectively and competitively disrupt the protein-protein interactions that are important to parasite motility.

  15. Measurement of Wγ and Zγ production in pp collisions at √{ s} = 7 TeV

    NASA Astrophysics Data System (ADS)

    Chatrchyan, S.; Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Bergauer, T.; Dragicevic, M.; Erö, J.; Fabjan, C.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hammer, J.; Hänsel, S.; Hoch, M.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Kasieczka, G.; Kiesenhofer, W.; Krammer, M.; Liko, D.; Mikulec, I.; Pernicka, M.; Rohringer, H.; Schöfbeck, R.; Strauss, J.; Teischinger, F.; Wagner, P.; Waltenberger, W.; Walzel, G.; Widl, E.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Benucci, L.; De Wolf, E. A.; Janssen, X.; Maes, J.; Maes, T.; Mucibello, L.; Ochesanu, S.; Roland, B.; Rougny, R.; Selvaggi, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Blekman, F.; Blyweert, S.; D'Hondt, J.; Devroede, O.; Gonzalez Suarez, R.; Kalogeropoulos, A.; Maes, M.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Villella, I.; Charaf, O.; Clerbaux, B.; De Lentdecker, G.; Dero, V.; Gay, A. P. R.; Hammad, G. H.; Hreus, T.; Marage, P. E.; Thomas, L.; Vander Velde, C.; Vanlaer, P.; Adler, V.; Cimmino, A.; Costantini, S.; Grunewald, M.; Klein, B.; Lellouch, J.; Marinov, A.; Mccartin, J.; Ryckbosch, D.; Thyssen, F.; Tytgat, M.; Vanelderen, L.; Verwilligen, P.; Walsh, S.; Zaganidis, N.; Basegmez, S.; Bruno, G.; Caudron, J.; Ceard, L.; Cortina Gil, E.; De Favereau De Jeneret, J.; Delaere, C.; Favart, D.; Giammanco, A.; Grégoire, G.; Hollar, J.; Lemaitre, V.; Liao, J.; Militaru, O.; Ovyn, S.; Pagano, D.; Pin, A.; Piotrzkowski, K.; Schul, N.; Beliy, N.; Caebergs, T.; Daubie, E.; Alves, G. A.; De Jesus Damiao, D.; Pol, M. E.; Souza, M. H. G.; Carvalho, W.; Da Costa, E. M.; De Oliveira Martins, C.; Fonseca De Souza, S.; Mundim, L.; Nogima, H.; Oguri, V.; Prado Da Silva, W. L.; Santoro, A.; Silva Do Amaral, S. M.; Sznajder, A.; Torres Da Silva De Araujo, F.; Dias, F. A.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Lagana, C.; Marinho, F.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Darmenov, N.; Dimitrov, L.; Genchev, V.; Iaydjiev, P.; Piperov, S.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Tcholakov, V.; Trayanov, R.; Vankov, I.; Dimitrov, A.; Hadjiiska, R.; Karadzhinova, A.; Kozhuharov, V.; Litov, L.; Mateev, M.; Pavlov, B.; Petkov, P.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Jiang, C. H.; Liang, D.; Liang, S.; Meng, X.; Tao, J.; Wang, J.; Wang, J.; Wang, X.; Wang, Z.; Xiao, H.; Xu, M.; Zang, J.; Zhang, Z.; Ban, Y.; Guo, S.; Guo, Y.; Li, W.; Mao, Y.; Qian, S. J.; Teng, H.; Zhang, L.; Zhu, B.; Zou, W.; Cabrera, A.; Gomez Moreno, B.; Ocampo Rios, A. A.; Osorio Oliveros, A. F.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Lelas, K.; Plestina, R.; Polic, D.; Puljak, I.; Antunovic, Z.; Dzelalija, M.; Brigljevic, V.; Duric, S.; Kadija, K.; Morovic, S.; Attikis, A.; Galanti, M.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Finger, M.; Finger, M.; Assran, Y.; Khalil, S.; Mahmoud, M. A.; Hektor, A.; Kadastik, M.; Müntel, M.; Raidal, M.; Rebane, L.; Azzolini, V.; Eerola, P.; Fedi, G.; Czellar, S.; Härkönen, J.; Heikkinen, A.; Karimäki, V.; Kinnunen, R.; Kortelainen, M. J.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Ungaro, D.; Wendland, L.; Banzuzi, K.; Korpela, A.; Tuuva, T.; Sillou, D.; Besancon, M.; Choudhury, S.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Ferri, F.; Ganjour, S.; Gentit, F. X.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Malcles, J.; Marionneau, M.; Millischer, L.; Rander, J.; Rosowsky, A.; Shreyber, I.; Titov, M.; Verrecchia, P.; Baffioni, S.; Beaudette, F.; Benhabib, L.; Bianchini, L.; Bluj, M.; Broutin, C.; Busson, P.; Charlot, C.; Dahms, T.; Dobrzynski, L.; Elgammal, S.; Granier de Cassagnac, R.; Haguenauer, M.; Miné, P.; Mironov, C.; Ochando, C.; Paganini, P.; Sabes, D.; Salerno, R.; Sirois, Y.; Thiebaux, C.; Wyslouch, B.; Zabi, A.; Agram, J.-L.; Andrea, J.; Bloch, D.; Bodin, D.; Brom, J.-M.; Cardaci, M.; Chabert, E. C.; Collard, C.; Conte, E.; Drouhin, F.; Ferro, C.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Greder, S.; Juillot, P.; Karim, M.; Le Bihan, A.-C.; Mikami, Y.; Van Hove, P.; Fassi, F.; Mercier, D.; Baty, C.; Beauceron, S.; Beaupere, N.; Bedjidian, M.; Bondu, O.; Boudoul, G.; Boumediene, D.; Brun, H.; Chasserat, J.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fay, J.; Gascon, S.; Ille, B.; Kurca, T.; Le Grand, T.; Lethuillier, M.; Mirabito, L.; Perries, S.; Sordini, V.; Tosi, S.; Tschudi, Y.; Verdier, P.; Lomidze, D.; Anagnostou, G.; Edelhoff, M.; Feld, L.; Heracleous, N.; Hindrichs, O.; Jussen, R.; Klein, K.; Merz, J.; Mohr, N.; Ostapchuk, A.; Perieanu, A.; Raupach, F.; Sammet, J.; Schael, S.; Sprenger, D.; Weber, H.; Weber, M.; Wittmer, B.; Ata, M.; Bender, W.; Dietz-Laursonn, E.; Erdmann, M.; Frangenheim, J.; Hebbeker, T.; Hinzmann, A.; Hoepfner, K.; Klimkovich, T.; Klingebiel, D.; Kreuzer, P.; Lanske, D.; Magass, C.; Merschmeyer, M.; Meyer, A.; Papacz, P.; Pieta, H.; Reithler, H.; Schmitz, S. A.; Sonnenschein, L.; Steggemann, J.; Teyssier, D.; Bontenackels, M.; Davids, M.; Duda, M.; Flügge, G.; Geenen, H.; Giffels, M.; Haj Ahmad, W.; Heydhausen, D.; Kress, T.; Kuessel, Y.; Linn, A.; Nowack, A.; Perchalla, L.; Pooth, O.; Rennefeld, J.; Sauerland, P.; Stahl, A.; Thomas, M.; Tornier, D.; Zoeller, M. H.; Aldaya Martin, M.; Behrenhoff, W.; Behrens, U.; Bergholz, M.; Bethani, A.; Borras, K.; Cakir, A.; Campbell, A.; Castro, E.; Dammann, D.; Eckerlin, G.; Eckstein, D.; Flossdorf, A.; Flucke, G.; Geiser, A.; Hauk, J.; Jung, H.; Kasemann, M.; Katkov, I.; Katsas, P.; Kleinwort, C.; Kluge, H.; Knutsson, A.; Krämer, M.; Krücker, D.; Kuznetsova, E.; Lange, W.; Lohmann, W.; Mankel, R.; Marienfeld, M.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mnich, J.; Mussgiller, A.; Olzem, J.; Pitzl, D.; Raspereza, A.; Raval, A.; Rosin, M.; Schmidt, R.; Schoerner-Sadenius, T.; Sen, N.; Spiridonov, A.; Stein, M.; Tomaszewska, J.; Walsh, R.; Wissing, C.; Autermann, C.; Blobel, V.; Bobrovskyi, S.; Draeger, J.; Enderle, H.; Gebbert, U.; Kaschube, K.; Kaussen, G.; Klanner, R.; Lange, J.; Mura, B.; Naumann-Emme, S.; Nowak, F.; Pietsch, N.; Sander, C.; Schettler, H.; Schleper, P.; Schröder, M.; Schum, T.; Schwandt, J.; Stadie, H.; Steinbrück, G.; Thomsen, J.; Barth, C.; Bauer, J.; Buege, V.; Chwalek, T.; De Boer, W.; Dierlamm, A.; Dirkes, G.; Feindt, M.; Gruschke, J.; Hackstein, C.; Hartmann, F.; Heinrich, M.; Held, H.; Hoffmann, K. H.; Honc, S.; Komaragiri, J. R.; Kuhr, T.; Martschei, D.; Mueller, S.; Müller, Th.; Niegel, M.; Oberst, O.; Oehler, A.; Ott, J.; Peiffer, T.; Piparo, D.; Quast, G.; Rabbertz, K.; Ratnikov, F.; Ratnikova, N.; Renz, M.; Saout, C.; Scheurer, A.; Schieferdecker, P.; Schilling, F.-P.; Schmanau, M.; Schott, G.; Simonis, H. J.; Stober, F. M.; Troendle, D.; Wagner-Kuhr, J.; Weiler, T.; Zeise, M.; Zhukov, V.; Ziebarth, E. B.; Daskalakis, G.; Geralis, T.; Kesisoglou, S.; Kyriakis, A.; Loukas, D.; Manolakos, I.; Markou, A.; Markou, C.; Mavrommatis, C.; Ntomari, E.; Petrakou, E.; Gouskos, L.; Mertzimekis, T. J.; Panagiotou, A.; Stiliaris, E.; Evangelou, I.; Foudas, C.; Kokkas, P.; Manthos, N.; Papadopoulos, I.; Patras, V.; Triantis, F. A.; Aranyi, A.; Bencze, G.; Boldizsar, L.; Hajdu, C.; Hidas, P.; Horvath, D.; Kapusi, A.; Krajczar, K.; Sikler, F.; Veres, G. I.; Vesztergombi, G.; Beni, N.; Molnar, J.; Palinkas, J.; Szillasi, Z.; Veszpremi, V.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Dhingra, N.; Gupta, R.; Jindal, M.; Kaur, M.; Kohli, J. M.; Mehta, M. Z.; Nishu, N.; Saini, L. K.; Sharma, A.; Singh, A. P.; Singh, J. B.; Singh, S. P.; Ahuja, S.; Bhattacharya, S.; Choudhary, B. C.; Gupta, P.; Jain, S.; Jain, S.; Kumar, A.; Ranjan, K.; Shivpuri, R. K.; Choudhury, R. K.; Dutta, D.; Kailas, S.; Kumar, V.; Mohanty, A. K.; Pant, L. M.; Shukla, P.; Aziz, T.; Guchait, M.; Gurtu, A.; Maity, M.; Majumder, D.; Majumder, G.; Mazumdar, K.; Mohanty, G. B.; Saha, A.; Sudhakar, K.; Wickramage, N.; Banerjee, S.; Dugad, S.; Mondal, N. K.; Arfaei, H.; Bakhshiansohi, H.; Etesami, S. M.; Fahim, A.; Hashemi, M.; Jafari, A.; Khakzad, M.; Mohammadi, A.; Mohammadi Najafabadi, M.; Paktinat Mehdiabadi, S.; Safarzadeh, B.; Zeinali, M.; Abbrescia, M.; Barbone, L.; Calabria, C.; Colaleo, A.; Creanza, D.; De Filippis, N.; De Palma, M.; Fiore, L.; Iaselli, G.; Lusito, L.; Maggi, G.; Maggi, M.; Manna, N.; Marangelli, B.; My, S.; Nuzzo, S.; Pacifico, N.; Pierro, G. A.; Pompili, A.; Pugliese, G.; Romano, F.; Roselli, G.; Selvaggi, G.; Silvestris, L.; Trentadue, R.; Tupputi, S.; Zito, G.; Abbiendi, G.; Benvenuti, A. C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Giunta, M.; Marcellini, S.; Masetti, G.; Meneghelli, M.; Montanari, A.; Navarria, F. L.; Odorici, F.; Perrotta, A.; Primavera, F.; Rossi, A. M.; Rovelli, T.; Siroli, G.; Travaglini, R.; Albergo, S.; Cappello, G.; Chiorboli, M.; Costa, S.; Tricomi, A.; Tuve, C.; Barbagli, G.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Frosali, S.; Gallo, E.; Gonzi, S.; Lenzi, P.; Meschini, M.; Paoletti, S.; Sguazzoni, G.; Tropiano, A.; Benussi, L.; Bianco, S.; Colafranceschi, S.; Fabbri, F.; Piccolo, D.; Fabbricatore, P.; Musenich, R.; Benaglia, A.; De Guio, F.; Di Matteo, L.; Gennai, S.; Ghezzi, A.; Malvezzi, S.; Martelli, A.; Massironi, A.; Menasce, D.; Moroni, L.; Paganoni, M.; Pedrini, D.; Ragazzi, S.; Redaelli, N.; Sala, S.; Tabarelli de Fatis, T.; Buontempo, S.; Carrillo Montoya, C. A.; Cavallo, N.; De Cosa, A.; Fabozzi, F.; Iorio, A. O. M.; Lista, L.; Merola, M.; Paolucci, P.; Azzi, P.; Bacchetta, N.; Bellan, P.; Bellato, M.; Biasotto, M.; Bisello, D.; Branca, A.; Carlin, R.; Checchia, P.; De Mattia, M.; Dorigo, T.; Gasparini, F.; Gozzelino, A.; Gulmini, M.; Lacaprara, S.; Lazzizzera, I.; Margoni, M.; Maron, G.; Meneguzzo, A. T.; Nespolo, M.; Perrozzi, L.; Pozzobon, N.; Ronchese, P.; Simonetto, F.; Torassa, E.; Tosi, M.; Triossi, A.; Vanini, S.; Zumerle, G.; Baesso, P.; Berzano, U.; Ratti, S. P.; Riccardi, C.; Torre, P.; Vitulo, P.; Viviani, C.; Biasini, M.; Bilei, G. M.; Caponeri, B.; Fanò, L.; Lariccia, P.; Lucaroni, A.; Mantovani, G.; Menichelli, M.; Nappi, A.; Romeo, F.; Santocchia, A.; Taroni, S.; Valdata, M.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Broccolo, G.; Castaldi, R.; D'Agnolo, R. T.; Dell'Orso, R.; Fiori, F.; Foà, L.; Giassi, A.; Kraan, A.; Ligabue, F.; Lomtadze, T.; Martini, L.; Messineo, A.; Palla, F.; Segneri, G.; Serban, A. T.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Del Re, D.; Di Marco, E.; Diemoz, M.; Franci, D.; Grassi, M.; Longo, E.; Nourbakhsh, S.; Organtini, G.; Pandolfi, F.; Paramatti, R.; Rahatlou, S.; Rovelli, C.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Biino, C.; Botta, C.; Cartiglia, N.; Castello, R.; Costa, M.; Demaria, N.; Graziano, A.; Mariotti, C.; Marone, M.; Maselli, S.; Migliore, E.; Mila, G.; Monaco, V.; Musich, M.; Obertino, M. M.; Pastrone, N.; Pelliccioni, M.; Romero, A.; Ruspa, M.; Sacchi, R.; Sola, V.; Solano, A.; Staiano, A.; Vilela Pereira, A.; Belforte, S.; Cossutti, F.; Della Ricca, G.; Gobbo, B.; Montanino, D.; Penzo, A.; Heo, S. G.; Nam, S. K.; Chang, S.; Chung, J.; Kim, D. H.; Kim, G. N.; Kim, J. E.; Kong, D. J.; Park, H.; Ro, S. R.; Son, D.; Son, D. C.; Son, T.; Kim, Zero; Kim, J. Y.; Song, S.; Choi, S.; Hong, B.; Jeong, M. S.; Jo, M.; Kim, H.; Kim, J. H.; Kim, T. J.; Lee, K. S.; Moon, D. H.; Park, S. K.; Rhee, H. B.; Seo, E.; Shin, S.; Sim, K. S.; Choi, M.; Kang, S.; Kim, H.; Park, C.; Park, I. C.; Park, S.; Ryu, G.; Choi, Y.; Choi, Y. K.; Goh, J.; Kim, M. S.; Kwon, E.; Lee, J.; Lee, S.; Seo, H.; Yu, I.; Bilinskas, M. J.; Grigelionis, I.; Janulis, M.; Martisiute, D.; Petrov, P.; Sabonis, T.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Lopez-Fernandez, R.; Magaña Villalba, R.; Sánchez-Hernández, A.; Villasenor-Cendejas, L. M.; Carrillo Moreno, S.; Vazquez Valencia, F.; Salazar Ibarguen, H. A.; Linares, E. Casimiro; Morelos Pineda, A.; Reyes-Santos, M. A.; Krofcheck, D.; Tam, J.; Yiu, C. H.; Butler, P. H.; Doesburg, R.; Silverwood, H.; Ahmad, M.; Ahmed, I.; Asghar, M. I.; Hoorani, H. R.; Khan, W. A.; Khurshid, T.; Qazi, S.; Brona, G.; Cwiok, M.; Dominik, W.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Frueboes, T.; Gokieli, R.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Wrochna, G.; Zalewski, P.; Almeida, N.; Bargassa, P.; David, A.; Faccioli, P.; Ferreira Parracho, P. G.; Gallinaro, M.; Musella, P.; Nayak, A.; Ribeiro, P. Q.; Seixas, J.; Varela, J.; Afanasiev, S.; Belotelov, I.; Bunin, P.; Golutvin, I.; Kamenev, A.; Karjavin, V.; Kozlov, G.; Lanev, A.; Moisenz, P.; Palichik, V.; Perelygin, V.; Shmatov, S.; Smirnov, V.; Volodko, A.; 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, A.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Kirsanov, M.; Krasnikov, N.; Matveev, V.; Pashenkov, A.; Toropin, A.; Troitsky, S.; Epshteyn, V.; Gavrilov, V.; Kaftanov, V.; Kossov, M.; Krokhotin, A.; Lychkovskaya, N.; Popov, V.; Safronov, G.; Semenov, S.; Stolin, V.; Vlasov, E.; Zhokin, A.; Boos, E.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Kodolova, O.; Lokhtin, I.; Markina, A.; Obraztsov, S.; Perfilov, M.; Petrushanko, S.; Sarycheva, L.; Savrin, V.; Snigirev, A.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Leonidov, A.; Rusakov, S. V.; Vinogradov, A.; Azhgirey, I.; Bitioukov, S.; Grishin, V.; Kachanov, V.; Konstantinov, D.; Korablev, A.; Krychkine, V.; Petrov, V.; Ryutin, R.; Slabospitsky, S.; Sobol, A.; Tourtchanovitch, L.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Djordjevic, M.; Krpic, D.; Milosevic, J.; Aguilar-Benitez, M.; Alcaraz Maestre, J.; Arce, P.; Battilana, C.; Calvo, E.; Cepeda, M.; Cerrada, M.; Chamizo Llatas, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Diez Pardos, C.; Domínguez Vázquez, D.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Ferrando, A.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Merino, G.; Puerta Pelayo, J.; Redondo, I.; Romero, L.; Santaolalla, J.; Soares, M. S.; Willmott, C.; Albajar, C.; Codispoti, G.; de Trocóniz, J. F.; Cuevas, J.; Fernandez Menendez, J.; Folgueras, S.; Gonzalez Caballero, I.; Lloret Iglesias, L.; Vizan Garcia, J. M.; Brochero Cifuentes, J. A.; Cabrillo, I. 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F.; Honma, A.; Innocente, V.; Janot, P.; Kaadze, K.; Karavakis, E.; Lecoq, P.; Lourenço, C.; Mäki, T.; Malberti, M.; Malgeri, L.; Mannelli, M.; Masetti, L.; Maurisset, A.; Meijers, F.; Mersi, S.; Meschi, E.; Moser, R.; Mozer, M. U.; Mulders, M.; Nesvold, E.; Nguyen, M.; Orimoto, T.; Orsini, L.; Perez, E.; Petrilli, A.; Pfeiffer, A.; Pierini, M.; Pimiä, M.; Polese, G.; Racz, A.; Rodrigues Antunes, J.; Rolandi, G.; Rommerskirchen, T.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Segoni, I.; Sharma, A.; Siegrist, P.; Simon, M.; Sphicas, P.; Spiropulu, M.; Stoye, M.; Tadel, M.; Tropea, P.; Tsirou, A.; Vichoudis, P.; Voutilainen, M.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Gabathuler, K.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; König, S.; Kotlinski, D.; Langenegger, U.; Meier, F.; Renker, D.; Rohe, T.; Sibille, J.; Starodumov, A.; Bortignon, P.; Caminada, L.; Chanon, N.; Chen, Z.; Cittolin, S.; Dissertori, G.; Dittmar, M.; Eugster, J.; Freudenreich, K.; Grab, C.; Hervé, A.; Hintz, W.; Lecomte, P.; Lustermann, W.; Marchica, C.; Martinez Ruiz del Arbol, P.; Meridiani, P.; Milenovic, P.; Moortgat, F.; Nägeli, C.; Nef, P.; Nessi-Tedaldi, F.; Pape, L.; Pauss, F.; Punz, T.; Rizzi, A.; Ronga, F. J.; Rossini, M.; Sala, L.; Sanchez, A. K.; Sawley, M.-C.; Stieger, B.; Tauscher, L.; Thea, A.; Theofilatos, K.; Treille, D.; Urscheler, C.; Wallny, R.; Weber, M.; Wehrli, L.; Weng, J.; Aguiló, E.; Amsler, C.; Chiochia, V.; De Visscher, S.; Favaro, C.; Ivova Rikova, M.; Millan Mejias, B.; Otiougova, P.; Regenfus, C.; Robmann, P.; Schmidt, A.; Snoek, H.; Chang, Y. H.; Chen, K. H.; Dutta, S.; Kuo, C. M.; Li, S. W.; Lin, W.; Liu, Z. K.; Lu, Y. J.; Mekterovic, D.; Volpe, R.; Wu, J. H.; Yu, S. S.; Bartalini, P.; Chang, P.; Chang, Y. H.; Chang, Y. W.; Chao, Y.; Chen, K. F.; Hou, W.-S.; Hsiung, Y.; Kao, K. Y.; Lei, Y. J.; Lu, R.-S.; Shiu, J. G.; Tzeng, Y. M.; Wang, M.; Adiguzel, A.; Bakirci, M. N.; Cerci, S.; Dozen, C.; Dumanoglu, I.; Eskut, E.; Girgis, S.; Gokbulut, G.; 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.; Uzun, D.; Vergili, L. N.; Vergili, M.; Akin, I. V.; Aliev, T.; Bilmis, S.; Deniz, M.; Gamsizkan, H.; Guler, A. M.; Ocalan, K.; Ozpineci, A.; Serin, M.; Sever, R.; Surat, U. E.; Yildirim, E.; Zeyrek, M.; Deliomeroglu, M.; Demir, D.; Gülmez, E.; Isildak, B.; Kaya, M.; Kaya, O.; Ozkorucuklu, S.; Sonmez, N.; Levchuk, L.; Bostock, F.; Brooke, J. J.; Cheng, T. L.; Clement, E.; Cussans, D.; Frazier, R.; Goldstein, J.; Grimes, M.; Hansen, M.; Hartley, D.; Heath, G. P.; Heath, H. F.; Kreczko, L.; Metson, S.; Newbold, D. M.; Nirunpong, K.; Poll, A.; Senkin, S.; Smith, V. 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E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Leslie, D.; Martin, W.; Reid, I. D.; Teodorescu, L.; Hatakeyama, K.; Bose, T.; Carrera Jarrin, E.; Fantasia, C.; Heister, A.; John, J. St.; Lawson, P.; Lazic, D.; Rohlf, J.; Sperka, D.; Sulak, L.; Avetisyan, A.; Bhattacharya, S.; Chou, J. P.; Cutts, D.; Ferapontov, A.; Heintz, U.; Jabeen, S.; Kukartsev, G.; Landsberg, G.; Narain, M.; Nguyen, D.; Segala, M.; Sinthuprasith, T.; Speer, T.; Tsang, K. V.; Breedon, R.; Calderon De La Barca Sanchez, M.; Chauhan, S.; Chertok, M.; Conway, J.; Cox, P. T.; Dolen, J.; Erbacher, R.; Friis, E.; Ko, W.; Kopecky, A.; Lander, R.; Liu, H.; Maruyama, S.; Miceli, T.; Nikolic, M.; Pellett, D.; Robles, J.; Salur, S.; Schwarz, T.; Searle, M.; Smith, J.; Squires, M.; Tripathi, M.; Vasquez Sierra, R.; Veelken, C.; Andreev, V.; Arisaka, K.; Cline, D.; Cousins, R.; Deisher, A.; Duris, J.; Erhan, S.; Farrell, C.; Hauser, J.; Ignatenko, M.; Jarvis, C.; Plager, C.; Rakness, G.; Schlein, P.; Tucker, J.; Valuev, V.; Babb, J.; Chandra, A.; Clare, R.; Ellison, J.; Gary, J. W.; Giordano, F.; Hanson, G.; Jeng, G. Y.; Kao, S. C.; Liu, F.; Liu, H.; Long, O. R.; Luthra, A.; Nguyen, H.; Shen, B. C.; Stringer, R.; Sturdy, J.; Sumowidagdo, S.; Wilken, R.; Wimpenny, S.; Andrews, W.; Branson, J. G.; Cerati, G. B.; Dusinberre, E.; Evans, D.; Golf, F.; Holzner, A.; Kelley, R.; Lebourgeois, M.; Letts, J.; Mangano, B.; Padhi, S.; Palmer, C.; Petrucciani, G.; Pi, H.; Pieri, M.; Ranieri, R.; Sani, M.; Sharma, V.; Simon, S.; Tu, Y.; Vartak, A.; Wasserbaech, S.; Würthwein, F.; Yagil, A.; Yoo, J.; Barge, D.; Bellan, R.; Campagnari, C.; D'Alfonso, M.; Danielson, T.; Flowers, K.; Geffert, P.; Incandela, J.; Justus, C.; Kalavase, P.; Koay, S. A.; Kovalskyi, D.; Krutelyov, V.; Lowette, S.; Mccoll, N.; Pavlunin, V.; Rebassoo, F.; Ribnik, J.; Richman, J.; Rossin, R.; Stuart, D.; To, W.; Vlimant, J. R.; Apresyan, A.; Bornheim, A.; Bunn, J.; Chen, Y.; Gataullin, M.; Ma, Y.; Mott, A.; Newman, H. B.; Rogan, C.; Shin, K.; Timciuc, V.; Traczyk, P.; Veverka, J.; Wilkinson, R.; Yang, Y.; Zhu, R. Y.; Akgun, B.; Carroll, R.; Ferguson, T.; Iiyama, Y.; Jang, D. W.; Jun, S. Y.; Liu, Y. F.; Paulini, M.; Russ, J.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Dinardo, M. E.; Drell, B. R.; Edelmaier, C. J.; Ford, W. T.; Gaz, A.; Heyburn, B.; Luiggi Lopez, E.; Nauenberg, U.; Smith, J. G.; Stenson, K.; Ulmer, K. A.; Wagner, S. R.; Zang, S. L.; Agostino, L.; Alexander, J.; Cassel, D.; Chatterjee, A.; Das, S.; Eggert, N.; Gibbons, L. K.; Heltsley, B.; Hopkins, W.; Khukhunaishvili, A.; Kreis, B.; Nicolas Kaufman, G.; Patterson, J. R.; Puigh, D.; Ryd, A.; Salvati, E.; Shi, X.; Sun, W.; Teo, W. D.; Thom, J.; Thompson, J.; Vaughan, J.; Weng, Y.; Winstrom, L.; Wittich, P.; Biselli, A.; Cirino, G.; Winn, D.; Abdullin, S.; Albrow, M.; Anderson, J.; Apollinari, G.; Atac, M.; Bakken, J. A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bloch, I.; Borcherding, F.; Burkett, K.; Butler, J. N.; Chetluru, V.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Cooper, W.; Eartly, D. P.; Elvira, V. D.; Esen, S.; Fisk, I.; Freeman, J.; Gao, Y.; Gottschalk, E.; Green, D.; Gunthoti, K.; Gutsche, O.; Hanlon, J.; Harris, R. M.; Hirschauer, J.; Hooberman, B.; Jensen, H.; Johnson, M.; Joshi, U.; Khatiwada, R.; Klima, B.; Kousouris, K.; Kunori, S.; Kwan, S.; Leonidopoulos, C.; Limon, P.; Lincoln, D.; Lipton, R.; Lykken, J.; Maeshima, K.; Marraffino, J. M.; Mason, D.; McBride, P.; Miao, T.; Mishra, K.; Mrenna, S.; Musienko, Y.; Newman-Holmes, C.; O'Dell, V.; Pordes, R.; Prokofyev, O.; Saoulidou, N.; Sexton-Kennedy, E.; Sharma, S.; Spalding, W. J.; Spiegel, L.; Tan, P.; Taylor, L.; Tkaczyk, S.; Uplegger, L.; Vaandering, E. W.; Vidal, R.; Whitmore, J.; Wu, W.; Yang, F.; Yumiceva, F.; Yun, J. C.; Acosta, D.; Avery, P.; Bourilkov, D.; Chen, M.; De Gruttola, M.; Di Giovanni, G. P.; Dobur, D.; Drozdetskiy, A.; Field, R. D.; Fisher, M.; Fu, Y.; Furic, I. K.; Gartner, J.; Kim, B.; Konigsberg, J.; Korytov, A.; Kropivnitskaya, A.; Kypreos, T.; Matchev, K.; Mitselmakher, G.; Muniz, L.; Prescott, C.; Remington, R.; Schmitt, M.; Scurlock, B.; Sellers, P.; Skhirtladze, N.; Snowball, M.; Wang, D.; Yelton, J.; Zakaria, M.; Ceron, C.; Gaultney, V.; Kramer, L.; Lebolo, L. M.; Linn, S.; Markowitz, P.; Martinez, G.; Mesa, D.; Rodriguez, J. L.; Adams, T.; Askew, A.; Bochenek, J.; Chen, J.; Diamond, B.; Gleyzer, S. V.; Haas, J.; Hagopian, S.; Hagopian, V.; Jenkins, M.; Johnson, K. F.; Prosper, H.; Quertenmont, L.; Sekmen, S.; Veeraraghavan, V.; Baarmand, M. M.; Dorney, B.; Guragain, S.; Hohlmann, M.; Kalakhety, H.; Ralich, R.; Vodopiyanov, I.; Adams, M. R.; Anghel, I. M.; Apanasevich, L.; Bai, Y.; Bazterra, V. E.; Betts, R. R.; Callner, J.; Cavanaugh, R.; Dragoiu, C.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Khalatyan, S.; Kunde, G. J.; Lacroix, F.; Malek, M.; O'Brien, C.; Silvestre, C.; Smoron, A.; Strom, D.; Varelas, N.; Akgun, U.; Albayrak, E. A.; Bilki, B.; Clarida, W.; Duru, F.; Lae, C. K.; McCliment, E.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Newsom, C. R.; Norbeck, E.; Olson, J.; Onel, Y.; Ozok, F.; Sen, S.; Wetzel, J.; Yetkin, T.; Yi, K.; Barnett, B. A.; Blumenfeld, B.; Bonato, A.; Eskew, C.; Fehling, D.; Giurgiu, G.; Gritsan, A. V.; Guo, Z. J.; Hu, G.; Maksimovic, P.; Rappoccio, S.; Swartz, M.; Tran, N. V.; Whitbeck, A.; Baringer, P.; Bean, A.; Benelli, G.; Grachov, O.; Kenny, R. P., Iii; Murray, M.; Noonan, D.; Sanders, S.; Wood, J. S.; Zhukova, V.; Barfuss, A. f.; Bolton, T.; Chakaberia, I.; Ivanov, A.; Khalil, S.; Makouski, M.; Maravin, Y.; Shrestha, S.; Svintradze, I.; Wan, Z.; Gronberg, J.; Lange, D.; Wright, D.; Baden, A.; Boutemeur, M.; Eno, S. C.; Ferencek, D.; Gomez, J. A.; Hadley, N. J.; Kellogg, R. G.; Kirn, M.; Lu, Y.; Mignerey, A. C.; Rumerio, P.; Santanastasio, F.; Skuja, A.; Temple, J.; Tonjes, M. B.; Tonwar, S. C.; Twedt, E.; Alver, B.; Bauer, G.; Bendavid, J.; Busza, W.; Butz, E.; Cali, I. A.; Chan, M.; Dutta, V.; Everaerts, P.; Gomez Ceballos, G.; Goncharov, M.; Hahn, K. A.; Harris, P.; Kim, Y.; Klute, M.; Lee, Y.-J.; Li, W.; Loizides, C.; Luckey, P. D.; Ma, T.; Nahn, S.; Paus, C.; Ralph, D.; Roland, C.; Roland, G.; Rudolph, M.; Stephans, G. S. F.; Stöckli, F.; Sumorok, K.; Sung, K.; Wenger, E. A.; Xie, S.; Yang, M.; Yilmaz, Y.; Yoon, A. S.; Zanetti, M.; Cooper, S. I.; Cushman, P.; Dahmes, B.; De Benedetti, A.; Dudero, P. R.; Franzoni, G.; Haupt, J.; Klapoetke, K.; Kubota, Y.; Mans, J.; Rekovic, V.; Rusack, R.; Sasseville, M.; Singovsky, A.; Cremaldi, L. M.; Godang, R.; Kroeger, R.; Perera, L.; Rahmat, R.; Sanders, D. A.; Summers, D.; Bloom, K.; Bose, S.; Butt, J.; Claes, D. R.; Dominguez, A.; Eads, M.; Keller, J.; Kelly, T.; Kravchenko, I.; Lazo-Flores, J.; Malbouisson, H.; Malik, S.; Snow, G. R.; Baur, U.; Godshalk, A.; Iashvili, I.; Jain, S.; Kharchilava, A.; Kumar, A.; Shipkowski, S. P.; Smith, K.; Alverson, G.; Barberis, E.; Baumgartel, D.; Boeriu, O.; Chasco, M.; Reucroft, S.; Swain, J.; Trocino, D.; Wood, D.; Zhang, J.; Anastassov, A.; Kubik, A.; Odell, N.; Ofierzynski, R. A.; Pollack, B.; Pozdnyakov, A.; Schmitt, M.; Stoynev, S.; Velasco, M.; Won, S.; Antonelli, L.; Berry, D.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kolb, J.; Kolberg, T.; Lannon, K.; Luo, W.; Lynch, S.; Marinelli, N.; Morse, D. M.; Pearson, T.; Ruchti, R.; Slaunwhite, J.; Valls, N.; Wayne, M.; Ziegler, J.; Bylsma, B.; Durkin, L. S.; Gu, J.; Hill, C.; Killewald, P.; Kotov, K.; Ling, T. Y.; Rodenburg, M.; Williams, G.; Adam, N.; Berry, E.; Elmer, P.; Gerbaudo, D.; Halyo, V.; Hebda, P.; Hunt, A.; Jones, J.; Laird, E.; Lopes Pegna, D.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Piroué, P.; Quan, X.; Saka, H.; Stickland, D.; Tully, C.; Werner, J. S.; Zuranski, A.; Acosta, J. G.; Huang, X. T.; Lopez, A.; Mendez, H.; Oliveros, S.; Ramirez Vargas, J. E.; Zatserklyaniy, A.; Alagoz, E.; Barnes, V. E.; Bolla, G.; Borrello, L.; Bortoletto, D.; Everett, A.; Garfinkel, A. F.; Gutay, L.; Hu, Z.; Jones, M.; Koybasi, O.; Kress, M.; Laasanen, A. T.; Leonardo, N.; Liu, C.; Maroussov, V.; Merkel, P.; Miller, D. H.; Neumeister, N.; Shipsey, I.; Silvers, D.; Svyatkovskiy, A.; Yoo, H. D.; Zablocki, J.; Zheng, Y.; Jindal, P.; Parashar, N.; Boulahouache, C.; Cuplov, V.; Ecklund, K. M.; Geurts, F. J. M.; Padley, B. P.; Redjimi, R.; Roberts, J.; Zabel, J.; Betchart, B.; Bodek, A.; Chung, Y. S.; Covarelli, R.; de Barbaro, P.; Demina, R.; Eshaq, Y.; Flacher, H.; Garcia-Bellido, A.; Goldenzweig, P.; Gotra, Y.; Han, J.; Harel, A.; Miner, D. C.; Orbaker, D.; Petrillo, G.; Vishnevskiy, D.; Zielinski, M.; Bhatti, A.; Ciesielski, R.; Demortier, L.; Goulianos, K.; Lungu, G.; Malik, S.; Mesropian, C.; Yan, M.; Atramentov, O.; Barker, A.; Duggan, D.; Gershtein, Y.; Gray, R.; Halkiadakis, E.; Hidas, D.; Hits, D.; Lath, A.; Panwalkar, S.; Patel, R.; Richards, A.; Rose, K.; Schnetzer, S.; Somalwar, S.; Stone, R.; Thomas, S.; Cerizza, G.; Hollingsworth, M.; Spanier, S.; Yang, Z. C.; York, A.; Asaadi, J.; Eusebi, R.; Gilmore, J.; Gurrola, A.; Kamon, T.; Khotilovich, V.; Montalvo, R.; Nguyen, C. N.; Osipenkov, I.; Pakhotin, Y.; Pivarski, J.; Safonov, A.; Sengupta, S.; Tatarinov, A.; Toback, D.; Weinberger, M.; Akchurin, N.; Bardak, C.; Damgov, J.; Jeong, C.; Kovitanggoon, K.; Lee, S. W.; Mane, P.; Roh, Y.; Sill, A.; Volobouev, I.; Wigmans, R.; Yazgan, E.; Appelt, E.; Brownson, E.; Engh, D.; Florez, C.; Gabella, W.; Issah, M.; Johns, W.; Kurt, P.; Maguire, C.; Melo, A.; Sheldon, P.; Snook, B.; Tuo, S.; Velkovska, J.; Arenton, M. W.; Balazs, M.; Boutle, S.; Cox, B.; Francis, B.; Hirosky, R.; Ledovskoy, A.; Lin, C.; Neu, C.; Yohay, R.; Gollapinni, S.; Harr, R.; Karchin, P. E.; Lamichhane, P.; Mattson, M.; Milstène, C.; Sakharov, A.; Anderson, M.; Bachtis, M.; Bellinger, J. N.; Carlsmith, D.; Dasu, S.; Efron, J.; Flood, K.; Gray, L.; Grogg, K. S.; Grothe, M.; Hall-Wilton, R.; Herndon, M.; Klabbers, P.; Klukas, J.; Lanaro, A.; Lazaridis, C.; Leonard, J.; Loveless, R.; Mohapatra, A.; Palmonari, F.; Reeder, D.; Ross, I.; Savin, A.; Smith, W. H.; Swanson, J.; Weinberg, M.; CMS Collaboration

    2011-07-01

    A measurement of Wγ and Zγ production in proton-proton collisions at √{ s} = 7 TeV is presented. Results are based on a data sample recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 36 pb-1. The electron and muon decay channels of the W and Z are used. The total cross sections are measured for photon transverse energy ETγ > 10 GeV and spatial separation from charged leptons in the plane of pseudorapidity and azimuthal angle ΔR (ℓ , γ) > 0.7, and with an additional dilepton invariant mass requirement of Mℓℓ > 50 GeV for the Zγ process. The following cross section times branching fraction values are found: σ (pp → Wγ + X) × B (W → ℓν) = 56.3 ± 5.0 (stat.) ± 5.0 (syst.) ± 2.3 (lumi.) pb and σ (pp → Zγ + X) × B (Z → ℓℓ) = 9.4 ± 1.0 (stat.) ± 0.6 (syst.) ± 0.4 (lumi.) pb. These measurements are in agreement with standard model predictions. The first limits on anomalous WWγ, ZZγ, and Zγγ trilinear gauge couplings at √{ s} = 7 TeV are set.

  16. Bioactive properties of peptides obtained from Argentinian defatted soy flour protein by Corolase PP hydrolysis.

    PubMed

    Coscueta, Ezequiel R; Amorim, Maria M; Voss, Glenise B; Nerli, Bibiana B; Picó, Guillermo A; Pintado, Manuela E

    2016-05-01

    Enzymatic hydrolysis of soybean meal protein isolate (SPI) obtained under two temperature conditions with Corolase PP was studied, assessing the impact of hydrolysis on potential antioxidant and antihypertensive activities. The protein was isolated from soybean meal under controlled conditions of time and temperature (70 °C, 1h; 90 °C, 30 min). Degree of hydrolysis assessed the progress of hydrolysis at different sampling times. For hydrolysates the antioxidant and angiotensin-converting-enzyme (ACE) inhibitory activities were measured. As observed, the DH was increasing until reaching 20% at 10h with disappearance of globular proteins and generation of low molecular weight peptides (less than 3kDa). A significant increase in antioxidant and ACE inhibitory capacities was observed. Five main peptides were identified, which may explain through their sequences the bioactive properties analyzed. Through this study was possible to obtain for the first time with Corolase PP soy hydrolysates with potential antioxidant and ACE inhibitory activities, which can be used to obtain new added value functional ingredients from soy meal.

  17. Energy dependence of J / ψ production in p+p collisions at STAR

    NASA Astrophysics Data System (ADS)

    Yang, Qian; STAR Collaboration

    2015-10-01

    J / ψ production in heavy-ion collisions is an important tool for studying the properties of Quark-Gluon Plasma (QGP). Interpretation of these results requires a good understanding of the production mechanisms in p+p collisions, which include direct production via gluon fusion, parton fragmentation, and feed down from excited charmonium states and B hadrons. Despite decades of efforts, the J / ψ production mechanism still remains a puzzle in high energy physics. J / ψ measurement at a new beam energy provides new insights on J / ψ production mechanism and constrains theoretical parameters. In 2013, a large fraction of the Muon Telescope Detector (MTD) was installed at mid-rapidity in STAR. This enables, for the first time, the measurement of J / ψ at STAR via the di-muon channel. In this talk, we will present the measurement on J / ψ production in p+p collisions at √{ s} = 200 and 500 GeV in a wide pT range up to 20 GeV/c, by combing measurements from the MTD and the other detectors. We will discuss the physics perspectives of J / ψ measurement in the forward pseudo-rapidity range 2 . 5 < η < 4 . 5 with the proposed future Forward Calorimeter System and Forward Tracking System at STAR.

  18. Regrouping of the beam in the IHEP PS for the UNK p-p programs

    NASA Astrophysics Data System (ADS)

    Myae, E. A.; Nelipovich, E. S.; Pashkov, P. T.; Smirnov, A. V.

    Possibilities to form particle bunches in the IHEP machine whose longitudinal parameters would satisfy the requirements imposed by the UNK p-p programs are analyzed. In the case of the 3 x 3 TeV p-p program the accelerated proton beam in the IHEP PS after preliminary quasiadiabatic debunching process will be recaptured into a stable oscillating mode at 33.3 MHz. The peculiarities of the RF system designed for these purposes with an account of strong beam loading are discussed. For the 0.4 x 3 TeV UNK colliding beam regime, it is necessary to compress the accelerated proton bunches in the IHEP PS so that their length will be 4 times less. The main difficulties arising during 'RF gymnastics' which is used for beam compressing, are caused by nonlinearities of the external accelerating field and also the fields induced in the RF cavities by the beam. The compensation of such effects with the help of the special RF system is discussed.

  19. A search for excited leptons in pp Collisions at sqrt(s) = 7 TeV

    SciTech Connect

    Chatrchyan, Serguei; et al.

    2011-10-01

    A search for excited leptons is carried out with the CMS detector at the LHC, using 36 inverse picobarns of pp collision data recorded at sqrt(s) = 7 TeV. The search is performed for associated production of a lepton and an oppositely charged excited lepton pp to l l*, followed by the decay l* to l gamma, resulting in the l l gamma final state, where l = electron or muon. No excess of events above the standard model expectation is observed. Interpreting the findings in the context of l* production through four-fermion contact interactions and subsequent decay via electroweak processes, first upper limits are reported for l* production at this collision energy. The exclusion region in the compositeness scale Lambda and excited lepton mass M(l*) parameter space is extended beyond previously established limits. For Lambda = M(l*), excited lepton masses are excluded below 1070 GeV/c^2 for e* and 1090 GeV/c^2 for mu* at the 95% confidence level.

  20. Comparison between two portable devices for widefield PpIX fluorescence during cervical intraepithelial neoplasia treatment

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia Mayumi; Lombardi, Welington; Cossetin, Natália Fernandez; Varoto, Cinthia; Kurachi, Cristina; Bagnato, Vanderlei Salvador

    2015-06-01

    The use of portable electronic devices, in particular mobile phones such as smartphones is increasing not only for all known applications, but also for diagnosis of diseases and monitoring treatments like topical Photodynamic Therapy. The aim of the study is to evaluate the production of the photosensitizer Protoporphyrin IX (PpIX) after topical application of a cream containing methyl aminolevulinate (MAL) in the cervix with diagnosis of Cervical Intraepithelial Neoplasia (CIN) through the fluorescence images captured after one and three hours and compare the images using two devices (a Sony Xperia® mobile and an Apple Ipod®. Was observed an increasing fluorescence intensity of the cervix three hours after cream application, in both portable electronic devices. However, because was used a specific program for the treatment of images using the Ipod® device, these images presented better resolution than observed by the Sony cell phone without a specific program. One hour after cream application presented a more selective fluorescence than the group of three hours. In conclusion, the use of portable devices to obtain images of PpIX fluorescence shown to be an effective tool and is necessary the improvement of programs for achievement of better results.

  1. Results from the first p+p runs of the ALICE High Level Trigger at LHC

    NASA Astrophysics Data System (ADS)

    Kanaki, Kalliopi; ALICE HLT Collaboration

    2011-12-01

    The High Level Trigger for the ALICE experiment at LHC is a powerful, sophisticated tool aimed at compressing the raw data volume and issuing selective triggers for events with desirable physics content. At its current state it integrates information from all major ALICE detectors, i. e. the inner tracking system, the time projection chamber, the electromagnetic calorimeters, the transition radiation detector and the muon spectrometer performing real-time event reconstruction. The steam engine behind HLT is a high performance computing cluster of several hundred nodes. It has to reduce the data rate from 25 GB/s to 1.25 GB/s for fitting the DAQ mass storage bandwidth. The cluster is served by a full GigaBit Ethernet network, in addition to an InfiniBand backbone network. To cope with the great challenge of Pb+Pb collisions in autumn 2010, its performance capabilities are being enhanced with the addition of new nodes. Towards the same end the first GPU co-processors are in place. During the first period of data taking with p+p collisions the HLT was extensively used to reconstruct, analyze and display data from the various participating detectors. Among other tasks it contributed to the monitoring of the detector performance, selected events for their calibration and efficiency studies, and estimated primary and secondary vertices from p+p collisions identifying V0 topologies. The experience gained during these first months of online operation will be presented.

  2. Azimuthal anisotropy harmonics from long-range correlations in high multiplicity pp collisions at CMS

    NASA Astrophysics Data System (ADS)

    Chen, Zhenyu

    2016-12-01

    Measurements of two-particle angular correlations in pp collisions at √{ s} = 7 TeV are presented as a function of charged-particle multiplicities. The data, corresponding to an integrated luminosity of about 6.2 pb-1, were collected during the 2010 LHC pp run using the CMS detector. In high-multiplicity events, a long-range (| Δη | > 2), near-side (Δϕ ≈ 0) structure is found in the two-particle Δη - Δϕ correlation functions. The second-order (v2) and third-order (v3) azimuthal anisotropy harmonics of charged particles, KS0 and Λ / Λ ‾ particles are extracted from long-range two-particle correlations as a function of particle multiplicity and transverse momentum, after correcting for the contribution of back-to-back jet correlations. A v2 and v3 value of about 4% and 1%, averaging over 0.3

  3. The serine/threonine phosphatase PPM1B (PP2Cβ) selectively modulates PPARγ activity.

    PubMed

    Tasdelen, Ismayil; van Beekum, Olivier; Gorbenko, Olena; Fleskens, Veerle; van den Broek, Niels J F; Koppen, Arjen; Hamers, Nicole; Berger, Ruud; Coffer, Paul J; Brenkman, Arjan B; Kalkhoven, Eric

    2013-04-01

    Reversible phosphorylation is a widespread molecular mechanism to regulate the function of cellular proteins, including transcription factors. Phosphorylation of the nuclear receptor PPARγ (peroxisome-proliferator-activated receptor γ) at two conserved serine residue (Ser(112) and Ser(273)) results in an altered transcriptional activity of this transcription factor. So far, only a very limited number of cellular enzymatic activities has been described which can dephosphorylate nuclear receptors. In the present study we used immunoprecipitation assays coupled to tandem MS analysis to identify novel PPARγ-regulating proteins. We identified the serine/threonine phosphatase PPM1B [PP (protein phosphatase), Mg(2+)/Mn(2+) dependent, 1B; also known as PP2Cβ] as a novel PPARγ-interacting protein. Endogenous PPM1B protein is localized in the nucleus of mature 3T3-L1 adipocytes where it can bind to PPARγ. Furthermore we show that PPM1B can directly dephosphorylate PPARγ, both in intact cells and in vitro. In addition PPM1B increases PPARγ-mediated transcription via dephosphorylation of Ser(112). Finally, we show that knockdown of PPM1B in 3T3-L1 adipocytes blunts the expression of some PPARγ target genes while leaving others unaltered. These findings qualify the phosphatase PPM1B as a novel selective modulator of PPARγ activity.

  4. A protein phosphatase 1 gamma (PP1γ) of the human protozoan parasite Trichomonas vaginalis is involved in proliferation and cell attachment to the host cell.

    PubMed

    Muñoz, Christian; Pérez, Mauricio; Orrego, Patricio R; Osorio, Luis; Gutiérrez, Bessy; Sagua, Hernán; Castillo, Juan L; Martínez-Oyanedel, Jose; Arroyo, Rossana; Meza-Cervantez, Patricia; da Silveira, Jose Franco; Midlej, Victor; Benchimol, Marlene; Cordero, Esteban; Morales, Patricio; Araya, Jorge E; González, Jorge

    2012-07-01

    In this work, evidence for a critical role of Trichomonas vaginalis protein phosphatase 1 gamma (TvPP1γ) in proliferation and attachment of the parasite to the mammalian cell is provided. Firstly, proliferation and attachment of T. vaginalis parasites to HeLa cells was blocked by calyculin A (CA), a potent PP1 inhibitor. Secondly, it was demonstrated that the enzyme activity of native and recombinant TvPP1γ proteins was inhibited by CA. Thirdly, reverse genetic studies confirmed that antisense oligonucleotides targeted to PP1γ but not PP1α or β inhibited proliferation and attachment of trichomonads CA-treated parasites underwent cytoskeletal modifications, including a lack of axostyle typical labelling, suggesting that cytoskeletal phosphorylation could be regulated by a CA-sensitive phosphatase where the role of PP1γ could not be ruled out. Analysis of subcellular distribution of TvPP1γ by cell fractionation and electron microscopy demonstrated the association between TvPP1γ and the cytoskeleton. The expression of adhesins, AP120 and AP65, at the cell surface was also inhibited by CA. The concomitant inhibition of expression of adhesins and changes in the cytoskeleton in CA-treated parasites suggest a specific role for PP1γ -dependent dephosphorylation in the early stages of the host-parasite interaction. Molecular modelling of TvPP1γ showed the conservation of residues critical for maintaining proper folding into the gross structure common to PP1 proteins. Taken together, these results suggest that TvPP1γ could be considered a potential novel drug target for treatment of trichomoniasis.

  5. Study of Protein Phosphatase 2A (PP2A) Activity in LPS-Induced Tolerance Using Fluorescence-Based and Immunoprecipitation-Aided Methodology.

    PubMed

    Sun, Lei; Ii, Adlai L Pappy; Pham, Tiffany T; Shanley, Thomas P

    2015-06-29

    Protein phosphatase 2A (PP2A) is one of the most abundant intracellular serine/threonine (Ser/Thr) phosphatases accounting for 1% of the total cellular protein content. PP2A is comprised of a heterodimeric core enzyme and a substrate-specific regulatory subunit. Potentially, at least seventy different compositions of PP2A exist because of variable regulatory subunit binding that accounts for various activity modulating numerous cell functions. Due to the constitutive phosphatase activity present inside cells, a sensitive assay is required to detect the changes of PP2A activity under various experimental conditions. We optimized a fluorescence assay (DIFMU assay) by combining it with prior anti-PP2A immunoprecipitation to quantify PP2A-specific phosphatase activity. It is also known that prior exposure to lipopolysaccharides (LPS) induces "immune tolerance" of the cells to subsequent stimulation. Herein we report that PP2A activity is upregulated in tolerized peritoneal macrophages, corresponding to decreased TNF-α secretion upon second LPS stimulation. We further examined the role of PP2A in the tolerance effect by using PP2ACαl°xl°x;lyM-Cre conditional knockout macrophages. We found that PP2A phosphatase activity cannot be further increased by tolerance. TNF-α secretion from tolerized PP2ACαl°xl°x;lyM-Cre macrophages is higher than tolerized control macrophages. Furthermore, we showed that the increased TNF-α secretion may be due to an epigenetic transcriptionally active signature on the promoter of TNF-α gene rather than regulation of the NFκB/IκB signaling pathway. These results suggest a role for increased PP2A activity in the regulation of immune tolerance.

  6. Effect of cyclical thermal to mechanical properties of Hybrid Laminate Composites (HLC) with skin recycle polypropylene/natural fiber/halloysite and core PP/KF composites

    NASA Astrophysics Data System (ADS)

    Sri Suharty, Neng; Ismail, Hanafi; Suci Handayani, Desi; Diharjo, Kuncoro; Rachman Wibowo, Fajar; Arnita Wuri, Margaretha

    2016-02-01

    This research has successfully synthesized six hybrid laminate composites (HLC). These HLC consist of two layers skin composites and one layer of core PP/KF composites. There are sticked with epoxy adhesive by using cold press method. In this research 6 types of skin are used, namely the rPP (recycled polypropylene, HC1); rPP/DVB/PP-g-AA/KF (HC2); rPP/DVB/PP-g-AA/Hall (HC3); rPP/DVB/PP-g-AA/Hall+ZB (HC4); rPP/DVB/PP-g-AA/KF/Hall (HC5) and rPP/DVB/PP-g-AA/KF/Hall+ZB (HC6) composites. The mechanical properties assessment tensile strength (TS) of various HLC before and after cyclical thermal (CT) was done by ASTM D638. While testing the flame retardant: such as time to ignition (TTI) and burning rate (BR) was done by ASTM D635. Heat stability of HLC can be recognized by conducting the CT treatment. It is to determine the effect of fluctuating heat loads on mechanical properties of HLC materials. The TS result of five HLCs (HC2, HC3, HC4, HC5 and HC6) before CT treatment were higher than HC1 (blank HLC). Those five HLC are also able to increase the TTI and reduce the BR compared to HC1. The CT treatment conditions performed at 45 oC as much as 125 times. After CT treatment, the TS values only slightly decline compared to before CT treatment.

  7. TaPP2C1, a Group F2 Protein Phosphatase 2C Gene, Confers Resistance to Salt Stress in Transgenic Tobacco

    PubMed Central

    Hu, Wei; Yan, Yan; Hou, Xiaowan; He, Yanzhen; Wei, Yunxie; Yang, Guangxiao; He, Guangyuan; Peng, Ming

    2015-01-01

    Group A protein phosphatases 2Cs (PP2Cs) are essential components of abscisic acid (ABA) signaling in Arabidopsis; however, the function of group F2 subfamily PP2Cs is currently less known. In this study, TaPP2C1 which belongs to group F2 was isolated and characterized from wheat. Expression of the TaPP2C1-GFP fusion protein suggested its ubiquitous localization within a cell. TaPP2C1 expression was downregulated by abscisic acid (ABA) and NaCl treatments, but upregulated by H2O2 treatment. Overexpression of TaPP2C1 in tobacco resulted in reduced ABA sensitivity and increased salt resistance of transgenic seedlings. Additionally, physiological analyses showed that improved resistance to salt stress conferred by TaPP2C1 is due to the reduced reactive oxygen species (ROS) accumulation, the improved antioxidant system, and the increased transcription of genes in the ABA-independent pathway. Finally, transgenic tobacco showed increased resistance to oxidative stress by maintaining a more effective antioxidant system. Taken together, these results demonstrated that TaPP2C1 negatively regulates ABA signaling, but positively regulates salt resistance. TaPP2C1 confers salt resistance through activating the antioxidant system and ABA-independent gene transcription process. PMID:26057628

  8. PATZ1 induces PP4R2 to form a negative feedback loop on IKK/NF-κB signaling in lung cancer

    PubMed Central

    Ho, Ming-Yi; Liang, Chi-Ming; Liang, Shu-Mei

    2016-01-01

    Activation of IKK enhances NF-κB signaling to facilitate cancer cell migration, invasion and metastasis. Here, we uncover the existence of a negative feedback loop of IKK. The transcription factor PATZ1 induces protein phosphatase-4 (PP4) regulatory subunit 2 (PP4R2) in an IKK-dependent manner. PP4R2 enhances the binding of PP4 to phosphorylated IKK to inactivate IKK/NF-κB signaling during sustained stimulation by cellular stimuli such as growth factors and inflammatory mediators. Matched pair studies reveal that primary lung cancers express more PATZ1 and PP4R2 than lymph node metastases in patients. Ectopic PATZ1 decreases invasion/colonization of lung cancers and prolongs the survival of xenograft mice. These effects of PATZ1 are reversed by downregulating PP4R2. Our results suggest that PATZ1 and PP4R2 provide negative feedback on IKK/NF-κB signaling to prevent cancer cells from over-stimulation from cellular stimuli; a decline in PATZ1 and PP4R2 is functionally associated with cancer migration/invasion and agents enhancing PATZ1 and PP4R2 are worth exploring to prevent invasion/metastasis of lung cancers. PMID:27391343

  9. TaPP2C1, a Group F2 Protein Phosphatase 2C Gene, Confers Resistance to Salt Stress in Transgenic Tobacco.

    PubMed

    Hu, Wei; Yan, Yan; Hou, Xiaowan; He, Yanzhen; Wei, Yunxie; Yang, Guangxiao; He, Guangyuan; Peng, Ming

    2015-01-01

    Group A protein phosphatases 2Cs (PP2Cs) are essential components of abscisic acid (ABA) signaling in Arabidopsis; however, the function of group F2 subfamily PP2Cs is currently less known. In this study, TaPP2C1 which belongs to group F2 was isolated and characterized from wheat. Expression of the TaPP2C1-GFP fusion protein suggested its ubiquitous localization within a cell. TaPP2C1 expression was downregulated by abscisic acid (ABA) and NaCl treatments, but upregulated by H2O2 treatment. Overexpression of TaPP2C1 in tobacco resulted in reduced ABA sensitivity and increased salt resistance of transgenic seedlings. Additionally, physiological analyses showed that improved resistance to salt stress conferred by TaPP2C1 is due to the reduced reactive oxygen species (ROS) accumulation, the improved antioxidant system, and the increased transcription of genes in the ABA-independent pathway. Finally, transgenic tobacco showed increased resistance to oxidative stress by maintaining a more effective antioxidant system. Taken together, these results demonstrated that TaPP2C1 negatively regulates ABA signaling, but positively regulates salt resistance. TaPP2C1 confers salt resistance through activating the antioxidant system and ABA-independent gene transcription process.

  10. The Phosphatase PP4c Controls Spindle Orientation to Maintain Proliferative Symmetric Divisions in the Developing Neocortex

    PubMed Central

    Xie, Yunli; Jüschke, Christoph; Esk, Christopher; Hirotsune, Shinji; Knoblich, Juergen A.

    2013-01-01

    Summary In the developing neocortex, progenitor cells expand through symmetric division before they generate cortical neurons through multiple rounds of asymmetric cell division. Here, we show that the orientation of the mitotic spindle plays a crucial role in regulating the transition between those two division modes. We demonstrate that the protein phosphatase PP4c regulates spindle orientation in early cortical progenitor cells. Upon removing PP4c, mitotic spindles fail to orient in parallel to the neuroepithelial surface and progenitors divide with random orientation. As a result, their divisions become asymmetric and neurogenesis starts prematurely. Biochemical and genetic experiments show that PP4c acts by dephosphorylating the microtubule binding protein Ndel1, thereby enabling complex formation with Lis1 to form a functional spindle orientation complex. Our results identify a key regulator of cortical development and demonstrate that changes in the orientation of progenitor division are responsible for the transition between symmetric and asymmetric cell division. PMID:23830831

  11. The role of PP2A-associated proteins and signal pathways in microcystin-LR toxicity.

    PubMed

    Liu, Jing; Sun, Yu

    2015-07-02

    Microcystins are a family of monocyclic heptapeptides produced by cyanobacteria during water blooms. Microcystin-LR (MC-LR) is the most common member of this family. Microcystins induce a variety of toxic cellular effects, including oxidative damage, apoptosis, cytoskeletal destabilization, and cancer cell invasion. Recent studies have examined the molecular mechanism of their toxicity. Protein phosphatase 2A (PP2A) is emerging as a critical regulator of the microcystin-induced molecular network. Furthermore, it has been shown that several molecules or signal pathways associated with PP2A play important roles in microcystin-induced toxic effects. This review summarizes the recent research progress of the molecular mechanism and focuses on the role of PP2A in MC-LR toxicity, which will contribute to a better understanding of the mechanism of microcystin toxicity, and will provide biomarkers for toxicity assessment and control.

  12. Observation of χcJ decaying into the pp̄K⁺K⁻ final state

    DOE PAGES

    Ablikim, M.; Achasov, M. N.; Alberto, D.; ...

    2011-06-27

    First measurements of the decays of the three χcJ states to pp̄K⁺K⁻ final states are presented. Intermediate Φ→K⁺K⁻ and Λ(1520)→pK⁻ resonance states are observed, and branching fractions for χcJ→p̄K⁺Λ(1520), Λ(1520)Λ¯¯¯(1520), and Φpp̄ are reported. We also measure branching fractions for direct χcJ→pp̄K⁺K⁻ decays. These are first observations of χcJ decays to unstable baryon resonances and provide useful information about the χcJ states. The experiment uses samples of χcJ mesons produced via radiative transitions from 106×10⁶ ψ' mesons collected in the BESIII detector at the BEPCII e⁺e⁻ collider.

  13. Functional characterization of the PP2C phosphatase CaPtc2p in the human fungal pathogen Candida albicans.

    PubMed

    Feng, Jinrong; Zhao, Jingwen; Li, Jing; Zhang, Lilin; Jiang, Linghuo

    2010-09-01

    Type 2C protein phosphatases (PP2C) are monomeric enzymes and their activities require the presence of magnesium or manganese ion. There are seven PP2C-like genes in Candida albicans. In this study, we demonstrate that CaPtc2p is a PP2C phosphatase. Surprisingly, in addition to the cytoplasmic localization, CaPtc2p is partially associated with mitochondria in yeast-form and filamentous cells of C. albicans. Expression of CaPTC2 is developmentally regulated during the serum-induced filamentation. Deletion of CaPTC2 renders C. albicans cells sensitive to SDS and azole antifungals, as well as the DNA methylation agent methylmethane sulphonate and the DNA synthesis inhibitor hydroxyurea. Therefore, CaPtc2p might fulfil multiple functions, including the regulation of mitochondrial physiology and checkpoint recovery from DNA damage in C. albicans cells.

  14. Quantification of PpIX concentration in basal cell carcinoma and squamous cell carcinoma models using spatial frequency domain imaging

    PubMed Central

    Sunar, Ulas; Rohrbach, Daniel J.; Morgan, Janet; Zeitouni, Natalie; Henderson, Barbara W.

    2013-01-01

    5-aminolaevulinic acid photodynamic therapy (ALA-PDT) is an attractive treatment option for nonmelanoma skin tumors, especially for multiple lesions and large areas. The efficacy of ALA-PDT is highly dependent on the photosensitizer (PS) concentration present in the tumor. Thus it is desirable to quantify PS concentration and distribution, preferably noninvasively to determine potential outcome. Here we quantified protoporphyrin IX (PpIX) distribution induced by topical and intra-tumoral (it) administration of the prodrug ALA in basal and squamous cell carcinoma murine models by using spatial frequency domain imaging (SFDI). The in vivo measurements were validated by analysis of the ex vivo extraction of PpIX. The study demonstrates the feasibility of non-invasive quantification of PpIX distributions in skin tumors. PMID:23577288

  15. Relationship of the first step in protein synthesis to ppGpp: formation of A(5')ppp(5')Gpp.

    PubMed Central

    Rapaport, E; Svihovec, S K; Zamecnik, P C

    1975-01-01

    In the presence of purified Escherichia coli lysyl-tRNA synthetase [L-lysine:tRNALys ligase (AMP-forming) EC 6.1.1.6], L-lysine, and ATP, addition of the nucleotide ppGpp results in formation of a unique product-A(5')ppp(5') Gpp. The same compound is also formed very rapidly in a cell-free protein-synthesizing system when ppGpp is added. The possible significance of this reaction in the rapid turnover of ppGpp and as a more general mechanism by which an AMP residue is activated and introduced onto a 5'-diphosphorylated species, including the 5'-end of an RNA, is further discussed. PMID:170611

  16. Measurement of the ZZ production cross section in pp¯ collisions at s=1.96TeV

    DOE PAGES

    Abazov, V. M.; Abbott, B.; Acharya, B. S.; ...

    2011-07-01

    The authors present a new measurement of the production cross section σ(pp = ZZ) at a center-of-mass energy √s = 1.96 TeV, obtained from the analysis of the four charged lepton final state ℓ+ℓ-ℓ`+ℓ`-(ℓ, ℓ` = e or μ). They observe ten candidate events with an expected background of 0.37 ± 0.13 events. The measured cross section σ(pp =ZZ) = 1.26-0.37+0.47 (stat) ± 0.14 (syst) pb is in agreement with NLO QCD predictions. This result is combined with a previous result from the ZZ = ℓ+ℓ- νν channel resulting in a combined cross section of σ(pp = ZZ) = 1.40-0.37-0.43more » (stat) ±0.14 (syst) pb.« less

  17. Rice plants expressing the moss sodium pumping ATPase PpENA1 maintain greater biomass production under salt stress.

    PubMed

    Jacobs, Andrew; Ford, Kristina; Kretschmer, Jodie; Tester, Mark

    2011-10-01

    High cytosolic concentrations of Na+ inhibit plant growth and development. To maintain low cytosolic concentrations of Na+ , higher plants use membrane-bound transporters that drive the efflux of Na+ or partition Na+ ions from the cytosol, either to the extracellular compartment or into the vacuole. Bryophytes also use an energy-dependent Na+ pumping ATPase, not found in higher plants, to efflux Na+ . To investigate whether this transporter can increase the salt tolerance of crop plants, Oryza sativa has been transformed with the Physcomitrella patens Na+ pumping ATPase (PpENA1). When grown in solutions containing 50 mm NaCl, plants constitutively expressing the PpENA1 gene are more salt tolerant and produce greater biomass than controls. Transgenics and controls accumulate similar amounts of Na+ in leaf and root tissues under stress, which indicates that the observed tolerance is not because of Na+ exclusion. Moreover, inductively coupled plasma analysis reveals that the concentration of other ions in the transformants and the controls is similar. The transgenic lines are developmentally normal and fertile, and the transgene expression levels remain stable in subsequent generations. GFP reporter fusions, which do not alter the ability of PpENA1 to complement a salt-sensitive yeast mutant, indicate that when it is expressed in plant tissues, the PpENA1 protein is located in the plasma membrane. PpENA1 peptides are found in plasma membrane fractions supporting the plasma membrane targeting. The results of this study demonstrate the utility of PpENA1 as a potential tool for engineering salinity tolerance in important crop species.

  18. Determinants for substrate specificity of the bacterial PP2C protein phosphatase tPphA from Thermosynechococcus elongatus.

    PubMed

    Su, Jiyong; Forchhammer, Karl

    2013-01-01

    Members of the Mg(2+)- or Mn(2+)-dependent protein phosphatases/PP2C-like serine/threonine phosphatases (PPM/PP2C) are abundant and widely distributed in prokaryotes and eukaryotes, where they regulate diverse signal transduction pathways. Despite low sequence conservation, the structure of their catalytic core is highly conserved except for a flexible loop termed the flap subdomain. Bacterial PPM/PP2C members without C- or N-terminal regulatory domains still recognize their substrates. Based on the crystal structure of tPphA (a PPM/PP2C member from the cyanobacterium Thermosynechococcus elongatus), variants of tPphA were generated by site-directed mutagenesis to identify substrate specificity determinants. Furthermore, a PPM/PP2C chimera containing the tPphA catalytic core and the flap subdomain of human PP2Cα was also generated. tPphA variants and the chimera were tested towards different artificial substrates and native phosphorylated P(II). A binding assay combining chemical crosslinking and pull-down was designed to analyze the binding of the various phosphatase variants to phosphoprotein P(II) . Together, these data showed that the metal 1-metal 2 cluster in the catalytic center, but not the catalytically active metal 3, is required for the binding of phosphorylated substrate. Residues outside the catalytic center are pivotal for the recognition and turnover of phosphorylated protein substrate. In particular, a histidine residue (His39) of tPphA was identified to play a specific role in protein substrate dephosphorylation. Furthermore, mutations in the variable flap subdomain can affect enzyme activity as well as substrate specificity.

  19. Protein phosphatase 2C (PP2C) is responsible for VP-induced dephosphorylation of AQP2 serine 261.

    PubMed

    Cheung, Pui W; Ueberdiek, Lars; Day, Jack; Bouley, Richard; Brown, Dennis

    2017-04-05

    AQP2 trafficking is regulated by phosphorylation and dephosphorylation of serine residues in the AQP2 c-terminus. Vasopressin (VP) binding to its receptor (V2R) leads to a cascade of events that result in the phosphorylation of serine 256 (S256), S264 and S269, but dephosphorylation of S261. To identify which phosphatase is responsible for VP-induced S261 dephosphorylation, we pretreated cells with different phosphatase inhibitors before VP stimulation. Only sanguinarine, a specific protein phosphatase 2C (PP2C) inhibitor, abolished VP-induced S261 dephosphorylation, but not inhibitors of PP1, PP2A (okadaic acid) or PP2B (cyclosporine). However, both sanguinarine and VP significantly increased phosphorylation of ERK, a kinase that can phosphorylate S261; inhibition of ERK by PD98059 partially decreased baseline S261 phosphorylation. These data support a role of ERK in S261 phosphorylation, but suggest that upon VP treatment, increased phosphatase activity overcomes the increase in ERK activity, resulting in overall dephosphorylation of S261. We also found that sanguinarine abolished VP-induced S261 dephosphorylation in cells expressing mutated AQP2 S256A, suggesting that the phosphorylation state of S261 is independent of S256. Sanguinarine alone did not induce AQP2 membrane trafficking, nor did it inhibit VP-induced AQP2 membrane accumulation in cells and kidney tissues, suggesting that S261 does not play an observable role in acute AQP2 membrane accumulation. In conclusion, PP2C activity is required for S261 AQP2 dephosphorylation upon VP stimulation, and this occurs independent of S256 phosphorylation. Understanding the pathways involved in modulating PP2C will help obtain a deeper understanding of the role of S261 in cellular events involving AQP2.

  20. A (p)ppGpp-null mutant of Haemophilus ducreyi is partially attenuated in humans due to multiple conflicting phenotypes.

    PubMed

    Holley, Concerta; Gangaiah, Dharanesh; Li, Wei; Fortney, Kate R; Janowicz, Diane M; Ellinger, Sheila; Zwickl, Beth; Katz, Barry P; Spinola, Stanley M

    2014-08-01

    (p)ppGpp responds to nutrient limitation through a global change in gene regulation patterns to increase survival. The stringent response has been implicated in the virulence of several pathogenic bacterial species. Haemophilus ducreyi, the causative agent of chancroid, has homologs of both relA and spoT, which primarily synthesize and hydrolyze (p)ppGpp in Escherichia coli. We constructed relA and relA spoT deletion mutants to assess the contribution of (p)ppGpp to H. ducreyi pathogenesis. Both the relA single mutant and the relA spoT double mutant failed to synthesize (p)ppGpp, suggesting that relA is the primary synthetase of (p)ppGpp in H. ducreyi. Compared to the parent strain, the double mutant was partially attenuated for pustule formation in human volunteers. The double mutant had several phenotypes that favored attenuation, including increased sensitivity to oxidative stress. The increased sensitivity to oxidative stress could be complemented in trans. However, the double mutant also exhibited phenotypes that favored virulence. When grown to the mid-log phase, the double mutant was significantly more resistant than its parent to being taken up by human macrophages and exhibited increased transcription of lspB, which is involved in resistance to phagocytosis. Additionally, compared to the parent, the double mutant also exhibited prolonged survival in the stationary phase. In E. coli, overexpression of DksA compensates for the loss of (p)ppGpp; the H. ducreyi double mutant expressed higher transcript levels of dksA than the parent strain. These data suggest that the partial attenuation of the double mutant is likely the net result of multiple conflicting phenotypes.