Science.gov

Sample records for selective isobar suppression

  1. An ion guide laser ion source for isobar-suppressed rare isotope beams

    SciTech Connect

    Raeder, Sebastian Ames, Friedhelm; Bishop, Daryl; Bricault, Pierre; Kunz, Peter; Mjøs, Anders; Heggen, Henning; Lassen, Jens Teigelhöfer, Andrea

    2014-03-15

    Modern experiments at isotope separator on-line (ISOL) facilities like ISAC at TRIUMF often depend critically on the purity of the delivered rare isotope beams. Therefore, highly selective ion sources are essential. This article presents the development and successful on-line operation of an ion guide laser ion source (IG-LIS) for the production of ion beams free of isobaric contamination. Thermionic ions from the hot ISOL target are suppressed by an electrostatic potential barrier, while neutral radio nuclides effusing out are resonantly ionized by laser radiation within a quadrupole ion guide behind this barrier. The IG-LIS was developed through detailed thermal and ion optics simulation studies and off-line tests with stable isotopes. In a first on-line run with a SiC target a suppression of surface-ionized Na contaminants in the ion beam of up to six orders of magnitude was demonstrated.

  2. The feasibility of isobaric suppression of 26Mg via post-accelerator foil stripping for the measurement of 26Al [The feasibility of isobaric suppression of 26Mg via post-accelerator foil stripping for the measurement of 26Al.

    DOE PAGES

    Tumey, Scott J.; Brown, Thomas A.; Finkel, Robert C.; ...

    2012-09-13

    Most accelerator mass spectrometry measurements of 26Al utilize the Al- ion despite lower source currents compared with AlO- since the stable isobar 26Mg does not form elemental negative ions. A gas-filled magnet allows sufficient suppression of 26Mg thus enabling the use of the more intense 26AlO- ion. However, most AMS systems do not include a gas-filled magnet. We therefore explored the feasibility of suppressing 26Mg by using a post-accelerator stripping foil. With this approach, combined with the use of alternative cathode matrices, we were able to suppress 26Mg by a factor of twenty. This suppression was insufficient to enable themore » use of 26AlO-, however further refinement of our system may permit its use in the future.« less

  3. Isobar Separation in a Multiple-Reflection Time-of-Flight Mass Spectrometer by Mass-Selective Re-Trapping

    NASA Astrophysics Data System (ADS)

    Dickel, Timo; Plaß, Wolfgang R.; Lippert, Wayne; Lang, Johannes; Yavor, Mikhail I.; Geissel, Hans; Scheidenberger, Christoph

    2017-03-01

    A novel method for (ultra-)high-resolution spatial mass separation in time-of-flight mass spectrometers is presented. Ions are injected into a time-of-flight analyzer from a radio frequency (rf) trap, dispersed in time-of-flight according to their mass-to-charge ratios and then re-trapped dynamically in the same rf trap. This re-trapping technique is highly mass-selective and after sufficiently long flight times can provide even isobaric separation. A theoretical treatment of the method is presented and the conditions for optimum performance of the method are derived. The method has been implemented in a multiple-reflection time-of-flight mass spectrometer and mass separation powers (FWHM) in excess of 70,000, and re-trapping efficiencies of up to 35% have been obtained for the protonated molecular ion of caffeine. The isobars glutamine and lysine (relative mass difference of 1/4000) have been separated after a flight time of 0.2 ms only. Higher mass separation powers can be achieved using longer flight times. The method will have important applications, including isobar separation in nuclear physics and (ultra-)high-resolution precursor ion selection in multiple-stage tandem mass spectrometry.

  4. Isobar Separation in a Multiple-Reflection Time-of-Flight Mass Spectrometer by Mass-Selective Re-Trapping.

    PubMed

    Dickel, Timo; Plaß, Wolfgang R; Lippert, Wayne; Lang, Johannes; Yavor, Mikhail I; Geissel, Hans; Scheidenberger, Christoph

    2017-03-15

    A novel method for (ultra-)high-resolution spatial mass separation in time-of-flight mass spectrometers is presented. Ions are injected into a time-of-flight analyzer from a radio frequency (rf) trap, dispersed in time-of-flight according to their mass-to-charge ratios and then re-trapped dynamically in the same rf trap. This re-trapping technique is highly mass-selective and after sufficiently long flight times can provide even isobaric separation. A theoretical treatment of the method is presented and the conditions for optimum performance of the method are derived. The method has been implemented in a multiple-reflection time-of-flight mass spectrometer and mass separation powers (FWHM) in excess of 70,000, and re-trapping efficiencies of up to 35% have been obtained for the protonated molecular ion of caffeine. The isobars glutamine and lysine (relative mass difference of 1/4000) have been separated after a flight time of 0.2 ms only. Higher mass separation powers can be achieved using longer flight times. The method will have important applications, including isobar separation in nuclear physics and (ultra-)high-resolution precursor ion selection in multiple-stage tandem mass spectrometry. Graphical Abstract ᅟ.

  5. Isobar Separator for Anions: Current status

    NASA Astrophysics Data System (ADS)

    Alary, Jean-François; Javahery, Gholamreza; Kieser, William; Zhao, Xiao-Lei; Litherland, Albert; Cousins, Lisa; Charles, Christopher

    2015-10-01

    The Isobar Separator for Anions (ISA) is an emerging separation technique of isobars applied first to the selective removal of 36S from 36Cl, achieving a relative suppression ratio of 6 orders of magnitude. Using a radio-frequency quadrupole (RFQ) column incorporating low energy gas cells, this innovative technique enables the use of a wide range of low energy ion-molecule reactions and collisional-induced dissociation processes for suppressing specific atomic of molecular anions with a high degree of selectivity. Other elemental pairs (analyte/isobar) successfully separated at AMS level include Ca/K, Sr/(Y, Zr), Cs/Ba, Hf/W and Pu/U. In view of these initial successes, an effort to develop a version of the ISA that can be used as a robust technique for routine AMS analysis has been undertaken. We will discuss the detailed layout of a practical ISA and the functional requirements that a combined ISA/AMS should meet. These concepts are currently being integrated in a pre-commercial ISA system that will be installed soon at the newly established A.E. Lalonde Laboratory in Ottawa, Canada.

  6. The feasibility of isobaric suppression of 26Mg via post-accelerator foil stripping for the measurement of 26Al [The feasibility of isobaric suppression of 26Mg via post-accelerator foil stripping for the measurement of 26Al.

    SciTech Connect

    Tumey, Scott J.; Brown, Thomas A.; Finkel, Robert C.; Rood, Dylan H.

    2012-09-13

    Most accelerator mass spectrometry measurements of 26Al utilize the Al- ion despite lower source currents compared with AlO- since the stable isobar 26Mg does not form elemental negative ions. A gas-filled magnet allows sufficient suppression of 26Mg thus enabling the use of the more intense 26AlO- ion. However, most AMS systems do not include a gas-filled magnet. We therefore explored the feasibility of suppressing 26Mg by using a post-accelerator stripping foil. With this approach, combined with the use of alternative cathode matrices, we were able to suppress 26Mg by a factor of twenty. This suppression was insufficient to enable the use of 26AlO-, however further refinement of our system may permit its use in the future.

  7. Attentional selection by distractor suppression.

    PubMed

    Caputo, G; Guerra, S

    1998-03-01

    Selective attention was studied in displays containing singletons popping out for their odd form or color. The target was defined as the form-singleton, the distractor as the color-singleton. The task was to discriminate the length of a longer line inside the target. Target-distractor similarity was controlled using a threshold measurement as dependent variable in experiments in which distractor presence vs absence, bottom-up vs top-down selection (through knowledge of target features), and target-distractor distance were manipulated. The results in the bottom-up condition showed that length threshold was elevated when a distractor was present and that this elevation progressively increased as the number of distractors was increased from one to two. This set-size effect was not accounted by the hypothesis that selective attention intervenes only at the stage of decision before response. Selective attention produced a suppressive surround in which discriminability of neighboring objects was strongly reduced, and a larger surround in which discriminability was reduced by an approximately constant amount. Different results were found in the top-down condition in which target discriminability was unaffected by distractor presence and no effect of target-distractor distance was found. On the other hand, response times in both bottom-up and top-down conditions were slower the shorter the target-distractor distance was. On the basis of the experimental results, selective attention is a parallel process of spatial filtering at an intermediate processing level operating after objects have been segmented. This filtering stage explores high level interactions between objects taking control on combinatorial explosion by operating over only a limited spatial extent: it picks out a selected object and inhibits the neighboring objects; then, non-selected objects are suppressed across the overall image. When no feature-based selection is available in the current behavior, this

  8. Selective memories: infants' encoding is enhanced in selection via suppression.

    PubMed

    Markant, Julie; Amso, Dima

    2013-11-01

    The present study examined the hypothesis that inhibitory visual selection mechanisms play a vital role in memory by limiting distractor interference during item encoding. In Experiment 1a we used a modified spatial cueing task in which 9-month-old infants encoded multiple category exemplars in the contexts of an attention orienting mechanism involving suppression (i.e. inhibition of return, IOR) versus one that does not (i.e. facilitation). At test, infants in the IOR condition showed both item-specific learning and abstraction of broader category information. In contrast, infants in the facilitation condition did not discriminate across novel and familiar test items. Experiment 1b confirmed that the learning observed in the IOR condition was specific to spatial cueing of attention and was not due to timing differences across the IOR and facilitation conditions. In Experiment 2, we replicated the results of Experiment 1, using a within-subjects design to explicitly examine learning and memory encoding in the context of concurrent suppression. These data show that developing inhibitory selective attention enhances efficacy of memory encoding for subsequent retrieval. Furthermore, these results highlight the importance of considering interactions between developing attention and memory systems.

  9. Isobar separator for radioactive nuclear beams project

    SciTech Connect

    Davids, C.N.; Nolen, J.A.

    1995-08-01

    In order to produce pure beams of radioactive products emanating from the production target/ion source system, both mass and isobar separation is required. A preliminary mass separation with a resolution {triangle}M/M of approximately 10{sup -3} will select the proper mass beam. An isobar separator is needed because the masses of adjacent isobars are usually quite close, especially for beams near stability. In general, a mass resolution of 5 x 10{sup -5} is needed for isobar separation in the A < 120 region, while a resolution of 3 x 10{sup -5} or better is needed for heavier masses. Magnets are used to obtain mass separation. However, in addition to having mass dispersion properties, magnets also have an equal energy dispersion. This means that an energy variation in the beam cannot be distinguished from a mass difference. This is important because ions emerge from the ion source having a small ({approximately} 10{sup -5} - 10{sup -4}) energy spread. In order to make the system respond only to mass differences, it must be made energy dispersion. This is normally accomplished by using a combination of electric and magnetic fields. The most convenient way of doing this is to use an electric deflection following the magnet separator. A preliminary isobar separator which achieves a mass resolution of 2.7 x 10{sup -5} is shown in Figure I-38. It uses two large 60{degrees} bending magnets to obtain a mass dispersion of 140 mm/%, and four electric dipoles with bending angles of 39{degrees} to cancel the energy dispersion. Sextupole and octupole correction elements are used to reduce the geometrical aberrations.

  10. Isobaric groundwater well

    DOEpatents

    Hubbell, Joel M.; Sisson, James B.

    1999-01-01

    A method of measuring a parameter in a well, under isobaric conditions, including such parameters as hydraulic gradient, pressure, water level, soil moisture content and/or aquifer properties the method as presented comprising providing a casing having first and second opposite ends, and a length between the ends, the casing supporting a transducer having a reference port; placing the casing lengthwise into the well, second end first, with the reference port vented above the water table in the well; and sealing the first end. A system is presented for measuring a parameter in a well, the system comprising a casing having first and second opposite ends, and a length between the ends and being configured to be placed lengthwise into a well second end first; a transducer, the transducer having a reference port, the reference port being vented in the well above the water table, the casing being screened across and above the water table; and a sealing member sealing the first end. In one embodiment, the transducer is a tensiometer transducer and in other described embodiments, another type transducer is used in addition to a tensiometer.

  11. Optical frequency tripling with improved suppression and sideband selection.

    PubMed

    Thakur, Manoj P; Medeiros, Maria C R; Laurêncio, Paula; Mitchell, John E

    2011-12-12

    A novel optical dispersion tolerant millimetre-wave radio-over-fibre system using optical frequency tripling technique with enhanced and selectable sideband suppression is demonstrated. The implementation utilises cascaded optical modulators to achieve either an optical single sideband (OSSB) or double sideband-suppressed carrier (DSB-SC) signal with high sideband suppression. Our analysis and simulation results indicate that the achievable suppression ratio of this configuration is only limited by other system factors such as optical noise and drifting of the operational conditions. The OSSB transmission system performance is assessed experimentally by the transport of 4 WiMax channels modulating a 10 GHz optical upconverted RF carrier as well as for optical frequency doubling and tripling. The 10 GHz and tripled carrier at 30 GHz are dispersion tolerant resulting both in an average relative constellation error (RCE) of -28.7 dB after 40 km of fibre.

  12. Signal enhancement and suppression during visual-spatial selective attention.

    PubMed

    Couperus, J W; Mangun, G R

    2010-11-04

    Selective attention involves the relative enhancement of relevant versus irrelevant stimuli. However, whether this relative enhancement involves primarily enhancement of attended stimuli, or suppression of irrelevant stimuli, remains controversial. Moreover, if both enhancement and suppression are involved, whether they result from a single mechanism or separate mechanisms during attentional control or selection is not known. In two experiments using a spatial cuing paradigm with task-relevant targets and irrelevant distractors, target, and distractor processing was examined as a function of distractor expectancy. Additionally, in the second study the interaction of perceptual load and distractor expectancy was explored. In both experiments, distractors were either validly cued (70%) or invalidly cued (30%) in order to examine the effects of distractor expectancy on attentional control as well as target and distractor processing. The effects of distractor expectancy were assessed using event-related potentials recorded during the cue-to-target period (preparatory attention) and in response to the task-relevant target stimuli (selective stimulus processing). Analyses of distractor-present displays (anticipated versus unanticipated), showed modulations in brain activity during both the preparatory period and during target processing. The pattern of brain responses suggest both facilitation of attended targets and suppression of unattended distractors. These findings provide evidence for a two-process model of visual-spatial selective attention, where one mechanism (facilitation) influences relevant stimuli and another (suppression) acts to filter distracting stimuli.

  13. Attention selection, distractor suppression and N2pc.

    PubMed

    Mazza, Veronica; Turatto, Massimo; Caramazza, Alfonso

    2009-01-01

    N2pc is generally interpreted as the electrocortical correlate of the distractor-suppression mechanisms through which attention selection takes place in humans. Here, we present data that challenge this common N2pc interpretation. In Experiment 1, multiple distractors induced greater N2pc amplitudes even when they facilitated target identification, despite the suppression account of the N2pc predicted the contrary; in Experiment 2, spatial proximity between target and distractors did not affect the N2pc amplitude, despite resulting in more interference in response times; in Experiment 3, heterogeneous distractors delayed response times but did not elicit a greater N2pc relative to homogeneous distractors again in contrast with what would have predicted the suppression hypothesis. These results do not support the notion that the N2pc unequivocally mirrors distractor-suppression processes. We propose that the N2pc indexes mechanisms involved in identifying and localizing relevant stimuli in the scene through enhancement of their features and not suppression of distractors.

  14. Suppression of eukaryotic translation termination by selected RNAs.

    PubMed Central

    Carnes, J; Frolova, L; Zinnen, S; Drugeon, G; Phillippe, M; Justesen, J; Haenni, A L; Leinwand, L; Kisselev, L L; Yarus, M

    2000-01-01

    Using selection-amplification, we have isolated RNAs with affinity for translation termination factors eRF1 and eRF1.eRF3 complex. Individual RNAs not only bind, but inhibit eRF1-mediated release of a model nascent chain from eukaryotic ribosomes. There is also significant but weaker inhibition of eRF1-stimulated eRF3 GTPase and eRF3 stimulation of eRF1 release activity. These latter selected RNAs therefore hinder eRF1.eRF3 interactions. Finally, four RNA inhibitors of release suppress a UAG stop codon in mammalian extracts dependent for termination on eRF1 from several metazoan species. These RNAs are therefore new specific inhibitors for the analysis of eukaryotic termination, and potentially a new class of omnipotent termination suppressors with possible therapeutic significance. PMID:11073222

  15. Magnetotail dynamics under isobaric constraints

    NASA Technical Reports Server (NTRS)

    Birn, Joachim; Schindler, Karl; Janicke, Lutz; Hesse, Michael

    1994-01-01

    Using linear theory and nonlinear MHD simulations, we investigate the resistive and ideal MHD stability of two-dimensional plasma configurations under the isobaric constraint dP/dt = 0, which in ideal MHD is equivalent to conserving the pressure function P = P(A), where A denotes the magnetic flux. This constraint is satisfied for incompressible modes, such as Alfven waves, and for systems undergoing energy losses. The linear stability analysis leads to a Schroedinger equation, which can be investigated by standard quantum mechanics procedures. We present an application to a typical stretched magnetotail configuration. For a one-dimensional sheet equilibrium characteristic properties of tearing instability are rediscovered. However, the maximum growth rate scales with the 1/7 power of the resistivity, which implies much faster growth than for the standard tearing mode (assuming that the resistivity is small). The same basic eigen-mode is found also for weakly two-dimensional equilibria, even in the ideal MHD limit. In this case the growth rate scales with the 1/4 power of the normal magnetic field. The results of the linear stability analysis are confirmed qualitatively by nonlinear dynamic MHD simulations. These results suggest the interesting possibility that substorm onset, or the thinning in the late growth phase, is caused by the release of a thermodynamic constraint without the (immediate) necessity of releasing the ideal MHD constraint. In the nonlinear regime the resistive and ideal developments differ in that the ideal mode does not lead to neutral line formation without the further release of the ideal MHD constraint; instead a thin current sheet forms. The isobaric constraint is critically discussed. Under perhaps more realistic adiabatic conditions the ideal mode appears to be stable but could be driven by external perturbations and thus generate the thin current sheet in the late growth phase, before a nonideal instability sets in.

  16. Targeting prion-like protein doppel selectively suppresses tumor angiogenesis

    PubMed Central

    Al-Hilal, Taslim A.; Chung, Seung Woo; Choi, Jeong Uk; Kim, Seong Who; Kim, Sang Yoon; Ahsan, Fakhrul; Kim, In-San

    2016-01-01

    Controlled and site-specific regulation of growth factor signaling remains a major challenge for current antiangiogenic therapies, as these antiangiogenic agents target normal vasculature as well tumor vasculature. In this article, we identified the prion-like protein doppel as a potential therapeutic target for tumor angiogenesis. We investigated the interactions between doppel and VEGFR2 and evaluated whether blocking the doppel/VEGFR2 axis suppresses the process of angiogenesis. We discovered that tumor endothelial cells (TECs), but not normal ECs, express doppel; tumors from patients and mouse xenografts expressed doppel in their vasculatures. Induced doppel overexpression in ECs enhanced vascularization, whereas doppel constitutively colocalized and complexed with VEGFR2 in TECs. Doppel inhibition depleted VEGFR2 from the cell membrane, subsequently inducing the internalization and degradation of VEGFR2 and thereby attenuating VEGFR2 signaling. We also synthesized an orally active glycosaminoglycan (LHbisD4) that specifically binds with doppel. We determined that LHbisD4 concentrates over the tumor site and that genetic loss of doppel in TECs decreases LHbisD4 binding and targeting both in vitro and in vivo. Moreover, LHbisD4 eliminated VEGFR2 from the cell membrane, prevented VEGF binding in TECs, and suppressed tumor growth. Together, our results demonstrate that blocking doppel can control VEGF signaling in TECs and selectively inhibit tumor angiogenesis. PMID:26950422

  17. Survey of Evaluated Isobaric Analog States

    SciTech Connect

    MacCormick, M.

    2014-06-15

    Isobaric analog states (IAS) can be used to estimate the masses of members belonging to the same isospin multiplet. Experimental and estimated IAS have been used frequently within the Atomic Mass Evaluation (AME) in the past, but the associated set of evaluated masses have been published for the first time in AME2012 and NUBASE2012. In this paper the current trends of the isobaric multiplet mass equation (IMME) coefficients are shown. The T = 2 multiplet is used as a detailed illustration.

  18. TITAN's multiple-reflection time-of-flight isobar separator

    NASA Astrophysics Data System (ADS)

    Reiter, Moritz Pascal; Titan Collaboration

    2016-09-01

    At the ISAC facility located at TRIUMF exotic nuclei are produced by the ISOL method. Exotic nuclei are separated by a magnetic separator and transported to TRIUMF's Ion Trap for Atomic and Nuclear science (TITAN). TITAN is a system of multiple ion traps for high precision mass measurements and in-trap decay spectroscopy. Although ISAC can deliver some of the highest yields for even many of the most exotic species many measurements suffer from a strong isobaric background. This background often prevents the high precision measurement of the species of interest. To overcome this limitation an additional isobar separator based on the Multiple-Reflection Time-Of-Flight Mass Spectrometry (MR-TOF-MS) technique has been developed for TITAN. Mass selection is achieved using dynamic re-trapping of the species of interest after a time-of-flight analysis in an electrostatic isochronous reflector system. Additionally the MR-TOF-MS will, on its own, enable mass measurements of very short-lived nuclides that are weakly produced. Being able to measure all isobars of a given mass number at the same time the MR-TOF-MS can be used for beam diagnostics or determination of beam compositions. Results from the offline commissioning showing mass resolving power and separation power will be presented.

  19. {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.

  20. Isochoric and isobaric freezing of fish muscle.

    PubMed

    Năstase, Gabriel; Lyu, Chenang; Ukpai, Gideon; Șerban, Alexandru; Rubinsky, Boris

    2017-02-19

    We have recently shown that, a living organism, which succumbs to freezing to -4 °C in an isobaric thermodynamic system (constant atmospheric pressure), can survive freezing to -4 °C in an isochoric thermodynamic system (constant volume). It is known that the mechanism of cell damage in an isobaric system is the freezing caused increase in extracellular osmolality, and, the consequent cell dehydration. An explanation for the observed survival during isochoric freezing is the thermodynamic modeling supported hypothesis that, in the isochoric frozen solution the extracellular osmolality is comparable to the cell intracellular osmolality. Therefore, cells in the isochoric frozen organism do not dehydrate, and the tissue maintains its morphological integrity. Comparing the histology of: a) fresh fish white muscle, b) fresh muscle frozen to -5 °C in an isobaric system and c) fresh muscle frozen to -5 °C I in an isochoric system, we find convincing evidence of the mechanism of cell dehydration during isobaric freezing. In contrast, the muscle tissue frozen to -5 °C in an isochoric system appears morphologically identical to fresh tissue, with no evidence of dehydration. This is the first experimental evidence in support of the hypothesis that in isochoric freezing there is no cellular dehydration and therefore the morphology of the frozen tissue remains intact.

  1. Selective suppression of interleukin-12 induction after macrophage receptor ligation.

    PubMed

    Sutterwala, F S; Noel, G J; Clynes, R; Mosser, D M

    1997-06-02

    Interleukin (IL)-12 is a monocyte- and macrophage-derived cytokine that plays a crucial role in both the innate and the acquired immune response. In this study, we examined the effects that ligating specific macrophage receptors had on the induction of IL-12 by lipopolysaccharide (LPS). We report that ligation of the macrophage Fcgamma, complement, or scavenger receptors inhibited the induction of IL-12 by LPS. Both mRNA synthesis and protein secretion were diminished to near-undetectable levels following receptor ligation. Suppression was specific to IL-12 since IL-10 and tumor necrosis factor-alpha (TNF-alpha) production were not inhibited by ligating macrophage receptors. The results of several different experimental approaches suggest that IL-12 downregulation was due to extracellular calcium influxes that resulted from receptor ligation. First, preventing extracellular calcium influxes, by performing the assays in EGTA, abrogated FcgammaR-mediated IL-12(p40) mRNA suppression. Second, exposure of macrophages to the calcium ionophores, ionomycin or A23187, mimicked receptor ligation and inhibited IL-12(p40) mRNA induction by LPS. Finally, bone marrow-derived macrophages from FcR gamma chain-deficient mice, which fail to flux calcium after receptor ligation, failed to inhibit IL-12(p40) mRNA induction. These results indicate that the calcium influxes that occur as a result of receptor ligation are responsible for inhibiting the induction of IL-12 by LPS. Hence, the ligation of phagocytic receptors on macrophages can lead to a dramatic decrease in IL-12 induction. This downregulation may be a way of limiting proinflammatory responses of macrophages to extracellular pathogens, or suppressing the development of cell-mediated immunity to intracellular pathogens.

  2. Effects of search efficiency on surround suppression during visual selection in frontal eye field.

    PubMed

    Schall, Jeffrey D; Sato, Takashi R; Thompson, Kirk G; Vaughn, Amanda A; Juan, Chi-Hung

    2004-06-01

    Previous research has shown that visually responsive neurons in the frontal eye field of macaque monkeys select the target for a saccade during efficient, pop-out visual search through suppression of the representation of the nontarget distractors. For a fraction of these neurons, the magnitude of this distractor suppression varied with the proximity of the target to the receptive field, exhibiting more suppression of the distractor representation when the target was nearby than when the target was distant. The purpose of this study was to determine whether the variation of distractor suppression related to target proximity varied with target-distractor feature similarity. The effect of target proximity on distractor suppression did not vary with target-distractor similarity and therefore may be an endogenous property of the selection process.

  3. Improvement of non-isobaric model for shock ignition

    NASA Astrophysics Data System (ADS)

    Farahbod, Amir Hossein; Abolfazl Ghasemi, Seyed; Jafar Jafari, Mohammad; Rezaei, Somayeh; Sobhanian, Samad

    2014-10-01

    In this paper, improved relations of total fuel energy, fuel gain, hot-spot radius and total areal density in a non-isobaric model of fuel assembly have been derived and compared with the numerical results of [J. Schmitt, J.W. Bates, S.P. Obenschain, S.T. Zalesak, D.E. Fyfe, Phys. Plasmas 17, 042701 (2010); S. Atzeni, A. Marocchino, A. Schiavi, G. Schurtz, New J. Phys. 15, 045004 (2013)] and several simulations performed by MULTI-1D radiation hydrodynamic code for shock ignition scenario. Our calculations indicate that the approximations made by [M.D. Rosen, J.D. Lindl, A.R. Thiessen, LLNL Laser Program Annual Report, UCRL-50021-83, pp. 3-5 (1983); J. Schmitt, J.W. Bates, S.P. Obenschain, S.T. Zalesak, D.E. Fyfe, Phys. Plasmas 17, 042701 (2010)] for the calculation of burn-up fraction are not accurate enough to give results consistent with simulations. Therefore, we have introduced more appropriate approximations for the burn-up fraction and total areal density of the fuel that are in more agreement with simulation results of shock ignition. Meanwhile, it is shown that the related formulas of the non-isobaric model for total fuel energy, fuel gain and also hot-spot radius cannot determine the model parameters independently, but improved model choose a better selection and less restrictions on determination of the parameters for the non-isobaric model. Such derivations can be used in theoretical studies of the ignition conditions and burn-up fraction of the fuel in shock ignition scenario.

  4. Pseudomonas fluorescens strains selectively suppress annual bluegrass (Poa annua L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Annual bluegrass (Poa annua L.) is a cool-season annual grass that is a major weed species in turf, turfgrass-seed production, sod production, and golf courses of the western United States. There are few selective herbicides available for the management of annual bluegrass. While the life cycles o...

  5. Isospin purity in the A=42 isobars

    SciTech Connect

    Orce, J.N.; McKay, C.J.; Choudry, S.N.; Lesher, S.L.; Mynk, M.; Bandyopadhyay, D.; Yates, S.W.; McEllistrem, M.T.; Petkov, P.

    2004-09-13

    The lifetime of the first 2{sub T=1}{sup +} state in 42Sc has been measured as 74(16) fs. This result gives a value for the isoscalar matrix element of M0=6.63(76). From the mirror nuclei, 42Ca and 42Ti, the isoscalar matrix element is given as 7.15(48) W.u., confirming isospin purity in the A=42 isobars.

  6. Selective two-photon fluorescence suppression by ultrafast pulse-pair excitation: control by selective one-color stimulated emission.

    PubMed

    Kumar De, Arijit; Roy, Debjit; Goswami, Debabrata

    2011-10-01

    Controlling two-photon molecular fluorescence leading to selective fluorophore excitation has been a long sought after goal in fluorescence microscopy. In this letter, we thoroughly explore selective fluorescence suppression through simultaneous two-photon absorption by two different fluorophores followed by selective one-photon stimulated emission for one particular fluorophore. We achieve this by precisely controlling the time delay between two identical ultrafast near infrared laser pulses.

  7. Frequency selectivity of the human cochlea: Suppression tuning of spontaneous otoacoustic emissions.

    PubMed

    Manley, Geoffrey A; van Dijk, Pim

    2016-06-01

    Frequency selectivity is a key functional property of the inner ear and since hearing research began, the frequency resolution of the human ear has been a central question. In contrast to animal studies, which permit invasive recording of neural activity, human studies must rely on indirect methods to determine hearing selectivity. Psychophysical studies, which used masking of a tone by other sounds, indicate a modest frequency selectivity in humans. By contrast, estimates using the phase delays of stimulus-frequency otoacoustic emissions (SFOAE) predict a remarkably high selectivity, unique among mammals. An alternative measure of cochlear frequency selectivity are suppression tuning curves of spontaneous otoacoustic emissions (SOAE). Several animal studies show that these measures are in excellent agreement with neural frequency selectivity. Here we contribute a large data set from normal-hearing young humans on suppression tuning curves (STC) of spontaneous otoacoustic emissions (SOAE). The frequency selectivities of human STC measured near threshold levels agree with the earlier, much lower, psychophysical estimates. They differ, however, from the typical patterns seen in animal auditory nerve data in that the selectivity is remarkably independent of frequency. In addition, SOAE are suppressed by higher-level tones in narrow frequency bands clearly above the main suppression frequencies. These narrow suppression bands suggest interactions between the suppressor tone and a cochlear standing wave corresponding to the SOAE frequency being suppressed. The data show that the relationship between pre-neural mechanical processing in the cochlea and neural coding at the hair-cell/auditory nerve synapse needs to be reconsidered.

  8. Lipid and water suppression by selective 1H homonuclear polarization transfer.

    PubMed

    Hardy, C J; Dumoulin, C L

    1987-07-01

    A pulse sequence is presented which uses Polarization Transfer by a Selective Homonuclear Technique (POTSHOT) to retain all resonances, in phase, from a selected coupled spin system while suppressing all other peaks, from both coupled and noncoupled spins. This technique, which is a selective form of Homonuclear Polarization Transfer (HPT), has been used in a 1.5-T whole-body system to generate edited 1H lactate spectra from lactate/oil phantoms and from excised dog hearts.

  9. Inclusive fitness effects can select for cancer suppression into old age

    PubMed Central

    Brown, Joel S.; Aktipis, C. Athena

    2015-01-01

    Natural selection can favour health at youth or middle age (high reproductive value) over health at old age (low reproductive value). This means, all else being equal, selection for cancer suppression should dramatically drop after reproductive age. However, in species with significant parental investment, the capacity to enhance inclusive fitness may increase the reproductive value of older individuals or even those past reproductive age. Variation in parental investment levels could therefore contribute to variation in cancer susceptibility across species. In this article, we describe a simple model and framework for the evolution of cancer suppression with varying levels of parental investment and use this model to make testable predictions about variation in cancer suppression across species. This model can be extended to show that selection for cancer suppression is stronger in species with cooperative breeding systems and intergenerational transfers. We consider three cases that can select for cancer suppression into old age: (i) extended parental care that increases the survivorship of their offspring, (ii) grandparents contributing to higher fecundity of their children and (iii) cooperative breeding where helpers forgo reproduction or even survivorship to assist parents in having higher fecundity. PMID:26056358

  10. Glucocorticoids Suppress Selected Components of the Senescence-Associated Secretory Phenotype

    PubMed Central

    Laberge, Remi-Martin; Zhou, Lili; Sarantos, Melissa R.; Rodier, Francis; Freund, Adam; de Keizer, Peter L.J.; Liu, Su; Demaria, Marco; Cong, Yu-Sheng; Kapahi, Pankaj; Desprez, Pierre-Yves; Hughes, Robert E.; Campisi, Judith

    2012-01-01

    SUMMARY Cellular senescence suppresses cancer by arresting the proliferation of cells at risk for malignant transformation. Recently, senescent cells were shown to secrete numerous cytokines, growth factors and proteases that can alter the tissue microenvironment and may promote age-related pathology. To identify small molecules that suppress the senescence-associated secretory phenotype (SASP), we developed a screening protocol using normal human fibroblasts and a library of compounds that are approved for human use. Among the promising library constituents was the glucocorticoid corticosterone. Both corticosterone and the related glucocorticoid cortisol decreased the production and secretion of selected SASP components, including several pro-inflammatory cytokines. Importantly, the glucocorticoids suppressed the SASP without reverting the tumor suppressive growth arrest, and were efficacious whether cells were induced to senesce by ionizing radiation or strong mitogenic signals delivered by oncogenic RAS or MAP kinase kinase 6 overexpression. Suppression of the prototypical SASP component IL-6 required the glucocorticoid receptor, which, in the presence of ligand, inhibited IL-1α signaling and NF-κB transactivation activity. Accordingly, co-treatments combining glucocorticoids with the glucocorticoid antagonist RU-486 or recombinant IL-1α efficiently reestablished NF-κB transcriptional activity and IL-6 secretion. Our findings demonstrate feasibility of screening for compounds that inhibit the effects of senescent cells. They further show that glucocorticoids inhibit selected components of the SASP, and suggest that corticosterone and cortisol, two FDA-approved drugs, might exert their effects in part by suppressing senescence-associated inflammation. PMID:22404905

  11. Glucocorticoids suppress selected components of the senescence-associated secretory phenotype.

    PubMed

    Laberge, Remi-Martin; Zhou, Lili; Sarantos, Melissa R; Rodier, Francis; Freund, Adam; de Keizer, Peter L J; Liu, Su; Demaria, Marco; Cong, Yu-Sheng; Kapahi, Pankaj; Desprez, Pierre-Yves; Hughes, Robert E; Campisi, Judith

    2012-08-01

    Cellular senescence suppresses cancer by arresting the proliferation of cells at risk for malignant transformation. Recently, senescent cells were shown to secrete numerous cytokines, growth factors, and proteases that can alter the tissue microenvironment and may promote age-related pathology. To identify small molecules that suppress the senescence-associated secretory phenotype (SASP), we developed a screening protocol using normal human fibroblasts and a library of compounds that are approved for human use. Among the promising library constituents was the glucocorticoid corticosterone. Both corticosterone and the related glucocorticoid cortisol decreased the production and secretion of selected SASP components, including several pro-inflammatory cytokines. Importantly, the glucocorticoids suppressed the SASP without reverting the tumor suppressive growth arrest and were efficacious whether cells were induced to senesce by ionizing radiation or strong mitogenic signals delivered by oncogenic RAS or MAP kinase kinase 6 overexpression. Suppression of the prototypical SASP component IL-6 required the glucocorticoid receptor, which, in the presence of ligand, inhibited IL-1α signaling and NF-κB transactivation activity. Accordingly, co-treatments combining glucocorticoids with the glucocorticoid antagonist RU-486 or recombinant IL-1α efficiently reestablished NF-κB transcriptional activity and IL-6 secretion. Our findings demonstrate feasibility of screening for compounds that inhibit the effects of senescent cells. They further show that glucocorticoids inhibit selected components of the SASP and suggest that corticosterone and cortisol, two FDA-approved drugs, might exert their effects in part by suppressing senescence-associated inflammation.

  12. Reaction chemistry and collisional processes in multiple devices for resolving isobaric interferences in ICP-MS.

    PubMed

    Bandura, D R; Baranov, V I; Tanner, S D

    2001-07-01

    A low-level review of the fundamentals of ion-molecule interactions is presented. These interactions are used to predict the efficiencies of collisional fragmentation, energy damping and reaction for a variety of neutral gases as a function of pressure in a rf-driven collision/reaction cell. It is shown that the number of collisions increases dramatically when the ion energies are reduced to near-thermal (< 0.1 eV), because of the ion-induced dipole and ion-dipole interaction. These considerations suggest that chemical reaction can be orders of magnitude more efficient at improving the analyte signal/background ratio than can collisional fragmentation. Considerations that lead to an appropriate selection of type of gas, operating pressure, and ion energies for efficient operation of the cell for the alleviation of spectral interferences are discussed. High efficiency (large differences between reaction efficiencies of the analyte and interference ions, and concomitant suppression of secondary chemistry) might be required to optimize the chemical resolution (determination of an analyte in the presence of an isobaric interference) when using ion-molecule chemistry to suppress the interfering ion. In many instances atom transfer to the analyte, which shifts the analytical m/z by the mass of the atom transferred, provides high chemical resolution, even when the efficiency of reaction is relatively low. Examples are given of oxidation, hydroxylation, and chlorination of analyte ions (V+, Fe+, As+, Se+, Sr+, Y+, and Zr+) to improve the capability of determination of complex samples. Preliminary results are given showing O-atom abstraction by CO from CaO+ to enable the determination of Fe in high-Ca samples.

  13. High-Resolution Enabled 12-Plex DiLeu Isobaric Tags for Quantitative Proteomics

    PubMed Central

    2015-01-01

    Multiplex isobaric tags (e.g., tandem mass tags (TMT) and isobaric tags for relative and absolute quantification (iTRAQ)) are a valuable tool for high-throughput mass spectrometry based quantitative proteomics. We have developed our own multiplex isobaric tags, DiLeu, that feature quantitative performance on par with commercial offerings but can be readily synthesized in-house as a cost-effective alternative. In this work, we achieve a 3-fold increase in the multiplexing capacity of the DiLeu reagent without increasing structural complexity by exploiting mass defects that arise from selective incorporation of 13C, 15N, and 2H stable isotopes in the reporter group. The inclusion of eight new reporter isotopologues that differ in mass from the existing four reporters by intervals of 6 mDa yields a 12-plex isobaric set that preserves the synthetic simplicity and quantitative performance of the original implementation. We show that the new reporter variants can be baseline-resolved in high-resolution higher-energy C-trap dissociation (HCD) spectra, and we demonstrate accurate 12-plex quantitation of a DiLeu-labeled Saccharomyces cerevisiae lysate digest via high-resolution nano liquid chromatography–tandem mass spectrometry (nanoLC–MS2) analysis on an Orbitrap Elite mass spectrometer. PMID:25405479

  14. QUANTITY: An Isobaric Tag for Quantitative Glycomics

    PubMed Central

    Yang, Shuang; Wang, Meiyao; Chen, Lijun; Yin, Bojiao; Song, Guoqiang; Turko, Illarion V.; Phinney, Karen W.; Betenbaugh, Michael J.; Zhang, Hui; Li, Shuwei

    2015-01-01

    Glycan is an important class of macromolecules that play numerous biological functions. Quantitative glycomics - analysis of glycans at global level - however, is far behind genomics and proteomics owing to technical challenges associated with their chemical properties and structural complexity. As a result, technologies that can facilitate global glycan analysis are highly sought after. Here, we present QUANTITY (Quaternary Amine Containing Isobaric Tag for Glycan), a quantitative approach that can not only enhance detection of glycans by mass spectrometry, but also allow high-throughput glycomic analysis from multiple biological samples. This robust tool enabled us to accomplish glycomic survey of bioengineered Chinese Hamster Ovary (CHO) cells with knock-in/out enzymes involved in protein glycosylation. Our results demonstrated QUANTITY is an invaluable technique for glycan analysis and bioengineering. PMID:26616285

  15. Selective Suppression of Local Circuits during Movement Preparation in the Mouse Motor Cortex.

    PubMed

    Hasegawa, Masashi; Majima, Kei; Itokazu, Takahide; Maki, Takakuni; Albrecht, Urban-Raphael; Castner, Nora; Izumo, Mariko; Sohya, Kazuhiro; Sato, Tatsuo K; Kamitani, Yukiyasu; Sato, Takashi R

    2017-03-14

    Prepared movements are more efficient than those that are not prepared for. Although changes in cortical activity have been observed prior to a forthcoming action, the circuits involved in motor preparation remain unclear. Here, we use in vivo two-photon calcium imaging to uncover changes in the motor cortex during variable waiting periods prior to a forepaw reaching task in mice. Consistent with previous reports, we observed a subset of neurons with increased activity during the waiting period; however, these neurons did not account for the degree of preparation as defined by reaction time (RT). Instead, the suppression of activity of distinct neurons in the same cortical area better accounts for RT. This suppression of neural activity resulted in a distinct and reproducible pattern when mice were well prepared. Thus, the selective suppression of network activity in the motor cortex may be a key feature of prepared movements.

  16. Selective suppression of high-order harmonics within phase-matched spectral regions.

    PubMed

    Lerner, Gavriel; Diskin, Tzvi; Neufeld, Ofer; Kfir, Ofer; Cohen, Oren

    2017-04-01

    Phase matching in high-harmonic generation leads to enhancement of multiple harmonics. It is sometimes desired to control the spectral structure within the phase-matched spectral region. We propose a scheme for selective suppression of high-order harmonics within the phase-matched spectral region while weakly influencing the other harmonics. The method is based on addition of phase-mismatched segments within a phase-matched medium. We demonstrate the method numerically in two examples. First, we show that one phase-mismatched segment can significantly suppress harmonic orders 9, 15, and 21. Second, we show that two phase-mismatched segments can efficiently suppress circularly polarized harmonics with one helicity over the other when driven by a bi-circular field. The new method may be useful for various applications, including the generation of highly helical bright attosecond pulses.

  17. Symmetry energy II: Isobaric analog states

    NASA Astrophysics Data System (ADS)

    Danielewicz, Pawel; Lee, Jenny

    2014-02-01

    Using excitation energies to isobaric analog states (IAS) and charge invariance, we extract nuclear symmetry coefficients, representing a mass formula, on a nucleus-by-nucleus basis. Consistently with charge invariance, the coefficients vary weakly across an isobaric chain. However, they change strongly with nuclear mass and range from aa˜10 MeV at mass A˜10 to aa˜22 MeV at A˜240. Variation with mass can be understood in terms of dependence of nuclear symmetry energy on density and the rise in importance of low densities within nuclear surface in smaller systems. At A≳30, the dependence of coefficients on mass can be well described in terms of a macroscopic volume-surface competition formula with aaV≃33.2 MeV and aaS≃10.7 MeV. Our further investigation shows, though, that the fitted surface symmetry coefficient likely significantly underestimates that for the limit of half-infinite matter. Following the considerations of a Hohenberg-Kohn functional for nuclear systems, we determine how to find in practice the symmetry coefficient using neutron and proton densities, even when those densities are simultaneously affected by significant symmetry-energy and Coulomb effects. These results facilitate extracting the symmetry coefficients from Skyrme-Hartree-Fock (SHF) calculations, that we carry out using a variety of Skyrme parametrizations in the literature. For the parametrizations, we catalog novel short-wavelength instabilities. In our further analysis, we retain only those parametrizations which yield systems that are adequately stable both in the long- and short-wavelength limits. In comparing the SHF and IAS results for the symmetry coefficients, we arrive at narrow (±2.4 MeV) constraints on the symmetry-energy values S(ρ) at 0.04≲ρ≲0.13 fm. Towards normal density the constraints significantly widen, but the normal value of energy aaV and the slope parameter L are found to be strongly correlated. To narrow the constraints, we reach for the

  18. Pion production via isobar giant resonance formation and decay

    NASA Technical Reports Server (NTRS)

    Townsend, L. W.; Deutchman, P. A.; Madigan, R. L.; Norbury, J. W.

    1984-01-01

    A spin, isotopic-spin formalism for the production of pions due to decays of isobar giant resonances formed in peripheral heavy-ion collisions is presented. The projectile nucleus isobar giant resonance state is assumed to coherently form and then incoherently decay to produce the pions. Total spin and isotopic spin for the system are conserved through the concomitant excitation of the target nucleus to an isobaric analog giant resonance state. Comparisons of the predicted total pion cross sections, over a range of energies, are made with heavy-ion pion data.

  19. Voluntary strategy suppresses the positive impact of preferential selection in prisoner’s dilemma

    NASA Astrophysics Data System (ADS)

    Sun, Lei; Lin, Pei-jie; Chen, Ya-shan

    2014-11-01

    Impact of aspiration is ubiquitous in social and biological disciplines. In this work, we try to explore the impact of such a trait on voluntary prisoners’ dilemma game via a selection parameter w. w=0 returns the traditional version of random selection. For positive w, the opponent of high payoff will be selected; while negative w means that the partner of low payoff will be chosen. We find that for positive w, cooperation will be greatly promoted in the interval of small b, at variance cooperation is inhibited with large b. For negative w, cooperation is fully restrained, irrespective of b value. It is found that the positive impact of preferential selection is suppressed by the voluntary strategy in prisoner’s dilemma. These observations can be supported by the spatial patterns. Our work may shed light on the emergence and persistence of cooperation with voluntary participation in social dilemma.

  20. Convergent recombination suppression suggests role of sexual selection in guppy sex chromosome formation

    PubMed Central

    Wright, Alison E.; Darolti, Iulia; Bloch, Natasha I.; Oostra, Vicencio; Sandkam, Ben; Buechel, Severine D.; Kolm, Niclas; Breden, Felix; Vicoso, Beatriz; Mank, Judith E.

    2017-01-01

    Sex chromosomes evolve once recombination is halted between a homologous pair of chromosomes. The dominant model of sex chromosome evolution posits that recombination is suppressed between emerging X and Y chromosomes in order to resolve sexual conflict. Here we test this model using whole genome and transcriptome resequencing data in the guppy, a model for sexual selection with many Y-linked colour traits. We show that although the nascent Y chromosome encompasses nearly half of the linkage group, there has been no perceptible degradation of Y chromosome gene content or activity. Using replicate wild populations with differing levels of sexually antagonistic selection for colour, we also show that sexual selection leads to greater expansion of the non-recombining region and increased Y chromosome divergence. These results provide empirical support for longstanding models of sex chromosome catalysis, and suggest an important role for sexual selection and sexual conflict in genome evolution. PMID:28139647

  1. Resonance ionization mass spectrometric study of the promethium/samarium isobaric pair

    SciTech Connect

    Shaw, R.W.; Young, J.P.; Smith, D.H.

    1988-01-01

    Samarium daughters are problematic in isotope ratio measurements of promethium because they are isobaric. Resonance ionization mass spectrometry was utilized to circumvent this problem. An ionization selectivity factor of at least 1000:1 has been measured for promethium over samarium at 584.6 nm. Resonance ionization spectra have been recorded for both elements over the 528-560 and 580-614 nm wavelength ranges.

  2. Selective Memories: Infants' Encoding Is Enhanced in Selection via Suppression

    ERIC Educational Resources Information Center

    Markant, Julie; Amso, Dima

    2013-01-01

    The present study examined the hypothesis that inhibitory visual selection mechanisms play a vital role in memory by limiting distractor interference during item encoding. In Experiment 1a we used a modified spatial cueing task in which 9-month-old infants encoded multiple category exemplars in the contexts of an attention orienting mechanism…

  3. Selective Estrogen Receptor Modulators Suppress Hif1α Protein Accumulation in Mouse Osteoclasts

    PubMed Central

    Iwasaki, Ryotaro; Kobayashi, Tami; Watanabe, Ryuichi; Oike, Takatsugu; Toyama, Yoshiaki; Matsumoto, Morio; Nakamura, Masaya; Kawana, Hiromasa; Nakagawa, Taneaki; Miyamoto, Takeshi

    2016-01-01

    Anti-bone resorptive drugs such as bisphosphonates, the anti-RANKL antibody (denosumab), or selective estrogen receptor modulators (SERMs) have been developed to treat osteoporosis. Mechanisms underlying activity of bisphosphonates or denosumab in this context are understood, while it is less clear how SERMs like tamoxifen, raloxifene, or bazedoxifene inhibit bone resorption. Recently, accumulation of hypoxia inducible factor 1 alpha (Hif1α) in osteoclasts was shown to be suppressed by estrogen in normal cells. In addition, osteoclast activation and decreased bone mass seen in estrogen-deficient conditions was found to require Hif1α. Here, we used western blot analysis of cultured osteoclast precursor cells to show that tamoxifen, raloxifene, or bazedoxifene all suppress Hif1α protein accumulation. The effects of each SERM on osteoclast differentiation differed in vitro. Our results suggest that interventions such as the SERMs evaluated here could be useful to inhibit Hif1α and osteoclast activity under estrogen-deficient conditions. PMID:27802325

  4. ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor.

    PubMed

    Nakanishi, Yoshito; Mizuno, Hideaki; Sase, Hitoshi; Fujii, Toshihiko; Sakata, Kiyoaki; Akiyama, Nukinori; Aoki, Yuko; Aoki, Masahiro; Ishii, Nobuya

    2015-12-01

    Drugs that target specific gene alterations have proven beneficial in the treatment of cancer. Because cancer cells have multiple resistance mechanisms, it is important to understand the downstream pathways of the target genes and monitor the pharmacodynamic markers associated with therapeutic efficacy. We performed a transcriptome analysis to characterize the response of various cancer cell lines to a selective fibroblast growth factor receptor (FGFR) inhibitor (CH5183284/Debio 1347), a mitogen-activated protein kinase kinase (MEK) inhibitor, or a phosphoinositide 3-kinase (PI3K) inhibitor. FGFR and MEK inhibition produced similar expression patterns, and the extracellular signal-regulated kinase (ERK) gene signature was altered in several FGFR inhibitor-sensitive cell lines. Consistent with these findings, CH5183284/Debio 1347 suppressed phospho-ERK in every tested FGFR inhibitor-sensitive cell line. Because the mitogen-activated protein kinase (MAPK) pathway functions downstream of FGFR, we searched for a pharmacodynamic marker of FGFR inhibitor efficacy in a collection of cell lines with the ERK signature and identified dual-specificity phosphatase 6 (DUSP6) as a candidate marker. Although a MEK inhibitor suppressed the MAPK pathway, most FGFR inhibitor-sensitive cell lines are insensitive to MEK inhibitors and we found potent feedback activation of several pathways via FGFR. We therefore suggest that FGFR inhibitors exert their effect by suppressing ERK signaling without feedback activation. In addition, DUSP6 may be a pharmacodynamic marker of FGFR inhibitor efficacy in FGFR-addicted cancers.

  5. Top-down suppression of incompatible motor activations during response selection under conflict.

    PubMed

    Klein, Pierre-Alexandre; Petitjean, Charlotte; Olivier, Etienne; Duque, Julie

    2014-02-01

    Top-down control is critical to select goal-directed actions in changeable environments, particularly when several options compete for selection. This control system is thought to involve a mechanism that suppresses activation of unwanted response representations. We tested this hypothesis, in humans, by measuring motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in a left finger muscle during motor preparation in an adapted Eriksen flanker task. Subjects reported, by a left or right button-press, the orientation of a left- or right-facing central arrow, flanked by two distractor arrows on each side. Central and peripheral arrows either pointed in the same (congruent trial) or in the opposite direction (incongruent trial). Top-down control was manipulated by changing the probability of congruent and incongruent trials in a given block. In the "mostly incongruent" (MI) blocks, 80% of trials were incongruent, producing a context in which subjects strongly anticipated that they would have to face conflict. In the "mostly congruent" (MC) blocks, 80% of trials were congruent and thus subjects barely anticipated conflict in that context. Thus, we assume that top-down control was stronger in the MI than in the MC condition. Accordingly, subjects displayed a lower error rate and shorter reaction times for the incongruent trials in the MI context than for similar trials in the MC context. More interestingly, we found that top-down control specifically reduced activation of the incompatible motor representation during response selection under high conflict. That is, when the central arrow specified a right hand response, left (non-selected) MEPs became smaller in the MI than in the MC condition, but only for incongruent trials, and this measure was positively correlated with performance. In contrast, MEPs elicited in the non-selected hand during congruent trials, or during all trials in which the left hand was selected, tended to increase

  6. Selection of motor programs for suppressing food intake and inducing locomotion in the Drosophila brain.

    PubMed

    Schoofs, Andreas; Hückesfeld, Sebastian; Schlegel, Philipp; Miroschnikow, Anton; Peters, Marc; Zeymer, Malou; Spieß, Roland; Chiang, Ann-Shyn; Pankratz, Michael J

    2014-06-01

    Central mechanisms by which specific motor programs are selected to achieve meaningful behaviors are not well understood. Using electrophysiological recordings from pharyngeal nerves upon central activation of neurotransmitter-expressing cells, we show that distinct neuronal ensembles can regulate different feeding motor programs. In behavioral and electrophysiological experiments, activation of 20 neurons in the brain expressing the neuropeptide hugin, a homolog of mammalian neuromedin U, simultaneously suppressed the motor program for food intake while inducing the motor program for locomotion. Decreasing hugin neuropeptide levels in the neurons by RNAi prevented this action. Reducing the level of hugin neuronal activity alone did not have any effect on feeding or locomotion motor programs. Furthermore, use of promoter-specific constructs that labeled subsets of hugin neurons demonstrated that initiation of locomotion can be separated from modulation of its motor pattern. These results provide insights into a neural mechanism of how opposing motor programs can be selected in order to coordinate feeding and locomotive behaviors.

  7. Selective suppression of the incorrect response implementation in choice behavior assessed by transcranial magnetic stimulation.

    PubMed

    Tandonnet, Christophe; Garry, Michael I; Summers, Jeffery J

    2011-04-01

    Selecting the adequate alternative in choice situations may involve an inhibition process. Here we assessed response implementation during the reaction time of a between-hand choice task with single- or paired-pulse (3 or 15 ms interstimulus intervals [ISIs]) transcranial magnetic stimulation of the motor cortex. The amplitude of the single-pulse motor evoked potential (MEP) initially increased for both hands. At around 130 ms, the single-pulse MEP kept increasing for the responding hand and decreased for the nonresponding hand. The paired-pulse MEP revealed a similar pattern for both ISIs with no effect on short intracortical inhibition and intracortical facilitation measures. The results suggest that the incorrect response implementation was selectively suppressed before execution of the correct response, preventing errors in choice context. The results favor models assuming that decision making involves an inhibition process.

  8. Isobar giant resonance formation in self-conjugate nuclei

    NASA Astrophysics Data System (ADS)

    Townsend, L. W.; Deutchman, P. A.

    1981-03-01

    The production of isobars with concomitant giant resonance excitations due to peripheral collisions of relativistic heavy ions is investigated. The interaction is described by a modified form of the central term in the one-pion-exchange potential (OPEP) where the projectile ordinary spin operator is replaced by a transition spin operator which describes the creation of an isobar from a nucleon. The scattering is analyzed using time-dependent harmonic perturbation theory to determine the reaction total cross sections. The results obtained, which are valid for reactions involving self-conjugate nuclei, are applied to the specific collison of 2.1 {GeV}/{nucleon}16O projectiles with 12C targets at rest. Cross sections are investigated using two different models for the nuclear spin states. In the first model, the many-body nuclear spin state is reduced, in the spirit of a particle-hole state, to an equivalent two-body state called a particle-core state. In the second model, the many-body spin states are described by unsymmetrized products of individual particle spins. Properties of the spin giant resonance and isobar giant resonance states are investigated. Finally, isobar decay and isobar/pion absorption effects are discussed.

  9. Direction Selectivity in Drosophila Emerges from Preferred-Direction Enhancement and Null-Direction Suppression

    PubMed Central

    Leong, Jonathan Chit Sing; Esch, Jennifer Judson; Poole, Ben; Ganguli, Surya

    2016-01-01

    Across animal phyla, motion vision relies on neurons that respond preferentially to stimuli moving in one, preferred direction over the opposite, null direction. In the elementary motion detector of Drosophila, direction selectivity emerges in two neuron types, T4 and T5, but the computational algorithm underlying this selectivity remains unknown. We find that the receptive fields of both T4 and T5 exhibit spatiotemporally offset light-preferring and dark-preferring subfields, each obliquely oriented in spacetime. In a linear-nonlinear modeling framework, the spatiotemporal organization of the T5 receptive field predicts the activity of T5 in response to motion stimuli. These findings demonstrate that direction selectivity emerges from the enhancement of responses to motion in the preferred direction, as well as the suppression of responses to motion in the null direction. Thus, remarkably, T5 incorporates the essential algorithmic strategies used by the Hassenstein–Reichardt correlator and the Barlow–Levick detector. Our model for T5 also provides an algorithmic explanation for the selectivity of T5 for moving dark edges: our model captures all two- and three-point spacetime correlations relevant to motion in this stimulus class. More broadly, our findings reveal the contribution of input pathway visual processing, specifically center-surround, temporally biphasic receptive fields, to the generation of direction selectivity in T5. As the spatiotemporal receptive field of T5 in Drosophila is common to the simple cell in vertebrate visual cortex, our stimulus-response model of T5 will inform efforts in an experimentally tractable context to identify more detailed, mechanistic models of a prevalent computation. SIGNIFICANCE STATEMENT Feature selective neurons respond preferentially to astonishingly specific stimuli, providing the neurobiological basis for perception. Direction selectivity serves as a paradigmatic model of feature selectivity that has been

  10. PRMT5-Selective Inhibitors Suppress Inflammatory T Cell Responses and Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Webb, Lindsay M.; Amici, Stephanie A.; Jablonski, Kyle A.; Savardekar, Himanshu; Panfil, Amanda R.; Li, Linsen; Zhou, Wei; Peine, Kevin; Karkhanis, Vrajesh; Bachelder, Eric M.; Ainslie, Kristy M.; Green, Patrick L.; Li, Chenglong; Baiocchi, Robert A.

    2017-01-01

    In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cell–mediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking. PRMT5 is the main PRMT responsible for symmetric dimethylation of arginine residues of histones and other proteins. PRMT5 drives embryonic development and cancer, but its role in T cells, if any, has not been investigated. In this article, we show that PRMT5 is an important modulator of CD4+ T cell expansion. PRMT5 was transiently upregulated during maximal proliferation of mouse and human memory Th cells. PRMT5 expression was regulated upstream by the NF-κB pathway, and it promoted IL-2 production and proliferation. Blocking PRMT5 with novel, highly selective small molecule PRMT5 inhibitors severely blunted memory Th expansion, with preferential suppression of Th1 cells over Th2 cells. In vivo, PRMT5 blockade efficiently suppressed recall T cell responses and reduced inflammation in delayed-type hypersensitivity and clinical disease in EAE mouse models. These data implicate PRMT5 in the regulation of adaptive memory Th cell responses and suggest that PRMT5 inhibitors may be a novel therapeutic approach for T cell–mediated inflammatory disease. PMID:28087667

  11. Nitric oxide selectively suppresses IH currents mediated by HCN1-containing channels

    PubMed Central

    Kopp-Scheinpflug, Cornelia; Pigott, Beatrice M; Forsythe, Ian D

    2015-01-01

    Key points The superior olivary complex (SOC) exhibits a spectrum of HCN1 and HCN2 subunit expression, which generate IH currents with fast and slow kinetics, respectively. Neuronal nitric oxide synthase (nNOS) was broadly distributed across the SOC. NO hyperpolarizes the half-activation voltage of HCN1-mediated currents and caused a slowing of the IH current kinetics in the respective nuclei (medial and lateral superior olives and superior paraolivary nucleus). This signalling was independent of cGMP. NO also caused a depolarizing shift in the half-activation voltage of HCN2-mediated IH currents, increasing activation at resting potentials; this was cGMP-dependent. Thus, NO signalling suppressed fast HCN1-mediated currents and potentiated slow HCN2-mediated currents, modulating the overall kinetics and magnitude of the endogenous IH. Abstract Hyperpolarization-activated non-specific cation-permeable channels (HCN) mediate IH currents, which are modulated by cGMP and cAMP and by nitric oxide (NO) signalling. Channel properties depend upon subunit composition (HCN1–4 and accessory subunits) as demonstrated in expression systems, but physiological relevance requires investigation in native neurons with intact intracellular signalling. Here we use the superior olivary complex (SOC), which exhibits a distinctive pattern of HCN1 and HCN2 expression, to investigate NO modulation of the respective IH currents, and compare properties in wild-type and HCN1 knockout mice. The medial nucleus of the trapezoid body (MNTB) expresses HCN2 subunits exclusively, and sends inhibitory projections to the medial and lateral superior olives (MSO, LSO) and the superior paraolivary nucleus (SPN). In contrast to the MNTB, these target nuclei possess an IH with fast kinetics, and they express HCN1 subunits. NO is generated in the SOC following synaptic activity and here we show that NO selectively suppresses HCN1, while enhancing IH mediated by HCN2 subunits. NO hyperpolarizes the half

  12. Removal of the samarium isobaric interference from promethium mass analysis

    SciTech Connect

    Shaw, R.W.; Young, J.P.; Smith, D.H.

    1988-02-01

    Resonance ionization mass spectroscopy (RIMS) is used to eliminate isobaric interference when determining the isotopic abundances of an element. In this application, RIMS is applied to the determination of promethium with the removal of samarium interference. In particular, promethium-147 is separated form samarium-147 and samarium-152.

  13. Improved water and lipid suppression for 3D PRESS CSI using RF band selective inversion with gradient dephasing (BASING).

    PubMed

    Star-Lack, J; Nelson, S J; Kurhanewicz, J; Huang, L R; Vigneron, D B

    1997-08-01

    A T1 insensitive solvent suppression technique-band selective inversion with gradient dephasing (BASING)-was developed to suppress water and lipids for 1H magnetic resonance spectroscopy (MRS). BASING, which consists of a frequency selective RF inversion pulse surrounded by spoiler gradient pulses of opposite signs, was used to dephase stopband resonances and minimally impact passband metabolites. Passband phase linearity was achieved with a dual BASING scheme. Using the Shinnar-Le Roux algorithm, a highpass filter was designed to suppress water and rephase the lactate methyl doublet independently of TE, and water/lipid bandstop filters were designed for the brain and prostate. Phantom and in vivo experimental 3D PRESS CSI data were acquired at 1.5 T to compare BASING with CHESS and STIR suppression. With BASING, the measured suppression factor was over 100 times higher than with CHESS or STIR causing baseline distortions to be removed. It was shown that BASING can be incorporated into a variety of sequences to offer improved suppression in the presence of B1 and T1 inhomogeneites.

  14. Dissipative Particle Dynamics at Isothermal, Isobaric Conditions Using Shardlow-Like Splitting Algorithms

    DTIC Science & Technology

    2013-09-01

    Dissipative Particle Dynamics at Isothermal, Isobaric Conditions Using Shardlow-Like Splitting Algorithms by John K. Brennan and Martin...5066 ARL-TR-6583 September 2013 Dissipative Particle Dynamics at Isothermal, Isobaric Conditions Using Shardlow-Like Splitting...From - To) May 2010–February 2013 4. TITLE AND SUBTITLE Dissipative Particle Dynamics at Isothermal, Isobaric Conditions Using Shardlow-Like

  15. Selective suppression of cytokine secretion in whole blood cell cultures of patients with colorectal cancer.

    PubMed Central

    Lahm, H.; Schindel, M.; Frikart, L.; Cerottini, J. P.; Yilmaz, A.; Givel, J. C.; Fischer, J. R.

    1998-01-01

    We have investigated the secretion of interferon alpha (IFN-alpha), IFN-gamma, interleukin-1alpha (IL-1alpha), IL-1beta, IL-2 and tumour necrosis factor alpha (TNF-alpha) in whole blood cell cultures (WBCCs) of colorectal cancer patients upon mitogen stimulation. Whereas the values for IL-1beta and TNF-alpha remained virtually unchanged in comparison with healthy control subjects, WBCCs of colorectal cancer patients secreted significantly lower amounts of IFN-alpha (P < 0.005), IFN-gamma (P < 0.0001), IL-1alpha (P < 0.0001) and IL-2 (P < 0.05). This reduction correlated with the progression of the disease. The total leucocyte and monocyte population were almost identical in both groups. In contrast, a dramatic depletion of lymphocytes was observed in colorectal cancer patients, which affected both lymphocyte counts (P < 0.0005) and their distribution (P < 0.0001). Our results suggest a selective suppression of cytokines in colorectal cancer patients that is related to tumour burden. Several mechanisms might account for this phenomenon, one of which might be lymphocyte depletion. PMID:9792144

  16. Selective suppression of harmful cyanobacteria in an entire lake with hydrogen peroxide.

    PubMed

    Matthijs, Hans C P; Visser, Petra M; Reeze, Bart; Meeuse, Jeroen; Slot, Pieter C; Wijn, Geert; Talens, Renée; Huisman, Jef

    2012-04-01

    Although harmful cyanobacteria form a major threat to water quality, few methods exist for the rapid suppression of cyanobacterial blooms. Since laboratory studies indicated that cyanobacteria are more sensitive to hydrogen peroxide (H(2)O(2)) than eukaryotic phytoplankton, we tested the application of H(2)O(2) in natural waters. First, we exposed water samples from a recreational lake dominated by the toxic cyanobacterium Planktothrix agardhii to dilute H(2)O(2). This reduced the photosynthetic vitality by more than 70% within a few hours. Next, we installed experimental enclosures in the lake, which revealed that H(2)O(2) selectively killed the cyanobacteria without major impacts on eukaryotic phytoplankton, zooplankton, or macrofauna. Based on these tests, we introduced 2 mg L(-1) (60 μM) of H(2)O(2) homogeneously into the entire water volume of the lake with a special dispersal device, called the water harrow. The cyanobacterial population as well as the microcystin concentration collapsed by 99% within a few days. Eukaryotic phytoplankton (including green algae, cryptophytes, chrysophytes and diatoms), zooplankton and macrofauna remained largely unaffected. Following the treatment, cyanobacterial abundances remained low for 7 weeks. Based on these results, we propose the use of dilute H(2)O(2) for the selective elimination of harmful cyanobacteria from recreational lakes and drinking water reservoirs, especially when immediate action is urgent and/or cyanobacterial control by reduction of eutrophication is currently not feasible. A key advantage of this method is that the added H(2)O(2) degrades to water and oxygen within a few days, and thus leaves no long-term chemical traces in the environment.

  17. Selection of genetically diverse Trichoderma spp. isolates for suppression of Phytophthora capsici on bell pepper.

    PubMed

    Roberts, Daniel P; Maul, Jude E; McKenna, Laurie F; Emche, Sarah E; Meyer, Susan L F; Collins, Ronald T; Bowers, John H

    2010-10-01

    Environmentally compatible control measures are needed for suppression of Phytophthora capsici on pepper. Twenty-three isolates of Trichoderma were screened for suppression of a mixture of 4 genetically distinct isolates of this pathogen on bell pepper (Capsicum anuum) in greenhouse pot assays. Of these 23 isolates, GL12, GL13, and Th23 provided significant suppression of P. capsici in at least 2 assays. These isolates were then compared with Trichoderma virens isolates GL3 and GL21 for suppression of this disease in the presence and absence of the harpin-based natural product Messenger. Isolates GL3 and Th23 provided significant disease suppression (P ≤ 0.05) in 3 of 4 assays, while GL12, GL13, and GL21 provided significant suppression in 2 of 4 assays. There was no apparent benefit from the application of Messenger. Phylogenetic analysis of these 5 isolates (based on the ITS1 region of the nuclear rDNA cluster and tef1), and an additional 9 isolates that suppressed P. capsici in at least 1 assay, separated isolates into 2 clades, with 1 clade containing GL3, GL12, GL13, and GL21. There were also 2 more distantly related isolates, one of which was Th23. We report here the identification of genetically distinct Trichoderma isolates for potential use in disease management strategies employing isolate combinations directed at suppression of P. capsici on pepper.

  18. Selection of genetically diverse trichoderma spp. isolates for suppression of phytophthora capsici on bell pepper

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Environmentally compatible control measures are needed for suppression of Phytophthora capsici on pepper. Twenty-four isolates of Trichoderma were screened for suppression of this pathogen on bell pepper in greenhouse pot assays. Of these twenty-four isolates, GL12, GL13, and Th23 provided signifi...

  19. Targeting tumor-associated immune suppression with selective protein kinase A type I (PKAI) inhibitors may enhance cancer immunotherapy.

    PubMed

    Hussain, Muzammal; Shah, Zahir; Abbas, Nasir; Javeed, Aqeel; Mukhtar, Muhammad Mahmood; Zhang, Jiancun

    2016-01-01

    Despite the tremendous progress in last few years, the cancer immunotherapy has not yet improved disease-free because of the tumor-associated immune suppression being a major barrier. Novel trends to enhance cancer immunotherapy aims at harnessing the therapeutic manipulation of signaling pathways mediating the tumor-associated immune suppression, with the general aims of: (a) reversing the tumor immune suppression; (b) enhancing the innate and adaptive components of anti-tumor immunosurveillance, and (c) protecting immune cells from the suppressive effects of T regulatory cells (Tregs) and the tumor-derived immunoinhibitory mediators. A particular striking example in this context is the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A type I (PKAI) pathway. Oncogenic cAMP/PKAI signaling has long been implicated in the initiation and progression of several human cancers. Emerging data indicate that cAMP/PKAI signaling also contributes to tumor- and Tregs-derived suppression of innate and adaptive arms of anti-tumor immunosurveillance. Therapeutically, selective PKAI inhibitors have been developed which have shown promising anti-cancer activity in pre-clinical and clinical settings. Rp-8-Br-cAMPS is a selective PKAI antagonist that is widely used as a biochemical tool in signal transduction research. Collateral data indicate that Rp-8-Br-cAMPS has shown immune-rescuing potential in terms of enhancing the innate and adaptive anti-tumor immunity, as well as protecting adaptive T cells from the suppressive effects of Tregs. Therefore, this proposal specifically implicates that combining selective PKAI antagonists/inhibitors with cancer immunotherapy may have multifaceted benefits, such as rescuing the endogenous anti-tumor immunity, enhancing the efficacy of cancer immunotherapy, and direct anti-cancer effects.

  20. Isobaric Analogue States Studied in Mirrored Fragmentation and Knockout Reactions

    SciTech Connect

    Bentley, M.A.; Pritychenko, B.; Paterson,I.; Brown,J.R.; Taylor,M.J.; Digen,C.Aa.; Adrich,P.; Bazin,D.; Cook.J.M.; Gade,A.; Glasmacher,T.; McDaniel,S.; Ratkiewicz,A.; Siwek,K.; D.Weisshaar,D.; Pritychenko,B.; Lenzi,S.M.

    2010-05-21

    A Gamma-ray spectroscopic study of excited states of isobaric multiplets has been performed in recent years, with a view to gaining a quantitative understanding of energy differences between excited states in terms of a range of Coulomb and other isospin breaking phenomena. Recently, the experimental programme has been augmented by a study of isobaric analogue states of mirror nuclei populated in mirrored fragmentation reactions. In this presentation, recent results on the T = 3/2 analogue states in the T{sub z} = {+-} 3/2 mirror pair {sup 53}Ni/{sup 53}Mn will be summarised. In this work, further strong evidence is found for the need to include an anomalous isospin-breaking two-body matrix element for angular-momentum couplings of J = 2, in addition the expected Coulomb contribution, in order to account for the experimental data.

  1. Isobaric Multiplet Yrast Energies and Isospin Nonconserving Forces

    NASA Astrophysics Data System (ADS)

    Zuker, A. P.; Lenzi, S. M.; Martínez-Pinedo, G.; Poves, A.

    2002-09-01

    The isovector and isotensor energy differences between yrast states of isobaric multiplets in the lower half of the pf region are quantitatively reproduced in a shell model context. The isospin nonconserving nuclear interactions are found to be at least as important as the Coulomb potential. Their isovector and isotensor channels are dominated by J=2 and J=0 pairing terms, respectively. The results are sensitive to the radii of the states, whose evolution along the yrast band can be accurately followed.

  2. Reference pressure changes and available potential energy in isobaric coordinates

    NASA Technical Reports Server (NTRS)

    Robertson, F. R.

    1985-01-01

    A formulation of the available potential energy (APE) equation in isobaric coordinates which alleviates the need for computing temporal derivatives of reference pressure and describes how work done relates to changes in the APE of a limited region is presented. The APE budget equation possesses terms analogous to those in Johnson's (1970) isentropic version. It is shown that APE changes result from either mechanical work inside the domain or an exchange of energy via boundary processes with the surrounding environment.

  3. Neutrino scattering rates in neutron star matter with {delta} isobars

    SciTech Connect

    Chen Yanjun; Guo Hua; Liu Yuxin

    2007-03-15

    We take the {delta}-isobar degrees of freedom into account in neutron star matter and evaluate their contributions to neutrino scattering cross sections and mean free paths. The neutron star matter is described by means of an effective hadronic model in the relativistic mean-field approximation. It is found that {delta} isobars may be present in neutron stars. The electron chemical potential does not decrease and the neutrino abundance does not increase with the increase of the density when neutrinos are trapped in the matter with {delta} isobars. The large vector coupling constant between the {delta}{sup -} and neutrino and the high spin of the {delta} influence significantly the neutrino scattering cross section and lead the contribution of the {delta}{sup -} to the dominance of the scattering rates. In neutrino-trapped case, the presence of {delta}s causes the neutrino mean free path to decrease drastically compared to that in the matter in which baryons are only nucleons.

  4. Escherichia coli persister cells suppress translation by selectively disassembling and degrading their ribosomes.

    PubMed

    Cho, Junho; Rogers, Janet; Kearns, Mark; Leslie, Macall; Hartson, Steven D; Wilson, Kevin S

    2015-01-01

    Bacterial persisters are rare, phenotypically distinct cells that survive exposure to multiple antibiotics. Previous studies indicated that formation and maintenance of the persister phenotype are regulated by suppressing translation. To examine the mechanism of this translational suppression, we developed novel methodology to rapidly purify ribosome complexes from persister cells. We purified His-tagged ribosomes from Escherichia coli cells that over-expressed HipA protein, which induces persister formation, and were treated with ampicillin to remove antibiotic-sensitive cells. We profiled ribosome complexes and analyzed the ribosomal RNA and protein components from these persister cells. Our results show that (i) ribosomes in persisters exist largely as inactive ribosomal subunits, (ii) rRNAs and tRNAs are mostly degraded and (iii) a small fraction of the ribosomes remain mostly intact, except for reduced amounts of seven ribosomal proteins. Our findings explain the basis for translational suppression in persisters and suggest how persisters survive exposure to multiple antibiotics.

  5. Effect of selective suppression of spatial frequency domain noise on visual detection of a sample object in an inhomogeneous background

    NASA Astrophysics Data System (ADS)

    Pietrzyk, Mariusz W.; McDonald, J. Scott; Brennan, Patrick C.; Bourne, Roger M.

    2012-02-01

    This study aims to investigate the effect of selective suppression of spatial frequency (SF) domain Gaussian white noise on visibility of a sample object in inhomogeneous backgrounds. SF-specific variation in signal-to-noise ratio due to selective signal averaging in the SF domain is a consequence of some of MRI acquisition methods. This study models the potential effect on visibility of an object in a complex image. A single disc was randomly positioned in 25 of 50 synthetic clustered lumpy background images. Neutral, low mid and high frequency suppressed Gaussian white noise was added in the frequency domain to simulate SF-weighted MRI signal averaging. Twelve readers performed visual searching and localization tasks on ordered sets. Subjects were asked to detect and locate discs and to rank confidence level. Sensitivity, specificity and ROC analyses were performed. Readers achieved significantly higher ROC AUC - Azscores - (p<0.001) and case-based sensitivity (p<0.001) and target-based sensitivity (p<0.001) with images in which low SF noise was suppressed. Also, significant higher cased-based sensitivity (p=0.005), target-based sensitivity (p=0.022) and Az-values (p=0.01) were scored under mid SF noise filtration. No significant differences were observed when images with SF-neutral noise suppression were compared with high SF noise suppression. In conclusion, increase of low and also mid SF signal signal-to-noise ratio significantly improves human performance in visual detection of simple targets in inhomogeneous backgrounds and suggests that a low SF bias in MRI signal averaging may enhance diagnostic quality.

  6. Reflexive and preparatory selection and suppression of salient information in the right and left posterior parietal cortex.

    PubMed

    Mevorach, Carmel; Humphreys, Glyn W; Shalev, Lilach

    2009-06-01

    Attentional cues can trigger activity in the parietal cortex in anticipation of visual displays, and this activity may, in turn, induce changes in other areas of the visual cortex, hence, implementing attentional selection. In a recent TMS study [Mevorach, C., Humphreys, G. W., & Shalev, L. Opposite biases in salience-based selection for the left and right posterior parietal cortex. Nature Neuroscience, 9, 740-742, 2006b], it was shown that the posterior parietal cortex (PPC) can utilize the relative saliency (a nonspatial property) of a target and a distractor to bias visual selection. Furthermore, selection was lateralized so that the right PPC is engaged when salient information must be selected and the left PPC when the salient information must be ignored. However, it is not clear how the PPC implements these complementary forms of selection. Here we used on-line triple-pulse TMS over the right or left PPC prior to or after the onset of global/local displays. When delivered after the onset of the display, TMS to the right PPC disrupted the selection of the more salient aspect of the hierarchical letter. In contrast, left PPC TMS delivered prior to the onset of the stimulus disrupted responses to the lower saliency stimulus. These findings suggest that selection and suppression of saliency, rather than being "two sides of the same coin," are fundamentally different processes. Selection of saliency seems to operate reflexively, whereas suppression of saliency relies on a preparatory phase that "sets up" the system in order to effectively ignore saliency.

  7. Laser ion source for isobaric heavy ion collider experiment

    SciTech Connect

    Kanesue, T. Okamura, M.; Kumaki, M.; Ikeda, S.

    2016-02-15

    Heavy-ion collider experiment in isobaric system is under investigation at Relativistic Heavy Ion Collider. For this experiment, ion source is required to maximize the abundance of the intended isotope. The candidate of the experiment is {sup 96}Ru + {sup 96}Zr. Since the natural abundance of particular isotope is low and composition of isotope from ion source depends on the composites of the target, an isotope enriched material may be needed as a target. We studied the performance of the laser ion source required for the experiment for Zr ions.

  8. Laser ion source for isobaric heavy ion collider experiment.

    PubMed

    Kanesue, T; Kumaki, M; Ikeda, S; Okamura, M

    2016-02-01

    Heavy-ion collider experiment in isobaric system is under investigation at Relativistic Heavy Ion Collider. For this experiment, ion source is required to maximize the abundance of the intended isotope. The candidate of the experiment is (96)Ru + (96)Zr. Since the natural abundance of particular isotope is low and composition of isotope from ion source depends on the composites of the target, an isotope enriched material may be needed as a target. We studied the performance of the laser ion source required for the experiment for Zr ions.

  9. Proton echo-planar spectroscopic imaging with highly effective outer volume suppression using combined presaturation and spatially selective echo dephasing.

    PubMed

    Chu, Archie; Alger, Jeffry R; Moore, Gregory J; Posse, Stefan

    2003-05-01

    A highly effective outer volume suppression (OVS) technique, termed spatially selective echo dephasing (SSED), which employs gradient dephasing of spatially selective spin echoes, is introduced. SSED, which is relatively insensitive to T(1) dispersion among lipid signals and B(1) inhomogeneity, was integrated with very high spatial resolution 2D proton echo-planar spectroscopic imaging (PEPSI) to assess residual lipid bleeding into cortical regions in the human brain. The method was optimized to minimize signal refocusing of secondary spin-echoes in areas of overlapping suppression slices. A comparison of spatial presaturation with single or double SSED, and with combined presaturation and SSED shows that the latter method has superior performance with spatially uniform lipid suppression factors in excess of 70. Metabolite mapping (choline, creatine, and NAA) with a 64 x 64 spatial matrix and 0.3 cm(3) voxels in close proximity to peripheral lipid regions was demonstrated at 1.5 T with a scan time of 32 min using the standard head coil.

  10. Selective slow wave sleep but not rapid eye movement sleep suppression impairs morning glucose tolerance in healthy men.

    PubMed

    Herzog, Nina; Jauch-Chara, Kamila; Hyzy, Franziska; Richter, Annekatrin; Friedrich, Alexia; Benedict, Christian; Oltmanns, Kerstin M

    2013-10-01

    Shortened nocturnal sleep impairs morning glucose tolerance. The underlying mechanism of this effect is supposed to involve a reduced fraction of slow wave sleep (SWS). However, it remains unanswered if impaired glucose tolerance occurs due to specific SWS reduction or a general disturbance of sleep. Sixteen healthy men participated in three experimental conditions in a crossover design: SWS suppression, rapid eye movement (REM)-sleep disturbance, and regular sleep. Selective sleep stage disturbance was performed by means of an acoustic tone (532Hz) with gradually rising sound intensity. Blood concentrations of glucoregulatory parameters were measured upon an oral glucose tolerance test the next morning. Our data show that morning plasma glucose and serum insulin responses were significantly increased after selective SWS suppression. Moreover, SWS suppression reduced postprandial insulin sensitivity up to 20%, as determined by Matsuda Index. Contrastingly, disturbed REM-sleep did not affect glucose homeostasis. We conclude that specifically SWS reduction is critically involved in the impairment of glucose tolerance associated with disturbed sleep. Therefore, glucose metabolism in subjects predisposed to reduced SWS (e.g. depression, aging, obstructive sleep apnea, pharmacological treatment) should be thoroughly monitored.

  11. Insect herbivores selectively suppress the HPL branch of the oxylipin pathway in host plants.

    PubMed

    Savchenko, Tatyana; Pearse, Ian S; Ignatia, Laura; Karban, Richard; Dehesh, Katayoon

    2013-02-01

    Insect herbivores have developed a myriad of strategies to manipulate the defense responses of their host plants. Here we provide evidence that chewing insects differentially alter the oxylipin profiles produced by the two main and competing branches of the plant defensive response pathway, the allene oxide synthase (AOS) and hydroperoxide lyase (HPL) branches, which are responsible for wound-inducible production of jasmonates (JAs), and green leafy volatiles (GLVs) respectively. Specifically, we used three Arabidopsis genotypes that were damaged by mechanical wounding or by insects of various feeding guilds (piercing aphids, generalist chewing caterpillars and specialist chewing caterpillars). We established that emission of GLVs is stimulated by wounding incurred mechanically or by aphids, but release of these volatiles is constitutively impaired by both generalist and specialist chewing insects. Simultaneously, however, these chewing herbivores stimulated JA production, demonstrating targeted insect suppression of the HPL branch of the oxylipin pathway. Use of lines engineered to express HPL constitutively, in conjunction with quantitative RT-PCR-based expression analyses, established a combination of transcriptional and post-transcriptional reprogramming of the HPL pathway genes as the mechanistic basis of insect-mediated suppression of the corresponding metabolites. Feeding studies suggested a potential evolutionary advantage of suppressing GLV production, as caterpillars preferably consumed leaf tissue from plants that had not been primed by these volatile cues.

  12. An objective isobaric/isentropic technique for upper air analysis

    NASA Technical Reports Server (NTRS)

    Mancuso, R. L.; Endlich, R. M.; Ehernberger, L. J.

    1981-01-01

    An objective meteorological analysis technique is presented whereby both horizontal and vertical upper air analyses are performed. The process used to interpolate grid-point values from the upper-air station data is the same as for grid points on both an isobaric surface and a vertical cross-sectional plane. The nearby data surrounding each grid point are used in the interpolation by means of an anisotropic weighting scheme, which is described. The interpolation for a grid-point potential temperature is performed isobarically; whereas wind, mixing-ratio, and pressure height values are interpolated from data that lie on the isentropic surface that passes through the grid point. Two versions (A and B) of the technique are evaluated by qualitatively comparing computer analyses with subjective handdrawn analyses. The objective products of version A generally have fair correspondence with the subjective analyses and with the station data, and depicted the structure of the upper fronts, tropopauses, and jet streams fairly well. The version B objective products correspond more closely to the subjective analyses, and show the same strong gradients across the upper front with only minor smoothing.

  13. Narrow-band injection seeding of a terahertz frequency quantum cascade laser: Selection and suppression of longitudinal modes

    SciTech Connect

    Nong, Hanond Markmann, Sergej; Hekmat, Negar; Jukam, Nathan; Pal, Shovon; Mohandas, Reshma A.; Dean, Paul; Li, Lianhe; Linfield, Edmund H.; Giles Davies, A.; Wieck, Andreas D.

    2014-09-15

    A periodically poled lithium niobate (PPLN) crystal with multiple poling periods is used to generate tunable narrow-bandwidth THz pulses for injection seeding a quantum cascade laser (QCL). We demonstrate that longitudinal modes of the quantum cascade laser close to the gain maximum can be selected or suppressed according to the seed spectrum. The QCL emission spectra obtained by electro-optic sampling from the quantum cascade laser, in the most favorable case, shows high selectivity and amplification of the longitudinal modes that overlap the frequency of the narrow-band seed. Proper selection of the narrow-band THz seed from the PPLN crystal discretely tunes the longitudinal mode emission of the quantum cascade laser. Moreover, the THz wave build-up within the laser cavity is studied as a function of the round-trip time. When the seed frequency is outside the maximum of the gain spectrum the laser emission shifts to the preferential longitudinal mode.

  14. A new gas lesion syndrome in man, induced by 'isobaric gas counterdiffusion'

    NASA Technical Reports Server (NTRS)

    Lambertsen, C. J.; Idicula, J.

    1975-01-01

    Normal men have been found to develop pruritis and gas bubble lesions in the skin, and disruption of vestibular function, when breathing nitrogen or neon with oxygen while surrounded by helium at increased ambient pressure. This phenomenon, which occurs at stable ambient pressures, at 1 or many ATA, has been designated the isobaric gas counterdiffusion syndrome. In a series of analyses and experiments in vivo and in vitro the cause of the syndrome has been established as due to gas accumulation and development of gas bubbles in tissues as a result of differences in selective diffusivities, for various respired and ambient gases, in the tissue substances between capillary blood and the surrounding atmosphere. The phenomenon described in man is an initial stage of a process shown later in animals to progress to continuous, massive, lethal, intravascular gas embolization.

  15. Selective enhancement and suppression of frog gustatory responses to amino acids

    PubMed Central

    1981-01-01

    Properties of the receptor sites for L-amino acids in taste cells of the bullfrog (Rana catesbeiana) were examined by measuring the neural activities of the glossopharyngeal nerve under various conditions. (a) The frogs responded to 12 amino acids, but the responses to the amino acids varied with individual frogs under natural conditions. The frog tongues, however, exhibited similar responses after an alkaline treatment that removes Ca2+ from the tissue. The variation in the responses under natural conditions was apparently due to the variation in the amount of Ca2+ bound to the receptor membrane. (b) The responses to hydrophilic L-amino acids (glycine, L-alanine, L-serine, L- threonine, L-cysteine, and L-proline) were of a tonic type, but those to hydrophobic L-amino acids (L-valine, L-leucine, L-isoleucine, L- methionine, L-phenylalanine, and L-tyrptophan) were usually composed of both phasic and tonic components. (c) The properties of the tonic component were quite different from those of the phasic component: the tonic component was largely enhanced by the alkaline treatment and suppressed by the acidic treatment that increases binding of Ca2+ to the tissue. Also, the tonic component was suppressed by the presence of low concentrations of salts, or the action of pronase E, whereas the phasic component was unchanged under these conditions. These properties of the phasic component were quite similar to those of the response to hydrophobic substances such as quinine. These results suggest that the hydrophilic L-amino acids stimulate receptor protein(s) and that the hydrophobic L-amino acids stimulate both the receptor protein and a receptor site similar to that for quinine. (d) On the basis of the suppression of the responses to amino acids by salts, the mechanism of generation of the receptor potential is discussed. PMID:6972437

  16. Alpha 1-adrenergic agonists selectively suppress voltage-dependent K+ current in rat ventricular myocytes.

    PubMed Central

    Apkon, M; Nerbonne, J M

    1988-01-01

    The effects of alpha 1-adrenergic agonists on the waveforms of action potentials and voltage-gated ionic currents were examined in isolated adult rat ventricular myocytes by the whole-cell patch-clamp recording technique. After "puffer" applications of either of two alpha 1 agonists, phenylephrine and methoxamine, action-potential durations were increased. In voltage-clamped cells, phenylephrine (5-20 microM) or methoxamine (5-10 microM) reduced the amplitudes of Ca2+-independent voltage-activated outward K+ currents (Iout); neither the kinetics nor the voltage-dependent properties of Iout were significantly affected. The effects of phenylephrine or methoxamine on Iout were larger and longer-lasting at higher concentrations and after prolonged or repeated exposures; in all experiments, however, Iout recovered completely when puffer applications were discontinued. The suppression of Iout is attributed to the activation of alpha 1-adrenergic receptors, as neither beta- nor alpha 2-adrenergic agonists had measurable effects on Iout; in addition, the effect of phenylephrine was attenuated in the presence of the alpha antagonist phentolamine (10 microM), but not in the presence of the beta antagonist propranolol (10 microM). Voltage-gated Ca2+ currents, in contrast, were not altered measurably by phenylephrine or methoxamine and no currents were activated directly by these agents. Suppression of Iout was also observed during puffer applications of either of two protein kinase C activators, phorbol 12-myristate 13-acetate (10 nM-1 microM) and 1-oleoyl-2-acetylglycerol (60 microM). We conclude that the activation of alpha 1-adrenergic receptors in adult rat ventricular myocytes leads to action-potential prolongation as a result of the specific suppression of Iout and that this effect may be mediated by activation of protein kinase C. PMID:2903506

  17. Thiol-Based Potent and Selective HDAC6 Inhibitors Promote Tubulin Acetylation and T-Regulatory Cell Suppressive Function.

    PubMed

    Segretti, Mariana C F; Vallerini, Gian Paolo; Brochier, Camille; Langley, Brett; Wang, Liqing; Hancock, Wayne W; Kozikowski, Alan P

    2015-11-12

    Several new mercaptoacetamides were synthesized and studied as HDAC6 inhibitors. One compound, 2b, bearing an aminoquinoline cap group, was found to show 1.3 nM potency at HDAC6, with >3000-fold selectivity over HDAC1. 2b also showed excellent efficacy at increasing tubulin acetylation in rat primary cortical cultures, inducing a 10-fold increase in acetylated tubulin at 1 μM. To assess possible therapeutic effects, compounds were assayed for their ability to increase T-regulatory (Treg) suppressive function. Some but not all of the compounds increased Treg function, and thereby decreased conventional T cell activation and proliferation in vitro.

  18. Thiol-Based Potent and Selective HDAC6 Inhibitors Promote Tubulin Acetylation and T-Regulatory Cell Suppressive Function

    PubMed Central

    2015-01-01

    Several new mercaptoacetamides were synthesized and studied as HDAC6 inhibitors. One compound, 2b, bearing an aminoquinoline cap group, was found to show 1.3 nM potency at HDAC6, with >3000-fold selectivity over HDAC1. 2b also showed excellent efficacy at increasing tubulin acetylation in rat primary cortical cultures, inducing a 10-fold increase in acetylated tubulin at 1 μM. To assess possible therapeutic effects, compounds were assayed for their ability to increase T-regulatory (Treg) suppressive function. Some but not all of the compounds increased Treg function, and thereby decreased conventional T cell activation and proliferation in vitro. PMID:26617971

  19. Nested sampling of isobaric phase space for the direct evaluation of the isothermal-isobaric partition function of atomic systems

    SciTech Connect

    Wilson, Blake A.; Nielsen, Steven O.; Gelb, Lev D.

    2015-10-21

    Nested Sampling (NS) is a powerful athermal statistical mechanical sampling technique that directly calculates the partition function, and hence gives access to all thermodynamic quantities in absolute terms, including absolute free energies and absolute entropies. NS has been used predominately to compute the canonical (NVT) partition function. Although NS has recently been used to obtain the isothermal-isobaric (NPT) partition function of the hard sphere model, a general approach to the computation of the NPT partition function has yet to be developed. Here, we describe an isobaric NS (IBNS) method which allows for the computation of the NPT partition function of any atomic system. We demonstrate IBNS on two finite Lennard-Jones systems and confirm the results through comparison to parallel tempering Monte Carlo. Temperature-entropy plots are constructed as well as a simple pressure-temperature phase diagram for each system. We further demonstrate IBNS by computing part of the pressure-temperature phase diagram of a Lennard-Jones system under periodic boundary conditions.

  20. Anti-coreceptor therapy drives selective T cell egress by suppressing inflammation-dependent chemotactic cues

    PubMed Central

    Martin, Aaron J.; Clark, Matthew; Gojanovich, Gregory; Manzoor, Fatima; Miller, Keith; Kline, Douglas E.; Morillon, Y. Maurice; Wang, Bo

    2016-01-01

    There continues to be a need for immunotherapies to treat type 1 diabetes in the clinic. We previously reported that nondepleting anti-CD4 and -CD8 Ab treatment effectively reverses diabetes in new-onset NOD mice. A key feature of the induction of remission is the egress of the majority of islet-resident T cells. How this occurs is undefined. Herein, the effects of coreceptor therapy on islet T cell retention were investigated. Bivalent Ab binding to CD4 and CD8 blocked TCR signaling and T cell cytokine production, while indirectly downregulating islet chemokine expression. These processes were required for T cell retention, as ectopic IFN-γ or CXCL10 inhibited Ab-mediated T cell purging. Importantly, treatment of humanized mice with nondepleting anti–human CD4 and CD8 Ab similarly reduced tissue-infiltrating human CD4+ and CD8+ T cells. These findings demonstrate that Ab binding of CD4 and CD8 interrupts a feed-forward circuit by suppressing T cell–produced cytokines needed for expression of chemotactic cues, leading to rapid T cell egress from the islets. Coreceptor therapy therefore offers a robust approach to suppress T cell–mediated pathology by purging T cells in an inflammation-dependent manner. PMID:27777971

  1. Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo

    PubMed Central

    Starenki, Dmytro

    2015-01-01

    Background Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the rearranged during transfection (RET) proto-oncogene. Not all patients with progressive MTC respond to current therapy inhibiting RET, demanding additional therapeutic strategies. We recently demonstrated that disrupting mitochondrial metabolism using a mitochondria-targeted agent or by depleting a mitochondrial chaperone effectively suppressed human MTC cells in culture and in mouse xenografts by inducing apoptosis and RET downregulation. These observations led us to hypothesize that mitochondria are potential therapeutic targets for MTC. This study further tests this hypothesis using1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4-oxothiazolidin-2-ylidenemethyl] pyridinium chloride (MKT-077), a water-soluble rhodocyanine dye analogue, which can selectively accumulate in mitochondria. Methods The effects of MKT-077 on cell proliferation, survival, expression of RET and tumor protein 53 (TP53), and mitochondrial activity were determined in the human MTC lines in culture and in mouse xenografts. Results MKT-077 induced cell cycle arrest in TT and MZ-CRC-1. Intriguingly, MKT-077 also induced RET downregulation and strong cell death responses in TT cells, but not in MZ-CRC-1 cells. This discrepancy was mainly due to the difference between the capacities of these cell lines to retain MKT-077 in mitochondria. The cytotoxicity of MKT-077 in TT cells was mainly attributed to oxidative stress while being independent of TP53. MKT-077 also effectively suppressed tumor growth of TT xenografts. Conclusion MKT-077 can suppress cell survival of certain MTC subtypes by accumulating in mitochondria and interfering with mitochondrial activity although it can also suppress cell proliferation via other mechanisms. These results consistently support the hypothesis that mitochondrial targeting has therapeutic potential for MTC. PMID:26485469

  2. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy.

    PubMed

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-10-15

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy.

  3. Innate-like CD4 T cells selected by thymocytes suppress adaptive immune responses against bacterial infections

    PubMed Central

    Qiao, Yu; Gray, Brian M.; Sofi, Mohammed H.; Bauler, Laura D.; Eaton, Kathryn A.; O'Riordan, Mary X. D.; Chang, Cheong-Hee

    2012-01-01

    We have reported a new innate-like CD4 T cell population that expresses cell surface makers of effector/memory cells and produce Th1 and Th2 cytokines immediately upon activation. Unlike conventional CD4 T cells that are selected by thymic epithelial cells, these CD4 T cells, named T-CD4 T cells, are selected by MHC class II expressing thymocytes. Previously, we showed that the presence of T-CD4 T cells protected mice from airway inflammation suggesting an immune regulatory role of T-CD4 T cells. To further understand the function of T-CD4 T cells, we investigated immune responses mediated by T-CD4 T cells during bacterial infection because the generation of antigen specific CD4 T cells contributes to clearance of infection and for the development of immune memory. The current study shows a suppressive effect of T-CD4 T cells on both CD8 and CD4 T cell-mediated immune responses during Listeria and Helicobacter infections. In the mouse model of Listeria monocytogenes infection, T-CD4 T cells resulted in decreasedfrequency of Listeria-specific CD8 T cells and the killing activity of them. Furthermore, mice with T-CD4 T cells developed poor immune memory, demonstrated by reduced expansion of antigen-specific T cells and high bacterial burden upon re-infection. Similarly, the presence of T-CD4 T cells suppressed the generation of antigen-specific CD4 T cells in Helicobacter pylori infected mice. Thus, our studies reveal a novel function of T-CD4 T cells in suppressing anti-bacterial immunity. PMID:23264931

  4. Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations.

    PubMed

    Emadi, Ashkan; Jun, Sung Ah; Tsukamoto, Takashi; Fathi, Amir T; Minden, Mark D; Dang, Chi V

    2014-04-01

    The incidence of mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) in de novo acute myeloid leukemia (AML) is approximately 20%. These mutations result in distinct metabolic characteristics including dependency of cancer cells on glutamine as the main source for α-ketoglutarate, which is consumed by leukemia cells to produce a cancer-derived metabolite, 2-hydroxyglutarate. We sought to exploit this glutamine addiction therapeutically in mutant IDH primary AML cells from patients by measuring cell growth after exposure to a small molecule glutaminase inhibitor, BPTES. We found that BPTES only suppressed the growth of AML cells expressing mutant IDH compared with those expressing wild type IDH. This study lays the groundwork for strategies to target a specific subtype of AML metabolically with IDH mutations with a unique reprogramming of intermediary metabolism that culminates in glutamine dependency of cancer cells for survival.

  5. A theory of the transition to critical period plasticity: inhibition selectively suppresses spontaneous activity.

    PubMed

    Toyoizumi, Taro; Miyamoto, Hiroyuki; Yazaki-Sugiyama, Yoko; Atapour, Nafiseh; Hensch, Takao K; Miller, Kenneth D

    2013-10-02

    What causes critical periods (CPs) to open? For the best-studied case, ocular dominance plasticity in primary visual cortex in response to monocular deprivation (MD), the maturation of inhibition is necessary and sufficient. How does inhibition open the CP? We present a theory: the transition from pre-CP to CP plasticity arises because inhibition preferentially suppresses responses to spontaneous relative to visually driven input activity, switching learning cues from internal to external sources. This differs from previous proposals in (1) arguing that the CP can open without changes in plasticity mechanisms when activity patterns become more sensitive to sensory experience through circuit development, and (2) explaining not simply a transition from no plasticity to plasticity, but a change in outcome of MD-induced plasticity from pre-CP to CP. More broadly, hierarchical organization of sensory-motor pathways may develop through a cascade of CPs induced as circuit maturation progresses from "lower" to "higher" cortical areas.

  6. Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

    SciTech Connect

    Niu, Mingshan; Shen, Yangling; Xu, Xiaoyu; Yao, Yao; Fu, Chunling; Yan, Zhiling; Wu, Qingyun; Cao, Jiang; Sang, Wei; Zeng, Lingyu; Li, Zhenyu; Liu, Xuejiao; and others

    2015-07-10

    Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys{sup 38} to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy.

  7. The isobaric multiplet mass equation for A≤71 revisited

    SciTech Connect

    Lam, Yi Hua; Blank, Bertram; Smirnova, Nadezda A.; Bueb, Jean Bernard; Antony, Maria Susai

    2013-11-15

    Accurate mass determination of short-lived nuclides by Penning-trap spectrometers and progress in the spectroscopy of proton-rich nuclei have triggered renewed interest in the isobaric multiplet mass equation (IMME). The energy levels of the members of T=1/2,1,3/2, and 2 multiplets and the coefficients of the IMME are tabulated for A≤71. The new compilation is based on the most recent mass evaluation (AME2011) and it includes the experimental results on energies of the states evaluated up to end of 2011. Taking into account the error bars, a significant deviation from the quadratic form of the IMME for the A=9,35 quartets and the A=32 quintet is observed.

  8. Rapid cooling of neutron stars by hyperons and Delta isobars

    NASA Technical Reports Server (NTRS)

    Prakash, Madappa; Prakash, Manju; Lattimer, James M.; Pethick, C. J.

    1992-01-01

    Direct Urca processes with hyperons and/or nucleon isobars can occur in dense matter as long as the concentration of Lambda hyperons exceeds a critical value that is less than 3 percent and is typically about 0.1 percent. The neutrino luminosities from the hyperon Urca processes are about 5-100 times less than the typical luminosity from the nucleon direct Urca process, if the latter process is not forbidden, but they are larger than those expected from other sources. These direct Urca processes provide avenues for rapid cooling of neutron stars which invoke neither exotic states nor the large proton fraction (of order 0.11-0.15) required for the nucleon direct Urca process.

  9. The isobaric multiplet mass equation for A≤71 revisited

    NASA Astrophysics Data System (ADS)

    Lam, Yi Hua; Blank, Bertram; Smirnova, Nadezda A.; Bueb, Jean Bernard; Antony, Maria Susai

    2013-11-01

    Accurate mass determination of short-lived nuclides by Penning-trap spectrometers and progress in the spectroscopy of proton-rich nuclei have triggered renewed interest in the isobaric multiplet mass equation (IMME). The energy levels of the members of T=1/2,1,3/2, and 2 multiplets and the coefficients of the IMME are tabulated for A≤71. The new compilation is based on the most recent mass evaluation (AME2011) and it includes the experimental results on energies of the states evaluated up to end of 2011. Taking into account the error bars, a significant deviation from the quadratic form of the IMME for the A=9,35 quartets and the A=32 quintet is observed.

  10. Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression

    PubMed Central

    Roy, Bijoyita; Friesen, Westley J.; Tomizawa, Yuki; Leszyk, John D.; Zhuo, Jin; Johnson, Briana; Dakka, Jumana; Trotta, Christopher R.; Xue, Xiaojiao; Mutyam, Venkateshwar; Keeling, Kim M.; Mobley, James A.; Rowe, Steven M.; Bedwell, David M.; Welch, Ellen M.; Jacobson, Allan

    2016-01-01

    A premature termination codon (PTC) in the ORF of an mRNA generally leads to production of a truncated polypeptide, accelerated degradation of the mRNA, and depression of overall mRNA expression. Accordingly, nonsense mutations cause some of the most severe forms of inherited disorders. The small-molecule drug ataluren promotes therapeutic nonsense suppression and has been thought to mediate the insertion of near-cognate tRNAs at PTCs. However, direct evidence for this activity has been lacking. Here, we expressed multiple nonsense mutation reporters in human cells and yeast and identified the amino acids inserted when a PTC occupies the ribosomal A site in control, ataluren-treated, and aminoglycoside-treated cells. We find that ataluren’s likely target is the ribosome and that it produces full-length protein by promoting insertion of near-cognate tRNAs at the site of the nonsense codon without apparent effects on transcription, mRNA processing, mRNA stability, or protein stability. The resulting readthrough proteins retain function and contain amino acid replacements similar to those derived from endogenous readthrough, namely Gln, Lys, or Tyr at UAA or UAG PTCs and Trp, Arg, or Cys at UGA PTCs. These insertion biases arise primarily from mRNA:tRNA mispairing at codon positions 1 and 3 and reflect, in part, the preferred use of certain nonstandard base pairs, e.g., U-G. Ataluren’s retention of similar specificity of near-cognate tRNA insertion as occurs endogenously has important implications for its general use in therapeutic nonsense suppression. PMID:27702906

  11. Hard breakup of the deuteron into two {Delta} isobars

    SciTech Connect

    Granados, Carlos G.; Sargsian, Misak M.

    2011-05-15

    We study high-energy photodisintegration of the deuteron into two {Delta} isobars at large center of mass angles within the QCD hard rescattering model (HRM). According to the HRM, the process develops in three main steps: the photon knocks a quark from one of the nucleons in the deuteron; the struck quark rescatters off a quark from the other nucleon sharing the high energy of the photon; then the energetic quarks recombine into two outgoing baryons which have large transverse momenta. Within the HRM, the cross section is expressed through the amplitude of pn{yields}{Delta}{Delta} scattering which we evaluated based on the quark-interchange model of hard hadronic scattering. Calculations show that the angular distribution and the strength of the photodisintegration is mainly determined by the properties of the pn{yields}{Delta}{Delta} scattering. We predict that the cross section of the deuteron breakup to {Delta}{sup ++}{Delta}{sup -} is 4-5 times larger than that of the breakup to the {Delta}{sup +}{Delta}{sup 0} channel. Also, the angular distributions for these two channels are markedly different. These can be compared with the predictions based on the assumption that two hard {Delta} isobars are the result of the disintegration of the preexisting {Delta}{Delta} components of the deuteron wave function. In this case, one expects the angular distributions and cross sections of the breakup in both {Delta}{sup ++}{Delta}{sup -} and {Delta}{sup +}{Delta}{sup 0} channels to be similar.

  12. Selective strong-field enhancement and suppression of ionization with short laser pulses

    NASA Astrophysics Data System (ADS)

    Hart, N. A.; Strohaber, J.; Kolomenskii, A. A.; Paulus, G. G.; Bauer, D.; Schuessler, H. A.

    2016-06-01

    We experimentally demonstrate robust selective excitation and attenuation of atomic Rydberg level populations in sodium vapor (Na i) using intense laser pulses in the strong-field limit (>1012W /c m2 ). Coherent control of the atomic population and related ionization channels is realized for intensities above the over-the-barrier ionization intensity. Moreover, atomic excitation selectivity and high ionization yield are simultaneously achieved without the need to tailor the spectral phase of the laser. A qualitative model confirms that this strong-field coherent control arises through the manifestation of a Freeman resonance.

  13. Salinomycin inhibits the tumor growth of glioma stem cells by selectively suppressing glioma-initiating cells.

    PubMed

    Chen, Tunan; Yi, Liang; Li, Fei; Hu, Rong; Hu, Shengli; Yin, Yi; Lan, Chuan; Li, Zhao; Fu, Chuhua; Cao, Liu; Chen, Zhi; Xian, Jishu; Feng, Hua

    2015-04-01

    Glioma‑initiating cells are a small population of cells that have the ability to undergo self‑renewal and initiate tumorigenesis. In the present study, the potential role of salinomycin, a polyether antibiotic, on the suppression of glioma cell growth was investigated. GL261 glioma cells were maintained in a stem‑cell‑like status [GL261 neurospheres (GL261‑NS)] or induced for differentiation [GL261 adherent cells (GL261‑AC)]. It was demonstrated that salinomycin significantly reduced the cell viability of GL261‑NS and GL261‑AC cells in a dose‑dependent manner, with a more substantial inhibition of GL261‑NS proliferation (P<0.05). The inhibitory effect of salinomycin on cell growth was more effective than that of 1‑(4‑amino‑2‑methyl‑5‑pyrimid l)‑methyl‑3‑(2‑chloroethyl)‑3‑nitrosourea hydrochloride and vincristine (P<0.05). Salinomycin depleted GL261‑NS from tumorspheres and induced cell apoptosis. In addition, salinomycin prolonged the median survival time of glioma‑bearing mice (P<0.05). Therefore, the present study indicated that salinomycin may preferentially inhibit glioma‑initiated cell growth by inducing apoptosis, suggesting that salinomycin may provide a valuable therapeutic strategy for the treatment of malignant glioma.

  14. Selective suppression of antisense transcription by Set2-mediated H3K36 methylation

    PubMed Central

    Venkatesh, Swaminathan; Li, Hua; Gogol, Madelaine M.; Workman, Jerry L.

    2016-01-01

    Maintenance of a regular chromatin structure over the coding regions of genes occurs co-transcriptionally via the ‘chromatin resetting' pathway. One of the central players in this pathway is the histone methyltransferase Set2. Here we show that the loss of Set2 in yeast, Saccharomyces cerevisiae, results in transcription initiation of antisense RNAs embedded within body of protein-coding genes. These RNAs are distinct from the previously identified non-coding RNAs and cover 11% of the yeast genome. These RNA species have been named Set2-repressed antisense transcripts (SRATs) since the co-transcriptional addition of the H3K36 methyl mark by Set2 over their start sites results in their suppression. Interestingly, loss of chromatin resetting factor Set2 or the subsequent production of SRATs does not affect the abundance of the sense transcripts. This difference in transcriptional outcomes of overlapping transcripts due to a strand-independent addition of H3K36 methylation is a key regulatory feature of interleaved transcriptomes. PMID:27892455

  15. Selective Disruption of Respiratory Supercomplexes as a New Strategy to Suppress Her2high Breast Cancer

    PubMed Central

    Sachaphibulkij, Karishma; Stursa, Jan; Bezawork-Geleta, Ayenachew; Blecha, Jan; Endaya, Berwini; Werner, Lukas; Cerny, Jiri; Zobalova, Renata; Goodwin, Jacob; Spacek, Tomas; Alizadeh Pesdar, Elham; Yan, Bing; Nguyen, Maria Nga; Vondrusova, Magdalena; Sobol, Margaryta; Jezek, Petr; Hozak, Pavel; Truksa, Jaroslav; Dong, Lan-Feng

    2017-01-01

    Abstract Aims: Expression of the HER2 oncogene in breast cancer is associated with resistance to treatment, and Her2 may regulate bioenergetics. Therefore, we investigated whether disruption of the electron transport chain (ETC) is a viable strategy to eliminate Her2high disease. Results: We demonstrate that Her2high cells and tumors have increased assembly of respiratory supercomplexes (SCs) and increased complex I-driven respiration in vitro and in vivo. They are also highly sensitive to MitoTam, a novel mitochondrial-targeted derivative of tamoxifen. Unlike tamoxifen, MitoTam efficiently suppresses experimental Her2high tumors without systemic toxicity. Mechanistically, MitoTam inhibits complex I-driven respiration and disrupts respiratory SCs in Her2high background in vitro and in vivo, leading to elevated reactive oxygen species production and cell death. Intriguingly, higher sensitivity of Her2high cells to MitoTam is dependent on the mitochondrial fraction of Her2. Innovation: Oncogenes such as HER2 can restructure ETC, creating a previously unrecognized therapeutic vulnerability exploitable by SC-disrupting agents such as MitoTam. Conclusion: We propose that the ETC is a suitable therapeutic target in Her2high disease. Antioxid. Redox Signal. 26, 84–103. PMID:27392540

  16. Selective suppression of antisense transcription by Set2-mediated H3K36 methylation.

    PubMed

    Venkatesh, Swaminathan; Li, Hua; Gogol, Madelaine M; Workman, Jerry L

    2016-11-28

    Maintenance of a regular chromatin structure over the coding regions of genes occurs co-transcriptionally via the 'chromatin resetting' pathway. One of the central players in this pathway is the histone methyltransferase Set2. Here we show that the loss of Set2 in yeast, Saccharomyces cerevisiae, results in transcription initiation of antisense RNAs embedded within body of protein-coding genes. These RNAs are distinct from the previously identified non-coding RNAs and cover 11% of the yeast genome. These RNA species have been named Set2-repressed antisense transcripts (SRATs) since the co-transcriptional addition of the H3K36 methyl mark by Set2 over their start sites results in their suppression. Interestingly, loss of chromatin resetting factor Set2 or the subsequent production of SRATs does not affect the abundance of the sense transcripts. This difference in transcriptional outcomes of overlapping transcripts due to a strand-independent addition of H3K36 methylation is a key regulatory feature of interleaved transcriptomes.

  17. P50 Suppression in Children with Selective Mutism: A Preliminary Report

    ERIC Educational Resources Information Center

    Henkin, Yael; Feinholz, Maya; Arie, Miri; Bar-Haim, Yair

    2010-01-01

    Evidence suggests that children with selective mutism (SM) display significant aberrations in auditory efferent activity at the brainstem level that may underlie inefficient auditory processing during vocalization, and lead to speech avoidance. The objective of the present study was to explore auditory filtering processes at the cortical level in…

  18. A selective inhibitor of intestinal ACAT, EAB309 suppresses both intestinal and hepatic cholesterol output and stimulates chylomicron removal.

    PubMed

    Umeda, Y; Hirano, T; Kako, Y; Kamagata, K; Okuyama, K; Suzuki, K

    1998-01-01

    The effect of a novel inhibitor of acylcoenzyme A:cholesterol acyltransferase (EC 2.3.1.26, ACAT), EAB309 (EAB) on plasma lipid metabolism was studied in cholesterol-fed rats. Orally administered EAB was not detected in the portal vein or the liver but distributed exclusively in the intestine, suggesting that this agent selectively inhibits intestinal ACAT. The rats were fed with either a cholesterol-diet or a cholesterol-diet containing 0.005% EAB (w/w) ad. libium for three weeks. ACAT activity in intestinal microsomes was significantly inhibited in EAB-treated rats. Hepatic ACAT activity was also decreased in EAB-treated rats, however, this was attenuated by the addition of excess cholesterol to the liver microsome, indicating that substrate availability is tightly associated with this enzyme's activity and the inhibition of hepatic ACAT by EAB is not direct. Incorporation of [3H]-cholesterol to cholesteryl ester (CE) in mesenteric lymph were markedly suppressed by EAB treatment. Chylomicrons (CMs) were doubly labeled with [3H]-vitamin A and [14C]-triglyceride (TG) in EAB-treated or non-treated rats and injected into normal chow-fed rats. The CMs from EAB-treated rats were cleared faster from the plasma and taken up more by the liver compared with the CMs from non-treated rats. The content of CE in newly secreted VLDL was remarkably decreased by EAB treatment without affecting TG output. These results demonstrate that EAB, a novel inhibitor of intestinal ACAT, significantly suppresses both intestinal and hepatic CE output and stimulates CM removal. This suggests that the inhibition of intestinal ACAT can subsequently suppress hepatic ACAT by decreased CE delivery from the intestine to the liver.

  19. Suppressed N2O formation during NH3 selective catalytic reduction using vanadium on zeolitic microporous TiO2.

    PubMed

    Lee, Seung Gwan; Lee, Hyun Jeong; Song, Inhak; Youn, Seunghee; Kim, Do Heui; Cho, Sung June

    2015-08-03

    Emission of N2O from mobile and off-road engine is now being currently regulated because of its high impact compared to that of CO2, thereby implying that N2O formation from the exhaust gas after-treatment system should be suppressed. Selective catalytic reduction using vanadium supported TiO2 catalyst in mobile and off-road engine has been considered to be major source for N2O emission in the system. Here we have demonstrated that vanadium catalyst supported on zeolitic microporous TiO2 obtained from the hydrothermal reaction of bulk TiO2 at 400 K in the presence of LiOH suppresses significantly the N2O emission compared to conventional VOx/TiO2 catalyst, while maintaining the excellent NOx reduction, which was ascribed to the location of VOx domain in the micropore of TiO2, resulting in the strong metal support interaction. The use of zeolitic microporous TiO2 provides a new way of preparing SCR catalyst with a high thermal stability and superior catalytic performance. It can be also extended further to the other catalytic system employing TiO2-based substrate.

  20. Suppressed N2O formation during NH3 selective catalytic reduction using vanadium on zeolitic microporous TiO2

    PubMed Central

    Lee, Seung Gwan; Lee, Hyun Jeong; Song, Inhak; Youn, Seunghee; Kim, Do Heui; Cho, Sung June

    2015-01-01

    Emission of N2O from mobile and off-road engine is now being currently regulated because of its high impact compared to that of CO2, thereby implying that N2O formation from the exhaust gas after-treatment system should be suppressed. Selective catalytic reduction using vanadium supported TiO2 catalyst in mobile and off-road engine has been considered to be major source for N2O emission in the system. Here we have demonstrated that vanadium catalyst supported on zeolitic microporous TiO2 obtained from the hydrothermal reaction of bulk TiO2 at 400 K in the presence of LiOH suppresses significantly the N2O emission compared to conventional VOx/TiO2 catalyst, while maintaining the excellent NOx reduction, which was ascribed to the location of VOx domain in the micropore of TiO2, resulting in the strong metal support interaction. The use of zeolitic microporous TiO2 provides a new way of preparing SCR catalyst with a high thermal stability and superior catalytic performance. It can be also extended further to the other catalytic system employing TiO2-based substrate. PMID:26235671

  1. Evaluation of Fat Suppression of Diffusion-weighted Imaging Using Section Select Gradient Reversal Technique on 3 T Breast MRI.

    PubMed

    Takemori, Daichi; Kimura, Daisuke; Yamada, Eiji; Higashida, Mitsuji

    2016-07-01

    This study evaluates fat suppression of diffusion-weighted imaging (DWI) using section select gradient reversal (SSGR) technique in clinical images on 3 T breast MRI. A total of 20 patients with breast cancer were examined at a Philips Ingenia 3 T MRI. We acquired DWI with SPAIR, SSGR-SPAIR, STIR, and SSGR-STIR. We evaluated contrast between the fat region and lesion, the coefficient of variance (CV) of the fat region and the apparent diffusion coefficient (ADC) of normal breast tissue and lesion. The contrast between the fat region and lesion was improved with SSGR technique. The CV of the fattest region did not have any significant difference in SPAIR technique (p>0.05), but it was significantly decreased in the STIR technique using SSGR technique (p<0.05). Positive correlation was observed in ADC value between SPAIR and other fat suppression techniques (SSGR-SPAIR, STIR, SSGR-STIR). DWI using SSGR technique was suggested to be effective on 3 T breast MRI.

  2. Bismuth as a modifier of Au Pd catalyst: Enhancing selectivity in alcohol oxidation by suppressing parallel reaction

    SciTech Connect

    Villa, Alberto; Wang, Di; Veith, Gabriel M; Prati, Laura

    2012-01-01

    Bi has been widely employed as a modifier for Pd and Pt based catalyst mainly in order to improve selectivity. We found that when Bi was added to the bimetallic system AuPd, the effect on activity in alcohol oxidation mainly depends on the amount of Bi regardless its position, being negligible when Bi was 0.1 wt% and detectably negative when the amount was increased to 3 wt%. However, the selectivity of the reactions notably varied only when Bi was deposited on the surface of metal nanoparticles suppressing parallel reaction in both benzyl alcohol and glycerol oxidation. After a careful characterization of all the catalysts and additional catalytic tests, we concluded that the Bi influence on the activity of the catalysts could be ascribed to electronic effect whereas the one on selectivity mainly to a geometric modification. Moreover, the Bi-modified AuPd/AC catalyst showed possible application in the production of tartronic acid, a useful intermediate, from glycerol.

  3. Active suppression of nonlinear composite beam vibrations by selected control algorithms

    NASA Astrophysics Data System (ADS)

    Warminski, Jerzy; Bochenski, Marcin; Jarzyna, Wojciech; Filipek, Piotr; Augustyniak, Michal

    2011-05-01

    This paper is focused on application of different control algorithms for a flexible, geometrically nonlinear beam-like structure with Macro Fiber Composite (MFC) actuator. Based on the mathematical model of a geometrically nonlinear beam, analytical solutions for Nonlinear Saturation Controller (NSC) are obtained using Multiple Scale Method. Effectiveness of different control strategies is evaluated by numerical simulations in Matlab-Simulink software. Then, the Digital Signal Processing (DSP) controller and selected control algorithms are implemented to the physical system to compare numerical and experimental results. Detailed analysis for the NSC system is carried out, especially for high level of amplitude and wide range of frequencies of excitation. Finally, the efficiency of the considered controllers is tested experimentally for a more complex autoparametric " L-shape" beam system.

  4. Gene replacement without selection: regulated suppression of amber mutations in Escherichia coli.

    PubMed

    Herring, Christopher D; Glasner, Jeremy D; Blattner, Frederick R

    2003-06-05

    We have developed a method called "gene gorging" to make precise mutations in the Escherichia coli genome at frequencies high enough (1-15%) to allow direct identification of mutants by PCR or other screen rather than by selection. Gene gorging begins by establishing a donor plasmid carrying the desired mutation in the target cell. This plasmid is linearized by in vivo expression of the meganuclease I-SceI, providing a DNA substrate for lambda Red mediated recombination. This results in efficient replacement of the wild type allele on the chromosome with the modified sequence. We demonstrate gene gorging by introducing amber stop codons into the genes xylA, melA, galK, fucI, citA, ybdO, and lacZ. To compliment this approach we developed an arabinose inducible amber suppressor tRNA. Controlled expression mediated by the suppressor was demonstrated for the lacZ and xylA amber mutants.

  5. A CB2-Selective Cannabinoid Suppresses T-Cell Activities and Increases Tregs and IL-10.

    PubMed

    Robinson, Rebecca H; Meissler, Joseph J; Fan, Xiaoxuan; Yu, Daohai; Adler, Martin W; Eisenstein, Toby K

    2015-06-01

    We have previously shown that agonists selective for the cannabinoid receptor 2 (CB2), including O-1966, inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro correlate of organ graft rejection, predominantly through effects on T-cells. Current studies explored the mechanism of this immunosuppression by O-1966 using mouse spleen cells. Treatment with O-1966 dose-relatedly decreased levels of the active nuclear forms of the transcription factors NF-κB and NFAT in wild-type T-cells, but not T-cells from CB2 knockout (CB2R k/o) mice. Additionally, a gene expression profile of purified T-cells from MLR cultures generated using a PCR T-cell activation array showed that O-1966 decreased mRNA expression of CD40 ligand and CyclinD3, and increased mRNA expression of Src-like-adaptor 2 (SLA2), Suppressor of Cytokine Signaling 5 (SOCS5), and IL-10. The increase in IL-10 was confirmed by measuring IL-10 protein levels in MLR culture supernatants. Further, an increase in the percentage of regulatory T-cells (Tregs) was observed in MLR cultures. Pretreatment with anti-IL-10 resulted in a partial reversal of the inhibition of proliferation and blocked the increase of Tregs. Additionally, O-1966 treatment caused a dose-related decrease in the expression of CD4 in MLR cultures from wild-type, but not CB2R k/o, mice. These data support the potential of CB2-selective agonists as useful therapeutic agents to prolong graft survival in transplant patients, and strengthens their potential as a new class of immunosuppressive agents with broader applicability.

  6. Compact high resolution isobar separator for study of exotic decays

    NASA Astrophysics Data System (ADS)

    Shchepunov, V.; Piechaczek, A.; Carter, H. K.; Batchelder, J. C.; Zganjar, E. F.

    2009-05-01

    A compact isobar separator, based on the Multi-Pass-Time-of-Flight (MTOF) principle, is developed. A mass resolving power (MRP) of 110,000 (FWHM) is achieved as spectrometer with a transmission of 50 - 80%. The transverse beam acceptance and the energy acceptance are 42 π mm mrad and about ± 2.5%. Operated as a separator, molecules of N2 and CO with δM/M = 1/2500 or 10.433 MeV were separated with a Bradbury Nielsen gate. In that mode of operation, the MRP (FWHM) is about 40,000 after 120 laps. To inject radioactive ion beams into the separator, and to further improve its MRP, cooler and buncher RF quadrupoles were designed^1 and tested. A bunch width of 30 ns at 1% of the peak height (FWHM = 9 ns) and a transmission in DC mode of 75 -- 80 % were achieved. With such bunch parameters, MRPs of ˜ 400,000 (FWHM) are expected for the MTOF separator. At HRIBF, it will provide pure samples of exotic nuclides around ^100Sn, of neutron deficient rare-earth nuclei and of neutron-rich nuclei. Incidental measurements of mass differences will determine Qβ values with accuracies of ˜ 1%. ^1 V. Shchepunov and V. Kozlovskiy et al., to be published

  7. Testing the chiral magnetic effect with isobaric collisions

    NASA Astrophysics Data System (ADS)

    Deng, Wei-Tian; Huang, Xu-Guang; Ma, Guo-Liang; Wang, Gang

    2016-10-01

    The quark-gluon matter produced in relativistic heavy-ion collisions may contain local domains in which parity (P ) and combined charge conjugation and parity (C P ) symmetries are not preserved. When coupled with an external magnetic field, such P - and C P -odd domains will generate electric currents along the magnetic field—a phenomenon called the chiral magnetic effect (CME). Recently, the STAR Collaboration at the BNL Relativistic Heavy Ion Collider (RHIC) and the ALICE Collaboration at the CERN Large Hadron Collider (LHC) released data of charge-dependent azimuthal-angle correlators with features consistent with the CME expectation. However, the experimental observable is contaminated with significant background contributions from elliptic-flow-driven effects, which makes the interpretation of the data ambiguous. We show that the collisions of isobaric nuclei, Ru9644+Ru9644 and Zr9640+Zr9640, provide an ideal tool to disentangle the CME signal from the background effects. Our simulation demonstrates that the two collision types at √{sN N}=200 GeV have more than 10 % difference in the CME signal and less than 2 % difference in the elliptic-flow-driven backgrounds for the centrality range of 20-60%.

  8. Selective suppression of excitatory synapses on GABAergic interneurons by norepinephrine in juvenile rat prefrontal cortical microcircuitry.

    PubMed

    Wang, H-X; Waterhouse, B D; Gao, W-J

    2013-08-29

    The noradrenergic system of the brain is thought to facilitate neuronal processes that promote behavioral activation, alertness, and attention. It is known that norepinephrine (NE) can be significantly elevated in the prefrontal cortex under normal conditions such as arousal and attention, and following the administration of psychostimulants and various other drugs prescribed for psychiatric disorders. However, how NE modulates neuronal activity and synapses in the local prefrontal circuitry remains elusive. In this study, we characterized the actions of NE on individual monosynaptic connections among layer V pyramidal neurons (P) and fast-spiking (FS) GABAergic interneurons in the juvenile (postnatal days 20-23) rat prefrontal local circuitry. We found that NE selectively depresses excitatory synaptic transmission in P-FS connections but has no detectable effect on the excitatory synapses in P-P connections and the inhibitory synapses in FS-P connections. NE apparently exerts distinctly different modulatory actions on identified synapses that target GABAergic interneurons but has no effect on those in the pyramidal neurons in this specific developmental period. These results indicate that, depending on the postsynaptic targets, the effects of NE in prefrontal cortex are synapse-specific, at least in the juvenile animals.

  9. Distractor suppression when attention fails: behavioral evidence for a flexible selective attention mechanism.

    PubMed

    Elliott, James C; Giesbrecht, Barry

    2015-01-01

    Despite consistent evidence showing that attention is a multifaceted mechanism that can operate at multiple levels of processing depending on the structure and demands of the task, investigations of the attentional blink phenomenon have consistently shown that the impairment in reporting the second of two targets typically occurs at a late, or post-perceptual, stage of processing. This suggests that the attentional blink phenomenon may represent the operation of a unique attentional mechanism that is not as flexible as other attentional mechanisms. To test whether the attentional blink is a fixed or flexible phenomenon, we manipulated first target task demands (i.e., difficulty) and measured the influence this had on processing a subsequently presented distractor and the second target. If the attentional blink represents a mechanism that is fixed and consistently fails at a single stage of processing, then manipulations of task difficulty should not affect distractor processing. However, if the attentional blink represents a more multifaceted and flexible mechanism, then task difficulty should modulate distractor processing. The results revealed that distractor processing during the AB was attenuated under high task difficulty. In addition, unlike previous studies, we failed to find a correlation between distractor processing and the severity of the attentional blink. Using a simulation, we demonstrate that the previously reported correlations may have been spurious and due to using variables that were not independent. Overall, the present results support the conclusion that the selectivity of attention during the AB is flexible and depends on the structure and demands of the task.

  10. Fluvoxamine, a selective serotonin reuptake inhibitor, and 5-HT2C receptor inactivation induce appetite-suppressing effects in mice via 5-HT1B receptors.

    PubMed

    Nonogaki, Katsunori; Nozue, Kana; Takahashi, Yukiko; Yamashita, Nobuyuki; Hiraoka, Shuichi; Kumano, Hiroaki; Kuboki, Tomifusa; Oka, Yohsitomo

    2007-10-01

    Serotonin (5-hydroxytryptamine; 5-HT) 2C receptors and the downstream melanocortin pathway are suggested to mediate the appetite-suppressing effects of 5-HT drugs such as m-chlorophenylpiperazine (mCPP) and fenfluramine. Here, we report that fluvoxamine (3-30 mg/kg), a selective serotonin reuptake inhibitor (SSRI), in the presence of SB 242084 (1-2 mg/kg), a selective 5-HT2C receptor antagonist, exerts appetite-suppressing effects while fluvoxamine or SB 242084 alone has no effect. The appetite-suppressing effects were attenuated in the presence of SB 224289 (5 mg/kg), a selective 5-HT1B receptor antagonist. Moreover, CP 94253 (5-10 mg/kg), a selective 5-HT1B receptor agonist, exerted appetite-suppressing effects and significantly increased hypothalamic pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) gene expression and decreased hypothalamic orexin gene expression. These results suggest that fluvoxamine and inactivation of 5-HT2C receptors exert feeding suppression through activation of 5-HT1B receptors, and that 5-HT1B receptors up-regulate hypothalamic POMC and CART gene expression and down-regulate hypothalamic orexin gene expression in mice.

  11. Selective suppression of the slow-inactivating potassium currents by nootropics in molluscan neurons.

    PubMed

    Bukanova, Julia V; Solntseva, Elena I; Skrebitsky, Vladimir G

    2002-09-01

    The role of the voltage-gated K+ channels in the effect of some nootropics was investigated. Earlier, the multiple effect of high concentrations of two nootropics, piracetam and its peptide analogue GVS-111 [Seredenin et al. (1995), US Patent No. 5,439,930], on Ca2+ and K+ currents of molluscan neurons was shown [Solntseva et al. (1997), General Pharmacology 29, 85-89]. In the present work, we describe the selective effect of low concentrations of these nootropics as well as vinpocetine on certain types of K+ current. The experiments were performed on isolated neurons of the land snail Helix pomatia using a two-microelectrode voltage-clamp method. The inward voltage-gated Ca2+ current (ICa) and three subtypes of the outward voltage-gated K+ current were recorded: Ca2+-dependent K+ current (IK(Ca)), delayed rectifying current (IKD), and fast-inactivating K+ current (IA). It has been found that I Ca was not changed in the presence of 30 microM vinpocetine, 100 microM piracetam or 10 nM GVS-111, while slow-inactivating, TEA-sensitive IK(Ca) and IKD were inhibited (IK(Ca) more strongly than IKD). In contrast, the fast-inactivating, 4-AP-sensitive K+ current (IA) was not diminished by low concentrations of piracetam and GVS-111, while vinpocetine even augmented it. A possible role of slow-inactivating subtypes of the K+ channels in the development of different forms of dementia is discussed.

  12. Selective suppression of Th2-mediated airway eosinophil infiltration by low-molecular weight CCR3 antagonists.

    PubMed

    Mori, Akio; Ogawa, Koji; Someya, Koichiro; Kunori, Yuichi; Nagakubo, Daisuke; Yoshie, Osamu; Kitamura, Fujiko; Hiroi, Takachika; Kaminuma, Osamu

    2007-08-01

    The effects of selective CC chemokine receptor (CCR)-3 antagonists on antigen-induced leukocyte accumulation in the lungs of mice adoptively transferred with in vitro-differentiated T(h)1 and T(h)2 were investigated. Inhalation of antigen by mice injected with T(h)1 and T(h)2 initiated the migration of T cells themselves into the lungs. Subsequently, neutrophils massively accumulated in T(h)1-transferred mice, whereas eosinophil infiltration was specifically induced by T(h)2. CCR3 antagonists, SB-297006 and/or SB-328437, suppressed antigen-induced accumulation of T(h)2 as well as eosinophils in the lungs, whereas they failed to affect T(h)1-mediated airway inflammation. Not only T(h)2 and eosinophil infiltration but also cellular mobilization in T(h)1-transferred mice was attenuated by an anti-CC chemokine ligand-11 antibody. CCR3 antagonists reduced chemokine production in the lungs of mice transferred with T(h)2 but not T(h)1, suggesting that down-regulation of chemokine synthesis is involved in the selective inhibition of T(h)2-mediated eosinophil infiltration by CCR3 antagonists.

  13. Rapid Analysis of Isobaric Exogenous Metabolites by Differential Mobility Spectrometry Mass Spectrometry

    SciTech Connect

    Parson, Whitney B; Schneider, Bradley B; Kertesz, Vilmos; Corr, Jay; Covey, Thomas R.; Van Berkel, Gary J

    2011-01-01

    The direct separation of isobaric glucuronide metabolites from propranolol dosed tissue extracts by differential mobility spectrometry mass spectrometry (DMS-MS) with the use of a polar gas-phase chemical modifier was demonstrated. The DMS gas-phase separation was able to resolve the isobaric metabolites with separation times on the order of ms instead of mins to hrs typically required when using pre-ionization chromatographic separation methods. Direct separation of isobaric metabolites from the complex tissue extract was validated using standards as well as implementing an HPLC separation prior to the DMS-MS analysis to pre-separate the species of interest. The ability to separate isobaric exogenous metabolites directly from a complex tissue extract is expected to facilitate the drug development process by increasing analytical throughput without the requirement for pre-ionization cleanup or separation strategies.

  14. New isobaric lignans from Refined Olive Oils as quality markers for Virgin Olive Oils.

    PubMed

    Cecchi, Lorenzo; Innocenti, Marzia; Melani, Fabrizio; Migliorini, Marzia; Conte, Lanfranco; Mulinacci, Nadia

    2017-03-15

    Herein we describe the influence of olive oil refining processes on the lignan profile. The detection of new isobaric lignans is suggested to reveal frauds in commercial extra-Virgin Olive Oils. We analyzed five commercial olive oils by HPLC-DAD-TOF/MS to evaluate their lignan content and detected, for the first time, some isobaric forms of natural (+)-pinoresinol and (+)-1-acetoxypinoresinol. Then we analyzed partially and fully-refined oils from Italy, Tunisia and Spain. The isobaric forms occur only during the bleaching step of the refining process and remain unaltered after the final deodorizing step. Molecular dynamic simulation helped to identify the most probable chemical structures corresponding to these new isobars with data in agreement with the chromatographic findings. The total lignan amounts in commercial olive oils was close to 2mg/L. Detection of these new lignans can be used as marker of undeclared refining procedures in commercial extra-virgin and/or Virgin Olive Oils.

  15. Neutrino mean free path in neutron star matter with {delta} isobars

    SciTech Connect

    Chen Yanjun; Yuan Yefei; Liu Yuxin

    2009-05-15

    The {delta}-isobar degrees of freedom are taken into account in neutron star matter and their contributions to neutrino mean free paths are evaluated. It is found that the charged-current contributions are comparable to those from the neutral-current reactions. The contributions of {delta}-isobars may be a leading sector of neutrino opacities in neutron star matter, but the effects of the process in which the baryon transforms between nucleon and {delta} are unimportant.

  16. Tagging of Isobars Using Energy Loss and Time-of-flight Measurements

    SciTech Connect

    Shapira, D.

    2001-11-02

    The technique for tagging isobars in a mixed beam by measuring energy loss by time-of-flight has been tested. With this method, isobar separation should improve by allowing more energy loss (thicker absorber), but only if one can control absorber homogeneity. Measurements of beam energy toss and energy spread obtained under such conditions were shown to be close to predicted values using both collisional and charge exchange contributions to energy straggling. The calculation of energy straggling allows us to study the efficacy of this method for isobar separation when applied to different mass ranges and beam energies. Separation in a most difficult case, an analyzed beam of A = 132 isobars at energies near 3 MeV/A has been demonstrated. The time-of-flight information can be added on line as an additional tag to the data stream for events of interest. Such event by event tagging enables one to study the effect of differences in isobaric mixture in the beam on the reaction outcome even when isobar separation is not complete.

  17. Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects.

    PubMed

    Bortolozzi, A; Castañé, A; Semakova, J; Santana, N; Alvarado, G; Cortés, R; Ferrés-Coy, A; Fernández, G; Carmona, M C; Toth, M; Perales, J C; Montefeltro, A; Artigas, F

    2012-06-01

    Depression is a major health problem worldwide. Most prescribed anti-depressants, the selective serotonin reuptake inhibitors (SSRI) show limited efficacy and delayed onset of action, partly due to the activation of somatodendritic 5-HT(1A)-autoreceptors by the excess extracellular serotonin (5-HT) produced by SSRI in the raphe nuclei. Likewise, 5-HT(1A) receptor (5-HT(1A)R) gene polymorphisms leading to high 5-HT(1A)-autoreceptor expression increase depression susceptibility and decrease treatment response. In this study, we report on a new treatment strategy based on the administration of small-interfering RNA (siRNA) to acutely suppress 5-HT(1A)-autoreceptor-mediated negative feedback mechanisms. We developed a conjugated siRNA (C-1A-siRNA) by covalently binding siRNA targeting 5-HT(1A) receptor mRNA with the SSRI sertraline in order to concentrate it in serotonin axons, rich in serotonin transporter (SERT) sites. The intracerebroventricular (i.c.v.) infusion of C-1A-siRNA to mice resulted in its selective accumulation in serotonin neurons. This evoked marked anti-depressant-like effects in the forced swim and tail suspension tests, but did not affect anxiety-like behaviors in the elevated plus-maze. In parallel, C-1A-siRNA administration markedly decreased 5-HT(1A)-autoreceptor expression and suppressed 8-OH-DPAT-induced hypothermia (a pre-synaptic 5-HT(1A)R effect in mice) without affecting post-synaptic 5-HT(1A)R expression in hippocampus and prefrontal cortex. Moreover, i.c.v. C-1A-siRNA infusion augmented the increase in extracellular serotonin evoked by fluoxetine in prefrontal cortex to the level seen in 5-HT(1A)R knockout mice. Interestingly, intranasal C-1A-siRNA administration produced the same effects, thus opening the way to the therapeutic use of C-1A-siRNA. Hence, C-1A-siRNA represents a new approach to treat mood disorders as monotherapy or in combination with SSRI.

  18. Selection of genes associated with variations in the Circle of Willis in gerbils using suppression subtractive hybridization.

    PubMed

    Li, Zhenkun; Huo, Xueyun; Zhang, Shuangyue; Lu, Jing; Li, Changlong; Guo, Meng; Fu, Rui; He, Zhengming; Du, Xiaoyan; Chen, Zhenwen

    2015-01-01

    Deformities in the Circle of Willis (CoW) can significantly increase the risk of cerebrovascular disease in humans. However, the molecular mechanisms underlying these deformities have not been understood. Based on our previous studies, variations in the CoW of gerbils are hereditary. A normal CoW is observed in approximately 60% of gerbils, a percentage that also applies to humans. Thus, gerbil is an ideal experimental model for studying variations in the CoW. To study the mechanisms underlying these variations, we selected genes associated with different types of the CoW using suppression subtractive hybridization (SSH). After evaluating the efficiency of SSH using quantitative real-time polymerase chain reaction (qPCR) on subtracted and unsubtracted cDNA and Southern blotting on SSH PCR products, 12 SSH libraries were established. We identified 4 genes (CST3, GNAS, GPx4 and PFN2) associated with variations in the CoW. These genes were identified with qPCR and Western blotting using 70 expressed sequence tags from the SSH libraries. Cloning and sequencing allowed us to demonstrate that the 4 genes were closely related to mouse genes. We may assume that these 4 genes play an important role in the development of variations in the CoW. This study provides a foundation for further research of genes related to development of variations in the CoW and the mechanisms of dysmorphosis of cerebral vessels.

  19. A Triple Knockout (TKO) Proteomics Standard for Diagnosing Ion Interference in Isobaric Labeling Experiments

    NASA Astrophysics Data System (ADS)

    Paulo, Joao A.; O'Connell, Jeremy D.; Gygi, Steven P.

    2016-10-01

    Isobaric labeling is a powerful strategy for quantitative mass spectrometry-based proteomic investigations. A complication of such analyses has been the co-isolation of multiple analytes of similar mass-to-charge resulting in the distortion of relative protein abundance measurements across samples. When properly implemented, synchronous precursor selection and triple-stage mass spectrometry (SPS-MS3) can reduce the occurrence of this phenomenon, referred to as ion interference. However, no diagnostic tool is available currently to rapidly and accurately assess ion interference. To address this need, we developed a multiplexed tandem mass tag (TMT)-based standard, termed the triple knockout (TKO). This standard is comprised of three yeast proteomes in triplicate, each from a strain deficient in a highly abundant protein (Met6, Pfk2, or Ura2). The relative abundance patterns of these proteins, which can be inferred from dozens of peptide measurements can demonstrate ion interference in peptide quantification. We expect no signal in channels where the protein is knocked out, permitting maximum sensitivity for measurements of ion interference against a null background. Here, we emphasize the need to investigate further ion interference-generated ratio distortion and promote the TKO standard as a tool to investigate such issues.

  20. Acute Aortic Dissection Biomarkers Identified Using Isobaric Tags for Relative and Absolute Quantitation

    PubMed Central

    Xiao, Ziya; Xue, Yuan; Gu, Guorong; Zhang, Yaping; Zhang, Jin; Fan, Fan; Luan, Xiao; Deng, Zhi; Tao, Zhengang; Song, Zhen-ju; Tong, Chaoyang; Wang, Haojun

    2016-01-01

    The purpose of this study was to evaluate the utility of potential serum biomarkers for acute aortic dissection (AAD) that were identified by isobaric Tags for Relative and Absolute Quantitation (iTRAQ) approaches. Serum samples from 20 AAD patients and 20 healthy volunteers were analyzed using iTRAQ technology. Protein validation was performed using samples from 120 patients with chest pain. A total of 355 proteins were identified with the iTRAQ approach; 164 proteins reached the strict quantitative standard, and 125 proteins were increased or decreased more than 1.2-fold (64 and 61 proteins were up- and downregulated, resp.). Lumican, C-reactive protein (CRP), thrombospondin-1 (TSP-1), and D-dimer were selected as candidate biomarkers for the validation tests. Receiver operating characteristic (ROC) curves show that Lumican and D-dimer have diagnostic value (area under the curves [AUCs] 0.895 and 0.891, P < 0.05). For Lumican, the diagnostic sensitivity and specificity were 73.33% and 98.33%, while the corresponding values for D-dimer were 93.33% and 68.33%. For Lumican and D-dimer AAD combined diagnosis, the sensitivity and specificity were 88.33% and 95%, respectively. In conclusion, Lumican has good specificity and D-dimer has good sensitivity for the diagnosis of AAD, while the combined detection of D-dimer and Lumican has better diagnostic value. PMID:27403433

  1. Atrial-selective Inhibition of Sodium Channel Current by Wenxin Keli is Effective in Suppressing Atrial Fibrillation

    PubMed Central

    Burashnikov, Alexander; Petroski, Alyssa; Hu, Dan; Barajas-Martinez, Hector; Antzelevitch, Charles

    2011-01-01

    BACKGROUND Wenxin Keli is a Chinese herb extract reported to be of benefit in the treatment of cardiac arrhythmias, cardiac inflammation and heart failure. METHODS AND RESULTS We evaluated the electrophysiologic effects of Wenxin Keli in isolated canine arterially-perfused right atrial preparations with a rim of right ventricular tissue (n=11). Transmembrane action potentials and a pseudo-electrocardiogram were simultaneously recorded. Acetylcholine (ACh, 1 μM) was used to induce atrial fibrillation (AF) and to test the anti-AF potential of Wenxin Keli (5 g/L). Wenxin Keli produced preferential abbreviation of action potential duration (APD90) in atria, but caused atrial-selective prolongation of effective refractory period, due to development of post-repolarization refractoriness. The maximum rate of rise of the action potential upstroke (Vmax) was preferentially reduced in atria. Diastolic threshold of excitation increased in both atria and ventricles, but much more in atria. The duration of the “P wave” (index of atrial conduction time) was prolonged to a much greater extent than the duration of the “QRS complex” (index of ventricular conduction time). Wenxin Keli significantly reduced INa and shifted steady-state inactivation to more negative potentials in HEK293 cells stably expressing SCN5A. Wenxin Keli prevented induction of persistent AF in 100% atria (6/6) and, in another experimental series was found to terminate persistent ACh-mediated AF in 100% of atria (3/3). CONCLUSION Wenxin Keli produces atrial-selective depression of INa-dependent parameters in canine isolated coronary perfused preparations via a unique mechanism and is effective in suppressing AF and preventing its induction, with minimal effects on ventricular electrophysiology. PMID:21884675

  2. Tigecycline-Amikacin Combination Effectively Suppresses the Selection of Resistance in Clinical Isolates of KPC-Producing Klebsiella pneumoniae

    PubMed Central

    Ni, Wentao; Wei, Chuanqi; Zhou, Chufei; Zhao, Jin; Liang, Beibei; Cui, Junchang; Wang, Rui; Liu, Youning

    2016-01-01

    By far, only tigecycline, colistin, and some aminoglycosides still show favorable in vitro activities against carbapenem-resistant Enterobacteriaceae. However, rapid emergence of resistance often occurs during long-term treatment in clinic, challenging these last resort antimicrobials. In this study, we measured mutant prevention concentration (MPC) and mutant selection window (MSW) of tigecycline, colistin and amikacin alone and in combination for clinical isolates of KPC-producing K. pneumoniae, and characterized the resistant mutants recovered. The MPC90 of 30 tested isolates for tigecycline, colistin, and amikacin were 16, >128, and 128 mg/L, respectively. The average MSW of tigecycline-amikacin, tigecycline-colistin, and amikacin-colistin combinations for four representative strains were 11.99, 200.13, and 372.38, respectively. A strong correlation was found between the MSWcombination and the product of MSW of each single drug. Combinations of 1 minimal inhibitory concentration (MIC) multiple tigecycline and 1 MIC multiple amikacin could result in 1000- to 10000-fold reduction in mutational frequency relative to their individual mutational frequencies, and combinations of 1 MIC multiple amikacin and 1.5–2 MIC multiple tigecycline could successfully restrict the recovery of resistant mutants on agar plates. However, 2 MIC multiple colistin in combination with 2 MIC multiple tigecycline or amikacin merely resulted in approximately 10-fold decrease in the mutational frequency. In conclusion, this study showed tigecycline-amikacin combination could effectively suppress the selection of resistance at low concentrations compared with the colistin-tigecycline and colistin-amikacin combinations, suggesting that this combination may be useful in clinical therapy. PMID:27594855

  3. Tigecycline-Amikacin Combination Effectively Suppresses the Selection of Resistance in Clinical Isolates of KPC-Producing Klebsiella pneumoniae.

    PubMed

    Ni, Wentao; Wei, Chuanqi; Zhou, Chufei; Zhao, Jin; Liang, Beibei; Cui, Junchang; Wang, Rui; Liu, Youning

    2016-01-01

    By far, only tigecycline, colistin, and some aminoglycosides still show favorable in vitro activities against carbapenem-resistant Enterobacteriaceae. However, rapid emergence of resistance often occurs during long-term treatment in clinic, challenging these last resort antimicrobials. In this study, we measured mutant prevention concentration (MPC) and mutant selection window (MSW) of tigecycline, colistin and amikacin alone and in combination for clinical isolates of KPC-producing K. pneumoniae, and characterized the resistant mutants recovered. The MPC90 of 30 tested isolates for tigecycline, colistin, and amikacin were 16, >128, and 128 mg/L, respectively. The average MSW of tigecycline-amikacin, tigecycline-colistin, and amikacin-colistin combinations for four representative strains were 11.99, 200.13, and 372.38, respectively. A strong correlation was found between the MSW combination and the product of MSW of each single drug. Combinations of 1 minimal inhibitory concentration (MIC) multiple tigecycline and 1 MIC multiple amikacin could result in 1000- to 10000-fold reduction in mutational frequency relative to their individual mutational frequencies, and combinations of 1 MIC multiple amikacin and 1.5-2 MIC multiple tigecycline could successfully restrict the recovery of resistant mutants on agar plates. However, 2 MIC multiple colistin in combination with 2 MIC multiple tigecycline or amikacin merely resulted in approximately 10-fold decrease in the mutational frequency. In conclusion, this study showed tigecycline-amikacin combination could effectively suppress the selection of resistance at low concentrations compared with the colistin-tigecycline and colistin-amikacin combinations, suggesting that this combination may be useful in clinical therapy.

  4. Delta. sub 33 -isobar contribution to the soft nucleon-nucleon potentials. I. 2. pi. -exchange potentials

    SciTech Connect

    Rijken, T.A.; Stoks, V.G.J. )

    1992-07-01

    Two-pion-exchange (TPE) nucleon-nucleon potentials are derived for one or two {Delta} isobars in the intermediate states. Strong dynamical pair suppression is assumed. At the {ital NN}{pi} and the {ital N}{Delta}{pi} vertices Gaussian form factors are incorporated into the relativistic two-body framework by using a dispersion representation for the one-pion-exchange amplitudes. The Fourier transformations are performed using factorization techniques for the energy denominators, taking into account the mass difference between the nucleon and the {Delta} isobar. Analytic expressions for the TPE potentials are obtained, which contain at most one-dimensional integrals. The TPE potentials are first calculated up to orders ({ital f}{sub {ital N}{ital N}{pi}} f{sub {ital N}{Delta}{pi}}){sup 2} and {ital f}{sub {ital N}{Delta}{pi}}{sup 4}. These come from the adiabatic contributions of all planar and crossed three-dimensional momentum-space TPE diagrams. We also give the contributions of the OPE iteration, which can be subtracted or not, depending on whether one performs a coupled-channel calculation for, e.g., the {ital NN}, {ital N}{Delta} system, or a single {ital NN}-channel calculation. Next, we calculate the ({ital m}{sub {pi}}/{ital M}) corrections. These are due to the 1/{ital M} terms in the pion-nucleon vertices, and the 1/{ital M} terms in the nonadiabatic expansion of the nucleon energies in the intermediate states.

  5. Periodicity of monoisotopic mass isomers and isobars in proteomics.

    PubMed

    Yu, Long; Xiong, Yan-Mei; Polfer, Nick C

    2011-10-15

    We report trends in the theoretically derived number of compositionally distinct peptides (i.e., peptides made up of different amino acid residues) up to a nominal mass of 1000. A total of 21 amino acid residues commonly found in proteomics studies are included in this study, 19 natural, nonisomeric amino acid residues as well as oxidated methione and acetamidated cysteine. The number of possibilities is found to increase in an exponential fashion with increasing nominal mass, and the data show a periodic oscillation that starts at mass ~200 and continues throughout to 1000. Note that similar effects are reported in the companion article on fragment ions from electron capture/transfer dissociation (ECD/ETD) (Mao et al. Anal. Chem.2011, DOI: 10.1021/ac201619t). The spacing of this oscillation is ~15 mass units at lower masses and ~14 mass units at higher nominal masses. This correlates with the most common mass differences between the amino acid building blocks. In other words, some mass differences are more common than others, thus determining the periodicity in this data. From an analytical point of view, nominal masses with a larger number of compositionally distinct peptides include a substantial number of isomers, which cannot be separated based on mass. Consequently, even ultrahigh mass accuracy (i.e., 0.5 ppm) does not lead to a substantially enhanced rate of identification. Conversely, for adjacent nominal masses with a lower number of isomers, moderately accurate mass (i.e., 10 ppm) gives a higher degree of certainty in identification. These effects are limited to the mass range between 200 and 500 Da. At higher masses, the percentage of uniquely identified peptides drops off to close to zero, independent of nominal mass, due the inherently high number of isomers. While the exact number of isobars/isomers at each nominal mass depends on the amino acid building blocks that are considered, the periodicity in the data is found to be remarkably robust; for

  6. The significance of monoisotopic and carbon-13 isobars for the identification of a 19-component dodecapeptide library by positive ion electrospray Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Ramjit, H G; Kruppa, G H; Spier, J P; Ross, C W; Garsky, V M

    2000-01-01

    Harnessing the ultra high resolution capabilities of Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and positive ion electrospray, we have demonstrated the significance and utility of cumulative mass defect high resolution mass separation stable isotope distribution, exact mass measurement and elemental formula as a means of simultaneously identifying 19 components of the dodecapeptide library Ac-ANKISYQS[X]STE-NH(2). With an instrument resolution of 275 000 (average), isobaric multiplets attributed to monoisotopic and carbon-13 components of peptides: Ac approximately SLS approximately NH(2); Ac approximately SNS approximately NH(2); Ac approximately SOS approximately NH(2); Ac approximately SDS approximately NH(2); within the mass window of 1380-1385 Da, and Ac approximately SQS approximately NH(2); Ac approximately SKS approximately NH(2); Ac approximately SES approximately NH(2); Ac approximately SMS approximately NH(2), within the mass window 1395-1400 Da, were mass resolved, accurately mass measured and identified from the computed molecular formulas. This experimental procedure enabled the separation of monoisotopic and carbon-13 isobars yielding enhanced selectivity and specificity and serves to illustrate the significance of monoisotopic and carbon-13 isobars in final product analysis. Chromatographic separation (HPLC) was of limited utility except for monitoring the overall extent of reaction and apparent product distribution. Positive ion electrospray-FTICR-MS and fast atom bombardment (FAB) MS were used to assess final product quality and apparent component distribution.

  7. Spectroscopy of the neutron-deficient isobars {sup 163}Re and {sup 163}W using tagging techniques

    SciTech Connect

    Joss, D. T.; Thomson, J.; Page, R. D.; Bianco, L.; Darby, I. G.; Grahn, T.; Pakarinen, J.; Paul, E. S.; Scholey, C.; Eeckhaudt, S.; Greenlees, P. T.; Jones, P. M.; Julin, R.; Juutinen, S.; Ketelhut, S.; Leino, M.; Leppaennen, A.-P.; Nyman, M.; Rahkila, P.; Sorri, J.

    2008-11-11

    Selective tagging techniques have been used to establish new band structures in the transitional isobars {sup 163}Re and {sup 163}W. These nuclei were produced in the {sup 106}Cd({sup 60}Ni, xp yn {gamma}) reaction at a bombarding energy of 270 MeV. Prompt {gamma} rays were detected at the target position using the JUROGAM spectrometer while recoiling ions were separated by the RITU separator and implanted into the GREAT spectrometer. At low spin, the yrast band of {sup 163}Re is shown to be a strongly coupled collective band based on a proton h{sub 11/2} configuration. In {sup 163}W, the decay path of the 13/2{sup +} isomeric state to the ground state has been identified and negative parity structures based on the ground state established.

  8. The role of iterative isobar processes in nuclear matter and the effective nucleon-nucleon interaction

    NASA Astrophysics Data System (ADS)

    Dey, J.; Samanta, B. C.; Dey, M.

    1980-09-01

    A calculation is performed using lowest order Brueckner theory in momentum space, with explicit isobar configurations included through the coupled channel mathod. The effective interaction for the1 S 0-5 D 0 channel is extracted from this calculation. Two different transition potentials are used — one due to Green and Niskanen (1976), the other, due to Green and co-workers (1978). The nucleon-nucleon (NN) interaction used is the Reid soft core potential, compensated for the inclusion of the explicit isobar channel. The effective interaction shows marked momentum dependence in the intermediate range. The loss of attraction depends on the transition potential one chooses. The correlation function involving the nucleon-isobar intermediate state is anti-correlated to the NN part.

  9. Covariant and self-consistent vertex corrections for pions and isobars in nuclear matter

    SciTech Connect

    Korpa, C. L.; Lutz, M. F. M.; Riek, F.

    2009-08-15

    We evaluate the pion and isobar propagators in cold nuclear matter self-consistently applying a covariant form of the isobar-hole model. Migdal's vertex correction effects are considered systematically in the absence of phenomenological soft form factors. Saturated nuclear matter is modeled by scalar and vector mean fields for the nucleon. It is shown that the short-range dressing of the {pi}N{delta} vertex has a significant effect on the pion and isobar properties. Using realistic parameters sets we predict a downward shift of about 50 MeV for the {delta} resonance at nuclear saturation density. The pionic soft modes are much less pronounced than in previous studies.

  10. Gas-phase purification enables accurate, large-scale, multiplexed proteome quantification with isobaric tagging

    PubMed Central

    Wenger, Craig D; Lee, M Violet; Hebert, Alexander S; McAlister, Graeme C; Phanstiel, Douglas H; Westphall, Michael S; Coon, Joshua J

    2011-01-01

    We describe a mass spectrometry method, QuantMode, which improves the accuracy of isobaric tag–based quantification by alleviating the pervasive problem of precursor interference—co-isolation of impurities—through gas-phase purification. QuantMode analysis of a yeast sample ‘contaminated’ with interfering human peptides showed substantially improved quantitative accuracy compared to a standard scan, with a small loss of spectral identifications. This technique will allow large-scale, multiplexed quantitative proteomics analyses using isobaric tagging. PMID:21963608

  11. Isobaric expansion coefficient and isothermal compressibility for a finite-size ideal Fermi gas system

    NASA Astrophysics Data System (ADS)

    Su, Guozhen; Chen, Liwei; Chen, Jincan

    2014-06-01

    Due to quantum size effects (QSEs), the isobaric thermal expansion coefficient and isothermal compressibility well defined for macroscopic systems are invalid for finite-size systems. The two parameters are redefined and calculated for a finite-size ideal Fermi gas confined in a rectangular container. It is found that the isobaric thermal expansion coefficient and isothermal compressibility are generally anisotropic, i.e., they are generally different in different directions. Moreover, it is found the thermal expansion coefficient may be negative in some directions under the condition that the pressures in all directions are kept constant.

  12. A sensitive dual-fluorescence reporter system enables positive selection of ras suppressors by suppression of ras-induced apoptosis.

    PubMed

    Dolnikov, Alla; Shen, Sylvie; Millington, Michelle; Passioura, Toby; Pedler, Michelle; Rasko, John Edward Joshua; Symonds, Geoff

    2003-10-01

    We have developed a novel dual-fluorescence reporter system incorporating green (GFP) and red (RFP) fluorescent proteins to monitor expression of the N-ras(m) gene and an N-ras(m) suppressor, respectively. Retroviral vectors were produced in which human N-ras(m) (codon 13 mutation) was coexpressed with GFP, and a ribozyme specifically targeting N-ras(m) was coexpressed with RFP. N-Ras(m) suppression was monitored by measurement of GFP fluorescence in dual-fluorescent (GFP and RFP) cells. We demonstrated that the degree of N-ras(m) suppression was dependent on the ribozyme dose, proportional to red fluorescence, in dual-fluorescent cells. We further showed that ribozyme-mediated N-ras(m)suppression inhibited growth of NIH3T3 and CD34-positive TF-1 cells. In these cultures, ras suppressor activity resulted in the depletion of suppressor-positive cells due to inhibition of cell growth. In contrast, N-ras(m) suppression produced a growth advantage to human leukemic K562 cells, presumably by inhibiting N-ras(m)-induced apoptosis. In K562 cells, ras suppression resulted in the outgrowth of suppressor-positive cells. This provides a platform to identify suppressors of ras that is based on function.

  13. Quantitation of isobaric phosphatidylcholine species in human plasma using a hybrid quadrupole linear ion trap mass spectrometer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phosphatidylcholine (PC) species in human plasma are used as biomarkers of disease. PC biomarkers are often limited by the inability to separate isobaric PC. In this work, we developed a targeted shotgun approach for analysis of isobaric and isomeric PC. This approach is comprised of two mass spectr...

  14. Proteomic Identification and Quantification of S-glutathionylation in Mouse Macrophages Using Resin-Assisted Enrichment and Isobaric Labeling

    PubMed Central

    Su, Dian; Gaffrey, Matthew J.; Guo, Jia; Hatchell, Kayla E.; Chu, Rosalie K.; Clauss, Therese R. W.; Aldrich, Joshua T.; Wu, Si; Purvine, Sam; Camp, David G.; Smith, Richard D.; Thrall, Brian D.; Qian, Wei-Jun

    2014-01-01

    S-glutathionylation (SSG) is an important regulatory posttranslational modification on protein cysteine (Cys) thiols, yet the role of specific cysteine residues as targets of modification is poorly understood. We report a novel quantitative mass spectrometry (MS)-based proteomic method for site-specific identification and quantification of S-glutathionylation across different conditions. Briefly, this approach consists of initial blocking of free thiols by alkylation, selective reduction of glutathionylated thiols and covalent capture of reduced thiols using thiol affinity resins, followed by on-resin tryptic digestion and isobaric labeling with iTRAQ (isobaric tags for relative and absolute quantitation) for MS-based identification and quantification. The overall approach was initially validated by application to RAW 264.7 mouse macrophages treated with different doses of diamide to induce glutathionylation. A total of 1071 Cys-sites from 690 proteins were identified in response to diamide treatment, with ~90% of the sites displaying >2-fold increases in SSG-modification compared to controls. This approach was extended to identify potential SSG- modified Cys-sites in response to H2O2, an endogenous oxidant produced by activated macrophages and many pathophysiological stimuli. The results revealed 364 Cys-sites from 265 proteins that were sensitive to S-glutathionylation in response to H2O2 treatment, thus providing a database of proteins and Cys-sites susceptible to this modification under oxidative stress. Functional analysis revealed that the most significantly enriched molecular function categories for proteins sensitive to SSG modifications were free radical scavenging and cell death/survival. Overall the results demonstrate that our approach is effective for site-specific identification and quantification of SSG-modified proteins. The analytical strategy also provides a unique approach to determining the major pathways and cellular processes most susceptible

  15. Proteomic Identification and Quantification of S-glutathionylation in Mouse Macrophages Using Resin-Assisted Enrichment and Isobaric Labeling

    SciTech Connect

    Su, Dian; Gaffrey, Matthew J.; Guo, Jia; Hatchell, Kayla E.; Chu, Rosalie K.; Clauss, Therese RW; Aldrich, Joshua T.; Wu, Si; Purvine, Samuel O.; Camp, David G.; Smith, Richard D.; Thrall, Brian D.; Qian, Weijun

    2014-02-11

    Protein S-glutathionylation (SSG) is an important regulatory posttranslational modification of protein cysteine (Cys) thiol redox switches, yet the role of specific cysteine residues as targets of modification is poorly understood. We report a novel quantitative mass spectrometry (MS)-based proteomic method for site-specific identification and quantification of S-glutathionylation across different conditions. Briefly, this approach consists of initial blocking of free thiols by alkylation, selective reduction of glutathionylated thiols and enrichment using thiol affinity resins, followed by on-resin tryptic digestion and isobaric labeling with iTRAQ (isobaric tags for relative and absolute quantitation) for MS-based identification and quantification. The overall approach was validated by application to RAW 264.7 mouse macrophages treated with different doses of diamide to induce glutathionylation. A total of 1071 Cys-sites from 690 proteins were identified in response to diamide treatment, with ~90% of the sites displaying >2-fold increases in SSG-modification compared to controls.. This approach was extended to identify potential SSG modified Cys-sites in response to H2O2, an endogenous oxidant produced by activated macrophages and many pathophysiological stimuli. The results revealed 364 Cys-sites from 265 proteins that were sensitive to S-glutathionylation in response to H2O2 treatment. These proteins covered a range of molecular types and molecular functions with free radical scavenging, and cell death and survival included as the most significantly enriched functional categories. Overall the results demonstrate that our approach is effective for site-specific identification and quantification of S-glutathionylated proteins. The analytical strategy also provides a unique approach to determining the major pathways and cell processes most susceptible to glutathionylation at a proteome-wide scale.

  16. Selective suppression of the human aryl hydrocarbon receptor function can be mediated through binding interference at the C-terminal half of the receptor.

    PubMed

    Ren, Lina; Thompson, John D; Cheung, Michael; Ngo, Katherine; Sung, Sarah; Leong, Scott; Chan, William K

    2016-05-01

    The human aryl hydrocarbon receptor is a cytosolic signaling molecule which affects immune response and aberrant cell growth. Canonical signaling of the receptor requires the recruitment of coactivators to the promoter region to remodel local chromatin structure. We predicted that interference of this recruitment would block the aryl hydrocarbon receptor function. To prove that, we employed phage display to identify nine peptides of twelve-amino-acid in length which target the C-terminal half of the human aryl hydrocarbon receptor, including the region where coactivators bind. Eight 12mer peptides, in the form of GFP fusion, suppressed the ligand-dependent transcription of six AHR target genes (cyp1a1, cyp1a2, cyp1b1, ugt1a1, nqo1, and ahrr) in different patterns in Hep3B cells, whereas the AHR antagonist CH-223191 suppressed all these target genes similarly. Three of the 12mer peptides (namely 11-3, 1-7, and 7-3) suppressed the 3MC-induced, CYP1A1-dependent EROD activity and the ROS production caused by benzo[a]pyrene. These 12mer peptides suppressed the AHR function synergistically with CH-223191. In conclusion, we provide evidence that targeting the C-terminal half of the human aryl hydrocarbon receptor is a viable, new approach to selectively block the receptor function.

  17. Residue Coulomb Interaction Among Isobars and Its Influence in Symmetry Energy of Neutron-Rich Fragment

    NASA Astrophysics Data System (ADS)

    Ma, Chun-Wang; Wang, Shan-Shan; Zhang, Yan-Li; Zhao, Yi-Long; Wei, Hui-Ling

    2015-09-01

    The residue Coulomb interaction (RCI), which affects the result of symmetry-energy coefficient of neutron-rich nucleus in isobaric yield ratio (IYR) method, is difficult to be determined. Four RCI approximations are investigated: (i) The M1-RCI adopting the ac/T (the ratio of Coulomb energy coefficient to temperature) determined from the IYR of mirror-nucleus fragments; (ii) The M2-RCI by fitting the difference between IYRs; (iii) The M3-RCI adopting the standard Coulomb energy at a temperature T = 2 MeV; and (iv) Neglecting the RCI among isobars. The M1-, M2- and M3-RCI are no larger than 0.4. In particular, the M2-RCI is very close to zero. The effects of RCI in asym/T of fragment are also studied. The M1- and M4-asym/T are found to be the lower and upper limitations of asym/T, respectively. The M2-asym/T overlaps the M4-asym/T, which indicates that the M2-RCI is negligible in the IYR method, and the RCI among the three isobars can be neglected. The relative consistent low values of M3-asym/T (7.5 ± 2.5) are found in very neutron-rich isobars. Supported by the Program for Science & Technology Innovation Talents in Universities of Henan Province (13HASTIT046), and Young Teacher Project in Henan Normal University (HNU), China

  18. MilQuant: a free, generic software tool for isobaric tagging-based quantitation.

    PubMed

    Zou, Xiao; Zhao, Minzhi; Shen, Hongyan; Zhao, Xuyang; Tong, Yuanpeng; Wang, Qingsong; Wei, Shicheng; Ji, Jianguo

    2012-09-18

    Isobaric tagging techniques such as iTRAQ and TMT are widely used in quantitative proteomics and especially useful for samples that demand in vitro labeling. Due to diversity in choices of MS acquisition approaches, identification algorithms, and relative abundance deduction strategies, researchers are faced with a plethora of possibilities when it comes to data analysis. However, the lack of generic and flexible software tool often makes it cumbersome for researchers to perform the analysis entirely as desired. In this paper, we present MilQuant, mzXML-based isobaric labeling quantitator, a pipeline of freely available programs that supports native acquisition files produced by all mass spectrometer types and collection approaches currently used in isobaric tagging based MS data collection. Moreover, aside from effective normalization and abundance ratio deduction algorithms, MilQuant exports various intermediate results along each step of the pipeline, making it easy for researchers to customize the analysis. The functionality of MilQuant was demonstrated by four distinct datasets from different laboratories. The compatibility and extendibility of MilQuant makes it a generic and flexible tool that can serve as a full solution to data analysis of isobaric tagging-based quantitation.

  19. Strategies for differentiation of isobaric flavonoids using liquid chromatography coupled to electrospray ionization mass spectrometry.

    PubMed

    Fridén, Mikael E; Sjöberg, Per J R

    2014-07-01

    Flavonoids are a class of secondary plant metabolites existing in great variety in nature. Due to this variety, identification can be difficult, especially as overlapping compounds in both chromatographic separations and mass spectrometric detection are common. Methods for distinguishing isobaric flavonoids using MS(2) and MS(3) have been developed. Chromatographic separation of various plant extracts was done with RP-HPLC and detected with positive ESI-MS operated in information-dependent acquisition (IDA) mode. Two methods for the determination of flavonoid identity and substitution pattern, both featuring IDA criteria, were used together with the HPLC equipment. A third method where the collision energy was ramped utilized direct infusion. With the developed strategies, it is possible to differentiate between many isobaric flavonoids. Various classes of flavonoids were found in all of the plant extracts, in the red onion extract 45 components were detected and for 29 of them the aglycone was characterized, while the substituents were tentatively identified for 31 of them. For the strawberry extract, those numbers were 66, 30 and 60, and for the cherry extract 99, 56 and 71. The great variety of flavonoids, several of them isobaric, found in each of the extracts highlights the need for reliable methods for flavonoid characterization. Methods capable of differentiating between most of the isobars analyzed have been developed.

  20. Tandem mass spectrometric analysis of a mixture of isobars using the survival yield technique.

    PubMed

    Memboeuf, Antony; Jullien, Laure; Lartia, Rémy; Brasme, Bernard; Gimbert, Yves

    2011-10-01

    Collision induced dissociation tandem mass spectrometry experiments were performed to unequivocally separate compounds from an isobaric mixture of two products. The Survival Yield curve was obtained and is shown to consist in a linear combination of the curves corresponding to the two components separately. For such a mixture, a plateau appears on the diagram in lieu of the continuous decrease expected allowing for the structural study of the two components separately. The width of the plateau critically relates to the fragmentation parameters of the two molecular ions, which need to be sufficiently different structurally for the plateau to be observed. However, at constant fragmentation parameters, we have observed the width significantly increases at large m/z. This makes the separation more and more efficient as isobars have larger m/z and the technique complementary to those applicable at low m/z only. We have observed that the vertical position of the plateau relates linearly to the relative concentration of the two compounds that may be useful for quantification. Repeatability was estimated at 2% on a quadrupole ion trap. An advantage of using survival yield curves only, is that a priori knowledge of the respective fragmentation patterns of the two isobars becomes unnecessary. Consequently, similar performances are obtained if fragments are isobaric, which is also demonstrated in our study. The critical case of reverse peptides, at low m/z and similar fragmentation parameters, is also presented as a limitation of the method.

  1. Formation of isobaric discontinuities in large-scale flute drift motions

    SciTech Connect

    Dreizin, Y.A.; Sokolov, E.P.

    1982-05-01

    The flute drift motion in MHD-stable plasma configurations with closed lines of force is analyzed qualitatively. The onset of this motion can lead to isobaric discontinuities in experimentally observable quantitites: the electric potential and the electron and ion densities and temperatures.

  2. The use of a selective saturation pulse to suppress t1 noise in two-dimensional 1H fast magic angle spinning solid-state NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Robertson, Aiden J.; Pandey, Manoj Kumar; Marsh, Andrew; Nishiyama, Yusuke; Brown, Steven P.

    2015-11-01

    A selective saturation pulse at fast magic angle spinning (MAS) frequencies (60+ kHz) suppresses t1 noise in the indirect dimension of two-dimensional 1H MAS NMR spectra. The method is applied to a synthetic nucleoside with an intense methyl 1H signal due to triisopropylsilyl (TIPS) protecting groups. Enhanced performance in terms of suppressing the methyl signal while minimising the loss of signal intensity of nearby resonances of interest relies on reducing spin diffusion - this is quantified by comparing two-dimensional 1H NOESY-like spin diffusion spectra recorded at 30-70 kHz MAS. For a saturation pulse centred at the methyl resonance, the effect of changing the nutation frequency at different MAS frequencies as well as the effect of changing the pulse duration is investigated. By applying a pulse of duration 30 ms and nutation frequency 725 Hz at 70 kHz MAS, a good compromise of significant suppression of the methyl resonance combined with the signal intensity of resonances greater than 5 ppm away from the methyl resonance being largely unaffected is achieved. The effectiveness of using a selective saturation pulse is demonstrated for both homonuclear 1H-1H double quantum (DQ)/single quantum (SQ) MAS and 14N-1H heteronuclear multiple quantum coherence (HMQC) two-dimensional solid-state NMR experiments.

  3. The use of a selective saturation pulse to suppress t1 noise in two-dimensional (1)H fast magic angle spinning solid-state NMR spectroscopy.

    PubMed

    Robertson, Aiden J; Pandey, Manoj Kumar; Marsh, Andrew; Nishiyama, Yusuke; Brown, Steven P

    2015-11-01

    A selective saturation pulse at fast magic angle spinning (MAS) frequencies (60+kHz) suppresses t1 noise in the indirect dimension of two-dimensional (1)H MAS NMR spectra. The method is applied to a synthetic nucleoside with an intense methyl (1)H signal due to triisopropylsilyl (TIPS) protecting groups. Enhanced performance in terms of suppressing the methyl signal while minimising the loss of signal intensity of nearby resonances of interest relies on reducing spin diffusion--this is quantified by comparing two-dimensional (1)H NOESY-like spin diffusion spectra recorded at 30-70 kHz MAS. For a saturation pulse centred at the methyl resonance, the effect of changing the nutation frequency at different MAS frequencies as well as the effect of changing the pulse duration is investigated. By applying a pulse of duration 30 ms and nutation frequency 725 Hz at 70 kHz MAS, a good compromise of significant suppression of the methyl resonance combined with the signal intensity of resonances greater than 5 ppm away from the methyl resonance being largely unaffected is achieved. The effectiveness of using a selective saturation pulse is demonstrated for both homonuclear (1)H-(1)H double quantum (DQ)/single quantum (SQ) MAS and (14)N-(1)H heteronuclear multiple quantum coherence (HMQC) two-dimensional solid-state NMR experiments.

  4. Nuclear matter properties from local chiral interactions with Δ isobar intermediate states

    NASA Astrophysics Data System (ADS)

    Logoteta, Domenico; Bombaci, Ignazio; Kievsky, Alejandro

    2016-12-01

    Using two-nucleon and three-nucleon interactions derived in the framework of chiral perturbation theory (ChPT) with and without the explicit Δ isobar contributions, we calculate the energy per particle of symmetric nuclear matter and pure neutron matter in the framework of the microscopic Brueckner-Hartree-Fock approach. In particular, we present for the first time nuclear matter calculations using the new fully local in coordinate-space two-nucleon interaction at the next-to-next-to-next-to-leading-order (N3LO) of ChPT with Δ isobar intermediate states (N 3 LO Δ ) recently developed by Piarulli et al. [arXiv:1606.06335]. We find that using this N 3 LO Δ potential, supplemented with a local N2LO three-nucleon interaction with explicit Δ isobar degrees of freedom, it is possible to obtain a satisfactory saturation point of symmetric nuclear matter. For this combination of two- and three-nucleon interactions we also calculate the nuclear symmetry energy and we compare our results with the empirical constraints on this quantity obtained using the excitation energies to isobaric analog states in nuclei and using experimental data on the neutron skin thickness of heavy nuclei, finding a very good agreement in all the considered nucleonic density range. In addition, we find that the explicit inclusion of Δ isobars diminishes the strength of the three-nucleon interactions needed to get a good saturation point of symmetric nuclear matter. We also compare the results of our calculations with those obtained by other research groups using chiral nuclear interactions with different many-body methods, finding in many cases a very satisfactory agreement.

  5. Identification of isobaric product ions in electrospray ionization mass spectra of fentanyl using multistage mass spectrometry and deuterium labeling.

    PubMed

    Wichitnithad, Wisut; McManus, Terence J; Callery, Patrick S

    2010-09-15

    Isobaric product ions cannot be differentiated by exact mass determinations, although in some cases deuterium labeling can provide useful structural information for identifying isobaric ions. Proposed fragmentation pathways of fentanyl were investigated by electrospray ionization ion trap mass spectrometry coupled with deuterium labeling experiments and spectra of regiospecific deuterium labeled analogs. The major product ion of fentanyl under tandem mass spectrometry (MS/MS) conditions (m/z 188) was accounted for by a neutral loss of N-phenylpropanamide. 1-(2-Phenylethyl)-1,2,3,6-tetrahydropyridine (1) was proposed as the structure of the product ion. However, further fragmentation (MS(3)) of the fentanyl m/z 188 ion gave product ions that were different from the product ion in the MS/MS fragmentation of synthesized 1, suggesting that the m/z 188 product ion from fentanyl includes an isobaric structure different from the structure of 1. MS/MS fragmentation of fentanyl in deuterium oxide moved one of the isobars to 1 Da higher mass, and left the other isobar unchanged in mass. Multistage mass spectral data from deuterium-labeled proposed isobaric structures provided support for two fragmentation pathways. The results illustrate the utility of multistage mass spectrometry and deuterium labeling in structural assignment of isobaric product ions.

  6. Orbital-selective singlet dimer formation and suppression of double exchange in 4d and 5d systems

    NASA Astrophysics Data System (ADS)

    Streltsov, Sergey; Cao, Gang; Khomskii, Daniel

    One of the main mechanisms of ferromagnetic ordering in conducting materials is the double exchange (DE). It is usually supposed in DE model that the Hund's coupling JH is much larger than electron hopping t; in this case one stabilizes the state with maximum spin per pair of ions, which finally leads to ferromagnetism in bulk systems. We show that in the dimerized 4 d / 5 d transition metal oxides for which JH is reduced and t is in contrast enhanced, another situation is possible, when formation of the spin-singlets on delocalized orbitals is more favorable. This leads to suppression of the DE and to a strong decrease of the total spin. The model calculations using the dynamical mean-field theory show that this effect survives even in the extended systems, not only for dimers. Such a situation is realized, e.g., in Y5Mo2O12, CrO2 under pressure and in many other 4 d / 5 d based materials. Another mechanism, which may suppress DE and which is also typical for 4 d / 5 d compounds is the spin-orbit coupling (SOC). We show on the example of Ba5AlIr2O11, that in this system it is the combination of molecular-orbital formation and SOC that strongly decreases magnetic moment on Ir. Civil Research and Development Foundation via FSCX-14-61025-0.

  7. Revalidation of the isobaric multiplet mass equation for the A=20 quintet

    DOE PAGES

    Glassman, B. E.; Pérez-Loureiro, D.; Wrede, C.; ...

    2015-10-29

    An unexpected breakdown of the isobaric multiplet mass equation in the A = 20, T = 2 quintet was recently reported, presenting a challenge to modern theories of nuclear structure. In the present work, the excitation energy of the lowest T = 2 state in Na-20 has been measured to be 6498.4 +/- 0.2stat ± 0.4syst keV by using the superallowed 0+ → 0+ beta decay of Mg-20 to access it and an array of high-purity germanium detectors to detect its gamma-ray deexcitation. This value differs by 27 keV (1.9 standard deviations) from the recommended value of 6525 ± 14more » keV and is a factor of 28 more precise. The isobaric multiplet mass equation is shown to be revalidated when the new value is adopted.« less

  8. Isobar model analysis of {pi}{sup 0{eta}} photoproduction on protons

    SciTech Connect

    Fix, A.; Lee, A.; Kashevarov, V. L.; Ostrick, M.

    2010-09-15

    Photoproduction of {pi}{sup 0{eta}} on protons in the energy range from threshold to 1.4 GeV is discussed. The data for representative angular distributions recently obtained at MAMI C are analyzed using an isobar model. The isobars considered are {Delta}(1232) and S{sub 11}(1535) for {pi}{sup 0}p and {eta}p states, respectively. In accordance with the results of earlier works, the main features of the reaction are explained through the dominance of the D{sub 33} wave with a relatively small admixture of positive parity resonances. Comparison with recent experimental results for the photon beam asymmetry is carried out.

  9. Isobars of an ideal Bose gas within the grand canonical ensemble

    SciTech Connect

    Jeon, Imtak; Park, Jeong-Hyuck; Kim, Sang-Woo

    2011-08-15

    We investigate the isobar of an ideal Bose gas confined in a cubic box within the grand canonical ensemble for a large yet finite number of particles, N. After solving the equation of the spinodal curve, we derive precise formulas for the supercooling and the superheating temperatures that reveal an N{sup -1/3} or N{sup -1/4} power correction to the known Bose-Einstein condensation temperature in the thermodynamic limit. Numerical computations confirm the accuracy of our analytical approximation, and further show that the isobar zigzags on the temperature-volume plane if N{>=}14 393. In particular, for the Avogadro's number of particles, the volume expands discretely about 10{sup 5} times. Our results quantitatively agree with a previous study on the canonical ensemble within 0.1% error.

  10. Isobars of an ideal Bose gas within the grand canonical ensemble

    NASA Astrophysics Data System (ADS)

    Jeon, Imtak; Kim, Sang-Woo; Park, Jeong-Hyuck

    2011-08-01

    We investigate the isobar of an ideal Bose gas confined in a cubic box within the grand canonical ensemble for a large yet finite number of particles, N. After solving the equation of the spinodal curve, we derive precise formulas for the supercooling and the superheating temperatures that reveal an N-1/3 or N-1/4 power correction to the known Bose-Einstein condensation temperature in the thermodynamic limit. Numerical computations confirm the accuracy of our analytical approximation, and further show that the isobar zigzags on the temperature-volume plane if N≥14393. In particular, for the Avogadro’s number of particles, the volume expands discretely about 105 times. Our results quantitatively agree with a previous study on the canonical ensemble within 0.1% error.

  11. Isobaric Heat Capacity, Isothermal Compressibility and Fluctuational Properties of 1-Bromoalkanes

    NASA Astrophysics Data System (ADS)

    Korotkovskii, V. I.; Ryshkova, O. S.; Neruchev, Yu. A.; Goncharov, A. L.; Postnikov, E. B.

    2016-06-01

    We present results of the experimental measurements of the isobaric heat capacity for 1-bromohexane, 1-bromoheptane, 1-bromooctane, 1-bromononane, 1-bromodecane, 1-bromoundecane, 1-bromododecane and 1-bromotetradecane at normal pressure and the speed of sound and the density for 1-bromotetradecane within the temperature range 298.15-423.15 K. These data on the isobaric heat capacity and the literature-based reference data for the density and the speed of sound were used to calculate the isothermal compressibility and the inverse reduced fluctuations. Based on the comparison of the results for pure n-alkanes and α ,ω -dibromoalkanes, we discuss the influence of bromine atom on the volume fluctuations.

  12. Oxygen chemisorption on V/sub 2/O/sub 5/: isotherms and isobars of adsorption

    SciTech Connect

    Rey, L.; Gambaro, L.A.; Thomas, H.J.

    1984-06-01

    Experimental results of oxygen adsorption on V/sub 2/O/sub 5/ (isotherms and isobars) are reported. In its normal state V/sub 2/O/sub 5/ is a nonstoichiometric oxide that shows oxygen vacancies with the subsequent formation of V/sup 4 +/ ions. A model is developed for the interaction between oxygen (gaseous, adsorbed, and bulk) and the solid phase (V/sub 2/O/sub 5/). 12 references, 4 figures, 1 table.

  13. A regression model for calculating the boiling point isobars of tetrachloromethane-based binary solutions

    NASA Astrophysics Data System (ADS)

    Preobrazhenskii, M. P.; Rudakov, O. B.

    2016-01-01

    A regression model for calculating the boiling point isobars of tetrachloromethane-organic solvent binary homogeneous systems is proposed. The parameters of the model proposed were calculated for a series of solutions. The correlation between the nonadditivity parameter of the regression model and the hydrophobicity criterion of the organic solvent is established. The parameter value of the proposed model is shown to allow prediction of the potential formation of azeotropic mixtures of solvents with tetrachloromethane.

  14. Isobaric vapor-liquid equilibria of methanol + 1-octanol and ethanol + 1-octanol mixtures

    SciTech Connect

    Arce, A.; Blanco, A.; Soto, A.; Tojo, J.

    1995-07-01

    Isobaric vapor-liquid equilibrium data for methanol + 1-octanol and ethanol + 1-octanol have been measured at 101.325 kPa. The results were checked for thermodynamic consistency using Fredenslund et al.`s test, correlated using Wilson, NRTL, and UNIQUAC equations for the liquid phase activity coefficients, and compared with the predictions of the ASOG, UNIFAC, and modified UNIFAC group contribution methods.

  15. Tofogliflozin, A Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation.

    PubMed

    Ishibashi, Y; Matsui, T; Yamagishi, S

    2016-03-01

    Ninety percent of glucose filtered by the glomerulus is reabsorbed by a sodium-glucose cotransporter 2 (SGLT2), which is mainly expressed on S1 and S2 segment of renal proximal tubules. Since SGLT-2-mediated glucose reabsorption is increased under diabetic conditions, selective inhibition of SGLT2 is a potential therapeutic target for the treatment of diabetes. We have recently shown that an inhibitor of SGLT2 has anti-inflammatory and antifibrotic effects on experimental diabetic nephropathy partly by suppressing advanced glycation end products formation and oxidative stress generation in the kidney. However, the direct effects of SGLT2 inhibitor on tubular cell damage remain unclear. In this study, we investigated the effects of tofogliflozin, a highly selective inhibitor of SGLT2 on oxidative stress generation, inflammatory and proapoptotic reactions in cultured human proximal tubular cells exposed to high glucose. Tofogliflozin dose-dependently suppressed glucose entry into tubular cells. High glucose exposure (30 mM) for 4 and 24 h significantly increased oxidative stress generation in tubular cells, which were suppressed by the treatment of tofogliflozin or an antioxidant N-acetylcysteine (NAC). Monocyte chemoattractant protein-1 (MCP-1) gene expression and apoptotic cell death were induced by 4 h- and 8 day-exposure to high glucose, respectively, both of which were also blocked by tofogliflozin or NAC. The present study suggests that SGLT2-mediated glucose entry into tubular cells could stimulate oxidative stress and evoke inflammatory and proapoptotic reactions in this cell type. Blockade of glucose reabsorption in tubular cells by SGLT2 inhibitor might exert beneficial effects on tubulointerstitial damage in diabetic nephropathy.

  16. A frequency-selective feedback model of auditory efferent suppression and its implications for the recognition of speech in noise.

    PubMed

    Clark, Nicholas R; Brown, Guy J; Jürgens, Tim; Meddis, Ray

    2012-09-01

    The potential contribution of the peripheral auditory efferent system to our understanding of speech in a background of competing noise was studied using a computer model of the auditory periphery and assessed using an automatic speech recognition system. A previous study had shown that a fixed efferent attenuation applied to all channels of a multi-channel model could improve the recognition of connected digit triplets in noise [G. J. Brown, R. T. Ferry, and R. Meddis, J. Acoust. Soc. Am. 127, 943-954 (2010)]. In the current study an anatomically justified feedback loop was used to automatically regulate separate attenuation values for each auditory channel. This arrangement resulted in a further enhancement of speech recognition over fixed-attenuation conditions. Comparisons between multi-talker babble and pink noise interference conditions suggest that the benefit originates from the model's ability to modify the amount of suppression in each channel separately according to the spectral shape of the interfering sounds.

  17. Selective β2-AR Blockage Suppresses Colorectal Cancer Growth Through Regulation of EGFR-Akt/ERK1/2 Signaling, G1-Phase Arrest, and Apoptosis.

    PubMed

    Chin, Chih-Chien; Li, Jhy-Ming; Lee, Kam-Fai; Huang, Yun-Ching; Wang, Kuan-Chieh; Lai, Hsiao-Ching; Cheng, Chih-Chung; Kuo, Yi-Hung; Shi, Chung-Sheng

    2016-02-01

    The stress-upregulated catecholamines-activated β1- and β2-adrenergic receptors (β1/2-ARs) have been shown to accelerate the progression of cancers such as colorectal cancer (CRC). We investigated the underlying mechanism of the inhibition of β1/2-ARs signaling for the treatment of CRC and elucidated the significance of β2-AR expression in CRC in vitro and in clinical samples. The impacts of β1/2-AR antagonists in CRC in vitro and CRC-xenograft in vivo were examined. We found that repression of β2-AR but not β1-AR signaling selectively suppressed cell viability, induced G1-phase cell cycle arrest, caused both intrinsic and extrinsic pathways-mediated apoptosis of specific CRC cells and inhibited CRC-xenograft growth in vivo. Moreover, the expression of β2-AR was not consistent with the progression of CRC in vitro or in clinical samples. Our data evidence that the expression profiles, signaling, and blockage of β2-AR have a unique pattern in CRC comparing to other cancers. β2-AR antagonism selectively suppresses the growth of CRC accompanying active β2-AR signaling, which potentially carries wild-type KRAS, in vitro and in vivo via the inhibition of β2-AR transactivated EFGR-Akt/ERK1/2 signaling pathway. Thus, β2-AR blockage might be a potential therapeutic strategy for combating the progressions of β2-AR-dependent CRC.

  18. Scaling phenomena of isobaric yields in projectile fragmentation, spallation, and fission reactions

    NASA Astrophysics Data System (ADS)

    Ma, Chun-Wang; Huang, Ling; Song, Yi-Dan

    2017-02-01

    Background: The isobaric ratio difference scaling phenomenon, which has been found for the fragments produced in projectile fragmentation reactions, is related to the nuclear density change in reaction systems. Purpose: To verify whether the isobaric ratio difference scaling exists in the fragments produced in the spallation and fission reactions. Methods: The isobaric ratio difference scaling, denoted by SΔ lnR21 , is in theory deduced within the framework of the canonical ensemble theory at the grand-canonical limitation. The fragments measured in a series of projectile fragmentation, spallation, and fission reactions have been analyzed. Results: A good SΔ lnR21 scaling phenomenon is shown for the fragments produced both in the projectile fragmentation reactions and in the spallation reactions, whereas the SΔ lnR21 scaling phenomenon for the fragments in the fission reaction is less obvious. Conclusions: The SΔ lnR21 scaling is used to probe the properties of the equilibrium system at the time of fragment formation. The good scaling of SΔ lnR21 suggests that the equilibrium state can be achieved in the projectile fragmentation and spallation reactions. Whereas in the fission reaction, the result of SΔ lnR21 indicates that the equilibrium of the system is hard to achieve.

  19. [Nursing Care of Lumbar Spine Fusion Surgery Using a Semi-Rigid Device (ISOBAR)].

    PubMed

    Wu, Meng-Shan; Su, Shu-Fen

    2016-04-01

    Aging frequently induces degenerative changes in the spine. Patients who suffer from lumbar degenerative disease tend to have lower back pain, neurological claudication, and neuropathy. Furthermore, incontinence may be an increasing issue as symptoms become severe. Lumbar spine fusion surgery is necessary if clinical symptoms continue to worsen or if the patient fails to respond to medication, physical therapy, or alternative treatments. However, this surgical procedure frequently induces adjacent segment disease (ASD), which is evidenced by the appearance of pathological changes in the upper and lower sections of the spinal surgical sites. In 1997, ISOBAR TTL dynamic rod stabilization was developed for application in spinal fusion surgery to prevent ASD-related complications. The device has proven effective in reducing pain in the lower back and legs, decreasing functional disability, improving quality of life, and retarding disc degeneration. However, the effectiveness of this intervention in decreasing the incidence of ASD requires further research investigation, and relevant literature and research in Taiwan is still lacking. This article discusses lumbar degenerative disease, its indications, the contraindications of lumbar spine fusion surgery using ISOBAR, and related postoperative nursing care. We hope this article provides proper and new knowledge to clinical nurses for the care of patients undergoing lumbar spine fusion surgery with ISOBAR.

  20. Coupled-channel Treatment of Isobaric Analog Resonances in (p,p‧) Capture Processes

    NASA Astrophysics Data System (ADS)

    Thompson, I. J.; Arbanas, G.

    2014-04-01

    With the advent of nuclear reactions on unstable isotopes, there has been a renewed interest in using isobaric analogue resonances (IAR) as a tool for probing the nuclear structure. The position and width of isobaric analogue resonances in nucleon-nucleus scattering are accurate and detailed indicators of the positions of resonances and bound states with good single-particle characters. We report on implementation within our coupled-channels code FRESCO of the charge-exchange interaction term that transforms an incident proton into a neutron. Isobaric analog resonances are seen as peaks in γ-ray spectrum when the proton is transformed into a neutron at an energy near a neutron bound state. The Lane coupled-channels formalism was extended to follow the non-orthogonality of this neutron channel with that configuration of an inelastic outgoing proton, and the target being left in a particle-hole excited state. This is tested for 208Pb, for which good (p,p'γ) coincidence data exists.

  1. Coupled-channel treatment of Isobaric Analog Resonances in (p,p') Capture Processes

    SciTech Connect

    Thompson, I J; Arbanas, Goran

    2013-01-01

    With the advent of nuclear reactions on unstable isotopes, there has been a renewed interest in using isobaric analogue resonances (IAR) as a tool for probing the nuclear structure. The position and width of isobaric analogue resonances in nucleon-nucleus scattering are accurate and detailed indicators of the positions of resonances and bound states with good single-particle characters. We report on implementation within our coupled-channels code FRESCO of the charge-exchange interaction term that transforms an incident proton into a neutron. Isobaric analog resonances are seen as peaks in gamma-ray spectrum when the proton is transformed into a neutron at an energy near a neutron bound state. The Lane coupled-channels formalism was extended to follow the nonorthogonality of this neutron channel with that configuration of an inelastic outgoing proton, and the target being left in a particle-hole excited state. This is tested for 208Pb, for which good (p,p g)

  2. Dialysate pressure isobars in a hollow-fiber dialyzer determined from magnetic resonance imaging and numerical simulation of dialysate flow.

    PubMed

    Osuga, T; Obata, T; Ikehira, H; Tanada, S; Sasaki, Y; Naito, H

    1998-10-01

    A procedure to determine dialysate pressure isobars by comparing the results of magnetic resonance imaging (MRI) and numerical simulation of the dialysate flow was established. The assumption used in the filtration analyses, that the dialysate pressure varies only in the central-axial direction, is supported by the finding that the determined isobars have no steep radial gradient. MRI of the contrast solution permeating the hollow fibers verifies the uniformity of the hollow fiber density in the dialyzer.

  3. Selective suppression of cocaine- versus food-maintained responding by monoamine releasers in rhesus monkeys: benzylpiperazine, (+)phenmetrazine, and 4-benzylpiperidine.

    PubMed

    Negus, S S; Baumann, M H; Rothman, R B; Mello, N K; Blough, B E

    2009-04-01

    Monoamine releasers constitute one class of drugs currently under investigation as potential agonist medications for the treatment of cocaine dependence. The efficacy and safety of monoamine releasers as candidate medications may be influenced in part by their relative potency to release dopamine and serotonin, and we reported previously that releasers with approximately 30-fold selectivity for dopamine versus serotonin release may be especially promising. The present study examined the effects of the releasers benzylpiperazine, (+)phenmetrazine, and 4-benzylpiperidine, which have 20- to 48-fold selectivity in vitro for releasing dopamine versus serotonin. In an assay of cocaine discrimination, rhesus monkeys were trained to discriminate 0.4 mg/kg i.m. cocaine from saline in a two-key, food-reinforced procedure. Each of the releasers produced a dose- and time-dependent substitution for cocaine. 4-Benzylpiperidine had the most rapid onset and shortest duration of action. Phenmetrazine and benzylpiperazine had slower onsets and longer durations of action. In an assay of cocaine self-administration, rhesus monkeys were trained to respond for cocaine injections and food pellets under a second order schedule. Treatment for 7 days with each of the releasers produced a dose-dependent and selective reduction in self-administration of cocaine (0.01 mg/kg/injection). The most selective effects were produced by phenmetrazine. Phenmetrazine also produced a downward shift in the cocaine self-administration dose effect curve, virtually eliminating responding maintained by a 30-fold range of cocaine doses (0.0032-0.1 mg/kg/injection) while having only small and transient effects on food-maintained responding. These findings support the potential utility of dopamine-selective releasers as candidate treatments for cocaine dependence.

  4. Lung tumorigenesis suppressing effects of a commercial kava extract and its selected compounds in A/J mice.

    PubMed

    Johnson, Thomas E; Hermanson, David; Wang, Lei; Kassie, Fekadu; Upadhyaya, Pramod; O'Sullivan, Michael G; Hecht, Stephen S; Lu, Junxuan; Xing, Chengguo

    2011-01-01

    Lung cancer is the most deadly malignancy in the US. Chemoprevention is potentially a complementary approach to smoking cessation for lung cancer control. Recently, we reported that a commercially available form of kava extract significantly inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(a)pyrene (BaP)-induced lung tumorigenesis in A/J mice at a dose of 10 mg per gram diet. In the present study, we examined the dose-dependent lung tumor inhibitory activities of kava and investigated potential active constituent(s). Mice treated with carcinogen alone contained 12.1±5.8 lung adenomas per mouse 22 weeks after final carcinogen administration. Mice that were fed diets containing kava at dosages of 1.25, 2.5, 5, and 10 mg/g of diet had 8.4±3.5, 6.6±3.5, 4.3±2.4, and 3.8±2.3 lung adenomas per mouse, respectively. This corresponds to a reduction of 31%, 46%, 65% and 69% in tumor multiplicity, which were all statistically significant (p < 0.05). Analyses of lung adenoma tissues derived from kava-treated animals revealed that kava significantly inhibited adenoma cell proliferation while it had no detectable effect on cell death, indicating that kava primarily suppressed lung tumorigenesis in A/J mice via inhibition of cell proliferation. Flavokawains A, B, and C, three chalcone-based components from kava, demonstrated greatly reduced chemopreventive efficacies even at concentrations much higher than their natural abundance, suggesting that they alone were unlikely to be responsible for kava's chemopreventive activity. Kava at all dosages and treatment regimens did not induce detectable adverse effects, particularly with respect to liver. Specifically, kava treatment showed no effect on liver integrity indicator enzymes or liver weight, indicating that kava may be potentially safe for long-term chemopreventive application.

  5. Selective suppression of two-photon fluorescence in laser scanning microscopy by ultrafast pulse-train excitation.

    PubMed

    De, Arijit Kumar; Roy, Debjit; Goswami, Debabrata

    2010-01-01

    Selective excitation of a particular fluorophore in the presence of others demands clever design of the optical field interacting with the molecules. We describe the use of 20- to 50-GHz pulse-train excitation leading to two-photon absorption, followed by successive one-photon stimulated emission as a potential technique in the context of controlling two-photon molecular fluorescence, with applications in microscopy.

  6. Selection of dinB Alleles Suppressing Survival Loss upon dinB Overexpression in Escherichia coli

    PubMed Central

    Benson, Ryan W.; Cafarelli, Tiziana M.; Rands, Thomas J.; Lin, Ida

    2014-01-01

    Escherichia coli strains overproducing DinB undergo survival loss; however, the mechanisms regulating this phenotype are poorly understood. Here we report a genetic selection revealing DinB residues essential to effect this loss-of-survival phenotype. The selection uses strains carrying both an antimutator allele of DNA polymerase III (Pol III) α-subunit (dnaE915) and either chromosomal or plasmid-borne dinB alleles. We hypothesized that dnaE915 cells would respond to DinB overproduction differently from dnaE+ cells because the dnaE915 allele is known to have an altered genetic interaction with dinB+ compared to its interaction with dnaE+. Notably, we observe a loss-of-survival phenotype in dnaE915 strains with either a chromosomal catalytically inactive dinB(D103N) allele or a low-copy-number plasmid-borne dinB+ upon DNA damage treatment. Furthermore, we find that the loss-of-survival phenotype occurs independently of DNA damage treatment in a dnaE915 strain expressing the catalytically inactive dinB(D103N) allele from a low-copy-number plasmid. The selective pressure imposed resulted in suppressor mutations that eliminated growth defects. The dinB intragenic mutations examined were either base pair substitutions or those that we inferred to be loss of function (i.e., deletions and insertions). Further analyses of selected novel dinB alleles, generated by single-base-pair substitutions in the dnaE915 strain, indicated that these no longer effect loss of survival upon overproduction in dnaE+ strains. These mutations are mapped to specific areas of DinB; this permits us to gain insights into the mechanisms underlying the DinB-mediated overproduction loss-of-survival phenotype. PMID:24914188

  7. Suppression of acetylpolyamine oxidase by selected AP-1 members regulates DNp73 abundance: mechanistic insights for overcoming DNp73-mediated resistance to chemotherapeutic drugs

    PubMed Central

    Bunjobpol, W; Dulloo, I; Igarashi, K; Concin, N; Matsuo, K; Sabapathy, K

    2014-01-01

    Enhanced resistance to chemotherapy has been correlated with high levels of Delta-Np73 (DNp73), an anti-apoptotic protein of the p53 tumor-suppressor family which inhibits the pro-apoptotic members such as p53 and TAp73. Although genotoxic drugs have been shown to induce DNp73 degradation, lack of mechanistic understanding of this process precludes strategies to enhance the targeting of DNp73 and improve treatment outcomes. Antizyme (Az) is a mediator of ubiquitin-independent protein degradation regulated by the polyamine biosynthesis pathway. We show here that acetylpolyamine oxidase (PAOX), a catabolic enzyme of this pathway, upregulates DNp73 levels by suppressing its degradation via the Az pathway. Conversely, downregulation of PAOX activity by siRNA-mediated knockdown or chemical inhibition leads to DNp73 degradation in an Az-dependent manner. PAOX expression is suppressed by several genotoxic drugs, via selected members of the activator protein-1 (AP-1) transcription factors, namely c-Jun, JunB and FosB, which are required for stress-mediated DNp73 degradation. Finally, chemical- and siRNA-mediated inhibition of PAOX significantly reversed the resistant phenotype of DNp73-overexpressing cancer cells to genotoxic drugs. Together, these data define a critical mechanism for the regulation of DNp73 abundance, and reveal that inhibition of PAOX could widen the therapeutic index of cytotoxic drugs and overcome DNp73-mediated chemoresistance in tumors. PMID:24722210

  8. SacB-SacR Gene Cassette As the Negative Selection Marker to Suppress Agrobacterium Overgrowth in Agrobacterium-Mediated Plant Transformation

    PubMed Central

    Liu, Yiming; Miao, Jiamin; Traore, Sy; Kong, Danyu; Liu, Yi; Zhang, Xunzhong; Nimchuk, Zachary L.; Liu, Zongrang; Zhao, Bingyu

    2016-01-01

    Agrobacterium overgrowth is a common problem in Agrobacterium-mediated plant transformation. To suppress the Agrobacterium overgrowth, various antibiotics have been used during plant tissue culture steps. The antibiotics are expensive and may adversely affect plant cell differentiation and reduce plant transformation efficiency. The SacB-SacR proteins are toxic to most Agrobacterium tumefaciens strains when they are grown on culture medium supplemented with sucrose. Therefore, SacB-SacR genes can be used as negative selection markers to suppress the overgrowth of A. tumefaciens in the plant tissue culture process. We generated a mutant A. tumefaciens strain GV2260 (recA-SacB/R) that has the SacB-SacR cassette inserted into the bacterial genome at the recA gene locus. The mutant Agrobacterium strain is sensitive to sucrose but maintains its ability to transform plant cells in both transient and stable transformation assays. We demonstrated that the mutant strain GV2260 (recA-SacB/R) can be inhibited by sucrose that reduces the overgrowth of Agrobacterium and therefore improves the plant transformation efficiency. We employed GV2260 (recA-SacB/R) to generate stable transgenic N. benthamiana plants expressing a CRISPR-Cas9 for knocking out a WRKY transcription factor. PMID:27833912

  9. SacB-SacR Gene Cassette As the Negative Selection Marker to Suppress Agrobacterium Overgrowth in Agrobacterium-Mediated Plant Transformation.

    PubMed

    Liu, Yiming; Miao, Jiamin; Traore, Sy; Kong, Danyu; Liu, Yi; Zhang, Xunzhong; Nimchuk, Zachary L; Liu, Zongrang; Zhao, Bingyu

    2016-01-01

    Agrobacterium overgrowth is a common problem in Agrobacterium-mediated plant transformation. To suppress the Agrobacterium overgrowth, various antibiotics have been used during plant tissue culture steps. The antibiotics are expensive and may adversely affect plant cell differentiation and reduce plant transformation efficiency. The SacB-SacR proteins are toxic to most Agrobacterium tumefaciens strains when they are grown on culture medium supplemented with sucrose. Therefore, SacB-SacR genes can be used as negative selection markers to suppress the overgrowth of A. tumefaciens in the plant tissue culture process. We generated a mutant A. tumefaciens strain GV2260 (recA-SacB/R) that has the SacB-SacR cassette inserted into the bacterial genome at the recA gene locus. The mutant Agrobacterium strain is sensitive to sucrose but maintains its ability to transform plant cells in both transient and stable transformation assays. We demonstrated that the mutant strain GV2260 (recA-SacB/R) can be inhibited by sucrose that reduces the overgrowth of Agrobacterium and therefore improves the plant transformation efficiency. We employed GV2260 (recA-SacB/R) to generate stable transgenic N. benthamiana plants expressing a CRISPR-Cas9 for knocking out a WRKY transcription factor.

  10. Triple negative breast cancer development can be selectively suppressed by sustaining an elevated level of cellular cyclic AMP through simultaneously blocking its efflux and decomposition

    PubMed Central

    Wang, Wei; Li, Yue; Zhu, Jessica Y.; Fang, Dongdong; Ding, Han-Fei; Dong, Zheng; Jing, Qing; Su, Shi-Bing; Huang, Shuang

    2016-01-01

    Triple negative breast cancer (TNBC) has the highest mortality among all breast cancer types and lack of targeted therapy is a key factor contributing to its high mortality rate. In this study, we show that 8-bromo-cAMP, a cyclic adenosine monophosphate (cAMP) analog at high concentration (> 1 mM) selectively suppresses TNBC cell growth. However, commonly-used cAMP-elevating agents such as adenylyl cyclase activator forskolin and pan phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) are ineffective. Inability of cAMP elevating agents to inhibit TNBC cell growth is due to rapid diminution of cellular cAMP through efflux and decomposition. By performing bioinformatics analyses with publically available gene expression datasets from breast cancer patients/established breast cancer cell lines and further validating using specific inhibitors/siRNAs, we reveal that multidrug resistance-associated protein 1/4 (MRP1/4) mediate rapid cAMP efflux while members PDE4 subfamily facilitate cAMP decomposition. When cAMP clearance is prevented by specific inhibitors, forskolin blocks TNBC's in vitro cell growth by arresting cell cycle at G1/S phase. Importantly, cocktail of forskolin, MRP inhibitor probenecid and PDE4 inhibitor rolipram suppresses TNBC in vivo tumor development. This study suggests that a TNBC-targeted therapeutic strategy can be developed by sustaining an elevated level of cAMP through simultaneously blocking its efflux and decomposition. PMID:27901486

  11. Selective class I histone deacetylase inhibitors suppress persistent spontaneous nociception and thermal hypersensitivity in a rat model of bee venom-induced inflammatory pain.

    PubMed

    Yang, Fan; Yang, Yan; Wang, Yan; Yang, Fei; Li, Chun-Li; Wang, Xiao-Liang; Li, Zhen; Chen, Jun

    2015-10-25

    To confirm whether class I histone deacetylase inhibitors (HDACIs) are effective in relief of peripheral inflammatory pain, the effects of two selective inhibitors, MS-275 and MGCD0103, were studied in rats inflamed by subcutaneous (s.c.) injection of bee venom (BV). The BV test is characterized by displaying both persistent spontaneous nociception (PSN) and primary hypersensitivity. Intrathecal (i.t.) pre-treatment of either MS-275 or MGCD0103 with a single dose of 60 nmol/20 μL resulted in profound suppression of both PSN and primary thermal hypersensitivity but without significant influence upon the primary mechanical hypersensitivity and mirror-image thermal hypersensitivity. Moreover, the up-regulation of both HDAC1 and HDAC2 induced by s.c. BV injection was completely suppressed by i.t. pre-treatment of MS-275. The present results provide with another new line of evidence showing involvement of epigenetic regulation of chromatin structure by HDAC1/2-mediated histone hypoacetylation in the BV-induced PSN and thermal hypersensitivity and demonstrate the beneficial effects of class I HDACIs in prevention of peripheral inflammatory pain from occurring.

  12. Quantitative Analysis of Single Amino Acid Variant Peptides Associated with Pancreatic Cancer in Serum by an Isobaric Labeling Quantitative Method

    PubMed Central

    2015-01-01

    Single amino acid variations are highly associated with many human diseases. The direct detection of peptides containing single amino acid variants (SAAVs) derived from nonsynonymous single nucleotide polymorphisms (SNPs) in serum can provide unique opportunities for SAAV associated biomarker discovery. In the present study, an isobaric labeling quantitative strategy was applied to identify and quantify variant peptides in serum samples of pancreatic cancer patients and other benign controls. The largest number of SAAV peptides to date in serum including 96 unique variant peptides were quantified in this quantitative analysis, of which five variant peptides showed a statistically significant difference between pancreatic cancer and other controls (p-value < 0.05). Significant differences in the variant peptide SDNCEDTPEAGYFAVAVVK from serotransferrin were detected between pancreatic cancer and controls, which was further validated by selected reaction monitoring (SRM) analysis. The novel biomarker panel obtained by combining α-1-antichymotrypsin (AACT), Thrombospondin-1 (THBS1) and this variant peptide showed an excellent diagnostic performance in discriminating pancreatic cancer from healthy controls (AUC = 0.98) and chronic pancreatitis (AUC = 0.90). These results suggest that large-scale analysis of SAAV peptides in serum may provide a new direction for biomarker discovery research. PMID:25393578

  13. 2-[(Carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids selectively suppressed proliferation of neoplastic human HeLa cells. A SAR/QSAR study.

    PubMed

    Drakulić, Branko J; Juranić, Zorica D; Stanojković, Tatjana P; Juranić, Ivan O

    2005-08-25

    A series of twenty alkyl-, halo-, and methoxy-aryl-substituted 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids were synthesized. The new compounds, called CSAB, suppressed proliferation of human cervix carcinoma, HeLa cells, in vitro in a concentration range of 0.644 to 29.48 microM/L. Two compounds exhibit antiproliferative activity in sub-micromolar concentrations. Five compounds act in low micromolar concentrations (<2 microM/L). The most active compounds exert lower cytotoxicity toward healthy human peripheral blood mononuclear cells (PBMC and PBMC+PHA) (selectivity indexes > 10). A strong structure-activity relationship, using estimated log P values and BCUT descriptors, was observed.

  14. Charge inversion, water splitting, and vortex suppression due to DNA sorption on ion-selective membranes and their ion-current signatures.

    PubMed

    Slouka, Zdenek; Senapati, Satyajyoti; Yan, Yu; Chang, Hsueh-Chia

    2013-07-02

    The physisorption of negatively charged single-stranded DNA (ssDNA) of different lengths onto the surface of anion-exchange membranes is sensitively shown to alter the anion flux through the membrane. At low surface concentrations, the physisorbed DNAs act to suppress an electroconvection vortex instability that drives the anion flux into the membrane and hence reduce the overlimiting current through the membrane. Beyond a critical surface concentration, determined by the total number of phosphate charges on the DNA, the DNA layer becomes a cation-selective membrane, and the combined bipolar membrane has a lower net ion flux, at low voltages, than the original membrane as a result of ion depletion at the junction between the cation- (DNA) and anion-selective membranes. However, beyond a critical voltage that is dependent on the ssDNA coverage, water splitting occurs at the junction to produce a larger overlimiting current than that of the original membrane. These two large opposite effects of polyelectrolyte counterion sorption onto membrane surfaces may be used to eliminate limiting current constraints of ion-selective membranes for liquid fuel cells, dialysis, and desalination as well as to suggest a new low-cost membrane surface assay that can detect and quantify the number of large biomolecules captured by probes functionalized on the membrane surface.

  15. PR-957, a selective inhibitor of immunoproteasome subunit low-MW polypeptide 7, attenuates experimental autoimmune neuritis by suppressing Th17 cell differentiation and regulating cytokine production.

    PubMed

    Liu, Haijie; Wan, Chunxiao; Ding, Yanan; Han, Ranran; He, Yating; Xiao, Jinting; Hao, Junwei

    2017-01-17

    Experimental autoimmune neuritis (EAN) is a CD4(+) T cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system. It has been replicated in an animal model of human inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome. In this study, we evaluated the therapeutic efficacy of a selective inhibitor of the immunoproteasome subunit, low-MW polypeptide 7 (PR-957) in rats with EAN. Our results showed that PR-957 significantly delayed onset day, reduced severity and shortened duration of EAN, and alleviated demyelination and inflammatory infiltration in sciatic nerves. In addition to significantly regulating expression of the cytokine profile, PR-957 treatment down-regulated the proportion of proinflammatory T helper (Th)17 cells in sciatic nerves and spleens of rats with EAN. Data presented show the role of PR-957 in the signal transducer and activator of transcription 3 (STAT3) pathway. PR-957 not only decreased expression of IL-6 and IL-23 but also led to down-regulation of STAT3 phosphorylation in CD4(+) T cells. Regulation of the STAT3 pathway led to a reduction in retinoid-related orphan nuclear receptor γ t and IL-17 production. Furthermore, reduction of STAT3 phosphorylation may have directly suppressed Th17 cell differentiation. Therefore, our study demonstrates that PR-957 could potently alleviate inflammation in rats with EAN and that it may be a likely candidate for treating Guillain-Barré syndrome.-Liu, H., Wan, C., Ding, Y., Han, R., He, Y., Xiao, J., Hao, J. PR-957, a selective inhibitor of immunoproteasome subunit low-MW polypeptide 7, attenuates experimental autoimmune neuritis by suppressing Th17 cell differentiation and regulating cytokine production.

  16. Limitations of short range Mexican hat connection for driving target selection in a 2D neural field: activity suppression and deviation from input stimuli

    PubMed Central

    Mégardon, Geoffrey; Tandonnet, Christophe; Sumner, Petroc; Guillaume, Alain

    2015-01-01

    Dynamic Neural Field models (DNF) often use a kernel of connection with short range excitation and long range inhibition. This organization has been suggested as a model for brain structures or for artificial systems involved in winner-take-all processes such as saliency localization, perceptual decision or target/action selection. A good example of such a DNF is the superior colliculus (SC), a key structure for eye movements. Recent results suggest that the superficial layers of the SC (SCs) exhibit relatively short range inhibition with a longer time constant than excitation. The aim of the present study was to further examine the properties of a DNF with such an inhibition pattern in the context of target selection. First we tested the effects of stimulus size and shape on when and where self-maintained clusters of firing neurons appeared, using three variants of the model. In each model variant, small stimuli led to rapid formation of a spiking cluster, a range of medium sizes led to the suppression of any activity on the network and hence to no target selection, while larger sizes led to delayed selection of multiple loci. Second, we tested the model with two stimuli separated by a varying distance. Again single, none, or multiple spiking clusters could occur, depending on distance and relative stimulus strength. For short distances, activity attracted toward the strongest stimulus, reminiscent of well-known behavioral data for saccadic eye movements, while for larger distances repulsion away from the second stimulus occurred. All these properties predicted by the model suggest that the SCs, or any other neural structure thought to implement a short range MH, is an imperfect winner-take-all system. Although, those properties call for systematic testing, the discussion gathers neurophysiological and behavioral data suggesting that such properties are indeed present in target selection for saccadic eye movements. PMID:26539103

  17. Isobaric vapor-liquid equilibria in the system methyl propanoate + n-butyl alcohol

    SciTech Connect

    Susial, P.; Ortega, J. . Lab. de Termodinamica y Fisicoquimica)

    1993-10-01

    Isobaric vapor-liquid equilibria were determined at 74.66, 101.32, and 127.99 kPa for binary mixtures containing methyl propanoate + n-butyl alcohol by using a dynamic still with vapor and liquid circulation. No azeotrope was detected. The data were found to be thermodynamically consistent according to the point to point test. Application of the group-contribution models ASOG, UNIFAC, and modified UNIFAC to the activity coefficients at the three pressures studied gives average errors of less than 10%, 11%, and 3%, respectively.

  18. Effect of isospin dependence of radius on transverse flow and fragmentation in isobaric pairs

    NASA Astrophysics Data System (ADS)

    Gautam, Sakshi

    2013-11-01

    We study the role of nuclear structure effects through radius in reaction dynamics via transverse flow and multifragmentation of isobaric colliding pairs. Our study reveals that isospin-dependent radius [proposed by Royer and Rousseau [Eur. Phys. J. A10.1140/epja/i2008-10745-8 42, 541 (2009)] has significant effect towards isospin effects. The collective flow behavior and fragmentation pattern of neutron-rich system with respect to neutron-deficient system is found to get reversed with isospin-dependent radius compared to that with liquid drop radius.

  19. Fragmentation in isotopic and isobaric systems as probe of density dependence of nuclear symmetry energy

    NASA Astrophysics Data System (ADS)

    Kaur, Mandeep; Gautam, Sakshi; Puri, Rajeev K.

    2016-11-01

    We probe the density-dependent behavior of symmetry energy using the yield of various fragments in central collisions of various isotopic and isobaric colliding pairs. We calculate the yields of free nucleons, light charged particles and intermediate mass fragments in neutron-rich colliding systems as well as the ratio of relative yields of above fragments and free nucleons. Our findings reveal that the ratio of relative yield of light charged particles poses better candidate to probe the density dependence of nuclear symmetry energy.

  20. Characterization of the vanadium-nitrogen system with nitrogen pressure isobars.

    SciTech Connect

    Wang, W.-E.; Kim, Y. S.; Hong, H. S.; Engineering Division; Univ. of California

    2000-01-01

    The partial thermodynamic functions of the V-N system from V to VN over the temperature range 1000 to 2100 K have been investigated. The discrepancies among the pressure-composition-temperature (p-C-T) relationships in the {delta}-VN single-phase region have been resolved. The p-C-T relationships for other phases, where no data were available from the literature, have been established by applying the appropriate thermodynamic constraints and a modified form of Sieverts law. The results are presented as the nitrogen isobars superimposed on the phase diagram.

  1. Moving stimuli are less effectively masked using traditional continuous flash suppression (CFS) compared to a moving Mondrian mask (MMM): a test case for feature-selective suppression and retinotopic adaptation.

    PubMed

    Moors, Pieter; Wagemans, Johan; de-Wit, Lee

    2014-01-01

    Continuous flash suppression (CFS) is a powerful interocular suppression technique, which is often described as an effective means to reliably suppress stimuli from visual awareness. Suppression through CFS has been assumed to depend upon a reduction in (retinotopically specific) neural adaptation caused by the continual updating of the contents of the visual input to one eye. In this study, we started from the observation that suppressing a moving stimulus through CFS appeared to be more effective when using a mask that was actually more prone to retinotopically specific neural adaptation, but in which the properties of the mask were more similar to those of the to-be-suppressed stimulus. In two experiments, we find that using a moving Mondrian mask (i.e., one that includes motion) is more effective in suppressing a moving stimulus than a regular CFS mask. The observed pattern of results cannot be explained by a simple simulation that computes the degree of retinotopically specific neural adaptation over time, suggesting that this kind of neural adaptation does not play a large role in predicting the differences between conditions in this context. We also find some evidence consistent with the idea that the most effective CFS mask is the one that matches the properties (speed) of the suppressed stimulus. These results question the general importance of retinotopically specific neural adaptation in CFS, and potentially help to explain an implicit trend in the literature to adapt one's CFS mask to match one's to-be-suppressed stimuli. Finally, the results should help to guide the methodological development of future research where continuous suppression of moving stimuli is desired.

  2. Selective ORAI1 inhibition ameliorates autoimmune CNS inflammation by suppressing effector but not regulatory T cell function

    PubMed Central

    Kaufmann, Ulrike; Shaw, Patrick J.; Kozhaya, Lina; Subramanian, Raju; Gaida, Kevin; Unutmaz, Derya; McBride, Helen J.; Feske, Stefan

    2015-01-01

    The function of CD4+ T cells is dependent on Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels formed by ORAI proteins. To investigate the role of ORAI1 in pro-inflammatory Th1 and Th17 cells and autoimmune diseases, we genetically and pharmacologically modulated ORAI1 function. Immunization of mice lacking Orai1 in T cells with MOG peptide resulted in attenuated severity of experimental autoimmune encephalomyelitis (EAE). The numbers of T cells and innate immune cells in the CNS of ORAI1-deficient animals were strongly reduced along with almost completely abolished production of IL-17, IFN-γ and GM-CSF despite only partially reduced Ca2+ influx. In Th1 and Th17 cells differentiated in vitro, ORAI1 was required for cytokine production but not the expression of Th1- and Th17-specific transcription factors T-bet and RORγt. The differentiation and function of induced iTreg cells, by contrast, was independent of ORAI1. Importantly, induced genetic deletion of Orai1 in adoptively transferred, MOG-specific T cells was able to halt EAE progression after disease onset. Likewise, treatment of wild-type mice with a selective CRAC channel inhibitor after EAE onset ameliorated disease. Genetic deletion of Orai1 and pharmacological ORAI1 inhibition reduced the leukocyte numbers in the CNS and attenuated Th1/Th17 cell-mediated cytokine production. In human CD4+ T cells, CRAC channel inhibition reduced the expression of IL-17, IFN-γ and other cytokines in a dose-dependent manner. Taken together, these findings support the conclusion that Th1 and Th17 cell function is particularly dependent on CRAC channels, which could be exploited as a therapeutic approach to T cell-mediated autoimmune diseases. PMID:26673135

  3. A novel small compound SH-2251 suppresses Th2 cell-dependent airway inflammation through selective modulation of chromatin status at the Il5 gene locus.

    PubMed

    Suzuki, Junpei; Kuwahara, Makoto; Tofukuji, Soichi; Imamura, Masashi; Kato, Fuminori; Nakayama, Toshinori; Ohara, Osamu; Yamashita, Masakatsu

    2013-01-01

    IL-5 is a key cytokine that plays an important role in the development of pathological conditions in allergic inflammation. Identifying strategies to inhibit IL-5 production is important in order to establish new therapies for treating allergic inflammation. We found that SH-2251, a novel thioamide-related small compound, selectively inhibits the differentiation of IL-5-producing Th2 cells. SH-2251 inhibited the induction of active histone marks at the Il5 gene locus during Th2 cell differentiation. The recruitment of RNA polymerase II, and following expression of the Th2 cell-specific intergenic transcripts around the Il5 gene locus was also inhibited. Furthermore, Th2 cell-dependent airway inflammation in mice was suppressed by the oral administration of SH-2251. Gfi1, a transcriptional repressor, was identified as a downstream target molecule of SH-2251 using a DNA microarray analysis. The Gfi1 expression dramatically decreased in SH-2251-treated Th2 cells, and the SH-2251-mediated inhibition of IL-5-producing Th2 cell differentiation was restored by transduction of Gfi1. Therefore, our study unearthed SH-2251 as a novel therapeutic candidate for allergic inflammation that selectively inhibits active histone marks at the Il5 gene locus.

  4. Replication-incompetent adenovirus vector-mediated MDA-7/IL-24 selectively induces growth suppression and apoptosis of hepatoma cell Line SMMC-7721.

    PubMed

    Wang, Congjun; Xue, Xinbo; Yi, Jilin; Wu, Zaide; Chen, Kun; Zheng, Jianwei; Ji, Wenwei; Yu, Yuan

    2008-02-01

    In order to investigate the effect of replication-incompetent adenovirus vector expressing MDA-7/IL-24 on tumor growth and apoptosis of human hepatocellular carcinoma (HCC) cell line SMMC-7721 and normal liver cell line L02, the recombinant replication-incompetent Ad.mda-7 virus vector was constructed and infected into the HCC cell line SMMC-7721 and normal liver cell line L02. RT-PCR was performed to examine the expression of MDA-7 mRNA. The concentrations of MDA-7/IL-4 in culture supernatants were determined by using ELISA. MTT and Hoechst staining assay were applied to observe the inhibitory and killing effects of MDA-7 on the HCC cells. By using flow cytometry, the apoptosis, cell cycle and proliferation of SMMC-7721 and L02 cells were measured. The results showed recombinant replication-incompetent virus expressing MDA-7/IL-24 was constructed successfully, and RT-PCR revealed that it could mediate the high expression of the exogenous gene MDA-7/IL-24 in SMMC-7721 and L02 cells. The expression of MDA-7/IL-24 proteins in the culture supernatant was detectable by ELISA. Ad.mda-7 infection induced apoptosis and growth suppression in SMMC-7721 cells and an increased percentage of HCC cells in the G2/M phase of the cell cycle, but not in L02 cells. It was concluded that mda-7/IL-24 gene, mediated with replication-incompetent adenovirus vector, could selectively induce growth suppression and apoptosis in HCC cell line SMMC-7721 but without any toxic side-effect on normal liver line L02.

  5. Osteoinductive LIM Mineralization Protein-1 Suppresses Activation of NF-κB and Selectively Regulates MAPK Pathways in Pre-osteoclasts

    PubMed Central

    Liu, Hui; Bargouti, Maggie; Zughaier, Susu; Zheng, Zhaomin; Liu, Yunshan; Sangadala, Sreedhara; Boden, Scott D.; Titus, Louisa

    2009-01-01

    LIM Mineralization Protein-1 (LMP-1) is an intracellular regulator of bone formation and has been shown to be osteoinductive in vitro and in vivo. The effect of LMP-1 on other aspects of bone homeostasis has not been previously studied. In a pilot study we observed that LMP-1 decreased nitric oxide (NO) production in pre-osteoclasts. Here we report a new anti-inflammatory effect of LMP-1 and define its mechanism of action in lipopolysaccharide (LPS)-stimulated RAW 264.7 pre-osteoclasts. We found that LMP-1 significantly inhibited LPS-induced NO production. LMP-1 also effectively inhibited the expression of inducible Nitric Oxide Synthase (iNOS), potently suppressed the transcriptional activity and nuclear translocation of nuclear factor kappa B (NF-κB), and prevented the phosphorylation of inhibitor of kappa B (IκB). Interestingly, LMP-1 had no effect on Receptor-Activator of Nuclear Factor B Ligand (RANKL)-induced activation of NF-κB. Furthermore, LMP-1 had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), whereas it did attenuate the phosphorylation of c-Jun NH2-terminal kinase (JNK) while enhancing phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK). These results suggest that LMP-1 has an anti-inflammatory effect, and this effect is, at least in part, due to the inhibition of NO production by the suppression of NF-κB activation and selective regulation of mitogen-activated protein kinase (MAPK) pathways. PMID:19931434

  6. Osteoinductive LIM mineralization protein-1 suppresses activation of NF-kappaB and selectively regulates MAPK pathways in pre-osteoclasts.

    PubMed

    Liu, Hui; Bargouti, Maggie; Zughaier, Susu; Zheng, Zhaomin; Liu, Yunshan; Sangadala, Sreedhara; Boden, Scott D; Titus, Louisa

    2010-05-01

    LIM mineralization protein-1 (LMP-1) is an intracellular regulator of bone formation and has been shown to be osteoinductive in vitro and in vivo. The effect of LMP-1 on other aspects of bone homeostasis has not been previously studied. In a pilot study we observed that LMP-1 decreased nitric oxide (NO) production in pre-osteoclasts. Here we report a new anti-inflammatory effect of LMP-1 and define its mechanism of action in lipopolysaccharide (LPS)-stimulated RAW 264.7 pre-osteoclasts. We found that LMP-1 significantly inhibited LPS-induced NO production. LMP-1 also effectively inhibited the expression of inducible nitric oxide synthase (iNOS), potently suppressed the transcriptional activity and nuclear translocation of nuclear factor kappa B (NF-kappaB), and prevented the phosphorylation of inhibitor of kappa B (IkappaB). Interestingly, LMP-1 had no effect on Receptor-Activator of Nuclear Factor B Ligand (RANKL)-induced activation of NF-kappaB. Furthermore, LMP-1 had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), whereas it did attenuate the phosphorylation of c-Jun NH2-terminal kinase (JNK) while enhancing phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK). These results suggest that LMP-1 has an anti-inflammatory effect, and this effect is, at least in part, due to the inhibition of NO production by the suppression of NF-kappaB activation and selective regulation of mitogen-activated protein kinase (MAPK) pathways.

  7. Suppression of cytokine-mediated complement factor gene expression through selective activation of the Ah receptor with 3',4'-dimethoxy-α-naphthoflavone.

    PubMed

    Murray, Iain A; Flaveny, Colin A; Chiaro, Christopher R; Sharma, Arun K; Tanos, Rachel S; Schroeder, Jennifer C; Amin, Shantu G; Bisson, William H; Kolluri, Siva K; Perdew, Gary H

    2011-03-01

    We have characterized previously a class of aryl hydrocarbon receptor (AHR) ligand termed selective AHR modulators (SAhRMs). SAhRMs exhibit anti-inflammatory properties, including suppression of cytokine-mediated acute phase genes (e.g., Saa1), through dissociation of non-dioxin-response element (DRE) AHR activity from DRE-dependent xenobiotic gene expression. The partial AHR agonist α-naphthoflavone (αNF) mediates the suppressive, non-DRE dependent effects on SAA1 expression and partial DRE-mediated CYP1A1 induction. These observations suggest that αNF may be structurally modified to a derivative exhibiting only SAhRM activity. A screen of αNF derivatives identifies 3',4'-dimethoxy-αNF (DiMNF) as a candidate SAhRM. Competitive ligand binding validates DiMNF as an AHR ligand, and DRE-dependent reporter assays with quantitative mRNA analysis of AHR target genes reveal minimal agonist activity associated with AHR binding. Consistent with loss of agonist activity, DiMNF fails to promote AHR binding to DRE probes as determined through electromobility shift assay. Importantly, mRNA analysis indicates that DiMNF retains the suppressive capacity of αNF regarding cytokine-mediated SAA1 expression in Huh7 cells. Interestingly, predictive docking modeling suggests that DiMNF adopts a unique orientation within the AHR ligand binding pocket relative to αNF and may facilitate the rational design of additional SAhRMs. Microarray studies with a non-DRE binding but otherwise functional AHR mutant identified complement factor C3 as a potential SAhRM target. We confirmed this observation in Huh7 cells using 10 μM DiMNF, which significantly repressed C3 mRNA and protein. These data expand the classes of AHR ligands exerting DRE-independent anti-inflammatory SAhRM activity, suggesting SAhRMs may have application in the amelioration of inflammatory disorders.

  8. Zr/Nb isobar separation experiment for future 93Zr AMS measurement

    NASA Astrophysics Data System (ADS)

    Lu, W.; Anderson, T.; Bowers, M.; Bauder, W.; Collon, P.; Kutschera, W.; Kashiv, Y.; Lachner, J.; Martschini, M.; Ostdiek, K.; Robertson, D.; Schmitt, C.; Skulski, M.; Steier, P.

    2015-10-01

    93Zr (t1/2 = 1.6 Ma) is mostly produced by the main s-process in low-to-intermediate mass AGB stars. Large uncertainty exists in the current 92Zr(n,γ)93Zr Maxwellian Average cross section. This could have significant impact on nucleosynthesis calculations. Large amounts of 93Zr are also produced in nuclear reactors and pose long-term environmental radioactivity. Hence, measurement of 93Zr by the AMS is important for both fields above. We report here on progress in the development of AMS method to measure 93Zr. Compared with 98 MeV beam energy, Zr/Nb isobar position separation was improved using 155.2 MeV beam energy and Gas-Filled Magnet. Energy loss measurement with increased beam energy inside the detector indicates that higher beam energy can improve isobar energy loss separation. A chemical procedure to reduce the Nb content in Zr samples has been developed and tested. It reduces the 93Nb content by a factor of 1000.

  9. Simultaneous quantitative analysis of isobars by tandem mass spectrometry from unresolved chromatographic peaks.

    PubMed

    Kushnir, Mark M; Rockwood, Alan L; Nelson, Gordon J

    2004-05-01

    A method was developed for the simultaneous quantitation of isobars from unresolved chromatographic peaks. The method is based on differences in branching ratios of ion abundances in their tandem mass spectra and an assumption that the product ion mass spectra of a mixture can be considered as a linear combination of the spectra of individual constituents. We present analytical equations and a matrix-based approach for deconvoluting the concentration of individual components from the total peak intensity for two and three isobars and also a matrix-based generalization to any number of compounds. The feasibility of the simultaneous analysis of mixtures containing two compounds was assessed. The approach was evaluated for the analysis of structural isomers of methylmalonic and succinic acids in human plasma and urine samples for a group of 270 samples. The linear regression equation, standard error and correlation coefficient for the agreement with a traditional method utilizing chromatographic separation of the isomers were y = 0.999x - 0.005, 0.024 micro mol l(-1), and 0.985, respectively. The utility of a spectral contrast angle as a predictor of analysis feasibility was evaluated.

  10. Isobaric yield ratios and the symmetry energy in heavy-ion reactions near the Fermi energy

    SciTech Connect

    Huang, M.; Chen, Z.; Kowalski, S.; Ma, Y. G.; Wada, R.; Hagel, K.; Barbui, M.; Bottosso, C.; Materna, T.; Natowitz, J. B.; Qin, L.; Rodrigues, M. R. D.; Sahu, P. K.; Keutgen, T.; Bonasera, A.; Wang, J.

    2010-04-15

    The relative isobaric yields of fragments produced in a series of heavy-ion-induced multifragmentation reactions have been analyzed in the framework of a modified Fisher model, primarily to determine the ratio of the symmetry energy coefficient to the temperature, a{sub sym}/T, as a function of fragment mass A. The extracted values increase from 5 to approx16 as A increases from 9 to 37. These values have been compared to the results of calculations using the antisymmetrized molecular dynamics (AMD) model together with the statistical decay code gemini. The calculated ratios are in good agreement with those extracted from the experiment. In contrast, the values extracted from the ratios of the primary isobars from the AMD model calculation are approx4 to 5 and show little variation with A. This observation indicates that the value of the symmetry energy coefficient derived from final fragment observables may be significantly different than the actual value at the time of fragment formation. The experimentally observed pairing effect is also studied within the same simulations. The Coulomb coefficient is also discussed.

  11. Isobaric molecular dynamics version of the generalized replica exchange method (gREM): Liquid–vapor equilibrium

    DOE PAGES

    Malolepsza, Edyta; Secor, Maxim; Keyes, Tom

    2015-09-23

    A prescription for sampling isobaric generalized ensembles with molecular dynamics is presented and applied to the generalized replica exchange method (gREM), which was designed for simulating first-order phase transitions. The properties of the isobaric gREM ensemble are discussed and a study is presented of the liquid-vapor equilibrium of the guest molecules given for gas hydrate formation with the mW water model. As a result, phase diagrams, critical parameters, and a law of corresponding states are obtained.

  12. Polymorphs of 1,1-diamino-2,2-dinitroethene (FOX-7): Isothermal compression versus isobaric heating

    NASA Astrophysics Data System (ADS)

    Dreger, Z. A.; Tao, Y.; Gupta, Y. M.

    2013-10-01

    Raman spectroscopy was used to examine polymorphic changes in 1,1-diamino-2,2-dinitroethene (FOX-7) single crystals under: isothermal compression to 15 GPa and isobaric heating to 500 K. Changes in the Raman spectra were observed at ˜2.0 and ˜4.5 GPa, and at ˜390 K and ˜450 K. These onsets are in general accord with previously reported onsets from IR measurements under isothermal compression and from X-ray diffraction measurements under isobaric heating, respectively. In contrast to recent suggestions, we show that the high pressure polymorphs have different vibrational structures, and likely different crystal structures, than the high temperature polymorphs.

  13. Dienogest, a selective progestin, reduces plasma estradiol level through induction of apoptosis of granulosa cells in the ovarian dominant follicle without follicle-stimulating hormone suppression in monkeys.

    PubMed

    Sasagawa, S; Shimizu, Y; Nagaoka, T; Tokado, H; Imada, K; Mizuguchi, K

    2008-07-01

    Dienogest is a selective progestin that has been shown to arrest ovarian follicular development in women, without affecting gonadotropin secretion. As luteal progesterone or exogeneous progestins are known to suppress ovarian folliculogenesis via the inhibition of gonadotropin secretion, this action of dienogest on ovaries seems to be unique. To examine the underlying mechanism of the antifolliculogenic effect of dienogest, female cynomolgus monkeys were treated with a single oral dose of 0.1 mg/kg dienogest on day 7 of the menstrual cycle. Plasma FSH, estradiol (E2), and progesterone levels were measured up to 15 days after dosing. In an additional experiment, ovaries were excised 24 h after dosing for histological examinations. As a result, plasma E2 level declined within 24 h after dosing, while dienogest did not decreased FSH level prior to E2 decline. After decline of E2 level, the low level of E2 was sustained for more than 11 days. It is considered that a single oral dose of dienogest induced atresia of the dominant follicle. In the histological examination, two out of three animals showed decline in E2 level. The ovarian dominant follicles from these animals showed apoptotic changes in granulosa cells with scattered aromatase expression within 24 h after dosing. These results indicate that the induction of atresia of the ovarian dominant follicle by direct action would be a possible mechanism of dienogest to inhibit plasma E2 level.

  14. Sulindac selectively inhibits colon tumor cell growth by activating the cGMP/PKG pathway to suppress Wnt/β-catenin signaling.

    PubMed

    Li, Nan; Xi, Yaguang; Tinsley, Heather N; Gurpinar, Evrim; Gary, Bernard D; Zhu, Bing; Li, Yonghe; Chen, Xi; Keeton, Adam B; Abadi, Ashraf H; Moyer, Mary P; Grizzle, William E; Chang, Wen-Chi; Clapper, Margie L; Piazza, Gary A

    2013-09-01

    Nonsteroidal anti-inflammatory drugs (NSAID) display promising antineoplastic activity for colorectal and other cancers, but toxicity from COX inhibition limits their long-term use for chemoprevention. Previous studies have concluded that the basis for their tumor cell growth inhibitory activity does not require COX inhibition, although the underlying mechanism is poorly understood. Here, we report that the NSAID sulindac sulfide inhibits cyclic guanosine 3',5'-monophosphate phosphodiesterase (cGMP PDE) activity to increase intracellular cGMP levels and activate cGMP-dependent protein kinase (PKG) at concentrations that inhibit proliferation and induce apoptosis of colon tumor cells. Sulindac sulfide did not activate the cGMP/PKG pathway, nor affect proliferation or apoptosis in normal colonocytes. Knockdown of the cGMP-specific PDE5 isozyme by siRNA and PDE5-specific inhibitors tadalafil and sildenafil also selectively inhibited the growth of colon tumor cells that expressed high levels of PDE5 compared with colonocytes. The mechanism by which sulindac sulfide and the cGMP/PKG pathway inhibits colon tumor cell growth involves the transcriptional suppression of β-catenin to inhibit Wnt/β-catenin T-cell factor transcriptional activity, leading to downregulation of cyclin D1 and survivin. These observations suggest that safer and more efficacious sulindac derivatives can be developed for colorectal cancer chemoprevention by targeting PDE5 and possibly other cGMP-degrading isozymes.

  15. Identification of differentially expressed genes in the oviduct of two rabbit lines divergently selected for uterine capacity using suppression subtractive hybridization.

    PubMed

    Ballester, M; Castelló, A; Peiró, R; Argente, M J; Santacreu, M A; Folch, J M

    2013-06-01

    Suppressive subtractive hybridization libraries from oviduct at 62 h post-mating of two lines of rabbits divergently selected for uterine capacity were generated to identify differentially expressed genes. A total of 438 singletons and 126 contigs were obtained by cluster assembly and sequence alignment of 704 expressed sequence tags (ESTs), of which 54% showed homology to known proteins of the non-redundant NCBI databases. Differential screening by dot blot validated 71 ESTs, of which 47 showed similarity to known genes. Transcripts of genes were functionally annotated in the molecular function and the biological process gene ontology categories using the BLAST2GO software and were assigned to reproductive developmental process, immune response, amino acid metabolism and degradation, response to stress and apoptosis terms. Finally, three interesting genes, PGR, HSD17B4 and ERO1L, were identified as overexpressed in the low line using RT-qPCR. Our study provides a list of candidate genes that can be useful to understanding the molecular mechanisms underlying the phenotypic differences observed in early embryo survival and development traits.

  16. Perinatal hypoxia-ischemia reduces α 7 nicotinic receptor expression and selective α 7 nicotinic receptor stimulation suppresses inflammation and promotes microglial Mox phenotype.

    PubMed

    Hua, Sansan; Ek, C Joakim; Mallard, Carina; Johansson, Maria E

    2014-01-01

    Inflammation plays a central role in neonatal brain injury. During brain inflammation the resident macrophages of the brain, the microglia cells, are rapidly activated. In the periphery, α 7 nicotinic acetylcholine receptors ( α 7R) present on macrophages can regulate inflammation by suppressing cytokine release. In the current study we investigated α 7R expression in neonatal mice after hypoxia-ischemia (HI). We further examined possible anti-inflammatory role of α 7R stimulation in vitro and microglia polarization after α 7R agonist treatment. Real-time PCR analysis showed a 33% reduction in α 7R expression 72 h after HI. Stimulation of primary microglial cells with LPS in combination with increasing doses of the selective α 7R agonist AR-R 17779 significantly attenuated TNF α release and increased α 7R transcript in microglial cells. Gene expression of M1 markers CD86 and iNOS, as well as M2 marker CD206 was not influenced by LPS and/or α 7R agonist treatment. Further, Mox markers heme oxygenase (Hmox1) and sulforedoxin-1 (Srx1) were significantly increased, suggesting a polarization towards the Mox phenotype after α 7R stimulation. Thus, our data suggest a role for the α 7R also in the neonatal brain and support the anti-inflammatory role of α 7R in microglia, suggesting that α 7R stimulation could enhance the polarization towards a reparative Mox phenotype.

  17. A Quantitative Tool to Distinguish Isobaric Leucine and Isoleucine Residues for Mass Spectrometry-Based De Novo Monoclonal Antibody Sequencing

    NASA Astrophysics Data System (ADS)

    Poston, Chloe N.; Higgs, Richard E.; You, Jinsam; Gelfanova, Valentina; Hale, John E.; Knierman, Michael D.; Siegel, Robert; Gutierrez, Jesus A.

    2014-07-01

    De novo sequencing by mass spectrometry (MS) allows for the determination of the complete amino acid (AA) sequence of a given protein based on the mass difference of detected ions from MS/MS fragmentation spectra. The technique relies on obtaining specific masses that can be attributed to characteristic theoretical masses of AAs. A major limitation of de novo sequencing by MS is the inability to distinguish between the isobaric residues leucine (Leu) and isoleucine (Ile). Incorrect identification of Ile as Leu or vice versa often results in loss of activity in recombinant antibodies. This functional ambiguity is commonly resolved with costly and time-consuming AA mutation and peptide sequencing experiments. Here, we describe a set of orthogonal biochemical protocols, which experimentally determine the identity of Ile or Leu residues in monoclonal antibodies (mAb) based on the selectivity that leucine aminopeptidase shows for n-terminal Leu residues and the cleavage preference for Leu by chymotrypsin. The resulting observations are combined with germline frequencies and incorporated into a logistic regression model, called Predictor for Xle Sites (PXleS) to provide a statistical likelihood for the identity of Leu at an ambiguous site. We demonstrate that PXleS can generate a probability for an Xle site in mAbs with 96% accuracy. The implementation of PXleS precludes the expression of several possible sequences and, therefore, reduces the overall time and resources required to go from spectra generation to a biologically active sequence for a mAb when an Ile or Leu residue is in question.

  18. NIPTL-Novo: Non-isobaric peptide termini labeling assisted peptide de novo sequencing.

    PubMed

    Zhang, Shen; Shan, Yichu; Zhang, Shurong; Sui, Zhigang; Zhang, Lihua; Liang, Zhen; Zhang, Yukui

    2017-02-10

    A simple and effective de novo sequencing strategy assisted by non-isobaric peptide termini labeling, NIPTL-Novo, was established. The y-series ions and b-series ions of peptides can be clearly distinguished according to the different mass tags incorporated in N-terminus and C-terminus. This is helpful for improving the accuracy of peptide sequencing and increasing the sequencing speed. For the spectra commonly identified by both de novo sequencing and database searching software (Mascot or Maxquant), NIPTL-Novo gave identical result to more than 85% of these spectra. Furthermore, the quantitative profiling of the sample can be performed simultaneously along with de novo sequencing. Finally, this strategy can be applied to discover the peptides with potential mutation sites by combining with mass-defect based isotopic labeling.

  19. Thermodynamic Quantities of Redlich-Kwong Gases in Isobaric Processes of Coexistence of Two Phases

    NASA Astrophysics Data System (ADS)

    Matsumoto, Akira

    2005-12-01

    The coexistence of gaseous and liquid phases in an isobaric process are investigated by applying the thermodynamic functions of the Redlich-Kwong equation. The boiling temperatures and the enthalpy changes of vaporization of 45 substances are obtained by numerical calculations. The results agree with the experimental data within a few percent for the 45 considered substances. Some thermodynamic quantities for C3H6 at 1 atm are calculated numerically as a function of T and drawn graphically. The Gibbs free energy indicates a polygonal line; entropy, volume and enthalpy jump from the liquid to the gaseous phase at the boiling point. The heat capacity does not diverge to infinity but shows a finite jump at the boiling point. This suggests that a first-order phase transition may occur at the boiling point.

  20. Intrathecal hyperbaric versus isobaric bupivacaine for adult non-caesarean-section surgery: systematic review protocol

    PubMed Central

    Uppal, Vishal; Shanthanna, Harsha; Prabhakar, Christopher; McKeen, Dolores M

    2016-01-01

    Introduction Bupivacaine is the most commonly used local anaesthetic for spinal anaesthesia (SA). There are two forms of commercially available bupivacaine; isobaric bupivacaine (IB): a formulation with a specific gravity or density equal to cerebrospinal fluid, and hyperbaric bupivacaine (HB): a formulation with density heavier than cerebrospinal fluid. The difference in densities of the two available preparations is believed to affect the diffusion pattern that determines the effectiveness, spread and side-effect profile of bupivacaine. This systematic review will summarise the best available evidence regarding the effectiveness and safety on the use of HB compared with IB, when used to provide SA for surgery. Primarily, we will analyse the need for conversion to general anaesthesia. As secondary outcomes, we will compare the incidence of hypotension, incidence of nausea/vomiting, the onset time and duration of anaesthesia. Methods and analysis We will search key electronic databases using search strategy (1) injections, spinal OR intrathecal OR subarachnoid; (2) bupivacaine OR levobupivacaine; (3) hypobaric OR isobaric OR plain; (4) baricity. We will search MEDLINE, EMBASE and Cochrane databases, from their inception for randomised controlled trials, with no restrictions on language. Caesarean section surgery will be excluded. 2 reviewers will independently extract the data using a standardised form. Extracted items will include study characteristics, risk of bias domains, as per modified Cochrane risk of bias, participant disposition and study outcomes. We will conduct a meta-analysis for variables that can be compared across the studies. We will evaluate clinical heterogeneity by qualitatively appraising differences in study characteristics in participants, interventions and the outcomes assessed. We will report our findings as relative risks (dichotomous), and weighted mean differences (continuous) for individual outcomes, along with their 95% CIs. Ethics and

  1. Geological, isothermal, and isobaric 3-D model construction in early stage of geothermal exploration

    NASA Astrophysics Data System (ADS)

    Saputra, M. P.; Suryantini; Catigtig, D.; Regandara, R.; Asnin, S. N.; Pratama, A. B.

    2016-09-01

    Construction of geology, thermal anomaly and pressure distribution of a geothermal system in the early stage of exploration where data is limited is described using a 3-D software, Leapfrog Geothermal. The geological 3-D model was developed from a topographic map (derived from DEM data), geological map and literature studies reported in an early geological survey. The isothermal 3-D model was constructed using reservoir temperature estimation from geothermometry calculated from chemical analyses on surface manifestations, available shallow gradient temperature hole data and the normal gradient temperature (3°C/100m) for a nonthermal area. The isobaric 3-D model was built using hydrostatic pressure where the hydrostatic pressure is determined by the product of the fluid density, acceleration due to gravity, and depth. Fluid density is given by saturated liquid density as a function of temperature. There are some constraints on the modelling result such as (1) within the predicted reservoir, the geothermal gradient is not constant but continues to increase, thus, creating an anomalously high temperature at depth, and (2) the lithology model is made by interpolating and extrapolating cross-sections whereas usually only two to three geology sections were available for this study. Hence, the modeller must understand the geology. An additional cross section was developed by the modeller which may not be as suitable as the geologist constructed sections. The results of this study can be combined with geophysical data such as gravity, geomagnetic, micro-tremor and resistivity data. The combination of geological, geochemical, isothermal, isobaric and geophysical data could be used in (1) estimating the geometry and size of the geothermal reservoir, (2) predicting the depth of top reservoir, and (3) creating well prognosis for exploration and production wells.

  2. Quantitation of isobaric phosphatidylcholine species in human plasma using a hybrid quadrupole linear ion-trap mass spectrometer.

    PubMed

    Zacek, Petr; Bukowski, Michael; Rosenberger, Thad A; Picklo, Matthew

    2016-12-01

    Phosphatidylcholine (PC) species in human plasma are used as biomarkers of disease. PC biomarkers are often limited by the inability to separate isobaric PCs. In this work, we developed a targeted shotgun approach for analysis of isobaric and isomeric PCs. This approach is comprised of two MS methods: a precursor ion scanning (PIS) of mass m/z 184 in positive mode (PIS m/z +184) and MS(3) fragmentation in negative mode, both performed on the same instrument, a hybrid triple quadrupole ion-trap mass spectrometer. The MS(3) experiment identified the FA composition and the relative abundance of isobaric and sn-1, sn-2 positional isomeric PC species, which were subsequently combined with absolute quantitative data obtained by PIS m/z +184 scan. This approach was applied to the analysis of a National Institute of Standards and Technology human blood plasma standard reference material (SRM 1950). We quantified more than 70 PCs and confirmed that a majority are present in isobaric and isomeric mixtures. The FA content determined by this method was comparable to that obtained using GC with flame ionization detection, supporting the quantitative nature of this MS method. This methodology will provide more in-depth biomarker information for clinical and mechanistic studies.

  3. Quantitation of isobaric phosphatidylcholine species in human plasma using a hybrid quadrupole linear ion-trap mass spectrometer[S

    PubMed Central

    Zacek, Petr; Bukowski, Michael; Rosenberger, Thad A.; Picklo, Matthew

    2016-01-01

    Phosphatidylcholine (PC) species in human plasma are used as biomarkers of disease. PC biomarkers are often limited by the inability to separate isobaric PCs. In this work, we developed a targeted shotgun approach for analysis of isobaric and isomeric PCs. This approach is comprised of two MS methods: a precursor ion scanning (PIS) of mass m/z 184 in positive mode (PIS m/z +184) and MS3 fragmentation in negative mode, both performed on the same instrument, a hybrid triple quadrupole ion-trap mass spectrometer. The MS3 experiment identified the FA composition and the relative abundance of isobaric and sn-1, sn-2 positional isomeric PC species, which were subsequently combined with absolute quantitative data obtained by PIS m/z +184 scan. This approach was applied to the analysis of a National Institute of Standards and Technology human blood plasma standard reference material (SRM 1950). We quantified more than 70 PCs and confirmed that a majority are present in isobaric and isomeric mixtures. The FA content determined by this method was comparable to that obtained using GC with flame ionization detection, supporting the quantitative nature of this MS method. This methodology will provide more in-depth biomarker information for clinical and mechanistic studies. PMID:27688258

  4. Isobaric Melt Productivity of Peridotite: Constraints from Simple and Complex Systems

    NASA Astrophysics Data System (ADS)

    Matzen, A.; Baker, M.; Stolper, E.

    2006-12-01

    Isobaric melt productivity, (dF/dT)P, is an important term in the expression for isentropic melt productivity, (dF/dP)S. Theoretical analysis [1] suggests that (dF/dT)P is low near the fertile peridotite solidus and increases with increasing melt fraction, F, but experimental studies on natural peridotite bulk compositions yield conflicting results; this ambiguity may reflect difficulty in achieving equilibrium, analyzing low-degree melts, and/or calculating F near the solidus. Five component systems based on CaO-MgO-Al2O3- SiO2 plus one of FeO, Na2O, or K2O capture much of the complexity of natural peridotites but are simple enough to allow detailed characterization of melting relations without resorting to rigorous thermodynamic modeling. We used parameterizations of solid and liquid compositions as functions of T and P in the systems CMASK [2], CMASNa [3], and CMASFe [4] to calculate F (by wt) of model peridotite compositions by mass balance. The selected bulk composition for each system maximized the range in F over which liquid coexists with ol+opx+cpx and either sp or pl (depending on P); F varied up to 0.2. For sp-lherzolite (lherz) at F=0.005, calculated (dF/dT)P for CMASK, CMASNa, and CMASFe are 0.00012, 0.00082, and 0.048/°C. In both CMASK and CMASNa, productivity increases dramatically with increasing F yielding strongly concave down curves (semi-log plot). CMASFe shows a limited increase in (dF/dT)P with increasing F. For pl- saturated melts, (dF/dT)P in CMASNa shows, like CMASFe, limited variation with increasing F and similar productivities. We also parameterized liquid and solid compositions in CMASCrK [5] and calculated F as a function of T. At F=0.005, productivity is nearly identical to that of CMASK but with increasing F, (dF/dT)P levels off and more closely tracks the variation shown by CMASNa (sp lherz); i.e., productivity does not reach the high values found in CMASK at high F. As discussed in [1], (dF/dT)P is inversely proportional to the

  5. Advances in surface ion suppression from RILIS: Towards the Time-of-Flight Laser Ion Source (ToF-LIS)

    NASA Astrophysics Data System (ADS)

    Rothe, S.; Catherall, R.; Crepieux, B.; Day Goodacre, T.; Fedosseev, V. N.; Giles, T.; Marsh, B. A.; Ramos, J. P.; Rossel, R. E.

    2016-06-01

    We present results from the development towards the Time-of-Flight Laser Ion Source (ToF-LIS) aiming for the suppression of isobaric contaminants through fast beam gating. The capability to characterize high resistance ion sources has been successfully demonstrated. A ninefold selectivity gain has been achieved through suppression of surface ionized potassium, while maintaining >90% transmission for laser-ionized gallium using a thin wall graphite ionizer cavity combined with a fast beam gate. Initial results from the investigation of glassy carbon as a potential hot cavity ion source are presented. Power-cycle tests of a newly designed mount for fragile ion source cavities indicates its capability to survive the thermal stress expected during operation in an ISOLDE target unit. Finally, we introduce fast ion beam switching at a rate of 10 kHz using the ISOLDE ion beam switchyard as a new concept for ion beam distribution and conclude by highlighting the potential applications of this ion beam multiplexing technique.

  6. Suppression of transverse-mode spurious responses for SAW resonators on SiO2/Al/LiNbO3 structure by selective removal of SiO2.

    PubMed

    Nakamura, Hiroyuki; Nakanishi, Hidekazu; Goto, Rei; Hashimoto, Ken-ya

    2011-10-01

    A SiO(2)/Al/LiNbO(3) structure has a large electromechanical coupling factor (K(2)) and good temperature coefficient of frequency (TCF) for applications as a SAW duplexer of the Universal Mobile Telecommunications System (UMTS) Band I. However, the SiO(2)/Al/LiNbO(3) structure also supports two unwanted spurious responses; one is caused by the Rayleigh mode and the other by the transverse mode. As the authors have previously discussed, the Rayleigh-mode spurious response can be suppressed by controlling the cross-sectional shape of a SiO(2) overlay deposited on resonator electrodes. In this paper, a new technique to suppress the transverse-mode spurious responses is proposed. In the technique, the SiO(2) overlay is selectively removed from the dummy electrode region. The spurious responses are analyzed by the laser probe system. The results indicate that the spurious responses in question were hybrid modes caused by the coupling between the main (SH) SAW and another (Rayleigh) SAW with different velocities. The hybrid-mode spurious behavior was dependent on the velocities in the IDT and the dummy regions (v(i) and v(d)). The hybrid-mode spurious responses could be suppressed by selectively removing SiO(2). Furthermore, the SAW energy confinement could be enhanced in the IDT electrode region when v(i) < v(d). The transverse-mode spurious responses were successfully suppressed without degrading the SAW resonator performances.

  7. Delayed neutralization of interleukin 6 reduces organ injury, selectively suppresses inflammatory mediator, and partially normalizes immune dysfunction following trauma and hemorrhagic shock.

    PubMed

    Zhang, Yong; Zhang, Jinxiang; Korff, Sebastian; Ayoob, Faez; Vodovotz, Yoram; Billiar, Timothy R

    2014-09-01

    An excessive and uncontrolled systemic inflammatory response is associated with organ failure, immunodepression, and increased susceptibility to nosocomial infection following trauma. Interleukin 6 (IL-6) plays a particularly prominent role in the host immune response after trauma with hemorrhage. However, as a result of its pleiotropic functions, the effect of IL-6 in trauma and hemorrhage is still controversial. It remains unclear whether suppression of IL-6 after hemorrhagic shock and trauma will attenuate organ injury and immunosuppression. In this study, C57BL/6 mice were treated with anti-mouse IL-6 monoclonal antibody immediately prior to resuscitation in an experimental model combining hemorrhagic shock and lower-extremity injury. Interleukin 6 levels and signaling were transiently suppressed following administrations of anti-IL-6 monoclonal antibody following hemorrhagic shock and lower-extremity injury. This resulted in reduced lung and liver injury, as well as suppression in the levels of key inflammatory mediators including IL-10, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and macrophage inhibitory protein 1α at both 6 and 24 h. Furthermore, the shift to TH2 cytokine production and suppressed lymphocyte response were partly prevented. These results demonstrate that IL-6 is not only a biomarker but also an important driver of injury-induced inflammation and immune suppression in mice. Rapid measurement of IL-6 levels in the early phase of postinjury care could be used to guide IL-6-based interventions.

  8. Differentiating Isobaric Steroid Hormone Metabolites Using Multi-Stage Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Tedmon, Lauren; Barnes, Jeremy S.; Nguyen, Hien P.; Schug, Kevin A.

    2013-03-01

    Steroid hormones and their metabolites are currently undergoing clinical trials as potential therapeutics for traumatic brain injury (TBI). To support this work, it is necessary to develop improved procedures for differentiating isobaric species in this compound class. Equilin sulfate (E-S), estrone sulfate (E1-S), 17α-dihydroequilin sulfate (ADHE-S), and 17β-dihydroequilin sulfate (BDHE-S) are primary constituents in hormone replacement therapies, such as Premarin, which are among pharmaceuticals being investigated for TBI treatment. The latter three compounds are isomers and can be difficult to differentiate in trace analytical determinations. In this work, a systematic study of the fragmentation of ADHE-S, BDHE-S, E1-S, and E-S under different stages of higher order tandem mass spectrometry (MSn) and variation of collision energy, allowed optimization of conditions for distinguishing the isomeric structures. For epimeric variants (e.g., ADHE-S versus BDHE-S; α- versus β-stereoisomerization in the C-17 position), differentiation was achieved at MS4 and fragmentation was demonstrated through MS5. Computational analysis was performed to further explore differences in the fragmentation pathways due to changes in stereochemistry.

  9. Excitation energies of double isobar-analog states in heavy nuclei

    SciTech Connect

    Poplavskii, I. V.

    1988-12-01

    Several new relationships are established for isomultiplets on the basis of a theory in which the Coulomb coupling constant (CCC) is allowed to be complex. In particular, the following rule is formulated: the energies for fission or decay of members of an isomultiplet into a charged cluster and members of the corresponding daughter isomultiplet are equidistant. This relationship is well satisfied for isomultiplets with /ital A/less than or equal to60. By extrapolating the rule for fission and decay energies to the region of heavy nuclei, the excitation energies /ital E//sub /ital x// of double isobar-analog states (DIASs) are found for the nuclei /sup 197,199/Hg, /sup 205/Pb, /sup 205 - -209/Po, /sup 209/At, and /sup 238/Pu. A comparison of the computed energies /ital E//sub /ital x// with the experimentally measured values for /sup 208/Po attest to the reliability and good accuracy of the method proposed here when used to determine the excitation energies of DIASs in heavy nuclei.

  10. Isobar channels and nucleon resonances in pi+ pi- electroproduction on protons

    SciTech Connect

    Fedotov, Gleb; Burkert, Volker; Golovach, Evgeny; Elouadrhiri, Latifa; Isupov, Evgeny; Ishkhanov, Boris; Mokeev, Viktor; Shvedunov, Nikolay

    2008-07-01

    http://dx.doi.org/10.1134/S1063778808070272
    A comprehensive set of differential cross sections for the reaction y v p--> pi - pi + p at the square of the photon 4-momentum in the range 0.2 < Q 2 < 0.6 GeV2 and the invariant mass of final-state hadrons in the range 1.3 < W < 1.6 GeV was first obtained with the CLAS detector at the Thomas Jefferson Laboratory. An analysis of these data on the basis of the phenomenological model developed by physicists from the Institute of Nuclear Physics at Moscow State University (INP MSU) and Thomas Jefferson Laboratory (INP MSU-Hall B at Jefferson Lab Collaboration) made it possible to determine, for the first time, the contributions of all isobar channels to the differential cross sections in question. The possibility of extracting the Q 2 dependences of the electromagnetic form factors for the P 11(1440) and D 13(1520) resonances in a kinematical region that is the most sensitive to the contribution of the meson-baryon cloud to the str

  11. Improved Isobaric Tandem Mass Tag Quantification by Ion Mobility-Mass Spectrometry

    PubMed Central

    Li, Lingjun

    2014-01-01

    Isobaric tandem mass tags are an attractive alternative to mass difference tags and label free approaches for quantitative proteomics due to the high degree of multiplexing that can be performed with their implementation. A drawback of tandem mass tags are that the co-isolation and co-fragmentation of labeled peptide precursors can result in chimeric MS/MS spectra that can underestimate the fold-change expression of each peptide. Two methods (QuantMode and MS3) have addressed this concern for ion trap and orbitrap instruments, but there is still a need to solve this problem for quadrupole time-of-flight (Q-TOF) instruments. Ion mobility (IM) separations coupled to Q-TOF instruments have the potential to mitigate MS/MS spectra chimeracy since IM-MS has the ability to separate ions based on charge, m/z, and collision cross section (CCS). This work presents results that showcase the power of IM-MS to improve tandem mass tag peptide quantitation accuracy by resolving co-isolated differently charged and same charged peptides prior to MS/MS fragmentation. PMID:24677527

  12. Sensitivity of N/Z ratio in projectile break-up of isobaric systems

    NASA Astrophysics Data System (ADS)

    De Filippo, E.; Pagano, A.; Russotto, P.; Acosta, L.; Auditore, L.; Baran, V.; Cap, T.; Cardella, G.; Colonna, M.; Francalanza, L.; Gnoffo, B.; Lanzalone, G.; Lombardo, I.; Marquínez-Durán, G.; Maiolino, C.; Minniti, T.; Norella, S.; Pagano, E. V.; Papa, M.; Piasecki, E.; Pirrone, S.; Politi, G.; Porto, F.; Quattrocchi, L.; Rizzo, F.; Rosato, E.; Trifirò, A.; Trimarchi, M.; Verde, G.; Vigilante, M.; Siwek-Wilczyńska, K.; Wilczyński, J.

    2016-05-01

    The binary break-up of projectile-like fragments in non central heavy-ion collisions follows different decay patterns, from equilibrated emission towards dynamical (prompt) fission. Recently, comparing two systems with different N/Z in the entrance channel, it has been shown that the dynamical emission cross-section is enhanced for the most neutron rich system while the statistical emission cross-section is independent from the isotopic composition. In order to understand this dependence and disentangle it from the initial size of the nuclei, we have studied the two isobaric systems 124Xe+64 Zn and 124Xe+64 Ni at 35 A MeV (InKiIsSy experiment), in comparison with the previous studied reactions (124Sn +64 Ni and 112Sn +58 Ni) at the same bombarding energy. We present the first results evidencing a striking similar effect in the dynamical decay as a function of the N/Z of the target for equal size systems.

  13. Quantifying the Chiral Magnetic Effect in Isobaric Heavy Ion Collisions Using Hydrodynamic Simulations

    NASA Astrophysics Data System (ADS)

    Lilleskov, Elias; Liao, Jinfeng; Jiang, Yin; Shi, Shuzhe

    2016-09-01

    The quark-gluon plasma created in heavy ion collisions is an exotic state of matter in which many unusual phenomena are manifested. One such phenomenon is the ``Chiral-Magnetic Effect'' (CME), wherein the powerful magnetic fields generated by colliding ions spin-polarize chiral quarks, causing a net transport effect in the direction of the fields. The CME predicts specific charge-dependent correlation observables, for which experimental evidence was reported, although the evidence is subject to background contamination. Isobaric collision experiments have been planned for 2018 at RHIC, which will study this effect by comparing 96Ru-96Ru and 96Zr-96Zr collisions. The two colliding systems are expected to have nearly identical bulk properties (including background contamination), yet about 10% difference in their magnetic fields due to different nuclear charges. This provides a unique opportunity to disentangle the CME observable and background effects. By simulating this effect using anomalous hydrodynamic simulations, we make a quantitative prediction for the CME-induced signal for several centralities in each of these two colliding systems. Our results suggest a significant enough difference in the signal to be experimentally detected- on the order of 15-20%. Thanks to the Indiana University REU program for their support.

  14. Volume crossover in deeply supercooled water adiabatically freezing under isobaric conditions.

    PubMed

    Aliotta, Francesco; Giaquinta, Paolo V; Pochylski, Mikolaj; Ponterio, Rosina C; Prestipino, Santi; Saija, Franz; Vasi, Cirino

    2013-05-14

    The irreversible return of a supercooled liquid to stable thermodynamic equilibrium often begins as a fast process which adiabatically drives the system to solid-liquid coexistence. Only at a later stage will solidification proceed with the expected exchange of thermal energy with the external bath. In this paper we discuss some aspects of the adiabatic freezing of metastable water at constant pressure. In particular, we investigated the thermal behavior of the isobaric gap between the molar volume of supercooled water and that of the warmer ice-water mixture which eventually forms at equilibrium. The available experimental data at ambient pressure, extrapolated into the metastable region within the scheme provided by the reference IAPWS-95 formulation, show that water ordinarily expands upon (partially) freezing under isenthalpic conditions. However, the same scheme also suggests that, for increasing undercoolings, the volume gap is gradually reduced and eventually vanishes at a temperature close to the currently estimated homogeneous ice nucleation temperature. This behavior is contrasted with that of substances which do not display a volumetric anomaly. The effect of increasing pressures on the alleged volume crossover from an expanded to a contracted ice-water mixture is also discussed.

  15. Type II shell evolution in A = 70 isobars from the N ≥ 40 island of inversion

    NASA Astrophysics Data System (ADS)

    Morales, A. I.; Benzoni, G.; Watanabe, H.; Tsunoda, Y.; Otsuka, T.; Nishimura, S.; Browne, F.; Daido, R.; Doornenbal, P.; Fang, Y.; Lorusso, G.; Patel, Z.; Rice, S.; Sinclair, L.; Söderström, P.-A.; Sumikama, T.; Wu, J.; Xu, Z. Y.; Yagi, A.; Yokoyama, R.; Baba, H.; Avigo, R.; Bello Garrote, F. L.; Blasi, N.; Bracco, A.; Camera, F.; Ceruti, S.; Crespi, F. C. L.; de Angelis, G.; Delattre, M.-C.; Dombradi, Zs.; Gottardo, A.; Isobe, T.; Kojouharov, I.; Kurz, N.; Kuti, I.; Matsui, K.; Melon, B.; Mengoni, D.; Miyazaki, T.; Modamio-Hoybjor, V.; Momiyama, S.; Napoli, D. R.; Niikura, M.; Orlandi, R.; Sakurai, H.; Sahin, E.; Sohler, D.; Schaffner, H.; Taniuchi, R.; Taprogge, J.; Vajta, Zs.; Valiente-Dobón, J. J.; Wieland, O.; Yalcinkaya, M.

    2017-02-01

    The level structures of 70Co and 70Ni, populated from the β decay of 70Fe, have been investigated using β-delayed γ-ray spectroscopy following in-flight fission of a 238U beam. The experimental results are compared to Monte-Carlo Shell-Model calculations including the pf +g9/2 +d5/2 orbitals. The strong population of a (1+) state at 274 keV in 70Co is at variance with the expected excitation energy of ∼1 MeV from near spherical single-particle estimates. This observation indicates a dominance of prolate-deformed intruder configurations in the low-lying levels, which coexist with the normal near spherical states. It is shown that the β decay of the neutron-rich A = 70 isobars from the new island of inversion to the Z = 28 closed-shell regime progresses in accordance with a newly reported type of shell evolution, the so-called Type II, which involves many particle-hole excitations across energy gaps.

  16. Differentiation of hydroxyproline isomers and isobars in peptides by tandem mass spectrometry.

    PubMed

    Kassel, D B; Biemann, K

    1990-08-01

    The isomeric 3- and 4-hydroxyprolines are isobaric with the isomers leucine and isoleucine, and all four have, therefore, the same "residue mass" of 113. Secondary fragmentation processes were found that differentiate the hydroxyproline isomers from each other and from the leucines. Variants of synthetic bradykinin containing one or two hydroxyproline moieties were prepared by using manual Edman degradation and/or enzymatic methods. The tandem mass spectra of these peptides were recorded. The C-terminal wn fragment ions allow the differentiation of 4-hydroxyproline from the 3-isomer and isoleucine, while the N-terminal an ions containing 4-hydroxyproline undergo H2O elimination to differentiate this amino acid from the 3-isomer and leucine. Lys-C digestion of a mussel adhesive protein produced a set of decapeptides varying in the degree of hydroxylation of proline and tyrosine. Heterogeneity with respect to 3-hydroxyproline and 4-hydroxyproline at a certain position in these peptides was assessed by tandem mass spectrometry based on the wn ion series in the CID spectra of these Lys-C peptides. Some N-terminal ions further allow for the differentiation of these two isomeric species.

  17. Adsorption of water vapor by poly(styrenesulfonic acid), sodium salt: isothermal and isobaric adsorption equilibria.

    PubMed

    Toribio, F; Bellat, J P; Nguyen, P H; Dupont, M

    2004-12-15

    Air conditioning and dehumidifying systems based on sorption on solids are of great interest, especially in humid climates, because they allow reduction of thermal loads and use of chlorofluorocarbons. Previous studies have shown that hydrophilic polymers such as sulfonic polymers can have very high performance in water adsorption from air. The aim of this study was to characterize the water vapor adsorption properties of fully sulfonated and monosulfonated poly(styrenesulfonic acid), sodium salt, and to elucidate the mechanism of adsorption on these materials. Adsorption isotherms have been determined by TGA between 298 and 317 K for pressures ranging from 0.1 to 45 hPa. They have type II of the IUPAC classification and a small hysteresis loop between adsorption and desorption processes was observed only for the monosulfonated sample. Water content is up to 80% weight at 80% relative humidity. Adsorption isotherms have been well fitted with the FHH model. Adsorption-desorption isobars have been determined by TGA under 37 hPa in the temperature range 298-373 K. They show that these polymers can be completely regenerated by heating at 313 K under humidified air. No degradation of the adsorption properties has been observed after several regenerations. Adsorption enthalpies and entropies have been deduced from the Clapeyron equation and from DSC measurements. A good agreement was found. A mechanism of adsorption is proposed considering two kinds of adsorbate: bounded water in electrostatic interaction with functional groups and free water resulting from condensation.

  18. A novel method for molecular dynamics simulation in the isothermal-isobaric ensemble

    NASA Astrophysics Data System (ADS)

    Huang, Cunkui; Li, Chunli; Choi, Phillip Y. K.; Nandakumar, K.; Kostiuk, Larry W.

    2011-01-01

    A novel algorithm is proposed to study fluid properties in the isothermal-isobaric (NPT) ensemble. The major feature of this approach is that the constant pressure in the NPT ensemble is created by two auto-adjusting boundaries that allow the system volume to fluctuate. Relative to other methods used to create the NPT ensemble, this approach is simpler to perform since no additional variables are introduced into the simulation system. To test this method, two systems with the same constant target pressure and temperature but different thermostats (Nose-Hoover and Berendsen) were performed by using a commonly used cut-off distance (i.e. r c = 2.5σ). The simulation results show that the proposed method works well in terms of creating spatially uniform mean temperature, pressure and density while still allowing appropriate levels of instantaneous fluctuations for observable quantities. The fluctuations of the system volume produced by this method were compared with that calculated by the theoretical equation. To test the reliability of the proposed method, additional simulations were carried out at eight different thermodynamic states but with the use of a longer cut-off distance (r c = 4.5σ). The results were compared with those obtained using the Nose-Hoover barostat with an r c of 4.5σ, as well as with experiments. The comparison shows that the results using the algorithm proposed in this article agree well with those obtained using other methods.

  19. Optimized proteomic analysis of a mouse model of cerebellar dysfunction using amine-specific isobaric tags

    PubMed Central

    Hu, Jun; Qian, Jin; Borisov, Oleg; Pan, Sanqiang; Li, Yan; Liu, Tong; Deng, Longwen; Wannemacher, Kenneth; Kurnellas, Michael; Patterson, Christa; Elkabes, Stella; Li, Hong

    2008-01-01

    Recent proteomic applications have demonstrated their potential for revealing the molecular mechanisms underlying neurodegeneration. The present study quantifies cerebellar protein changes in mice that are deficient in plasma membrane calcium ATPase 2 (PMCA2), an essential neuronal pump that extrudes calcium from cells and is abundantly expressed in Purkinje neurons. PMCA2-null mice display motor dyscoordination and unsteady gait deficits observed in neurological diseases such as multiple sclerosis and ataxia. We optimized an amine-specific isobaric tags (iTRAQ™)-based shotgun proteomics workflow for this study. This workflow took consideration of analytical variance as a function of ion signal intensity and employed biological repeats to aid noise reduction. Even with stringent protein identification criteria, we could reliably quantify nearly 1000 proteins, including many neuronal proteins that are important for synaptic function. We identified 21 proteins that were differentially expressed in PMCA2-null mice. These proteins are involved in calcium homeostasis, cell structure and chromosome organization. Our findings shed light on the molecular changes that underlie the neurological deficits observed in PMCA2-null mice. The optimized workflow presented here will be valuable for others who plan to implement the iTRAQ method. PMID:16800037

  20. Proteomic analysis of astrocytic secretion that regulates neurogenesis using quantitative amine-specific isobaric tagging

    SciTech Connect

    Yan, Hu; Zhou, Wenhao; Wei, Liming; Zhong, Fan; Yang, Yi

    2010-01-08

    Astrocytes are essential components of neurogenic niches that affect neurogenesis through membrane association and/or the release of soluble factors. To identify factors released from astrocytes that could regulate neural stem cell differentiation and proliferation, we used mild oxygen-glucose deprivation (OGD) to inhibit the secretory capacity of astrocytes. Using the Transwell co-culture system, we found that OGD-treated astrocytes could not promote neural stem cell differentiation and proliferation. Next, isobaric tagging for the relative and absolute quantitation (iTRAQ) proteomics techniques was performed to identify the proteins in the supernatants of astrocytes (with or without OGD). Through a multi-step analysis and gene ontology classification, 130 extracellular proteins were identified, most of which were involved in neuronal development, the inflammatory response, extracellular matrix composition and supportive functions. Of these proteins, 44 had never been reported to be produced by astrocytes. Using ProteinPilot software analysis, we found that 60 extracellular proteins were significantly altered (27 upregulated and 33 downregulated) in the supernatant of OGD-treated astrocytes. Among these proteins, 7 have been reported to be able to regulate neurogenesis, while others may have the potential to regulate neurogenesis. This study profiles the major proteins released by astrocytes, which play important roles in the modulation of neurogenesis.

  1. Parametric study and characterization of the isobaric thermomechanical transformation fatigue of nickel-rich NiTi SMA actuators

    NASA Astrophysics Data System (ADS)

    Bertacchini, Olivier W.; Schick, Justin; Lagoudas, Dimitris C.

    2009-03-01

    The recent development of various aerospace applications utilizing Ni-rich NiTi Shape memory Alloys (SMAs) as actuators motivated the need to characterize the cyclic response and the transformation fatigue behavior of such alloys. The fatigue life validation and certification of new designs is required in order to be implemented and used in future applications. For that purpose, a custom built fatigue test frame was designed to perform isobaric thermally induced transformation cycles on small dogbones SMA actuators (test gauge cross-section up to: 1.270 x 0.508 mm2). A parametric study on the cyclic response and transformation fatigue behavior of Ni-rich NiTi SMAs led to the optimization of several material/process and test parameters, namely: the applied stress range, the heat treatment, the heat treatment environment and the specimen thickness. However, fatigue testing was performed in a chilled waterless glycol environment maintained at a temperature of 5°C that showed evidence of corrosion-assisted transformation fatigue failure. Therefore, it was necessary to build a fatigue test frame that would employ a dry and inert cooling methodology to get away from any detrimental interactions between the specimens and the cooling medium (corrosion). The selected cooling method was gaseous nitrogen, sprayed into a thermally insulated chamber, maintaining a temperature of -20°C. The design of the gaseous nitrogen cooling was done in such a way that the actuation frequency is similar to the one obtained using the original design (~ 0.1 Hz). For both cooling methods, Joule resistive heating was used to heat the specimens. In addition and motivated by the difference in surface quality resulting from different material processing such as EDM wire cutting and heat treatments, EDM recast layer and oxide layer were removed. The removal was followed by an ultra-fine polish (0.05 μm) that was performed on a subset of the fatigue specimens. Experimental results are presented

  2. Large-Scale and Deep Quantitative Proteome Profiling Using Isobaric Labeling Coupled with Two-Dimensional LC-MS/MS.

    PubMed

    Gritsenko, Marina A; Xu, Zhe; Liu, Tao; Smith, Richard D

    2016-01-01

    Comprehensive, quantitative information on abundances of proteins and their posttranslational modifications (PTMs) can potentially provide novel biological insights into diseases pathogenesis and therapeutic intervention. Herein, we introduce a quantitative strategy utilizing isobaric stable isotope-labeling techniques combined with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) for large-scale, deep quantitative proteome profiling of biological samples or clinical specimens such as tumor tissues. The workflow includes isobaric labeling of tryptic peptides for multiplexed and accurate quantitative analysis, basic reversed-phase LC fractionation and concatenation for reduced sample complexity, and nano-LC coupled to high resolution and high mass accuracy MS analysis for high confidence identification and quantification of proteins. This proteomic analysis strategy has been successfully applied for in-depth quantitative proteomic analysis of tumor samples and can also be used for integrated proteome and PTM characterization, as well as comprehensive quantitative proteomic analysis across samples from large clinical cohorts.

  3. Influence of multiple scattering and absorption on the full scattering profile and the isobaric point in tissue.

    PubMed

    Duadi, Hamootal; Fixler, Dror

    2015-05-01

    Light reflectance and transmission from soft tissue has been utilized in noninvasive clinical measurement devices such as the photoplethysmograph (PPG) and reflectance pulse oximeter. Incident light on the skin travels into the underlying layers and is in part reflected back to the surface, in part transferred and in part absorbed. Most methods of near infrared (NIR) spectroscopy focus on the volume reflectance from a semi-infinite sample, while very few measure transmission. We have previously shown that examining the full scattering profile (angular distribution of exiting photons) provides more comprehensive information when measuring from a cylindrical tissue. Furthermore, an isobaric point was found which is not dependent on changes in the reduced scattering coefficient. The angle corresponding to this isobaric point depends on the tissue diameter. We investigated the role of multiple scattering and absorption on the full scattering profile of a cylindrical tissue. First, we define the range in which multiple scattering occurs for different tissue diameters. Next, we examine the role of the absorption coefficient in the attenuation of the full scattering profile. We demonstrate that the absorption linearly influences the intensity at each angle of the full scattering profile and, more importantly, the absorption does not change the position of the isobaric point. The findings of this work demonstrate a realistic model for optical tissue measurements such as NIR spectroscopy, PPG, and pulse oximetery.

  4. Quantification of Cell-Penetrating Peptide Associated with Polymeric Nanoparticles Using Isobaric-Tagging and MALDI-TOF MS/MS

    NASA Astrophysics Data System (ADS)

    Chiu, Jasper Z. S.; Tucker, Ian G.; McDowell, Arlene

    2016-11-01

    High sensitivity quantification of the putative cell-penetrating peptide di-arginine-histidine (RRH) associated with poly (ethyl-cyanoacrylate) (PECA) nanoparticles was achieved without analyte separation, using a novel application of isobaric-tagging and high matrix-assisted laser desorption/ionization coupled to time-of-flight (MALDI-TOF) mass spectrometry. Isobaric-tagging reaction equilibrium was reached after 5 min, with 90% or greater RRH peptide successfully isobaric-tagged after 60 min. The accuracy was greater than 90%, which indicates good reliability of using isobaric-tagged RRH as an internal standard for RRH quantification. The sample intra- and inter-spot coefficients of variations were less than 11%, which indicate good repeatability. The majority of RRH peptides in the nanoparticle formulation were physically associated with the nanoparticles (46.6%), whereas only a small fraction remained unassociated (13.7%). The unrecovered RRH peptide (~40%) was assumed to be covalently associated with PECA nanoparticles.

  5. Ability of intermittent androgen suppression to selectively create a non-trivial periodic orbit for a type of prostate cancer patients.

    PubMed

    Hirata, Yoshito; Aihara, Kazuyuki

    2015-11-07

    Intermittent androgen suppression is becoming a standard clinical option for patients who suffer from recurrence after an initial treatment of prostate cancer such as radiation therapy and radical prostatectomy. In the first mathematical model of intermittent androgen suppression (Ideta et al., 2008), the authors tried to control the trajectory of the model to a periodic orbit to enable patients to coexist with prostate cancer, even if it cannot be eradicated. Recently, we proposed a mathematical model capable of improving the quantitative reproduction of the behavior of prostate cancer under intermittent androgen suppression (Hirata et al., 2010a). Here we examine whether such a stable periodic orbit can be created for patients who eventually will have to experience the relapse of cancer at a later stage. By using a mathematical analysis, we found that the above model of Hirata et al. does not contain a non-zero periodic orbit that can be targeted for such patients, namely patients of type (ii) or type (iii) for whom intermittent androgen suppression cannot stabilize the origin where no cancer cells exist. This result might suggest that the patients must seek to delay the relapse as much as possible if the cancer cannot be eradicated. We further classify type (i) into subclasses where such a non-zero periodic orbit can either be stabilized or asymptotically stabilized.

  6. MRI analysis of the ISOBAR TTL internal fixation system for the dynamic fixation of intervertebral discs: a comparison with rigid internal fixation

    PubMed Central

    2014-01-01

    Objectives Using magnetic resonance imaging (MRI), we analyzed the efficacy of the posterior approach lumbar ISOBAR TTL internal fixation system for the dynamic fixation of intervertebral discs, with particular emphasis on its effects on degenerative intervertebral disc disease. Methods We retrospectively compared the MRIs of 54 patients who had previously undergone either rigid internal fixation of the lumbar spine or ISOBAR TTL dynamic fixation for the treatment of lumbar spondylolisthesis. All patients had received preoperative and 6-, 12-, and 24-month postoperative MRI scans of the lumbar spine with acquisition of both routine and diffusion-weighted images (DWI). The upper-segment discs of the fusion were subjected to Pfirrmann grading, and the lumbar intervertebral discs in the DWI sagittal plane were manually drawn; the apparent diffusion coefficient (ADC) value was measured. Results ADC values in the ISOBAR TTL dynamic fixation group measured at the 6-, 12-, and 24-month postoperative MRI studies were increased compared to the preoperative ADC values. The ADC values in the ISOBAR TTL dynamic fixation group at 24 months postoperatively were significantly different from the preoperative values (P < 0.05). At 24 months, the postoperative ADC values were significantly different between the rigid fixation group and the ISOBAR TTL dynamic fixation group (P < 0.05). Conclusion MRI imaging findings indicated that the posterior approach lumbar ISOBAR TTL internal fixation system can prevent or delay the degeneration of intervertebral discs. PMID:24898377

  7. Light-front representation of chiral dynamics with Δ isobar and large-Nc relations

    DOE PAGES

    Granados, C.; Weiss, C.

    2016-06-13

    Transverse densities describe the spatial distribution of electromagnetic current in the nucleon at fixed light-front time. At peripheral distances b = O(Mπ–1) the densities are governed by chiral dynamics and can be calculated model-independently using chiral effective field theory (EFT). Recent work has shown that the EFT results can be represented in first-quantized form, as overlap integrals of chiral light-front wave functions describing the transition of the nucleon to soft-pion-nucleon intermediate states, resulting in a quantum-mechanical picture of the peripheral transverse densities. We now extend this representation to include intermediate states with Δ isobars and implement relations based on themore » large-Nc limit of QCD. We derive the wave function overlap formulas for the Δ contributions to the peripheral transverse densities by way of a three-dimensional reduction of relativistic chiral EFT expressions. Our procedure effectively maintains rotational invariance and avoids the ambiguities with higher-spin particles in the light-front time-ordered approach. We study the interplay of πN and πΔ intermediate states in the quantum-mechanical picture of the densities in a transversely polarized nucleon. We show that the correct Nc-scaling of the charge and magnetization densities emerges as the result of the particular combination of currents generated by intermediate states with degenerate N and Δ. The off-shell behavior of the chiral EFT is summarized in contact terms and can be studied easily. As a result, the methods developed here can be applied to other peripheral densities and to moments of the nucleon's generalized parton distributions.« less

  8. Light-front representation of chiral dynamics with Δ isobar and large- N c relations

    NASA Astrophysics Data System (ADS)

    Granados, C.; Weiss, C.

    2016-06-01

    Transverse densities describe the spatial distribution of electromagnetic current in the nucleon at fixed light-front time. At peripheral distances b = O( M π - 1 ) the densities are governed by chiral dynamics and can be calculated model-independently using chiral effective field theory (EFT). Recent work has shown that the EFT results can be represented in first-quantized form, as overlap integrals of chiral light-front wave functions describing the transition of the nucleon to soft-pion-nucleon intermediate states, resulting in a quantum-mechanical picture of the peripheral transverse densities. We now extend this representation to include intermediate states with Δ isobars and implement relations based on the large- N c limit of QCD. We derive the wave function overlap formulas for the Δ contributions to the peripheral transverse densities by way of a three-dimensional reduction of relativistic chiral EFT expressions. Our procedure effectively maintains rotational invariance and avoids the ambiguities with higher-spin particles in the light-front time-ordered approach. We study the interplay of π N and πΔ intermediate states in the quantum-mechanical picture of the densities in a transversely polarized nucleon. We show that the correct N c -scaling of the charge and magnetization densities emerges as the result of the particular combination of currents generated by intermediate states with degenerate N and Δ. The off-shell behavior of the chiral EFT is summarized in contact terms and can be studied easily. The methods developed here can be applied to other peripheral densities and to moments of the nucleon's generalized parton distributions.

  9. Amplitude, isobar and grey-scale imaging of ultrasonic shadows behind rigid, elastic and gaseous spheres.

    PubMed

    Filipczyński, L; Kujawska, T; Tymkiewicz, R; Wójcik, J

    1996-01-01

    The theory of wave reflection from spherical obstacles was applied for determination of the cause of the shadow created by plane wave pulses incident on rigid, steel, gaseous spheres and on spheres made of kidney stones. The spheres were immersed in water which was assumed to be a tissue-like medium. Acoustic pressure distributions behind the spheres with the radii of 1 mm, 2.5 mm and 3.5 mm were determined at the frequency of 5 MHz. The use of the exact wave theory enabled us to take into account the diffraction effects. The computed pressure distributions were verified experimentally at the frequency of 5 MHz for a steel sphere with a 2.5-mm radius. The experimental and theoretical pulses were composed of about three ultrasonic frequency periods. Acoustic pressure distributions in the shadow zone of all spheres were shown in the amplitude axonometric projection, in the grey scale and also as acoustic isobar patterns. Our analysis confirmed existing simpler descriptions of the shadow from the point of view of reflection and refraction effects; however, our approach is more general, also including diffraction effects and assuming the pulse mode. The analysis has shown that gaseous spherical inclusions caused shadows with very high dynamics of acoustic pressures that were about 15 dB higher in relation to all the other spheres. The shadow length, determined as the length at which one observes a 6-dB drop of the acoustic pressure, followed the relation r-6dB = 3.7a2/lambda with the accuracy of about 20% independent of the sphere type. lambda denotes the wavelength and a the sphere radius. Thus, a theoretical possibility of differentiating between gaseous and other inclusions and of estimation of the inclusion size in the millimeter range from the shadow was shown. The influence of the frequency-dependent attenuation on the shadow will be considered in the next study.

  10. Nimesulide, a cyclooxygenase-2 selective inhibitor, suppresses obesity-related non-alcoholic fatty liver disease and hepatic insulin resistance through the regulation of peroxisome proliferator-activated receptor γ

    PubMed Central

    Tsujimoto, Shunsuke; Kishina, Manabu; Koda, Masahiko; Yamamoto, Yasutaka; Tanaka, Kohei; Harada, Yusuke; Yoshida, Akio; Hisatome, Ichiro

    2016-01-01

    Cyclooxygenase (COX)-2 selective inhibitors suppress non-alcoholic fatty liver disease (NAFLD); however, the precise mechanism of action remains unknown. The aim of this study was to examine how the COX-2 selective inhibitor nimesulide suppresses NAFLD in a murine model of high-fat diet (HFD)-induced obesity. Mice were fed either a normal chow diet (NC), an HFD, or HFD plus nimesulide (HFD-nime) for 12 weeks. Body weight, hepatic COX-2 mRNA expression and triglyceride accumulation were significantly increased in the HFD group. Triglyceride accumulation was suppressed in the HFD-nime group. The mRNA expression of hepatic peroxisome proliferator-activated receptor γ (PPARγ) and the natural PPARγ agonist 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) were significantly increased in the HFD group and significantly suppressed in the HFD-nime group. Glucose metabolism was impaired in the HFD group compared with the NC group, and it was significantly improved in the HFD-nime group. In addition, the plasma insulin levels in the HFD group were increased compared with those in the NC group, and were decreased in the HFD-nime group. These results indicate that HFD-induced NAFLD is mediated by the increased hepatic expression of COX-2. We suggest that the production of 15d-PGJ2, which is mediated by COX-2, induces NAFLD and hepatic insulin resistance by activating PPARγ. Furthermore, the mRNA expression of tissue inhibitor of metalloproteinases-1 (TIMP-1), procollagen-1 and monocyte chemoattractant protein-1 (MCP-1), as well as the number of F4/80-positive hepatic (Kupffer) cells, were significantly increased in the HFD group compared with the NC group, and they were reduced by nimesulide. In conclusion, COX-2 may emerge as a molecular target for preventing the development of NAFLD and insulin resistance in diet-related obesity. PMID:27431935

  11. Quantitative Proteomic Analysis of Serum from Pregnant Women Carrying a Fetus with Conotruncal Heart Defect Using Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Labeling

    PubMed Central

    Zhang, Ying; Kang, Yuan; Zhou, Qiongjie; Zhou, Jizi; Wang, Huijun; Jin, Hong; Liu, Xiaohui; Ma, Duan; Li, Xiaotian

    2014-01-01

    Objective To identify differentially expressed proteins from serum of pregnant women carrying a conotruncal heart defects (CTD) fetus, using proteomic analysis. Methods The study was conducted using a nested case-control design. The 5473 maternal serum samples were collected at 14–18 weeks of gestation. The serum from 9 pregnant women carrying a CTD fetus, 10 with another CHD (ACHD) fetus, and 11 with a normal fetus were selected from the above samples, and analyzed by using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography-tandem mass spectrometry(2D LC-MS/MS). The differentially expressed proteins identified by iTRAQ were further validated with Western blot. Results A total of 105 unique proteins present in the three groups were identified, and relative expression data were obtained for 92 of them with high confidence by employing the iTRAQ-based experiments. The downregulation of gelsolin in maternal serum of fetus with CTD was further verified by Western blot. Conclusions The identification of differentially expressed protein gelsolin in the serum of the pregnant women carrying a CTD fetus by using proteomic technology may be able to serve as a foundation to further explore the biomarker for detection of CTD fetus from the maternal serum. PMID:25393621

  12. Suppression of isotope scrambling in cell-free protein synthesis by broadband inhibition of PLP enymes for selective 15N-labelling and production of perdeuterated proteins in H2O.

    PubMed

    Su, Xun-Cheng; Loh, Choy-Theng; Qi, Ruhu; Otting, Gottfried

    2011-05-01

    Selectively isotope labelled protein samples can be prepared in vivo or in vitro from selectively labelled amino acids but, in many cases, metabolic conversions between different amino acids result in isotope scrambling. The best results are obtained by cell-free protein synthesis, where metabolic enzymes are generally less active, but isotope scrambling can never be suppressed completely. We show that reduction of E. coli S30 extracts with NaBH(4) presents a simple and inexpensive way to achieve cleaner selective isotope labelling in cell-free protein synthesis reactions. The purpose of the NaBH(4) is to inactivate all pyridoxal-phosphate (PLP) dependent enzymes by irreversible reduction of the Schiff bases formed between PLP and lysine side chains of the enzymes or amino groups of free amino acids. The reduced S30 extracts retain their activity of protein synthesis, can be stored as well as conventional S30 extracts and effectively suppress conversions between different amino acids. In addition, inactivation of PLP-dependent enzymes greatly stabilizes hydrogens bound to α-carbons against exchange with water, minimizing the loss of α-deuterons during cell-free production of proteins from perdeuterated amino acids in H(2)O solution. This allows the production of highly perdeuterated proteins that contain protons at all exchangeable positions, without having to back-exchange labile deuterons for protons as required for proteins that have been synthesized in D(2)O.

  13. Injections of the selective adenosine A2A antagonist MSX-3 into the nucleus accumbens core attenuate the locomotor suppression induced by haloperidol in rats

    PubMed Central

    Ishiwari, Keita; Madson, Lisa J.; Farrar, Andrew M.; Mingote, Susana M.; Valenta, John P.; DiGianvittorio, Michael D.; Frank, Lauren E.; Correa, Merce; Hockemeyer, Jörg; Müller, Christa; Salamone, John D.

    2009-01-01

    There is considerable evidence of interactions between adenosine A2A receptors and dopamine D2 receptors in striatal areas, and antagonists of the A2A receptor have been shown to reverse the motor effects of DA antagonists in animal models. The D2 antagonist haloperidol produces parkinsonism in humans, and also induces motor effects in rats, such as suppression of locomotion. The present experiments were conducted to study the ability of the adenosine A2A antagonist MSX-3 to reverse the locomotor effects of acute or subchronic administration of haloperidol in rats. Systemic (i.p.) injections of MSX-3 (2.5–10.0 mg/kg) were capable of attenuating the suppression of locomotion induced by either acute or repeated (i.e., 14 day) administration of 0.5 mg/kg haloperidol. Bilateral infusions of MSX-3 directly into the nucleus accumbens core (2.5 µg or 5.0 µg in 0.5 µl per side) produced a dose-related increase in locomotor activity in rats treated with 0.5 mg/kg haloperidol either acutely or repeatedly. There were no overall significant effects of MSX-3 infused directly into the dorsomedial nucleus accumbens shell or the ventrolateral neostriatum. These results indicate that antagonism of adenosine A2A receptors can attenuate the locomotor suppression produced by DA antagonism, and that this effect may be at least partially mediated by A2A receptors in the nucleus accumbens core. These studies suggest that adenosine and dopamine systems interact to modulate the locomotor and behavioral activation functions of nucleus accumbens core. PMID:17223207

  14. Application of the aerodynamic energy concept to the selection of transfer functions for flutter suppression and gust alleviation using active controls

    NASA Technical Reports Server (NTRS)

    Nissim, E.

    1977-01-01

    Changes are introduced in the aerodynamic energy approach which lead to an increase in the effectiveness of both the trailing-edge (TE) and the leading-edge (LE)-TE control systems. Control laws are determined, using realizable transfer functions, which permit the introduction of aerodynamic damping and stiffness terms in accordance with the requirements of any specific system. It is shown that flutter suppression and gust alleviation problems can successfully be treated either by a TE or by a LE-TE control system. The results obtained are applicable to a very wide class of aircraft operating within the subsonic Mach number range.

  15. Limits of the energy-spin phase space beyond the proton drip line : entry distributions fo Pt and Au isobars.

    SciTech Connect

    Smith, M. B.; Cizewski, J. A.; Carpenter, M. P.; Kondev, F. G.; Khoo, T. L.; Lauritsen, T.; Janssens, R. V. F.; Abu Saleem, K.; Ahmad, I.; Amro, H.; Danchev, M.; Davids, C. N.; Hartley, D. J.; Heinz, A.; Lister, C. J.; Ma, W. C.; Poli, G. L.; Ressler, J. J.; Reviol, W.; Riedinger, L. L.; Seweryniak, D.; Wiedenhoever, I.; Rutgers univ.; Illinois Inst. of Tech.; Mississippi State Univ.; Univ. of Tennessee; Univ. of Maryland; Washington Univ.

    2003-01-09

    Entry distributions in angular momentum and excitation energy have been measured for several very proton-rich isotopes of Pt and Au. This is the first systematic study of the energy-spin phase space for nuclei near and beyond the proton drip line. Comparisons are made between the distributions associated with proton-unbound Au nuclei and more stable Pt isobars. In {sup 173}Au the first evidence is seen for the limits of excitation energy and angular momentum which a nucleus beyond the proton drip line can sustain.

  16. The Isospin Admixture of The Ground State and The Properties of The Isobar Analog Resonances In Deformed Nuclei

    SciTech Connect

    Aygor, H. Ali; Maras, Ismail; Cakmak, Necla; Selam, Cevad

    2008-11-11

    Within quasiparticle random phase approximation (QRPA), Pyatov-Salamov method for the self-consistent determination of the isovector effective interaction strength parameter, restoring a broken isotopic symmetry for the nuclear part of the Hamiltonian, is used. The isospin admixtures in the ground state of the parent nucleus, and the isospin structure of the isobar analog resonance (IAR) state are investigated by including the pairing correlations between nucleons for {sup 72-80}Kr isotopes. Our results are compared with the spherical case and with other theoretical results.

  17. Drug Insight: appetite suppressants.

    PubMed

    Bray, George A

    2005-02-01

    The term 'appetite suppressant' is used to denote drugs that act primarily on the neurochemical transmitters of the central nervous system to reduce food intake. In addition to drugs that release or mimic the effect of norepinephrine (noradrenaline), this could include drugs that inhibit: reuptake of norepinephrine or 5-hydroxytryptamine (also known as serotonin); bind to the gamma-aminobutyric acid receptors or the cannabinoid receptors; and some peptides that reduce food intake. The sympathomimetic drugs phentermine, diethylpropion, benzphetamine, and phendimetrazine--so named because they mimic many effects of norepinephrine--are only approved in a few countries, and then only for short-term use. Sibutramine, a norepinephrine-5-hydroxytryptamine reuptake inhibitor, is approved for long-term use. Several new mechanisms for drug action are under investigation. Appetite suppressants should be viewed as useful adjuncts to diet and physical activity and might help selected patients to achieve and maintain weight loss.

  18. Investigational small-molecule drug selectively suppresses constitutive CYP2B6 activity at the gene transcription level: physiologically based pharmacokinetic model assessment of clinical drug interaction risk.

    PubMed

    Zamek-Gliszczynski, Maciej J; Mohutsky, Michael A; Rehmel, Jessica L F; Ke, Alice B

    2014-06-01

    The glycogen synthase kinase-3 inhibitor LY2090314 specifically impaired CYP2B6 activity during in vitro evaluation of cytochrome P450 (P450) enzyme induction in human hepatocytes. CYP2B6 catalytic activity was significantly decreased following 3-day incubation with 0.1-10 μM LY2090314, on average by 64.3% ± 5.0% at 10 μM. These levels of LY2090314 exposure were not cytotoxic to hepatocytes and did not reduce CYP1A2 and CYP3A activities. LY2090314 was not a time-dependent CYP2B6 inhibitor, did not otherwise inhibit enzyme activity at concentrations ≤10 μM, and was not metabolized by CYP2B6. Thus, mechanism-based inactivation or other direct interaction with the enzyme could not explain the observed reduction in CYP2B6 activity. Instead, LY2090314 significantly reduced CYP2B6 mRNA levels (Imax = 61.9% ± 1.4%; IC50 = 0.049 ± 0.043 μM), which were significantly correlated with catalytic activity (r(2) = 0.87, slope = 0.77; Imax = 57.0% ± 10.8%, IC50 = 0.057 ± 0.027 μM). Direct inhibition of constitutive androstane receptor by LY2090314 is conceptually consistent with the observed CYP2B6 transcriptional suppression (Imax = 100.0% ± 10.8% and 57.1% ± 2.4%; IC50 = 2.5 ± 1.2 and 2.1 ± 0.4 μM for isoforms 1 and 3, respectively) and may be sufficiently extensive to overcome the weak but potent activation of pregnane X receptor by ≤10 μM LY2090314 (19.3% ± 2.2% of maximal rifampin response, apparent EC50 = 1.2 ± 1.1 nM). The clinical relevance of these findings was evaluated through physiologically based pharmacokinetic model simulations. CYP2B6 suppression by LY2090314 is not expected clinically, with a projected <1% decrease in hepatic enzyme activity and <1% decrease in hydroxybupropion exposure following bupropion coadministration. However, simulations showed that observed CYP2B6 suppression could be clinically relevant for a drug with different pharmacokinetic properties from LY2090314.

  19. Epigallocatechin-3-gallate increases autophagy signaling in resting and unloaded plantaris muscles but selectively suppresses autophagy protein abundance in reloaded muscles of aged rats.

    PubMed

    Takahashi, Hideyuki; Suzuki, Yutaka; Mohamed, Junaith S; Gotoh, Takafumi; Pereira, Suzette L; Alway, Stephen E

    2017-03-07

    We have previously found that Epigallocatechin-3-gallate (EGCg), an abundant catechin in green tea, reduced apoptotic signaling and improved muscle recovery in response to reloading after hindlimb suspension (HS). In this study, we investigated if EGCg altered autophagy signaling in skeletal muscle of old rats in response to HS or reloading after HS. Fischer 344×Brown Norway inbred rats (age 34months) were given 1ml/day of purified EGCg (50mg/kg body weight), or the same sample volume of the vehicle by gavage. One group of animals received HS for 14days and the second group of rats received 14days of HS, then the HS was removed and they were allowed to recover by ambulating normally around the cage for two weeks. EGCg decreased a small number of autophagy genes in control muscles, but it increased the expression of other autophagy genes (e.g., ATG16L2, SNCA, TM9SF1, Pink1, PIM-2) and HS did not attenuate these increases. HS increased Beclin1, ATG7 and LC3-II/I protein abundance in hindlimb muscles. Relative to vehicle treatment, EGCg treatment had greater ATG12 protein abundance (35.8%, P<0.05), but decreased Beclin1 protein levels (-101.1%, P<0.05) after HS. However, in reloaded muscles, EGCg suppressed Beclin1 and LC3-II/I protein abundance as compared to vehicle treated muscles. EGCg appeared to "prime" autophagy signaling before and enhance autophagy gene expression and protein levels during unloading in muscles of aged rats, perhaps to improve the clearance of damaged organelles. However, EGCg suppressed autophagy signaling after reloading, potentially to increase the recovery of hindlimb muscles mass and function after loading is restored.

  20. Thermodynamic properties of supercritical n-m Lennard-Jones fluids and isochoric and isobaric heat capacity maxima and minima.

    PubMed

    Mairhofer, Jonas; Sadus, Richard J

    2013-10-21

    Molecular dynamics simulations are reported for the thermodynamic properties of n-m Lennard-Jones fluids, where n = 10 and 12, and m = 5 and 6. Results are reported for the thermal expansion coefficient, isothermal and adiabatic compressibilities, isobaric and isochoric heat capacities, Joule-Thomson coefficient, and speed of sound at supercritical conditions covering a wide range of fluid densities. The thermodynamic criteria for maxima∕minima in the isochoric and isobaric heat capacities are identified and the simulation results are also compared with calculations from Lennard-Jones equations of state. The Johnson et al. [Mol. Phys. 78, 591 (1993)] equation of state can be used to reproduce all heat capacity phenomena reported [T. M. Yigzawe and R. J. Sadus, J. Chem. Phys. 138, 194502 (2013)] from molecular dynamics simulations for the 12-6 Lennard-Jones potential. Significantly, these calculations and molecular dynamics results for other n-m Lennard-Jones potentials support the existence of Cp minima at supercritical conditions. The values of n and m also have a significant influence on many other thermodynamic properties.

  1. Thermodynamic properties of supercritical n-m Lennard-Jones fluids and isochoric and isobaric heat capacity maxima and minima

    NASA Astrophysics Data System (ADS)

    Mairhofer, Jonas; Sadus, Richard J.

    2013-10-01

    Molecular dynamics simulations are reported for the thermodynamic properties of n-m Lennard-Jones fluids, where n = 10 and 12, and m = 5 and 6. Results are reported for the thermal expansion coefficient, isothermal and adiabatic compressibilities, isobaric and isochoric heat capacities, Joule-Thomson coefficient, and speed of sound at supercritical conditions covering a wide range of fluid densities. The thermodynamic criteria for maxima/minima in the isochoric and isobaric heat capacities are identified and the simulation results are also compared with calculations from Lennard-Jones equations of state. The Johnson et al. [Mol. Phys. 78, 591 (1993)] equation of state can be used to reproduce all heat capacity phenomena reported [T. M. Yigzawe and R. J. Sadus, J. Chem. Phys. 138, 194502 (2013)] from molecular dynamics simulations for the 12-6 Lennard-Jones potential. Significantly, these calculations and molecular dynamics results for other n-m Lennard-Jones potentials support the existence of Cp minima at supercritical conditions. The values of n and m also have a significant influence on many other thermodynamic properties.

  2. Large-Scale and Deep Quantitative Proteome Profiling Using Isobaric Labeling Coupled with Two-Dimensional LC-MS/MS

    SciTech Connect

    Gritsenko, Marina A.; Xu, Zhe; Liu, Tao; Smith, Richard D.

    2016-02-12

    Comprehensive, quantitative information on abundances of proteins and their post-translational modifications (PTMs) can potentially provide novel biological insights into diseases pathogenesis and therapeutic intervention. Herein, we introduce a quantitative strategy utilizing isobaric stable isotope-labelling techniques combined with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) for large-scale, deep quantitative proteome profiling of biological samples or clinical specimens such as tumor tissues. The workflow includes isobaric labeling of tryptic peptides for multiplexed and accurate quantitative analysis, basic reversed-phase LC fractionation and concatenation for reduced sample complexity, and nano-LC coupled to high resolution and high mass accuracy MS analysis for high confidence identification and quantification of proteins. This proteomic analysis strategy has been successfully applied for in-depth quantitative proteomic analysis of tumor samples, and can also be used for integrated proteome and PTM characterization, as well as comprehensive quantitative proteomic analysis across samples from large clinical cohorts.

  3. A randomized controlled study comparing intrathecal hyperbaric bupivacaine-fentanyl mixture and isobaric bupivacaine-fentanyl mixture in common urological procedures

    PubMed Central

    Upadya, Madhusudan; Neeta, S; Manissery, Jesni Joseph; Kuriakose, Nigel; Singh, Rakesh Raushan

    2016-01-01

    Background and Aims: Bupivacaine is available in isobaric and hyperbaric forms for intrathecal use and opioids are used as additives to modify their effects. The aim of this study was to compare the efficacy and haemodynamic effect of intrathecal isobaric bupivacaine-fentanyl mixture and hyperbaric bupivacaine-fentanyl mixture in common urological procedures. Methods: One hundred American Society of Anesthesiologists physical status 1 and 2 patients undergoing urological procedures were randomized into two groups. Group 1 received 3 ml of 0.5% isobaric bupivacaine with 25 μg fentanyl while Group 2 received 3 ml of 0.5% hyperbaric bupivacaine with 25 μg fentanyl. The parameters measured include heart rate, blood pressure, respiratory rate, onset and duration of motor and sensory blockade. Student's unpaired t-test and the χ2 test were used to analyse the results, using the SPSS version 11.5 software. Results: The haemodynamic stability was better with isobaric bupivacaine fentanyl mixture (Group 1) than with hyperbaric bupivacaine fentanyl mixture (Group 2). The mean onset time in Group 1 for both sensory block (4 min) and motor block (5 min) was longer compared with Group 2. The duration of sensory block (127.8 ± 38.64 min) and motor block (170.4 ± 27.8 min) was less with isobaric bupivacaine group compared with hyperbaric bupivacaine group (sensory blockade 185.4 ± 16.08 min and motor blockade 201.6 ± 14.28 min). Seventy percent of patients in Group 2 had maximum sensory block level of T6 whereas it was 53% in Group 1. More patients in Group 1 required sedation compared to Group 2. Conclusion: Isobaric bupivacaine fentanyl mixture was found to provide adequate anaesthesia with minimal incidence of haemodynamic instability. PMID:26962255

  4. Next generation fire suppressants

    NASA Technical Reports Server (NTRS)

    Brown, Jerry A.

    1995-01-01

    Spectrex, Inc., located in Cedar Grove, NJ is a manufacturer of fire detection and suppression equipment. Spectrex is one of the original pioneers in high speed fire detection and suppression systems for combat vehicles. Spectrex has installed fire suppressions systems in thousands of combat vehicles and ships throughout the world. Additionally, they manufacture flame explosion detectors, ship damage control systems, and optical gas and vapor detectors. The culmination of several years of research and development has recently produced an innovative electro-optical continuous monitoring systems called SharpEye 20/20I IR(sup 3) and SAFEYE that provide fast and reliable gas, vapor, aerosol, flame, and explosion detection. SharpEye 20/20I IR(sup 3) is a self-contained triple spectrum flame detector which scans for oscillating IR radiation (1 to 10 Hz) in the spectral bands ranging from 4.0 to 5.0 microns and uses programmed algorithms to check the ratio and correlation of data received by the three sensors to make the system highly immune to false alarms. It is extremely sensitive as it can detect a 1 x 1 square foot gasoline pan fire at 200 feet in less than 3 seconds. The sensitivity is user programmable, offering 4 ranges of detection. SAFEYE is comprised of a selected number of multispectral ban microprocessors controlled detectors which are in communication with one or more radiation sources that is projected along a 600 feet optical path. The signals from the selected narrow bands are processed and analyzed by highly sophisticated algorithms. It is ideal for high risk, remote, large areas such as petroleum and chemical manufacturing sites, waste dumps, aircraft cargo bays, and ship compartments. The SAFEYE will perform direct readings of the presence or rate of rise of concentrations of gases, vapors, or aerosols at the range of parts per million and provide alarms at various set points at different levels of concentrations.

  5. Aerobic glycolysis suppresses p53 activity to provide selective protection from apoptosis upon loss of growth signals or inhibition of BCR-Abl

    PubMed Central

    Mason, Emily F.; Zhao, Yuxing; Goraksha-Hicks, Pankuri; Coloff, Jonathan L.; Gannon, Hugh; Jones, Stephen N.; Rathmell, Jeffrey C.

    2010-01-01

    Unlike the growth factor-dependence of normal cells, cancer cells can maintain growth factor-independent glycolysis and survival through expression of oncogenic kinases, such as BCR-Abl. While targeted kinase inhibition can promote cancer cell death, therapeutic resistance develops frequently and further mechanistic understanding is needed. Cell metabolism may be central to this cell death pathway, as we have shown that growth factor deprivation leads to decreased glycolysis that promotes apoptosis via p53 activation and induction of the pro-apoptotic protein Puma. Here, we extend these findings to demonstrate that elevated glucose metabolism, characteristic of cancer cells, can suppress PKCδ-dependent p53 activation to maintain cell survival after growth factor withdrawal. In contrast, DNA damage-induced p53 activation was PKCδ-independent and was not metabolically sensitive. Both stresses required p53 serine 18 phosphorylation for maximal activity but led to unique patterns of p53 target gene expression, demonstrating distinct activation and response pathways for p53 that were differentially regulated by metabolism. Consistent with oncogenic kinases acting to replace growth factors, treatment of BCR-Abl-expressing cells with the kinase inhibitor imatinib led to reduced metabolism and p53- and Puma-dependent cell death. Accordingly, maintenance of glucose uptake inhibited p53 activation and promoted imatinib resistance. Furthermore, inhibition of glycolysis enhanced imatinib sensitivity in BCR-Abl-expressing cells with wild type p53 but had little effect on p53 null cells. These data demonstrate that distinct pathways regulate p53 after DNA damage and metabolic stress and that inhibiting glucose metabolism may enhance the efficacy of and overcome resistance to targeted molecular cancer therapies. PMID:20876800

  6. No selection of CXCR4-using variants in cell reservoirs of dual-mixed HIV-infected patients on suppressive maraviroc therapy.

    PubMed

    Raymond, Stéphanie; Nicot, Florence; Carcenac, Romain; Jeanne, Nicolas; Cazabat, Michelle; Requena, Mary; Cuzin, Lise; Delobel, Pierre; Izopet, Jacques

    2016-03-27

    We used ultradeep sequencing to investigate the evolution of the frequency of CXCR4-using viruses in the peripheral blood mononuclear cells of 22 patients infected with both CCR5 and CXCR4-using viruses treated with the CCR5 antagonist maraviroc for 24 weeks and a stable antiviral therapy. The mean CXCR4-using virus frequency in peripheral blood mononuclear cells was 59% before maraviroc intensification and 52% after 24 weeks of effective treatment, indicating no selection by maraviroc.

  7. The Emotional Gatekeeper: A Computational Model of Attentional Selection and Suppression through the Pathway from the Amygdala to the Inhibitory Thalamic Reticular Nucleus

    PubMed Central

    Bullock, Daniel; Barbas, Helen

    2016-01-01

    In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN) is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective ‘framing’ effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders. PMID:26828203

  8. The Emotional Gatekeeper: A Computational Model of Attentional Selection and Suppression through the Pathway from the Amygdala to the Inhibitory Thalamic Reticular Nucleus.

    PubMed

    John, Yohan J; Zikopoulos, Basilis; Bullock, Daniel; Barbas, Helen

    2016-02-01

    In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN) is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective 'framing' effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders.

  9. Selective blockade of 5-hydroxytryptamine (5-HT)7 receptors enhances 5-HT transmission, antidepressant-like behavior, and rapid eye movement sleep suppression induced by citalopram in rodents.

    PubMed

    Bonaventure, Pascal; Kelly, Lisa; Aluisio, Leah; Shelton, Jonathan; Lord, Brian; Galici, Ruggero; Miller, Kirsten; Atack, John; Lovenberg, Timothy W; Dugovic, Christine

    2007-05-01

    Evidence has accumulated supporting a role for 5-hydroxytryptamine (5-HT)7 receptors in circadian rhythms, sleep, and mood disorders, presumably as a consequence of the modulation of 5-HT-mediated neuronal activity. We hypothesized that a selective 5-HT7 receptor antagonist, (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]-pyrrolidine (SB-269970), should increase activity of 5-HT neurons and potentiate the effect of selective serotonin reuptake inhibitors (citalopram). In rats, administration of 3 mg/kg s.c. citalopram alone increased the extracellular concentration of 5-HT. This effect of citalopram on extracellular 5-HT concentration was significantly enhanced by an ineffective dose of SB-269970. Combining this dose of SB-269970 with a low dose of citalopram also resulted in a significant increase in extracellular concentration of 5-HT, suggesting a potentiation of neurochemical effects. In mice, citalopram and SB-269970 dose-dependently decreased immobility time in the tail suspension test. The dose-effect curve of citalopram was shifted leftward by coadministration of an effective dose of SB-269970. Furthermore, combining ineffective doses of citalopram and SB-269970 also resulted in a significant decrease of immobility time in the tail suspension test, suggesting potentiation of antidepressant-like effects. In rats, SB-269970 potentiated the increase of rapid eye movement (REM) latency and the REM sleep decrease induced by citalopram. SB-269970 also reversed the increase in sleep fragmentation induced by citalopram. Rat plasma and brain concentrations of citalopram were not affected by coadministration of SB-269970, arguing for a pharmacodynamic rather than a pharmacokinetic mechanism. Overall, these results indicate that selective blockade of 5-HT7 receptors may enhance the antidepressant efficacy of citalopram and may provide a novel therapy to alleviate sleep disturbances associated with depression.

  10. GS 455534 selectively suppresses binge eating of palatable food and attenuates dopamine release in the accumbens of sugar-bingeing rats.

    PubMed

    Bocarsly, Miriam E; Hoebel, Bartley G; Paredes, Daniel; von Loga, Isabell; Murray, Susan M; Wang, Miaoyuan; Arolfo, Maria P; Yao, Lina; Diamond, Ivan; Avena, Nicole M

    2014-04-01

    Binge eating palatable foods has been shown to have behavioral and neurochemical similarities to drug addiction. GS 455534 is a highly selective reversible aldehyde dehydrogenase 2 inhibitor that has been shown to reduce alcohol and cocaine intake in rats. Given the overlaps between binge eating and drug abuse, we examined the effects of GS 455534 on binge eating and subsequent dopamine release. Sprague-Dawley rats were maintained on a sugar (experiment 1) or fat (experiment 2) binge eating diet. After 25 days, GS 455534 was administered at 7.5 and 15 mg/kg by an intraperitoneal injection, and food intake was monitored. In experiment 3, rats with cannulae aimed at the nucleus accumbens shell were maintained on the binge sugar diet for 25 days. Microdialysis was performed, during which GS 455534 15 mg/kg was administered, and sugar was available. Dialysate samples were analyzed to determine extracellular levels of dopamine. In experiment 1, GS 455534 selectively decreased sugar intake food was made available in the Binge Sugar group but not the Ad libitum Sugar group, with no effect on chow intake. In experiment 2, GS 455534 decreased fat intake in the Binge Fat group, but not the Ad libitum Fat group, however, it also reduced chow intake. In experiment 3, GS 455534 attenuated accumbens dopamine release by almost 50% in binge eating rats compared with the vehicle injection. The findings suggest that selective reversible aldehyde dehydrogenase 2 inhibitors may have the therapeutic potential to reduce binge eating of palatable foods in clinical populations.

  11. Observation of the double isobaric analog transition 18O(π+,π-) 18Ne at 50 MeV

    NASA Astrophysics Data System (ADS)

    Altman, A.; Johnson, R. R.; Wienands, U.; Hessey, N.; Barnett, B. M.; Forster, B. M.; Grion, N.; Mills, D.; Rozon, F. M.; Smith, G. R.; Trelle, And R.; Gill, D. R.; Sheffer, G.; Anderl, T.

    1985-09-01

    The angular distribution of the differential cross sections for the transition to the double isobaric analog state in the reaction 18(π+,π-) 18Ne was measured at six angles from 20° to 120°. Extrapolation of the differential cross section results in 5.3+/-0.5 μb/sr at 0° and an angle-integrated cross section of 16.7+/-1.2 μb. The forward peaking and magnitude of the cross sections differ from those predicted by simple sequential models and the trends of data at higher energies. The results are compared to recent data for the same transition on 14C at 50 MeV and to a calculation in the six-quark bag model.

  12. Molecular dynamics in the isothermal-isobaric ensemble: the requirement of a "shell" molecule. III. Discontinuous potentials.

    PubMed

    Uline, Mark J; Corti, David S

    2008-07-07

    Based on the approach of Gruhn and Monson [Phys. Rev. E 63, 061106 (2001)], we present a new method for deriving the collisions dynamics for particles that interact via discontinuous potentials. By invoking the conservation of the extended Hamiltonian, we generate molecular dynamics (MD) algorithms for simulating the hard-sphere and square-well fluids within the isothermal-isobaric (NpT) ensemble. Consistent with the recent rigorous reformulation of the NpT ensemble partition function, the equations of motion impose a constant external pressure via the introduction of a shell particle of known mass [M. J. Uline and D. S. Corti, J. Chem. Phys. 123, 164101 (2005); 123, 164102 (2005)], which serves to define uniquely the volume of the system. The particles are also connected to a temperature reservoir through the use of a chain of Nose-Hoover thermostats, the properties of which are not affected by a hard-sphere or square-well collision. By using the Liouville operator formalism and the Trotter expansion theorem to integrate the equations of motion, the update of the thermostat variables can be decoupled from the update of the positions of the particles and the momentum changes upon a collision. Hence, once the appropriate collision dynamics for the isobaric-isenthalpic (NpH) equations of motion is known, the adaptation of the algorithm to the NpT ensemble is straightforward. Results of MD simulations for the pure component square-well fluid are presented and serve to validate our algorithm. Finally, since the mass of the shell particle is known, the system itself, and not a piston of arbitrary mass, controls the time scales for internal pressure and volume fluctuations. We therefore consider the influence of the shell particle algorithm on the dynamics of the square-well fluid.

  13. Suppression of eosinophil function by RP 73401, a potent and selective inhibitor of cyclic AMP-specific phosphodiesterase: comparison with rolipram.

    PubMed Central

    Souness, J. E.; Maslen, C.; Webber, S.; Foster, M.; Raeburn, D.; Palfreyman, M. N.; Ashton, M. J.; Karlsson, J. A.

    1995-01-01

    1. We have investigated the inhibitory potency of RP 73401, a novel, highly selective and potent inhibitor of cyclic AMP-specific phosphodiesterase (PDE IV), against partially-purified PDE isoenzymes from smooth muscle and the particulate PDE IV from guinea-pig eosinophils. The inhibitory effects of RP 73401 on the generation of superoxide (.O2-), major basic protein (MBP) and eosinophil cationic protein (ECP) from guinea-pig eosinophils have also been studied. 2. RP 73401 potently inhibited partially-purified cyclic AMP-specific phosphodiesterase (PDE IV) from pig aortic smooth muscle (IC50 = 1.2 nM); it was similarly potent against the particulate PDE IV from guinea-pig peritoneal eosinophils (IC50 = 0.7 nM). It displayed at least a 19000 fold selectivity for PDE IV compared to its potencies against other PDE isoenzymes. Rolipram was approximately 2600 fold less potent than RP 73401 against pig aortic smooth muscle PDE IV (IC50 = 3162 nM) and about 250 times less potent against eosinophil PDE IV (IC50 = 186 nM). 3. Solubilization of the eosinophil particulate PDE IV increased the potency of rolipram 10 fold but did not markedly affect the potency of RP 73401. A similar (10 fold) increase in the PDE IV inhibitory potency of rolipram, but not RP 73401, was observed when eosinophil membranes were exposed to vanadate/glutathione complex (V/GSH). 4. Reverse transcription polymerase chain reaction (RT-PCR), using primer pairs designed against specific sequences in four distinct rat PDE IV subtype cDNA clones (PDE IVA-D), showed only mRNA for PDE IVD in guinea-pig eosinophils. PDE IVD was also the predominant subtype expressed in pig aortic smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 6 PMID:7647982

  14. Rapid Discovery and Structure–Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase

    PubMed Central

    2016-01-01

    Novel pyrazolopyrimidines displaying high potency and selectivity toward SRC family kinases have been developed by combining ligand-based design and phenotypic screening in an iterative manner. Compounds were derived from the promiscuous kinase inhibitor PP1 to search for analogs that could potentially target a broad spectrum of kinases involved in cancer. Phenotypic screening against MCF7 mammary adenocarcinoma cells generated target-agnostic structure–activity relationships that biased subsequent designs toward breast cancer treatment rather than to a particular target. This strategy led to the discovery of two potent antiproliferative leads with phenotypically distinct anticancer mode of actions. Kinase profiling and further optimization resulted in eCF506, the first small molecule with subnanomolar IC50 for SRC that requires 3 orders of magnitude greater concentration to inhibit ABL. eCF506 exhibits excellent water solubility, an optimal DMPK profile and oral bioavailability, halts SRC-associated neuromast migration in zebrafish embryos without inducing life-threatening heart defects, and inhibits SRC phosphorylation in tumor xenografts in mice. PMID:27115835

  15. (-)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis.

    PubMed

    Alberti, Thaís Barbosa; Barbosa, Wagner Luiz Ramos; Vieira, José Luiz Fernandes; Raposo, Nádia Rezende Barbosa; Dutra, Rafael Cypriano

    2017-04-01

    (-)-β-caryophyllene (BCP), a cannabinoid receptor type 2 (CB2)-selective phytocannabinoid, has already been shown in precedent literature to exhibit both anti-inflammatory and analgesic effects in mouse models of inflammatory and neuropathic pain. Herein, we endeavored to investigate the therapeutic potential of BCP on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Furthermore, we sought to demonstrate some of the mechanisms that underlie the modulation BCP exerts on autoimmune activated T cells, the pro-inflammatory scenery of the central nervous system (CNS), and demyelination. Our findings demonstrate that BCP significantly ameliorates both the clinical and pathological parameters of EAE. In addition, data hereby presented indicates that mechanisms underlying BCP immunomodulatory effect seems to be linked to its ability to inhibit microglial cells, CD4+ and CD8+ T lymphocytes, as well as protein expression of pro-inflammatory cytokines. Furthermore, it diminished axonal demyelination and modulated Th1/Treg immune balance through the activation of CB2 receptor. Altogether, our study represents significant implications for clinical research and strongly supports the effectiveness of BCP as a novel molecule to target in the development of effective therapeutic agents for MS.

  16. Dinaciclib potently suppresses MCL-1 and selectively induces the cell death in human iPS cells without affecting the viability of cardiac tissue

    PubMed Central

    Alsayegh, Khaled; Matsuura, Katsuhisa; Sekine, Hidekazu; Shimizu, Tatsuya

    2017-01-01

    Induced pluripotent stem (iPS) cells hold great potential for being a major source of cells for regenerative medicine. One major issue that hinders their advancement to clinic is the persistence of undifferentiated iPS cells in iPS-derived tissue. In this report, we show that the CDKs inhibitor, Dinaciclib, selectively eliminates iPS cells without affecting the viability of cardiac cells. We found that low nanomolar concentration of dinaciclib increased DNA damage and p53 protein levels in iPSCs. This was accompanied by negative regulation of the anti-apoptotic protein MCL-1. Gene knockdown experiments revealed that p53 downregulation only increased the threshold of dinaciclib induced apoptosis in iPS cells. Dinaciclib also inhibited the phosphorylation of Serine 2 of the C-terminal domain of RNA Polyemrase II through CDK9 inhibition. This resulted in the inhibition of transcription of MCL-1 and the pluripotency genes, NANOG and c-MYC. Even though dinaciclib caused a slight downregulation of MCL-1 in iPS-derived cardiac cells, the viability of the cells was not significantly affected, and beating iPS-derived cardiac cell sheet could still be fabricated. These findings suggest a difference in tolerance of MCL-1 downregulation between iPSCs and iPS-derived cardiac cells which could be exploited to eliminate remaining iPS cells in bioengineered cell sheet tissues. PMID:28361959

  17. Suppression subtractive hybridization.

    PubMed

    Ghorbel, Mohamed T; Murphy, David

    2011-01-01

    Comparing two RNA populations that differ from the effects of a single independent variable, such as a drug treatment or a specific genetic defect, can establish differences in the abundance of specific transcripts that vary in a population dependent manner. There are different methods for identifying differentially expressed genes. These methods include microarray, Serial Analysis of Gene Expression (SAGE), and quantitative Reverse-Transcriptase Polymerase Chain Reaction (qRT-PCR). Herein, the protocol describes an easy and cost-effective alternative that does not require prior knowledge of the transcriptomes under examination. It is specifically relevant when low levels of RNA starting material are available. This protocol describes the use of Switching Mechanism At RNA Termini Polymerase Chain Reaction (SMART-PCR) to amplify cDNA from small amounts of RNA. The amplified cDNA populations under comparison are then subjected to Suppression Subtractive Hybridization (SSH-PCR). SSH-PCR is a technique that couples subtractive hybridization with suppression PCR to selectively amplify fragments of differentially expressed genes. The resulting products are cDNA populations enriched for significantly overrepresented transcripts in either of the two input RNAs. These cDNA populations can then be cloned to generate subtracted cDNA library. Microarrays made with clones from the subtracted forward and reverse cDNA libraries are then screened for differentially expressed genes using targets generated from tester and driver total RNAs.

  18. Loss of Jak2 selectively suppresses DC-mediated innate immune response and protects mice from lethal dose of LPS-induced septic shock.

    PubMed

    Zhong, Jixin; Yang, Ping; Muta, Kenjiro; Dong, Robert; Marrero, Mario; Gong, Feili; Wang, Cong-Yi

    2010-03-09

    Given the importance of Jak2 in cell signaling, a critical role for Jak2 in immune cells especially dendritic cells (DCs) has long been proposed. The exact function for Jak2 in DCs, however, remained poorly understood as Jak2 deficiency leads to embryonic lethality. Here we established Jak2 deficiency in adult Cre(+/+)Jak2(fl/fl) mice by tamoxifen induction. Loss of Jak2 significantly impaired DC development as manifested by reduced BMDC yield, smaller spleen size and reduced percentage of DCs in total splenocytes. Jak2 was also crucial for the capacity of DCs to mediate innate immune response. Jak2(-/-) DCs were less potent in response to inflammatory stimuli and showed reduced capacity to secrete proinflammatory cytokines such as TNFalpha and IL-12. As a result, Jak2(-/-) mice were defective for the early clearance of Listeria after infection. However, their potency to mediate adaptive immune response was not affected. Unlike DCs, Jak2(-/-) macrophages showed similar capacity secretion of proinflammatory cytokines, suggesting that Jak2 selectively modulates innate immune response in a DC-dependent manner. Consistent with these results, Jak2(-/-) mice were remarkably resistant to lethal dose of LPS-induced septic shock, a deadly sepsis characterized by the excessive innate immune response, and adoptive transfer of normal DCs restored their susceptibility to LPS-induced septic shock. Mechanistic studies revealed that Jak2/SATA5 signaling is pivotal for DC development and maturation, while the capacity for DCs secretion of proinflammatory cytokines is regulated by both Jak2/STAT5 and Jak2/STAT6 signaling.

  19. Olanzapine augments the effect of selective serotonin reuptake inhibitors by suppressing GABAergic inhibition via antagonism of 5-HT₆ receptors in the dorsal raphe nucleus.

    PubMed

    Asaoka, Nozomi; Nagayasu, Kazuki; Nishitani, Naoya; Yamashiro, Mayumi; Shirakawa, Hisashi; Nakagawa, Takayuki; Kaneko, Shuji

    2015-08-01

    The combination of the selective serotonin reuptake inhibitors (SSRIs) and atypical antipsychotic drugs shows better therapeutic efficacy than SSRI monotherapy in the treatment of depression. However, the underlying mechanisms responsible for the augmenting effects of olanzapine are not fully understood. Here, we report that olanzapine enhances the SSRI-induced increase in extracellular serotonin (5-HT) levels and antidepressant-like effects by inhibiting GABAergic neurons through 5-HT6 receptor antagonism in the dorsal raphe nucleus (DRN). In organotypic raphe slice cultures, treatment with olanzapine (1-100 μM) enhanced the increase in extracellular 5-HT levels in the presence of fluoxetine (10 μM) or citalopram (1 μM). The enhancing effect of olanzapine was not further augmented by the GABAA receptor antagonist bicuculline. Electrophysiological analysis revealed that olanzapine (50 μM) decreased the firing frequency of GABAergic neurons in acute DRN slices. Among many serotonergic agents, the 5-HT6 receptor antagonist SB399885 (1-100 μM) mimicked the effects of olanzapine by enhancing the SSRI-induced increase in extracellular 5-HT levels, which was not further augmented by bicuculline or olanzapine. SB399885 (50 μM) also decreased the firing frequency of GABAergic neurons in the DRN. In addition, an intraperitoneal administration of SB399885 (10 mg/kg) to mice significantly enhanced the antidepressant-like effect of a subeffective dose of citalopram (3 mg/kg) in the tail-suspension test. These results suggest that olanzapine decreases local inhibitory GABAergic tone in the DRN through antagonism of 5-HT6 receptors, thereby increasing the activity of at least part of serotonergic neurons, which may contribute to the augmentation of the efficacy of SSRIs.

  20. DACH1, a zona glomerulosa selective gene in the human adrenal, activates transforming growth factor-β signaling and suppresses aldosterone secretion.

    PubMed

    Zhou, Junhua; Shaikh, Lalarukh Haris; Neogi, Sudeshna G; McFarlane, Ian; Zhao, Wanfeng; Figg, Nichola; Brighton, Cheryl A; Maniero, Carmela; Teo, Ada E D; Azizan, Elena A B; Brown, Morris J

    2015-05-01

    Common somatic mutations in CACNAID and ATP1A1 may define a subgroup of smaller, zona glomerulosa (ZG)-like aldosterone-producing adenomas. We have therefore sought signature ZG genes, which may provide insight into the frequency and pathogenesis of ZG-like aldosterone-producing adenomas. Twenty-one pairs of zona fasciculata and ZG and 14 paired aldosterone-producing adenomas from 14 patients with Conn's syndrome and 7 patients with pheochromocytoma were assayed by the Affymetrix Human Genome U133 Plus 2.0 Array. Validation by quantitative real-time polymerase chain reaction was performed on genes >10-fold upregulated in ZG (compared with zona fasciculata) and >10-fold upregulated in aldosterone-producing adenomas (compared with ZG). DACH1, a gene associated with tumor progression, was further analyzed. The role of DACH1 on steroidogenesis, transforming growth factor-β, and Wnt signaling activity was assessed in the human adrenocortical cell line, H295R. Immunohistochemistry confirmed selective expression of DACH1 in human ZG. Silencing of DACH1 in H295R cells increased CYP11B2 mRNA levels and aldosterone production, whereas overexpression of DACH1 decreased aldosterone production. Overexpression of DACH1 in H295R cells activated the transforming growth factor-β and canonical Wnt signaling pathways but inhibited the noncanonical Wnt signaling pathway. Stimulation of primary human adrenal cells with angiotensin II decreased DACH1 mRNA expression. Interestingly, there was little overlap between our top ZG genes and those in rodent ZG. In conclusion, (1) the transcriptome profile of human ZG differs from rodent ZG, (2) DACH1 inhibits aldosterone secretion in human adrenals, and (3) transforming growth factor-β signaling pathway is activated in DACH1 overexpressed cells and may mediate inhibition of aldosterone secretion in human adrenals.

  1. From a natural product lead to the identification of potent and selective benzofuran-3-yl-(indol-3-yl)maleimides as glycogen synthase kinase 3beta inhibitors that suppress proliferation and survival of pancreatic cancer cells.

    PubMed

    Gaisina, Irina N; Gallier, Franck; Ougolkov, Andrei V; Kim, Ki H; Kurome, Toru; Guo, Songpo; Holzle, Denise; Luchini, Doris N; Blond, Sylvie Y; Billadeau, Daniel D; Kozikowski, Alan P

    2009-04-09

    Recent studies have demonstrated that glycogen synthase kinase 3beta (GSK-3beta) is overexpressed in human colon and pancreatic carcinomas, contributing to cancer cell proliferation and survival. Here, we report the design, synthesis, and biological evaluation of benzofuran-3-yl-(indol-3-yl)maleimides, potent GSK-3beta inhibitors. Some of these compounds show picomolar inhibitory activity toward GSK-3beta and an enhanced selectivity against cyclin-dependent kinase 2 (CDK-2). Selected GSK-3beta inhibitors were tested in the pancreatic cancer cell lines MiaPaCa-2, BXPC-3, and HupT3. We determined that some of these compounds, namely compounds 5, 6, 11, 20, and 26, demonstrate antiproliferative activity against some or all of the pancreatic cancer cells at low micromolar to nanomolar concentrations. We found that the treatment of pancreatic cancer cells with GSK-3beta inhibitors 5 and 26 resulted in suppression of GSK-3beta activity and a distinct decrease of the X-linked inhibitor of apoptosis (XIAP) expression, leading to significant apoptosis. The present data suggest a possible role for GSK-3beta inhibitors in cancer therapy, in addition to their more prominent applications in CNS disorders.

  2. ZERO SUPPRESSION FOR RECORDERS

    DOEpatents

    Fort, W.G.S.

    1958-12-30

    A zero-suppression circuit for self-balancing recorder instruments is presented. The essential elements of the circuit include a converter-amplifier having two inputs, one for a reference voltage and the other for the signal voltage under analysis, and a servomotor with two control windings, one coupled to the a-c output of the converter-amplifier and the other receiving a reference input. Each input circuit to the converter-amplifier has a variable potentiometer and the sliders of the potentiometer are ganged together for movement by the servoinotor. The particular noveity of the circuit resides in the selection of resistance values for the potentiometer and a resistor in series with the potentiometer of the signal circuit to ensure the full value of signal voltage variation is impressed on a recorder mechanism driven by servomotor.

  3. Large-Scale Identification and Analysis of Suppressive Drug Interactions

    PubMed Central

    Cokol, Murat; Weinstein, Zohar B.; Yilancioglu, Kaan; Tasan, Murat; Doak, Allison; Cansever, Dilay; Mutlu, Beste; Li, Siyang; Rodriguez-Esteban, Raul; Akhmedov, Murodzhon; Guvenek, Aysegul; Cokol, Melike; Cetiner, Selim; Giaever, Guri; Iossifov, Ivan; Nislow, Corey; Shoichet, Brian; Roth, Frederick P.

    2014-01-01

    SUMMARY One drug may suppress the effects of another. Although knowledge of drug suppression is vital to avoid efficacy-reducing drug interactions or discover countermeasures for chemical toxins, drug-drug suppression relationships have not been systematically mapped. Here, we analyze the growth response of Saccharomyces cerevisiae to anti-fungal compound (“drug”) pairs. Among 440 ordered drug pairs, we identified 94 suppressive drug interactions. Using only pairs not selected on the basis of their suppression behavior, we provide an estimate of the prevalence of suppressive interactions between anti-fungal compounds as 17%. Analysis of the drug suppression network suggested that Bromopyruvate is a frequently suppressive drug and Staurosporine is a frequently suppressed drug. We investigated potential explanations for suppressive drug interactions, including chemogenomic analysis, coaggregation, and pH effects, allowing us to explain the interaction tendencies of Bromopyruvate. PMID:24704506

  4. Neutron-skin effects in isobaric yield ratios for mirror nuclei in a statistical abrasion-ablation model

    NASA Astrophysics Data System (ADS)

    Ma, Chun-Wang; Wei, Hui-Ling; Ma, Yu-Gang

    2013-10-01

    Background: The isobaric yield ratio for mirror nuclei [IYR(m)] in heavy-ion collisions, which is assumed to depend linearly on x=2(Z-1)/A1/3 of a fragment, is applied to study some coefficients of the energy terms in the binding energy, as well as the difference between the chemical potentials of a neutron and proton. It is found that the IYR(m) has a systematic dependence on the reaction, which has been explained as the volume and/or the isospin effects in previous studies. However, neither the volume nor the isospin effects can fully interpret the data.Purpose: We suppose that the IYR(m) depends on the neutron-skin thickness (δnp) of the projectile, and check the idea of whether the neutron-skin thickness effects can fully explain the systematic dependence of the IYR(m).Methods: A modified statistical abrasion-ablation model is used to calculate the reactions induced by projectiles of three series: (1) the calcium isotopes from 36Ca to 56Ca as projectiles with different limitations on the impact parameters (bmax) to show the volume effects according to bmax; (2) the A=45 isobars as the projectiles having different isospins and δnp; and (3) projectiles having similar δnp to show whether the IYR(m) depends on the volume or the isospin of the projectile.Results: The IYR(m) shows a distribution of a linear part in the small-x fragments, and a nonlinear part in the large-x fragments. The linear part of IYR(m) is fitted. (1) In the calcium isotopic reactions, the IYR(m) depends on the isospin or the volume of the projectile, but δnp greatly influences the nonlinear part of the IYR(m). The IYR(m) does not depend on the colliding source in reactions of small bmax for the nonneutron-rich projectiles, and does not depend on the collision sources in reactions by the neutron-rich projectiles. (2) In reactions of the A=45 isobars, though IYR(m) depends on the isospin of projectile, IYR(m) shows small dependence on isospin if δnp>0. (3) In the reactions of projectiles

  5. Dexamethasone suppression test

    MedlinePlus

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

  6. Charge-Exchange Excitation of the Isobaric Analog State and Implication for the Nuclear Symmetry Energy and Neutron Skin

    NASA Astrophysics Data System (ADS)

    Khoa, Dao T.; Loc, Bui Minh; Zegers, R. G. T.

    The charge-exchange (p, n) or (3He,t) reaction can be considered as elastic scattering of proton or 3He by the isovector term of the optical potential that flips the projectile isospin. Therefore, the accurately measured charge-exchange scattering cross section for the isobaric analog states can be a good probe of the isospin dependence of the optical potential, which is determined exclusively within the folding model by the difference between the neutron and proton densities and isospin dependence of the nucleon-nucleon interaction. On the other hand, the same isospin- and density-dependent nucleon-nucleon interaction can also be used in a Hartree-Fock calculation of asymmetric nuclear matter, to estimate the nuclear matter energy and its asymmetry part. As a result, the fine-tuning of the isospin dependence of the effective nucleon-nucleon interaction against the measured (p, n) or (3He,t) cross sections should allow us to make some realistic prediction of the nuclear symmetry energy and its density dependence. Moreover, given the neutron skin of the target related directly to the neutron-proton difference of the ground-state density, it can be well probed in the analysis of the charge-exchange (3He,t) reactions at medium energies when the two-step processes can be neglected and the t-matrix interaction can be used in the folding calculation.

  7. Multichannel study on the fragmentation of the 1g9/2 isobaric analog resonance in 53Mn

    NASA Astrophysics Data System (ADS)

    Sziklai, J.; Cameron, J. A.; Szöghy, I. M.; Vass, T.

    1994-02-01

    Fragments of the 1g9/2 isobaric analog resonance in 53Mn corresponding to the 3.715 MeV state (Sn=0.57) in 53Cr were located using the 52Cr(p,p0), 52Cr(p,p1), 52Cr(p,p1γ), 52Cr(p,p2γ), and 52Cr(p,γ)53Mn reactions. Differential cross sections were measured in the 4.06-4.28 MeV, and the γ-excitation curves in the 4.04-4.35 MeV proton energy region. Spins, parities, and partial widths were determined with the aid of R-matrix analysis for all resonances observed in the region. The spins of the 1g9/2 resonance fragments were found independently from (p,p1γ), (p,p2γ), and (p,γ) angular distribution measurements and their analyses. Nineteen fragments were identified and their γ-branching ratios to low lying levels of 53Mn were also deduced. Partial widths for each fragment in all four channels were derived. Channel-channel correlations were calculated. Fine structure analyses were carried out in all open channels. Inelastic spectroscopic factors and Coulomb displacement energy for the 1g9/2 state were also derived.

  8. Extracting survival parameters from isothermal, isobaric, and "iso-concentration" inactivation experiments by the "3 end points method".

    PubMed

    Corradini, M G; Normand, M D; Newcomer, C; Schaffner, D W; Peleg, M

    2009-01-01

    Theoretically, if an organism's resistance can be characterized by 3 survival parameters, they can be found by solving 3 simultaneous equations that relate the final survival ratio to the lethal agent's intensity. (For 2 resistance parameters, 2 equations will suffice.) In practice, the inevitable experimental scatter would distort the results of such a calculation or render the method unworkable. Averaging the results obtained with more than 3 final survival ratio triplet combinations, determined in four or more treatments, can remove this impediment. This can be confirmed by the ability of a kinetic inactivation model derived from the averaged parameters to predict survival patterns under conditions not employed in their determination, as demonstrated with published isothermal survival data of Clostridium botulinum spores, isobaric data of Escherichia coli under HPP, and Pseudomonas exposed to hydrogen peroxide. Both the method and the underlying assumption that the inactivation followed a Weibull-Log logistic (WeLL) kinetics were confirmed in this way, indicating that when an appropriate survival model is available, it is possible to predict the entire inactivation curves from several experimental final survival ratios alone. Where applicable, the method could simplify the experimental procedure and lower the cost of microbial resistance determinations. In principle, the methodology can be extended to deteriorative chemical reactions if they too can be characterized by 2 or 3 kinetic parameters.

  9. Accounting for an isobaric interference allows correct determination of folate vitamers in serum by isotope dilution-liquid chromatography-tandem mass spectrometry1, 2, 3

    PubMed Central

    Fazili, Zia; Pfeiffer, Christine M.

    2017-01-01

    Mild and prolonged oxidative degradation of 5-methyltetrahydrofolate (5-methylTHF) leads to the biologically inactive pyrazino-s-triazine derivative of 4α-hydroxy-5-methylTHF (MeFox). MeFox and the biologically active 5-formyltetrahydrofolate (5-formylTHF) are isobaric compounds that behave similarly during chromatographic and mass separation, making coelution and misidentification likely. Our published routine LC-MS/MS method did not discern between 5-formylTHF and MeFox, measuring the sum of these compounds at mass/charge ratio [m/z] 474→327 as 5-formylTHF. We modified this method to separate MeFox and 5-formylTHF either by chromatography or by unique mass transitions and then applied the two methods to serum specimens to determine typical concentrations of these compounds. The two unique transitions (m/z: 5-formylTHF 474→299; MeFox 474→284) showed good sensitivity (LOD [nmol/L]: 5-formylTHF 0.21; MeFox 0.34), selectivity (no interfering peaks), spiking recovery (mean±SD: 5-formylTHF 103%±3.4%; MeFox 94%±10%), and low imprecision (CV: 5-formylTHF 3.9% at 2.4 nmol/L; MeFox 5.1% at 2.9 nmol/L). The mass separation method detected 5-formylTHF in the same specimens as the chromatographic separation method. Analysis of several thousand serum specimens showed that the majority (~85%) contained MeFox at <3 nmol/L, but no detectable 5-formylTHF concentrations; some (~14%) contained 5-formylTHF at <0.5 nmol/L; a few specimens contained 5-formylTHF at >1 nmol/L and MeFox at >10 nmol/L. In summary, serum can contain 5-formylTHF high enough to contribute to total folate and contains MeFox that will bias total folate if not separated appropriately. Including measurements of MeFox and 5-formylTHF along with the other folate vitamers will enhance assessments of the association between biologically active folate and health effects. PMID:23173171

  10. Revalidation of the isobaric multiplet mass equation for the A=20 quintet

    SciTech Connect

    Glassman, B. E.; Pérez-Loureiro, D.; Wrede, C.; Allen, J.; Bardayan, D. W.; Bennett, M. B.; Brown, B. A.; Chipps, K. A.; Febbraro, M.; Fry, C.; Hall, M. R.; Hall, O.; Liddick, S. N.; O'Malley, P.; Ong, W.; Pain, S. D.; Schwartz, S. B.; Shidling, P.; Sims, H.; Thompson, P.; Zhang, H.

    2015-10-29

    An unexpected breakdown of the isobaric multiplet mass equation in the A = 20, T = 2 quintet was recently reported, presenting a challenge to modern theories of nuclear structure. In the present work, the excitation energy of the lowest T = 2 state in Na-20 has been measured to be 6498.4 +/- 0.2stat ± 0.4syst keV by using the superallowed 0+ → 0+ beta decay of Mg-20 to access it and an array of high-purity germanium detectors to detect its gamma-ray deexcitation. This value differs by 27 keV (1.9 standard deviations) from the recommended value of 6525 ± 14 keV and is a factor of 28 more precise. The isobaric multiplet mass equation is shown to be revalidated when the new value is adopted.

  11. Spectroscopy of {sup 20}Mg: The isobaric mass multiplet equation for the 2{sup +} states of the A=20, T=2 quintet and distant mirror nuclei

    SciTech Connect

    Gade, A.; Bowen, M. D.; Brown, B. A.; Campbell, C. M.; Cook, J. M.; Glasmacher, T.; McDaniel, S.; Siwek, K.; Adrich, P.; Bazin, D.; Obertelli, A.; Weisshaar, D.; Hosier, K.; McGlinchery, D.; Riley, L. A.

    2007-08-15

    We report on the first determination of the 2{sub 1}{sup +} energy of {sup 20}Mg, the most neutron-deficient Mg isotope known to exist. The result, E(2{sub 1}{sup +})=1598(10) keV, obtained from in-beam {gamma}-ray spectroscopy following the two-neutron removal from a {sup 22}Mg secondary beam, is discussed in the framework of the isobaric mass multiplet equation (IMME). Resulting predictions for the excitation energies of the T=2,2{sup +} states in the {sup 20}F and {sup 20}Na isobars are presented. The mirror energy difference, E(2{sub 1}{sup +},{sup 20}Mg)-E(2{sub 1}{sup +},{sup 20}O)=-77(10) keV, is compared to a recent prediction within the nuclear shell model based on the 'USD'm - gap Z14<'' modification of the universal sd (USD) effective interaction.

  12. Identification of the Lowest T =2 , Jπ=0+ Isobaric Analog State in 52Co and Its Impact on the Understanding of β -Decay Properties of 52Ni

    NASA Astrophysics Data System (ADS)

    Xu, X.; Zhang, P.; Shuai, P.; Chen, R. J.; Yan, X. L.; Zhang, Y. H.; Wang, M.; Litvinov, Yu. A.; Xu, H. S.; Bao, T.; Chen, X. C.; Chen, H.; Fu, C. Y.; Kubono, S.; Lam, Y. H.; Liu, D. W.; Mao, R. S.; Ma, X. W.; Sun, M. Z.; Tu, X. L.; Xing, Y. M.; Yang, J. C.; Yuan, Y. J.; Zeng, Q.; Zhou, X.; Zhou, X. H.; Zhan, W. L.; Litvinov, S.; Blaum, K.; Audi, G.; Uesaka, T.; Yamaguchi, Y.; Yamaguchi, T.; Ozawa, A.; Sun, B. H.; Sun, Y.; Dai, A. C.; Xu, F. R.

    2016-10-01

    Masses of 52g,52mCo were measured for the first time with an accuracy of ˜10 keV , an unprecedented precision reached for short-lived nuclei in the isochronous mass spectrometry. Combining our results with the previous β -γ measurements of 52Ni, the T =2 , Jπ=0+ isobaric analog state (IAS) in 52Co was newly assigned, questioning the conventional identification of IASs from the β -delayed proton emissions. Using our energy of the IAS in 52Co, the masses of the T =2 multiplet fit well into the isobaric multiplet mass equation. We find that the IAS in 52Co decays predominantly via γ transitions while the proton emission is negligibly small. According to our large-scale shell model calculations, this phenomenon has been interpreted to be due to very low isospin mixing in the IAS.

  13. Effect of isobaric breathing gas shifts from air to heliox mixtures on resolution of air bubbles in lipid and aqueous tissues of recompressed rats.

    PubMed

    Hyldegaard, O; Kerem, D; Melamed, Y

    2011-09-01

    Deep tissue isobaric counterdiffusion that may cause unwanted bubble formation or transient bubble growth has been referred to in theoretical models and demonstrated by intravascular gas formation in animals, when changing inert breathing gas from nitrogen to helium after hyperbaric air breathing. We visually followed the in vivo resolution of extravascular air bubbles injected at 101 kPa into nitrogen supersaturated rat tissues: adipose, spinal white matter, skeletal muscle or tail tendon. Bubbles were observed during isobaric breathing-gas shifts from air to normoxic (80:20) heliox mixture while at 285 kPa or following immediate recompression to either 285 or 405 kPa, breathing 80:20 and 50:50 heliox mixtures. During the isobaric shifts, some bubbles in adipose tissue grew marginally for 10-30 min, subsequently they shrank and disappeared at a rate similar to or faster than during air breathing. No such bubble growth was observed in spinal white matter, skeletal muscle or tendon. In spinal white matter, an immediate breathing gas shift after the hyperbaric air exposure from air to both (80:20) and (50:50) heliox, coincident with recompression to either 285 or 405 kPa, caused consistent shrinkage of all air bubbles, until they disappeared from view. Deep tissue isobaric counterdiffusion may cause some air bubbles to grow transiently in adipose tissue. The effect is marginal and of no clinical consequence. Bubble disappearance rate is faster with heliox breathing mixtures as compared to air. We see no reason for reservations in the use of heliox breathing during treatment of air-diving-induced decompression sickness.

  14. Aqua Ions-Graphene Interfacial and Confinement Behavior: Insights from isobaric-isothermal molecular dynamics

    SciTech Connect

    Chialvo, Ariel A; Cummings, Peter T

    2011-01-01

    We carry out a systematic micro-structural characterization of the solidfluid interface (SFI) of water and simple metal chloride aqueous solutions in contact with a free standing plate or with two such plates separated by an inter-plate distance 0 ! h( ) ! 30 at ambient conditions via isothermalisobaric molecular dynamics. With this characterization we target the interrogation of the system in search for answers to fundamental questions regarding the structure of the external and internal (confined) SFI s, the effect of the differential hydration behavior among species and its link to species expulsion from confinement. For water at ambient conditions we found that the structure of the external SFI s is independent of the interplate distance h in the range 0 ! h( ) ! 30 , i.e., the absence of wallmediated correlation effects between external and internal SFI s, and that for h < 9 the slit-pores de-wet. Moreover, we observed a selective expulsion of ions caused by the differential hydration between the anion and the cations with a consequent charging of the slit-pore. All these observations were interpreted in terms of the axial profiles for precisely defined order parameters including tetrahedral configuration, hydrogen bonding, and species coordination numbers.

  15. Production of radioactive Ag ion beams with a chemically selective laser ion source

    NASA Astrophysics Data System (ADS)

    Jading, Y.; Catherall, R.; Jokinen, A.; Jonsson, O. C.; Kugler, E.; Lettry, J.; Ravn, H. L.; Tengblad, O.; Kautzsch, T.; Klöckl, I.; Kratz, K.-L.; Scheerer, F.; Fedoseyev, V. N.; Mishin, V. I.; van Duppen, P.; Wöhr, A.; Walters, W. B.

    1996-04-01

    We have developed a chemically selective laser ion source at the CERN-ISOLDE facility in order to study neutron-rich Ag nuclides. A pulsed laser system with high repetition rate has been used based on high-power copper-vapour pump lasers and dye lasers. With this source significant reductions of the isobaric background has been achieved.

  16. Fire Suppression and Response

    NASA Technical Reports Server (NTRS)

    Ruff, Gary A.

    2004-01-01

    This report is concerned with the following topics regarding fire suppression:What is the relative effectiveness of candidate suppressants to extinguish a representative fire in reduced gravity, including high-O2 mole fraction, low -pressure environments? What are the relative advantages and disadvantages of physically acting and chemically-acting agents in spacecraft fire suppression? What are the O2 mole fraction and absolute pressure below which a fire cannot exist? What effect does gas-phase radiation play in the overall fire and post-fire environments? Are the candidate suppressants effective to extinguish fires on practical solid fuels? What is required to suppress non-flaming fires (smoldering and deep seated fires) in reduced gravity? How can idealized space experiment results be applied to a practical fire scenario? What is the optimal agent deployment strategy for space fire suppression?

  17. X-ray continuum as a measure of pressure and fuel–shell mix in compressed isobaric hydrogen implosion cores

    SciTech Connect

    Epstein, R.; Goncharov, V. N.; Marshall, F. J.; Betti, R.; Nora, R.; Christopherson, A. R.; Golovkin, I. E.; MacFarlane, J. J.

    2015-02-01

    Pressure, by definition, characterizes the conditions within an isobaric implosion core at peak compression [Gus’kov et al., Nucl. Fusion 16, 957 (1976); Betti et al., Phys. Plasmas 8, 5257 (2001)] and is a key parameter in quantifying its near-ignition performance [Lawson, Proc. Phys. Soc. London, B 70, 6 (1957); Betti et al., Phys. Plasmas 17, 058102 (2010); Goncharov et al., Phys. Plasmas 21, 056315 (2014); and Glenzer et al., Phys. Plasmas 19, 056318 (2012)]. At high spectral energy, where the x-ray emission from an imploded hydrogen core is optically thin, the emissivity profile can be inferred from the spatially resolved core emission. This emissivity, which can be modeled accurately under hot-core conditions, is dependent almost entirely on the pressure when measured within a restricted spectral range matched to the temperature range anticipated for the emitting volume. In this way, the hot core pressure at the time of peak emission can be inferred from the measured free-free emissivity profile. The pressure and temperature dependences of the x-ray emissivity and the neutron-production rate explain a simple scaling of the total filtered x-ray emission as a constant power of the total neutron yield for implosions of targets of similar design over a broad range of shell implosion isentropes. This scaling behavior has been seen in implosion simulations and is confirmed by measurements of high-isentrope implosions [Sangster et al., Phys. Plasmas 20, 056317 (2013)] on the OMEGA laser system [Boehly et al., Opt. Commun. 133, 495 (1997)]. Attributing the excess emission from less-stable, low-isentrope implosions, above the level expected from this neutron-yield scaling, to the higher emissivity of shell carbon mixed into the implosion’s central hot spot, the hot-spot “fuel–shell” mix mass can be inferred.

  18. X-ray continuum as a measure of pressure and fuel–shell mix in compressed isobaric hydrogen implosion cores

    SciTech Connect

    Epstein, R.; Goncharov, V. N.; Marshall, F. J.; Betti, R.; Nora, R.; Christopherson, A. R.; Golovkin, I. E.; MacFarlane, J. J.

    2015-02-15

    Pressure, by definition, characterizes the conditions within an isobaric implosion core at peak compression [Gus'kov et al., Nucl. Fusion 16, 957 (1976); Betti et al., Phys. Plasmas 8, 5257 (2001)] and is a key parameter in quantifying its near-ignition performance [Lawson, Proc. Phys. Soc. London, B 70, 6 (1957); Betti et al., Phys. Plasmas 17, 058102 (2010); Goncharov et al., Phys. Plasmas 21, 056315 (2014); and Glenzer et al., Phys. Plasmas 19, 056318 (2012)]. At high spectral energy, where the x-ray emission from an imploded hydrogen core is optically thin, the emissivity profile can be inferred from the spatially resolved core emission. This emissivity, which can be modeled accurately under hot-core conditions, is dependent almost entirely on the pressure when measured within a restricted spectral range matched to the temperature range anticipated for the emitting volume. In this way, the hot core pressure at the time of peak emission can be inferred from the measured free-free emissivity profile. The pressure and temperature dependences of the x-ray emissivity and the neutron-production rate explain a simple scaling of the total filtered x-ray emission as a constant power of the total neutron yield for implosions of targets of similar design over a broad range of shell implosion isentropes. This scaling behavior has been seen in implosion simulations and is confirmed by measurements of high-isentrope implosions [Sangster et al., Phys. Plasmas 20, 056317 (2013)] on the OMEGA laser system [Boehly et al., Opt. Commun. 133, 495 (1997)]. Attributing the excess emission from less-stable, low-isentrope implosions, above the level expected from this neutron-yield scaling, to the higher emissivity of shell carbon mixed into the implosion's central hot spot, the hot-spot “fuel–shell” mix mass can be inferred.

  19. Quantitative analysis of human cerebrospinal fluid proteins using a combination of cysteine tagging and amine-reactive isobaric labeling.

    PubMed

    Giron, Priscille; Dayon, Loïc; Turck, Natacha; Hoogland, Christine; Sanchez, Jean-Charles

    2011-01-07

    Highly complex and dynamic protein mixtures are hardly comprehensively resolved by direct shotgun proteomic analysis. As many proteins of biological interest are of low abundance, numerous analytical methodologies have been developed to reduce sample complexity and go deeper into proteomes. The present work describes an analytical strategy to perform cysteinyl-peptide subset enrichment and relative quantification through successive cysteine and amine-isobaric tagging. A cysteine-reactive covalent capture tag (C³T) allowed derivatization of cysteines and specific isolation on a covalent capture (CC) resin. The 6-plex amine-reactive tandem mass tags (TMT) served for relative quantification of the targeted peptides. The strategy was first evaluated on a model protein mixture with increasing concentrations to assess the specificity of the enrichment and the quantitative performances of the workflow. It was then applied to human cerebrospinal fluid (CSF) from post-mortem and ante-mortem samples. These studies confirmed the specificity of the C³T and the CC technique to cysteine-containing peptides. The model protein mixture analysis showed high precision and accuracy of the quantification with coefficients of variation and mean absolute errors of less than 10% on average. The CSF experiments demonstrated the potential of the strategy to study complex biological samples and identify differential brain-related proteins. In addition, the quantification data were highly correlated with a classical TMT experiment (i.e., without C³T cysteine-tagging and enrichment steps). Altogether, these results legitimate the use of this quantitative C³T strategy to enrich and relatively quantify cysteine-containing peptides in complex mixtures.

  20. Differential proteomics analysis of liver failure in peripheral blood mononuclear cells using isobaric tags for relative and absolute quantitation

    PubMed Central

    Lin, Hua; Tan, Qiu-Pei; Sui, Wei-Guo; Chen, Wen-Biao; Peng, Wu-Jian; Liu, Xing-Chao; Dai, Yong

    2017-01-01

    The aim of the present study was to examine differentially expressed proteome profiles for candidate biomarkers in peripheral blood mononuclear cells (PBMCs) of liver failure (LF) patients. Ten patients were diagnosed as LF and 10 age- and gender-matched subjects were recruited as healthy controls. Isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic technology is efficiently applicable for identification and relative quantitation of the proteomes of PBMCs. Eight-plex iTRAQ coupled with strong cation exchange chromatography, and liquid chromatography coupled with tandem mass spectrometry were used to analyze total proteins in LF patients and healthy control subjects. Molecular variations were detected using the iTRAQ method, and western blotting was used to verify the results. LF is a complex type of medical emergency that evolves following a catastrophic insult to the liver, and its outcome remains the most ominous of all gastroenterologic diseases. Serious complications tend to occur during the course of the disease and further exacerbate the problems. Using the iTRAQ method, differentially expressed proteome profiles of LF patients were determined. In the present study, 627 proteins with different expression levels were identified in LF patients compared with the control subjects; with 409 proteins upregulated and 218 proteins downregulated. Among them, four proteins were significantly differentially expressed; acylaminoacyl-peptide hydrolase and WW domain binding protein 2 were upregulated, and resistin and tubulin β 2A class IIa were downregulated. These proteins demonstrated differences in their expression levels compared with other proteins with normal expression levels and the significant positive correlation with LF. The western blot results were consistent with the results from iTRAQ. Thus, investigation of the molecular mechanism of the proteins involved in LF may facilitate an improved understanding of the

  1. Light-front representation of chiral dynamics with Δ isobar and large-Nc relations

    SciTech Connect

    Granados, C.; Weiss, C.

    2016-06-13

    Transverse densities describe the spatial distribution of electromagnetic current in the nucleon at fixed light-front time. At peripheral distances b = O(Mπ–1) the densities are governed by chiral dynamics and can be calculated model-independently using chiral effective field theory (EFT). Recent work has shown that the EFT results can be represented in first-quantized form, as overlap integrals of chiral light-front wave functions describing the transition of the nucleon to soft-pion-nucleon intermediate states, resulting in a quantum-mechanical picture of the peripheral transverse densities. We now extend this representation to include intermediate states with Δ isobars and implement relations based on the large-Nc limit of QCD. We derive the wave function overlap formulas for the Δ contributions to the peripheral transverse densities by way of a three-dimensional reduction of relativistic chiral EFT expressions. Our procedure effectively maintains rotational invariance and avoids the ambiguities with higher-spin particles in the light-front time-ordered approach. We study the interplay of πN and πΔ intermediate states in the quantum-mechanical picture of the densities in a transversely polarized nucleon. We show that the correct Nc-scaling of the charge and magnetization densities emerges as the result of the particular combination of currents generated by intermediate states with degenerate N and Δ. The off-shell behavior of the chiral EFT is summarized in contact terms and can be studied easily. As a result, the methods developed here can be applied to other peripheral densities and to moments of the nucleon's generalized parton distributions.

  2. High-Field Asymmetric-Waveform Ion Mobility Spectrometry and Electron Detachment Dissociation of Isobaric Mixtures of Glycosaminoglycans

    NASA Astrophysics Data System (ADS)

    Kailemia, Muchena J.; Park, Melvin; Kaplan, Desmond A.; Venot, Andre; Boons, Geert-Jan; Li, Lingyun; Linhardt, Robert J.; Amster, I. Jonathan

    2013-11-01

    High-field asymmetric waveform ion mobility spectrometry (FAIMS) is shown to be capable of resolving isomeric and isobaric glycosaminoglycan negative ions and to have great utility for the analysis of this class of molecules when combined with Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and tandem mass spectrometry. Electron detachment dissociation (EDD) and other ion activation methods for tandem mass spectrometry can be used to determine the sites of labile sulfate modifications and for assigning the stereochemistry of hexuronic acid residues of glycosaminoglycans (GAGs). However, mixtures with overlapping mass-to-charge values present a challenge, as their precursor species cannot be resolved by a mass analyzer prior to ion activation. FAIMS is shown to resolve two types of mass-to-charge overlaps. A mixture of chondroitin sulfate A (CSA) oligomers with 4-10 saccharides units produces ions of a single mass-to-charge by electrospray ionization, as the charge state increases in direct proportion to the degree of polymerization for these sulfated carbohydrates. FAIMS is shown to resolve the overlapping charge. A more challenging type of mass-to-charge overlap occurs for mixtures of diastereomers. FAIMS is shown to separate two sets of epimeric GAG tetramers. For the epimer pairs, the complexity of the separation is reduced when the reducing end is alkylated, suggesting that anomers are also resolved by FAIMS. The resolved components were activated by EDD and the fragment ions were analyzed by FTICR-MS. The resulting tandem mass spectra were able to distinguish the two epimers from each other.

  3. X-ray continuum as a measure of pressure and fuel-shell mix in compressed isobaric hydrogen implosion cores

    NASA Astrophysics Data System (ADS)

    Epstein, R.; Goncharov, V. N.; Marshall, F. J.; Betti, R.; Nora, R.; Christopherson, A. R.; Golovkin, I. E.; MacFarlane, J. J.

    2015-02-01

    Pressure, by definition, characterizes the conditions within an isobaric implosion core at peak compression [Gus'kov et al., Nucl. Fusion 16, 957 (1976); Betti et al., Phys. Plasmas 8, 5257 (2001)] and is a key parameter in quantifying its near-ignition performance [Lawson, Proc. Phys. Soc. London, B 70, 6 (1957); Betti et al., Phys. Plasmas 17, 058102 (2010); Goncharov et al., Phys. Plasmas 21, 056315 (2014); and Glenzer et al., Phys. Plasmas 19, 056318 (2012)]. At high spectral energy, where the x-ray emission from an imploded hydrogen core is optically thin, the emissivity profile can be inferred from the spatially resolved core emission. This emissivity, which can be modeled accurately under hot-core conditions, is dependent almost entirely on the pressure when measured within a restricted spectral range matched to the temperature range anticipated for the emitting volume. In this way, the hot core pressure at the time of peak emission can be inferred from the measured free-free emissivity profile. The pressure and temperature dependences of the x-ray emissivity and the neutron-production rate explain a simple scaling of the total filtered x-ray emission as a constant power of the total neutron yield for implosions of targets of similar design over a broad range of shell implosion isentropes. This scaling behavior has been seen in implosion simulations and is confirmed by measurements of high-isentrope implosions [Sangster et al., Phys. Plasmas 20, 056317 (2013)] on the OMEGA laser system [Boehly et al., Opt. Commun. 133, 495 (1997)]. Attributing the excess emission from less-stable, low-isentrope implosions, above the level expected from this neutron-yield scaling, to the higher emissivity of shell carbon mixed into the implosion's central hot spot, the hot-spot "fuel-shell" mix mass can be inferred.

  4. Search for potential markers for prostate cancer diagnosis, prognosis and treatment in clinical tissue specimens using amine-specific isobaric tagging (iTRAQ) with two-dimensional liquid chromatography and tandem mass spectrometry.

    PubMed

    Garbis, Spiros D; Tyritzis, Stavros I; Roumeliotis, Theodoros; Zerefos, Panagiotis; Giannopoulou, Eugenia G; Vlahou, Antonia; Kossida, Sophia; Diaz, Jose; Vourekas, Stavros; Tamvakopoulos, Constantin; Pavlakis, Kitty; Sanoudou, Despina; Constantinides, Constantinos A

    2008-08-01

    This study aimed to identify candidate new diagnosis and prognosis markers and medicinal targets of prostate cancer (PCa), using state of the art proteomics. A total of 20 prostate tissue specimens from 10 patients with benign prostatic hyperplasia (BPH) and 10 with PCa (Tumour Node Metastasis [TNM] stage T1-T3) were analyzed by isobaric stable isotope labeling (iTRAQ) and two-dimensional liquid chromatography-tandem mass spectrometry (2DLC-MS/MS) approaches using a hybrid quadrupole time-of-flight system (QqTOF). The study resulted in the reproducible identification of 825 nonredundant gene products (p < or = 0.05) of which 30 exhibited up-regulation (> or =2-fold) and another 35 exhibited down-regulation (< or =0.5-fold) between the BPH and PCa specimens constituting a major contribution toward their global proteomic assessment. Selected findings were confirmed by immunohistochemical analysis of prostate tissue specimens. The proteins determined support existing knowledge and uncover novel and promising PCa biomarkers. The PCa proteome found can serve as a useful aid for the identification of improved diagnostic and prognostic markers and ultimately novel chemopreventive and therapeutic targets.

  5. Isobaric Inert Gas Counterdiffusion,

    DTIC Science & Technology

    1982-11-01

    20 minutes. A second group of animals pretreated with 10 milligrams of valium, intramuscularly, showed a time lag of 248 minutes with an SE of 24...low z 20 - T x Pf Is. Cc) tPo L Q" TIME - 15- . N 200 w X N= a30 _. Dr O N=aIO " H 1 0 z1 0-- , / a- . 0 05 1- 20 CRUSHING PRESSURE PCRUSH Pm-Po

  6. Vadose zone isobaric well

    DOEpatents

    Hubbell, Joel M.; Sisson, James B.

    2001-01-01

    A deep tensiometer is configured with an outer guide tube having a vented interval along a perforate section at its lower end, which is isolated from atmospheric pressure at or above grade. A transducer having a monitoring port and a reference port is located within a coaxial inner guide tube. The reference port of the transducer is open to the vented interval of the outer guide tube, which has the same gas pressure as in the sediment surrounding the tensiometer. The reference side of the pressure transducer is thus isolated from the effects of atmospheric pressure changes and relative to pressure changes in the material surrounding the tensiometer measurement location and so it is automatically compensated for such pressure changes.

  7. Quantitative Proteomic Analysis of Wheat Seeds during Artificial Ageing and Priming Using the Isobaric Tandem Mass Tag Labeling

    PubMed Central

    Lv, Yangyong; Zhang, Shuaibing; Wang, Jinshui; Hu, Yuansen

    2016-01-01

    Wheat (Triticum aestivum L.) is an important crop worldwide. The physiological deterioration of seeds during storage and seed priming is closely associated with germination, and thus contributes to plant growth and subsequent grain yields. In this study, wheat seeds during different stages of artificial ageing (45°C; 50% relative humidity; 98%, 50%, 20%, and 1% Germination rates) and priming (hydro-priming treatment) were subjected to proteomics analysis through a proteomic approach based on the isobaric tandem mass tag labeling. A total of 162 differentially expressed proteins (DEPs) mainly involved in metabolism, energy supply, and defense/stress responses, were identified during artificial ageing and thus validated previous physiological and biochemical studies. These DEPs indicated that the inability to protect against ageing leads to the incremental decomposition of the stored substance, impairment of metabolism and energy supply, and ultimately resulted in seed deterioration. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the up-regulated proteins involved in seed ageing were mainly enriched in ribosome, whereas the down-regulated proteins were mainly accumulated in energy supply (starch and sucrose metabolism) and stress defense (ascorbate and aldarate metabolism). Proteins, including hemoglobin 1, oleosin, agglutinin, and non-specific lipid-transfer proteins, were first identified in aged seeds and might be regarded as new markers of seed deterioration. Of the identified proteins, 531 DEPs were recognized during seed priming compared with unprimed seeds. In contrast to the up-regulated DEPs in seed ageing, several up-regulated DEPs in priming were involved in energy supply (tricarboxylic acid cycle, glycolysis, and fatty acid oxidation), anabolism (amino acids, and fatty acid synthesis), and cell growth/division. KEGG and protein-protein interaction analysis indicated that the up-regulated proteins in seed priming were mainly

  8. Quantitative Proteomic Analysis of Wheat Seeds during Artificial Ageing and Priming Using the Isobaric Tandem Mass Tag Labeling.

    PubMed

    Lv, Yangyong; Zhang, Shuaibing; Wang, Jinshui; Hu, Yuansen

    2016-01-01

    Wheat (Triticum aestivum L.) is an important crop worldwide. The physiological deterioration of seeds during storage and seed priming is closely associated with germination, and thus contributes to plant growth and subsequent grain yields. In this study, wheat seeds during different stages of artificial ageing (45°C; 50% relative humidity; 98%, 50%, 20%, and 1% Germination rates) and priming (hydro-priming treatment) were subjected to proteomics analysis through a proteomic approach based on the isobaric tandem mass tag labeling. A total of 162 differentially expressed proteins (DEPs) mainly involved in metabolism, energy supply, and defense/stress responses, were identified during artificial ageing and thus validated previous physiological and biochemical studies. These DEPs indicated that the inability to protect against ageing leads to the incremental decomposition of the stored substance, impairment of metabolism and energy supply, and ultimately resulted in seed deterioration. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the up-regulated proteins involved in seed ageing were mainly enriched in ribosome, whereas the down-regulated proteins were mainly accumulated in energy supply (starch and sucrose metabolism) and stress defense (ascorbate and aldarate metabolism). Proteins, including hemoglobin 1, oleosin, agglutinin, and non-specific lipid-transfer proteins, were first identified in aged seeds and might be regarded as new markers of seed deterioration. Of the identified proteins, 531 DEPs were recognized during seed priming compared with unprimed seeds. In contrast to the up-regulated DEPs in seed ageing, several up-regulated DEPs in priming were involved in energy supply (tricarboxylic acid cycle, glycolysis, and fatty acid oxidation), anabolism (amino acids, and fatty acid synthesis), and cell growth/division. KEGG and protein-protein interaction analysis indicated that the up-regulated proteins in seed priming were mainly

  9. Simultaneous quantification of protein phosphorylation sites using liquid chromatography-tandem mass spectrometry-based targeted proteomics: a linear algebra approach for isobaric phosphopeptides.

    PubMed

    Xu, Feifei; Yang, Ting; Sheng, Yuan; Zhong, Ting; Yang, Mi; Chen, Yun

    2014-12-05

    As one of the most studied post-translational modifications (PTM), protein phosphorylation plays an essential role in almost all cellular processes. Current methods are able to predict and determine thousands of phosphorylation sites, whereas stoichiometric quantification of these sites is still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted proteomics is emerging as a promising technique for site-specific quantification of protein phosphorylation using proteolytic peptides as surrogates of proteins. However, several issues may limit its application, one of which relates to the phosphopeptides with different phosphorylation sites and the same mass (i.e., isobaric phosphopeptides). While employment of site-specific product ions allows for these isobaric phosphopeptides to be distinguished and quantified, site-specific product ions are often absent or weak in tandem mass spectra. In this study, linear algebra algorithms were employed as an add-on to targeted proteomics to retrieve information on individual phosphopeptides from their common spectra. To achieve this simultaneous quantification, a LC-MS/MS-based targeted proteomics assay was first developed and validated for each phosphopeptide. Given the slope and intercept of calibration curves of phosphopeptides in each transition, linear algebraic equations were developed. Using a series of mock mixtures prepared with varying concentrations of each phosphopeptide, the reliability of the approach to quantify isobaric phosphopeptides containing multiple phosphorylation sites (≥ 2) was discussed. Finally, we applied this approach to determine the phosphorylation stoichiometry of heat shock protein 27 (HSP27) at Ser78 and Ser82 in breast cancer cells and tissue samples.

  10. Rare evidence for formation of garnet + corundum during isobaric cooling of ultrahigh temperature metapelites: New insights for retrograde P-T trajectory of the Highland Complex, Sri Lanka

    NASA Astrophysics Data System (ADS)

    Dharmapriya, P. L.; Malaviarachchi, Sanjeeva P. K.; Galli, Andrea; Su, Ben-Xun; Subasinghe, N. D.; Dissanayake, C. B.

    2015-04-01

    We report the occurrence of coexisting garnet + corundum in spinel- and corundum-bearing, garnet-sillimanite-biotite-graphite gneiss (pelitic granulites) from the Highland Complex (HC), Sri Lanka. In the investigated pelitic granulites, two domains such as quartz-saturated and quartz-undersaturated are distinguishable. The quartz-saturated domains consist of porphyroblastic garnet, quartz, plagioclase, alkali-feldspar and biotite flakes rimming garnet. The quartz-undersaturated domains are constituted of two generations of garnet (Grt1 and Grt2), sillimanite, plagioclase, alkali-feldspar, corundum, spinel and biotite. Grt1 encloses rare Ti-rich biotite and numerous rutile needles and apatite rods. Grt2 contains rare sillimanite and/or spinel inclusions. Corundum occurs in mutual contact with Grt2, partially embedded at the rim or as an inclusions in Grt2. Thermobarometry on inclusion phases in Grt1 indicates that during the prograde history pelitic granulites attained a P of 10.5-11 kbar at T of ~ 850 °C. Textural observations coupled with both pseudosections calculated in the NCKFMASHTMnO system and Ti-in-Garnet geothermobarometry suggest that peak metamorphism occurred at ultrahigh temperature (UHT) conditions of 950-975 °C and pressures of 9-9.5 kbar. Peak T was followed by a period of isobaric cooling that formed corundum and Grt2 at approx. 930 °C along with exsolution of rutile needles and apatite rods in Grt1. Thermodynamic modelling confirms that corundum appears along an isobaric cooling path at about 920-930 °C and 9-9.5 kbar. Therefore, the investigated granulites provide a rare example of post-peak crystallization of garnet + corundum along a retrograde metamorphic trajectory under UHT conditions. Thus, isobaric cooling at the base of the crust could be regarded as an alternative process to form coexisting garnet + corundum.

  11. Measurement and isobar-model analysis of the doubly differential cross section for the. pi. /sup +/ produced in. pi. /sup -/p. -->. pi. /sup +/. pi. /sup -/n

    SciTech Connect

    Manley, D.M.

    1981-11-01

    The doubly differential cross section d/sup 2/sigma/d..cap omega..dT for ..pi../sup +/ mesons produced in the reaction ..pi../sup -/p ..-->.. ..pi../sup +/..pi../sup -/n was measured at 203, 230, 256, and 358 MeV with a single-arm magnetic spectrometer. A set of five previous measurements at 254, 280, 292, 331, and 356 MeV was reanalyzed with the new measurements. Integrated cross sections were calculated for the combined data set with unprecedented accuracy for this energy range. The chiral-symmetry-breaking parameter was determined to be epsilon = -0.03 +- 0.26 by extrapolating the mean square modulus of the matrix element to threshold and comparing the threshold matrix element with the prediction of soft-pion theory. This value of epsilon is consistent with zero as required by the Weinberg Lagrangian. Measurements at the three highest energies were compared with the results of an isobar-model analysis of bubble-chamber events by an LBL-SLAC collaboration. After allowing for an overall normalization difference, the measurements at 331 and 358 MeV were in excellent agreement with the results of their analysis. The measurement at 292 MeV required variation of the PS11(epsilonN) amplitude, as well as the overall normalization, which could be due to the limited number of bubble-chamber events available for the LBL-SLAC analysis at this energy. A partial-wave analysis of the measurements was also carried out with the VPI isobar model. Within this model, the matrix element contains a background term calculated from a phenomenological ..pi..N Lagrangian that is consistent with the hypotheses of current algebra and PCAC. The reaction was found to be dominated by the initial P11 wave. Production of the ..delta.. isobar from initial D waves was found to be significant at the two highest energies.

  12. Hail suppression and society.

    PubMed

    Changnon, S A; Farhar, B C; Swanson, E R

    1978-04-28

    An interdisciplinary assessment of hail suppression in the past, present, and future has shown it to be currently scientifically uncertain but a potentially beneficial future technology. An established suppression technology would be widely adopted in the Great Plains, providing benefits to agriculture and secondarily to the American consumer. Development of a reliable technology will require a sizable longterm federal commitment to atmospheric and social research. Subcritical funding would be a mistake. Orderly future usage of hail suppression, with its scientific complexities and regional character, will necessitate development of governmental regulations, evaluation procedures, interstate arrangements, and means for compensating those who lose from modification.

  13. Growth hormone suppression test

    MedlinePlus

    GH suppression test; Glucose loading test; Acromegaly - blood test; Gigantism - blood test ... At least 3 blood samples are taken. The test is done in the following way: The first blood sample is collected between 6 ...

  14. Jet Noise Suppression

    NASA Technical Reports Server (NTRS)

    Gliebe, P. R.; Brausch, J. F.; Majjigi, R. K.; Lee, R.

    1991-01-01

    The objectives of this chapter are to review and summarize the jet noise suppression technology, to provide a physical and theoretical model to explain the measured jet noise suppression characteristics of different concepts, and to provide a set of guidelines for evolving jet noise suppression designs. The underlying principle for all jet noise suppression devices is to enhance rapid mixing (i.e., diffusion) of the jet plume by geometric and aerothermodynamic means. In the case of supersonic jets, the shock-cell broadband noise reduction is effectively accomplished by the elimination or mitigation of the shock-cell structure. So far, the diffusion concepts have predominantly concentrated on jet momentum and energy (kinetic and thermal) diffusion, in that order, and have yielded better noise reduction than the simple conical nozzles. A critical technology issue that needs resolution is the effect of flight on the noise suppression potential of mechanical suppressor nozzles. A more thorough investigation of this mechanism is necessary for the successful development and design of an acceptable noise suppression device for future high-speed civil transports.

  15. Isobaric Quantification of Cerebrospinal Fluid Amyloid-β Peptides in Alzheimer's Disease: C-Terminal Truncation Relates to Early Measures of Neurodegeneration.

    PubMed

    Rogeberg, Magnus; Almdahl, Ina Selseth; Wettergreen, Marianne; Nilsson, Lars N G; Fladby, Tormod

    2015-11-06

    The amyloid beta (Aβ) peptide is the main constituent of the plaques characteristic of Alzheimer's disease (AD). Measurement of Aβ1-42 in cerebrospinal fluid (CSF) is a valuable marker in AD research, where low levels indicate AD. Although the use of immunoassays measuring Aβ1-38 and Aβ1-40 in addition to Aβ1-42 has increased, quantitative assays of other Aβ peptides remain rarely explored. We recently discovered novel Aβ peptides in CSF using antibodies recognizing the Aβ mid-domain region. Here we have developed a method using both Aβ N-terminal and mid-domain antibodies for immunoprecipitation in combination with isobaric labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for relative quantification of endogenous Aβ peptides in CSF. The developed method was used in a pilot study to produce Aβ peptide profiles from 38 CSF samples. Statistical comparison between CSF samples from 19 AD patients and 19 cognitively healthy controls revealed no significant differences at group level. A significant correlation was found between several larger C-terminally truncated Aβ peptides and protein biomarkers for neuronal damage, particularly prominent in the control group. Comparison of the isobaric quantification with immunoassays measuring Aβ1-38 or Aβ1-40 showed good correlation (r(2) = 0.84 and 0.85, respectively) between the two analysis methods. The developed method could be used to assess disease-modifying therapies directed at Aβ production or degradation.

  16. Extensive Peptide Fractionation and y1 Ion-Based Interference Detection Method for Enabling Accurate Quantification by Isobaric Labeling and Mass Spectrometry.

    PubMed

    Niu, Mingming; Cho, Ji-Hoon; Kodali, Kiran; Pagala, Vishwajeeth; High, Anthony A; Wang, Hong; Wu, Zhiping; Li, Yuxin; Bi, Wenjian; Zhang, Hui; Wang, Xusheng; Zou, Wei; Peng, Junmin

    2017-02-22

    Isobaric labeling quantification by mass spectrometry (MS) has emerged as a powerful technology for multiplexed large-scale protein profiling, but measurement accuracy in complex mixtures is confounded by the interference from coisolated ions, resulting in ratio compression. Here we report that the ratio compression can be essentially resolved by the combination of pre-MS peptide fractionation, MS2-based interference detection, and post-MS computational interference correction. To recapitulate the complexity of biological samples, we pooled tandem mass tag (TMT)-labeled Escherichia coli peptides at 1:3:10 ratios and added in ∼20-fold more rat peptides as background, followed by the analysis of two-dimensional liquid chromatography (LC)-MS/MS. Systematic investigation shows that quantitative interference was impacted by LC fractionation depth, MS isolation window, and peptide loading amount. Exhaustive fractionation (320 × 4 h) can nearly eliminate the interference and achieve results comparable to the MS3-based method. Importantly, the interference in MS2 scans can be estimated by the intensity of contaminated y1 product ions, and we thus developed an algorithm to correct reporter ion ratios of tryptic peptides. Our data indicate that intermediate fractionation (40 × 2 h) and y1 ion-based correction allow accurate and deep TMT profiling of more than 10 000 proteins, which represents a straightforward and affordable strategy in isobaric labeling proteomics.

  17. Collective-coupling analysis of spectra of mass-7 isobars: {sup 7}He, {sup 7}Li, {sup 7}Be, and {sup 7}B

    SciTech Connect

    Canton, L.; Pisent, G.; Amos, K.; Karataglidis, S.; Svenne, J. P.; Knijff, D. van der

    2006-12-15

    A nucleon-nucleus interaction model has been applied to ascertain the underlying character of the negative-parity spectra of four isobars of mass-7, from neutron- to proton-emitter drip lines. With a single nuclear potential defined by a simple coupled-channel model, a multichannel algebraic scattering approach (MCAS) has been used to determine the bound and resonant spectra of the four nuclides, of which {sup 7}He and {sup 7}B are particle unstable. Incorporation of Pauli blocking into the model enables a description of all known spin-parity states of the mass-7 isobars. We have also obtained spectra of similar quality by using a large space no-core shell model. Additionally, we have studied {sup 7}Li and {sup 7}Be using a dicluster model. We have found a dicluster-model potential that can reproduce the lowest four states of the two nuclei, as well as the relevant low-energy elastic scattering cross sections. But, with this model, the rest of the energy spectra cannot be obtained.

  18. Explosion suppression system

    DOEpatents

    Sapko, Michael J.; Cortese, Robert A.

    1992-01-01

    An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

  19. Heparin suppresses the induction of c-fos and c-myc mRNA in murine fibroblasts by selective inhibition of a protein kinase C-dependent pathway.

    PubMed Central

    Wright, T C; Pukac, L A; Castellot, J J; Karnovsky, M J; Levine, R A; Kim-Park, H Y; Campisi, J

    1989-01-01

    Heparin is a complex glycosaminoglycan that inhibits the proliferation of several cell types in culture and in vivo. To begin to define the mechanism(s) by which heparin exerts its antiproliferative effects, we asked whether heparin interferes with the expression of the growth factor-inducible protooncogenes c-fos and c-myc. We show that heparin suppressed the induction of c-fos and c-myc mRNA by serum in murine (BALB/c) 3T3 fibroblasts. Using purified mitogens, we further show that suppression was most marked when protooncogene expression was induced by phorbol 12-myristate 13-acetate, an activator of protein kinase C. By contrast, there was little or no suppression when the cells were stimulated by epidermal growth factor, which, in these cells, utilizes a protein kinase C-independent pathway for the induction of gene expression. Heparin also inhibited the change in cell morphology induced by the phorbol ester but had no effect on the morphological change induced by epidermal growth factor and agents that raise intracellular cAMP. Heparin did not inhibit intracellular protein kinase C activity, phorbol ester-induced down-regulation of protein kinase C, or phosphorylation of the 80-kDa intracellular protein kinase C substrate. These results suggest that heparin inhibits a protein kinase C-dependent pathway for cell proliferation and suppresses the induction of c-fos and c-myc mRNA at a site distal to activation of the kinase. Images PMID:2541434

  20. Sensory suppression during feeding

    PubMed Central

    Foo, H.; Mason, Peggy

    2005-01-01

    Feeding is essential for survival, whereas withdrawal and escape reactions are fundamentally protective. These critical behaviors can compete for an animal's resources when an acutely painful stimulus affects the animal during feeding. One solution to the feeding-withdrawal conflict is to optimize feeding by suppressing pain. We examined whether rats continue to feed when challenged with a painful stimulus. During feeding, motor withdrawal responses to noxious paw heat either did not occur or were greatly delayed. To investigate the neural basis of sensory suppression accompanying feeding, we recorded from brainstem pain-modulatory neurons involved in the descending control of pain transmission. During feeding, pain-facilitatory ON cells were inhibited and pain-inhibitory OFF cells were excited. When a nonpainful somatosensory stimulus preactivated ON cells and preinhibited OFF cells, rats interrupted eating to react to painful stimuli. Inactivation of the brainstem region containing ON and OFF cells also blocked pain suppression during eating, demonstrating that brainstem pain-modulatory neurons suppress motor reactions to external stimulation during homeostatic behaviors. PMID:16275919

  1. Orientation-tuned surround suppression in mouse visual cortex.

    PubMed

    Self, Matthew W; Lorteije, Jeannette A M; Vangeneugden, Joris; van Beest, Enny H; Grigore, Mihaela E; Levelt, Christiaan N; Heimel, J Alexander; Roelfsema, Pieter R

    2014-07-09

    The firing rates of neurons in primary visual cortex (V1) are suppressed by large stimuli, an effect known as surround suppression. In cats and monkeys, the strength of suppression is sensitive to orientation; responses to regions containing uniform orientations are more suppressed than those containing orientation contrast. This effect is thought to be important for scene segmentation, but the underlying neural mechanisms are poorly understood. We asked whether it is possible to study these mechanisms in the visual cortex of mice, because of recent advances in technology for studying the cortical circuitry in mice. It is unknown whether neurons in mouse V1 are sensitive to orientation contrast. We measured the orientation selectivity of surround suppression in the different layers of mouse V1. We found strong surround suppression in layer 4 and the superficial layers, part of which was orientation tuned: iso-oriented surrounds caused more suppression than cross-oriented surrounds. Surround suppression was delayed relative to the visual response and orientation-tuned suppression was delayed further, suggesting two separate suppressive mechanisms. Previous studies proposed that surround suppression depends on the activity of inhibitory somatostatin-positive interneurons in the superficial layers. To test the involvement of the superficial layers we topically applied lidocaine. Silencing of the superficial layers did not prevent orientation-tuned suppression in layer 4. These results show that neurons in mouse V1, which lacks orientation columns, show orientation-dependent surround suppression in layer 4 and the superficial layers and that surround suppression in layer 4 does not require contributions from neurons in the superficial layers.

  2. Nuclear structure beyond the neutron drip line: The lowest energy states in 9He via their T = 5/2 isobaric analogs in 9Li

    NASA Astrophysics Data System (ADS)

    Uberseder, E.; Rogachev, G. V.; Goldberg, V. Z.; Koshchiy, E.; Roeder, B. T.; Alcorta, M.; Chubarian, G.; Davids, B.; Fu, C.; Hooker, J.; Jayatissa, H.; Melconian, D.; Tribble, R. E.

    2016-03-01

    The level structure of the very neutron rich and unbound 9He nucleus has been the subject of significant experimental and theoretical study. Many recent works have claimed that the two lowest energy 9He states exist with spins Jπ = 1 /2+ and Jπ = 1 /2- and widths on the order of 100-200 keV. These findings cannot be reconciled with our contemporary understanding of nuclear structure. The present work is the first high-resolution study with low statistical uncertainty of the relevant excitation energy range in the 8He+n system, performed via a search for the T = 5 / 2 isobaric analog states in 9Li populated through 8He+p elastic scattering. The present data show no indication of any narrow structures. Instead, we find evidence for a broad Jπ = 1 /2+ state in 9He located approximately 3 MeV above the neutron decay threshold.

  3. First online multireflection time-of-flight mass measurements of isobar chains produced by fusion-evaporation reactions: Toward identification of superheavy elements via mass spectroscopy

    NASA Astrophysics Data System (ADS)

    Schury, P.; Wada, M.; Ito, Y.; Kaji, D.; Arai, F.; MacCormick, M.; Murray, I.; Haba, H.; Jeong, S.; Kimura, S.; Koura, H.; Miyatake, H.; Morimoto, K.; Morita, K.; Ozawa, A.; Rosenbusch, M.; Reponen, M.; Söderström, P.-A.; Takamine, A.; Tanaka, T.; Wollnik, H.

    2017-01-01

    Using a multireflection time-of-flight mass spectrograph located after a gas cell coupled with the gas-filled recoil ion separator GARIS-II, the masses of several α -decaying heavy nuclei were directly and precisely measured. The nuclei were produced via fusion-evaporation reactions and separated from projectilelike and targetlike particles using GARIS-II before being stopped in a helium-filled gas cell. Time-of-flight spectra for three isobar chains, 204Fr-204Rn-204At-204Po , 205Fr-205Rn-205At-205Po-205Bi , and 206Fr-206Rn-206At , were observed. Precision atomic mass values were determined for Fr-206204, Rn,205204, and At,205204. Identifications of 205Bi, Po,205204, 206Rn, and 206At were made with N ≲10 detected ions, representing the next step toward use of mass spectrometry to identify exceedingly low-yield species such as superheavy element ions.

  4. Isobaric Tags for Relative and Absolute Quantitation (iTRAQ)-Based Comparative Proteome Analysis of the Response of Ramie under Drought Stress

    PubMed Central

    An, Xia; Zhang, Jingyu; Dai, Lunjin; Deng, Gang; Liao, Yiwen; Liu, Lijun; Wang, Bo; Peng, Dingxiang

    2016-01-01

    In this study, we conducted the first isobaric tags for relative and absolute quantitation (isobaric tags for relative and absolute quantitation (iTRAQ))-based comparative proteomic analysis of ramie plantlets after 0 (minor drought stress), 24 (moderate drought stress), and 72 h (severe drought stress) of treatment with 15% (w/v) poly (ethylene glycol)6000 (PEG6000) to simulate drought stress. In our study, the association analysis of proteins and transcript expression revealed 1244 and 968 associated proteins identified in leaves and roots, respectively. L1, L2, and L3 are leaf samples which were harvested at 0, 24, and 72 h after being treated with 15% PEG6000, respectively. Among those treatment groups, a total of 118, 216, and 433 unique proteins were identified as differentially expressed during L1 vs. L2, L2 vs. L3, and L1 vs. L3, respectively. R1, R2, and R3 are root samples which were harvested at 0, 24, and 72 h after being treated with 15% PEG6000, respectively. Among those treatment groups,a total of 124, 27, and 240 unique proteins were identified as differentially expressed during R1 vs. R2, R2 vs. R3, and R1 vs. R3, respectively. Bioinformatics analysis indicated that glycolysis/gluconeogenesis was significantly upregulated in roots in response to drought stress. This enhancement may result in more glycolytically generated adenosine triphosphate (ATP) in roots to adapt to adverse environmental conditions. To obtain complementary information related to iTRAQ data, the mRNA levels of 12 proteins related to glycolysis/gluconeogenesis in leaves and 7 in roots were further analyzed by qPCR. Most of their expression levels were higher in R3 than R1 and R2, suggesting that these compounds may promote drought tolerance by modulating the production of available energy. PMID:27689998

  5. Structure of even-even A=138 isobars and the yrast spectra of semi-magic Sn isotopes above the {sup 132}Sn core

    SciTech Connect

    Sarkar, S.; Sarkar, M. Saha

    2008-08-15

    Large basis untruncated shell model (SM) calculations have been done for the A=138 neutron-rich nuclei in the {pi}(gdsh)+{nu}(hfpi) valence space above the {sup 132}Sn core using two (1+2) -body nuclear Hamiltonians, viz., realistic CWG and empirical SMPN. Calculated binding energies, excitation spectra, and wave function structures are compared for even-even A=138 isobars for which experimental data are available. The nearly vibrational states in {sup 138}Te, Xe, and the B(E2;2{sup +}{yields}0{sup +}) value in {sup 138}Xe are excellently reproduced by both the interactions. For {sup 138}Ba, the calculated spectra and the B(E2;2{sup +}{yields}0{sup +}) value also agree very well with the experimental results. But the two theoretical results differ dramatically for {sup 138}Sn, a nucleus on the r-process path. CWG predicts nearly constant energies of 2{sub 1}{sup +} states for the even-even Sn isotopes above the {sup 132}Sn core, normally expected for semi-magic nuclei. But SMPN predicts a remarkable new feature: decreasing E(2{sub 1}{sup +}) energies with increasing neutron number. The predicted energies for the Sn isotopes fit in the systematics for the E(2{sub 1}{sup +}) energies of their isotones with Z>50. Despite their differences, both interactions predict the 6{sub 1}{sup +} state to be a {approx_equal}0.3 {mu}s isomer in {sup 138}Sn. Calculated magnetic dipole moments and electric quadrupole moments of the states in these isobars are compared with the experimental data wherever available. The appearance of deformation and evolution of collectivity in nuclei in this valence space are discussed.

  6. Suppression of branches in Eucalyptus trees.

    PubMed

    Senthalir, P; Sharanya, S; Paramathma, M

    2004-06-01

    The effect of neem oil, which acts as a suckericide in tobacco, on branch suppression in Eucalyptus tereticornis was assessed to help maximize stem biomass. Lateral branches of selected trees were pruned, and neem oil solutions at concentrations of either 80%, 40%, 20%, 10%, or 0% (untreated control) were applied to leaf axils of the pruned branches. Regeneration of branches was suppressed, and the magnitude of suppression was proportional to the concentration of neem oil. Compared to the control, the percentage reduction in branching at 80% neem oil was 41.6%. When regenerated branches were repruned and neem oil applied at either 100%, 80%, or 0% (control), the regenerating ability of these branches was severely repressed by 78% at 100% neem oil relative to the control. Apical shoots were also topped and treated at either 100% or 0% (control) neem oil to identify the principal suppressive component in neem oil. The principal component azadirachtin was tested at 375, 750, 1500, 3125, 6250, 12 500, 25 000, 50 000, and 100 000 ppm and 0 ppm as the control. Reduction in the coppicing shoot was as high as 85%. Azadirachtin was responsible for the suppression. By pruning the lateral branches with neem oil, wasteful consumption of photosynthates can be precluded and the stem biomass maximized.

  7. Learning motion discrimination with suppressed and un-suppressed MT.

    PubMed

    Thompson, Benjamin; Liu, Zili

    2006-06-01

    Perceptual learning of motion direction discrimination is generally thought to rely on the middle temporal area of the brain (MT/V5). A recent study investigating learning of motion discrimination when MT was psychophysically suppressed found that learning was possible with suppressed MT, but only when the task was sufficiently easy [Lu, H., Qian, N., Liu, Z. (2004). Learning motion discrimination with suppressed MT. Vision Research 44, 1817-1825]. We investigated whether this effect was indeed due to MT suppression or whether it could be explained by task difficulty alone. By comparing learning of motion discrimination when MT was suppressed vs. un-suppressed, at different task difficulties, we found that task difficulty alone could not explain the effects. At the highest difficulty, learning was not possible with suppressed MT, confirming [Lu, H., Qian, N., Liu, Z. (2004). Learning motion discrimination with suppressed MT. Vision Research 44, 1817-1825]. In comparison, learning was possible with un-suppressed MT at the same difficulty level. At the intermediate task difficulty, there was a clear learning disadvantage when MT was suppressed. Only for the easiest level of difficulty, did learning become equally possible for both suppressed and un-suppressed conditions. These findings suggest that MT plays an important role in learning to discriminate relatively fine differences in motion direction.

  8. Pressure suppression containment system

    DOEpatents

    Gluntz, D.M.; Townsend, H.E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of-coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto. 6 figures.

  9. Pressure suppression containment system

    DOEpatents

    Gluntz, Douglas M.; Townsend, Harold E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto.

  10. Monitoring chloramines and bromamines in a humid environment using selected ion flow tube mass spectrometry.

    PubMed

    Hu, Wan-Ping; Langford, Vaughan S; McEwan, Murray J; Milligan, Daniel B; Storer, Malina K; Dummer, Jack; Epton, Michael J

    2010-06-30

    The selectivity and sensitivity of selected ion flow tube mass spectrometry (SIFT-MS) for individual breath analysis of haloamines has been improved by heating the flow tube in a commercial instrument to around 106 degrees C. Data is presented showing the marked reduction in the number density of water clusters of product ions of common breath metabolites that are isobaric with the product ions from monochloramine and monobromamine that are used to monitor the haloamine concentrations. These results have direct relevance to the real-time monitoring of chloramines in drinking water, swimming pools and food processing plants. However, once the isobaric overlaps from water cluster ions are reduced at the higher temperatures, there is no conclusive evidence showing the presence of haloamines on single breath exhalations in the mid parts per trillion range from examination of the breaths of volunteers.

  11. Tactile suppression of displacement.

    PubMed

    Ziat, Mounia; Hayward, Vincent; Chapman, C Elaine; Ernst, Marc O; Lenay, Charles

    2010-10-01

    In vision, the discovery of the phenomenon of saccadic suppression of displacement has made important contributions to the understanding of the stable world problem. Here, we report a similar phenomenon in the tactile modality. When scanning a single Braille dot with two fingers of the same hand, participants were asked to decide whether the dot was stationary or whether it was displaced from one location to another. The stimulus was produced by refreshable Braille devices that have dots that can be swiftly raised and recessed. In some conditions, the dot was stationary. In others, a displacement was created by monitoring the participant's finger position and by switching the dot activation when it was not touched by either finger. The dot displacement was of either 2.5 mm or 5 mm. We found that in certain cases, displaced dots were felt to be stationary. If the displacement was orthogonal to the finger movements, tactile suppression occurred effectively when it was of 2.5 mm, but when the displacement was of 5 mm, the participants easily detected it. If the displacement was medial-lateral, the suppression effect occurred as well, but less often when the apparent movement of the dot opposed the movement of the finger. In such cases, the stimulus appeared sooner than when the brain could predict it from finger movement, supporting a predictive rather than a postdictive differential processing hypothesis.

  12. An electrophysiological assessment of distractor suppression in visual search tasks.

    PubMed

    Mazza, Veronica; Turatto, Massimo; Caramazza, Alfonso

    2009-07-01

    We investigated whether the N2pc is unequivocally linked to distractor-suppression mechanisms, as is commonly assumed. According to the distractor-suppression account of the N2pc, no suppression, and thus no N2pc, should occur when homogeneous distractors help in selecting the target, such as when the target feature is unpredictable. Participants performed a simple detection or a finer discrimination on a singleton target, which had either a variable or a constant color. Contrary to the distractor-suppression account, an N2pc was present for both the variable and the constant conditions, and for both tasks. Additionally, target feature consistency correlated with earlier N2pc onsets relative to variable blocks. Both results indicate that the N2pc is not unequivocally linked to distractor-suppression mechanisms, but may index mechanisms involved in identifying and localizing relevant stimuli through enhancement of their features.

  13. Pharmacology of appetite suppression.

    PubMed

    Halford, J C; Blundell, J E

    2000-01-01

    Despite a rising worldwide epidemic of obesity there is currently only a very small number of anti-obesity drugs available to manage the problem. Large numbers of differing pharmacological agents reliably produce a reduction in food intake when administered acutely to animals, and when administered chronically they result in a significant decrease in body mass. Behavioural analysis of drug-induced anorexia in animals demonstrates that various compounds profoundly effect feeding behaviour in differing ways. This indicates the variety of mechanisms by which pharmacological agents can induce changes in food intake, body weight and eventually body composition. Some of the same drugs produce decreases in food intake and weight loss in humans. Some of these drugs do so by modifying the functioning of the appetite system as measured by subjective changes in feelings of hunger and fullness (indices of satiety). Such drugs can be considered as "appetite suppressants" with clinical potential as anti-obesity agents. Other drugs induce changes in food intake and body weight through various physiological mechanisms inducing feelings of nausea or even by side effect related malaise. Of the drugs considered suitable candidates for appetite suppressants are agents which act via peripherally satiety peptide systems (such as CCK, Bombesin/GRP, Enterostatin and GLP-1), or alter the CNS levels of various hypothalamic neuropeptides (NPY, Galanin, Orexin and Melanocortins) or levels of the key CNS appetite monoamine neurotransmitters such as serotonin (5-HT) and noradrenaline (NA). Recently, the hormone leptin has been regarded as a hormonal signal linking adipose tissue status with a number of key central nervous system circuits. The peptide itself stimulates leptin receptors and it links with POMC and MC-4 receptors. These receptors may also provide drug targets for the control of appetite. Any changes induced by a potential appetite suppressant should be considered in terms of the (i

  14. Sustained and selective suppression of intestinal cholesterol synthesis by Ro 48-8071, an inhibitor of 2,3-oxidosqualene:lanosterol cyclase, in the BALB/c mouse.

    PubMed

    Chuang, Jen-Chieh; Valasek, Mark A; Lopez, Adam M; Posey, Kenneth S; Repa, Joyce J; Turley, Stephen D

    2014-04-01

    The small intestine plays a fundamentally important role in regulating whole body cholesterol balance and plasma lipoprotein composition. This is articulated through the interplay of a constellation of genes that ultimately determines the net amount of chylomicron cholesterol delivered to the liver. Major advances in our insights into regulation of the cholesterol absorption pathway have been made using genetically manipulated mouse models and agents such as ezetimibe. One unresolved question is how a sustained pharmacological inhibition of intestinal cholesterol synthesis in vivo may affect cholesterol handling by the absorptive cells. Here we show that the lanosterol cyclase inhibitor, Ro 48-8071, when fed to BALB/c mice in a chow diet (20 mg/day/kg body weight), leads to a rapid and sustained inhibition (>50%) of cholesterol synthesis in the whole small intestine. Sterol synthesis was also reduced in the large intestine and stomach. In contrast, hepatic cholesterol synthesis, while markedly suppressed initially, rebounded to higher than baseline rates within 7 days. Whole body cholesterol synthesis, fractional cholesterol absorption, and fecal neutral and acidic sterol excretion were not consistently changed with Ro 48-8071 treatment. There were no discernible effects of this agent on intestinal histology as determined by H&E staining and the level of Ki67, an index of proliferation. The mRNA expression for multiple genes involved in intestinal cholesterol regulation including NPC1L1 was mostly unchanged although there was a marked rise in the mRNA level for the PXR target genes CYP3A11 and CES2A.

  15. Butrin, Isobutrin, and Butein from Medicinal Plant Butea monosperma Selectively Inhibit Nuclear Factor-κB in Activated Human Mast Cells: Suppression of Tumor Necrosis Factor-α, Interleukin (IL)-6, and IL-8

    PubMed Central

    Rasheed, Zafar; Akhtar, Nahid; Khan, Abubakar; Khan, Khursheed A.

    2010-01-01

    Activation of mast cells in rheumatoid synovial tissue has often been associated with tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 production and disease pathogenesis by adjacent cell types. Butea monosperma (BM) is a well known medicinal plant in India and the tropics. The aim of this study was to examine whether a standardized extract of BM flower (BME) could inhibit inflammatory reactions in human mast cells (HMC) using activated HMC-1 cells as a model. Four previously characterized polyphenols—butrin, isobutrin, isocoreopsin, and butein—were isolated from BME by preparative thin layer chromatography, and their purity and molecular weights were determined by liquid chromatography/mass spectrometry analysis. Our results showed that butrin, isobutrin, and butein significantly reduced the phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced inflammatory gene expression and production of TNF-α, IL-6, and IL-8 in HMC-1 cells by inhibiting the activation of NF-κB. In addition, isobutrin was most potent in suppressing the NF-κB p65 activation by inhibiting IκBα degradation, whereas butrin and butein were relatively less effective. In vitro kinase activity assay revealed that isobutrin was a potent inhibitor of IκB kinase complex activity. This is the first report identifying the molecular basis of the reported anti-inflammatory effects of BME and its constituents butrin, isobutrin, and butein. The novel pharmacological actions of these polyphenolic compounds indicate potential therapeutic value for the treatment of inflammatory and other diseases in which activated mast cells play a role. PMID:20164300

  16. Pressure suppression system

    DOEpatents

    Gluntz, Douglas M.

    1994-01-01

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein.

  17. Pressure suppression system

    DOEpatents

    Gluntz, D.M.

    1994-10-04

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein. 3 figs.

  18. Ultrasonic Frost Suppression

    NASA Astrophysics Data System (ADS)

    Adachi, Kazunari; Saiki, Kazushi; Sato, Hiroki; Ito, Takahiro

    2003-02-01

    The authors have observed the accumulation of frost on the surface of a rectangular aluminum alloy (duralumin) plate flexurally vibrating at approximately 37 kHz in an atmosphere of almost 100% relative humidity at 2°C. The plate surface, which had been prepolished with abrasive slurry for maintaining its average surface roughness of about 100 nm, was refrigerated at a temperature of -20°C with cold carbon-dioxide gas as coolant. Experiments have been conducted with and without fine silver oxide powder spread on the plate surface so as to examine the effect of artificial ice crystal nuclei. Ultrasonic vibrations with an amplitude of 3.4 μm (rms) are found to suppress frost accumulation by approximately 60%. The phenomenon cannot be ascribed directly to the heat generation caused by high-amplitude vibration, but may have a complex mechanical and/or acoustical effect on small ice crystals.

  19. Factors influencing dust suppressant effectiveness

    SciTech Connect

    Copeland, C.R.; Eisele, T.C.; Chesney, D.J.; Kawatra, S.K.

    2008-11-15

    Water sprays are a common method used to reduce particulate matter (PM) emissions. Various factors such as wettability, surface area coverage, fine particle engulfment rates, interparticle adhesion forces, suppressant penetration and suppressant longevity have all been suggested as critical factors in achieving effective PM control. However, it has not been established which of these factors are the most important. Experimental work indicated that suppressant penetration is the most critical of these factors. The length of time after application that suppressants were effective was also improved by using hygroscopic reagents that retained moisture to prevent evaporation. Maximizing suppressant penetration and improving suppressant longevity led to an average 86% reduction in PM10 concentrations in laboratory dust tower tests.

  20. Global Metabolomic and Isobaric Tagging Capillary Liquid Chromatography–Tandem Mass Spectrometry Approaches for Uncovering Pathway Dysfunction in Diabetic Mouse Aorta

    PubMed Central

    2015-01-01

    Despite the prevalence of diabetes and the global health risks it poses, the biochemical pathogenesis of diabetic complications remains poorly understood with few effective therapies. This study employs capillary liquid chromatography (capLC) and tandem mass spectrometry (MS/MS) in conjunction with both global metabolomics and isobaric tags specific to amines and carbonyls to probe aortic metabolic content in diabetic mice with hyperglycemia, hyperlipidemia, hypertension, and stenotic vascular damage. Using these combined techniques, metabolites well-characterized in diabetes as well as novel pathways were investigated. A total of 53 986 features were detected, 719 compounds were identified as having significant fold changes (thresholds ≥2 or ≤0.5), and 48 metabolic pathways were found to be altered with at least 2 metabolite hits in diabetic samples. Pathways related to carbonyl stress, carbohydrate metabolism, and amino acid metabolism showed the greatest number of metabolite changes. Three novel pathways with previously limited or undescribed roles in diabetic complications—vitamin B6, propanoate, and butanoate metabolism—were also shown to be altered in multiple points along the pathway. These discoveries support the theory that diabetic vascular complications arise from the interplay of a myriad of metabolic pathways in conjunction with oxidative and carbonyl stress, which may provide not only new and much needed biomarkers but also insights into novel therapeutic targets. PMID:25368974

  1. Ambient isobaric heat capacities, C(p,m), for ionic solids and liquids: an application of volume-based thermodynamics (VBT).

    PubMed

    Glasser, Leslie; Jenkins, H Donald Brooke

    2011-09-05

    Thermodynamic properties, such as standard entropy, among others, have been shown to correlate well with formula volume, V(m), thus permitting prediction of these properties on the basis of chemical formula and density alone, with no structural detail required. We have termed these procedures "volume-based thermodynamics" (VBT). We here extend these studies to ambient isobaric heat capacities, C(p,m), of a wide range of materials. We show that heat capacity is strongly linearly correlated with formula volume for large sets of minerals, for ionic solids in general, and for ionic liquids and that the results demonstrate that the Neumann-Kopp rule (additivity of heat capacity contributions per atom) is widely valid for ionic materials, but the smaller heat capacity contribution per unit volume for ionic liquids is noted and discussed. Using these correlations, it is possible to predict values of ambient (298 K) heat capacities quite simply. We also show that the heat capacity contribution of water molecules of crystallization is remarkably constant, at 41.3 ± 4.7 J K(-1) (mol of water)(-1), so that the heat capacities of various hydrates may be reliably estimated from the values of their chemical formula neighbors. This result complements similar observations that we have reported for other thermodynamic differences of hydrates.

  2. First and Second-Phase Transitions of Gases at Isobaric Process; Lennard-Jones (9,6) Gases with a Hard Core

    NASA Astrophysics Data System (ADS)

    Matsumoto, Akira

    2014-12-01

    The thermodynamic functions for Lennard-Jones (9,6) gases with a hard core that are evaluated till the third virial coefficients, are investigated at an isobaric process. Some thermodynamic functions are analytically expressed as functions of intensive variables, temperature, and pressure. Some thermodynamic quantities for carbon dioxide are calculated numerically and drawn graphically. In critical states, the heat capacity diverges to infinity at the critical point while the Gibbs free energy, volume, enthalpy, and entropy are continuous at the critical point. In the coexistence of two phases, the boiling temperatures and the enthalpy changes of vaporization are obtained by numerical calculations for 20 substances. The Gibbs free energy indicates a polygonal line; entropy, volume, and enthalpy jump from the liquid to gaseous phase at the boiling point. The heat capacity does not diverge to infinity but shows a finite discrepancy at boiling point. This suggests that a first-order phase transition at the boiling point and a second-order phase transition may occur at the critical point.

  3. Nuclear structure beyond the neutron drip line. The lowest energy states in 9He via their T=5/2 isobaric analogs in 9Li

    DOE PAGES

    Uberseder, E.; Rogachev, G. V.; Goldberg, V. Z.; ...

    2016-03-01

    The level structure of the very neutron rich and unbound 9He nucleus has been the subject of significant experimental and theoretical study. Many recent works have claimed that the two lowest energy 9He states exist with spins Jπ=1/2+and Jπ=1/2-and widths on the order of 100–200 keV. These find-ings cannot be reconciled with our contemporary understanding of nuclear structure. Our present work is the first high-resolution study with low statistical uncertainty of the relevant excitation energy range in the 8He+n system, performed via a search for the T =5/2 isobaric analog states in 9Li populated through 8He+p elastic scattering. Moreover, themore » present data show no indication of any narrow structures. Instead, we find evidence for a broad Jπ=1/2+state in 9He located approximately 3 MeV above the neutron decay threshold.« less

  4. Large-Scale Hybrid Density Functional Theory Calculations in the Condensed-Phase: Ab Initio Molecular Dynamics in the Isobaric-Isothermal Ensemble

    NASA Astrophysics Data System (ADS)

    Ko, Hsin-Yu; Santra, Biswajit; Distasio, Robert A., Jr.; Wu, Xifan; Car, Roberto

    Hybrid functionals are known to alleviate the self-interaction error in density functional theory (DFT) and provide a more accurate description of the electronic structure of molecules and materials. However, hybrid DFT in the condensed-phase has a prohibitively high associated computational cost which limits their applicability to large systems of interest. In this work, we present a general-purpose order(N) implementation of hybrid DFT in the condensed-phase using Maximally localized Wannier function; this implementation is optimized for massively parallel computing architectures. This algorithm is used to perform large-scale ab initio molecular dynamics simulations of liquid water, ice, and aqueous ionic solutions. We have performed simulations in the isothermal-isobaric ensemble to quantify the effects of exact exchange on the equilibrium density properties of water at different thermodynamic conditions. We find that the anomalous density difference between ice I h and liquid water at ambient conditions as well as the enthalpy differences between ice I h, II, and III phases at the experimental triple point (238 K and 20 Kbar) are significantly improved using hybrid DFT over previous estimates using the lower rungs of DFT This work has been supported by the Department of Energy under Grants No. DE-FG02-05ER46201 and DE-SC0008626.

  5. A paired ions scoring algorithm based on Morpheus for simultaneous identification and quantification of proteome samples prepared by isobaric peptide termini labeling strategies.

    PubMed

    Zhang, Shen; Wu, Qi; Shan, Yichu; Sui, Zhigang; Zhang, Lihua; Zhang, Yukui

    2015-06-01

    The isobaric peptide termini labeling (IPTL) method is a promising strategy in quantitative proteomics for its high accuracy, while the increased complexity of MS2 spectra originated from the paired b, y ions has adverse effect on the identification and the coverage of quantification. Here, a paired ions scoring algorithm (PISA) based on Morpheus, a database searching algorithm specifically designed for high-resolution MS2 spectra, was proposed to address this issue. PISA was first tested on two 1:1 mixed IPTL datasets, and increases in peptide to spectrum matchings, distinct peptides and protein groups compared to Morpheus itself and MASCOT were shown. Furthermore, the quantification is simultaneously performed and 100% quantification coverage is achieved by PISA since each of the identified peptide to spectrum matchings has several pairs of fragment ions which could be used for quantification. Then the PISA was applied to the relative quantification of human hepatocellular carcinoma cell lines with high and low metastatic potentials prepared by an IPTL strategy.

  6. The site of saccadic suppression.

    PubMed

    Thilo, Kai V; Santoro, Loredana; Walsh, Vincent; Blakemore, Colin

    2004-01-01

    During rapid eye movements, or saccades, stable vision is maintained by active reduction of visual sensitivity. The site of this saccadic suppression remains uncertain. Here we show that phosphenes--small illusory visual perceptions--induced by transcranial magnetic stimulation (TMS) to the human occipital cortex are immune to saccadic suppression, whereas phosphenes induced by retinal stimulation are not, thus providing direct physiological evidence that saccadic suppression occurs between the retina and the occipital visual cortex.

  7. Selective inhibition of extracellular signal-regulated kinases 1/2 blocks nerve growth factor to brain-derived neurotrophic factor signaling and suppresses the development of and reverses already established pain behavior in rats.

    PubMed

    Matsuoka, Y; Yang, J

    2012-03-29

    Brain-derived neurotrophic factor (BDNF) plays a key role in the development of pathological pain. Although it is known that nerve growth factor (NGF) induces BDNF mRNA through extracellular signal-regulated kinases (ERK), whether ERK1/2 or ERK5, two closely related members of the ERK family, mediate this signal is still unclear because classical MEK inhibitors block both pathways. We studied the involvement of ERK-signaling in NGF induction of BDNF in PC12 cells, cultured dorsal root ganglia neurons, and in rats subjected to neuropathic pain models using ERK1/2- and ERK5-specific tools. Selective activation of ERK1/2 upregulated BDNF mRNA in PC12 cells, whereas selective ERK5 activation did not. AZD6244, a potent selective inhibitor of ERK1/2 activation, blocked NGF induction of BDNF mRNA in vitro suggesting that NGF induction of BDNF is mediated by ERK1/2. siRNA experiments indicated that both ERK1 or ERK2 can signal suggesting that both pathways must be blocked to prevent NGF-induced increase in BDNF mRNA. I.p. injection of AZD6244 prevented the development of pain in rats subjected to the chronic constriction injury and reversed already established pain in the spared nerve injury model. Immunohistochemical studies showed decreased phospho-ERK1/2-immunoreactivity in dorsal root ganglia and BDNF immunoreactivity in ipsilateral spinal dorsal horn in the drug-treated rats. Our results suggest the possible use of AZD6244, already in human clinical trials as an anticancer agent, for the treatment of pathological pain.

  8. STRV Cryocooler Tip Motion Suppression

    NASA Technical Reports Server (NTRS)

    Glaser, R.; Ross, R. G., Jr.; Johnson, D. L.

    1994-01-01

    The Space Technology Research Vehicle (STRV-1b) scheduled to fly at the beginning of June 1994, has a cryocooler vibration suppression experiment aboard doing motion suppression of the tip of the coldfinger. STRV-1b is a bread box sized satellite to be launched on the next flight of the Ariane-4.

  9. An Alternative to Thought Suppression?

    ERIC Educational Resources Information Center

    Boice, Robert

    2012-01-01

    Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

  10. Inducing amnesia through systemic suppression

    PubMed Central

    Hulbert, Justin C.; Henson, Richard N.; Anderson, Michael C.

    2016-01-01

    Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

  11. Painful consequences of anger suppression.

    PubMed

    Quartana, Phillip J; Burns, John W

    2007-05-01

    The authors experimentally examined the effects of anger suppression on pain perception. On the basis of ironic process theory, they proposed that efforts to suppress experiential or expressive components of anger may paradoxically enhance cognitive accessibility of anger-related thoughts and feelings, thereby contaminating perception of succeeding pain in an anger-congruent manner. Participants were randomly assigned to nonsuppression or experiential or expressive suppression conditions during mental arithmetic with or without harassment. A cold-pressor task followed. Results revealed that participants instructed to suppress experiential or expressive components of emotion during harassment not only reported the greatest pain levels, but also rated the anger-specific dimensions of pain uniquely strong. Results suggest that attempts to suppress anger may amplify pain sensitivity by ironically augmenting perception of the irritating and frustrating qualities of pain.

  12. Surround suppression and sparse coding in visual and barrel cortices

    PubMed Central

    Sachdev, Robert N. S.; Krause, Matthew R.; Mazer, James A.

    2012-01-01

    During natural vision the entire retina is stimulated. Likewise, during natural tactile behaviors, spatially extensive regions of the somatosensory surface are co-activated. The large spatial extent of naturalistic stimulation means that surround suppression, a phenomenon whose neural mechanisms remain a matter of debate, must arise during natural behavior. To identify common neural motifs that might instantiate surround suppression across modalities, we review models of surround suppression and compare the evidence supporting the competing ideas that surround suppression has either cortical or sub-cortical origins in visual and barrel cortex. In the visual system there is general agreement lateral inhibitory mechanisms contribute to surround suppression, but little direct experimental evidence that intracortical inhibition plays a major role. Two intracellular recording studies of V1, one using naturalistic stimuli (Haider et al., 2010), the other sinusoidal gratings (Ozeki et al., 2009), sought to identify the causes of reduced activity in V1 with increasing stimulus size, a hallmark of surround suppression. The former attributed this effect to increased inhibition, the latter to largely balanced withdrawal of excitation and inhibition. In rodent primary somatosensory barrel cortex, multi-whisker responses are generally weaker than single whisker responses, suggesting multi-whisker stimulation engages similar surround suppressive mechanisms. The origins of suppression in S1 remain elusive: studies have implicated brainstem lateral/internuclear interactions and both thalamic and cortical inhibition. Although the anatomical organization and instantiation of surround suppression in the visual and somatosensory systems differ, we consider the idea that one common function of surround suppression, in both modalities, is to remove the statistical redundancies associated with natural stimuli by increasing the sparseness or selectivity of sensory responses. PMID:22783169

  13. NASA Instep/mdmsc Jitter Suppression Experiment (JITTER)

    NASA Technical Reports Server (NTRS)

    White, Edward V.

    1992-01-01

    The objectives are the following: (1) to develop and demonstrate in-space performance of both passive and active damping systems for suppression of micro-amplitude vibration on an actual application structure and operate despite uncertain dynamics and uncertain disturbance characteristics; and (2) to correlate ground and in-space performance - the performance metric is vibration attenuation. The goals are to achieve vibration suppression equivalent to 5 percent passive damping in selected models and 15 percent active damping in selected modes. Various aspects of this experiment are presented in viewgraph form.

  14. A curcumin derivative, 2,6-bis(2,5-dimethoxybenzylidene)-cyclohexanone (BDMC33) attenuates prostaglandin E2 synthesis via selective suppression of cyclooxygenase-2 in IFN-γ/LPS-stimulated macrophages.

    PubMed

    Lee, Ka-Heng; Abas, Faridah; Alitheen, Noorjahan Banu Mohamed; Shaari, Khozirah; Lajis, Nordin Haji; Ahmad, Syahida

    2011-11-23

    Our preliminary screening had shown that the curcumin derivative [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] or BDMC33 exhibited improved anti-inflammatory activity by inhibiting nitric oxide synthesis in activated macrophage cells. In this study, we further investigated the anti-inflammatory properties of BDMC33 on PGE(2 )synthesis and cyclooxygenase (COX) expression in IFN-γ/LPS-stimulated macrophages. We found that BDMC33 significantly inhibited PGE(2) synthesis in a concentration-dependent manner albeit at a low inhibition level with an IC(50) value of 47.33 ± 1.00 µM. Interestingly, the PGE(2) inhibitory activity of BDMC33 is not attributed to inhibition of the COX enzyme activities, but rather BDMC33 selectively down-regulated the expression of COX-2. In addition, BDMC33 modulates the COX expression by sustaining the constitutively COX-1 expression in IFN-γ/LPS-treated macrophage cells. Collectively, the experimental data suggest an immunodulatory action of BDMC33 on PGE(2) synthesis and COX expression, making it a possible treatment for inflammatory disorders with minimal gastrointestinal-related side effects.

  15. Label-free Relative Quantification of Co-eluting Isobaric Phosphopeptides of Insulin Receptor Substrate-1 by HPLC-ESI-MS/MS

    PubMed Central

    Langlais, Paul; Mandarino, Lawrence J.; Yi, Zhengping

    2010-01-01

    Intracellular signal transduction is often regulated by transient protein phosphorylation in response to external stimuli. Insulin signaling is dependent on specific protein phosphorylation events, and analysis of insulin receptor substrate-1 (IRS-1) phosphorylation reveals a complex interplay between tyrosine, serine, and threonine phosphorylation. The phosphospecific antibody-based quantification approach for analyzing changes in site-specific phosphorylation of IRS-1 is difficult due to the dearth of phospho-antibodies compared with the large number of known IRS-1 phosphorylation sites. We previously published a method detailing a peak area-based mass spectrometry approach, using precursor ions for peptides, to quantify the relative abundance of site-specific phosphorylation in the absence or presence of insulin. We now present an improvement wherein site-specific phosphorylation is quantified by determining the peak area of fragment ions respective to the phospho-site of interest. This provides the advantage of being able to quantify co-eluting isobaric phosphopeptides (differentially phosphorylated versions of the same peptide), allowing for a more comprehensive analysis of protein phosphorylation. Quantifying human IRS-1 phosphorylation sites at Ser303, Ser323, Ser330, Ser348, Ser527, and Ser531 shows that this method is linear (n = 3; r2 = 0.85 ± 0.05, 0.96 ± 0.01, 0.96 ± 0.02, 0.86 ± 0.07, 0.90 ± 0.03, 0.91 ± 0.04, respectively) over an approximate 10-fold range of concentrations and reproducible (n = 4; coefficient of variation = 0.12, 0.14, 0.29, 0.30, 0.12, 0.06, respectively). This application of label-free, fragment ion-based quantification to assess relative phosphorylation changes of specific proteins will prove useful for understanding how various cell stimuli regulate protein function by phosphorylation. PMID:20594869

  16. Characterization of complex, heterogeneous lipid A samples using HPLC-MS/MS technique I. Overall analysis with respect to acylation, phosphorylation and isobaric distribution.

    PubMed

    Sándor, Viktor; Dörnyei, Ágnes; Makszin, Lilla; Kilár, Ferenc; Péterfi, Zoltán; Kocsis, Béla; Kilár, Anikó

    2016-11-01

    We established a new reversed phase-high performance liquid chromatography method combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry for the simultaneous determination and structural characterization of different lipid A types in bacteria (Escherichia coli O111, Salmonella adelaide O35 and Proteus morganii O34) showing serological cross-reactivity. The complex lipid A mixtures (obtained by simple extraction and acid hydrolysis of the outer membrane lipopolysaccharides) were separated and detected without phosphate derivatization. Several previously unidentified ions were detected, which differed in the number and type of acyl chains and number of phosphate groups. In several cases, we observed the different retention of isobaric lipid A species, which had different secondary fatty acyl distribution at the C2' or the C3' sites. The fragmentation of the various, C4' monophosphorylated lipid A species in deprotonated forms provided structural assignment for each component. Fragmentation pathways of the tri-acylated, tetra-acylated, penta-acylated, hexa-acylated and hepta-acylated lipid A components and of the lipid A partial structures are suggested. As standards, the hexa-acylated ion at m/z 1716 with the E. coli-type acyl distribution and the hepta-acylated ion at m/z 1954 with the Salmonella-type acyl distribution were used. The results confirmed the presence of multiple forms of lipid A in all strains analyzed. In addition, the negative-ion mode MS permitted efficient detection for non-phosphorylated lipid A components, too. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Equation of state of a dense plasma by orbital-free and quantum molecular dynamics: examination of two isothermal-isobaric mixing rules.

    PubMed

    Danel, J-F; Kazandjian, L

    2015-01-01

    We test two isothermal-isobaric mixing rules, respectively based on excess-pressure and total-pressure equilibration, applied to the equation of state of a dense plasma. While the equation of state is generally known for pure species, that of arbitrary mixtures is not available so that the validation of accurate mixing rules, that implies resorting to first-principles simulations, is very useful. Here we consider the case of a plastic with composition C(2)H(3) and we implement two complementary ab initio approaches adapted to the dense plasma domain: quantum molecular dynamics, limited to low temperature by its computational cost, and orbital-free molecular dynamics, that can be implemented at high temperature. The temperature and density range considered is 1-10 eV and 0.6-10 g/cm(3) for quantum molecular dynamics, and 5-1000 eV and 1-10 g/cm(3) for orbital-free molecular dynamics. Simulations for the full C(2)H(3) mixture are the benchmark against which to assess the mixing rules, and both pressure and internal energy are compared. We find that the mixing rule based on excess-pressure equilibration is overall more accurate than that based on total-pressure equilibration; except for quantum molecular dynamics and a thermodynamic domain characterized by very low or negative excess pressures, it gives pressures which are generally within statistical error or within 1% of the exact ones. Besides, its superiority is amplified in the calculation of a principal Hugoniot.

  18. High-precision buffer circuit for suppression of regenerative oscillation

    NASA Technical Reports Server (NTRS)

    Tripp, John S.; Hare, David A.; Tcheng, Ping

    1995-01-01

    Precision analog signal conditioning electronics have been developed for wind tunnel model attitude inertial sensors. This application requires low-noise, stable, microvolt-level DC performance and a high-precision buffered output. Capacitive loading of the operational amplifier output stages due to the wind tunnel analog signal distribution facilities caused regenerative oscillation and consequent rectification bias errors. Oscillation suppression techniques commonly used in audio applications were inadequate to maintain the performance requirements for the measurement of attitude for wind tunnel models. Feedback control theory is applied to develop a suppression technique based on a known compensation (snubber) circuit, which provides superior oscillation suppression with high output isolation and preserves the low-noise low-offset performance of the signal conditioning electronics. A practical design technique is developed to select the parameters for the compensation circuit to suppress regenerative oscillation occurring when typical shielded cable loads are driven.

  19. A model for tumor suppression using H-1 parvovirus.

    PubMed Central

    Telerman, A; Tuynder, M; Dupressoir, T; Robaye, B; Sigaux, F; Shaulian, E; Oren, M; Rommelaere, J; Amson, R

    1993-01-01

    A model system is proposed to investigate, at the molecular level, the pathways of tumor suppression. As a tool for the selection of cells with a suppressed phenotype, we used the H-1 parvovirus that preferentially kills various neoplastic cells. From the human K562 leukemia cells, we isolated a clone, KS, that is resistant to the cytopathic effect of the H-1 virus and displays a suppressed malignant phenotype. The suppressed malignancy and the cellular resistance to H-1 killing appear to depend on the activity of wild-type p53. Whereas the KS cells express wild-type p53, the protein is undetectable in the parental K562 cells. Experiments with p53 mutants suggest that wild-type p53, in its functionally intact state, contributes to the resistance against the cytopathic effect of H-1 parvovirus. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8378352

  20. Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds.

    PubMed

    Yoshida, Ryusuke; Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F; Ninomiya, Yuzo

    2015-11-01

    Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds.

  1. Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds

    PubMed Central

    Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F.

    2015-01-01

    Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor–deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds. PMID:26116698

  2. Effectors from Wheat Rust Fungi Suppress Multiple Plant Defense Responses.

    PubMed

    Ramachandran, Sowmya R; Yin, Chuntao; Kud, Joanna; Tanaka, Kiwamu; Mahoney, Aaron K; Xiao, Fangming; Hulbert, Scot H

    2017-01-01

    Fungi that cause cereal rust diseases (genus Puccinia) are important pathogens of wheat globally. Upon infection, the fungus secretes a number of effector proteins. Although a large repository of putative effectors has been predicted using bioinformatic pipelines, the lack of available high-throughput effector screening systems has limited functional studies on these proteins. In this study, we mined the available transcriptomes of Puccinia graminis and P. striiformis to look for potential effectors that suppress host hypersensitive response (HR). Twenty small (<300 amino acids), secreted proteins, with no predicted functions were selected for the HR suppression assay using Nicotiana benthamiana, in which each of the proteins were transiently expressed and evaluated for their ability to suppress HR caused by four cytotoxic effector-R gene combinations (Cp/Rx, ATR13/RPP13, Rpt2/RPS-2, and GPA/RBP-1) and one mutated R gene-Pto(Y207D). Nine out of twenty proteins, designated Shr1 to Shr9 (suppressors of hypersensitive response), were found to suppress HR in N. benthamiana. These effectors varied in the effector-R gene defenses they suppressed, indicating these pathogens can interfere with a variety of host defense pathways. In addition to HR suppression, effector Shr7 also suppressed PAMP-triggered immune response triggered by flg22. Finally, delivery of Shr7 through Pseudomonas fluorescens EtHAn suppressed nonspecific HR induced by Pseudomonas syringae DC3000 in wheat, confirming its activity in a homologous system. Overall, this study provides the first evidence for the presence of effectors in Puccinia species suppressing multiple plant defense responses.

  3. Simple suppression of radiation damping.

    PubMed

    Khitrin, A K; Jerschow, Alexej

    2012-12-01

    Radiation damping is known to cause line-broadening and frequency shifts of strong resonances in NMR spectra. While several techniques exist for the suppression of these effects, many require specialized hardware, or are only compatible with the presence of few strong resonances. We describe a simple pulse sequence for radiation damping suppression in spectra with many strong resonances. The sequence can be used as-is to generate simple spectra or as a signal excitation part in more advanced experiments.

  4. Functional imaging correlates of impaired distractor suppression following sleep deprivation.

    PubMed

    Kong, Danyang; Soon, Chun Siong; Chee, Michael W L

    2012-05-15

    Sleep deprivation (SD) has been shown to affect selective attention but it is not known how two of its component processes: target enhancement and distractor suppression, are affected. To investigate, young volunteers either attended to houses or were obliged to ignore them (when attending to faces) while viewing superimposed face-house pictures. MR signal enhancement and suppression in the parahippocampal place area (PPA) were determined relative to a passive viewing control condition. Sleep deprivation was associated with lower PPA activation across conditions. Critically SD specifically impaired distractor suppression in selective attention, leaving target enhancement relatively preserved. These findings parallel some observations in cognitive aging. Additionally, following SD, attended houses were not significantly better recognized than ignored houses in a post-experiment test of recognition memory contrasting with the finding of superior recognition of attended houses in the well-rested state. These results provide evidence for co-encoding of distracting information with targets into memory when one is sleep deprived.

  5. Suppressed Charmed B Decay

    SciTech Connect

    Snoek, Hella Leonie

    2009-06-02

    This thesis describes the measurement of the branching fractions of the suppressed charmed B0 → D*- a0+ decays and the non-resonant B0 → D*- ηπ+ decays in approximately 230 million Υ(4S) → B$\\bar{B}$ events. The data have been collected with the BABAR detector at the PEP-II B factory at the Stanford Linear Accelerator Center in California. Theoretical predictions of the branching fraction of the B0 → D*- a{sub 0}+ decays show large QCD model dependent uncertainties. Non-factorizing terms, in the naive factorization model, that can be calculated by QCD factorizing models have a large impact on the branching fraction of these decay modes. The predictions of the branching fractions are of the order of 10-6. The measurement of the branching fraction gives more insight into the theoretical models. In general a better understanding of QCD models will be necessary to conduct weak interaction physics at the next level. The presence of CP violation in electroweak interactions allows the differentiation between matter and antimatter in the laws of physics. In the Standard Model, CP violation is incorporated in the CKM matrix that describes the weak interaction between quarks. Relations amongst the CKM matrix elements are used to present the two relevant parameters as the apex of a triangle (Unitarity Triangle) in a complex plane. The over-constraining of the CKM triangle by experimental measurements is an important test of the Standard Model. At this moment no stringent direct measurements of the CKM angle γ, one of the interior angles of the Unitarity Triangle, are available. The measurement of the angle γ can be performed using the decays of neutral B mesons. The B0 → D*- a0+ decay is sensitive to the angle γ and, in comparison to the current decays that are being employed, could significantly

  6. SWET for secure water suppression on probes with high quality factor.

    PubMed

    Wu, Peter S C; Otting, Gottfried

    2005-07-01

    Water suppression by selective preirradiation is increasingly difficult to achieve on probeheads with high quality factor because of the opposing forces of radiation damping. Here we show that a simple modification to the WET scheme provides reliable water suppression in aqueous solutions of proteins and peptides with minimal saturation of the H(alpha) protons. The scheme is shown to work also with dilute peptide solutions. It is recommended to maintain the water suppression during the evolution time of COSY experiments by weak selective irradiation that causes only minimal Bloch-Siegert shifts. The new water-suppression scheme suppresses the water magnetization by spatial scrambling. Traditional water suppression by preirradiation is similarly based more on water scrambling due to the radiofrequency inhomogeneity than on relaxation effects.

  7. Influence of the opening angle of a conical supersonic nozzle on the structure of initial interval of non-isobaric jet

    NASA Astrophysics Data System (ADS)

    Vetlutsky, V. N.; Ganimedov, V. L.; Muchnaya, M. I.

    2008-06-01

    The ideal gas exhaustion from an infinite volume into a gas at rest through a supersonic conical Laval nozzle is considered. The problem was solved numerically by steadying in time in a unified formulation for the regions inside the nozzle and in the ambient environment. In such a statement, the nozzle outlet section is no internal boundary of the region under consideration, and there is no need of specifying the boundary conditions here. Local subsonic zones arising in the flow lie inside the region under consideration, which eliminates the possibility of using a marching technique along one of the coordinates. The numerical solution is constructed by a unified algorithm for the entire flow region, which gives a possibility of obtaining a higher accuracy. The computations are carried out in the jet initial interval, where, according to monograph [1], the wave phenomena predominate over the viscous effects. The exhaustion process is described by the system of gas dynamics equations. Their solution is constructed with the aid of a finite difference Harten’s TVD (Total Variation Diminishing) scheme [2], which has the second approximation order in space. The second approximation order in time is achieved with the aid of a five-stage Runge-Kutta method. The solution algorithm has been parallelized in space and implemented on the multi-processor computer systems of the ITAM SB RAS and the MVS-128 of the Siberian Supercomputer Center of SB RAS. The influence of the semi-apex angle of the nozzle supersonic part and the pressure jump between the nozzle outlet section and the ambient environment on the flow in the initial interval of a non-isobaric jet is investigated in the work. A comparison with experimental data is presented. The computations are carried out for the semi-apex angles of the nozzle supersonic part from 0 (parallel flow) to 20 degrees. For all considered nozzles, the Mach number in the nozzle outlet section, which was computed from the one

  8. Effects of {Delta}-isobar degrees of freedom on the reactions {sup 3}He(n,{gamma}){sup 4}He and {sup 3}He(p,e{sup +}{nu}{sub e}){sup 4}He at low-energy

    SciTech Connect

    Schiavilla, R.

    1991-12-31

    The cross sections of the radiative {sup 3}He(n,{gamma}){sup 4}He and weak {sup 3}He(p,e{sup +}{nu}{sub e}){sup 4}He capture reactions at thermal neutron and keV proton energies have been calculated with the Variational Monte Carlo method. The ground state and low-energy continuum wave functions have been determined variationally from a realistic Hamiltonian, and include both nucleon and {Delta}-isobar degrees of freedom. The electroweak transition operator contains one- and two-body components in the N + {Delta} Hilbert space.

  9. Effects of. Delta. -isobar degrees of freedom on the reactions sup 3 He(n,. gamma. ) sup 4 He and sup 3 He(p,e sup +. nu. sub e ) sup 4 He at low-energy

    SciTech Connect

    Schiavilla, R.

    1991-01-01

    The cross sections of the radiative {sup 3}He(n,{gamma}){sup 4}He and weak {sup 3}He(p,e{sup +}{nu}{sub e}){sup 4}He capture reactions at thermal neutron and keV proton energies have been calculated with the Variational Monte Carlo method. The ground state and low-energy continuum wave functions have been determined variationally from a realistic Hamiltonian, and include both nucleon and {Delta}-isobar degrees of freedom. The electroweak transition operator contains one- and two-body components in the N + {Delta} Hilbert space.

  10. Coating Thermoelectric Devices To Suppress Sublimation

    NASA Technical Reports Server (NTRS)

    Sakamoto, Jeffrey; Caillat, Thierry; Fleurial, Jean-Pierre; Snyder, G. Jeffrey

    2007-01-01

    A technique for suppressing sublimation of key elements from skutterudite compounds in advanced thermoelectric devices has been demonstrated. The essence of the technique is to cover what would otherwise be the exposed skutterudite surface of such a device with a thin, continuous film of a chemically and physically compatible metal. Although similar to other sublimation-suppression techniques, this technique has been specifically tailored for application to skutterudite antimonides. The primary cause of deterioration of most thermoelectric materials is thermal decomposition or sublimation - one or more elements sublime from the hot side of a thermoelectric couple, changing the stoichiometry of the device. Examples of elements that sublime from their respective thermoelectric materials are Ge from SiGe, Te from Pb/Te, and now Sb from skutterudite antimonides. The skutterudite antimonides of primary interest are CoSb3 [electron-donor (n) type] and CeFe(3-x)Co(x)Sb12 [electron-acceptor (p) type]. When these compounds are subjected to typical operating conditions [temperature of 700 C and pressure <10(exp -5) torr (0.0013 Pa)], Sb sublimes from their surfaces, with the result that Sb depletion layers form and advance toward their interiors. As the depletion layer advances in a given device, the change in stoichiometry diminishes the thermal-to-electric conversion efficiency of the device. The problem, then, is to prevent sublimation, or at least reduce it to an acceptably low level. In preparation for an experiment on suppression of sublimation, a specimen of CoSb3 was tightly wrapped in a foil of niobium, which was selected for its chemical stability. In the experiment, the wrapped specimen was heated to a temperature of 700 C in a vacuum of residual pressure <10(exp -5) torr (0.0013 Pa), then cooled and sectioned. Examination of the sectioned specimen revealed that no depletion layer had formed, indicating the niobium foil prevented sublimation of antimony at 700 C

  11. Detection of Burst Suppression Patterns in EEG Using Recurrence Rate

    PubMed Central

    Ren, Yongshao; Sleigh, Jamie; Li, Xiaoli

    2014-01-01

    Burst suppression is a unique electroencephalogram (EEG) pattern commonly seen in cases of severely reduced brain activity such as overdose of general anesthesia. It is important to detect burst suppression reliably during the administration of anesthetic or sedative agents, especially for cerebral-protective treatments in various neurosurgical diseases. This study investigates recurrent plot (RP) analysis for the detection of the burst suppression pattern (BSP) in EEG. The RP analysis is applied to EEG data containing BSPs collected from 14 patients. Firstly we obtain the best selection of parameters for RP analysis. Then, the recurrence rate (RR), determinism (DET), and entropy (ENTR) are calculated. Then RR was selected as the best BSP index one-way analysis of variance (ANOVA) and multiple comparison tests. Finally, the performance of RR analysis is compared with spectral analysis, bispectral analysis, approximate entropy, and the nonlinear energy operator (NLEO). ANOVA and multiple comparison tests showed that the RR could detect BSP and that it was superior to other measures with the highest sensitivity of suppression detection (96.49%, P = 0.03). Tracking BSP patterns is essential for clinical monitoring in critically ill and anesthetized patients. The purposed RR may provide an effective burst suppression detector for developing new patient monitoring systems. PMID:24883378

  12. Ketamine selectively suppresses synchronized afterdischarges in immature hippocampus.

    PubMed

    Brady, R J; Swann, J W

    1986-08-29

    The role of excitatory amino acid neurotransmission in epileptogenesis was investigated in the developing hippocampus. Bath application of ketamine blocked penicillin-induced, synchronized afterdischarges in immature rat CA3 hippocampal neurons. Ketamine also decreased the duration of the preceding intracellularly recorded depolarization shift but had no measurable effect on the resting membrane potential or input impedance of pyramidal cells. Concentrations of ketamine that blocked afterdischarge generation dramatically depressed intracellular depolarizations produced by iontophoretic application of N-methyl-D-aspartate (NMDA) but not quisqualate. The effects of the NMDA antagonist 2-amino-7-phosphonoheptanoic acid on epileptiform discharges were identical to those of ketamine. These results suggest that an endogenous excitatory amino acid acting on an NMDA receptor plays a key role in the pronounced capacity of immature hippocampus for seizures.

  13. The amphetamine appetite suppressant saga.

    PubMed

    2004-02-01

    (1) In 1999, all amphetamine derivatives still sold in France as appetite suppressants were withdrawn from the market because of serious cardiovascular adverse effects. Sibutramine, marketed in France since 2001, is closely related to this group of drugs. (2) The adverse effects shared by these drugs are mainly neuropsychiatric (due to a psychostimulant action) and cardiovascular (arterial hypertension and tachycardia). (3) More specific cardiovascular adverse effects, such as pulmonary hypertension and severe cardiac valve damage, emerged after several years of use. The first reports date back to the 1960s. (4) The pulmonary hypertension associated with appetite suppressants can be fatal or necessitate transplantation. (5) Cardiac valve damage due to appetite suppressants is generally irreversible and sometimes requires surgery.

  14. Visual Surround Suppression in Schizophrenia

    PubMed Central

    Tibber, Marc S.; Anderson, Elaine J.; Bobin, Tracy; Antonova, Elena; Seabright, Alice; Wright, Bernice; Carlin, Patricia; Shergill, Sukhwinder S.; Dakin, Steven C.

    2013-01-01

    Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast – a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies. PMID:23450069

  15. Noise suppressing capillary separation system

    DOEpatents

    Yeung, Edward S.; Xue, Yongjun

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans.

  16. Light induced suppression of sulfur in a cesium sputter ion source

    PubMed Central

    Martschini, Martin; Rohlén, Johan; Andersson, Pontus; Golser, Robin; Hanstorp, Dag; Lindahl, Anton O.; Priller, Alfred; Steier, Peter; Forstner, Oliver

    2012-01-01

    New techniques for suppression of atomic isobars in negative ion beams are of great interest for accelerator mass spectrometry (AMS). Especially small and medium-sized facilities can significantly extend their measurement capabilities to new interesting isotopes with a technique independent of terminal voltage. In a new approach, the effect of continuous wave laser light directed towards the cathode surface in a cesium sputter ion source of the Middleton type was studied. The laser light induced a significant change in oxygen, sulfur and chlorine negative ion production from a AgCl target. Approximately 100 mW of laser light reduced the sulfur to chlorine ratio by one order of magnitude. The effect was found to depend on laser power and ion source parameters but not on the laser wavelength. The time constant of the effect varied from a few seconds up to several minutes. Experiments were first performed at the ion beam facility GUNILLA at University of Gothenburg with macroscopic amounts of sulfur. The results were then reproduced at the VERA AMS facility with chemically cleaned AgCl targets containing ∼1 ppm sulfur. The physical explanation behind the effect is still unclear. Nevertheless, the technique has been successfully applied during a regular AMS measurement of 36Cl. PMID:23576897

  17. Light induced suppression of sulfur in a cesium sputter ion source.

    PubMed

    Martschini, Martin; Rohlén, Johan; Andersson, Pontus; Golser, Robin; Hanstorp, Dag; Lindahl, Anton O; Priller, Alfred; Steier, Peter; Forstner, Oliver

    2012-04-01

    New techniques for suppression of atomic isobars in negative ion beams are of great interest for accelerator mass spectrometry (AMS). Especially small and medium-sized facilities can significantly extend their measurement capabilities to new interesting isotopes with a technique independent of terminal voltage. In a new approach, the effect of continuous wave laser light directed towards the cathode surface in a cesium sputter ion source of the Middleton type was studied. The laser light induced a significant change in oxygen, sulfur and chlorine negative ion production from a AgCl target. Approximately 100 mW of laser light reduced the sulfur to chlorine ratio by one order of magnitude. The effect was found to depend on laser power and ion source parameters but not on the laser wavelength. The time constant of the effect varied from a few seconds up to several minutes. Experiments were first performed at the ion beam facility GUNILLA at University of Gothenburg with macroscopic amounts of sulfur. The results were then reproduced at the VERA AMS facility with chemically cleaned AgCl targets containing ∼1 ppm sulfur. The physical explanation behind the effect is still unclear. Nevertheless, the technique has been successfully applied during a regular AMS measurement of (36)Cl.

  18. Distinction and quantitation of leucine-isoleucine isomers and lysine-glutamine isobars by electrospray ionization tandem mass spectrometry (MS(n), n = 2, 3) of copper(II)-diimine complexes.

    PubMed

    Seymour, J L; Turecek, F

    2000-04-01

    Electrospray ionization of mixtures of isomeric and isobaric amino acids was investigated with the goal of distinguishing and quantifying the components. Isomeric amino acids leucine and isoleucine were readily distinguished and quantified in 90 : 10 to 10 : 90 binary mixtures using two-stage (MS(2)) and three-stage (MS(3)) tandem mass spectrometric dissociations of ternary Cu(2+)-2, 2'-bipyridyl (bpy) complexes, [Cu(AA - H)bpy](+). The complexes self-assembled in solution upon mixing the components and provided a convenient means of efficient derivatization that increased the efficiency of amino acid ionization by electrospray and shifted the mass of the analytes to a region which was free of solvent interferences. Low-energy dissociations of [Cu(AA - H)bpy](+) complexes in a quadrupole ion trap were achieved at >90% conversions and >80% trapping efficiencies for the MS(2) and MS(3) precursor and fragment ions. Isobaric amino acids glutamine and lysine were also distinguished through MS(2) and MS(3) of their ternary complexes with Cu(2+) and bpy. ESI of [Cu(Gln - H)bpy](+) was enhanced in the presence of [Cu(Lys - H)bpy](+), which resulted in non-linear response at low Lys concentrations.

  19. Inhibition of saccades elicits attentional suppression.

    PubMed

    Dhawan, Saurabh; Deubel, Heiner; Jonikaitis, Donatas

    2013-05-17

    Visuospatial attention has been shown to have a central role in planning and generation of saccades but what role, if any, it plays in inhibition of saccades remains unclear. In this study, we used an oculomotor delayed match- or nonmatch-to-sample task in which a cued location has to be encoded and memorized for one of two very different goals-to plan a saccade to it or to avoid making a saccade to it. We measured the spatial allocation of attention during the delay and found that while marking a location as a future saccade target resulted in an attentional benefit at that location, marking it as forbidden to saccades led to an attentional cost. Additionally, saccade trajectories were found to deviate away more from the "don't look" location than from a saccade-irrelevant distractor confirming greater inhibition of an actively forbidden location in oculomotor programming. Our finding that attention is suppressed at locations forbidden to saccades confirms and complements the claim of a selective and obligatory coupling between saccades and attention-saccades at the memorized location could neither be planned nor suppressed independent of a corresponding effect on attentional performance.

  20. Antisense RNA suppression of peroxidase gene expression

    SciTech Connect

    Lagrimini, L.M.; Bradford, S.; De Leon, F.D. )

    1989-04-01

    The 5{prime} half the anionic peroxidase cDNA of tobacco was inserted into a CaMV 35S promoter/terminator expression cassette in the antisense configuration. This was inserted into the Agrobacterium-mediated plant transformation vector pCIBIO which includes kanamycin selection, transformed into two species of tobacco (N. tabacum and M. sylvestris), and plants were subsequently regenerated on kanamycin. Transgenic plants were analyzed for peroxidase expression and found to have 3-5 fold lower levels of peroxidase than wild-type plants. Isoelectric focusing demonstrated that the antisense RNA only suppressed the anionic peroxidase. Wound-induced peroxidase expression was found not to be affected by the antisense RNA. Northern blots show a greater than 5 fold suppression of anionic peroxidase mRNA in leaf tissue, and the antisense RNA was expressed at a level 2 fold over the endogenous mRNA. Plants were self-pollinated and F1 plants showed normal segregation. N. sylvestris transgenic plants with the lowest level of peroxidase are epinastic, and preliminary results indicate elevated auxin levels. Excised pith tissue from both species of transgenic plants rapidly collapse when exposed to air, while pith tissue from wild-type plants showed little change when exposed to air. Further characterization of these phenotypes is currently being made.

  1. Suppression of Dopamine Neurons Mediates Reward

    PubMed Central

    Yamagata, Nobuhiro; Abe, Ayako; Tanimoto, Hiromu

    2016-01-01

    Massive activation of dopamine neurons is critical for natural reward and drug abuse. In contrast, the significance of their spontaneous activity remains elusive. In Drosophila melanogaster, depolarization of the protocerebral anterior medial (PAM) cluster dopamine neurons en masse signals reward to the mushroom body (MB) and drives appetitive memory. Focusing on the functional heterogeneity of PAM cluster neurons, we identified that a single class of PAM neurons, PAM-γ3, mediates sugar reward by suppressing their own activity. PAM-γ3 is selectively required for appetitive olfactory learning, while activation of these neurons in turn induces aversive memory. Ongoing activity of PAM-γ3 gets suppressed upon sugar ingestion. Strikingly, transient inactivation of basal PAM-γ3 activity can substitute for reward and induces appetitive memory. Furthermore, we identified the satiety-signaling neuropeptide Allatostatin A (AstA) as a key mediator that conveys inhibitory input onto PAM-γ3. Our results suggest the significance of basal dopamine release in reward signaling and reveal a circuit mechanism for negative regulation. PMID:27997541

  2. Conditioned suppression, punishment, and aversion

    NASA Technical Reports Server (NTRS)

    Orme-Johnson, D. W.; Yarczower, M.

    1974-01-01

    The aversive action of visual stimuli was studied in two groups of pigeons which received response-contingent or noncontingent electric shocks in cages with translucent response keys. Presentation of grain for 3 sec, contingent on key pecking, was the visual stimulus associated with conditioned punishment or suppression. The responses of the pigeons in three different experiments are compared.

  3. Eigenspace techniques for active flutter suppression

    NASA Technical Reports Server (NTRS)

    Garrard, William L.; Liebst, Bradley S.; Farm, Jerome A.

    1987-01-01

    The use of eigenspace techniques for the design of an active flutter suppression system for a hypothetical research drone is discussed. One leading edge and two trailing edge aerodynamic control surfaces and four sensors (accelerometers) are available for each wing. Full state control laws are designed by selecting feedback gains which place closed loop eigenvalues and shape closed loop eigenvectors so as to stabilize wing flutter and reduce gust loads at the wing root while yielding accepatable robustness and satisfying constrains on rms control surface activity. These controllers are realized by state estimators designed using an eigenvalue placement/eigenvector shaping technique which results in recovery of the full state loop transfer characteristics. The resulting feedback compensators are shown to perform almost as well as the full state designs. They also exhibit acceptable performance in situations in which the failure of an actuator is simulated.

  4. Preparatory activity in visual cortex indexes distractor suppression during covert spatial orienting.

    PubMed

    Serences, John T; Yantis, Steven; Culberson, Andrew; Awh, Edward

    2004-12-01

    The deployment of spatial attention induces retinotopically specific increases in neural activity that occur even before a target stimulus is presented. Although this preparatory activity is thought to prime the attended regions, thereby improving perception and recognition, it is not yet clear whether this activity is a manifestation of signal enhancement at the attended locations or suppression of interference from distracting stimuli (or both). We investigated the functional role of these preparatory shifts by isolating a distractor suppression component of selection. Behavioral data have shown that manipulating the probability that visual distractors will appear modulates distractor suppression without concurrent changes in signal enhancement. In 2 experiments, functional magnetic resonance imaging revealed increased cue-evoked activity in retinotopically specific regions of visual cortex when increased distractor suppression was elicited by a high probability of distractors. This finding directly links cue-evoked preparatory activity in visual cortex with a distractor suppression component of visual selective attention.

  5. Suppression of proinflammatory cytokines in monocytes by a tetravalent guanylhydrazone

    PubMed Central

    1996-01-01

    An overproduction of proinflammatory cytokines by activated macrophages/monocytes mediates the injurious sequelae of inflammation, septic shock, tissue injury, and cachexia. We recently synthesized a tetravalent guanylhydrazone compound (CNI-1493) that inhibits cytokine- inducible arginine transport and nitric oxide (NO) production in macrophages, and protects mice against lethal endotoxemia and carrageenan-induced inflammation. During these investigations we noticed that CNI-1493 effectively prevented lipopolysaccharide (LPS)- induced NO production, even when added in concentrations 10-fold less than required to competitively inhibit L-arginine uptake, suggesting that the suppressive effects of this guanylhydrazone compound might extend to other LPS-induced responses. Here, we report that CNI-1493 suppressed the LPS-stimulated production of proinflammatory cytokines (tumor necrosis factor [TNF], interleukins 1beta and 6, macrophage inflammatory proteins 1alpha and 1beta) from human peripheral blood mononuclear cells. Cytokine suppression was specific, in that CNI-1493 did not inhibit either the constitutive synthesis of transforming growth factor beta or the upregulation of major histocompatibility complex class II by interferon gamma (IFN-gamma). In contrast to the macrophage suppressive actions of dexamethasone, which are overridden in the presence of IFN-gamma, CNI-1493 retained its suppressive effects even in the presence of IFN-gamma. The mechanism of cytokine- suppressive action by CNI-1493 was independent of extracellular L- arginine content and NO production and is not restricted to induction by LPS. As a selective inhibitor of macrophage activation that prevents TNF production, this tetravalent guanylhydrazone could be useful in the development of cytokine-suppressive agents for the treatment of diseases mediated by overproduction of cytokines. PMID:8642296

  6. Evaluation of CO2, N2 and He as Fire Suppression Agents in Microgravity

    NASA Technical Reports Server (NTRS)

    Ruff, Gary A.; Hicks, Michael; Pettegrew, Richard

    2004-01-01

    The U.S. modules of the International Space Station use gaseous CO2 as the fire extinguishing agent. This was selected as a result of extensive experience with CO2 as a fire suppressant in terrestrial applications, trade studies on various suppressants, and experiments. The selection of fire suppressants and suppression strategies for NASA s Lunar and Martian exploration missions will be based on the same studies and normal-gravity data unless reduced gravity fire suppression data is obtained. In this study, the suppressant agent concentrations required to extinguish a flame in low velocity convective flows within the 20-sec of low gravity on the KC-135 aircraft were investigated. Suppressant gas mixtures of CO2, N2, and He with the balance being oxygen/nitrogen mixtures with either 21% or 25% O2 were used to suppress flames on a 19-mm diameter PMMA cylinder in reduced gravity. For each of the suppressant mixtures, limiting concentrations were established that would extinguish the flame at any velocity. Similarly, concentrations were established that would not extinguish the flame. The limiting concentrations were generally consistent with previous studies but did suggest that geometry had an effect on the limiting conditions. Between the extinction and non-extinction limits, the suppression characteristics depended on the extinguishing agent, flow velocity, and O2 concentration. The limiting velocity data from the CO2, He, and N2 suppressants were well correlated using an effective mixture enthalpy per mole of O2, indicating that all act via O2 displacement and cooling mechanisms. In reduced gravity, the agent concentration required to suppress the flames increased as the velocity increased, up to approximately 10 cm/s (the maximum velocity evaluated in this experiment). The effective enthalpy required to extinguish flames at velocities of 10 cm/s is approximately the same as the concentrations in normal gravity. A computational study is underway to further

  7. Reversible Smad-dependent signaling between tumor suppression and oncogenesis.

    PubMed

    Sekimoto, Go; Matsuzaki, Koichi; Yoshida, Katsunori; Mori, Shigeo; Murata, Miki; Seki, Toshihito; Matsui, Hirofumi; Fujisawa, Jun-ichi; Okazaki, Kazuichi

    2007-06-01

    Cancer cells often gain advantage by reducing the tumor-suppressive activity of transforming growth factor-beta (TGF-beta) together with stimulation of its oncogenic activity as in Ras-transformed cells; however, molecular mechanisms remain largely unknown. TGF-beta activates both its type I receptor (TbetaRI) and c-Jun NH2-terminal kinase (JNK), which phosphorylate Smad2 and Smad3 at the COOH-terminal (pSmad2/3C) and linker regions (pSmad2/3L). Here, we report that Ras transformation suppresses TbetaRI-mediated pSmad3C signaling, which involves growth inhibition by down-regulating c-Myc. Instead, hyperactive Ras constitutively stimulates JNK-mediated pSmad2/3L signaling, which fosters tumor invasion by up-regulating plasminogen activator inhibitor-1 and matrix metalloproteinase-1 (MMP-1), MMP-2, and MMP-9. Conversely, selective blockade of linker phosphorylation by a mutant Smad3 lacking JNK-dependent phosphorylation sites results in preserved tumor-suppressive function via pSmad3C in Ras-transformed cells while eliminating pSmad2/3L-mediated invasive capacity. Thus, specific inhibition of the JNK/pSmad2/3L pathway should suppress cancer progression by shifting Smad-dependent signaling from oncogenesis to tumor suppression.

  8. Noise suppressing capillary separation system

    DOEpatents

    Yeung, E.S.; Xue, Y.

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans. 13 figs.

  9. Older Adults Can Suppress Unwanted Memories When Given an Appropriate Strategy

    PubMed Central

    2015-01-01

    Memory suppression refers to the ability to exclude distracting memories from conscious awareness, and this ability can be assessed with the think/no-think paradigm. Recent research with older adults has provided evidence suggesting both intact and deficient memory suppression. The present studies seek to understand the conditions contributing to older adults’ ability to suppress memories voluntarily. We report 2 experiments indicating that the specificity of the think/no-think task instructions contributes to older adults’ suppression success: When older adults receive open-ended instructions that require them to develop a retrieval suppression strategy on their own, they show diminished memory suppression compared with younger adults. Conversely, when older adults receive focused instructions directing them to a strategy thought to better isolate inhibitory control, they show suppression-induced forgetting similar to that exhibited by younger adults. Younger adults demonstrate memory suppression regardless of the specificity of the instructions given, suggesting that the ability to select a successful suppression strategy spontaneously may be compromised in older adults. If so, this deficit may be associated with diminished control over unwanted memories in naturalistic settings if impeded strategy development reduces the successful deployment of inhibitory control. PMID:25602491

  10. Suppression of operant vs consummatory behavior.

    PubMed

    DeCosta, M J; Ayres, J J

    1971-07-01

    The magnitude and variability of conditioned suppression of bar pressing and dipper licking were compared. In two steady-state experiments, suppression of bar pressing was more profound and more stable from day to day. The two measures of suppression were uncorrelated as indexed by Pearson product-moment correlation coefficients computed for adjacent trials. Correlations within measures (internal consistency) were somewhat higher for the bar-press system except when a high proportion of rats completely suppressed on one of the correlated trials. In a transient state experiment in which possible adventitious punishment of both response systems was eliminated, suppression of bar pressing was again more profound and considerably slower to extinguish.

  11. Fire suppression and detection equipment

    SciTech Connect

    E.E. Bates

    2006-01-15

    Inspection and testing guidelines go beyond the 'Code of Federal Regulation'. Title 30 of the US Code of Federal Regulations (30 CFR) contains requirements and references to national standards for inspection, testing and maintenance of fire suppression and detection equipment for mine operators. However, federal requirements have not kept pace with national standards and best practices. The article lists National Fire Protection (NFPA) standards that are referenced by the US Mine Safety and Health Administration (MSHA) in 30 CFR. It then discusses other NFPA Standards excluded from 30 CFR and explains the NFPA standard development process. 2 refs., 3 tabs., 5 photos.

  12. Menstrual suppression in special circumstances.

    PubMed

    Kirkham, Yolanda A; Ornstein, Melanie P; Aggarwal, Anjali; McQuillan, Sarah; Allen, Lisa; Millar, Debra; Dalziel, Nancy; Gascon, Suzy; Hakim, Julie; Ryckman, Julie; Spitzer, Rachel; Van Eyk, Nancy

    2014-10-01

    Objectif : Offrir, aux fournisseurs de soins de santé, un document de consensus canadien comptant des recommandations pour ce qui est de la suppression menstruelle chez les patientes qui font face à des obstacles physiques et/ou cognitifs ou chez les patientes qui font l’objet d’un traitement contre le cancer et pour lesquelles les règles pourraient exercer un effet délétère sur la santé. Options : Le présent document analyse les options disponibles aux fins de la suppression menstruelle, les indications, les contre-indications et les effets indésirables (tant immédiats qu’à long terme) propres à cette dernière, et les explorations et le monitorage nécessaires tout au long de la suppression. Issues : Les cliniciens seront mieux renseignés au sujet des options et des indications propres à la suppression menstruelle chez les patientes qui présentent des déficiences cognitives et/ou physiques et chez les patientes qui font l’objet d’une chimiothérapie, d’une radiothérapie ou d’autres traitements contre le cancer. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans Medline, EMBASE, OVID et The Cochrane Library au moyen d’un vocabulaire contrôlé et de mots clés appropriés (p. ex. « heavy menstrual bleeding », « menstrual suppression », « chemotherapy/radiation », « cognitive disability », « physical disability », « learning disability »). Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés, aux études observationnelles et aux études pilotes. Aucune restriction n’a été imposée en matière de langue ou de date. Les recherches ont été mises à jour de façon régulière et du nouveau matériel a été intégré à la directive clinique jusqu’en septembre 2013. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d

  13. A Comparison of Urge Intensity and the Probability of Tic Completion During Tic Freely and Tic Suppression Conditions.

    PubMed

    Specht, Matt W; Nicotra, Cassandra M; Kelly, Laura M; Woods, Douglas W; Ricketts, Emily J; Perry-Parrish, Carisa; Reynolds, Elizabeth; Hankinson, Jessica; Grados, Marco A; Ostrander, Rick S; Walkup, John T

    2014-03-01

    Tic-suppression-based treatments (TSBTs) represent a safe and effective treatment option for Chronic Tic Disorders (CTDs). Prior research has demonstrated that treatment naive youths with CTDs have the capacity to safely and effectively suppress tics for prolonged periods. It remains unclear how tic suppression is achieved. The current study principally examines how effective suppression is achieved and preliminary correlates of the ability to suppress tics. Twelve youths, ages 10 to 17 years, with moderate-to-marked CTDs participated in an alternating sequence of tic freely and reinforced tic suppression conditions during which urge intensity and tic frequency were frequently assessed. Probability of tics occurring was half as likely following high-intensity urges during tic suppression (31%) in contrast to low-intensity urges during tic freely conditions (60%). Age was not associated with ability to suppress. Intelligence indices were associated with or trended toward greater ability to suppress tics. Attention difficulties were not associated with ability to suppress but were associated with tic severity. In contrast to our "selective suppression" hypothesis, we found participants equally capable of suppressing their tics regardless of urge intensity during reinforced tic suppression. Tic suppression was achieved with an "across-the-board" effort to resist urges. Preliminary data suggest that ability to suppress may be associated with general cognitive variables rather than age, tic severity, urge severity, and attention. Treatment naive youths appear to possess a capacity for robust tic suppression. TSBTs may bolster these capacities and/or enable their broader implementation, resulting in symptom improvement.

  14. Orientation-tuned suppression in binocular rivalry reveals general and specific components of rivalry suppression.

    PubMed

    Stuit, Sjoerd M; Cass, John; Paffen, Chris L E; Alais, David

    2009-10-16

    During binocular rivalry (BR), conflicting monocular images are alternately suppressed from awareness. During suppression of an image, contrast sensitivity for probes is reduced by approximately 0.3-0.5 log units relative to when the image is in perceptual dominance. Previous studies on rivalry suppression have led to controversies concerning the nature and extent of suppression during BR. We tested for feature-specific suppression using orthogonal rivaling gratings and measuring contrast sensitivity to small grating probes at a range of orientations in a 2AFC orientation discrimination task. Results indicate that suppression is not uniform across orientations: suppression was much greater for orientations close to that of the suppressed grating. The higher suppression was specific to a narrow range around the suppressed rival grating, with a tuning similar to V1 orientation bandwidths. A similar experiment tested for spatial frequency tuning and found that suppression was stronger for frequencies close to that of the suppressed grating. Interestingly, no tuned suppression was observed when a flicker-and-swap paradigm was used, suggesting that tuned suppression occurs only for lower-level, interocular rivalry. Together, the results suggest there are two components to rivalry suppression: a general feature-invariant component and an additional component specifically tuned to the rivaling features.

  15. Suppressed epidemics in multirelational networks

    NASA Astrophysics Data System (ADS)

    Xu, Elvis H. W.; Wang, Wei; Xu, C.; Tang, Ming; Do, Younghae; Hui, P. M.

    2015-08-01

    A two-state epidemic model in networks with links mimicking two kinds of relationships between connected nodes is introduced. Links of weights w1 and w0 occur with probabilities p and 1 -p , respectively. The fraction of infected nodes ρ (p ) shows a nonmonotonic behavior, with ρ drops with p for small p and increases for large p . For small to moderate w1/w0 ratios, ρ (p ) exhibits a minimum that signifies an optimal suppression. For large w1/w0 ratios, the suppression leads to an absorbing phase consisting only of healthy nodes within a range pL≤p ≤pR , and an active phase with mixed infected and healthy nodes for p pR . A mean field theory that ignores spatial correlation is shown to give qualitative agreement and capture all the key features. A physical picture that emphasizes the intricate interplay between infections via w0 links and within clusters formed by nodes carrying the w1 links is presented. The absorbing state at large w1/w0 ratios results when the clusters are big enough to disrupt the spread via w0 links and yet small enough to avoid an epidemic within the clusters. A theory that uses the possible local environments of a node as variables is formulated. The theory gives results in good agreement with simulation results, thereby showing the necessity of including longer spatial correlations.

  16. Water Mist fire suppression experiment

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Water Mist commercial research program is scheduled to fly an investigation on STS-107 in 2002. This investigation will be flown as an Experimental Mounting Structure (EMS) insert into the updated Combustion Module (CM-2), a sophisticated combustion chamber plus diagnostic equipment. (The investigation hardware is shown here mounted in a non-flight frame similar to the EMS.) Water Mist is a commercial research program by the Center for Commercial Applications of Combustion in Space (CCACS), a NASA Commercial Space Center located at the Colorado School of Mines, in Golden, CO and Industry Partner Environmental Engineering Concepts. The program is focused on developing water mist as a replacement for bromine-based chemical fire suppression agents (halons). By conducting the experiments in microgravity, interference from convection currents is minimized and fundamental knowledge can be gained. This knowledge is incorporated into models, which can be used to simulate a variety of physical environments. The immediate objective of the project is to study the effect of a fine water mist on a laminar propagating flame generated in a propane-air mixture at various equivalence ratios. The effects of droplet size and concentration on the speed of the flame front is used as a measure of the effectiveness of fire suppression in this highly controlled experimental environment.

  17. Using multiple perspectives to suppress information and complexity

    SciTech Connect

    Kelsey, R.L. |; Webster, R.B.; Hartley, R.T.

    1998-09-01

    Dissemination of battlespace information involves getting information to particular warfighters that is both useful and in a form that facilitates the tasks of those particular warfighters. There are two issues which motivate this problem of dissemination. The first issue deals with disseminating pertinent information to a particular warfighter. This can be thought of as information suppression. The second issue deals with facilitating the use of the information by tailoring the computer interface to the specific tasks of an individual warfighter. This can be thought of as interface complexity suppression. This paper presents a framework for suppressing information using an object-based knowledge representation methodology. This methodology has the ability to represent knowledge and information in multiple perspectives. Information can be suppressed by creating a perspective specific to an individual warfighter. In this way, only the information pertinent and useful to a warfighter is made available to that warfighter. Information is not removed, lost, or changed, but spread among multiple perspectives. Interface complexity is managed in a similar manner. Rather than have one generalized computer interface to access all information, the computer interface can be divided into interface elements. Interface elements can then be selected and arranged into a perspective-specific interface. This is done in a manner to facilitate completion of tasks contained in that perspective. A basic battlespace domain containing ground and air elements and associated warfighters is used to exercise the methodology.

  18. Distinct Mechanisms for Distractor Suppression and Target Facilitation

    PubMed Central

    Adamian, Nika; Pike, Alexandra; Printzlau, Frida; Crittenden, Ben M.; Stokes, Mark G.

    2016-01-01

    this paradox, it is often assumed that distractor suppression is controlled via similar top-down mechanisms of attention that prepare brain areas for target enhancement. In particular, low-frequency oscillations in visual cortex appear especially well suited for gating task-irrelevant information. We describe the results of a series of studies exploring distractor suppression and challenge this popular notion. We draw on behavioral and EEG evidence to show that selective distractor suppression operates via an alternative mechanism, such as expectation suppression within a predictive coding framework. PMID:26865606

  19. How to suppress undesired synchronization.

    PubMed

    Louzada, V H P; Araújo, N A M; Andrade, J S; Herrmann, H J

    2012-01-01

    Examples of synchronization can be found in a wide range of phenomena such as neurons firing, lasers cascades, chemical reactions, and opinion formation. However, in many situations the formation of a coherent state is not pleasant and should be mitigated. For example, the onset of synchronization can be the root of epileptic seizures, traffic congestion in networks, and the collapse of constructions. Here we propose the use of contrarians to suppress undesired synchronization. We perform a comparative study of different strategies, either requiring local or total knowledge, and show that the most efficient one solely requires local information. Our results also reveal that, even when the distribution of neighboring interactions is narrow, significant improvement is observed when contrarians sit at the highly connected elements. The same qualitative results are obtained for artificially generated networks and two real ones, namely, the Routers of the Internet and a neuronal network.

  20. Elastic Suppression of Viscous Fingering

    NASA Astrophysics Data System (ADS)

    Peng, Gunnar; Lister, John

    2016-11-01

    Consider peeling an elastic tape or beam away from a rigid base to which it is stuck by a film of viscous liquid. The peeling motion requires air to invade the viscous liquid and is thus susceptible to the Saffman-Taylor fingering instability. We analyse the fundamental travelling-wave solution and show that the advancing air-liquid interface remains linearly stable at higher capillary numbers than in a standard Hele-Shaw cell. A short-wavelength expansion yields an analytical expression for the growth rate which is valid for all unstable modes throughout the parameter space, allowing us to identify and quantify four distinct physical mechanisms that each help suppress the instability. Applying our method to the experiments by Pihler-Puzovic et al. (2012) reveals that the radial geometry and time-variation stabilize the system further.

  1. How to suppress undesired synchronization

    PubMed Central

    Louzada, V. H. P.; Araújo, N. A. M.; Andrade, J. S.; Herrmann, H. J.

    2012-01-01

    Examples of synchronization can be found in a wide range of phenomena such as neurons firing, lasers cascades, chemical reactions, and opinion formation. However, in many situations the formation of a coherent state is not pleasant and should be mitigated. For example, the onset of synchronization can be the root of epileptic seizures, traffic congestion in networks, and the collapse of constructions. Here we propose the use of contrarians to suppress undesired synchronization. We perform a comparative study of different strategies, either requiring local or total knowledge, and show that the most efficient one solely requires local information. Our results also reveal that, even when the distribution of neighboring interactions is narrow, significant improvement is observed when contrarians sit at the highly connected elements. The same qualitative results are obtained for artificially generated networks and two real ones, namely, the Routers of the Internet and a neuronal network. PMID:22993685

  2. Tactile stimulation can suppress visual perception

    PubMed Central

    Ide, Masakazu; Hidaka, Souta

    2013-01-01

    An input (e.g., airplane takeoff sound) to a sensory modality can suppress the percept of another input (e.g., talking voices of neighbors) of the same modality. This perceptual suppression effect is evidence that neural responses to different inputs closely interact with each other in the brain. While recent studies suggest that close interactions also occur across sensory modalities, crossmodal perceptual suppression effect has not yet been reported. Here, we demonstrate that tactile stimulation can suppress the percept of visual stimuli: Visual orientation discrimination performance was degraded when a tactile vibration was applied to the observer's index finger of hands. We also demonstrated that this tactile suppression effect on visual perception occurred primarily when the tactile and visual information were spatially and temporally consistent. The current findings would indicate that neural signals could closely and directly interact with each other, sufficient to induce the perceptual suppression effect, even across sensory modalities. PMID:24336391

  3. Tactile stimulation can suppress visual perception.

    PubMed

    Ide, Masakazu; Hidaka, Souta

    2013-12-13

    An input (e.g., airplane takeoff sound) to a sensory modality can suppress the percept of another input (e.g., talking voices of neighbors) of the same modality. This perceptual suppression effect is evidence that neural responses to different inputs closely interact with each other in the brain. While recent studies suggest that close interactions also occur across sensory modalities, crossmodal perceptual suppression effect has not yet been reported. Here, we demonstrate that tactile stimulation can suppress the percept of visual stimuli: Visual orientation discrimination performance was degraded when a tactile vibration was applied to the observer's index finger of hands. We also demonstrated that this tactile suppression effect on visual perception occurred primarily when the tactile and visual information were spatially and temporally consistent. The current findings would indicate that neural signals could closely and directly interact with each other, sufficient to induce the perceptual suppression effect, even across sensory modalities.

  4. MEK5 suppresses osteoblastic differentiation

    SciTech Connect

    Kaneshiro, Shoichi; Otsuki, Dai; Yoshida, Kiyoshi; Yoshikawa, Hideki; Higuchi, Chikahisa

    2015-07-31

    Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. - Highlights: • MEK5 inhibitor BIX02189 suppresses proliferation of osteoblasts. • MEK5 knockdown and MEK5 inhibitor promote differentiation of osteoblasts. • MEK5 overexpression inhibits differentiation of osteoblasts.

  5. Endomorphin-suppressed nitric oxide release from mice peritoneal macrophages.

    PubMed

    Balog, Tihomir; Sarić, Ana; Sobocanec, Sandra; Kusić, Borka; Marotti, Tatjana

    2010-02-01

    Endomorphins are newly discovered mu-opioid receptor selective immunocompetent opioid peptides. Endomorphin 1 is predominantly distributed in brain, while endomorphin 2 is widely allocated in the spinal cord. Lately, endomorphins have been investigated as modulators of reactive oxygen and nitrogen species. Nitric oxide is short lived radical involved in various biological processes such as regulation of blood vessel contraction, inflammation, neurotransmission and apoptosis. The aim of this work was to investigate the in vivo effects of endomorphins on nitric oxide release and NOS 2 isoenzyme upregulation in mice peritoneal macrophages additionally challenged ex vivo with lipopolysaccharide. The results showed that endomorphin 1 or endomorphin 2 in vitro did not change NO release from peritoneal mouse macrophages during a 48 h incubation period. On the other hand in vivo endomorphins had suppressive effect on NO release as well as on NOS 2 and IL-1 protein concentration. The most of suppressive effect in vivo of both endomorphins was blocked with 30 min pretreatment with mu-receptor selective antagonist beta-FNA, which proved involvement of opioid receptor pathway in suppressive effects of endomorphins.

  6. Two Techniques For Suppressing Vibrations In Structures

    NASA Technical Reports Server (NTRS)

    Chen, Gun-Shing; Garba, John A.; Wada, Ben K.

    1991-01-01

    Two techniques intended to be used together to suppress vibrations in large, complicated truss structure involve combination of active and passive damping. Based on bridge feedback and criterion for placement of actuators. Research continues to develop system using these and other techniques to suppress vibrations in, and help control shape of, truss structure in outer space that supports precise, segmented reflector of communication antenna. On Earth, developmental techniques applicable to suppression of vibrations in bridges and tall buildings.

  7. Acoustic Suppression Systems and Related Methods

    NASA Technical Reports Server (NTRS)

    Kolaini, Ali R. (Inventor); Kern, Dennis L. (Inventor)

    2013-01-01

    An acoustic suppression system for absorbing and/or scattering acoustic energy comprising a plurality of acoustic targets in a containment is described, the acoustic targets configured to have resonance frequencies allowing the targets to be excited by incoming acoustic waves, the resonance frequencies being adjustable to suppress acoustic energy in a set frequency range. Methods for fabricating and implementing the acoustic suppression system are also provided.

  8. ISS Update: Burning and Suppression of Solids

    NASA Video Gallery

    ISS Update Commentator Pat Ryan interviews Paul Ferkul, Principal Investigator for the Burning and Suppression of Solids (BASS) experiment, about performing combustion experiments in microgravity. ...

  9. Issues in Numerical Simulation of Fire Suppression

    SciTech Connect

    Tieszen, S.R.; Lopez, A.R.

    1999-04-12

    This paper outlines general physical and computational issues associated with performing numerical simulation of fire suppression. Fire suppression encompasses a broad range of chemistry and physics over a large range of time and length scales. The authors discuss the dominant physical/chemical processes important to fire suppression that must be captured by a fire suppression model to be of engineering usefulness. First-principles solutions are not possible due to computational limitations, even with the new generation of tera-flop computers. A basic strategy combining computational fluid dynamics (CFD) simulation techniques with sub-grid model approximations for processes that have length scales unresolvable by gridding is presented.

  10. My Cousin, My Enemy: quasispecies suppression of drug resistance

    PubMed Central

    Kirkegaard, Karla; van Buuren, Nicholas J; Mateo, Roberto

    2017-01-01

    If a freshly minted genome contains a mutation that confers drug resistance, will it be selected in the presence of the drug? Not necessarily. During viral infections, newly synthesized viral genomes occupy the same cells as parent and other progeny genomes. If the antiviral target is chosen so that the drug-resistant progeny’s growth is dominantly inhibited by the drug-susceptible members of its intracellular family, its outgrowth can be suppressed. Precedent for ‘dominant drug targeting’ as a deliberate approach to suppress the outgrowth of inhibitor-resistant viruses has been established for envelope variants of vesicular stomatitis virus and for capsid variants of poliovirus and dengue virus. Small molecules that stabilize oligomeric assemblages are a promising means to an unfit family to destroy the effectiveness of a newborn drug-resistant relative due to the co-assembly of drug-susceptible and drug-resistant monomers. PMID:27764731

  11. Bone suppression technique for chest radiographs

    NASA Astrophysics Data System (ADS)

    Huo, Zhimin; Xu, Fan; Zhang, Jane; Zhao, Hui; Hobbs, Susan K.; Wandtke, John C.; Sykes, Anne-Marie; Paul, Narinder; Foos, David

    2014-03-01

    High-contrast bone structures are a major noise contributor in chest radiographic images. A signal of interest in a chest radiograph could be either partially or completely obscured or "overshadowed" by the highly contrasted bone structures in its surrounding. Thus, removing the bone structures, especially the posterior rib and clavicle structures, is highly desirable to increase the visibility of soft tissue density. We developed an innovative technology that offers a solution to suppress bone structures, including posterior ribs and clavicles, on conventional and portable chest X-ray images. The bone-suppression image processing technology includes five major steps: 1) lung segmentation, 2) rib and clavicle structure detection, 3) rib and clavicle edge detection, 4) rib and clavicle profile estimation, and 5) suppression based on the estimated profiles. The bone-suppression software outputs an image with both the rib and clavicle structures suppressed. The rib suppression performance was evaluated on 491 images. On average, 83.06% (±6.59%) of the rib structures on a standard chest image were suppressed based on the comparison of computer-identified rib areas against hand-drawn rib areas, which is equivalent to about an average of one rib that is still visible on a rib-suppressed image based on a visual assessment. Reader studies were performed to evaluate reader performance in detecting lung nodules and pneumothoraces with and without a bone-suppression companion view. Results from reader studies indicated that the bone-suppression technology significantly improved radiologists' performance in the detection of CT-confirmed possible nodules and pneumothoraces on chest radiographs. The results also showed that radiologists were more confident in making diagnoses regarding the presence or absence of an abnormality after rib-suppressed companion views were presented

  12. New approaches to hard bubble suppression

    NASA Technical Reports Server (NTRS)

    Henry, R. D.; Besser, P. J.; Warren, R. G.; Whitcomb, E. C.

    1973-01-01

    Description of a new double-layer method for the suppression of hard bubbles that is more versatile than previously reported suppression techniques. It is shown that it may be possible to prevent hard bubble generation without recourse to exchange coupling of multilayer films.

  13. Growth suppression caused by corticosteroid eye drops.

    PubMed

    Wolthers, Ole D

    2011-01-01

    Scarce data on systemic activity of corticosteroid eye drops are available in children. Two weeks treatment with fluorometholone eye drops in a case series of five children caused growth suppression detected by knemometry. The suppression had no impact on height growth during the following year.

  14. Suppressive soils: back on the radar screen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Suppressive soils are those in which a pathogen does not establish or persist, establishes but causes little or no damage, or establishes and causes disease for a while but thereafter the disease is less important, although the pathogen may persist in the soil (Weller, 2002). ‘General suppression,’ ...

  15. Ferromagnetic resonance probe liftoff suppression apparatus

    DOEpatents

    Davis, Thomas J.; Tomeraasen, Paul L.

    1985-01-01

    A liftoff suppression apparatus utilizing a liftoff sensing coil to sense the amount a ferromagnetic resonance probe lifts off the test surface during flaw detection and utilizing the liftoff signal to modulate the probe's field modulating coil to suppress the liftoff effects.

  16. Polypyrrole actuators for tremor suppression

    NASA Astrophysics Data System (ADS)

    Skaarup, Steen; Mogensen, Naja; Bay, Lasse; West, Keld

    2003-07-01

    Neurological tremor affecting limbs can be divided into at least 6 different types with frequencies ranging from 2 to about 20 Hz. In order to alleviate the symptoms by suppressing the tremor, sensing and actuation systems able to perform at these frequencies are needed. Electroactive polymers exemplify "soft actuator" technology that may be especially suitable for use in conjunction with human limbs. The electrochemical and mechanical properties of polypyrrole dodecyl benzene sulphonate actuator films have been studied with this application in mind. The results show that the time constants for the change of length and for the stiffness change are significantly different; the stiffness change being about 10 times faster. Both force measurements and Electrochemical Quartz Crystal Microbalance measurements indicate that the actuation process is complex and involves at least two different processes. The EQCM results make it possible to formulate a hypothesis for the two different time constants: Sodium ions enter the polymer correlated with a fast mass change that probably involves a few (~4) strongly bound water molecules as well. On further reduction, about 10 additional water molecules enter the polymer in a slower process driven by osmotic pressure. Earlier work has tended to focus on achieving the maximum length change, therefore taking the time needed to include all processes. However, since the slower process described above is associated with the lowest strength of the actuator, concentrating on the faster stiffness change results in only a small reduction in the work done by the actuator. This may make actuation at higher frequencies feasible.

  17. Multicopy Suppression Underpins Metabolic Evolvability

    PubMed Central

    Patrick, Wayne M.; Quandt, Erik M.; Swartzlander, Dan B.; Matsumura, Ichiro

    2009-01-01

    Our understanding of the origins of new metabolic functions is based upon anecdotal genetic and biochemical evidence. Some auxotrophies can be suppressed by overexpressing substrate-ambiguous enzymes (i.e., those that catalyze the same chemical transformation on different substrates). Other enzymes exhibit weak but detectable catalytic promiscuity in vitro (i.e., they catalyze different transformations on similar substrates). Cells adapt to novel environments through the evolution of these secondary activities, but neither their chemical natures nor their frequencies of occurrence have been characterized en bloc. Here, we systematically identified multifunctional genes within the Escherichia coli genome. We screened 104 single-gene knockout strains and discovered that many (20%) of these auxotrophs were rescued by the overexpression of at least one noncognate E. coli gene. The deleted gene and its suppressor were generally unrelated, suggesting that promiscuity is a product of contingency. This genome-wide survey demonstrates that multifunctional genes are common and illustrates the mechanistic diversity by which their products enhance metabolic robustness and evolvability. PMID:17884825

  18. Transport suppression by shear reduction

    NASA Astrophysics Data System (ADS)

    Martinell, Julio; Del-Castillo-Negrete, Diego

    2009-11-01

    The relationship between transport and shear is a problem of considerable interest to magnetically confined plasmas. It is well known that there are cases in which an increase of flow shear can lead to a reduction of turbulent transport. However, this is not a generic result, and there are transport problems in which the opposite is the case. In particular, as originally discussed in Ref. footnotetextdel-Castillo-Negrete and Morrison, Phys. Fluids A 5, 948 (1993), barriers to chaotic transport typically form in regions of vanishing shear. This property, which is generic to the so-called non-twist Hamiltonian systems footnotetextdel-Castillo-Negrete, Greene, and Morrison, Physica D 91, 1 (1996), explains the observed resilience of transport barriers in non-monotonic zonal flows in plasmas and fluids and the robustness of shearless magnetic surfaces in reverse shear configurations. Here we study the role of finite Larmor radius (FLR) effects on the suppression of chaotic transport by shear reduction in a simplified model. Following Ref. footnotetextdel-Castillo-Negrete, Phys. Plasmas, 7, 1702 (2000) we consider a model consisting of a superposition of drift waves and a non-monotonic zonal flow. The FLR effects are incorporated by gyroaveraging the E xB velocity, and transport is studied by following the evolution of ensembles of test particles.

  19. Impacts of suppressing guide on information spreading

    NASA Astrophysics Data System (ADS)

    Xu, Jinghong; Zhang, Lin; Ma, Baojun; Wu, Ye

    2016-02-01

    It is quite common that guides are introduced to suppress the information spreading in modern society for different purposes. In this paper, an agent-based model is established to quantitatively analyze the impacts of suppressing guides on information spreading. We find that the spreading threshold depends on the attractiveness of the information and the topology of the social network with no suppressing guides at all. Usually, one would expect that the existence of suppressing guides in the spreading procedure may result in less diffusion of information within the overall network. However, we find that sometimes the opposite is true: the manipulating nodes of suppressing guides may lead to more extensive information spreading when there are audiences with the reversal mind. These results can provide valuable theoretical references to public opinion guidance on various information, e.g., rumor or news spreading.

  20. Mu suppression - A good measure of the human mirror neuron system?

    PubMed

    Hobson, Hannah M; Bishop, Dorothy V M

    2016-09-01

    Mu suppression has been proposed as a signature of the activity of the human mirror neuron system (MNS). However the mu frequency band (8-13 Hz) overlaps with the alpha frequency band, which is sensitive to attentional fluctuation, and thus mu suppression could potentially be confounded by changes in attentional engagement. The specific baseline against which mu suppression is assessed may be crucial, yet there is little consistency in how this is defined. We examined mu suppression in 61 typical adults, the largest mu suppression study so far conducted. We compared different methods of baselining, and examined activity at central and occipital electrodes, to both biological (hands) and non-biological (kaleidoscope) moving stimuli, to investigate the involvement of attention and alpha activity in mu suppression. We also examined changes in beta power, another candidate index of MNS engagement. We observed strong mu suppression restricted to central electrodes when participants performed hand movements, demonstrating that mu is indeed responsive to the activity of the motor cortex. However, when we looked for a similar signature of mu suppression to passively observed stimuli, the baselining method proved to be crucial. Selective suppression for biological versus non-biological stimuli was seen at central electrodes only when we used a within-trial baseline based on a static stimulus: this method greatly reduced trial-by-trial variation in the suppression measure compared with baselines based on blank trials presented in separate blocks. Even in this optimal condition, 16-21% of participants showed no mu suppression. Changes in beta power also did not match our predicted pattern for MNS engagement, and did not seem to offer a better measure than mu. Our conclusions are in contrast to those of a recent meta-analysis, which concluded that mu suppression is a valid means to examine mirror neuron activity. We argue that mu suppression can be used to index the human MNS

  1. Label-Free Relative Quantitation of Isobaric and Isomeric Human Histone H2A and H2B Variants by Fourier Transform Ion Cyclotron Resonance Top-Down MS/MS.

    PubMed

    Dang, Xibei; Singh, Amar; Spetman, Brian D; Nolan, Krystal D; Isaacs, Jennifer S; Dennis, Jonathan H; Dalton, Stephen; Marshall, Alan G; Young, Nicolas L

    2016-09-02

    Histone variants are known to play a central role in genome regulation and maintenance. However, many variants are inaccessible by antibody-based methods or bottom-up tandem mass spectrometry due to their highly similar sequences. For many, the only tractable approach is with intact protein top-down tandem mass spectrometry. Here, ultra-high-resolution FT-ICR MS and MS/MS yield quantitative relative abundances of all detected HeLa H2A and H2B isobaric and isomeric variants with a label-free approach. We extend the analysis to identify and relatively quantitate 16 proteoforms from 12 sequence variants of histone H2A and 10 proteoforms of histone H2B from three other cell lines: human embryonic stem cells (WA09), U937, and a prostate cancer cell line LaZ. The top-down MS/MS approach provides a path forward for more extensive elucidation of the biological role of many previously unstudied histone variants and post-translational modifications.

  2. Capillary isoelectric focusing-tandem mass spectrometry and reversed-phase liquid chromatography-tandem mass spectrometry for quantitative proteomic analysis of differentiating PC12 cells by eight-plex isobaric tags for relative and absolute quantification.

    PubMed

    Zhu, Guijie; Sun, Liangliang; Keithley, Richard B; Dovichi, Norman J

    2013-08-06

    We report the application of capillary isoelectric focusing for quantitative analysis of a complex proteome. Biological duplicates were generated from PC12 cells at days 0, 3, 7, and 12 following treatment with nerve growth factor. These biological duplicates were digested with trypsin, labeled using eight-plex isobaric tags for relative and absolute quantification (iTRAQ) chemistry, and pooled. The pooled peptides were separated into 25 fractions using reversed-phase liquid chromatography (RPLC). Technical duplicates of each fraction were separated by capillary isoelectric focusing (cIEF) using a set of amino acids as ampholytes. The cIEF column was interfaced to an Orbitrap Velos mass spectrometer with an electrokinetically pumped sheath-flow nanospray interface. This HPLC-cIEF-electrospray-tandem mass spectrometry (ESI-MS/MS) approach identified 835 protein groups and produced 2,329 unique peptides IDs. The biological duplicates were analyzed in parallel using conventional strong-cation exchange (SCX)-RPLC-ESI-MS/MS. The iTRAQ peptides were first separated into eight fractions using SCX. Each fraction was then analyzed by RPLC-ESI-MS/MS. The SCX-RPLC approach generated 1,369 protein groups and 3,494 unique peptide IDs. For protein quantitation, 96 and 198 differentially expressed proteins were obtained with RPLC-cIEF and SCX-RPLC, respectively. The combined set identified 231 proteins. Protein expression changes measured by RPLC-cEIF and SCX-RPLC were highly correlated.

  3. Nuclear structure beyond the neutron drip line. The lowest energy states in 9He via their T=5/2 isobaric analogs in 9Li

    SciTech Connect

    Uberseder, E.; Rogachev, G. V.; Goldberg, V. Z.; Koshchiy, E.; Roeder, B. T.; Alcorta, M.; Chubarian, G.; Davids, B.; Fu, C.; Hooker, J.; Jayatissa, H.; Melconian, D.; Tribble, R. E.

    2016-03-01

    The level structure of the very neutron rich and unbound 9He nucleus has been the subject of significant experimental and theoretical study. Many recent works have claimed that the two lowest energy 9He states exist with spins Jπ=1/2+and Jπ=1/2-and widths on the order of 100–200 keV. These find-ings cannot be reconciled with our contemporary understanding of nuclear structure. Our present work is the first high-resolution study with low statistical uncertainty of the relevant excitation energy range in the 8He+n system, performed via a search for the T =5/2 isobaric analog states in 9Li populated through 8He+p elastic scattering. Moreover, the present data show no indication of any narrow structures. Instead, we find evidence for a broad Jπ=1/2+state in 9He located approximately 3 MeV above the neutron decay threshold.

  4. Changes in protein abundance between tender and tough meat from bovine longissimus thoracis muscle assessed by isobaric Tag for Relative and Absolute Quantitation (iTRAQ) and 2-dimensional gel electrophoresis analysis.

    PubMed

    Bjarnadóttir, S G; Hollung, K; Høy, M; Bendixen, E; Codrea, M C; Veiseth-Kent, E

    2012-06-01

    The aim of this study was to find potential biomarkers for meat tenderness in bovine Longissimus thoracis muscle and to compare results from isobaric Tag for Relative and Absolute Quantitation (iTRAQ) and 2-dimensional gel electrophoresis (2-DE) analysis. The experiment included 4 tender and 4 tough samples, based on shear force measurements at 7 d postmortem, from young Norwegian red (NRF) bulls, taken at 1 h postmortem. A number of the proteins which have previously been related to tenderness were found to change in abundance between tender and tough samples, both in iTRAQ (P < 0.1) and 2-DE analysis (P < 0.05). Furthermore, 3 proteins that have not previously been related to tenderness were found to change significantly in abundance between tender and tough meat samples in the present study. These include proteins related to control of flux through the tricarboxylate cycle [2-oxoglutarate dehydrogenase complex component E2 (OGDC-E2)], apoptosis (galectin-1) and regulatory role in the release of Ca(2+) from intracellular stores (annexin A6). Even though the overlap in significantly changing proteins was relatively low between iTRAQ and 2-DE analysis, certain proteins predicted to have the same function were found in both analyses and showed similar changes between the groups, such as structural proteins and proteins related to apoptosis and energy metabolism.

  5. Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

    NASA Astrophysics Data System (ADS)

    Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

    2013-10-01

    Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

  6. Clutter suppression using recursive and nonrecursive MTI filters

    NASA Astrophysics Data System (ADS)

    Liu, Bede

    1988-05-01

    The author calculates the effectiveness of clutter suppression of a moving-target-indicator (MTI) filter in tandem with a fast-Fourier-transform (FFT) Doppler filter bank, taking into account the transient response of the MTI filter. Both recursive and nonrecursive filters are considered. The analysis is extended to the high-pulse-repetition-frequency (PRF) case with clutter fold over. The results can be used to select key design parameters, including the MTI filter, the window size, and the initial transient segment to be discarded. Numerical examples are included.

  7. Helicopter air resonance modeling and suppression using active control

    NASA Technical Reports Server (NTRS)

    Takahashi, M. D.; Friedmann, P. P.

    1991-01-01

    A coupled rotor/fuselage helicopter analysis with the important effects of blade torsional flexibility, unsteady aerodynamics, and forward flight is presented. Using this mathematical model, a nominal configuration is selected with an air resonance instability throughout most of its flight envelope. A multivariable compensator is then designed using two swashplate inputs and a single-body roll rate measurement. The controller design is based on the linear quadratic Gaussian technique and the loop transfer recovery method. The controller is shown to suppress the air resonance instability throughout a wide range of helicopter loading conditions and forward flight speeds.

  8. Mutual Suppression: Comment on Paulhus et Al. (2004)

    ERIC Educational Resources Information Center

    Nickerson, Carol

    2008-01-01

    Paulhus, Robins, Trzesniewski, and Tracy ("Multivariate Behavioral Research," 2004, 39, 305-328) suggested that the three types of two-predictor suppression situations--classical suppression, cooperative suppression, and net suppression--can all be considered special cases of mutual suppression, in that the magnitude of each of the two…

  9. Spider mites suppress tomato defenses downstream of jasmonate and salicylate independently of hormonal crosstalk

    PubMed Central

    Alba, Juan M; Schimmel, Bernardus C J; Glas, Joris J; Ataide, Livia M S; Pappas, Maria L; Villarroel, Carlos A; Schuurink, Robert C; Sabelis, Maurice W; Kant, Merijn R

    2015-01-01

    Plants respond to herbivory by mounting a defense. Some plant-eating spider mites (Tetranychus spp.) have adapted to plant defenses to maintain a high reproductive performance. From natural populations we selected three spider mite strains from two species, Tetranychus urticae and Tetranychus evansi, that can suppress plant defenses, using a fourth defense-inducing strain as a benchmark, to assess to which extent these strains suppress defenses differently. We characterized timing and magnitude of phytohormone accumulation and defense-gene expression, and determined if mites that cannot suppress defenses benefit from sharing a leaf with suppressors. The nonsuppressor strain induced a mixture of jasmonate- (JA) and salicylate (SA)-dependent defenses. Induced defense genes separated into three groups: ‘early’ (expression peak at 1 d postinfestation (dpi)); ‘intermediate’ (4 dpi); and ‘late’, whose expression increased until the leaf died. The T. evansi strains suppressed genes from all three groups, but the T. urticae strain only suppressed the late ones. Suppression occurred downstream of JA and SA accumulation, independently of the JA–SA antagonism, and was powerful enough to boost the reproductive performance of nonsuppressors up to 45%. Our results show that suppressing defenses not only brings benefits but, within herbivore communities, can also generate a considerable ecological cost when promoting the population growth of a competitor. PMID:25297722

  10. Cerebral regions associated with verbal response initiation, suppression and strategy use.

    PubMed

    de Zubicaray, G I; Zelaya, F O; Andrew, C; Williams, S C; Bullmore, E T

    2000-01-01

    Cerebral activation associated with performance on a novel task involving two conditions was investigated with functional magnetic resonance imaging (fMRI). In the response initiation condition, subjects nominated the general superordinate category to which each of a series of exemplars (concrete nouns) belonged. In the response suppression condition, subjects were required to nominate a general superordinate category to which each exemplar did not belong, with the instruction that they were not to nominate the same category response twice in a row. Both conditions produced distinct patterns of activation relative to an articulation control condition employing identical stimuli. When initiation and suppression conditions were directly compared, response suppression produced activation in the right frontal pole, orbital frontal cortex and anterior cingulate, left dorsolateral prefrontal cortex and posterior cingulate, and bilaterally in the precuneus, visual association cortex and cerebellum. Response latencies were significantly longer in the suppression condition. Two broadly-defined strategies associated with the correct production of words during the suppression condition were a self-ordered selection from among the superordinate categories identified during the first section of the task and the generation of novel category responses. The neuroanatomical correlates of response initiation, suppression and strategy use are discussed, as are the respective roles of response suppression and strategy generation.

  11. Psychopathology and Thought Suppression: A Quantitative Review

    PubMed Central

    Magee, Joshua C.; Harden, K. Paige; Teachman, Bethany A.

    2012-01-01

    Recent theories of psychopathology have suggested that thought suppression intensifies the persistence of intrusive thoughts, and proposed that difficulty with thought suppression may differ between groups with and without psychopathology. The current meta-analytic review evaluates empirical evidence for difficulty with thought suppression as a function of the presence and specific type of psychopathology. Based on theoretical proposals from the psychopathology literature, diagnosed and analogue samples were expected to show greater recurrence of intrusive thoughts during thought suppression attempts than non-clinical samples. However, results showed no overall differences in the recurrence of thoughts due to thought suppression between groups with and without psychopathology. There was, nevertheless, variation in the recurrence of thoughts across different forms of psychopathology, including relatively less recurrence during thought suppression for samples with symptoms of Obsessive-Compulsive Disorder, compared to non-clinical samples. However, these differences were typically small and provided only mixed support for existing theories. Implications for cognitive theories of intrusive thoughts are discussed, including proposed mechanisms underlying thought suppression. PMID:22388007

  12. Suppression effects in feature-based attention

    PubMed Central

    Wang, Yixue; Miller, James; Liu, Taosheng

    2015-01-01

    Attending to a feature enhances visual processing of that feature, but it is less clear what occurs to unattended features. Single-unit recording studies in middle temporal (MT) have shown that neuronal modulation is a monotonic function of the difference between the attended and neuron's preferred direction. Such a relationship should predict a monotonic suppressive effect in psychophysical performance. However, past research on suppressive effects of feature-based attention has remained inconclusive. We investigated the suppressive effect for motion direction, orientation, and color in three experiments. We asked participants to detect a weak signal among noise and provided a partially valid feature cue to manipulate attention. We measured performance as a function of the offset between the cued and signal feature. We also included neutral trials where no feature cues were presented to provide a baseline measure of performance. Across three experiments, we consistently observed enhancement effects when the target feature and cued feature coincided and suppression effects when the target feature deviated from the cued feature. The exact profile of suppression was different across feature dimensions: Whereas the profile for direction exhibited a “rebound” effect, the profiles for orientation and color were monotonic. These results demonstrate that unattended features are suppressed during feature-based attention, but the exact suppression profile depends on the specific feature. Overall, the results are largely consistent with neurophysiological data and support the feature-similarity gain model of attention. PMID:26067533

  13. Simple Suppression of Spurious Peaks in TROSY Experiments

    NASA Astrophysics Data System (ADS)

    Kojima, Chojiro; Kainosho, Masatsune

    2000-04-01

    In 1H-15N TROSY experiments of proteins and nucleic acids, where the second coherence transfer delay time τ‧ has been fixed as 5.6 ms, 1/(21JNH), in order to achieve complete spin-state selection, spurious negative peaks are observed along the 15N axes. These peaks are often annoyingly large, especially for nucleic acids. A simple product operator calculation, however, indicated that the shortening of the second delay time τ‧, which is next to the t1 period, would efficiently suppress these spurious peaks, without sacrificing the sensitivities of the TROSY peaks too much. We have shown for three systems, two 11- and 17-kDa proteins and one 8-kDa DNA duplex, that these spurious peaks can be effectively suppressed with delay times of 3.3 ms for the two proteins and 2.3 ms for the DNA. These delay times, optimized by trial and error, for the spurious peak suppression did not depend on the magnetic field strength and the temperature very much. Although the shortened τ‧ delay times attenuate the TROSY peak intensities by about 10 and 20% for the two proteins and the DNA, respectively, this simple modification will be useful for the quantitative uses of TROSY peaks and will result in cleaner spectra for various TROSY-based multiple resonance experiments.

  14. Sample multiplexing with cysteine-selective approaches: cysDML and cPILOT.

    PubMed

    Gu, Liqing; Evans, Adam R; Robinson, Renã A S

    2015-04-01

    Cysteine-selective proteomics approaches simplify complex protein mixtures and improve the chance of detecting low abundant proteins. It is possible that cysteinyl-peptide/protein enrichment methods could be coupled to isotopic labeling and isobaric tagging methods for quantitative proteomics analyses in as few as two or up to 10 samples, respectively. Here we present two novel cysteine-selective proteomics approaches: cysteine-selective dimethyl labeling (cysDML) and cysteine-selective combined precursor isotopic labeling and isobaric tagging (cPILOT). CysDML is a duplex precursor quantification technique that couples cysteinyl-peptide enrichment with on-resin stable-isotope dimethyl labeling. Cysteine-selective cPILOT is a novel 12-plex workflow based on cysteinyl-peptide enrichment, on-resin stable-isotope dimethyl labeling, and iodoTMT tagging on cysteine residues. To demonstrate the broad applicability of the approaches, we applied cysDML and cPILOT methods to liver tissues from an Alzheimer's disease (AD) mouse model and wild-type (WT) controls. From the cysDML experiments, an average of 850 proteins were identified and 594 were quantified, whereas from the cPILOT experiment, 330 and 151 proteins were identified and quantified, respectively. Overall, 2259 unique total proteins were detected from both cysDML and cPILOT experiments. There is tremendous overlap in the proteins identified and quantified between both experiments, and many proteins have AD/WT fold-change values that are within ~20% error. A total of 65 statistically significant proteins are differentially expressed in the liver proteome of AD mice relative to WT. The performance of cysDML and cPILOT are demonstrated and advantages and limitations of using multiple duplex experiments versus a single 12-plex experiment are highlighted.

  15. Sample Multiplexing with Cysteine-Selective Approaches: cysDML and cPILOT

    NASA Astrophysics Data System (ADS)

    Gu, Liqing; Evans, Adam R.; Robinson, Renã A. S.

    2015-04-01

    Cysteine-selective proteomics approaches simplify complex protein mixtures and improve the chance of detecting low abundant proteins. It is possible that cysteinyl-peptide/protein enrichment methods could be coupled to isotopic labeling and isobaric tagging methods for quantitative proteomics analyses in as few as two or up to 10 samples, respectively. Here we present two novel cysteine-selective proteomics approaches: cysteine-selective dimethyl labeling (cysDML) and cysteine-selective combined precursor isotopic labeling and isobaric tagging (cPILOT). CysDML is a duplex precursor quantification technique that couples cysteinyl-peptide enrichment with on-resin stable-isotope dimethyl labeling. Cysteine-selective cPILOT is a novel 12-plex workflow based on cysteinyl-peptide enrichment, on-resin stable-isotope dimethyl labeling, and iodoTMT tagging on cysteine residues. To demonstrate the broad applicability of the approaches, we applied cysDML and cPILOT methods to liver tissues from an Alzheimer's disease (AD) mouse model and wild-type (WT) controls. From the cysDML experiments, an average of 850 proteins were identified and 594 were quantified, whereas from the cPILOT experiment, 330 and 151 proteins were identified and quantified, respectively. Overall, 2259 unique total proteins were detected from both cysDML and cPILOT experiments. There is tremendous overlap in the proteins identified and quantified between both experiments, and many proteins have AD/WT fold-change values that are within ~20% error. A total of 65 statistically significant proteins are differentially expressed in the liver proteome of AD mice relative to WT. The performance of cysDML and cPILOT are demonstrated and advantages and limitations of using multiple duplex experiments versus a single 12-plex experiment are highlighted.

  16. Research on 3D marine electromagnetic interferometry with synthetic sources for suppressing the airwave interference

    NASA Astrophysics Data System (ADS)

    Zhang, Jian-Guo; Wu, Xin; Qi, You-Zheng; Huang, Ling; Fang, Guang-You

    2013-12-01

    In order to suppress the airwave noise in marine controlled-source electromagnetic (CSEM) data, we propose a 3D deconvolution (3DD) interferometry method with a synthetic aperture source and obtain the relative anomaly coefficient (RAC) of the EM field reflection responses to show the degree for suppressing the airwave. We analyze the potential of the proposed method for suppressing the airwave, and compare the proposed method with traditional methods in their effectiveness. A method to select synthetic source length is derived and the effect of the water depth on RAC is examined via numerical simulations. The results suggest that 3DD interferometry method with a synthetic source can effectively suppress the airwave and enhance the potential of marine CSEM to hydrocarbon exploration.

  17. Target resolution in visual search involves the direct suppression of distractors: evidence from electrophysiology.

    PubMed

    Hilimire, Matthew R; Hickey, Clayton; Corballis, Paul M

    2012-04-01

    Attentional selection requires both the enhancement of target stimuli and the suppression of distractors. Target enhancement and distractor suppression have been associated with separable components of the lateralized event-related potential: the target negativity and distractor positivity (Pd). We examined the distractor suppression mechanisms indexed by the Pd. The Pd may reflect mechanisms that guide attention away from distractors during search or mechanisms involved in the subsequent resolution of target features. To determine which of these alternatives was more likely, we had participants view search arrays that contained only a target, only a distractor, or both. The Pd elicited by distractors was substantially larger when the display also contained a target, consistent with the idea that this component reflects a mechanism of distractor suppression activated during the resolution and disambiguation of target features.

  18. Integrin endosomal signalling suppresses anoikis

    PubMed Central

    Alanko, Jonna; Mai, Anja; Jacquemet, Guillaume; Schauer, Kristine; Kaukonen, Riina; Saari, Markku; Goud, Bruno; Ivaska, Johanna

    2016-01-01

    to enhanced signalling of co-trafficked receptor tyrosine kinases10, 11 it has remained unclear whether endocytosed active integrins signal in endosomes. Here, we demonstrate that integrin signalling is not restricted to focal adhesions as previously described and that endocytosis is necessary for full ECM-induced, integrin mediated ERK, AKT and FAK signalling. We find that FAK binds directly to and can become activated on purified endosomes. Moreover, the FERM-domain of FAK is able to bind purified integrin containing endosomes, suggesting the potential for integrin signalling complexes to assemble on endosomes after internalization of active integrins. Importantly, FAK is required for anchorage-independent growth and suppression of anoikis 12. Integrin endosomal signalling correlates with reduced anoikis sensitivity in normal cells and anchorage-independent growth and metastasis in breast cancer cells. PMID:26436690

  19. Molecular Mechanisms for Sweet-suppressing Effect of Gymnemic Acids*

    PubMed Central

    Sanematsu, Keisuke; Kusakabe, Yuko; Shigemura, Noriatsu; Hirokawa, Takatsugu; Nakamura, Seiji; Imoto, Toshiaki; Ninomiya, Yuzo

    2014-01-01

    Gymnemic acids are triterpene glycosides that selectively suppress taste responses to various sweet substances in humans but not in mice. This sweet-suppressing effect of gymnemic acids is diminished by rinsing the tongue with γ-cyclodextrin (γ-CD). However, little is known about the molecular mechanisms underlying the sweet-suppressing effect of gymnemic acids and the interaction between gymnemic acids versus sweet taste receptor and/or γ-CD. To investigate whether gymnemic acids directly interact with human (h) sweet receptor hT1R2 + hT1R3, we used the sweet receptor T1R2 + T1R3 assay in transiently transfected HEK293 cells. Similar to previous studies in humans and mice, gymnemic acids (100 μg/ml) inhibited the [Ca2+]i responses to sweet compounds in HEK293 cells heterologously expressing hT1R2 + hT1R3 but not in those expressing the mouse (m) sweet receptor mT1R2 + mT1R3. The effect of gymnemic acids rapidly disappeared after rinsing the HEK293 cells with γ-CD. Using mixed species pairings of human and mouse sweet receptor subunits and chimeras, we determined that the transmembrane domain of hT1R3 was mainly required for the sweet-suppressing effect of gymnemic acids. Directed mutagenesis in the transmembrane domain of hT1R3 revealed that the interaction site for gymnemic acids shared the amino acid residues that determined the sensitivity to another sweet antagonist, lactisole. Glucuronic acid, which is the common structure of gymnemic acids, also reduced sensitivity to sweet compounds. In our models, gymnemic acids were predicted to dock to a binding pocket within the transmembrane domain of hT1R3. PMID:25056955

  20. Selective mutism

    MedlinePlus

    ... in selective mutism. Treatment Treating selective mutism involves behavior changes. The child's family and school should be involved. Certain medicines that treat anxiety and social phobia have been used safely and successfully. Support ...

  1. Effects of tic suppression: ability to suppress, rebound, negative reinforcement, and habituation to the premonitory urge.

    PubMed

    Specht, Matt W; Woods, Douglas W; Nicotra, Cassandra M; Kelly, Laura M; Ricketts, Emily J; Conelea, Christine A; Grados, Marco A; Ostrander, Rick S; Walkup, John T

    2013-01-01

    The comprehensive behavioral intervention for tics (CBIT) represents a safe, effective non-pharmacological treatment for Tourette's disorder that remains underutilized as a treatment option. Contributing factors include the perceived negative consequences of tic suppression and the lack of a means through which suppression results in symptom improvement. Participants (n = 12) included youth ages 10-17 years with moderate-to-marked tic severity and noticeable premonitory urges who met Tourette's or chronic tic disorder criteria. Tic frequency and urge rating data were collected during an alternating sequence of tic freely or reinforced tic suppression periods. Even without specific instructions regarding how to suppress tics, youth experienced a significant, robust (72%), stable reduction in tic frequency under extended periods (40 min) of contingently reinforced tic suppression in contrast to periods of time when tics were ignored. Following periods of prolonged suppression, tic frequency returned to pre-suppression levels. Urge ratings did not show the expected increase during the initial periods of tic suppression, nor a subsequent decline in urge ratings during prolonged, effective tic suppression. Results suggest that environments conducive to tic suppression result in reduced tic frequency without adverse consequences. Additionally, premonitory urges, underrepresented in the literature, may represent an important enduring etiological consideration in the development and maintenance of tic disorders.

  2. Suppression of immune response to Listeria monocytogenes: mechanism(s) of immune complex suppression.

    PubMed Central

    Virgin, H W; Wittenberg, G F; Bancroft, G J; Unanue, E R

    1985-01-01

    We have investigated possible mechanisms underlying immune complex suppression of resistance to Listeria monocytogenes. Inhibition of resistance was found when immune complexes were formed in vivo in immune mice or in nonimmune mice adoptively transferred with specific antibody. Suppression was also found when nonimmune mice were injected with immune complexes preformed in vitro. We investigated the role of complement by decomplementing mice with cobra venom factor purified by high-pressure liquid chromatography. Complete depletion of serum C3 did not eliminate immune complex suppression of resistance to L. monocytogenes, suggesting that complement activation is not required for immune complex suppression. Infection-induced changes in the surface phenotype and functional properties of macrophages from normal and immune complex-suppressed mice were also investigated. Macrophage expression of both H-2K and Ia molecules increased during the response of normal mice to L. monocytogenes. However, these changes were not found in immune complex-suppressed mice. In contrast, membrane interleukin 1 expression was increased in macrophages from suppressed mice compared with macrophages from normal mice. Macrophages from L. monocytogenes-infected normal and immune complex-suppressed mice expressed cytotoxicity against tumor cells in vitro. We conclude that immune complexes do not inhibit resistance to L. monocytogenes by activation of complement or decreasing macrophage cytotoxic activity. Rather, defects in Ia expression by macrophages from suppressed mice might be one component responsible for immune complex suppression of resistance to L. monocytogenes. PMID:3932204

  3. Suppression factors in diffractive photoproduction of dijets

    NASA Astrophysics Data System (ADS)

    Klasen, Michael; Kramer, Gustav

    2010-11-01

    Now that new publications of H1 data for the diffractive photoproduction of dijets, which overlap with the earlier published H1 data and the recently published data of the ZEUS collaboration, have appeared, we have recalculated the cross sections for this process in next-to-leading order (NLO) of perturbative QCD to see whether they can be interpreted consistently. The results of these calculations are compared to the data of both collaborations. We find that the NLO cross sections disagree with the data, showing that factorization breaking occurs at that order. If direct and resolved contributions are both suppressed by the same amount, the global suppression factor depends on the transverse-energy cut. However, by suppressing only the resolved contribution, also reasonably good agreement with all the data is found with a suppression factor independent of the transverse-energy cut.

  4. METHOD OF SUPPRESSING GASTROINTESTINAL UREASE ACTIVITY

    DOEpatents

    Visek, W.J.

    1963-04-23

    This patent shows a method of increasing the growth rate of chicks. Certain diacyl substituted ureas such as alloxan, murexide, and barbituric acid are added to their feed, thereby suppressing gastrointestinal urease activity and thus promoting growth. (AEC)

  5. Suppression as a stereotype control strategy.

    PubMed

    Monteith, M J; Sherman, J W; Devine, P G

    1998-01-01

    Recent research reveals that efforts to suppress stereotypic thoughts can backfire and produce a rebound effect, such that stereotypic thinking increases to a level that is even greater than if no attempt at stereotype control was initially exercised (e.g., Macrae, Bodenhausen, Milne, & Jetten, 1994). The primary goal of this article is to present an in-depth theoretical analysis of stereotype suppression that identifies numerous potential moderators of the effect of stereotype suppression on the likelihood of subsequent rebound. Our analysis of stereotype suppression focuses on two broad issues: the influence of level of prejudice and the influence of processing goals on the activation versus application of stereotypes. Although stereotype rebound occurs under some circumstances, we suggest that a complete understanding of this phenomenon requires consideration of the full array of possible moderating influences.

  6. Marihuana smoking suppresses luteinizing hormone in women.

    PubMed

    Mendelson, J H; Mello, N K; Ellingboe, J; Skupny, A S; Lex, B W; Griffin, M

    1986-06-01

    Smoking a single 1-g marihuana cigarette containing 1.8% delta 9-tetrahydrocannabinol induced a 30% suppression of plasma luteinizing hormone levels (P less than .02) in women during the luteal phase of the menstrual cycle. After marihuana placebo cigarette smoking, no luteinizing hormone suppression was observed in the same women under double-blind conditions. Marihuana may have adverse effects upon reproductive function during the luteal phase of the menstrual cycle as a consequence of gonadotropin inhibition.

  7. Investigation of refracting flows for acoustic suppression

    NASA Technical Reports Server (NTRS)

    Sloan, D.; Purves, R. B.; Farquhar, B. W.

    1977-01-01

    An experimental investigation to determine the possibility of using refracting flows for the suppression of aircraft inlet noise is described. Observations of wave refraction in duct flows and measurements of the increase in effectiveness of acoustic linings due to refraction have suggested methods for the design of engine inlet ducts which can either suppress noise internally or direct it to where it causes less annoyance.

  8. Flame Suppression Agent, System and Uses

    NASA Technical Reports Server (NTRS)

    Parrish, Clyde F. (Inventor)

    2013-01-01

    Aqueous droplets encapsulated in a flame retardant polymer are useful in suppressing combustion. Upon exposure to a flame, the encapsulated aqueous droplets rupture and vaporize, removing heat and displacing oxygen to retard the combustion process. The polymer encapsulant, through decomposition, may further add free radicals to the combustion atmosphere, thereby further retarding the combustion process. The encapsulated aqueous droplets may be used as a replacement to halon, water mist and dry powder flame suppression systems.

  9. Measurement of myeloid cell immune suppressive activity.

    PubMed

    Dolcetti, Luigi; Peranzoni, Elisa; Bronte, Vincenzo

    2010-11-01

    This unit presents simple methods to assess the immunosuppressive properties of immunoregulatory cells of myeloid origin, such as myeloid-derived suppressor cells (MDSCs), both in vitro and in vivo. These methods are general and could be adapted to test the impact of different suppressive populations on T cell activation, proliferation, and cytotoxic activity; moreover they could be useful to assess the influence exerted on immune suppressive pathways by genetic modifications, chemical inhibitors, and drugs.

  10. Method for Transducer Transient Suppression. I. Theory

    DTIC Science & Technology

    1992-09-01

    Vol. 92, No. 3, September 1992 Method for transducer transient suppression. I: Theory Jean C. Piquette Naval Research Laboratory. Underwater Sound...TITLE AND SUBTITLE 5. FUNDING NUMBERS Method for transducer transient suppression. I: Theo:y PE - 61153N TA - RROII-08-42 WU - DN220-161 6. AUTHOR(S) Jean...STATEMENT 12b. DISTRIBUTION CODE Approved for public release; distribution unlimited. 13. ABSTRACT (Maximum 200 words) The problem of driving a transducer in

  11. Noise suppression in surface microseismic data

    USGS Publications Warehouse

    Forghani-Arani, Farnoush; Batzle, Mike; Behura, Jyoti; Willis, Mark; Haines, Seth S.; Davidson, Michael

    2012-01-01

    We introduce a passive noise suppression technique, based on the τ − p transform. In the τ − p domain, one can separate microseismic events from surface noise based on distinct characteristics that are not visible in the time-offset domain. By applying the inverse τ − p transform to the separated microseismic event, we suppress the surface noise in the data. Our technique significantly improves the signal-to-noise ratios of the microseismic events and is superior to existing techniques for passive noise suppression in the sense that it preserves the waveform. We introduce a passive noise suppression technique, based on the τ − p transform. In the τ − p domain, one can separate microseismic events from surface noise based on distinct characteristics that are not visible in the time-offset domain. By applying the inverse τ − p transform to the separated microseismic event, we suppress the surface noise in the data. Our technique significantly improves the signal-to-noise ratios of the microseismic events and is superior to existing techniques for passive noise suppression in the sense that it preserves the waveform.

  12. Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

    PubMed

    Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

    2012-06-01

    What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

  13. The temporal frequency tuning of continuous flash suppression reveals peak suppression at very low frequencies

    PubMed Central

    Han, Shui’er; Lunghi, Claudia; Alais, David

    2016-01-01

    Continuous flash suppression (CFS) is a psychophysical technique where a rapidly changing Mondrian pattern viewed by one eye suppresses the target in the other eye for several seconds. Despite the widespread use of CFS to study unconscious visual processes, the temporal tuning of CFS suppression is currently unknown. In the present study we used spatiotemporally filtered dynamic noise as masking stimuli to probe the temporal characteristics of CFS. Surprisingly, we find that suppression in CFS peaks very prominently at approximately 1 Hz, well below the rates typically used in CFS studies (10 Hz or more). As well as a strong bias to low temporal frequencies, CFS suppression is greater for high spatial frequencies and increases with increasing masker contrast, indicating involvement of parvocellular/ventral mechanisms in the suppression process. These results are reminiscent of binocular rivalry, and unifies two phenomenon previously thought to require different explanations. PMID:27767078

  14. Suppression of Puerperal Lactation with an Ergot Alkaloid: A Double-blind Study

    PubMed Central

    Varga, L.; Lutterbeck, P. M.; Pryor, J. S.; Wenner, R.; Erb, H.

    1972-01-01

    A double-blind trial was performed in 60 women to establish the effectiveness of an ergot alkaloid, 2-Br-alpha-ergocryptine (ergocryptine; CB 154), in suppressing puerperal lactation and to compare it with stilboestrol and a placebo. At the doses selected ergocryptine and stilboestrol were equally effective. PMID:4556543

  15. Antibiosis and acidification by Panoea agglomerans strain E325 may contribute to suppression of Erwinia amylovora

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pantoea agglomerans strain E325, a commercially-available antagonist for fire blight of apple and pear, was originally selected through broad screening based on suppression of Erwinia amylovora on flower stigmas, but specific mechanisms were unknown. Bacterial modification of pH was evaluated as a p...

  16. METHOD OF SUPPRESSING UAl$sub 4$ FORMATION IN U-Al ALLOYS

    DOEpatents

    Picklesimer, M.L.; Thurber, W.C.

    1960-08-23

    A method is given for suppressing the formation of UAl/sub 4/ in uranium- - aluminum alloys, thereby rendering these alloys more easily workable. The method comprises incorporating in the base alloy a Group Four element selected from the group consisting of Si, Ti, Ge, Zr, and Sn, the addition preferably being within the range of 0.5to20at.%.

  17. A checkerboard selective absorber with excellent spectral selectivity

    SciTech Connect

    Yang, Liu; Mo, Lei; Chen, Tuo; Forsberg, Erik; He, Sailing

    2015-11-14

    A selective absorber with excellent spectral selectivity is proposed and analyzed. The absorber is based on a germanium (Ge) checkerboard on top of a tantalum (Ta) substrate. At wavelengths shorter than the 1.2 μm cutoff, a very high absorption is achieved due to strong cavity resonances in the Ge nanosquares, and their interactions with adjacent nanocavities and the bottom Ta substrate. At longer wavelengths, absorption is greatly suppressed due to destructive interference between the transparent checkerboard layer and the highly reflective Ta substrate. To better describe the superior selectivity of our configuration, a new figure of merit (FOM) is introduced. We observe a FOM value of 0.88 compared to 0.69 for its planar counterpart. We also conduct a thermal analysis to verify the excellent selectivity of our absorber. A high temperature can be achieved and maintained, promising good potential for applications in solar thermophotovoltaic systems.

  18. Feature-based attention modulates surround suppression

    PubMed Central

    Flevaris, Anastasia V.; Murray, Scott O.

    2015-01-01

    Stimuli appearing in the surround of the classical receptive field (CRF) can reduce neuronal firing and perceived contrast of a preferred stimulus in the CRF, a phenomenon referred to as surround suppression. Suppression is greatest when the surrounding stimulus has the same orientation and spatial frequency (SF) as the central target. Although spatial attention has been shown to influence surround suppression, the effects of feature-based attention have yet to be characterized. Using behavioral contrast adaptation in humans, we examined center-surround interactions between SF and orientation, and asked whether attending to one feature dimension versus the other influenced suppression. A center-surround triplet comprised of a central target Gabor and two flanking Gabors were used for adaptation. The flankers could have the same SF and orientation as the target, or differ in one or both of the feature dimensions. Contrast thresholds were measured for the target before and after adapting to center-surround triplets, and postadaptation thresholds were taken as an indirect measure of surround suppression. Both feature dimensions contributed to surround suppression and did not summate. Moreover, when center and surround had the same feature value in one dimension (e.g., same orientation) but had different values in the other dimension (e.g., different SF), there was more suppression when attention was directed to the feature dimension that matched between center and surround than when attention was directed to the feature dimension that differed. These results demonstrate that feature-based attention can influence center-surround interactions by enhancing the effects of the attended dimension. PMID:25630380

  19. The time course of contrast masking reveals two distinct mechanisms of human surround suppression

    PubMed Central

    Petrov, Yury; McKee, Suzanne P.

    2010-01-01

    We explored the time course of surround suppression and found clear evidence for two distinct mechanisms: one strong, transient, and largely monocular, the other weaker, sustained, and binocular. We measured detection thresholds for a Gabor target at 8 deg eccentricity surrounded by a large annulus of matching spatial frequency and orientation. At short stimulus durations surround suppression was very strong, but the suppression strength decreased precipitously for durations longer than ~100 msec. The strong transient component did not transfer between the eyes and occurred almost instantaneously (<1 frame delay, 12 msec) irrespective of the separation between target and surround. Both suppression components were tightly tuned to orientation, peaking at target orientation, but neither was tuned to target spatial phase. These results are in good agreement with surround suppression properties measured in macaque V1 neurons. The absence of interocular transfer, the strong orientation selectivity, and the high propagation speed incommensurate with slow horizontal connections in V1 suggest that the transient component of suppression originates between input layers and the subsequent layers in V1. PMID:19271891

  20. Suppression of strike-slip fault systems

    NASA Astrophysics Data System (ADS)

    Curren, I. S.

    2012-12-01

    depth. Selected areas on Earth with anomalously undeveloped strike-slip faulting where plate models would predict otherwise were compared with results from the analog model experiments in this study. Physical similarities between this model and Brothers Fault Zone (BFZ), Walker Lane (WL) and the South Iceland Seismic Zone (SISZ) imply that strike-slip faulting may be suppressed at the surface in these regions due to the presence of pre-existing structures. Filled circles show offset required for breakthrough faulting, empty circles denote lower limit of breakthrough. Triangles show clay offset as a fraction of box offset. Note that clays with pre-existing structures showed larger offsets although breakthrough did not occur.

  1. CONDITIONS FOR CSR MICROBUNCHING GAIN SUPPRESSION

    SciTech Connect

    Tsai, Cheng Ying; Douglas, David R.; Li, Rui; Tennant, Christopher D.; di Mitri, Simone

    2016-05-01

    The coherent synchrotron radiation (CSR) of a high brightness electron beam traversing a series of dipoles, such as transport arcs, may result in phase space degradation. On one hand, the CSR can perturb electron transverse motion in dispersive regions along the beamline, causing emittance growth. On the other hand, the CSR effect on the longitudinal beam dynamics could result in microbunching gain enhancement. For transport arcs, several schemes have been proposed* to suppress the CSR-induced emittance growth. Similarly, several scenarios have been introduced** to suppress CSR-induced microbunching gain, which however mostly aim for linac-based machines. In this paper we try to provide sufficient conditions for suppression of CSR-induced microbunching gain along a transport arc, analogous to*. Several example lattices are presented, with the relevant microbunching analyses carried out by our semi-analytical Vlasov solver***. The simulation results show that lattices satisfying the proposed conditions indeed have microbunching gain suppressed. We expect this analysis can shed light on lattice design approach that could suppress the CSR-induced microbunching gain.

  2. Selective Mutism

    PubMed Central

    2010-01-01

    Selective mutism is a rare and multidimensional childhood disorder that typically affects children entering school age. It is characterized by the persistent failure to speak in select social settings despite possessing the ability to speak and speak comfortably in more familiar settings. Many theories attempt to explain the etiology of selective mutism. Comorbidities and treatment. Selective mutism can present a variety of comorbidities including enuresis, encopresis, obsessive-compulsive disorder, depression, premorbid speech and language abnormalities, developmental delay, and Asperger's disorders. The specific manifestations and severity of these comorbidities vary based on the individual. Given the multidimensional manifestations of selective mutism, treatment options are similarly diverse. They include individual behavioral therapy, family therapy, and psychotherapy with antidepressants and anti-anxiety medications. Future directions. While studies have helped to elucidate the phenomenology of selective mutism, limitations and gaps in knowledge still persist. In particular, the literature on selective mutism consists primarily of small sample populations and case reports. Future research aims to develop an increasingly integrated, multidimensional framework for evaluating and treating children with selective mutism. PMID:20436772

  3. Cholinergic suppression of excitatory synaptic transmission in layers II/III of the parasubiculum.

    PubMed

    Glasgow, S D; Glovaci, I; Karpowicz, L S; Chapman, C A

    2012-01-10

    Layer II of the parasubiculum (PaS) receives excitatory synaptic input from the CA1 region of the hippocampus and sends a major output to layer II of the medial and lateral entorhinal cortex. The PaS also receives heavy cholinergic innervation from the medial septum, which contributes to the generation of theta-frequency (4-12 Hz) electroencephalographic (EEG) activity. Cholinergic receptor activation exerts a wide range of effects in other areas of the hippocampal formation, including membrane depolarization, changes in neuronal excitability, and suppression of excitatory synaptic responses. The present study was aimed at determining how cholinergic receptor activation modulates excitatory synaptic input to the layer II/III neurons of the PaS in acute brain slices. Field excitatory postsynaptic potentials (fEPSPs) in layer II/III of the PaS were evoked by stimulation of either layer I afferents, or ascending inputs from layer V. Bath-application of the cholinergic agonist carbachol (0.5-10 μM) suppressed the amplitude of fEPSPs evoked by both superficial- and deep layer stimulation, and also enhanced paired-pulse facilitation. Constant bath-application of the GABA(A) antagonist bicuculline (10 μM) failed to eliminate the suppression, indicating that the cholinergic suppression of fEPSPs is not due to increased inhibitory tone. The muscarinic receptor antagonist atropine (1 μM) blocked the suppression of fEPSPs, and the selective M(1)-preferring receptor antagonist pirenzepine (1 μM), but not the M(2)-preferring antagonist methoctramine (1-5 μM), also significantly attenuated the suppression. Therefore, cholinergic receptor activation suppresses excitatory synaptic input to layer II/III neurons of the PaS, and this suppression is mediated in part by M(1) receptor activation.

  4. Tactical Checkpoint: Hail/Warn Suppress/Stop (Poster)

    DTIC Science & Technology

    2010-11-15

    distractor , optical suppression , human behavior, checkpoint, ambient light, driver suppression , human experimentation, light, paintball, obscuration...HAIL/WARN AND - SUPPRESS /STOP Poster Presented at the 2010 Directed Energies Professional Society Meeting, 15-19 November 2010. 5a. CONTRACT NUMBER...warning to a driver that is approaching a checkpoint. The laser, MCNC light, and the windshield obscuration were evaluated for their suppression

  5. Appetite suppressants and valvular heart disease.

    PubMed

    Weissman, N J

    2001-04-01

    The association between valvular heart disease and diet pills was discovered several years ago in a small cohort of patients. Subsequent uncontrolled surveys and reports suggested a prevalence of cardiac abnormalities as high as 30%. These results led to widespread concern by millions of appetite suppressant users and the withdrawal of both fenfluramine and dexfenfluramine from the market. Through this review of the literature, it becomes apparent that we have better defined the association between valvular heart disease and appetite suppressants; nonetheless, many questions and controversies remain. Most large scale, multicenter, controlled studies have shown that a prevalence of significant valve regurgitation is between 2 and 12% and that the likelihood of disease increases with increasing dose and/or duration of appetite suppressant use, but several other issues, such as the mechanism of action, remain unanswered.

  6. Wing rock suppression using forebody vortex control

    NASA Technical Reports Server (NTRS)

    Ng, T. T.; Ong, L. Y.; Suarez, C. J.; Malcolm, G. N.

    1991-01-01

    Static and free-to-roll tests were conducted in a water tunnel with a configuration that consisted of a highly-slender forebody and 78-deg sweep delta wings. Flow visualization was performed and the roll angle histories were obtained. The fluid mechanisms governing the wing rock of this configuration were identified. Different means of suppressing wing rock by controlling the forebody vortices using small blowing jets were also explored. Steady blowing was found to be capable of suppressing wing rock, but significant vortex asymmetries had to be induced at the same time. On the other hand, alternating pulsed blowing on the left and right sides of the forebody was demonstrated to be potentially an effective means of suppressing wing rock and eliminating large asymmetric moments at high angles of attack.

  7. The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression.

    PubMed

    Brown, Joel S; Cunningham, Jessica J; Gatenby, Robert A

    2015-07-19

    Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed--a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler-Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the 'cost' (decreased fecundity) of suppression verses the 'cost' of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%.

  8. The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression

    PubMed Central

    Brown, Joel S.; Cunningham, Jessica J.; Gatenby, Robert A.

    2015-01-01

    Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed—a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler–Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the ‘cost’ (decreased fecundity) of suppression verses the ‘cost’ of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%. PMID:26056365

  9. Implicitly learned suppression of irrelevant spatial locations.

    PubMed

    Leber, Andrew B; Gwinn, Rachael E; Hong, Yoolim; O'Toole, Ryan J

    2016-12-01

    How do we ignore a salient, irrelevant stimulus whose location is predictable? A variety of studies using instructional manipulations have shown that participants possess the capacity to exert location-based suppression. However, for the visual search challenges we face in daily life, we are not often provided explicit instructions and are unlikely to consciously deliberate on what our best strategy might be. Instead, we might rely on our past experience-in the form of implicit learning-to exert strategic control. In this paper, we tested whether implicit learning could drive spatial suppression. In Experiment 1, participants searched displays in which one location contained a target, while another contained a salient distractor. An arrow cue pointed to the target location with 70 % validity. Also, unbeknownst to the participants, the same arrow cue predicted the distractor location with 70 % validity. Results showed facilitated RTs to the predicted target location, confirming target enhancement. Critically, distractor interference was reduced at the predicted distractor location, revealing that participants used spatial suppression. Further, we found that participants had no explicit knowledge of the cue-distractor contingencies, confirming that the learning was implicit. In Experiment 2, to seek further evidence for suppression, we modified the task to include occasional masked probes following the arrow cue; we found worse probe identification accuracy at the predicted distractor location than control locations, providing converging evidence that observers spatially suppressed the predicted distractor locations. These results reveal an ecologically desirable mechanism of suppression, which functions without the need for conscious knowledge or externally guided instructions.

  10. Feature-selective attention in healthy old age: a selective decline in selective attention?

    PubMed

    Quigley, Cliodhna; Müller, Matthias M

    2014-02-12

    Deficient selection against irrelevant information has been proposed to underlie age-related cognitive decline. We recently reported evidence for maintained early sensory selection when older and younger adults used spatial selective attention to perform a challenging task. Here we explored age-related differences when spatial selection is not possible and feature-selective attention must be deployed. We additionally compared the integrity of feedforward processing by exploiting the well established phenomenon of suppression of visual cortical responses attributable to interstimulus competition. Electroencephalogram was measured while older and younger human adults responded to brief occurrences of coherent motion in an attended stimulus composed of randomly moving, orientation-defined, flickering bars. Attention was directed to horizontal or vertical bars by a pretrial cue, after which two orthogonally oriented, overlapping stimuli or a single stimulus were presented. Horizontal and vertical bars flickered at different frequencies and thereby elicited separable steady-state visual-evoked potentials, which were used to examine the effect of feature-based selection and the competitive influence of a second stimulus on ongoing visual processing. Age differences were found in feature-selective attentional modulation of visual responses: older adults did not show consistent modulation of magnitude or phase. In contrast, the suppressive effect of a second stimulus was robust and comparable in magnitude across age groups, suggesting that bottom-up processing of the current stimuli is essentially unchanged in healthy old age. Thus, it seems that visual processing per se is unchanged, but top-down attentional control is compromised in older adults when space cannot be used to guide selection.

  11. Vibration Isolation, Suppression, Steering, and Pointing (VISSP)

    NASA Technical Reports Server (NTRS)

    Wada, Ben K.; Rahman, Zahidul; Kedikian, Roland

    1996-01-01

    The design of a six degree of freedom flight vibration isolation suppression and steering (VISS) subsystem for a mid-wave infrared camera on the top of a spacecraft is presented. The development of a long stroke piezoelectric, redundant, compact, low stiffness and power efficient actuator is summarized. A subsystem that could be built and validated for flight within 15 months was investigated. The goals of the VISS are 20 dB vibration isolation above 2 Hz, 15 dB vibration suppression of disturbances at about 60 Hz and 120 Hz, and +/- 0.3 deg steering at 2 Hz and 4 Hz.

  12. Active Suppression Of Vibrations On Aircraft Structures

    NASA Technical Reports Server (NTRS)

    Maestrello, Lucio

    1995-01-01

    Method of active suppression of nonlinear and nonstationary vibrations developed to reduce sonic fatigue and interior noise in high-speed aircraft. Structure of aircraft exhibits periodic, chaotic, and random vibrations when forced by high-intensity sound from jet engines, shock waves, turbulence, and separated flows. Method of suppressing vibrations involves feedback control: Strain gauges or other sensors mounted in paths of propagation of vibrations on structure sense vibrations; outputs of sensors processed into control signal applied to actuator mounted on structure, inducing compensatory forces.

  13. Immune suppressive mechanisms in the tumor microenvironment.

    PubMed

    Munn, David H; Bronte, Vincenzo

    2016-04-01

    Effective immunotherapy, whether by checkpoint blockade or adoptive cell therapy, is limited in most patients by a key barrier: the immunosuppressive tumor microenvironment. Suppression of tumor-specific T cells is orchestrated by the activity of a variety of stromal myeloid and lymphoid cells. These often display inducible suppressive mechanisms that are triggered by the same anti-tumor inflammatory response that the immunotherapy intends to create. Therefore, a more comprehensive understanding of how the immunosuppressive milieu develops and persists is critical in order to harness the full power of immunotherapy of cancer.

  14. Corticosteroids and Immune Suppressive Therapies in Horses.

    PubMed

    Leclere, Mathilde

    2017-04-01

    Immune suppressive therapies target exaggerated and deleterious responses of the immune system. Triggered by exogenous or endogenous factors, these improper responses can lead to immune or inflammatory manifestations, such as urticaria, equine asthma, or autoimmune and immune-mediated diseases. Glucocorticoids are the most commonly used immune suppressive drugs and the only ones supported by robust evidence of clinical efficacy in equine medicine. In some conditions, combining glucocorticoids with other pharmacologic and nonpharmacologic treatments, such as azathioprine, antihistamine, bronchodilators, environmental management, or desensitization, can help to decrease dosages and associated side effects.

  15. Chemical diffusion during isobaric degassing of magma

    NASA Astrophysics Data System (ADS)

    von Aulock, Felix W.; Kennedy, Ben M.; Lavallée, Yan; Henton-de Angelis, Sarah; Oze, Christopher; Morgan, Daniel J.; Clesham, Steve

    2014-05-01

    During ascent of magma, volatiles exsolve and bubbles form. Volatiles can either escape through a permeable network of bubbles in an open system or be trapped in non-connected pores during closed system degassing. Geochemical studies have shown that in most cases both- open system and closed system degassing take place at the same time. During cooling of the melt, diffusion slows down and eventually diffusional gradients get frozen in, preserving a history of degassing and rehydration during bubble growth, bubble collapse and crystal growth. We present data from experiments in which natural obsidian was degassed at atmospheric pressures at 950ºC over timescales of 3-24h. During bubble growth, a skin formed, at the outer edge of the sample, effectively prohibiting any degassing of its interior. Diffusion gradients were measured across the glass surrounding vesicles, and across this impermeable skin. Water contents were analyzed with synchrotron sourced Fourier transform infrared spectroscopy and several major, minor and trace elements were mapped using synchrotron sourced X-ray fluorescence spectroscopy. The samples show a dimpled surface, as well as signs of oxidation and growth of submicroscopic crystals. Water contents around bubbles decrease in simple heating experiments (from ~0.13 wt. % down to ~0.1 wt. %), whereas slight rehydration of the vesicle wall can be observed when a second, cooler step at 850ºC follows the initial 950ºC. Water gradients towards the outside of the sample decrease linearly to a minimum of ~0.045 wt. %, far below the solubility of water in melts at these temperatures. We mapped the distribution of K, Ca, Fe, Ti, Mn, Rb, Sr, Y and Zr. Especially the trace elements show a decrease towards the outside of the sample, whereas K, Fe, Ca and Ti generally do not show significant partitioning between melt and gas/crystal phase. Several effects could attribute to the distribution of these elements, such as the crystal growth and exchange with atmospheric oxygen, and detailed models of the diffusion of these elements will have to verify the mechanisms of elemental partitioning during degassing Our experiments show that even on a small scale, open system and closed system degassing inherently coexist. This manifests itself in different elemental distribution in the quenched glass. Water distribution gradients can be explained with diffusion during exsolution and rehydration during cooling, however, the surface of the sample is undersaturated in water. Some trace elements follow the same pattern, even though they might not be considered as volatile. Therefore we suggest that chemical gradients may be partially induced by the growth of sub-microscopic crystals and by exchange with the atmosphere. Crystal rich, volatile poor outer skins, as produced in the experiments of this study, have locally drastically increased viscosities and can therefore withstand higher pressures during foaming of the interior of the sample. This self sealing of magma could be an important process on different scales of magma degassing, from bread crust bombs to rising magma in conduits.

  16. Suppression of Bedbug's Reproduction by RNA Interference of Vitellogenin.

    PubMed

    Moriyama, Minoru; Hosokawa, Takahiro; Tanahashi, Masahiko; Nikoh, Naruo; Fukatsu, Takema

    2016-01-01

    Recent resurgence of the bedbug Cimex lectularius is a global problem on the public health. On account of the worldwide rise of insecticide-resistant bedbug populations, exploration of new approaches to the bedbug control and management is anticipated. In this context, gene silencing by RNA interference (RNAi) has been considered for its potential application to pest control and management, because RNAi enables specific suppression of target genes and thus flexible selection of target traits to be disrupted. In this study, in an attempt to develop a control strategy targeting reproduction of the bedbug, we investigated RNAi-mediated gene silencing of vitellogenin (Vg), a major yolk protein precursor essential for oogenesis. From the bedbug transcriptomes, we identified a typical Vg gene and a truncated Vg gene, which were designated as ClVg and ClVg-like, respectively. ClVg gene was highly expressed mainly in the fat body of adult females, which was more than 100 times higher than the expression level of ClVg-like gene, indicating that ClVg gene is the primary functional Vg gene in the bedbug. RNAi-mediated suppression of ClVg gene expression in adult females resulted in drastically reduced egg production, atrophied ovaries, and inflated abdomen due to hypertrophied fat bodies. These phenotypic consequences are expected not only to suppress the bedbug reproduction directly but also to deteriorate its feeding and survival indirectly via behavioral modifications. These results suggest the potential of ClVg gene as a promising target for RNAi-based population management of the bedbug.

  17. Distinct neural mechanisms of distractor suppression in the frontal and parietal lobe.

    PubMed

    Suzuki, Mototaka; Gottlieb, Jacqueline

    2013-01-01

    The posterior parietal cortex and the prefrontal cortex are associated with eye movements and visual attention, but their specific contributions are poorly understood. We compared the dorsolateral prefrontal cortex (dlPFC) and the lateral intraparietal area (LIP) in monkeys using a memory saccade task in which a salient distractor flashed at a variable timing and location during the memory delay. We found that the two areas had similar responses to target selection, but made distinct contributions to distractor suppression. Distractor responses were more strongly suppressed and more closely correlated with performance in the dlPFC relative to LIP. Moreover, reversible inactivation of the dlPFC produced much larger increases in distractibility than inactivation of LIP. These findings suggest that LIP and dlPFC mediate different aspects of selective attention. Although both areas can contribute to the perceptual selection of salient information, the dlPFC has a decisive influence on whether and how attended stimulus is linked with actions.

  18. Selecting Interventions.

    ERIC Educational Resources Information Center

    Langdon, Danny G.

    1997-01-01

    Describes a systematic approach to selecting instructional designs, discussing performance analysis, gaps, elements (inputs, conditions, process, outputs, consequences, feedback), matrices, changes in performance state (establishing, improving, maintaining, and extinguishing performance), intervention interference, and involving others in…

  19. Selected References.

    ERIC Educational Resources Information Center

    Allen, Walter C.

    1987-01-01

    This extensive bibliography on library building includes 15 categories: bibliography; background; general; planning teams; building programs; alternatives to new buildings; academic libraries; public libraries; school libraries; special libraries; site selection; interior planning and equipment; maintenance; security; and moving. (MES)

  20. Neural evidence for distracter suppression during visual search in real-world scenes.

    PubMed

    Seidl, Katharina N; Peelen, Marius V; Kastner, Sabine

    2012-08-22

    Selecting visual information from cluttered real-world scenes involves the matching of visual input to the observer's attentional set--an internal representation of objects that are relevant for current behavioral goals. When goals change, a new attentional set needs to be instantiated, requiring the suppression of the previous set to prevent distraction by objects that are no longer relevant. In the present fMRI study, we investigated how such suppression is implemented at the neural level. We measured human brain activity in response to natural scene photographs that could contain objects from (1) a currently relevant (target) category, (2) a previously but not presently relevant (distracter) category, and/or (3) a never relevant (neutral) category. Across conditions, multivoxel response patterns in object-selective cortex carried information about objects present in the scenes. However, this information strongly depended on the task relevance of the objects. As expected, information about the target category was significantly increased relative to the neutral category, indicating top-down enhancement of task-relevant information. Importantly, information about the distracter category was significantly reduced relative to the neutral category, indicating that the processing of previously relevant objects was suppressed. Such active suppression at the level of high-order visual cortex may serve to prevent the erroneous selection of, or interference from, objects that are no longer relevant to ongoing behavior. We conclude that the enhancement of relevant information and the suppression of distracting information both contribute to the efficient selection of visual information from cluttered real-world scenes.

  1. Population characteristics and the suppression of nonnative Burbot

    USGS Publications Warehouse

    Klein, Zachary B.; Quist, Michael; Rhea, Darren T.; Senecal, Anna C.

    2016-01-01

    Burbot Lota lota were illegally introduced into the Green River, Wyoming, drainage and have since proliferated throughout the system. Burbot in the Green River pose a threat to native species and to socially, economically, and ecologically important recreational fisheries. Therefore, managers of the Green River are interested in implementing a suppression program for Burbot. We collected demographic data on Burbot in the Green River (summer and autumn 2013) and used the information to construct an age-based population model (female-based Leslie matrix) to simulate the population-level response of Burbot to the selective removal of different age-classes. Burbot in the Green River grew faster, matured at relatively young ages, and were highly fecund compared with other Burbot populations within the species’ native distribution. The age-structured population model, in conjunction with demographic information, indicated that the Burbot population in the Green River could be expected to increase under current conditions. The model also indicated that the Burbot population in the Green River would decline once total annual mortality reached 58%. The population growth of Burbot in the Green River was most sensitive to age-0 and age-1 mortality. The age-structured population model indicated that an increase in mortality, particularly for younger age-classes, would result in the effective suppression of the Burbot population in the Green River.

  2. Neuroligin-1 Knockdown Suppresses Seizure Activity by Regulating Neuronal Hyperexcitability.

    PubMed

    Fang, Min; Wei, Jin-Lai; Tang, Bo; Liu, Jing; Chen, Ling; Tang, Zhao-Hua; Luo, Jing; Chen, Guo-Jun; Wang, Xue-Feng

    2016-01-01

    Abnormally synchronized synaptic transmission in the brain leads to epilepsy. Neuroligin-1 (NL1) is a synaptic cell adhesion molecule localized at excitatory synapses. NL1 modulates synaptic transmission and determines the properties of neuronal networks in the mammalian central nervous system. We showed that the expression of NL1 and its binding partner neurexin-1β was increased in temporal lobe epileptic foci in patients and lithium-pilocarpine-treated epileptic rats. We investigated electrophysiological and behavioral changes in epileptic rats after lentivirally mediated NL1 knockdown in the hippocampus to determine whether NL1 suppression prevented seizures and, if so, to explore the probable underlying mechanisms. Our behavioral studies revealed that NL1 knockdown in epileptic rats reduced seizure severity and increased seizure latency. Whole-cell patch-clamp recordings of CA1 pyramidal neurons in hippocampal slices from NL1 knockdown epileptic rats revealed a decrease in spontaneous action potential frequency and a decrease in miniature excitatory postsynaptic current (mEPSC) frequency but not amplitude. The amplitude of N-methyl-D-aspartate receptor (NMDAR)-dependent EPSCs was also selectively decreased. Notably, NL1 knockdown reduced total NMDAR1 expression and the surface/total ratio in the hippocampus of epileptic rats. Taken together, these data indicate that NL1 knockdown in epileptic rats may reduce the frequency and severity of seizures and suppress neuronal hyperexcitability via changes in postsynaptic NMDARs.

  3. Alamethicin Suppresses Methanogenesis and Promotes Acetogenesis in Bioelectrochemical Systems

    PubMed Central

    Zhu, Xiuping; Siegert, Michael; Yates, Matthew D.

    2015-01-01

    Microbial electrosynthesis (MES) systems with mixed cultures often generate a variety of gaseous and soluble chemicals. Methane is the primary end product in mixed-culture MES because it is the thermodynamically most favorable reduction product of CO2. Here, we show that the peptaibol alamethicin selectively suppressed the growth of methanogens in mixed-culture MES systems, resulting in a shift of the solution and cathode communities to an acetate-producing system dominated by Sporomusa, a known acetogenic genus in MES systems. Archaea in the methane-producing control were dominated by Methanobrevibacter species, but no Archaea were detected in the alamethicin-treated reactors. No methane was detected in the mixed-culture reactors treated with alamethicin over 10 cycles (∼3 days each). Instead, acetate was produced at an average rate of 115 nmol ml−1 day−1, similar to the rate reported previously for pure cultures of Sporomusa ovata on biocathodes. Mixed-culture control reactors without alamethicin generated methane at nearly 100% coulombic recovery, and no acetate was detected. These results show that alamethicin is effective for the suppression of methanogen growth in MES systems and that its use enables the production of industrially relevant organic compounds by the inhibition of methanogenesis. PMID:25819972

  4. Suppression of methanogenesis in hydrogen fermentation by intermittent feeding.

    PubMed

    Yun, Jeonghee; Kim, Tae Gwan; Cho, Kyung-Suk

    2015-01-01

    This study investigated whether intermittent feeding by using a concentrated carbon source is an appropriate method for selective enrichment of hydrogenesis by means of methanogen suppression. In a conventional reactor fed continuously for 10 d, methanogens increased from 2.8 × 10(7) to 1.1 × 10(9) gene copy number (GCN)/mg-cell dry weight, and methane concentration in the resulting biogas was 5.8%. However, when a carbon source was intermittently supplied for 10 d to the reactor, the number of methanogens was reduced 98.9% from 2.77 × 10(7) to 1.2 × 10(3) GCN/mg-cell dry weight, and methane was not detected during this period of intermittent feeding. Intermittent feeding shifted the dominants in the reactor from Clostridiaceae (70.5%) and Lactobacillaceae (11.0%) to Acetobacteraceae (62.0%) and Clostridiaceae (38.0%). In the reactor operated in continuous feeding mode after intermittent feeding, methane concentration was below 0.3% and the portion of methanogens in the bacterial community was maintained below 0.2%. These results suggest that the intermittent feeding of a carbon source during hydrogen production processes is a suitable method to suppress the activity of methanogens.

  5. Reward association facilitates distractor suppression in human visual search.

    PubMed

    Gong, Mengyuan; Yang, Feitong; Li, Sheng

    2016-04-01

    Although valuable objects are attractive in nature, people often encounter situations where they would prefer to avoid such distraction while focusing on the task goal. Contrary to the typical effect of attentional capture by a reward-associated item, we provide evidence for a facilitation effect derived from the active suppression of a high reward-associated stimulus when cuing its identity as distractor before the display of search arrays. Selection of the target is shown to be significantly faster when the distractors were in high reward-associated colour than those in low reward-associated or non-rewarded colours. This behavioural reward effect was associated with two neural signatures before the onset of the search display: the increased frontal theta oscillation and the strengthened top-down modulation from frontal to anterior temporal regions. The former suggests an enhanced working memory representation for the reward-associated stimulus and the increased need for cognitive control to override Pavlovian bias, whereas the latter indicates that the boost of inhibitory control is realized through a frontal top-down mechanism. These results suggest a mechanism in which the enhanced working memory representation of a reward-associated feature is integrated with task demands to modify attentional priority during active distractor suppression and benefit behavioural performance.

  6. The Suppression of Dominant Acoustic Frequencies in MRI

    NASA Astrophysics Data System (ADS)

    Shou, Xingxian; Brown, Robert

    2011-03-01

    Patient discomfort and brain imaging distortion are serious MRI acoustic noise problems arising from the rapid switching on and off of gradient coils in the presence of the strong Larmor magnetic field. A study is made of dominant frequencies in the acoustic noise spectrum and, motivated by both spring and string ideas, we propose the cancellation of selected frequencies by appropriate gradient pulse sequence design. From both simulations and experiments, vibrations resulting from an impulsive force associated with a ramping up of a gradient pulse are shown to be cancelled upon the application of another impulsive force coming from the appropriately timed ramping down of that pulse. A method for the suppression of multiple-frequency contributions involving a series of gradient pulses with variable timings is developed and confirmed by experiment. Whether we refer to reduction in terms of dB (about 30-40 dB per peak), or to the verdict of a listener, the conclusion is that a marked reduction in sound can be achieved when at least three of the dominant frequency peaks are suppressed. A variety of pulse profiles and timing combinations can be used to attenuate important contributions to the acoustic spectrum. Supported by the Ohio Third Frontier Program.

  7. Flavivirus Infection Uncouples Translation Suppression from Cellular Stress Responses

    PubMed Central

    Roth, Hanna; Magg, Vera; Uch, Fabian; Mutz, Pascal; Klein, Philipp; Haneke, Katharina; Lohmann, Volker; Bartenschlager, Ralf; Fackler, Oliver T.; Locker, Nicolas; Stoecklin, Georg

    2017-01-01

    ABSTRACT As obligate parasites, viruses strictly depend on host cell translation for the production of new progeny, yet infected cells also synthesize antiviral proteins to limit virus infection. Modulation of host cell translation therefore represents a frequent strategy by which viruses optimize their replication and spread. Here we sought to define how host cell translation is regulated during infection of human cells with dengue virus (DENV) and Zika virus (ZIKV), two positive-strand RNA flaviviruses. Polysome profiling and analysis of de novo protein synthesis revealed that flavivirus infection causes potent repression of host cell translation, while synthesis of viral proteins remains efficient. Selective repression of host cell translation was mediated by the DENV polyprotein at the level of translation initiation. In addition, DENV and ZIKV infection suppressed host cell stress responses such as the formation of stress granules and phosphorylation of the translation initiation factor eIF2α (α subunit of eukaryotic initiation factor 2). Mechanistic analyses revealed that translation repression was uncoupled from the disruption of stress granule formation and eIF2α signaling. Rather, DENV infection induced p38-Mnk1 signaling that resulted in the phosphorylation of the eukaryotic translation initiation factor eIF4E and was essential for the efficient production of virus particles. Together, these results identify the uncoupling of translation suppression from the cellular stress responses as a conserved strategy by which flaviviruses ensure efficient replication in human cells. PMID:28074025

  8. MPLM fire detection and suppression: architecture and analysis

    SciTech Connect

    Balocco, P.; Potenza, F.; Cafero, E. |

    1993-12-31

    The Mini Pressurized Logistics Module (MPLM) is a servicer of the Space Station Freedom (SSF), whose purpose is to provide location for both subsystems and payload racks (active racks i.e. namely a freezer and a freezer/refrigerator, is to be serviced, and passive racks). The MPLM will be used to supply and return a pressurized cargo to and from the SSF via the National Space Transportation System (NSTS), optimizing the NSTS cargo capabilities. Being a pressurized module, the MPLM is characterized by an Environmental Control System that consists of two sections: The Enviromental Control and Life Support System (ECLSS) and the Internal Thermal Control System (ITCS). The ECLSS is constituted by other subsections, among which is the Fire Detection and Suppression (FDS) Subsystem. The fire suppression method, selected at SSF level, is the CO2 discharge and diffusion in the affected enclosed areas. As far as the mathematical simulation of the FDS aspects is concerned, a big effort has been made and is still on-going. The related mathematical modelization is quite complex, involving two-phase phenomena, chocked flow and gas diffusion: this means the implementation and running of dedicated Computational Fluid Dynamics (CFD) models. The diffusion analysis is particularly time-consuming, due to the complexity of the geometry with respect to modelization capability.

  9. Betulin Derivatives Effectively Suppress Inflammation in Vitro and in Vivo.

    PubMed

    Laavola, Mirka; Haavikko, Raisa; Hämäläinen, Mari; Leppänen, Tiina; Nieminen, Riina; Alakurtti, Sami; Moreira, Vânia M; Yli-Kauhaluoma, Jari; Moilanen, Eeva

    2016-02-26

    Betulin is a pharmacologically active triterpenoid found in the bark of the birch tree (Betula sp. L.). Betulin and betulinic acid are structurally related to anti-inflammatory steroids, but little is known about their potential anti-inflammatory properties. In the present study, the inflammatory gene expression and the anti-inflammatory properties of betulin, betulinic acid, and 16 semisynthetic betulin derivatives were investigated. Betulin derivatives 3, 4, and 5 selectively inhibited the expression of the inducible nitric oxide synthase (iNOS) in a post-transcriptional manner. They also inhibited nitric oxide (NO) production but had no effect on the other inflammatory factors studied. More interestingly, a new anti-inflammatory betulin derivative 9 with a wide-spectrum anti-inflammatory activity was discovered. Compound 9 was found to suppress the expression of cytokines interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1), as well as that of prostaglandin synthase-2 (COX-2) in addition to iNOS. The in vivo anti-inflammatory effect of compound 9 was indicated via significant suppression of the carrageenan-induced paw inflammation in mice. The results show, for the first time, that the pyrazole-fused betulin derivative (9) and related compounds have anti-inflammatory properties that could be utilized in drug development.

  10. Prevention of melatonin suppression by nocturnal lighting: relevance to cancer.

    PubMed

    Kayumov, Leonid; Lowe, Alan; Rahman, Shadab A; Casper, Robert F; Shapiro, Colin M

    2007-08-01

    The decreased melatonin production in humans and animals caused by environmental lighting, especially short wavelength lighting (between 470 and 525 nm) has been shown to be associated with an increased risk of cancer. The purpose of this study was to investigate whether blocking light in this wavelength range under bright light may prevent the suppression of melatonin, which could help to prevent cancer. Optical filter lenses were designed, allowing selective exclusion of all wavelengths below 530 nm. Salivary melatonin levels were measured under dim light (<5 lux), bright light (800 lux) and filtered light (800 lux) at hourly intervals between 2000 and 0800 h in 11 healthy young male participants (mean age 23.5+/-1.5 years). The measurements were taken during three nonconsecutive nights over a 2-week period. The Dim Light Melatonin Onset test was used as a marker of circadian phase. Nine of the 11 participants demonstrated preserved melatonin levels in filtered light similar to their dim light secretion profile. With filtered light, the participants had a mean relative amount of melatonin of 91.2 (P>0.05 between dim light and experimental condition). Unfiltered bright light drastically suppressed melatonin production with a mean relative amount of melatonin of 25.4 (P<0.05 between dim light and experimental condition). Preventing melatonin deficiencies using lenses that block light of low wavelength from reaching the retina presents a cost-effective, practical solution to the problem of increased malignancy rates in shift workers.

  11. Suppressive competition: how sounds may cheat sight.

    PubMed

    Kayser, Christoph; Remedios, Ryan

    2012-02-23

    In this issue of Neuron, Iurilli et al. (2012) demonstrate that auditory cortex activation directly engages local GABAergic circuits in V1 to induce sound-driven hyperpolarizations in layer 2/3 and layer 6 pyramidal neurons. Thereby, sounds can directly suppress V1 activity and visual driven behavior.

  12. Suppression Situations in Multiple Linear Regression

    ERIC Educational Resources Information Center

    Shieh, Gwowen

    2006-01-01

    This article proposes alternative expressions for the two most prevailing definitions of suppression without resorting to the standardized regression modeling. The formulation provides a simple basis for the examination of their relationship. For the two-predictor regression, the author demonstrates that the previous results in the literature are…

  13. Characterization of Immune Suppression Induced by Polyribonucleotides.

    DTIC Science & Technology

    1985-12-01

    RD-0162 482 CHARACTERIZATION OF IMMUNE SUPPRESSION INDUCED Y v i POLYRIDONUCLEOTIDES(U) MINNESOTA UNIV DULUTH DEPT OF MEDICAL MICROBIOLOGY AND...Polyribonucleotides by Marilyn J. Odean and Arthur G. Johnson Dept. of Medical Microbiology /Immunology University of Minnesota-Duluth 55812 DTICS ELECTE DEC 18

  14. Active suppression after involuntary capture of attention.

    PubMed

    Sawaki, Risa; Luck, Steven J

    2013-04-01

    After attention has been involuntarily captured by a distractor, how is it reoriented toward a target? One possibility is that attention to the distractor passively fades over time, allowing the target to become attended. Another possibility is that the captured location is actively suppressed so that attention can be directed toward the target location. The present study investigated this issue with event-related potentials (ERPs), focusing on the N2pc component (a neural measure of attentional deployment) and the Pd component (a neural measure of attentional suppression). Observers identified a color-defined target in a search array, which was preceded by a task-irrelevant cue array. When the cue array contained an item that matched the target color, this item captured attention (as measured both behaviorally and with the N2pc component). This capture of attention was followed by active suppression (indexed by the Pd component), and this was then followed by a reorienting of attention toward the target in the search array (indexed by the N2pc component). These findings indicate that the involuntary capture of attention by a distractor is followed by an active suppression process that presumably facilitates the subsequent voluntary orienting of attention to the target.

  15. Sound-suppressing structure with thermal relief

    NASA Technical Reports Server (NTRS)

    Nash, D. O.; Holowach, J. (Inventor)

    1978-01-01

    Sound-suppressing structure comprising stacked acoustic panels wherein the inner high frequency panel is mounted for thermal expansion with respect to the outer low frequency panel is discussed. Slip joints eliminate the potential for thermal stresses, and a thermal expansion gap between the panels provides for additional relative thermal growth while reducing heat convection into the low frequency panel.

  16. Suppressed Carrier Synchronizers for ISI Channels

    NASA Technical Reports Server (NTRS)

    Hinedi, Sami M.; Simon, Marvin K.

    1996-01-01

    We demonstrate a class of suppressed carrier synchronization loops that are motivated by MAP estimation theory and in the presence of ISI outperform the conventional I-Q loop which is designed on the basis of zero ISI (wideband assumption). The measure of comparison used is the so-called.

  17. Radio science measurements with suppressed carrier

    NASA Astrophysics Data System (ADS)

    Asmar, S.; Divsalar, D.; Oudrhiri, K.; Hamkins, J.

    Radio Science started when it became apparent with early deep space missions that occultations by planetary atmospheres would affect the quality of radio communications. Since then the atmospheric properties and other aspects of planetary science, solar science, and fundamental physics were studied by scientists. Radio Science data was always extracted from a received pure residual carrier (without data modulation). For some missions, it is very desirable to obtain Radio Science data from a suppressed carrier modulation. In this paper we propose a method to extract Radio Science data when a coded suppressed carrier modulation is used in deep space communications. The type of modulation can be BPSK, QPSK, OQPSK, MPSK or even GMSK. However we concentrate mostly on BPSK modulation. The proposed method for suppressed carrier simply tries to wipe out data that acts as an interference for Radio Science measurements. In order to measure the estimation errors in amplitude and phase of the Radio Science data we use the Cramer-Rao bound (CRB). The CRB for suppressed carrier modulation with non-ideal data wiping is then compared with residual carrier modulation under the same noise condition. The method of derivation of the CRB for non-ideal data wiping is an innovative method that is presented here. Some numerical results are provided for a coded system.

  18. Radio Science Measurements with Suppressed Carrier

    NASA Technical Reports Server (NTRS)

    Asmar, Sami; Divsalar, Dariush; Oudrhiri, Kamal

    2013-01-01

    Radio Science started when it became apparent with early Solar missions that occultations by planetary atmospheres would affect the quality of radio communications. Since then the atmospheric properties and other aspects of planetary science, solar science, and fundamental physics were studied by scientists. Radio Science data was always extracted from a received pure residual carrier (without data modulation). For some missions, it is very desirable to obtain Radio Science data from a suppressed carrier modulation. In this paper we propose a method to extract Radio Science data when a coded suppressed carrier modulation is used in deep space communications. Type of modulation can be BPSK, QPSK, OQPSK, MPSK or even GMSK. However we concentrate mostly on BPSK modulation. The proposed method for suppressed carrier simply tries to wipe out data that acts as an interference for Radio Science measurements. In order to measure the estimation errors in amplitude and phase of the Radio Science data we use Cramer-Rao bound (CRB). The CRB for the suppressed carrier modulation with non-ideal data wiping is then compared with residual carrier modulation under the same noise condition. The method of derivation of CRB for non-ideal data wiping is an innovative method that presented here. Some numerical results are provided for coded system.

  19. Government Doublethink: Protection or Suppression in Information.

    ERIC Educational Resources Information Center

    Drake, Miriam A.

    2003-01-01

    Discusses regulations and actions related to government withholding, suppressing, and altering information since September 11, 2001. Topics include conflicting goals of an informed citizenry versus national security, science and technology progress versus protection of sensitive information, and public health versus ideology; political pressure;…

  20. Collective suppression of linewidths in circuit QED.

    PubMed

    Nissen, Felix; Fink, Johannes M; Mlynek, Jonas A; Wallraff, Andreas; Keeling, Jonathan

    2013-05-17

    We report the experimental observation and a theoretical explanation of collective suppression of linewidths for multiple superconducting qubits coupled to a good cavity. This demonstrates how strong qubit-cavity coupling can significantly modify the dephasing and dissipation processes that might be expected for individual qubits, and can potentially improve coherence times in many-body circuit QED.

  1. Spacecraft Fire Suppression: Testing and Evaluation

    NASA Technical Reports Server (NTRS)

    Abbud-Madrid, Angel; McKinnon, J. Thomas; Delplanque, Jean-Pierre; Kailasanath, Kazhikathra; Gokoglu, Suleyman; Wu, Ming-Shin

    2004-01-01

    The objective of this project is the testing and evaluation of the effectiveness of a variety of fire suppressants and fire-response techniques that will be used in the next generation of spacecraft (Crew Exploration Vehicle, CEV) and planetary habitats. From the many lessons learned in the last 40 years of space travel, there is common agreement in the spacecraft fire safety community that a new fire suppression system will be needed for the various types of fire threats anticipated in new space vehicles and habitats. To date, there is no single fire extinguishing system that can address all possible fire situations in a spacecraft in an effective, reliable, clean, and safe way. The testing conducted under this investigation will not only validate the various numerical models that are currently being developed, but it will provide new design standards on fire suppression that can then be applied to the next generation of spacecraft extinguishment systems. The test program will provide validation of scaling methods by conducting small, medium, and large scale fires. A variety of suppression methods will be tested, such as water mist, carbon dioxide, and nitrogen with single and multiple injection points and direct or distributed agent deployment. These injection methods cover the current ISS fire suppression method of a portable hand-held fire extinguisher spraying through a port in a rack and also next generation spacecraft units that may have a multi-point suppression delivery system built into the design. Consideration will be given to the need of a crew to clean-up the agent and recharge the extinguishers in flight in a long-duration mission. The fire suppression methods mentioned above will be used to extinguish several fire scenarios that have been identified as the most relevant to spaceflight, such as overheated wires, cable bundles, and circuit boards, as well as burning cloth and paper. Further testing will be conducted in which obstructions and

  2. Bone suppression in CT angiography data by region-based multiresolution segmentation

    NASA Astrophysics Data System (ADS)

    Blaffert, Thomas; Wiemker, Rafael; Lin, Zhong Min

    2003-05-01

    Multi slice CT (MSCT) scanners have the advantage of high and isotropic image resolution, which broadens the range of examinations for CT angiography (CTA). A very important method to present the large amount of high-resolution 3D data is the visualization by maximum intensity projections (MIP). A problem with MIP projections in angiography is that bones often hide the vessels of interest, especially the scull and vertebral column. Software tools for a manual selection of bone regions and their suppression in the MIP are available, but processing is time-consuming and tedious. A highly computer-assisted of even fully automated suppression of bones would considerably speed up the examination and probably increase the number of examined cases. In this paper we investigate the suppression (or removal) of bone regions in 3D CT data sets for vascular examinations of the head with a visualization of the carotids and the circle of Willis.

  3. Posing for awareness: proprioception modulates access to visual consciousness in a continuous flash suppression task.

    PubMed

    Salomon, Roy; Lim, Melanie; Herbelin, Bruno; Hesselmann, Guido; Blanke, Olaf

    2013-06-03

    The rules governing the selection of which sensory information reaches consciousness are yet unknown. Of our senses, vision is often considered to be the dominant sense, and the effects of bodily senses, such as proprioception, on visual consciousness are frequently overlooked. Here, we demonstrate that the position of the body influences visual consciousness. We induced perceptual suppression by using continuous flash suppression. Participants had to judge the orientation a target stimulus embedded in a task-irrelevant picture of a hand. The picture of the hand could either be congruent or incongruent with the participants' actual hand position. When the viewed and the real hand positions were congruent, perceptual suppression was broken more rapidly than during incongruent trials. Our findings provide the first evidence of a proprioceptive bias in visual consciousness, suggesting that proprioception not only influences the perception of one's own body and self-consciousness, but also visual consciousness.

  4. Iterative method for zero-order suppression in off-axis digital holography.

    PubMed

    Pavillon, Nicolas; Arfire, Cristian; Bergoënd, Isabelle; Depeursinge, Christian

    2010-07-19

    We propose a method to suppress the so-called zero-order term in a hologram, based on an iterative principle. During the hologram acquisition process, the encoded information includes the intensities of the two beams creating the interference pattern, which do not contain information about the recorded complex wavefront, and that can disrupt the reconstructed signal. The proposed method selectively suppresses the zero-order term by employing the information obtained during wavefront reconstruction in an iterative procedure, thus enabling its suppression without any a priori knowledge about the object. The method is analyzed analytically and its convergence is studied. Then, its performance is shown experimentally. Its robustness is assessed by applying the procedure on various types of holograms, such as topographic images of microscopic specimens or speckle holograms.

  5. Nordihydroguaiaretic acid impairs prostate cancer cell migration and tumor metastasis by suppressing neuropilin 1

    PubMed Central

    Li, Xin; Fan, Shengjun; Pan, Xueyang; Xiaokaiti, Yilixiati; Duan, Jianhui; Shi, Yundi; Pan, Yan; Tie, Lu; Wang, Xin; Li, Yuhua; Li, Xuejun

    2016-01-01

    Tumor metastasis is a major cause leading to the deaths of cancer patients. Nordihydroguaiaretic acid (NDGA) is a natural product that has been demonstrated to show therapeutic values in multiple diseases. In this study, we report that NDGA can inhibit cell migration and tumor metastasis via a novel mechanism. NDGA suppresses NRP1 function by downregulating its expression, which leads to attenuated cell motility, cell adhesion to ECM and FAK signaling in cancer cells. Moreover, due to its cross-cell type activity on NRP1 suppression, NDGA also impairs angiogenesis function of endothelial cells and fibronectin assembly by fibroblasts, both of which are critical to promote metastasis. Based on these comprehensive effects, NDGA effectively suppresses tumor metastasis in nude mice model. Our findings reveal a novel mechanism underlying the anti-metastasis function of NDGA and indicate the potential value of NDGA in NRP1 targeting therapy for selected subtypes of cancer. PMID:27863391

  6. Harpagoside suppresses IL-6 expression in primary human osteoarthritis chondrocytes.

    PubMed

    Haseeb, Abdul; Ansari, Mohammad Yunus; Haqqi, Tariq M

    2017-02-01

    There is growing evidence in support of the involvement of inflammatory response in the pathogenesis of osteoarthritis (OA). Harpagoside, one of the bioactive components of Harpagophytum procumbens (Hp), has been shown to possess anti-inflammatory properties. Here we used an in vitro model of inflammation in OA to investigate the potential of harpagoside to suppress the production of inflammatory cytokines/chemokines such as IL-6 and matrix degrading proteases. We further investigated the likely targets of harpagoside in primary human OA chondrocytes. OA chondrocytes were pre-treated with harpagoside before stimulation with IL-1β. mRNA expression profile of 92 cytokines/chemokines was determined using TaqMan Human Chemokine PCR Array. Expression levels of selected mRNAs were confirmed using TaqMan assays. Protein levels of IL-6 and MMP-13 were assayed by ELISA and immunoblotting. Total protein levels and phosphorylation of signaling proteins were determined by immunoblotting. Cellular localization of IL-6 and c-Fos was performed by immunofluorescence and confocal microscopy. DNA binding activity of c-FOS/AP-1 was determined by ELISA. Harpagoside significantly altered the global chemokine expression profile in IL-1β-stimulated OA chondrocytes. Expression of IL-6 was highly induced by IL-1β, which was significantly inhibited by pre-treatment of OA chondrocytes with harpagoside. Harpagoside did not inhibit the IL-1β-induced activation of NF-κB and C/EBPβ transcription factors but suppressed the IL-1β-triggered induction, phosphorylation, and DNA binding activity of c-FOS, one of the main components of AP-1 transcription factors. Further, harpagoside significantly inhibited the expression of MMP-13 in OA chondrocytes under pathological conditions. siRNA-mediated knockdown of IL-6 resulted in suppressed expression and secretion of MMP-13 directly linking the role of IL-6 with MMP-13 expression. Taken together, the present study suggests that harpagoside exerts a

  7. Automatic Laser Glare Suppression in Electro-Optical Sensors

    PubMed Central

    Ritt, Gunnar; Eberle, Bernd

    2015-01-01

    Progress in laser technology has led to very compact but nevertheless powerful laser sources. In the visible and near infrared spectral region, lasers of any wavelength can be purchased. Continuous wave laser sources pose an especially serious threat to the human eye and electro-optical sensors due to their high proliferation and easy availability. The manifold of available wavelengths cannot be covered by conventional safety measures like absorption or interference filters. We present a protection concept for electro-optical sensors to suppress dazzling in the visible spectral region. The key element of the concept is the use of a digital micromirror device (DMD) in combination with wavelength multiplexing. This approach allows selective spectral filtering in defined regions of interest in the scene. The system offers the possibility of automatic attenuation of dazzling laser radiation. PMID:25569754

  8. Background suppression in fluorescence nanoscopy with stimulated emission double depletion

    NASA Astrophysics Data System (ADS)

    Gao, Peng; Prunsche, Benedikt; Zhou, Lu; Nienhaus, Karin; Nienhaus, G. Ulrich

    2017-01-01

    Stimulated emission depletion (STED) fluorescence nanoscopy is a powerful super-resolution imaging technique based on the confinement of fluorescence emission to the central subregion of an observation volume through de-excitation of fluorophores in the periphery via stimulated emission. Here, we introduce stimulated emission double depletion (STEDD) as a method to selectively remove artificial background intensity. In this approach, a first, conventional STED pulse is followed by a second, delayed Gaussian STED pulse that specifically depletes the central region, thus leaving only background. Thanks to time-resolved detection we can remove this background intensity voxel by voxel by taking the weighted difference of photons collected before and after the second STED pulse. STEDD thus yields background-suppressed super-resolved images as well as STED-based fluorescence correlation spectroscopy data. Furthermore, the proposed method is also beneficial when considering lower-power, less redshifted depletion pulses.

  9. Ultratrace Uranium Fingerprinting with Isotope Selective Laser Ionization Spectrometry

    SciTech Connect

    Ziegler, Summer L.; Bushaw, Bruce A.

    2008-08-01

    Uranium isotope ratios can provide source information for tracking uranium contamination in a variety of fields, ranging from occupational bioassay to monitoring aftereffects of nuclear accidents. We describe the development of Isotope Selective Laser Ionization Spectrometry (ISLIS) for ultratrace measurement of the minor isotopes 234U, 235U, and 236U with respect to 238U. Optical isotopic selectivity in three-step excitation with single-mode continuous wave lasers is capable of measuring the minor isotopes at relative abundances below 1 ppm, and is not limited by isobaric interferences such as 235UH+ during measurement of 236U. This relative abundance limit approaches the threshold for measurement of uranium minor isotopes with conventional mass spectrometry, typically 10-7, but without mass spectrometric analysis of the laser-created ions. Uranyl nitrate standards from an international blind comparison were used to test analytical performance for different isotopic compositions and with quantities ranging from 11 ng to 10 µg total uranium. Isotopic ratio determination was demonstrated over a linear dynamic range of 7 orders of magnitude with a few percent relative precision and detection limits below 500 fg for the minor isotopes.

  10. Activated chemical defenses suppress herbivory on freshwater red algae.

    PubMed

    Goodman, Keri M; Hay, Mark E

    2013-04-01

    The rapid life cycles of freshwater algae are hypothesized to suppress selection for chemical defenses against herbivores, but this notion remains untested. Investigations of chemical defenses are rare for freshwater macrophytes and absent for freshwater red algae. We used crayfish to assess the palatability of five freshwater red algae relative to a palatable green alga and a chemically defended aquatic moss. We then assessed the roles of structural, nutritional, and chemical traits in reducing palatability. Both native and non-native crayfish preferred the green alga Cladophora glomerata to four of the five red algae. Batrachospermum helminthosum, Kumanoa holtonii, and Tuomeya americana employed activated chemical defenses that suppressed feeding by 30-60 % following damage to algal tissues. Paralemanea annulata was defended by its cartilaginous structure, while Boldia erythrosiphon was palatable. Activated defenses are thought to reduce ecological costs by expressing potent defenses only when actually needed; thus, activation might be favored in freshwater red algae whose short-lived gametophytes must grow and reproduce rapidly over a brief growing season. The frequency of activated chemical defenses found here (three of five species) is 3-20× higher than for surveys of marine algae or aquatic vascular plants. If typical for freshwater red algae, this suggests that (1) their chemical defenses may go undetected if chemical activation is not considered and (2) herbivory has been an important selective force in the evolution of freshwater Rhodophyta. Investigations of defenses in freshwater rhodophytes contribute to among-system comparisons and provide insights into the generality of plant-herbivore interactions and their evolution.

  11. Age-related decline in global form suppression.

    PubMed

    Wiegand, Iris; Finke, Kathrin; Töllner, Thomas; Starman, Kornelija; Müller, Hermann J; Conci, Markus

    2015-12-01

    Visual selection of illusory 'Kanizsa' figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form--an instance of 'global precedence' in visual processing. Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global-local task requiring selection of either a 'global' Kanizsa- or a 'local' non-Kanizsa configuration (in the presence of the respectively other configuration) by analyzing event-related lateralizations (ERLs). Behaviorally, older participants showed a more pronounced global-precedence effect. Electrophysiologically, this effect was accompanied by an early (150-225 ms) 'positivity posterior contralateral' (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing differences in the subsequent (250-500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanizsa, as compared to non-Kanizsa, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages--indicative of older observers having difficulties with disengaging from a global default selection mode and switching to the required local state of attentional resolution.

  12. Coatings of polyethylene glycol for suppressing adhesion between solid microspheres and flat surfaces.

    PubMed

    Upadhyayula, Srigokul; Quinata, Timothy; Bishop, Stephen; Gupta, Sharad; Johnson, Noah Ray; Bahmani, Baharak; Bozhilov, Kliment; Stubbs, Jeremy; Jreij, Pamela; Nallagatla, Pratima; Vullev, Valentine I

    2012-03-20

    This article describes the development and the examination of surface coatings that suppress the adhesion between glass surfaces and polymer microspheres. Superparamagnetic doping allowed for exerting magnetic forces on the microbeads. The carboxyl functionalization of the polymer provided the means for coating the beads with polyethylene glycol (PEG) with different molecular weight. Under gravitational force, the microbeads settled on glass surfaces with similar polymer coatings. We examined the efficacy of removing the beads from the glass surfaces by applying a pulling force of ~1.2 pN. The percent beads remaining on the surface after applying the pulling force for approximately 5 s served as an indication of the adhesion propensity. Coating of PEG with molecular weight ranging between 3 and 10 kDa was essential for suppressing the adhesion. For the particular substrates, surface chemistry and aqueous media we used, coatings of 5 kDa manifested optimal suppression of adhesion: that is, only 3% of the microbeads remained on the surface after applying the pulling magnetic force. When either the glass or the beads were not PEGylated, the adhesion between them was substantial. Addition of a noncharged surfactant, TWEEN, above its critical micelle concentrations (CMCs) suppressed the adhesion between noncoated substrates. The extent of this surfactant-induced improvement of the adhesion suppression, however, did not exceed the quality of preventing the adhesion that we attained by PEGylating both substrates. In addition, the use of surfactants did not significantly improve the suppression of bead-surface adhesion when both substrates were PEGylated. These findings suggest that such surfactant additives tend to be redundant and that covalently grafted coatings of PEGs with selected chain lengths provide sufficient suppression of nonspecific interfacial interactions.

  13. Lenalidomide potentiates CD4(+)CD25(+)Treg-related suppression of lymphoma B-cell proliferation.

    PubMed

    Grygorowicz, Monika Anna; Borycka, Ilona Sara; Nowak, Eliza; Paszkiewicz-Kozik, Ewa; Rymkiewicz, Grzegorz; Błachnio, Katarzyna; Biernacka, Marzena; Bujko, Mateusz; Walewski, Jan; Markowicz, Sergiusz

    2016-03-10

    We have previously found that ex vivo expanded human CD4(+)CD25(+)Treg cells suppress proliferation of lymphoma B-cell lines. Here we demonstrate that the immunomodulatory drug lenalidomide potentiates suppression of lymphoma B-cell proliferation by freshly isolated CD4(+)CD25(+)Tregs, as well as suppression by Tregs expanded polyclonally in the presence of rapamycin from CD4(+)CD25(+)T cells or CD4(+)CD25(+)CD127(lo)T cells. The regulation of lymphoma cell proliferation by Tregs pre-expanded with "third-party" allogeneic MoDCs in the presence of rapamycin was also potentiated by lenalidomide. Lenalidomide contributed to the suppression exerted by Tregs despite concomitant downregulation of Treg proliferation. Lenalidomide did not reduce the suppression of conventional T cells by expanded Tregs. The exposure of polyclonally expanded Tregs to lenalidomide did not significantly alter their phenotype. There was no uniform pattern of lenalidomide effect on Treg-mediated regulation of lymphoma B cells freshly isolated from patients. Freshly isolated lymphoma cells activated with multimeric CD40L and IL-4 to support their survival in vitro varied in their sensitivity to lenalidomide, and the regulatory effect of Tregs on such lymphoma cells ranged from suppression to help in individual patients. Lenalidomide potentiated or attenuated Treg effects on the survival of freshly isolated lymphoma cells. A combination of lenalidomide treatment with adoptive transfer of CD4(+)CD25(+)Tregs or CD4(+)CD25(+)CD127(lo)Tregs expanded ex vivo could be used to suppress proliferation of residual lymphoma in select patients with lymphoma responsive to the regulation by Tregs and sensitive to lenalidomide.

  14. Benchmark enclosure fire suppression experiments - phase 1 test report.

    SciTech Connect

    Figueroa, Victor G.; Nichols, Robert Thomas; Blanchat, Thomas K.

    2007-06-01

    A series of fire benchmark water suppression tests were performed that may provide guidance for dispersal systems for the protection of high value assets. The test results provide boundary and temporal data necessary for water spray suppression model development and validation. A review of fire suppression in presented for both gaseous suppression and water mist fire suppression. The experimental setup and procedure for gathering water suppression performance data are shown. Characteristics of the nozzles used in the testing are presented. Results of the experiments are discussed.

  15. Daidzin inhibits mitochondrial aldehyde dehydrogenase and suppresses ethanol intake of Syrian golden hamsters.

    PubMed

    Keung, W M; Klyosov, A A; Vallee, B L

    1997-03-04

    Daidzin is the major active principle in extracts of radix puerariae, a traditional Chinese medication that suppresses the ethanol intake of Syrian golden hamsters. It is the first isoflavone recognized to have this effect. Daidzin is also a potent and selective inhibitor of human mitochondrial aldehyde dehydrogenase (ALDH-2). To establish a link between these two activities, we have tested a series of synthetic structural analogs of daidzin. The results demonstrate a direct correlation between ALDH-2 inhibition and ethanol intake suppression and raise the possibility that daidzin may, in fact, suppress ethanol intake of golden hamsters by inhibiting ALDH-2. Hamster liver contains not only mitochondrial ALDH-2 but also high concentrations of a cytosolic form, ALDH-1, which is a very efficient catalyst of acetaldehyde oxidation. Further, the cytosolic isozyme is completely resistant to daidzin inhibition. This unusual property of the hamster ALDH-1 isozyme accounts for the fact we previously observed that daidzin can suppress ethanol intake of this species without blocking acetaldehyde metabolism. Thus, the mechanism by which daidzin suppresses ethanol intake in golden hamsters clearly differs from that proposed for the classic ALDH inhibitor disulfiram. We postulate that a physiological pathway catalyzed by ALDH-2, so far undefined, controls ethanol intake of golden hamsters and mediates the antidipsotropic effect of daidzin.

  16. MRI visualization of pathological forms by suppression of normal tissue signals

    NASA Astrophysics Data System (ADS)

    Pirogov, Yuri A.; Anisimov, Nikolai V.; Gubskiy, Leonid V.; Babich, Piotr I.

    2005-04-01

    To improve the visualization and 3D-reconstruction of some pathological formations of the brain, it is offered to use a new method of processing of MR images with suppression of signals from normal tissues. The special attention is offered to be given suppression of signals of fatty tissue, free water and partially bound water of mucous membranes. For such way realization, it is offered to lead two scans with simultaneous suppression of two normal components and to multiply the obtained images. Simultaneous suppression of signals from two normal tissues is realized with the help of pulse sequence twice using inversion-recovery effect. Delays in pulse sequence are selected in accordance with the times of longitudinal relaxation of fat, free water and partially bound water. In comparison with earlier described technique of simultaneous suppression of signals of water and fat, the new method is especially useful at research of pathological formations when the zone of defeat is placed in a zone of nose bosoms. Besides allocation of a zone of defeat, MIP reconstruction becomes simpler. The offered technique well proves at research of tumors and hemorrhages.

  17. Inability to suppress salient distractors predicts low visual working memory capacity.

    PubMed

    Gaspar, John M; Christie, Gregory J; Prime, David J; Jolicœur, Pierre; McDonald, John J

    2016-03-29

    According to contemporary accounts of visual working memory (vWM), the ability to efficiently filter relevant from irrelevant information contributes to an individual's overall vWM capacity. Although there is mounting evidence for this hypothesis, very little is known about the precise filtering mechanism responsible for controlling access to vWM and for differentiating low- and high-capacity individuals. Theoretically, the inefficient filtering observed in low-capacity individuals might be specifically linked to problems enhancing relevant items, suppressing irrelevant items, or both. To find out, we recorded neurophysiological activity associated with attentional selection and active suppression during a competitive visual search task. We show that high-capacity individuals actively suppress salient distractors, whereas low-capacity individuals are unable to suppress salient distractors in time to prevent those items from capturing attention. These results demonstrate that individual differences in vWM capacity are associated with the timing of a specific attentional control operation that suppresses processing of salient but irrelevant visual objects and restricts their access to higher stages of visual processing.

  18. The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors

    PubMed Central

    Fortin, Samantha M; Chartoff, Elena H; Roitman, Mitchell F

    2016-01-01

    Unconditioned rewarding stimuli evoke phasic increases in dopamine concentration in the nucleus accumbens (NAc) while discrete aversive stimuli elicit pauses in dopamine neuron firing and reductions in NAc dopamine concentration. The unconditioned effects of more prolonged aversive states on dopamine release dynamics are not well understood and are investigated here using the malaise-inducing agent lithium chloride (LiCl). We used fast-scan cyclic voltammetry to measure phasic increases in NAc dopamine resulting from electrical stimulation of dopamine cell bodies in the ventral tegmental area (VTA). Systemic LiCl injection reduced electrically evoked dopamine release in the NAc of both anesthetized and awake rats. As some behavioral effects of LiCl appear to be mediated through glucagon-like peptide-1 receptor (GLP-1R) activation, we hypothesized that the suppression of phasic dopamine by LiCl is GLP-1R dependent. Indeed, peripheral pretreatment with the GLP-1R antagonist exendin-9 (Ex-9) potently attenuated the LiCl-induced suppression of dopamine. Pretreatment with Ex-9 did not, however, affect the suppression of phasic dopamine release by the kappa-opioid receptor agonist, salvinorin A, supporting a selective effect of GLP-1R stimulation in LiCl-induced dopamine suppression. By delivering Ex-9 to either the lateral or fourth ventricle, we highlight a population of central GLP-1 receptors rostral to the hindbrain that are involved in the LiCl-mediated suppression of NAc dopamine release. PMID:26211731

  19. Evolutionary Agroecology: the potential for cooperative, high density, weed-suppressing cereals

    PubMed Central

    Weiner, Jacob; Andersen, Sven B; Wille, Wibke K-M; Griepentrog, Hans W; Olsen, Jannie M

    2010-01-01

    Evolutionary theory can be applied to improve agricultural yields and/or sustainability, an approach we call Evolutionary Agroecology. The basic idea is that plant breeding is unlikely to improve attributes already favored by millions of years of natural selection, whereas there may be unutilized potential in selecting for attributes that increase total crop yield but reduce plants’ individual fitness. In other words, plant breeding should be based on group selection. We explore this approach in relation to crop-weed competition, and argue that it should be possible to develop high density cereals that can utilize their initial size advantage over weeds to suppress them much better than under current practices, thus reducing or eliminating the need for chemical or mechanical weed control. We emphasize the role of density in applying group selection to crops: it is competition among individuals that generates the ‘Tragedy of the Commons’, providing opportunities to improve plant production by selecting for attributes that natural selection would not favor. When there is competition for light, natural selection of individuals favors a defensive strategy of ‘shade avoidance’, but a collective, offensive ‘shading’ strategy could increase weed suppression and yield in the high density, high uniformity cropping systems we envision. PMID:25567940

  20. Evolutionary Agroecology: the potential for cooperative, high density, weed-suppressing cereals.

    PubMed

    Weiner, Jacob; Andersen, Sven B; Wille, Wibke K-M; Griepentrog, Hans W; Olsen, Jannie M

    2010-09-01

    Evolutionary theory can be applied to improve agricultural yields and/or sustainability, an approach we call Evolutionary Agroecology. The basic idea is that plant breeding is unlikely to improve attributes already favored by millions of years of natural selection, whereas there may be unutilized potential in selecting for attributes that increase total crop yield but reduce plants' individual fitness. In other words, plant breeding should be based on group selection. We explore this approach in relation to crop-weed competition, and argue that it should be possible to develop high density cereals that can utilize their initial size advantage over weeds to suppress them much better than under current practices, thus reducing or eliminating the need for chemical or mechanical weed control. We emphasize the role of density in applying group selection to crops: it is competition among individuals that generates the 'Tragedy of the Commons', providing opportunities to improve plant production by selecting for attributes that natural selection would not favor. When there is competition for light, natural selection of individuals favors a defensive strategy of 'shade avoidance', but a collective, offensive 'shading' strategy could increase weed suppression and yield in the high density, high uniformity cropping systems we envision.