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. Efficient Isobar Suppression by Photodetachment in a RF Quadrupole Ion Cooler

    SciTech Connect

    Liu, Yuan; Havener, Charles C; Lewis, Thomas L.; Galindo-Uribarri, Alfredo {nmn}; Beene, James R

    2009-01-01

    A highly efficient method for suppressing isobar contaminants in negative radioactive ion beams by photodetachment is demonstrated. A laser beam having the appropriate photon energy is used to selectively neutralize the contaminant if the electron affinity of the contaminant is lower than the electron affinity of the desired radioactive ions. The photodetachment efficiency can be dramatically increased when the laser-ion interaction is made inside a radio frequency quadrupole ion beam cooler where the ion residence time can be a few milliseconds. In off-line experiments with ion beams of stable isotopes, more than 99.9% suppression of S- and O- ions by photodetachment has been obtained. These ions would be the contaminants of desired beams of Cl- and F-, respectively. Under similar conditions no reduction in Cl- and F- ions was observed. The off-line results demonstrate the potential of this technique for on-line purification of a number of interesting radioactive beams and possible applications in accelerator mass spectrometry.

  3. 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.; 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 themore » use of 26AlO-, however further refinement of our system may permit its use in the future.« less

  4. The laser ion source trap for highest isobaric selectivity in online exotic isotope productiona)

    NASA Astrophysics Data System (ADS)

    Schwellnus, F.; Blaum, K.; Catherall, R.; Crepieux, B.; Fedosseev, V.; Gottwald, T.; Kluge, H.-J.; Marsh, B.; Mattolat, C.; Rothe, S.; Stora, T.; Wendt, K.

    2010-02-01

    The improvement in the performance of a conventional laser ion source in the laser ion source and trap (LIST) project is presented, which envisages installation of a repeller electrode and a linear Paul trap/ion guide structure. This approach promises highest isobaric purity and optimum temporal and spatial control of the radioactive ion beam produced at an online isotope separator facility. The functionality of the LIST was explored at the offline test separators of University of Mainz (UMz) and ISOLDE/CERN, using the UMz solid state laser system. Ionization efficiency and selectivity as well as time structure and transversal emittance of the produced ion beam was determined. Next step after complete characterization is the construction and installation of the radiation-hard final trap structure and its first online application.

  5. The laser ion source trap for highest isobaric selectivity in online exotic isotope production.

    PubMed

    Schwellnus, F; Blaum, K; Catherall, R; Crepieux, B; Fedosseev, V; Gottwald, T; Kluge, H-J; Marsh, B; Mattolat, C; Rothe, S; Stora, T; Wendt, K

    2010-02-01

    The improvement in the performance of a conventional laser ion source in the laser ion source and trap (LIST) project is presented, which envisages installation of a repeller electrode and a linear Paul trap/ion guide structure. This approach promises highest isobaric purity and optimum temporal and spatial control of the radioactive ion beam produced at an online isotope separator facility. The functionality of the LIST was explored at the offline test separators of University of Mainz (UMz) and ISOLDE/CERN, using the UMz solid state laser system. Ionization efficiency and selectivity as well as time structure and transversal emittance of the produced ion beam was determined. Next step after complete characterization is the construction and installation of the radiation-hard final trap structure and its first online application. PMID:20192370

  6. High precision Pu isotope ratios using MC-ICPMS equipped with collision-cell technology to suppress U isobaric interferences

    NASA Astrophysics Data System (ADS)

    Granet, M.; Isnard, H.; Nonell, A.; Quidelleur, S.; Chartier, F.

    2009-04-01

    The measurement of Pu isotope ratios is of prime interest in both the environmental and nuclear research fields. First, new chronometric tracers need to be developed in order to understand and quantify the mechanisms and time-scales controlling the landscape evolution since it gives informations on climatic variations. Additionally, the analysis of Pu isotopes after irradiation of 235U is required in the transmutation field in order to determine basic neutronic data such as cross sections and reaction rates. High precision isotope ratios measurements are usually performed with sector field mass spectrometers, either by Thermal Ionization Mass Spectrometry (TIMS) or by Multiple Collection Inductively Coupled Plasma Mass Spectrometry (MC-ICP-MS). One of the major drawbacks in analysing Pu isotopes is the occurrence of U isobaric interferences: 238U-238Pu and 238UH+-239Pu. Here we propose to suppress these interferences by adding reactive gases in the collision-reaction cell of the MC-ICP-MS (Isoprobe, GV Instruments, Manchester, UK). The difference of reactivity for U and Pu towards these gases allows the measurement of Pu isotopes with precision and accuracy similar to those obtained after a previous chemical separation of Pu from U using anion-exchange resin. This study thus confirms that collision-reaction cells are powerful tools to perform isotopic measurements of soils, river sediments or irradiated materials without former systematic chemical separations as U interferences are completely removed in situ. References Granet et al. (2008), Spectrochimica Acta Part B 63, 1309-1314. Moureau et al. (2008), JAAS 23, 1538-1544.

  7. 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.

  8. 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.

  9. Proactive selective response suppression is implemented via the basal ganglia.

    PubMed

    Majid, D S Adnan; Cai, Weidong; Corey-Bloom, Jody; Aron, Adam R

    2013-08-14

    In the welter of everyday life, people can stop particular response tendencies without affecting others. A key requirement for such selective suppression is that subjects know in advance which responses need stopping. We hypothesized that proactively setting up and implementing selective suppression relies on the basal ganglia and, specifically, regions consistent with the inhibitory indirect pathway for which there is scant functional evidence in humans. Consistent with this hypothesis, we show, first, that the degree of proactive motor suppression when preparing to stop selectively (indexed by transcranial magnetic stimulation) corresponds to striatal, pallidal, and frontal activation (indexed by functional MRI). Second, we demonstrate that greater striatal activation at the time of selective stopping correlates with greater behavioral selectivity. Third, we show that people with striatal and pallidal volume reductions (those with premanifest Huntington's disease) have both absent proactive motor suppression and impaired behavioral selectivity when stopping. Thus, stopping goals are used to proactively set up specific basal ganglia channels that may then be triggered to implement selective suppression. By linking this suppression to the striatum and pallidum, these results provide compelling functional evidence in humans of the basal ganglia's inhibitory indirect pathway.

  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. PMID:22274056

  12. 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.

  13. Transient and selective suppression of neural activity with infrared light

    PubMed Central

    Duke, Austin R.; Jenkins, Michael W.; Lu, Hui; McManus, Jeffrey M.; Chiel, Hillel J.; Jansen, E. Duco

    2013-01-01

    Analysis and control of neural circuitry requires the ability to selectively activate or inhibit neurons. Previous work showed that infrared laser light selectively excited neural activity in endogenous unmyelinated and myelinated axons. However, inhibition of neuronal firing with infrared light was only observed in limited cases, is not well understood and was not precisely controlled. Using an experimentally tractable unmyelinated preparation for detailed investigation and a myelinated preparation for validation, we report that it is possible to selectively and transiently inhibit electrically-initiated axonal activation, as well as to both block or enhance the propagation of action potentials of specific motor neurons. Thus, in addition to previously shown excitation, we demonstrate an optical method of suppressing components of the nervous system with functional spatiotemporal precision. We believe this technique is well-suited for non-invasive investigations of diverse excitable tissues and may ultimately be applied for treating neurological disorders. PMID:24009039

  14. 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

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

    PubMed

    Al-Hilal, Taslim A; Chung, Seung Woo; Choi, Jeong Uk; Alam, Farzana; Park, Jooho; Kim, Seong Who; Kim, Sang Yoon; Ahsan, Fakhrul; Kim, In-San; Byun, Youngro

    2016-04-01

    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

  16. 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.

  17. Selective suppression of endothelial cytokine production by progesterone receptor.

    PubMed

    Goddard, Lauren M; Ton, Amy N; Org, Tõnis; Mikkola, Hanna K A; Iruela-Arispe, M Luisa

    2013-01-01

    Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues. PMID:23747964

  18. 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.

  19. The Suppression of Selected Acoustic Noise Frequencies in MRI

    NASA Astrophysics Data System (ADS)

    Shou, Xingxian

    Problems due to Magnetic Resonance Imaging (MRI) acoustic noise have long been an important concern, both in research and clinical applications. A study is made of certain dominant frequencies in the acoustic noise spectrum of the MRI system. Motivated by both spring and string ideas, we investigate whether the contributions to the sound from certain frequencies can be cancelled by the appropriate the gradient pulse sequence design. Ideas for cancelling these frequencies are investigated by carrying out theoretical string calculations. The MRI gradient assembly is modeled as a string and the gradient pulse sequences as a driving force for that string. Analytical results are obtained with different input gradient pulses including boxcars, trapezoids, and multiple trapezoids, along with special "quadratic" pulses. Pulse trains composed of repetitions of these pulse structures are studied. For comparison and to test these ideas, both simulations and experiments are carried out to verify our analytical results for the cancellations of selected frequency peaks. The idea that vibrations resulting from an impulsive force associated with a ramping up of a gradient pulse are shown to be cancelled immediately upon the application of another impulsive force coming from the subsequent appropriately timed ramping down of that pulse is verified both by simulations and experiments. A general approach to suppression of multiple-frequency contributions involving a series of gradient pulses with variable timings is given for the cancellations between pairs of impulse forces. The various examples investigated with string analytics and simulations and the associated MRI experiments are a physical embodiments of general time-invariant linear response theory. The present study also provides a foundation to explain results in previous papers on this subject. The method suggests that a variety of pulse profiles and timing combinations can be used to attenuate important contributions to

  20. Suppressed Conductance From Spin Selection Rules in F-CNT-F Quantum Dots

    NASA Astrophysics Data System (ADS)

    Hartman, Nikolaus; Morgan-Wall, Tyler; Markovic, Nina

    Conductance through a quantum dot can be suppressed due to spin selection rules governing the hoping of an additional electron onto an already-occupied quantum dot. Measurements of this effect in a carbon nanotube quantum dot with ferromagnetic contacts will be presented. Suppressed conductance peaks are observed in the Coulomb diamond plots at zero field and explained using spin selection rules. The pattern of suppressed peaks is observed to change with applied magnetic field as the spin ground state of the occupied quantum dot changes. This work was supported by NSF DMR-1106167.

  1. Riboflavin-binding protein exhibits selective sweet suppression toward protein sweeteners.

    PubMed

    Maehashi, Kenji; Matano, Mami; Kondo, Azusa; Yamamoto, Yasushi; Udaka, Shigezo

    2007-02-01

    Riboflavin-binding protein (RBP) is well known as a riboflavin carrier protein in chicken egg and serum. A novel function of RBP was found as a sweet-suppressing protein. RBP, purified from hen egg white, suppressed the sweetness of protein sweeteners such as thaumatin, monellin, and lysozyme, whereas it did not suppress the sweetness of low molecular weight sweeteners such as sucrose, glycine, D-phenylalanine, saccharin, cyclamate, aspartame, and stevioside. Therefore, the sweet-suppressing activity of RBP was apparently selective to protein sweeteners. The sweet suppression by RBP was independent of binding of riboflavin with its molecule. Yolk RBP, with minor structural differences compared with egg white RBP, also elicited a weaker sweet suppression. However, other commercially available proteins including ovalbumin, ovomucoid, beta-lactogloblin, myoglobin, and albumin did not substantially alter the sweetness of protein sweeteners. Because a prerinse with RBP reduced the subsequent sweetness of protein sweeteners, whereas the enzymatic activity of lysozyme and the elution profile of lysozyme on gel permeation chromatography were not affected by RBP, it is suggested that the sweet suppression is caused by an interaction of RBP with a sweet taste receptor rather than with the protein sweeteners themselves. The selectivity in the sweet suppression by RBP is consistent with the existence of multiple interaction sites within a single sweet taste receptor.

  2. 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...

  3. 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. PMID:27139323

  4. 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.

  5. 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

  6. High-resolution enabled 12-plex DiLeu isobaric tags for quantitative proteomics.

    PubMed

    Frost, Dustin C; Greer, Tyler; Li, Lingjun

    2015-02-01

    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 (13)C, (15)N, and (2)H 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-MS(2)) analysis on an Orbitrap Elite mass spectrometer. PMID:25405479

  7. 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

  8. Selective suppression of high order axial modes of the gyrotron backward-wave oscillator

    SciTech Connect

    Pao, K. F.; Fan, C. T.; Chang, T. H.; Chiu, C. C.; Chu, K. R.

    2007-09-15

    Selective suppression of high order axial modes of the gyrotron backward-wave oscillator (gyro-BWO) is investigated in theory and in experiment. The gyro-BWO interaction is much more efficient in a down-tapered interaction structure, while it is also more susceptible to the problem of axial mode competition in such a structure. Because higher order axial modes (at a higher oscillation frequency) penetrate deeper into the interaction structure, application of distributed wall loss at the downstream end of the interaction structure is shown to be effective for selective suppression of these modes with minor effects on the efficiency of the desired fundamental axial mode. A stable gyro-BWO operating in a single mode throughout the entire beam pulse is demonstrated on the basis of this principle. Theoretical and experimental results are found to be in good agreement.

  9. 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…

  10. 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.

  11. Directionally selective retinal ganglion cells suppress luminance responses during natural viewing

    PubMed Central

    Im, Maesoon; Fried, Shelley I.

    2016-01-01

    The ON-OFF directionally selective cells of the retina respond preferentially to movement in a preferred direction, but under laboratory conditions they are also sensitive to changes in the luminance of the stationary stimulus. If the response of these neurons contains information about both direction and luminance downstream neurons are faced with the challenge of extracting the motion component, a computation that may be difficult under certain viewing conditions. Here, we show that during natural viewing the response to luminance is suppressed, leaving a relatively pure motion signal that gets transmitted to the brain. PMID:27759086

  12. Dioxonaphthoimidazoliums are Potent and Selective Rogue Stem Cell Clearing Agents with SOX2-Suppressing Properties.

    PubMed

    Ho, Si-Han Sherman; Ali, Azhar; Ng, Yi-Cheng; Lam, Kuen-Kuen Millie; Wang, Shu; Chan, Woon-Khiong; Chin, Tan-Min; Go, Mei-Lin

    2016-09-01

    Pluripotent stem cells are uniquely positioned for regenerative medicine, but their clinical potential can only be realized if their tumorigenic tendencies are decoupled from their pluripotent properties. Deploying small molecules to remove remnant undifferentiated pluripotent cells, which would otherwise transform into teratomas and teratomacarcinomas, offers several advantages over non-pharmacological methods. Dioxonapthoimidazolium YM155, a survivin suppressant, induced selective and potent cell death of undifferentiated stem cells. Herein, the structural requirements for stemotoxicity were investigated and found to be closely aligned with those essential for cytotoxicity in malignant cells. There was a critical reliance on the quinone and imidazolium moieties but a lesser dependence on ring substituents, which served mainly to fine-tune activity. Several potent analogues were identified which, like YM155, suppressed survivin and decreased SOX2 in stem cells. The decrease in SOX2 would cause an imbalance in pluripotent factors that could potentially prompt cells to differentiate and hence decrease the risk of aberrant teratoma formation. As phosphorylation of the NF-κB p50 subunit was also suppressed, the crosstalk between phospho-p50, SOX2, and survivin could implicate a causal role for NF-κB signaling in mediating the stem cell clearing properties of dioxonaphthoimidazoliums.

  13. Intercellular redistribution of cAMP underlies selective suppression of cancer cell growth by connexin26.

    PubMed

    Chandrasekhar, Anjana; Kalmykov, Edward A; Polusani, Srikanth R; Mathis, Sandra A; Zucker, Shoshanna N; Nicholson, Bruce J

    2013-01-01

    Connexins (Cx), which constitute gap junction intercellular channels in vertebrates, have been shown to suppress transformed cell growth and tumorigenesis, but the mechanism(s) still remain largely speculative. Here, we define the molecular basis by which Cx26, but less frequently Cx43 or Cx32, selectively confer growth suppression on cancer cells. Functional intercellular coupling is shown to be required, producing partial blocks of the cell cycle due to prolonged activation of several mitogenic kinases. PKA is both necessary and sufficient for the Cx26 induced growth inhibition in low serum and the absence of anchorage. Activation of PKA was not associated with elevated cAMP levels, but appeared to result from a redistribution of cAMP throughout the cell population, eliminating the cell cycle oscillations in cAMP required for efficient cell cycle progression. Cx43 and Cx32 fail to mediate this redistribution as, unlike Cx26, these channels are closed during the G2/M phase of the cell cycle when cAMP levels peak. Comparisons of tumor cell lines indicate that this is a general pattern, with growth suppression by connexins occurring whenever cAMP oscillates with the cell cycle, and the gap junction remain open throughout the cell cycle. Thus, gap junctional coupling, in the absence of any external signals, provides a general means to limit the mitotic rate of cell populations. PMID:24312655

  14. Suppression of Experimental Arthritis and Associated Bone Loss by a Tissue-Selective Estrogen Complex.

    PubMed

    Andersson, Annica; Bernardi, Angelina I; Nurkkala-Karlsson, Merja; Stubelius, Alexandra; Grahnemo, Louise; Ohlsson, Claes; Carlsten, Hans; Islander, Ulrika

    2016-03-01

    In addition to the systemic inflammation present in rheumatoid arthritis (RA), decreased estradiol levels in postmenopausal RA patients further accelerate bone loss in these patients. The tissue-selective estrogen complex (TSEC), an estrogen combined with a selective estrogen receptor modulator, is a new hormone replacement therapy option. The first approved TSEC, containing conjugated estrogens and bazedoxifene (BZA), reduces menopausal symptoms and prevents osteoporosis with an improved safety profile compared with conventional hormone replacement therapy. Previous studies have shown that estrogens strongly inhibit experimental arthritis whereas BZA is mildly suppressive. In this study the antiarthritic potential of combined BZA and estradiol is explored for the first time. Female ovariectomized DBA/1 mice were subjected to collagen-induced arthritis, an experimental postmenopausal RA model, and treated with BZA, 17β-estradiol (E2), combined BZA and E2 (BZA/E2), or vehicle. BZA/E2 suppressed arthritis severity and frequency, synovitis, and joint destruction, equally efficient as E2 alone. Unwanted estrogenic proliferative effects on the endometrium were blocked by the addition of BZA, determined by collecting uterine weights. Bone mineral density was measured by peripheral quantitative computed tomography, and all treatments protected collagen-induced arthritis mice from both trabecular and cortical bone loss. Moreover, BZA/E2, but not E2 alone, inhibited preosteoclast formation and reduced serum anticollagen type II antibodies. In conclusion, a TSEC, herein combined BZA/E2, suppresses experimental arthritis and prevents associated bone loss as efficiently as E2 alone but with minimal uterine effects, highlighting the need for clinical trials that evaluate the addition of a TSEC to conventional postmenopausal RA treatment. PMID:26745543

  15. Identification of a novel GPR81-selective agonist that suppresses lipolysis in mice without cutaneous flushing.

    PubMed

    Sakurai, Taku; Davenport, Richard; Stafford, Stuart; Grosse, Johannes; Ogawa, Kazumasa; Cameron, Jennifer; Parton, Laura; Sykes, Andy; Mack, Stephen; Bousba, Sarah; Parmar, Alka; Harrison, David; Dickson, Louise; Leveridge, Mathew; Matsui, Junji; Barnes, Matt

    2014-03-15

    GPR81, which exhibits a high degree of homology with GPR109a, has been recently identified as a lactate receptor. Similar to GPR109a, the activation of GPR81 by lactate suppresses lipolysis, suggesting that GPR81 may be a potential drug target for treating dyslipidemia. In addition, the fact that GPR81 is expressed only in adipocytes, whereas GPR109a is expressed in various tissues and cells, including Langerhans cells, which are considered responsible for flushing, indicates that targeting GPR81 could lead to the development of antidyslipidemia agents with a reduced risk of this side effect. However, the pharmacological role of GPR81 remains largely unclear, mainly because of the lack of potent and selective surrogate GPR81 agonists suitable for in vivo studies. In the present study, we showed that lactate-induced suppression of lipolysis in explants of white adipose tissue (WAT) depends on the presence of GPR81. We also performed high-throughput screening (HTS) and identified four novel chemical clusters as GPR81 agonists. Chemical optimization of aminothiazole derivatives led to the discovery of a lead compound with improved potency. The compound inhibited lipolysis in differentiated 3T3-L1 adipocytes. Finally, intraperitoneal administration of this compound suppressed lipolysis in mice at doses that did not cause cutaneous flushing. This is the first description of a 50nM GPR81 selective agonist with in vivo efficacy, without the side effect, i.e., flushing. These results suggest that GPR81 is an attractive drug target for treating dyslipidemia without the risk of flushing.

  16. 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.

  17. Suppressant effects of selective 5-HT2 antagonists on rapid eye movement sleep in rats.

    PubMed

    Tortella, F C; Echevarria, E; Pastel, R H; Cox, B; Blackburn, T P

    1989-04-24

    The effects of the novel, highly selective serotonin-2 (5-HT2) antagonists, ICI 169,369 and ICI 170,809, on 24 h EEG sleep-wake activity were studied in the rat. Both compounds caused a dose-related increase in the latency to rapid eye movement sleep (REMS) and significantly suppressed cumulative REMS time up to 12 h postinjection. In contrast, neither drug disrupted slow-wave sleep continuity in as much as the latency to non-REMS (NREMS) and cumulative NREMS time were unchanged. However, at the highest dose tested (20 mg/kg) ICI 170,809 did produce a significant increase in total NREMS time during the second half of the sleep-awake cycle. These results demonstrate effects of selective 5-HT2 antagonists on sleep in rats which appear to be specific for REMS behavior, suggesting that the priming influence of serotonin on REMS may involve 5-HT2 receptor subtypes. The relationship between the REMS suppressant actions of these compounds and their consideration as therapeutic agents in depression is discussed.

  18. Selection for increased mass-independent maximal metabolic rate suppresses innate but not adaptive immune function

    PubMed Central

    Downs, Cynthia J.; Brown, Jessi L.; Wone, Bernard; Donovan, Edward R.; Hunter, Kenneth; Hayes, Jack P.

    2013-01-01

    Both appropriate metabolic rates and sufficient immune function are essential for survival. Consequently, eco-immunologists have hypothesized that animals may experience trade-offs between metabolic rates and immune function. Previous work has focused on how basal metabolic rate (BMR) may trade-off with immune function, but maximal metabolic rate (MMR), the upper limit to aerobic activity, might also trade-off with immune function. We used mice artificially selected for high mass-independent MMR to test for trade-offs with immune function. We assessed (i) innate immune function by quantifying cytokine production in response to injection with lipopolysaccharide and (ii) adaptive immune function by measuring antibody production in response to injection with keyhole limpet haemocyanin. Selection for high mass-independent MMR suppressed innate immune function, but not adaptive immune function. However, analyses at the individual level also indicate a negative correlation between MMR and adaptive immune function. By contrast BMR did not affect immune function. Evolutionarily, natural selection may favour increasing MMR to enhance aerobic performance and endurance, but the benefits of high MMR may be offset by impaired immune function. This result could be important in understanding the selective factors acting on the evolution of metabolic rates. PMID:23303541

  19. TAK-603 selectively suppresses Th1-type cytokine production and inhibits the progression of adjuvant arthritis.

    PubMed Central

    Ohta, Y; Yamane, M; Sohda, T; Makino, H

    1997-01-01

    We have shown that TAK-603, a new anti-rheumatic drug, is more effective in animal models in which cellular immunity plays a central role. Here, we studied the effect of the drug on Th1 cytokines, which are dominantly produced in this type of immune reaction, in an in vitro system and an in vivo model. We established Th1- and Th2-dominant T-cell lines, and studied the effect of TAK-603 on their cytokine production. Th1 cell lines were BALB/c mouse allo-reactive T cells and C57BL mouse mite antigen-reactive T cells, and the Th2 cell line was BALB/c mouse ovalbumin-reactive T cells. TAK-603 suppressed the production of Th1 cytokines [interferon-gamma (IFN-gamma) and interleukin-2 (IL-2)] and not that of Th2 cytokines (IL-4, IL-5) in these cell lines. Furthermore, selective suppression of Th1 cytokine production was also observed in the T-cell clones obtained from the ovalbumin-reactive T-cell line. To investigate the effect on cytokine production in animal models of arthritis, we analysed the expression of cytokine messenger RNA using reverse transcription-polymerase chain reaction. In adjuvant arthritis rats, Th1-dominant cytokine production was observed both in the arthritic joint and the spleen, and the time-course paralleled the progression of arthritis. On the other hand, in type-II collagen-induced arthritis, in which TAK-603 has little effect, Th1-dominant cytokine production was not observed and Th2 cytokines were shown to be more important. The adjuvant arthritis rats treated with TAK-603 (6.25 mg/kg/day, per os) showed significantly lower cytokine mRNA expression both locally and systemically. These data suggest that TAK-603 selectively suppresses Th1 cytokine production, which is consistent with its effect on cellular immunity in animal models. Images Figure 4 PMID:9370927

  20. Selective suppression of plasticity in amygdala inputs from temporal association cortex by the external capsule.

    PubMed

    Morozov, Alexei; Sukato, Daniel; Ito, Wataru

    2011-01-01

    GABAergic neurons in the external capsule (EC) provide feedforward inhibition in the lateral amygdala (LA), but how EC affects synaptic transmission and plasticity in inputs from specific cortical areas remains unknown; this is because axonal fibers from different cortical areas are intermingled in the amygdala and cannot be activated selectively using conventional electrical stimulation. Here, we achieved selective activation of fibers from the temporal association cortex (TeA) or the anterior cingulate cortex (ACC) by using channelrhodopsin-2. Long-term potentiation (LTP) in the TeA-LA pathway, which runs through EC, was enabled by cutting connections between EC and LA or by blocking GABA(A) receptor-mediated transmission. In contrast, LTP in the ACC-LA pathway, which bypasses EC, was GABA(A) receptor independent. The EC transection shifted balance between inhibitory and excitatory responses in the TeA-LA pathway toward excitation, but had no effect on the ACC-LA pathway. Thus, EC provides pathway-specific suppression of amygdala plasticity. PMID:21209220

  1. Selective electrochemical reactivity of rutile VO2 towards the suppression of metal-insulator transition

    NASA Astrophysics Data System (ADS)

    Singh, Sujay; Abtew, Tesfaye A.; Horrocks, Gregory; Kilcoyne, Colin; Marley, Peter M.; Stabile, Adam A.; Banerjee, Sarbajit; Zhang, Peihong; Sambandamurthy, G.

    2016-03-01

    We demonstrate through electrolyte gating measurements of a single nanobeam that the rultile phase of VO2 is electrochemically more reactive than the monoclinic phase. Our results show that the complete suppression of the metal-insulator transition and stabilization of the metallic phase is possible when gate voltage is applied in the rutile metallic phase. The results are discussed based on the formation of oxygen vacancies wherein accommodation of a high concentration of vacancies in the rutile phase selectively stabilizes it by disrupting dimerization of adjacent V-V pairs required for a transition to the monoclinic phase. The creation of oxygen vacancies is proposed to proceed through the oxidation of the electrolyte. Raman spectroscopy data suggest surface metallization upon electrolyte gating with an initial coexistence of insulating monoclinic and metallic domains. The selective electrochemical reactivity of the rutile phase and the resulting defect-induced stabilization of this phase across a vastly expanded temperature window suggest a facile defect engineering route to tune electronic phase transitions.

  2. Suppression of cancer-initiating cells and selection of adipose-derived stem cells cultured on biomaterials having specific nanosegments.

    PubMed

    Kao, Ta-Chun; Lee, Henry Hsin-Chung; Higuchi, Akon; Ling, Qing-Dong; Yu, Wan-Chun; Chou, Yu-Hsuan; Wang, Pin-Yu; Suresh Kumar, S; Chang, Yu; Hung Chen, Yung; Chang, Yung; Chen, Da-Chung; Hsu, Shih-Tien

    2014-04-01

    Cancer-initiating cells [cancer stem cells (CSCs)] in colon cancer cells can be selectively suppressed when they are cultured on Pluronic (nanosegment)-grafted dishes, whereas CSCs are maintained on conventional tissue culture dishes and extracellular matrix-coated dishes. CSCs persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumorigenic clones. The purification or depletion (suppression) of CSCs should be useful for analyzing CSC characteristics and for clinical application. CSCs can be selectively suppressed from colon cancer cells containing adipose-derived stem cells (ADSCs) on Pluronic-grafted dishes, while ADSCs remain on the dishes. ADSCs on Pluronic-grafted dishes after the suppression of the CSCs can differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, and neuronal cells. The CSCs and ADSCs exhibited different characteristics. The selection of ADSCs was possible on Pluronic-grafted dishes that suppressed the CSCs from the fat tissues of cancer patients (i.e., cell-sorting dishes), which was explained by specific biomedical characteristics of Pluronic. PMID:24039170

  3. 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.

  4. An exotic invasive plant selects for increased competitive tolerance, but not competitive suppression, in a native grass.

    PubMed

    Fletcher, Rebecca A; Callaway, Ragan M; Atwater, Daniel Z

    2016-06-01

    Exotic invasive plants can exert strong selective pressure for increased competitive ability in native plants. There are two fundamental components of competitive ability: suppression and tolerance, and the current paradigm that these components have equal influences on a species' overall competitive ability has been recently questioned. If these components do not have equal influences on overall ability, then selection on competitive tolerance and suppression may be disproportionate. We used naturally invaded communities to study the effects of selection caused by an invasive forb, Centaurea stoebe, on a native grass, Pseudoroegneria spicata. P. spicata plants were harvested from within dense C. stoebe patches and from nearby uninvaded areas, divided clonally into replicates, then transplanted into a common garden where they grew alone or competed with C. stoebe. We found that P. spicata plants collected from within C. stoebe patches were significantly more tolerant of competition with C. stoebe than P. spicata plants collected from uninvaded areas, but plants from inside invaded patches were not superior at suppressing C. stoebe. These results are consistent with the hypothesis that strong competitors may select for tolerance to competition more than for the ability to suppress neighbors. This has important implications for how native plant communities may respond to invasion over time, and how invasive and native species may ultimately coexist. PMID:26897605

  5. 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

  6. 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.

  7. 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. PMID:22112924

  8. 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.

  9. 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.

  10. Sampling the isothermal-isobaric ensemble by Langevin dynamics.

    PubMed

    Gao, Xingyu; Fang, Jun; Wang, Han

    2016-03-28

    We present a new method of conducting fully flexible-cell molecular dynamics simulation in isothermal-isobaric ensemble based on Langevin equations of motion. The stochastic coupling to all particle and cell degrees of freedoms is introduced in a correct way, in the sense that the stationary configurational distribution is proved to be consistent with that of the isothermal-isobaric ensemble. In order to apply the proposed method in computer simulations, a second order symmetric numerical integration scheme is developed by Trotter's splitting of the single-step propagator. Moreover, a practical guide of choosing working parameters is suggested for user specified thermo- and baro-coupling time scales. The method and software implementation are carefully validated by a numerical example. PMID:27036433

  11. 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.

  12. A general method for diagonal peak suppression in homonuclear correlated NMR spectra by spatially and frequency selective pulses☆

    PubMed Central

    Glanzer, Simon; Schrank, Evelyne; Zangger, Klaus

    2013-01-01

    Homonuclear two- and multidimensional NMR spectra are standard experiments for the structure determination of small to medium-sized molecules. In the large majority of homonuclear correlated spectra the diagonal contains the most intense peaks. Cross-peaks near the diagonal could overlap with huge tails of diagonal peaks and can therefore be easily overlooked. Here we present a general method for the suppression of peaks along the diagonal in homonuclear correlated spectra. It is based on a spatially selective excitation followed by the suppression of magnetization which has not changed the frequency during the mixing process. In addition to the auto correlation removal, these experiments are also less affected by magnetic field inhomogeneities due to the slice selective excitation, which on the other side leads to a reduced intensity compared to regular homonuclear correlated spectra. PMID:23665403

  13. 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.

  14. 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.

  15. Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation.

    PubMed

    Huang, Zhi H; Reardon, Catherine A; Getz, Godfrey S; Maeda, Nobuyo; Mazzone, Theodore

    2015-02-01

    apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE levels. These mice had less adipose tissue with smaller adipocytes containing fewer lipids, but no change in adipocyte number compared with control mice. Adipocyte TG synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced, but adiponectin, PGC-1, and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin, and glucose levels, and glucose and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart, and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state.

  16. 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. PMID:12704763

  17. 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.

  18. 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.

  19. 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.

  20. Comparison of two channel selection criteria for noise suppression in cochlear implants

    PubMed Central

    Hazrati, Oldooz; Loizou, Philipos C.

    2013-01-01

    The performance of current channel selection criteria used in cochlear implant (CI) devices (e.g., maximum selection criterion used in ACE) degrades significantly in the presence of noise. In noisy backgrounds, coding strategies that select the “right” channels for stimulation could potentially produce substantial improvements in intelligibility. In this study, the performance of two alternative channel selection criteria is assessed in terms of intelligibility and subjective quality with CI users in noise. The performance is compared against that of the maximum selection scheme employed in the ACE strategy (comparison is also made with the CIS strategy). Sentences were presented to seven CI users in speech weighted noise (−5, 0, and 5 dB SNR). Both channel selection criteria were implemented under ideal conditions where a priori knowledge of the target and masker was assumed. This was done to assess the full potential benefit of selecting the “right” channels for stimulation in noisy backgrounds. Substantial intelligibility improvement relative to the CI users' daily strategy (i.e., ACE or CIS) was achieved with the two different channel selection criteria under all noisy conditions considered. No significant difference in subjective quality of noisy speech processed by the two channel selection criteria was observed. PMID:23464031

  1. Age-related differences in enhancement and suppression of neural activity underlying selective attention in matched young and old adults.

    PubMed

    Haring, A E; Zhuravleva, T Y; Alperin, B R; Rentz, D M; Holcomb, P J; Daffner, K R

    2013-03-01

    Selective attention reflects the top-down control of sensory processing that is mediated by enhancement or inhibition of neural activity. ERPs were used to investigate age-related differences in neural activity in an experiment examining selective attention to color under Attend and Ignore conditions, as well as under a Neutral condition in which color was task-irrelevant. We sought to determine whether differences in neural activity between old and young adult subjects were due to differences in age rather than executive capacity. Old subjects were matched to two groups of young subjects on the basis of neuropsychological test performance: one using age-appropriate norms and the other using test scores not adjusted for age. We found that old and young subject groups did not differ in the overall modulation of selective attention between Attend and Ignore conditions, as indexed by the size of the anterior Selection Positivity. However, in contrast to either young adult group, old subjects did not exhibit reduced neural activity under the Ignore relative to Neutral condition, but showed enhanced activity under the Attend condition. The onset and peak of the Selection Positivity occurred later for old than young subjects. In summary, older adults execute selective attention less efficiently than matched younger subjects, with slowed processing and failed suppression under Ignore. Increased enhancement under Attend may serve as a compensatory mechanism.

  2. The Oak Ridge Isobar and Isomer Separator and Spectrometer (ORISS)

    NASA Astrophysics Data System (ADS)

    Piechaczek, Andreas; Batchelder, J. C.; Carter, H. K.; Reed, C. A.; Yair, O.; Shchepunov, V.; Zganjar, E. F.; Blalock, A.; Berridge, S.; Todd, R.; Armstrong, G.; Omoumi, K.; Fleury, A. R.; Hu, Y.

    2011-04-01

    ORISS is an electrostatic high-resolution isobar and isomer spectrometer and separator to provide pure beams for decay spectroscopy of exotic nuclei. It consists of an RFQ, low emittance, ion cooler and buncher, a multi-pass time-of-flight spectrometer, and a time-of-flight detector to register time-of-flight spectra, or a Bradbury Nielsen (BN) gate to physically separate isobars and isomers of interest. Presently, ORISS uses an off-line ion source. Ion bunches as short as 8 ns FWHM have been produced in the buncher, and a BN gate with transition times open/closed of 15 ns was built. These results of individual component tests together with ion optical calculations predict a mass resolving power of 400,000 and transmission of 50% for the completed system. In the future, radioactive ions from the Holifield Radioactive Ion Beam Facility at ORNL will be injected. Results of first test measurements of the complete off-line system will be presented.

  3. Isobaric (gasless) laparoscopic liver and kidney biopsy in standing steers

    PubMed Central

    Chiesa, O. Alberto; von Bredow, Jurgen; Li, Hui; Smith, Michelle

    2009-01-01

    The purpose of the current study was to investigate the suitability of an isobaric laparoscopic procedure, using a single port, for obtaining serial kidney and liver biopsy samples from standing steers. The samples were used in support of a pharmacokinetic tissue–fluid correlation study. Laparoscopic access was performed 3 times in each of 8 healthy Holstein steers, alternating from the right side to the left side and then to the right side again. The surgery was performed in standing stocks after the animals were given 3 doses of sulfadimethoxine sulfate intravenously and fasted for at least 18 h. Sedation and analgesia were achieved with acepromazine and xylazine. Lidocaine 2% was injected at the center of the paralumbar fossa (left or right), and an incision was made for introduction of a trocar–cannula assembly. Room air was allowed to enter the abdomen through the cannula at the time of insertion. Once the peritoneal cavity was reached, an operating endoscope was inserted. No pressurized insufflation was performed. A biopsy forceps was introduced into the operating channel of the endoscope to obtain a 100-mg kidney or liver sample. No complications were encountered. The 24 laparoscopic procedures provided 24 kidney and 16 liver samples. The results suggest that the isobaric (gasless) single-port laparoscopic technique is feasible for kidney and liver biopsy on standing steers. The procedure can be performed in a reliable and efficient manner in the sedated standing bovine. PMID:19337395

  4. 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

  5. Selective impact of CDK4/6 suppression on patient-derived models of pancreatic cancer

    PubMed Central

    Witkiewicz, Agnieszka K.; Borja, Nicholas A.; Franco, Jorge; Brody, Jonathan R.; Yeo, Charles J.; Mansour, John; Choti, Michael A.; McCue, Peter; Knudsen, Erik S.

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDA) harbors an exceedingly poor prognosis, and is generally considered a therapy-recalcitrant disease due to poor response to conventional chemotherapy coupled with non-actionable genetic drivers (e.g. KRAS mutations). However, PDA frequently loses p16ink4a, thereby leading to deregulation of CDK4/6. Surprisingly, in established cell models and xenografts, CDK4/6 inhibition has a modest effect on proliferation and resistance develops rapidly. To determine if such weak response was an intrinsic feature of PDA, we developed primary tumor explants that maintain the tumor environment and recapitulate feuture of primary PDA. The CDK4/6 inhibitor PD-0332991 was highly efficient at suppressing proliferation in 14 of the 15 explants. In the single resistant explant, we identified the rare loss of the RB tumor suppressor as the basis for resistance. Patient-derived xenografts (PDXs) were developed in parallel, and unlike the xenografts emerging from established cell lines, the PDXs maintained the histoarchitecture of the primary tumor. These PDXs were highly sensitive to CDK4/6 inhibition, yielding a complete suppression of PDA proliferation. Together, these data indicate that primary PDA is sensitive to CDK4/6 inhibition, that specific biomarkers can delineate intrinsic resistance, and that established cell line models may not represent an adequate means for evaluating therapeutic sensitivities. PMID:26158861

  6. Selective impact of CDK4/6 suppression on patient-derived models of pancreatic cancer.

    PubMed

    Witkiewicz, Agnieszka K; Borja, Nicholas A; Franco, Jorge; Brody, Jonathan R; Yeo, Charles J; Mansour, John; Choti, Michael A; McCue, Peter; Knudsen, Erik S

    2015-06-30

    Pancreatic ductal adenocarcinoma (PDA) harbors an exceedingly poor prognosis, and is generally considered a therapy-recalcitrant disease due to poor response to conventional chemotherapy coupled with non-actionable genetic drivers (e.g. KRAS mutations). However, PDA frequently loses p16ink4a, thereby leading to deregulation of CDK4/6. Surprisingly, in established cell models and xenografts, CDK4/6 inhibition has a modest effect on proliferation and resistance develops rapidly. To determine if such weak response was an intrinsic feature of PDA, we developed primary tumor explants that maintain the tumor environment and recapitulate feuture of primary PDA. The CDK4/6 inhibitor PD-0332991 was highly efficient at suppressing proliferation in 14 of the 15 explants. In the single resistant explant, we identified the rare loss of the RB tumor suppressor as the basis for resistance. Patient-derived xenografts (PDXs) were developed in parallel, and unlike the xenografts emerging from established cell lines, the PDXs maintained the histoarchitecture of the primary tumor. These PDXs were highly sensitive to CDK4/6 inhibition, yielding a complete suppression of PDA proliferation. Together, these data indicate that primary PDA is sensitive to CDK4/6 inhibition, that specific biomarkers can delineate intrinsic resistance, and that established cell line models may not represent an adequate means for evaluating therapeutic sensitivities.

  7. 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.

  8. 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.

  9. Urinary bladder instability induced by selective suppression of the murine small conductance calcium-activated potassium (SK3) channel

    PubMed Central

    Herrera, Gerald M; Pozo, Maria J; Zvara, Peter; Petkov, Georgi V; Bond, Chris T; Adelman, John P; Nelson, Mark T

    2003-01-01

    Small conductance, calcium-activated potassium (SK) channels have an important role in determining the excitability and contractility of urinary bladder smooth muscle. Here, the role of the SK isoform SK3 was examined by altering expression levels of the SK3 gene using a mouse model that conditionally overexpresses SK3 channels (SK3T/T). Prominent SK3 immunostaining was found in both the smooth muscle (detrusor) and urothelium layers of the urinary bladder. SK currents were elevated 2.4-fold in isolated myocytes from SK3T/T mice. Selective suppression of SK3 expression by dietary doxycycline (DOX) decreased SK current density in isolated myocytes, increased phasic contractions of isolated urinary bladder smooth muscle strips and exposed high affinity effects of the blocker apamin of the SK isoforms (SK1–3), suggesting an additional participation from SK2 channels. The role of SK3 channels in urinary bladder function was assessed using cystometry in conscious, freely moving mice. The urinary bladders of SK3T/T had significantly greater bladder capacity, and urine output exceeded the infused saline volume. Suppression of SK3 channel expression did not alter filling pressure, threshold pressure or bladder capacity, but micturition pressure was elevated compared to control mice. However, SK3 suppression did eliminate excess urine production and caused a marked increase in non-voiding contractions. The ability to examine bladder function in mice in which SK3 channel expression is selectively altered reveals that these channels have a significant role in the control of non-voiding contractions in vivo. Activation of these channels may be a therapeutic approach for management of non-voiding contractions, a condition which characterizes many types of urinary bladder dysfunctions including urinary incontinence. PMID:12813145

  10. 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.

  11. 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.

  12. Neural repetition suppression: evidence for perceptual expectation in object-selective regions

    PubMed Central

    Mayrhauser, Lisa; Bergmann, Jürgen; Crone, Julia; Kronbichler, Martin

    2014-01-01

    It is an established finding that neuronal activity is decreased for repeated stimuli. Recent studies revealed that repetition suppression (RS) effects are altered by manipulating the probability with which stimuli are repeated. RS for faces is more pronounced when the probability of repetition is high than when it is low. This response pattern is interpreted with reference to the predictive coding (PC) account, which assumes that RS is influenced by top-down expectations. Recent findings challenge the generality of PC accounts of RS by showing repetition probability does not modulate RS for other visual stimuli than faces. However, a number of findings on visual processing are in line with PC. Thus, the influence of repetition probability on RS effects during object processing requires careful reinvestigations. In the present fMRI study, object pictures were presented in a high (75%) or low (25%) repetition probability context. We found increased RS in the high-probability context compared to the low-probability context in the left lateral occipital complex (LOC). The dorsal-caudal and the ventral-anterior subdivisions of the LOC revealed similar neuronal responses. These results indicate that repetition probability effects can be found for other visual objects than faces and provide evidence in favor of the PC account. PMID:24860461

  13. A scheme for noise suppression and spectral enhancement of speech to alleviate speech reception problems from loss of frequency selectivity

    NASA Astrophysics Data System (ADS)

    Lyzenga, Johannes; Festen, Joost M.; Houtgast, Tammo

    2002-05-01

    Even after sufficient amplification, hearing-impaired listeners often experience problems in understanding speech under noisy conditions. This may be caused by suprathreshold deficits such as loss of compression and reduced frequency selectivity. In this project we investigate a scheme in which speech and noise are processed before presentation to try and alleviate intelligibility problems caused by reduced frequency selectivity. The scheme contains three strategies, one in which the peak-to-valley ratios of selected modulations in the speech spectrum are enlarged, a second in which the overall speech spectrum is modified, and a third in which noise is suppressed before the two enhancement steps. An overlap-and-add (OLA) algorithm is used in the implementation. The effect of the speech processing is evaluated by measuring speech-reception thresholds (SRT) for sentences in speech noise, estimating the signal-to-noise ratio at which listeners can correctly reproduce 50% of presented sentences. Hearing-impaired and normal-hearing listeners were used. To simulate the hearing impairment resulting from a loss of frequency selectivity, we spectrally smeared the stimuli presented to the normal-hearing listeners. We found that the preprocessing scheme achieved a modest improvement of nearly 2 dB in the SRT for normal-hearing listeners. Data for hearing-impaired listeners are presently being collected.

  14. 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…

  15. 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.

  16. 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.

  17. Hesperetin, a Selective Phosphodiesterase 4 Inhibitor, Effectively Suppresses Ovalbumin-Induced Airway Hyperresponsiveness without Influencing Xylazine/Ketamine-Induced Anesthesia.

    PubMed

    Shih, Chung-Hung; Lin, Ling-Hung; Hsu, Hsin-Te; Wang, Kuo-Hsien; Lai, Chi-Yin; Chen, Chien-Ming; Ko, Wun-Chang

    2012-01-01

    Hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, is present in the traditional Chinese medicine, "Chen Pi." Therefore, we were interested in investigating its effects on ovalbumin- (OVA-) induced airway hyperresponsiveness, and clarifying its rationale for ameliorating asthma and chronic obstructive pulmonary disease (COPD). Hesperetin was revealed to have a therapeutic (PDE4(H)/PDE4(L)) ratio of >11. Hesperetin (10 ~ 30 μmol/kg, intraperitoneally (i.p.)) dose-dependently and significantly attenuated the airway hyperresponsiveness induced by methacholine. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF). It dose-dependently and significantly suppressed total and OVA-specific immunoglobulin E levels in the BALF and serum. However, hesperetin did not influence xylazine/ketamine-induced anesthesia, suggesting that hesperetin has few or no emetic effects. In conclusion, the rationales for ameliorating allergic asthma and COPD by hesperetin are anti-inflammation, immunoregulation, and bronchodilation.

  18. 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

  19. Hesperetin, a Selective Phosphodiesterase 4 Inhibitor, Effectively Suppresses Ovalbumin-Induced Airway Hyperresponsiveness without Influencing Xylazine/Ketamine-Induced Anesthesia.

    PubMed

    Shih, Chung-Hung; Lin, Ling-Hung; Hsu, Hsin-Te; Wang, Kuo-Hsien; Lai, Chi-Yin; Chen, Chien-Ming; Ko, Wun-Chang

    2012-01-01

    Hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, is present in the traditional Chinese medicine, "Chen Pi." Therefore, we were interested in investigating its effects on ovalbumin- (OVA-) induced airway hyperresponsiveness, and clarifying its rationale for ameliorating asthma and chronic obstructive pulmonary disease (COPD). Hesperetin was revealed to have a therapeutic (PDE4(H)/PDE4(L)) ratio of >11. Hesperetin (10 ~ 30 μmol/kg, intraperitoneally (i.p.)) dose-dependently and significantly attenuated the airway hyperresponsiveness induced by methacholine. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF). It dose-dependently and significantly suppressed total and OVA-specific immunoglobulin E levels in the BALF and serum. However, hesperetin did not influence xylazine/ketamine-induced anesthesia, suggesting that hesperetin has few or no emetic effects. In conclusion, the rationales for ameliorating allergic asthma and COPD by hesperetin are anti-inflammation, immunoregulation, and bronchodilation. PMID:22454667

  20. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    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.

  2. Development of novel DIF-1 derivatives that selectively suppress innate immune responses.

    PubMed

    Nguyen, Van Hai; Kikuchi, Haruhisa; Kubohara, Yuzuru; Takahashi, Katsunori; Katou, Yasuhiro; Oshima, Yoshiteru

    2015-08-01

    The multiple pharmacological activities of differentiation-inducing factor-1 (DIF-1) of the cellular slime mold Dictyostelium discoideum led us to examine the use of DIF-1 as a 'drug template' to develop promising seed compounds for drug discovery. DIF-1 and its derivatives were synthesized and evaluated for their regulatory activities in innate immune responses. We found two new derivatives (4d and 5e) with highly selective inhibitory activities against production of the antimicrobial peptide attacin in Drosophila S2 cells and against production of interleukin-2 in Jurkat cells. PMID:26122773

  3. 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.

  4. A CB2-Selective Cannabinoid Suppresses T-cell Activities and Increases Tregs and IL-10

    PubMed Central

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

    2015-01-01

    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. PMID:25980325

  5. 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.

  6. 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. PMID:12366875

  7. High-dose corticosterone after fear conditioning selectively suppresses fear renewal by reducing anxiety-like response.

    PubMed

    Wang, Hongbo; Xing, Xiaoli; Liang, Jing; Bai, Yunjing; Lui, Zhengkui; Zheng, Xigeng

    2014-09-01

    Exposure therapy is widely used to treat anxiety disorders, including posttraumatic stress disorder (PTSD). However, preventing the return of fear is still a major challenge after this behavioral treatment. An increasing number of studies suggest that high-dose glucocorticoid treatment immediately after trauma can alleviate the symptoms of PTSD in humans. Unknown is whether high-dose glucocorticoid treatment following fear conditioning suppresses the return of fear. In the present study, a typical fear renewal paradigm (AAB) was used, in which the fear response to an auditory cue can be restored in a novel context (context B) when both training and extinction occur in the same context (context A). We trained rats for auditory fear conditioning and administered corticosterone (CORT; 5 and 25mg/kg, i.p.) or vehicle with different delays (1 and 24h). Forty-eight hours after drug injection, extinction was conducted with no drug in the training context, followed by a test of tone-induced freezing behavior in the same (AAA) or a shifted (AAB) context. Both immediate and delayed administration of high-dose CORT after fear conditioning reduced fear renewal. To examine the anxiolytic effect of CORT, independent rats were trained for cued or contextual fear conditioning, followed by an injection of CORT (5 and 25mg/kg, i.p.) or vehicle at a 1 or 24h delay. One week later, anxiety-like behavior was assessed in the elevated plus maze (EPM) before and after fear expression. We found that high-dose CORT decreased anxiety-like behavior without changing tone- or context-induced freezing. These findings indicate that a single high-dose CORT administration given after fear conditioning may selectively suppress fear renewal by reducing anxiety-like behavior and not by altering the consolidation, retrieval, or extinction of fear memory.

  8. Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence

    PubMed Central

    1984-01-01

    We studied the mechanism of lymphocytic choriomeningitis virus (LCMV) persistence and the suppression of cytotoxic T lymphocyte (CTL) responses in BALB/c WEHI mice infected at birth with LCMV Armstrong strain. Using adoptive transfer experiments we found that spleen cells from persistently infected (carrier) mice actively suppressed the expected LCMV-specific CTL response of spleen cells from normal adult mice. The suppression was specific for the CTL response and LCMV - specific antibody responses were not affected. Associated with the specific CTL suppression was the establishment of persistent LCMV infection. The transfer of spleen or lymph node cells containing LCMV - specific CTL resulted in virus clearance and prevented establishment of the carrier state. The suppression of LCMV -specific CTL responses by carrier spleen cells is not mediated by a suppressor cell, but is due to the presence of genetic variants of LCMV in spleens of carrier mice. Such virus variants selectively suppress LCMV-specific CTL responses and cause persistent infections in immunocompetent mice. In striking contrast, wild-type LCMV Armstrong, from which these variants were generated, induces a potent CTL response in immunocompetent mice and the LCMV infection is rapidly cleared. Our results show that LCMV variants that emerge during infection in vivo play a crucial role in the suppression of virus-specific CTL responses and in the maintenance of virus persistence. PMID:6332167

  9. 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

  10. 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.

  11. A Novel Function for Arabidopsis CYCLASE1 in Programmed Cell Death Revealed by Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Analysis of Extracellular Matrix Proteins.

    PubMed

    Smith, Sarah J; Kroon, Johan T M; Simon, William J; Slabas, Antoni R; Chivasa, Stephen

    2015-06-01

    Programmed cell death is essential for plant development and stress adaptation. A detailed understanding of the signal transduction pathways that regulate plant programmed cell death requires identification of the underpinning protein networks. Here, we have used a protagonist and antagonist of programmed cell death triggered by fumonisin B1 as probes to identify key cell death regulatory proteins in Arabidopsis. Our hypothesis was that changes in the abundance of cell death-regulatory proteins induced by the protagonist should be blocked or attenuated by concurrent treatment with the antagonist. We focused on proteins present in the mobile phase of the extracellular matrix on the basis that they are important for cell-cell communications during growth and stress-adaptive responses. Salicylic acid, a plant hormone that promotes programmed cell death, and exogenous ATP, which can block fumonisin B1-induced cell death, were used to treat Arabidopsis cell suspension cultures prior to isobaric-tagged relative and absolute quantitation analysis of secreted proteins. A total of 33 proteins, whose response to salicylic acid was suppressed by ATP, were identified as putative cell death-regulatory proteins. Among these was CYCLASE1, which was selected for further analysis using reverse genetics. Plants in which CYCLASE1 gene expression was knocked out by insertion of a transfer-DNA sequence manifested dramatically increased cell death when exposed to fumonisin B1 or a bacterial pathogen that triggers the defensive hypersensitive cell death. Although pathogen inoculation altered CYCLASE1 gene expression, multiplication of bacterial pathogens was indistinguishable between wild type and CYCLASE1 knockout plants. However, remarkably severe chlorosis symptoms developed on gene knockout plants in response to inoculation with either a virulent bacterial pathogen or a disabled mutant that is incapable of causing disease in wild type plants. These results show that CYCLASE1, which

  12. BIOLOGICAL CONTROL OF WHEAT TAKE-ALL DISEASE: II – RAPID SELECTION OF BACTERIA SUPPRESSIVE TO GAEUMANNOMYCES GRAMINIS VAR. TRITICI IN LABORATORY WITH GREENHOUSE AND FIELD CONFIRMATION TRIALS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Screening large collections of bacteria for potential biological control activity on economically important diseases is often difficult. A quick test tube assay was developed to rapidly screen selected bacterial isolates for their ability to suppress take-all disease of wheat, caused by Gaeumannomyc...

  13. 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.

  14. Antioxidant-induced changes of the AP-1 transcription complex are paralleled by a selective suppression of human papillomavirus transcription.

    PubMed Central

    Rösl, F; Das, B C; Lengert, M; Geletneky, K; zur Hausen, H

    1997-01-01

    Considering the involvement of a redox-regulatory pathway in the expression of human papillomaviruses (HPVs), HPV type 16 (HPV-16)-immortalized human keratinocytes were treated with the antioxidant pyrrolidine-dithiocarbamate (PDTC). PDTC induces elevated binding of the transcription factor AP-1 to its cognate recognition site within the viral regulatory region. Despite of increased AP-1 binding, normally indispensable for efficient HPV-16 transcription, viral gene expression was selectively suppressed at the level of initiation of transcription. Electrophoretic mobility supershift assays showed that the composition of the AP-1 complex, predominantly consisting of Jun homodimers in untreated cells, was altered. Irrespective of enhanced c-fos expression, c-jun was phosphorylated and became primarily heterodimerized with fra-1, which was also induced after PDTC incubation. Additionally, there was also an increased complex formation between c-jun and junB. Because both fra-1 and junB overexpression negatively interferes with c-jun/c-fos trans-activation of AP-1-responsive genes, our results suggest that the observed block in viral transcription is mainly the consequence of an antioxidant-induced reconstitution of the AP-1 transcription complex. Since expression of the c-jun/c-fos gene family is tightly regulated during cellular differentiation, defined reorganization of a central viral transcription factor may represent a novel mechanism controlling the transcription of pathogenic HPVs during keratinocyte differentiation and in the progression to cervical cancer. PMID:8985358

  15. 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. PMID:27594855

  16. 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

  17. Heat dissipation does not suppress an immune response in laboratory mice divergently selected for basal metabolic rate (BMR).

    PubMed

    Książek, Aneta; Konarzewski, Marek

    2016-05-15

    The capacity for heat dissipation is considered to be one of the most important constraints on rates of energy expenditure in mammals. To date, the significance of this constraint has been tested exclusively under peak metabolic demands, such as during lactation. Here, we used a different set of metabolic stressors, which do not induce maximum energy expenditures and yet are likely to expose the potential constraining effect of heat dissipation. We compared the physiological responses of mice divergently selected for high (H-BMR) and low basal metabolic rate (L-BMR) to simultaneous exposure to the keyhole limpet haemocyanin (KLH) antigen and high ambient temperature (Ta). At 34°C (and at 23°C, used as a control), KLH challenge resulted in a transient increase in core body temperature (Tb) in mice of both line types (by approximately 0.4°C). Warm exposure did not produce line-type-dependent differences in Tb (which was consistently higher by ca. 0.6°C in H-BMR mice across both Ta values), nor did it result in the suppression of antibody synthesis. These findings were also supported by the lack of between-line-type differences in the mass of the thymus, spleen or lymph nodes. Warm exposure induced the downsizing of heat-generating internal organs (small intestine, liver and kidneys) and an increase in intrascapular brown adipose tissue mass. However, these changes were similar in scope in both line types. Mounting a humoral immune response in selected mice was therefore not affected by ambient temperature. Thus, a combined metabolic challenge of high Ta and an immune response did not appreciably compromise the capacity to dissipate heat, even in the H-BMR mice. PMID:26944492

  18. 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.

  19. LC-MS/MS bioanalytical method development for AMG 900: resolution of an isobaric interference in rodent in vivo studies.

    PubMed

    Be, Xuhai; Moore, Earl S; Zhao, Zhiyang; Wells, Mary C

    2013-02-23

    AMG 900 is an orally available small molecule that is a highly potent and selective pan-aurora kinase inhibitor currently in development for the treatment of advanced human cancers. A co-eluting, isobaric interference was discovered in preliminary LC-MS/MS analyses of rodent in vivo pharmacokinetic samples during preclinical evaluation of AMG 900. The interference was identified as a major circulating N-oxide metabolite which partially converted to an [M+H-O](+) ion under the conditions of atmospheric pressure chemical ionization. A selective liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of AMG 900 and its N-oxide metabolite in plasma was developed and successfully applied for the bioanalysis of discovery stage preclinical rodent pharmacokinetic studies.

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

    PubMed

    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. Graphical Abstract ᅟ. PMID:27400695

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

    PubMed

    Xiao, Ziya; Xue, Yuan; Yao, Chenling; 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

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

    NASA Astrophysics Data System (ADS)

    Pleik, Stefanie; Spengler, Bernhard; Schäfer, Thomas; Urbach, Dieter; Luhn, Steven; Kirsch, Dieter

    2016-07-01

    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.

  3. Pseudo isobaric peptide termini labelling for relative proteome quantification by SWATH MS acquisition.

    PubMed

    Zhang, Shen; Chen, Lingfan; Shan, Yichu; Sui, Zhigang; Wu, Qi; Zhang, Lihua; Liang, Zhen; Zhang, Yukui

    2016-08-01

    The pseudo isobaric peptide termini labeling (IPTL) method is a remarkable strategy in quantitative proteomics, and has been efficiently applied in biological studies due to its high quantitative accuracy. However, irreproducible precursor ion selection caused by data dependent acquisition and the chromatographic shift caused by isotope effects limit the wide application of this method. Herein, we expand the use of pseudo IPTL to SWATH MS application and develop a novel quantitative strategy, termed SWATH-pseudo-IPTL, by which the relative quantification could be achieved by comparing the "complete" extracted ion chromatogram (XIC) intensity of MS/MS scan instead of a single intensity measurement in DDA-pseudo-IPTL which only reflected the peptide abundances at that given time. The quantitative analysis of various proportions of mixed HeLa samples revealed the strong accuracy and precision of our SWATH-pseudo-IPTL method, both of which were better than that of the DDA-pseudo-IPTL strategy. SWATH-pseudo-IPTL was also applied to the quantitative profiling of the proteome from human hepatocellular carcinoma cell lines with high and low metastatic potential, and most of the differentially expressed proteins were related to tumorigenesis and tumor metastasis, demonstrating the feasibility of this methodology for biological applications.

  4. 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.

  5. 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

  6. Selective intracellular drug delivery from pH-responsive polyion complex micelle for enhanced malignancy suppression in vivo.

    PubMed

    Wang, Jixue; Xu, Weiguo; Guo, Hui; Ding, Jianxun; Chen, Jinjin; Guan, Jingjing; Wang, Chunxi

    2015-11-01

    The pH-triggered intracellular drug delivery platforms have attracted great interest in malignancy therapy. Herein, a pH-responsive polyion complex (PIC) micelle from anionic acid-sensitive methoxy poly(ethylene glycol)-block-poly(N(ϵ)-((1-carboxy-cis-cyclohexene)-2-carbonyl)-L-lysine) (mPEG-b-PCLL) and cationic doxorubicin (DOX), a model anthracycline antitumor drug, was constructed by electrostatic interaction for directional intracellular drug delivery in malignancy chemotherapy. The PIC micelle kept constant diameter at physiological condition (i.e., pH 7.4), while gradually swelled and finally disassembled at mimicking intratumoral pH (i.e., 6.8) and especially intracellular endo/lysosomal pH (i.e., 5.5). The DOX release from the PIC micelle at pH 7.4 was slow, whereas obviously accelerated at the intracellular acidic condition of pH 5.5. These results should be related to the rapid cleavage of the side amide bond of mPEG-b-PCLL in an acidic environment. The PIC micelle exhibited satisfactory tumor suppression toward the H22 hepatoma-bearing BALB/c mouse model compared with free DOX, which was demonstrated by the upregulated tumor inhibition rate, and the increased necrotic and apoptosis areas in tumor tissue. Furthermore, the enhanced security was also observed in the PIC micelle group in relation to that of free DOX. The above results strongly supported that the acid-sensitive PIC micelle was promising for selective intracellular drug delivery along with upregulated malignancy inhibition.

  7. Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia.

    PubMed

    Xu, Bowen; On, Doan M; Ma, Anqi; Parton, Trevor; Konze, Kyle D; Pattenden, Samantha G; Allison, David F; Cai, Ling; Rockowitz, Shira; Liu, Shichong; Liu, Ying; Li, Fengling; Vedadi, Masoud; Frye, Stephen V; Garcia, Benjamin A; Zheng, Deyou; Jin, Jian; Wang, Gang Greg

    2015-01-01

    Enhancer of zeste homolog 2 (EZH2) and related EZH1 control gene expression and promote tumorigenesis via methylating histone H3 at lysine 27 (H3K27). These methyltransferases are ideal therapeutic targets due to their frequent hyperactive mutations and overexpression found in cancer, including hematopoietic malignancies. Here, we characterized a set of small molecules that allow pharmacologic manipulation of EZH2 and EZH1, which include UNC1999, a selective inhibitor of both enzymes, and UNC2400, an inactive analog compound useful for assessment of off-target effect. UNC1999 suppresses global H3K27 trimethylation/dimethylation (H3K27me3/2) and inhibits growth of mixed lineage leukemia (MLL)-rearranged leukemia cells. UNC1999-induced transcriptome alterations overlap those following knockdown of embryonic ectoderm development, a common cofactor of EZH2 and EZH1, demonstrating UNC1999's on-target inhibition. Mechanistically, UNC1999 preferentially affects distal regulatory elements such as enhancers, leading to derepression of polycomb targets including Cdkn2a. Gene derepression correlates with a decrease in H3K27me3 and concurrent gain in H3K27 acetylation. UNC2400 does not induce such effects. Oral administration of UNC1999 prolongs survival of a well-defined murine leukemia model bearing MLL-AF9. Collectively, our study provides the detailed profiling for a set of chemicals to manipulate EZH2 and EZH1 and establishes specific enzymatic inhibition of polycomb repressive complex 2 (PRC2)-EZH2 and PRC2-EZH1 by small-molecule compounds as a novel therapeutics for MLL-rearranged leukemia.

  8. Dehydroeffusol inhibits gastric cancer cell growth and tumorigenicity by selectively inducing tumor-suppressive endoplasmic reticulum stress and a moderate apoptosis.

    PubMed

    Zhang, Bin; Han, Hongyan; Fu, Shilong; Yang, Ping; Gu, Zhenlun; Zhou, Quansheng; Cao, Zhifei

    2016-03-15

    Gastric cancer is ranked as the third leading cause of cancer-related death in the world. Although extensive efforts have been made in recent decades to treat gastric cancer with various anticancer drugs, effective anti-gastric cancer therapeutics to cure the disease are still lacking in the clinics. Therefore, potent novel anti-gastric cancer drugs are greatly needed. In this study, we explored a novel anti-gastric cancer agent from a medicinal herb named Juncus effusus and found that the active component dehydroeffusol (DHE), a small molecular phenanthrene, effectively inhibited gastric cancer cell proliferation and tumorigenesis by inducing tumor suppressive endoplasmic reticulum (ER) stress and by triggering moderate apoptosis. Mechanistic studies revealed that DHE selectively activated the intracellular tumor suppressive stress response by promoting the overexpression of the key ER stress marker DNA damage-inducible transcript 3 (DDIT3), through upregulation of activating transcription factor 4 (ATF4). Concurrently, DHE suppressed the expression of the cell survival and ER stress marker glucose regulated protein of molecular mass 78 (GRP78) via downregulation of the transcription factor ATF6. In addition, DHE markedly activated the stress response signaling pathway MEKK4-MKK3/6-p38-DDIT3, but significantly inhibited ERK signaling. Our data suggest that DHE inhibits gastric cancer cell growth and tumorigenicity through selectively inducing a robust tumor suppressive ER stress response and a moderate apoptosis response. Therefore, DHE may provide a novel drug candidate for further development of potential anti-gastric cancer therapeutics. PMID:26774454

  9. New Therapeutic Approach to Suppress Castration-Resistant Prostate Cancer Using ASC-J9 via Targeting Androgen Receptor in Selective Prostate Cells

    PubMed Central

    Lai, Kuo-Pao; Huang, Chiung-Kuei; Chang, Yu-Jia; Chung, Chin-Ying; Yamashita, Shinichi; Li, Lei; Lee, Soo Ok; Yeh, Shuyuan; Chang, Chawnshang

    2014-01-01

    Using androgen receptor (AR) knockout mice to determine AR functions in selective prostate cancer (PCa) cells, we determined that AR might play differential roles in various cell types, either to promote or suppress PCa development/progression. These observations partially explain the failure of current androgen deprivation therapy (ADT) to reduce/prevent androgen binding to AR in every cell. Herein, we identified the AR degradation enhancer ASC-J9, which selectively degrades AR protein via interruption of the AR-AR selective coregulator interaction. Such selective interruption could, therefore, suppress AR-mediated PCa growth in the androgen-sensitive stage before ADT and in the castration-resistant stage after ADT. Mechanistic dissection suggested that ASC-J9 could activate the proteasome-dependent pathway to promote AR degradation through the enhanced association of AR-Mdm2 complex. The consequences of ASC-J9-promoted AR degradation included reduced androgen binding to AR, AR N-C terminal interaction, and AR nuclear translocation. Such inhibitory regulation could then result in suppression of AR transactivation and AR-mediated cell growth in eight different mouse models, including intact or castrated nude mice xenografted with androgen-sensitive LNCaP cells or androgen-insensitive C81 cells and castrated nude mice xenografted with castration-resistant C4-2 and CWR22Rv1 cells, and TRAMP and Pten+/− mice. These results demonstrate that ASC-J9 could serve as an AR degradation enhancer that effectively suppresses PCa development/progression in the androgen-sensitive and castration-resistant stages. PMID:23219429

  10. 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.

  11. Cost-effective isobaric tagging for quantitative phosphoproteomics using DiART reagents.

    PubMed

    Ramsubramaniam, Nikhil; Tao, Feng; Li, Shuwei; Marten, Mark R

    2013-12-01

    We describe the use of an isobaric tagging reagent, Deuterium isobaric Amine Reactive Tag (DiART), for quantitative phosphoproteomic experiments. Using DiART tagged custom mixtures of two phosphorylated peptides from alpha casein and their non-phosphorylated counterparts, we demonstrate the compatibility of DiART with TiO2 affinity purification of phosphorylated peptides. Comparison of theoretical vs. experimental reporter ion ratios reveals accurate quantification of phosphorylated peptides over a dynamic range of more than 15-fold. Using DiART labelling and TiO2 enrichment (DiART-TiO2) with large quantities of proteins (8 mg) from the cell lysate of model fungus Aspergillus nidulans, we quantified 744 unique phosphopeptides. Overlap of median values of TiO2 enriched phosphopeptides with theoretical values indicates accurate trends. Altogether these findings confirm the feasibility of performing quantitative phosphoproteomic experiments in a cost-effective manner using isobaric tagging reagents, DiART.

  12. Wound retraction system for isobaric laparoendoscopic single-site surgery to treat adnexal tumors: pilot study.

    PubMed

    Takeda, Akihiro; Imoto, Sanae; Mori, Masahiko; Nakano, Tomoko; Nakamura, Hiromi

    2010-01-01

    Transumbilical laparoendoscopic single-site (LESS) surgery is a recent advancement in minimally invasive surgery. However, this procedure usually requires a specialized multichannel port for introducing the laparoscope and instruments under pneumoperitoneum. In an isobaric procedure, a wound retractor alone can conveniently be used for transumbilical single-site access. Fourteen isobaric LESS adnexal surgeries including 1 emergency procedure with adnexal torsion were performed using multiple instruments inserted through the wound retractor. No extraumbilical incisions or conversion to standard multiple-port laparoscopic surgery were required. Port-related complications were not noted, and the cosmetic results were excellent. A wound retractor offers safe and reliable access for isobaric LESS adnexal surgery as an alternative to the current specialized port systems. PMID:20579942

  13. 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

  14. Isobar separation of 93Zr and 93Nb at 24 MeV with a new multi-anode ionization chamber

    NASA Astrophysics Data System (ADS)

    Martschini, Martin; Buchriegler, Josef; Collon, Philippe; Kutschera, Walter; Lachner, Johannes; Lu, Wenting; Priller, Alfred; Steier, Peter; Golser, Robin

    2015-10-01

    93Zr with a half-life of 1.6 Ma is produced with high yield in nuclear fission, and thus should be present as a natural or anthropogenic trace isotope in all compartments of the general environment. Sensitive measurements of this isotope would immediately find numerous applications, however, its detection at sufficiently low levels has not yet been achieved. AMS measurements of 93Zr suffer from the interference of the stable isobar 93Nb. At the Vienna Environmental Research Accelerator VERA a new multi-anode ionization chamber was built. It is optimized for isobar separation in the medium mass range and is based on the experience from AMS experiments of 36Cl at our 3-MV tandem accelerator facility. The design provides high flexibility in anode configuration and detector geometry. After validating the excellent energy resolution of the detector with 36S, it was recently used to study iron-nickel and zirconium-niobium-molybdenum isobar separation. To our surprise, the separation of 94Zr (Z = 40) from 94Mo (Z = 42) was found to be much better than that of 58Fe (Z = 26) from 58Ni (Z = 28), despite the significantly larger ΔZ/Z of the latter pair. This clearly contradicts results from SRIM-simulations and suggests that differences in the stopping behavior may unexpectedly favor identification of 93Zr. At 24 MeV particle energy, a 93Nb (Z = 41) suppression factor of 1000 is expected based on a synthetic 93Zr spectrum obtained by interpolation between experimental spectra from the two neighboring stable isotopes 92Zr and 94Zr. Assuming realistic numbers for chemical niobium reduction, a detection level of 93Zr/Zr below 10-9 seems feasible.

  15. Rational design of antisense oligonucleotides targeting single nucleotide polymorphisms for potent and allele selective suppression of mutant Huntingtin in the CNS

    PubMed Central

    Østergaard, Michael E.; Southwell, Amber L.; Kordasiewicz, Holly; Watt, Andrew T.; Skotte, Niels H.; Doty, Crystal N.; Vaid, Kuljeet; Villanueva, Erika B.; Swayze, Eric E.; Frank Bennett, C.; Hayden, Michael R.; Seth, Punit P.

    2013-01-01

    Autosomal dominant diseases such as Huntington’s disease (HD) are caused by a gain of function mutant protein and/or RNA. An ideal treatment for these diseases is to selectively suppress expression of the mutant allele while preserving expression of the wild-type variant. RNase H active antisense oligonucleotides (ASOs) or small interfering RNAs can achieve allele selective suppression of gene expression by targeting single nucleotide polymorphisms (SNPs) associated with the repeat expansion. ASOs have been previously shown to discriminate single nucleotide changes in targeted RNAs with ∼5-fold selectivity. Based on RNase H enzymology, we enhanced single nucleotide discrimination by positional incorporation of chemical modifications within the oligonucleotide to limit RNase H cleavage of the non-targeted transcript. The resulting oligonucleotides demonstrate >100-fold discrimination for a single nucleotide change at an SNP site in the disease causing huntingtin mRNA, in patient cells and in a completely humanized mouse model of HD. The modified ASOs were also well tolerated after injection into the central nervous system of wild-type animals, suggesting that their tolerability profile is suitable for advancement as potential allele-selective HD therapeutics. Our findings lay the foundation for efficient allele-selective downregulation of gene expression using ASOs—an outcome with broad application to HD and other dominant genetic disorders. PMID:23963702

  16. 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...

  17. 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.

  18. 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.

  19. Masses of proton-rich T/sub z/<0 nuclei via the isobaric mass equation

    SciTech Connect

    Pape, A.; Antony, M.S.

    1988-07-01

    Masses of T/sub z/<0 nuclei through the element Sm, corresponding to Aless than or equal to117, have been calculated with the isobaric multiplet mass equation using parameterizations of its constant b and T/sub z/>0 reference masses of Wapstra, Audi, and Hoekstra. copyright 1988 Academic Press, Inc.

  20. 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.

  1. Differential quantification of isobaric phosphopeptides using data-independent acquisition mass spectrometry

    PubMed Central

    Sidoli, Simone; Fujiwara, Rina; Kulej, Katarzyna; Garcia, Benjamin A.

    2016-01-01

    Phosphorylation is a post-translational modification (PTM) fundamental for processes such as signal transduction and enzyme activity. We propose to apply data-independent acquisition (DIA) using mass spectrometry (MS) to determine unexplored phosphorylation events on isobarically modified peptides. Such peptides are commonly not quantitatively discriminated in phosphoproteomics due to their identical mass. PMID:27301801

  2. 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.

  3. Suppressive Effects of Selected Food Phytochemicals on CD74 Expression in NCI-N87 Gastric Carcinoma Cells

    PubMed Central

    Sekiguchi, Hirotaka; Washida, Kazuto; Murakami, Akira

    2008-01-01

    Helicobacter pylori (H. pylori) is one of the most widespread human pathogens, and plays major roles in chronic gastritis and gastric cancer. CD74 of gastric epithelial cells has recently been identified as an adhesion molecule to urease in H. pylori. In this study, we found that CD74 is highly expressed in a constitutive manner in NCI-N87 human gastric carcinoma cells at both the protein and mRNA levels as compared with Hs738St./Int fetal gastric cells. Subsequently, a novel cell-based ELISA able to rapidly screen the suppressive agents of CD74 expression was established. NCI-N87 cells were treated separately with 25 different food phytochemicals (4–100 µM) for 48 h and subjected to our novel assay. From those results, a citrus coumarin, bergamottin, was indicated to be the most promising compound with an LC50/IC50 value greater than 7.1, followed by luteolin (>5.4), nobiletin (>5.3), and quercetin (>5.1). Our findings suggest that these CD74 suppressants are unique candidates for preventing H. pylori adhesion and subsequent infection with reasonable action mechanisms. PMID:18818744

  4. 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.

  5. 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.

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

    DOE PAGES

    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.; et al

    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

  7. 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.

  8. Dependence of the isobaric specific heat capacity of water vapor on the pressure and temperature

    NASA Astrophysics Data System (ADS)

    Vestfálová, Magda; Šafařík, Pavel

    2016-03-01

    The fundamental base for the calculation of the thermodynamic properties of substances is the thermal equation of state and the dependence of some of the basic specific heat capacities on temperature. Dependence of isobaric specific heat capacity on the pressure can already be deduced from these relations. International standards of the properties of water and steam are based on the new scientific formulation IAPWS-95. The equation is in the form of Helmholtz dimensionless function with very much parameters. The aim of this paper is to design the simple dependence of the isobaric specific heat capacity of water vapor on the pressure and temperature in the range in which the steam occurs in the atmospheric moist air.

  9. 'Coulomb' description of basic relaxation parameters of isobar analog and charge-exchange giant monopole resonances

    SciTech Connect

    Gorelik, M. L.; Rykovanov, V. S.; Urin, M. G.

    2010-12-15

    Within a semimicroscopic approach, basic relaxation parameters of the isobaric analog resonance and of the charge-exchange giant monopole resonance, which is an overtone of the isobaric analog resonance, are interpreted in terms of the mean Coulomb field of a nucleus. The continuum version of the random-phase approximation, allowance for an approximate isospin conservation in nuclei in an explicit form, and a phenomenological description of the fragmentation effect are basic ingredients of the approach used. The aforementioned parameters were calculated for a number of magic and near-magic nuclei by using a partly self-consistent phenomenological nuclear mean field and the isovector part of the Landau-Migdal interaction in the particle-hole channel. The results of the calculations are compared with corresponding experimental data.

  10. 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.

  11. Phase Structure of the T-matrix and Multichannel Unitary Isobar Model

    NASA Astrophysics Data System (ADS)

    Razavi, S.; Nakayama, K.

    2015-04-01

    By exploiting the full phase structure of the meson-baryon coupled channels reaction amplitude-here including also the photon-baryon channel-an isobar model is constructed which fulfills automatically the unitarity and analyticity conditions of the S-matrix, in addition to gauge invariance in the case of photoproduction. In particular, it is shown that the unitarity of the (resonance) pole amplitude arises from the dressing mechanism inherent in the basic T-matrix equation, requiring no extra unitarity condition on the pole amplitude as is the case in earlier works on isobar models. As an example, the present model is applied in the description of the meson-nucleon reactions including the πN , ηN , σN , ρN and πΔ channels. The latter three account effectively for the ππN channel. FFE-COSY Grant No. 41788390.

  12. Quantitation of protein post-translational modifications using isobaric tandem mass tags.

    PubMed

    Liang, Hui-Chung; Lahert, Emma; Pike, Ian; Ward, Malcolm

    2015-01-01

    Post-translational modifications (PTMs) of proteins are known to modulate many cellular processes and their qualitative and quantitative evaluation is fundamental for understanding the mechanisms of biological events. Over the past decade, improvements in sample preparation techniques and enrichment strategies, the development of quantitative labeling strategies, the launch of a new generation of mass spectrometers and the creation of bioinformatics tools for the interrogation of ever larger datasets has established MS-based quantitative proteomics as a powerful workflow for global proteomics, PTM analysis and the elucidation of key biological mechanisms. With the advantage of their multiplexing capacity and the flexibility of an ever-growing family of different peptide-reactive groups, isobaric tandem mass tags facilitate quantitative proteomics and PTM experiments and enable higher sample throughput. In this review, we focus on the technical concept and utility of the isobaric tandem mass tag labeling approach to PTM analysis, including phosphorylation, glycosylation and S-nitrosylation. PMID:25697195

  13. 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.

  14. Densities, isobaric thermal expansion coefficients and isothermal compressibilities of linear alkylbenzene

    NASA Astrophysics Data System (ADS)

    Zhou, X.; Zhang, Q. M.; Liu, Q.; Zhang, Z. Y.; Ding, Y. Y.; Zhou, L.; Cao, J.

    2015-05-01

    We report the measurements of the densities of linear alkylbenzene at three temperatures over 4 to 23 °C with pressures up to 10 MPa. The measurements have been analysed to yield the isobaric thermal expansion coefficients and, so far for the first time, isothermal compressibilities of linear alkylbenzene. Relevance of results for current generation (i.e., Daya Bay) and next generation (i.e. JUNO) large liquid scintillator neutrino detectors are discussed.

  15. 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.

  16. Nonresonant Background in Isobaric Models of Photoproduction of η-Mesons on Nucleons

    NASA Astrophysics Data System (ADS)

    Tryasuchev, V. A.; Alekseev, B. A.; Yakovleva, V. S.; Kondratyeva, A. G.

    2016-07-01

    Within the framework of isobaric models of pseudoscalar meson photoproduction, the nonresonant background of photoproduction of η-mesons on nucleons is investigated as a function of energy. A bound on the magnitude of the pseudoscalar coupling constant of the η-meson with a nucleon is obtained: g η NN 2 /4π ≤ 0.01, and a bound on vector meson exchange models is also obtained.

  17. CONSTANd : A Normalization Method for Isobaric Labeled Spectra by Constrained Optimization.

    PubMed

    Maes, Evelyne; Hadiwikarta, Wahyu Wijaya; Mertens, Inge; Baggerman, Geert; Hooyberghs, Jef; Valkenborg, Dirk

    2016-08-01

    In quantitative proteomics applications, the use of isobaric labels is a very popular concept as they allow for multiplexing, such that peptides from multiple biological samples are quantified simultaneously in one mass spectrometry experiment. Although this multiplexing allows that peptide intensities are affected by the same amount of instrument variability, systematic effects during sample preparation can also introduce a bias in the quantitation measurements. Therefore, normalization methods are required to remove this systematic error. At present, a few dedicated normalization methods for isobaric labeled data are at hand. Most of these normalization methods include a framework for statistical data analysis and rely on ANOVA or linear mixed models. However, for swift quality control of the samples or data visualization a simple normalization technique is sufficient. To this aim, we present a new and easy-to-use data-driven normalization method, named CONSTANd. The CONSTANd method employs constrained optimization and prior information about the labeling strategy to normalize the peptide intensities. Further, it allows maintaining the connection to any biological effect while reducing the systematic and technical errors. As a result, peptides can not only be compared directly within a multiplexed experiment, but are also comparable between other isobaric labeled datasets from multiple experimental designs that are normalized by the CONSTANd method, without the need to include a reference sample in every experimental setup. The latter property is especially useful when more than six, eight or ten (TMT/iTRAQ) biological samples are required to detect differential peptides with sufficient statistical power and to optimally make use of the multiplexing capacity of isobaric labels. PMID:27302888

  18. 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.

  19. 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)

  20. Enhanced sample multiplexing for nitrotyrosine-modified proteins using combined precursor isotopic labeling and isobaric tagging.

    PubMed

    Robinson, Renã A S; Evans, Adam R

    2012-06-01

    Current strategies for identification and quantification of 3-nitrotyrosine (3NT) post-translationally modified proteins (PTM) generally rely on biotin/avidin enrichment. Quantitative approaches have been demonstrated which employ isotopic labeling or isobaric tagging in order to quantify differences in the relative abundances of 3NT-modified proteins in two or potentially eight samples, respectively. Here, we present a novel strategy which uses combined precursor isotopic labeling and isobaric tagging (cPILOT) to increase the multiplexing capability of quantifying 3NT-modified proteins to 12 or 16 samples using commercially available tandem mass tags (TMT) or isobaric tags for relative and absolute quantification (iTRAQ), respectively. This strategy employs "light" and "heavy" labeled acetyl groups to block both N-termini and lysine residues of tryptic peptides. Next, 3NT is reduced to 3-aminotyrosine (3AT) using sodium dithionite followed by derivatization of light and heavy labeled 3AT-peptides with either TMT or iTRAQ multiplex reagents. We demonstrate the proof-of-principle utility of cPILOT with in vitro nitrated bovine serum albumin (BSA) and mouse splenic proteins using TMT(0), TMT(6), and iTRAQ(8) reagents and discuss limitations of the strategy. PMID:22509719

  1. Discrimination of large maltooligosaccharides from isobaric dextran and pullulan using ion mobility mass spectrometry

    PubMed Central

    Rashid, Abdul M; Saalbach, Gerhard; Bornemann, Stephen

    2013-01-01

    RATIONALE Ion mobility mass spectrometry (IMMS) has previously been shown to resolve small isobaric oligosaccharides, but larger alpha-oligoglucans are also abundant in biology and are of industrial importance. If conformational differences between such isomers are retained in the gas phase, IMMS could be used to address questions in biology and industry. METHODS Negative mode electrospray ionization (ESI) travelling-wave IMMS was used to resolve large isobaric α-glucan ions on the basis of their different gas-phase conformations. α,ω-Dicarboxy-terminated polystyrene was used to calibrate the instrument allowing the collision cross-sections (CCSs) of ions to be determined. RESULTS α-1,4-Linked maltooligosaccharides with a degree of polymerisation of up to 35 could be discriminated from α-1,6-linked dextran and α-1,4/1,6-linked pullulan using IMMS. Fragmentation spectra of ions separated by IMMS could also distinguish isomers. Two conformational isomers of maltohexaose were resolvable by IMMS, likely reflecting extended and V6 helical conformations. IMMS was also able to identify a product within a mixture of maltooligosaccharides treated with the potential anti-tuberculosis drug target Mycobacterium tuberculosis GlgB branching enzyme. CONCLUSIONS Biological samples of complex isobaric oligosaccharides can be analysed using IMMS in the negative mode providing facile analyses and high sensitivity without the need for either derivatisation or chromatographic separation. © 2013 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd. PMID:24338967

  2. [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. PMID:27026564

  3. Suppressed Microglial E Prostanoid Receptor 1 Signaling Selectively Reduces TNFα and IL-6 Secretion from Toll-like Receptor 3 Activation

    PubMed Central

    Li, Xianwu; Cudaback, Eiron; Keene, C. Dirk; Breyer, Richard M.; Montine, Thomas J.

    2010-01-01

    Activation of innate immunity via Toll-like receptors (TLRs) is associated with neurodegenerative diseases, and some effectors, like tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), directly contribute to neurodegeneration. We tested the hypothesis that prostaglandin (PG) E2 receptor subtype 1 (EP1) was necessary for induction of microglial cytokines following activation of innate immunity. Primary murine microglia had cytokine secretion by activators of TLR3 > TLR9 >TLR4 > TLR2. TLR3 activation induced early expression of cyclooxygenase 2 (COX2) and delayed expression of membranous PGE synthase and secretion of PGE2. Non-selective and COX2-selective inhibitors blocked TLR3 induction of TNFα and IL-6. Moreover, of the eight out of twenty cytokines and chemokines induced by TLR3 activation, only TNFα and IL-6 were significantly dependent on EP1 signaling as determined using microglia from mice homozygous deficient for EP1 gene or wild type (WT) microglia co-incubated with an EP1 antagonist. These results were confirmed by blocking intracellular Ca2+ release with 2-aminoethoxy-diphenyl borate (2-APB) or Xestospongin C (XC), inhibitors of IP3 receptors. Our results show that suppression of microglial EP1 signaling achieves much of the desired effect of COX inhibitors by selectively blocking TLR3-induced microglial secretion of two major effectors of paracrine neuron damage. In combination with the ability of EP1 suppression to ameliorate excitotoxicity, these data point to blockade of EP1 as an attractive candidate therapeutic for neurodegenerative diseases. PMID:21319223

  4. Suppression of anodal break excitation by electrical stimulation with down-staircase waveform for distance-selective nerve recruitment.

    PubMed

    Ueno, Ayako; Karashima, Akihiro; Nakao, Mitsuyuki; Katayama, Norihiro

    2012-01-01

    Electrical nerve stimulation using extracellular electrodes is widely performed in clinical medicine as well as basic medical science. It has been reported that selective recruitment of nerve fibers on the basis of the distance between the electrode and the axon is possible without moving the electrode and only by modifying the waveform of electrical stimulation. However, computer simulations have not reproduced the complete nature of the distance-selectivity of the stimulus owing to the difficulty in numerical analysis. In this paper, we propose a minor modification to the myelinated axon model to overcome this difficulty. We confirm that this modification improves the numerical stability of the simulation and enables us to obtain the spatio-temporal dynamics of axons, including the electrode-to-axon distance-dependency. In addition, we propose a novel stimulation method using a down-staircase waveform for distance-selective nerve recruitment. Simulations confirm that the method works well. We show the spatial distribution of axons activated by the down-staircase stimulation, which would be helpful to determine the stimulation parameters for distance-selective nerve recruitment. PMID:23365868

  5. 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. PMID:19151247

  6. A New Technology for Elimination of Isobaric Interferences in Ultra-Sensitive Isotope Measurements

    NASA Astrophysics Data System (ADS)

    Eliades, J.; Zhao, X.; Litherland, T.; Kieser, L.; Cousins, L.; Ye, J.

    2009-05-01

    Accelerator Mass Spectrometry (AMS) is a technique used for ultra-sensitive abundance ratio measurements. Applications in the earth sciences typically involve the measurement of 10Be, 14C, 26Al, 36Cl, 41Ca and 129I, for example in exposure dating and ground water studies, sometimes yielding ratios of unstable to stable isotope at 10-15 or less. AMS is most effective when the stable atomic isobar does not form a stable negative ion. When this is not the case larger accelerators have been required. Here we report preliminary tests of a prototype radio-frequency quadrupole collision cell system for the removal of isobaric interferences for Accelerator Mass Spectrometry (AMS) and for studies of anion-gas interactions at low energy. A fully developed ISA could allow smaller AMS systems to handle a wider range of samples. This system, known as an Isobar Separator for Anions (ISA), decelerates a mass-analyzed beam of anions from an energy typically generated by an AMS ion source (˜20 keV) down to < 10 eV. Radiofrequency quardrupoles and electrostatic lenses then guide the ions through the collision cell where ion-gas reactions attenuate most of the unwanted isobars and ion-gas elastic collisions reduce the ion energy and energy spread of the ion beam (cool the ions). The anions are then reaccelerated to their original energy for injection into the rest of the AMS system. With the ISA installed on a full 3MV AMS system, attenuations of 32S-, 12C3-, and 39K- by six, seven, and > ten orders of magnitude respectively have been achieved using NO2 gas in the collision cell. Transmission of a non-reactive anion is approximately 10-20% through the ISA. Further measurements of four 36Cl standards (4 x 10-13 < 36Cl/Cl < 4 x 10-11) and an estimate of the attenuation of the interfering isobars 36S-and 12C3-is also described.

  7. 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. PMID:26490061

  8. Effects of persistent selective suppression of ganglionic butyrylcholinesterase on steady state and regenerating levels of acetylcholinesterase: implications regarding function of butyrylcholinesterase and regulation of protein synthesis.

    PubMed Central

    Koelle, W A; Koelle, G B; Smyrl, E G

    1976-01-01

    Persistent selective suppression of the butyrylcholinesterase (cholinesterase; acylcholine acyl-hydrolase, EC 3.1.1.8) activity of the superior cervical, stellate, and ciliary ganglia of cats by the daily administration of tetramonoisopropyl pyrophosphortetramide, 3.0 mumol/kg, intravenously, for 6 days produced a significant elevation in the levels of ganglionic acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7). When the same procedure was preceded by the inactivation of over 95% of the ganglionic acetylcholinesterase by sarin, 2.0 mumol/kg, intravenously, the rate of regeneration of acetylcholinesterase was decreased. Results are interpreted as evidence that ganglionic butyrylcholinesterase may serve as a precursor to acetylcholinesterase, and that the level of butyrylcholinesterase may regulate the rate of acetylcholinesterase synthesis. PMID:1066704

  9. Increased intracellular Ca2+ selectively suppresses IL-1-induced NO production by reducing iNOS mRNA stability

    PubMed Central

    1995-01-01

    This study addresses the role of intracellular calcium (Ca2+) in the expression of iNOS, an IL-1 inducible gene in human articular chondrocytes. The calcium ionophore A23187 and ionomycin did not induce NO release or iNOS expression but inhibited dose dependently IL-1- induced NO release with IC50 of 200 nM and 100 nM, respectively. Increased intracellular Ca2+ induced by thapsigargin or cyclopiazonic acid, inhibitors of the endoplasmic reticulum Ca2+ ATPase, had similar inhibitory effects with IC50 of 1 nM and 3 microM, respectively. LPS and TNF alpha induced NO production were also suppressed by these Ca2+ elevating drugs. Levels of IL-1-induced iNOS protein were reduced by A23187, thapsigargin, and cyclopiazonic acid. These drugs as well as Bay K 8644 and KCl inhibited IL-1-induced iNOS mRNA expression. To analyze the role of Ca2+ in the expression of other IL-1 responsive genes in chondrocytes, these Ca2+ modulating drugs were tested for effects on COXII. In contrast to the inhibitory effects on iNOS mRNA, these drugs induced COXII mRNA expression and in combination with IL-1, enhanced COXII mRNA levels. Ca2+ mediated increases in COXII mRNA expression were associated with an increase in COXII protein. The kinetics of Ca2+ effects on IL-1-induced iNOS mRNA levels suggested a posttranscriptional mechanism. Analysis of iNOS mRNA half life showed that it was 6-7 h in IL-1-stimulated cells and decreased by A23187 to 2- 3 h. In conclusion, these results show that Ca2+ inhibits IL-1-induced NO release, iNOS protein, and mRNA expression in human articular chondrocytes by reducing iNOS mRNA stability. Under identical conditions increased Ca2+ enhances IL-1-induced COXII gene and protein expression. PMID:7540612

  10. 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

    2013-07-01

    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.

  11. Novel retinoblastoma mutation abrogating the interaction to E2F2/3, but not E2F1, led to selective suppression of thyroid tumors

    PubMed Central

    Toki, Hideaki; Inoue, Maki; Minowa, Osamu; Motegi, Hiromi; Saiki, Yuriko; Wakana, Shigeharu; Masuya, Hiroshi; Gondo, Yoichi; Shiroishi, Toshihiko; Yao, Ryoji; Noda, Tetsuo

    2014-01-01

    Mutant mouse models are indispensable tools for clarifying gene functions and elucidating the pathogenic mechanisms of human diseases. Here, we describe novel cancer models bearing point mutations in the retinoblastoma gene (Rb1) generated by N-ethyl-N-nitrosourea mutagenesis. Two mutations in splice sites reduced Rb1 expression and led to a tumor spectrum and incidence similar to those observed in the conventional Rb1 knockout mice. The missense mutant, Rb1D326V/+, developed pituitary tumors, but thyroid tumors were completely suppressed. Immunohistochemical analyses of thyroid tissue revealed that E2F1, but not E2F2/3, was selectively inactivated, indicating that the mutant Rb protein (pRb) suppressed thyroid tumors by inactivating E2F1. Interestingly, Rb1D326V/+ mice developed pituitary tumors that originated from the intermediate lobe of the pituitary, despite selective inactivation of E2F1. Furthermore, in the anterior lobe of the pituitary, other E2F were also inactivated. These observations show that pRb mediates the inactivation of E2F function and its contribution to tumorigenesis is highly dependent on the cell type. Last, by using a reconstitution assay of synthesized proteins, we showed that the D326V missense pRb bound to E2F1 but failed to interact with E2F2/3. These results reveal the effect of the pRb N-terminal domain on E2F function and the impact of the protein on tumorigenesis. Thus, this mutant mouse model can be used to investigate human Rb family-bearing mutations at the N-terminal region. PMID:25088905

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

    PubMed

    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.

  13. 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

  14. Selective CDK7 inhibition with BS-181 suppresses cell proliferation and induces cell cycle arrest and apoptosis in gastric cancer

    PubMed Central

    Wang, Bo-Yong; Liu, Quan-Yan; Cao, Jun; Chen, Ji-Wei; Liu, Zhi-Su

    2016-01-01

    Cyclin-dependent kinase (CDK) family members have been considered as attractive therapeutic targets for cancer. In this study, we aim to investigate the anticancer effects of a selective CDK7 inhibitor, BS-181, in gastric cancer (GC) cell line. Human GC cells (BGC823) were cultured with or without BS-181 at different concentrations for 24–72 hours. BS-181 significantly reduced the activity of CDK7 with downregulation of cyclin D1 and XIAP in GC cells. Treatment with BS-181 induced cell cycle arrest and apoptosis. The expression of Bax and caspase-3 was significantly increased, while Bcl-2 expression was decreased in cells treated with BS-181. In addition, the inhibition of CDK7 with BS-181 resulted in reduced rates of proliferation, migration, and invasion of gastric cells. Those results demonstrated the anticancer activities of selective CDK7 inhibitor BS-181 in BGC823 cells, suggesting that CDK7 may serve as a novel therapeutic target or the treatment of GC. PMID:27042010

  15. Conception of PIPERADE: A high-capacity Penning-trap mass separator for high isobaric contamination at DESIR

    NASA Astrophysics Data System (ADS)

    Minaya Ramirez, E.; Alfaurt, P.; Aouadi, M.; Ascher, P.; Blank, B.; Blaum, K.; Cam, J.-F.; Chauveau, P.; Daudin, L.; Delahaye, P.; Delalee, F.; Dupré, P.; El Abbeir, S.; Gerbaux, M.; Grévy, S.; Guérin, H.; Lunney, D.; Metz, F.; Naimi, S.; Perrot, L.; de Roubin, A.; Serani, L.; Thomas, B.; Thomas, J.-C.

    2016-06-01

    The DESIR (decay, excitation and storage of radioactive ions) facility at GANIL-SPIRAL2 will receive a large variety of exotic nuclei at low energy (up to 60 keV) with high intensities. However, the production methods of radioactive beams are non selective, limiting the purity of the beams of interest. Moreover, the high precision needed for nuclear structure and astrophysics studies using beta decay spectroscopy, laser spectroscopy and trap-based experiments at DESIR requires highly pure samples of exotic nuclei. The aim of the double-Pennig-trap mass separator PIPERADE is to deliver large and very pure samples of exotic nuclei to the different experiments in DESIR. New excitation schemes and a large inner diameter of the first trap will mitigate space charge effects to attempt trapping of up to 105 ions per pulse. The purification cycle will be performed in a few milliseconds so that short-lived nuclei can be purified. To extract the nuclides of interest from the large amount of isobaric contaminants, a resolving power of 105 is mandatory. Afterwards the ions of interest will be accumulated in the second trap until they constitute a sufficiently pure sample for the measurements. The status of the project is presented.

  16. Selective ATP-competitive inhibitors of TOR suppress rapamycin-insensitive function of TORC2 in Saccharomyces cerevisiae.

    PubMed

    Liu, Qingsong; Ren, Tao; Fresques, Tara; Oppliger, Wolfgang; Niles, Brad J; Hur, Wooyoung; Sabatini, David M; Hall, Michael N; Powers, Ted; Gray, Nathanael S

    2012-06-15

    The target of rapamycin (TOR) is a critical regulator of growth, survival, and energy metabolism. The allosteric TORC1 inhibitor rapamycin has been used extensively to elucidate the TOR related signal pathway but is limited by its inability to inhibit TORC2. We used an unbiased cell proliferation assay of a kinase inhibitor library to discover QL-IX-55 as a potent inhibitor of S. cerevisiae growth. The functional target of QL-IX-55 is the ATP-binding site of TOR2 as evidenced by the discovery of resistant alleles of TOR2 through rational design and unbiased selection strategies. QL-IX-55 is capable of potently inhibiting both TOR complex 1 and 2 (TORC1 and TORC2) as demonstrated by biochemical IP kinase assays (IC(50) <50 nM) and cellular assays for inhibition of substrate YPK1 phosphorylation. In contrast to rapamycin, QL-IX-55 is capable of inhibiting TORC2-dependent transcription, which suggests that this compound will be a powerful probe to dissect the Tor2/TORC2-related signaling pathway in yeast.

  17. 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.

  18. 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.

  19. Preprocessing significantly improves the peptide/protein identification sensitivity of high-resolution isobarically labeled tandem mass spectrometry data.

    PubMed

    Sheng, Quanhu; Li, Rongxia; Dai, Jie; Li, Qingrun; Su, Zhiduan; Guo, Yan; Li, Chen; Shyr, Yu; Zeng, Rong

    2015-02-01

    Isobaric labeling techniques coupled with high-resolution mass spectrometry have been widely employed in proteomic workflows requiring relative quantification. For each high-resolution tandem mass spectrum (MS/MS), isobaric labeling techniques can be used not only to quantify the peptide from different samples by reporter ions, but also to identify the peptide it is derived from. Because the ions related to isobaric labeling may act as noise in database searching, the MS/MS spectrum should be preprocessed before peptide or protein identification. In this article, we demonstrate that there are a lot of high-frequency, high-abundance isobaric related ions in the MS/MS spectrum, and removing isobaric related ions combined with deisotoping and deconvolution in MS/MS preprocessing procedures significantly improves the peptide/protein identification sensitivity. The user-friendly software package TurboRaw2MGF (v2.0) has been implemented for converting raw TIC data files to mascot generic format files and can be downloaded for free from https://github.com/shengqh/RCPA.Tools/releases as part of the software suite ProteomicsTools. The data have been deposited to the ProteomeXchange with identifier PXD000994. PMID:25435543

  20. Preprocessing significantly improves the peptide/protein identification sensitivity of high-resolution isobarically labeled tandem mass spectrometry data.

    PubMed

    Sheng, Quanhu; Li, Rongxia; Dai, Jie; Li, Qingrun; Su, Zhiduan; Guo, Yan; Li, Chen; Shyr, Yu; Zeng, Rong

    2015-02-01

    Isobaric labeling techniques coupled with high-resolution mass spectrometry have been widely employed in proteomic workflows requiring relative quantification. For each high-resolution tandem mass spectrum (MS/MS), isobaric labeling techniques can be used not only to quantify the peptide from different samples by reporter ions, but also to identify the peptide it is derived from. Because the ions related to isobaric labeling may act as noise in database searching, the MS/MS spectrum should be preprocessed before peptide or protein identification. In this article, we demonstrate that there are a lot of high-frequency, high-abundance isobaric related ions in the MS/MS spectrum, and removing isobaric related ions combined with deisotoping and deconvolution in MS/MS preprocessing procedures significantly improves the peptide/protein identification sensitivity. The user-friendly software package TurboRaw2MGF (v2.0) has been implemented for converting raw TIC data files to mascot generic format files and can be downloaded for free from https://github.com/shengqh/RCPA.Tools/releases as part of the software suite ProteomicsTools. The data have been deposited to the ProteomeXchange with identifier PXD000994.

  1. On the Statistical Significance of Compressed Ratios in Isobaric Labeling: A Cross-Platform Comparison.

    PubMed

    Martinez-Val, Ana; Garcia, Fernando; Ximénez-Embún, Pilar; Ibarz, Nuria; Zarzuela, Eduardo; Ruppen, Isabel; Mohammed, Shabaz; Munoz, Javier

    2016-09-01

    Isobaric labeling is gaining popularity in proteomics due to its multiplexing capacity. However, copeptide fragmentation introduces a bias that undermines its accuracy. Several strategies have been shown to partially and, in some cases, completely solve this issue. However, it is still not clear how ratio compression affects the ability to identify a protein's change of abundance as statistically significant. Here, by using the "two proteomes" approach (E. coli lysates with fixed 2.5 ratios in the presence or absence of human lysates acting as the background interference) and manipulating isolation width values, we were able to model isobaric data with different levels of accuracy and precision in three types of mass spectrometers: LTQ Orbitrap Velos, Impact, and Q Exactive. We determined the influence of these variables on the statistical significance of the distorted ratios and compared them to the ratios measured without impurities. Our results confirm previous findings1-4 regarding the importance of optimizing acquisition parameters in each instrument in order to minimize interference without compromising precision and identification. We also show that, under these experimental conditions, the inclusion of a second replicate increases statistical sensitivity 2-3-fold and counterbalances to a large extent the issue of ratio compression.

  2. Weed control and yield potential for a promising rice line, STG06L-35-061, selected from crosses between weed-suppressive indicas and commercial long-grain rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sustainable weed control is an ongoing challenge in rice production. Indica rice lines such as PI 312777 that can suppress Echinochloa crus-galli and other troublesome C4 grass weeds have been evaluated extensively in Arkansas for more than a decade. In an ongoing breeding/selection program, we are...

  3. 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. PMID:23804703

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

    PubMed Central

    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.

    2013-01-01

    NSAIDs display promising antineoplastic activity for colorectal and other cancers, but toxicity from cyclooxygenase (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 required COX inhibition, although the underlying mechanism is poorly understood. Here we report that the NSAID, sulindac sulfide (SS) inhibits cyclic guanosine 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. SS 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 SS and the cGMP/PKG pathway inhibits colon tumor cell growth appears to involve the transcriptional suppression of β-catenin to inhibit Wnt/β-catenin TCF transcriptional activity, leading to down-regulation 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. PMID:23804703

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

    SciTech Connect

    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.

  6. PIPERADE: A Penning-trap isobar separator for the DESIR low-energy facility of SPIRAL2

    NASA Astrophysics Data System (ADS)

    Ascher, P.; Blank, B.; Blaum, K.; Dupré, P.; Gerbaux, M.; Grévy, S.; Guérin, H.; Heck, M.; Lunney, D.; Naimi, S.; de Roubin, A.

    2014-03-01

    A Penning-trap isobar separator is currently under construction at CENBG (Bordeaux, France) and MPIK (Heidelberg, Germany) for a future installation at the SPIRAL2/DESIR facility. This device aims at purifying the radioactive ion beams from undesired species, in order to deliver highly pure samples of exotic nuclei to the different set-ups which will be installed in the DESIR hall. The present manuscript describes the context and the motivations to build such a system, the targeted characteristics, and the studies to find an efficient purification method for large samples of isobaric species.

  7. Isobaric Molecular Dynamics Version of the Generalized Replica Exchange Method (gREM): Liquid-Vapor Equilibrium.

    PubMed

    Małolepsza, Edyta; Secor, Maxim; Keyes, Tom

    2015-10-22

    A prescription for sampling isobaric generalized ensembles with molecular dynamics is presented and applied to the generalized replica exchange method (gREM), which was designed to simulate first-order phase transitions. The properties of the isobaric gREM ensemble are discussed, and a study is presented for the liquid-vapor equilibrium of the guest molecules given for gas hydrate formation with the mW water model. Phase diagrams, critical parameters, and a law of corresponding states are obtained. PMID:26398582

  8. 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.

  9. Weather maps classification over Greek domain based on isobaric line patterns. A pattern recognition approach

    NASA Astrophysics Data System (ADS)

    Zagouras, Athanassios; Argiriou, Athanassios A.; Economou, George; Fotopoulos, Spiros; Flocas, Helena A.

    2013-11-01

    The paper presents a semi-supervised weather classification method based on 850-hPa isobaric level maps. A preprocessing step is employed, where isolines of geopotential height are extracted from weather map images via an image processing procedure. Α feature extraction stage follows where two techniques are applied. The first technique implements phase space reconstruction, and yields multidimensional delay distributions. The second technique is based on chain code representation of signals, from which histogram features are derived. Similarity measures are used to compare multidimensional data and the k-means algorithm is applied in the final stage. The method is applied over the area of Greece, and the resulting catalogues are compared to a subjective classification for this area. Numerical experiments with datasets derived from the European Meteorological Bulletin archives exhibit an up to 91 % accurate agreement with the subjective weather patterns.

  10. Ultrahigh-temperature metamorphism under isobaric heating: New evidence from the North China Craton

    NASA Astrophysics Data System (ADS)

    Yang, Qiong-Yan; Santosh, M.; Tsunogae, Toshiaki

    2014-12-01

    The Khondalite Belt within Inner Mongolia Suture Zone (IMSZ) in the North China Craton (NCC) preserves evidence for extreme crustal metamorphism under ultra-high temperature (UHT) conditions at ca. 1.92 Ga, associated with the subduction-collision tectonics between the Yinshan and Ordos Blocks. Here we report a new locality in Hongsigou where cordierite- and spinel-bearing granulites record UHT metamorphism. The prograde, peak, and retrograde mineral assemblages in these pelitic granulites have been identified based on petrography and mineral chemistry as: Bt1 + Grt1 + Sil1 + Kfs1 + Pl1 + Ilm + Qtz1, Grt1 + Sil2 + Kfs2 + Pl2 + Spl + Ilm + Qtz2 + Liq, and Crd + Grt2 + Sil3 + Kfs2 + Pl2 + Ilm + Qtz2 respectively. The peak metamorphic conditions of the pelitic granulite were estimated as 930-1050 °C and 6.5-7.5 kbar based on pseudosection analysis in the system NCKFMASHTO, suggesting extreme thermal metamorphism. We report LA-ICPMS zircon U-Pb data from the granulite which show weighted mean 207Pb/206Pb age of 1881 ± 6.6 Ma, marking the timing of UHT metamorphism. Lu-Hf analyses of the zircons show εHf(t) values within a restricted range of -4.2 to 0.3 and together with Hf model ages, a Paleoproterozoic arc magmatic source is inferred for the detrital zircons. The estimated P-T path for the UHT granulite suggests isobaric heating followed by cooling and decompression along a clockwise trajectory, different from the anti-clockwise P-T paths defined in earlier studies for the 1.92 Ga UHT rocks from the IMSZ. The younger age and the isobaric heating trajectory suggest that the Hongsigou UHT rocks are related to heat input from underplated mafic magmas following continental collision.

  11. Premixed hydrogen-oxygen flames. Part II: Quasi-isobaric ignition near the flammability limits

    SciTech Connect

    He, Longting; Clavin, P. Univ. d'Aix-Marseille )

    1993-06-01

    A numerical study of one-dimensional and time-dependent problems in quasi-isobaric combustion of H2-02 mixtures is carried out with a complex chemical network and detailed molecular transport mechanisms. A first numerical result shows that a diffusive-thermal instability corresponding to a Hopf bifurcation appears in the propagation of planar flames in the neighborhood of the H2-rich flammability limit. The corresponding critical mole fraction of H2 is 0.947 at ordinary conditions with a flame velocity of about 45 cm/s, compared with 0.96 for the flammability limit. The quasi-isobaric ignition by a hot pocket of combustion products is also investigated numerically. The critical size of the hot pockets is determined as a function of the equivalence ratio. It is found that when the H2-rich flammability limit is approached, the critical radius becomes much larger than the flame thickness and moreover, it diverges before reaching the planar flammability limit, at a critical H2 mole fraction about 0.945 at ordinary conditions (compared with 0.96). Thus, planar flames cannot be ignited in this way in the range of H2 mole fractions between 0.945 and 0.96 where the burning velocity varies from about 50 cm/s to few millimeters per second. Near the H2 lean flammability limit the situation is quite different. The critical size is smaller than the planar flame thickness, and spherical flames with a very small initial radius may grow in lean mixtures even beyond the flammability limit of planar flames. These phenomena are explained by an elementary analytical study of a minimal model coupling preferential diffusion mechanisms with the kinetic effects controlling the planar flammability limits.

  12. 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

  13. 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.

  14. 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.

  15. Isobaric multiplet mass equation in the A =31 ,T =3 /2 quartets

    NASA Astrophysics Data System (ADS)

    Bennett, M. B.; Wrede, C.; Brown, B. A.; Liddick, S. N.; Pérez-Loureiro, D.; Bardayan, D. W.; Chen, A. A.; Chipps, K. A.; Fry, C.; Glassman, B. E.; Langer, C.; Larson, N. R.; McNeice, E. I.; Meisel, Z.; Ong, W.; O'Malley, P. D.; Pain, S. D.; Prokop, C. J.; Schwartz, S. B.; Suchyta, S.; Thompson, P.; Walters, M.; Xu, X.

    2016-06-01

    Background: The observed mass excesses of analog nuclear states with the same mass number A and isospin T can be used to test the isobaric multiplet mass equation (IMME), which has, in most cases, been validated to a high degree of precision. A recent measurement [Kankainen et al., Phys. Rev. C 93, 041304(R) (2016), 10.1103/PhysRevC.93.041304] of the ground-state mass of 31Cl led to a substantial breakdown of the IMME for the lowest A =31 ,T =3 /2 quartet. The second-lowest A =31 ,T =3 /2 quartet is not complete, due to uncertainties associated with the identity of the 31S member state. Purpose: Our goal is to populate the two lowest T =3 /2 states in 31S and use the data to investigate the influence of isospin mixing on tests of the IMME in the two lowest A =31 ,T =3 /2 quartets. Methods: Using a fast 31Cl beam implanted into a plastic scintillator and a high-purity Ge γ -ray detection array, γ rays from the 31Cl(β γ )31S sequence were measured. Shell-model calculations using USDB and the recently-developed USDE interactions were performed for comparison. Results: Isospin mixing between the 31S isobaric analog state (IAS) at 6279.0(6) keV and a nearby state at 6390.2(7) keV was observed. The second T =3 /2 state in 31S was observed at Ex=7050.0 (8 ) keV. Calculations using both USDB and USDE predict a triplet of isospin-mixed states, including the lowest T =3 /2 state in 31P, mirroring the observed mixing in 31S, and two isospin-mixed triplets including the second-lowest T =3 /2 states in both 31S and 31P. Conclusions: Isospin mixing in 31S does not by itself explain the IMME breakdown in the lowest quartet, but it likely points to similar isospin mixing in the mirror nucleus 31P, which would result in a perturbation of the 31P IAS energy. USDB and USDE calculations both predict candidate 31P states responsible for the mixing in the energy region slightly above Ex=6400 keV. The second quartet has been completed thanks to the identification of the second 31S T

  16. Rectal reservoir and sensory function studied by graded isobaric distension in normal man.

    PubMed Central

    Akervall, S; Fasth, S; Nordgren, S; Oresland, T; Hultén, L

    1989-01-01

    The rectal expansion and concomitant sensory function on graded, isobaric, rectal distension within the interval 5-60 cm H2O was investigated in 36 healthy young volunteers. Anal pressure and electromyography (EMG) from the external anal sphincter were simultaneously recorded. Rectal distension caused an initial rapid expansion followed by transient, often repeated, reflex rectal contractions and a slow gradual increase of rectal volume. The maximal volume displaced by the first reflex rectal contraction was 18 (13) ml, which was less than 10% of the volume at 60 s. The pressure threshold for appreciation of rectal filling was 12 cm H2O (95% CL 5-15 cm H2O) and coincided with the threshold for rectoanal inhibition. Urge to defecate was experienced at 28 cm H2O (15-50 cm H2O) distension pressure, which was close to the threshold for maximal rectal contraction, also coinciding with the appearance of the external anal sphincter reflex. The interindividual variation of rectal volume on distension with defined pressures varied widely, indicating a considerable variation of rectal compliance in normal man. No correlation was found between rectal volume and sex or anthropometric variables. The relative variations in pressure thresholds for eliciting rectal sensation and rectoanal reflexes were less than the corresponding threshold volumes. It was concluded that the dynamic rectal response to distension reflects a well graded reflex adjustment ideal for a reservoir. PMID:2714682

  17. Isobaric analog resonances of Mg31 and the border of the island of inversion

    NASA Astrophysics Data System (ADS)

    Imai, N.; Mukai, M.; Cederkäll, J.; Aghai, H.; Golubev, P.; Johansson, H. T.; Kahl, D.; Kurcewics, J.; Teranishi, T.; Watanabe, Y. X.

    2014-07-01

    The evolution of the nuclear shell structure in the region of the neutron-rich shell-breaking nucleus Mg32 has been the subject of considerable interest. We present here the first determination of the overlap of the ground and two first excited states in Mg31 with a neutron coupled to the ground state in Mg30 based on studies of its isobaric analog resonances in Al31. The excitation function for proton resonant elastic scattering on Mg30 was measured close to 0∘ in the laboratory frame by bombarding a thick polyethylene target with a Mg30 beam at an energy of 2.92 MeV/nucleon at the REX-ISOLDE facility at CERN. Three resonances were successfully resolved, and angular momenta and total and proton resonance widths were determined by using R-matrix analysis. The deduced spectroscopic factor for the ground state in Mg31 is consistent with the shell-model calculation, whereas those for the first and second excited states could not be reproduced. These results show that a drastic change in structure occurs between Mg30 and Mg31 and that the onset of structural change in this region therefore occurs between these two isotopes.

  18. 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

  19. Precision Test of the Isobaric Multiplet Mass Equation in the A = 32, T = 2 Quintet

    NASA Astrophysics Data System (ADS)

    Ferrer, R.; Kwiatkowski, A. A.; Bollen, G.; Campbell, C. M.; Folden, C. M., III; Lincoln, D.; Morrissey, D. J.; Pang, G. K.; Prinke, A.; Savory, J.; Schwarz, S.

    2008-10-01

    Masses of the radionuclides ^32,33Si and ^34P and of the stable nuclide ^32S have been measured with the Low Energy Beam and Ion Trap (LEBIT) Penning trap mass spectrometer. Relative mass uncertainties of 3 x 10-8 and better have been achieved. The measured mass value of ^32Si differs from the literature value [1,2] by four standard deviations. The precise mass determination of ^32Si and ^32S have been employed to test the isobaric multiplet mass equation for the A = 32, T= 2 isospin quintet. The experimental results indicate a significant deviation from the quadratic form. This work has been supported by Michigan State University, the NSF under contract number PHY- 0606007, and the DOE under the contract DE-FG02-00ER41144. References: 1. G. Audi, A.H. Wapstra, and C. Thibault, Nucl. Phys. A729 (2003) 337 2. A. Paul, S. R"ottger, A. Zimbal, and U. Keyser, Hyperfine Interact. 132 (2001) 189

  20. Mass of astrophysically relevant 31Cl and the breakdown of the isobaric multiplet mass equation

    NASA Astrophysics Data System (ADS)

    Kankainen, A.; Canete, L.; Eronen, T.; Hakala, J.; Jokinen, A.; Koponen, J.; Moore, I. D.; Nesterenko, D.; Reinikainen, J.; Rinta-Antila, S.; Voss, A.; ńystö, J.

    2016-04-01

    The mass of 31Cl has been measured with the JYFLTRAP double-Penning-trap mass spectrometer at the Ion Guide Isotope Separator On-Line (IGISOL) facility. The determined mass-excess value, -7034.7 (34 ) keV, is 15 times more precise than in the Atomic Mass Evaluation 2012. The quadratic form of the isobaric multiplet mass equation for the T =3 /2 quartet at A =31 fails (χn2=11.6 ) and a nonzero cubic term, d =-3.5 (11 ) keV, is obtained when the new mass value is adopted. 31Cl has been found to be less proton-bound, with a proton separation energy of Sp=264.6 (34 ) keV. Energies for the excited states in 31Cl and the photodisintegration rate on 31Cl have been determined with significantly improved precision by using the new Sp value. The improved photodisintegration rate helps to constrain astrophysical conditions where 30S can act as a waiting point in the rapid proton capture process in type-I x-ray bursts.

  1. Flow structure behind the Mach disk in supersonic non-isobaric jet

    NASA Astrophysics Data System (ADS)

    Zapryagaev, V. I.; Boiko, V. M.; Kavun, I. N.; Kiselev, N. P.; Pivovarov, A. A.

    2016-10-01

    The flow structure behind the Mach disk in the first cell of free supersonic underexpanded jets exhuasting from nozzles of different geometric Mach numbers at nozzle exit was examined. Flow visualization pictures obtained with the help of the direct-shadow method, the schlieren method, and the laser sheet technique are presented. It is shown that, in the subsonic zone behind the Mach disk of free supersonic non-isobaric jets exhausting from conical nozzles with Ma = 2.5 and Ma = 3 in a wide range of gas-dynamic regimes, the shape of the Mach disk corresponds to that of a normal shock, and this shape undergoes no deformation, i.e. no recirculation region is registered behind the Mach disk. Experiments using the contactless panoramic laser PIV method were performed. From measured fields of flow velocity at outflow regimes of free supersonic jet with Npr = 8.5 and Ma = 1.5, the non-occurrence of flow recirculation zone behind the Mach disk was demonstrated.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Effect of spinal anesthesia for elective cesarean section on cerebral blood oxygenation changes: comparison of hyperbaric and isobaric bupivacaine.

    PubMed

    Kondo, Yuko; Sakatani, Kaoru; Hirose, Noriya; Maeda, Takeshi; Kato, Jitsu; Ogawa, Setsuro; Katayama, Yoichi

    2013-01-01

    We used near-infrared spectroscopy (NIRS) to evaluate cerebral blood oxygenation changes in subjects undergoing cesarean section under spinal anesthesia (SP) with hyperbaric bupivacaine (group H, 27 subjects) or isobaric bupivacaine (group I, 15 subjects). In group H, total-Hb, oxy-Hb, and mean blood pressure (MBP) within 20 min after SP were significantly lower than the baseline values. In contrast, there was no significant change from baseline in total-Hb, oxy-Hb, or MBP in group I after SP. Total-Hb and MBP in group H were significantly lower than those in group I within 10 min after SP. There was no significant change of deoxy-Hb, tissue oxygen index, or heart rate from baseline in either of the groups. These results suggest that isobaric bupivacaine may be superior to hyperbaric bupivacaine for preventing a decrease of maternal cerebral blood flow after SP for cesarean section.

  8. 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  10. 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.

  11. 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

    2016-09-01

    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.

  12. 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.

  13. 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

  14. 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. PMID:21989882

  15. 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.

  16. 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

  17. A comparative quantitative analysis of the IDEAL (iterative decomposition of water and fat with echo asymmetry and least-squares estimation) and the CHESS (chemical shift selection suppression) techniques in 3.0 T L-spine MRI

    NASA Astrophysics Data System (ADS)

    Kim, Eng-Chan; Cho, Jae-Hwan; Kim, Min-Hye; Kim, Ki-Hong; Choi, Cheon-Woong; Seok, Jong-min; Na, Kil-Ju; Han, Man-Seok

    2013-03-01

    This study was conducted on 20 patients who had undergone pedicle screw fixation between March and December 2010 to quantitatively compare a conventional fat suppression technique, CHESS (chemical shift selection suppression), and a new technique, IDEAL (iterative decomposition of water and fat with echo asymmetry and least squares estimation). The general efficacy and usefulness of the IDEAL technique was also evaluated. Fat-suppressed transverse-relaxation-weighed images and longitudinal-relaxation-weighted images were obtained before and after contrast injection by using these two techniques with a 1.5T MR (magnetic resonance) scanner. The obtained images were analyzed for image distortion, susceptibility artifacts and homogenous fat removal in the target region. The results showed that the image distortion due to the susceptibility artifacts caused by implanted metal was lower in the images obtained using the IDEAL technique compared to those obtained using the CHESS technique. The results of a qualitative analysis also showed that compared to the CHESS technique, fewer susceptibility artifacts and more homogenous fat removal were found in the images obtained using the IDEAL technique in a comparative image evaluation of the axial plane images before and after contrast injection. In summary, compared to the CHESS technique, the IDEAL technique showed a lower occurrence of susceptibility artifacts caused by metal and lower image distortion. In addition, more homogenous fat removal was shown in the IDEAL technique.

  18. 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

  19. Isobaric Tags for Relative and Absolute Quantitation-Based Proteomic Analysis of Patent and Constricted Ductus Arteriosus Tissues Confirms the Systemic Regulation of Ductus Arteriosus Closure.

    PubMed

    Hong, Haifa; Ye, Lincai; Chen, Huiwen; Xia, Yu; Liu, Yue; Liu, Jinfen; Lu, Yanan; Zhang, Haibo

    2015-08-01

    We aimed to evaluate global changes in protein expression associated with patency by undertaking proteomic analysis of human constricted and patent ductus arteriosus (DA). Ten constricted and 10 patent human DAs were excised from infants with ductal-dependent heart disease during surgery. Using isobaric tags for relative and absolute quantitation-based quantitative proteomics, 132 differentially expressed proteins were identified. Of 132 proteins, voltage-gated sodium channel 1.3 (SCN3A), myosin 1d (Myo1d), Rho GTPase activating protein 26 (ARHGAP26), and retinitis pigmentosa 1 (RP1) were selected for validation by Western blot and quantitative real-time polymerase chain reaction analyses. Significant upregulation of SCN3A, Myo1d, and RP1 messenger RNA, and protein levels was observed in the patent DA group (all P ≤ 0.048). ARHGAP26 messenger RNA and protein levels were decreased in patent DA tissue (both P ≤ 0.018). Immunohistochemistry analysis revealed that Myo1d, ARHGAP26, and RP1 were specifically expressed in the subendothelial region of constricted DAs; however, diffuse expression of these proteins was noted in the patent group. Proteomic analysis revealed global changes in the expression of proteins that regulate oxygen sensing, ion channels, smooth muscle cell migration, nervous system, immune system, and metabolism, suggesting a basis for the systemic regulation of DA patency by diverse signaling pathways, which will be confirmed in further studies.

  20. Neuronal apoptosis induced by selective inhibition of Rac GTPase versus global suppression of Rho family GTPases is mediated by alterations in distinct mitogen-activated protein kinase signaling cascades.

    PubMed

    Stankiewicz, Trisha R; Ramaswami, Sai Anandi; Bouchard, Ron J; Aktories, Klaus; Linseman, Daniel A

    2015-04-10

    Rho family GTPases play integral roles in neuronal differentiation and survival. We have shown previously that Clostridium difficile toxin B (ToxB), an inhibitor of RhoA, Rac1, and Cdc42, induces apoptosis of cerebellar granule neurons (CGNs). In this study, we compared the effects of ToxB to a selective inhibitor of the Rac-specific guanine nucleotide exchange factors Tiam1 and Trio (NSC23766). In a manner similar to ToxB, selective inhibition of Rac induces CGN apoptosis associated with enhanced caspase-3 activation and reduced phosphorylation of the Rac effector p21-activated kinase. In contrast to ToxB, caspase inhibitors do not protect CGNs from targeted inhibition of Rac. Also dissimilar to ToxB, selective inhibition of Rac does not inhibit MEK1/2/ERK1/2 or activate JNK/c-Jun. Instead, targeted inhibition of Rac suppresses distinct MEK5/ERK5, p90Rsk, and Akt-dependent signaling cascades known to regulate the localization and expression of the Bcl-2 homology 3 domain-only protein Bad. Adenoviral expression of a constitutively active mutant of MEK5 is sufficient to attenuate neuronal cell death induced by selective inhibition of Rac with NSC23766 but not apoptosis induced by global inhibition of Rho GTPases with ToxB. Collectively, these data demonstrate that global suppression of Rho family GTPases with ToxB causes a loss of MEK1/2/ERK1/2 signaling and activation of JNK/c-Jun, resulting in diminished degradation and enhanced transcription of the Bcl-2 homology 3 domain-only protein Bim. In contrast, selective inhibition of Rac induces CGN apoptosis by repressing unique MEK5/ERK5, p90Rsk, and Akt-dependent prosurvival pathways, ultimately leading to enhanced expression, dephosphorylation, and mitochondrial localization of proapoptotic Bad.

  1. Neuronal Apoptosis Induced by Selective Inhibition of Rac GTPase versus Global Suppression of Rho Family GTPases Is Mediated by Alterations in Distinct Mitogen-activated Protein Kinase Signaling Cascades*

    PubMed Central

    Stankiewicz, Trisha R.; Ramaswami, Sai Anandi; Bouchard, Ron J.; Aktories, Klaus; Linseman, Daniel A.

    2015-01-01

    Rho family GTPases play integral roles in neuronal differentiation and survival. We have shown previously that Clostridium difficile toxin B (ToxB), an inhibitor of RhoA, Rac1, and Cdc42, induces apoptosis of cerebellar granule neurons (CGNs). In this study, we compared the effects of ToxB to a selective inhibitor of the Rac-specific guanine nucleotide exchange factors Tiam1 and Trio (NSC23766). In a manner similar to ToxB, selective inhibition of Rac induces CGN apoptosis associated with enhanced caspase-3 activation and reduced phosphorylation of the Rac effector p21-activated kinase. In contrast to ToxB, caspase inhibitors do not protect CGNs from targeted inhibition of Rac. Also dissimilar to ToxB, selective inhibition of Rac does not inhibit MEK1/2/ERK1/2 or activate JNK/c-Jun. Instead, targeted inhibition of Rac suppresses distinct MEK5/ERK5, p90Rsk, and Akt-dependent signaling cascades known to regulate the localization and expression of the Bcl-2 homology 3 domain-only protein Bad. Adenoviral expression of a constitutively active mutant of MEK5 is sufficient to attenuate neuronal cell death induced by selective inhibition of Rac with NSC23766 but not apoptosis induced by global inhibition of Rho GTPases with ToxB. Collectively, these data demonstrate that global suppression of Rho family GTPases with ToxB causes a loss of MEK1/2/ERK1/2 signaling and activation of JNK/c-Jun, resulting in diminished degradation and enhanced transcription of the Bcl-2 homology 3 domain-only protein Bim. In contrast, selective inhibition of Rac induces CGN apoptosis by repressing unique MEK5/ERK5, p90Rsk, and Akt-dependent prosurvival pathways, ultimately leading to enhanced expression, dephosphorylation, and mitochondrial localization of proapoptotic Bad. PMID:25666619

  2. 41Ca ultratrace determination with isotopic selectivity > 10(12) by diode-laser-based RIMS.

    PubMed

    Müller, P; Bushaw, B A; Blaum, K; Diel, S; Geppert, C; Nähler, A; Trautmann, N; Nörtershäuser, W; Wendt, K

    2001-07-01

    41Ca ultratrace determination by diode-laser-based resonance ionization mass spectrometry with extremely high isotopic selectivity is presented. Application to environmental dosimetry of nuclear reactor components, to cosmochemical investigations of production cross sections, and biomedical isotope-tracer studies of human calcium kinetics are discussed. Future investigations are possible use in 41Ca-radiodating. Depending on the application, 41Ca isotopic abundances in the range of 10(-9) to 10(-15) relative to the dominant stable isotope 40Ca must be determined. Either double- or triple-resonance optical excitation with narrow-band extended cavity diode lasers and subsequent non-resonant photoionization of calcium in a collimated atomic beam were used. The resulting photoions are detected with a quadrupole mass spectrometer optimized for background reduction and neighboring mass suppression. Applying the full triple-resonance scheme provides a selectivity of approximately 5 x 10(12) in the suppression of neighboring isotopes and > 10(8) for isobars, together with an overall detection efficiency of approximately 5 x 10(-5). Measurements on a variety of sample types are discussed; the accuracy and reproducibility of the resulting 41Ca/40Ca isotope ratios was better than 5%.

  3. 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.

  4. 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. PMID:26867748

  5. [Spinal anesthesia using a low dose of isobaric bupivacaine in a patient with pulmonary artery hypertension and mixed obstructive and restrictive lung disease undergoing repeated femoral fracture surgery].

    PubMed

    Uzawa, Koji; Hakone, Masako; Nakazawa, Harumasa; Yasuda, Hiroyuki; Moriyama, Kiyoshi; Yorozu, Tomoko

    2014-02-01

    A 75-year-old woman with primary pulmonary hypertension was on medical therapy and ambulatory oxygen inhalation therapy for 7 years. The patient had right femoral fracture and was admitted to our hospital. She had also suffered from asthma for 2 years, and her vital capacity was 1.35 l with forced expiratory volume in 1 second 0.79 l, and with her mean pulmonary artery pressure 60 mmHg. Open reduction and internal fixation were performed under spinal anesthesia using isobaric bupivacaine 6 mg with fentanyl 10 microg, and the patient was discharged on postoperative 31 day with no major complications. One year after the surgery, she had left femoral fracture, and surgery was performed under spinal anesthesia using isobaric bupivacaine 6 mg with fentanyl 10 microg. With its minimal effects on hemodynamics, we speculate that spinal anesthesia using a low dose of isobaric bupivacaine can be a choice for patients with pulmonary hypertension. PMID:24601108

  6. Next generation fire suppressants

    SciTech Connect

    Brown, J.A.

    1995-03-01

    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 band microprocessor 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.

  7. 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.

  8. SPARC Expression Is Selectively Suppressed in Tumor Initiating Urospheres Isolated from As+3- and Cd+2-Transformed Human Urothelial Cells (UROtsa) Stably Transfected with SPARC

    PubMed Central

    Slusser-Nore, Andrea; Larson-Casey, Jennifer L.; Zhang, Ruowen; Zhou, Xu Dong; Somji, Seema; Garrett, Scott H.; Sens, Donald A.; Dunlevy, Jane R.

    2016-01-01

    Background This laboratory previously analyzed the expression of SPARC in the parental UROtsa cells, their arsenite (As+3) and cadmium (Cd+2)-transformed cell lines, and tumor transplants generated from the transformed cells. It was demonstrated that SPARC expression was down-regulated to background levels in Cd+2-and As+3-transformed UROtsa cells and tumor transplants compared to parental cells. In the present study, the transformed cell lines were stably transfected with a SPARC expression vector to determine the effect of SPARC expression on the ability of the cells to form tumors in immune-compromised mice. Methods Real time PCR, western blotting, immunohistochemistry, and immunofluorescence were used to define the expression of SPARC in the As+3-and Cd+2-transformed cell lines, and urospheres isolated from these cell lines, following their stable transfection with an expression vector containing the SPARC open reading frame (ORF). Transplantation of the cultured cells into immune-compromised mice by subcutaneous injection was used to assess the effect of SPARC expression on tumors generated from the above cell lines and urospheres. Results It was shown that the As+3-and Cd+2-transformed UROtsa cells could undergo stable transfection with a SPARC expression vector and that the transfected cells expressed both SPARC mRNA and secreted protein. Tumors formed from these SPARC-transfected cells were shown to have no expression of SPARC. Urospheres isolated from cultures of the SPARC-transfected As+3-and Cd+2-transformed cell lines were shown to have only background expression of SPARC. Urospheres from both the non-transfected and SPARC-transfected cell lines were tumorigenic and thus fit the definition for a population of tumor initiating cells. Conclusions Tumor initiating cells isolated from SPARC-transfected As+3-and Cd+2-transformed cell lines have an inherent mechanism to suppress the expression of SPARC mRNA. PMID:26783756

  9. 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. PMID:26752281

  10. 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.

  11. A novel discovery of IK1 channel agonist: zacopride selectively enhances IK1 current and suppresses triggered arrhythmias in the rat.

    PubMed

    Liu, Qing-Hua; Li, Xiao-Li; Xu, Yan-Wu; Lin, Yuan-Yuan; Cao, Ji-Min; Wu, Bo-Wei

    2012-01-01

    Modulation of the inward rectifier K current (IK1) has profound effect on cardiac excitability and underlies new antiarrhythmic strategies. However, IK1-specific pharmacological tools, especially the selective IK1 agonists, are still lacking in the market. Zacopride, a gastrointestinal prokinetic drug, was found to be a selective IK1 channel agonist. By using the whole-cell patch clamp technique, it was found that zacopride (0.1-10 μmole/L) dose dependently enhanced the IK1 current in isolated rat cardiomyocytes, had no effects on other ion channels, transporters, or pumps. At the same dosage range, zacopride hyperpolarized the resting potential and shortened the action potential duration. When applied at the optimal dose of 1.0 μmole/L, zacopride could prevent or eliminate aconitine induced after depolarization and triggered activity in isolated cardiomyocytes. In a rat model of aconitine-induced arrhythmias both ex vivo and in vivo, zacopride (1.0 μmole/L or 25 μg/kg, respectively) treatment apparently protected the heart from ventricular tachyarrhythmias, which compares favorably with 7.5 mg/kg of lidocaine, a classical aconitine antidote. In conclusion, zacopride was found to be a selective IK1 agonist, and agonizing IK1 could prevent or eliminate aconitine-induced arrhythmias in the rat.

  12. 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

  13. 2p-2p decay of {sup 8}C and isospin-allowed 2p decay of the isobaric-analog state in {sup 8}B

    SciTech Connect

    Charity, R. J.; Elson, J. M.; Manfredi, J.; Shane, R.; Sobotka, L. G.; Chajecki, Z.; Coupland, D.; Iwasaki, H.; Kilburn, M.; Lee, Jenny; Lynch, W. G.; Sanetullaev, A.; Tsang, M. B.; Winkelbauer, J.; Youngs, M.; Marley, S. T.; Shetty, D. V.; Wuosmaa, A. H.; Ghosh, T. K.

    2010-10-15

    {sup 8}C is found to decay to four protons and an {alpha} particle in two 2p emission steps. The correlations between the protons in the first step ({sup 8}C to {sup 6}Be) exhibit a significant enhancement in the region of the decay phase space where the two protons have small relative energy, a region sometimes called the diproton region. The decay of the isobaric analog of {sup 8}C in {sup 8}B is also found to decay by 2p emission. This is the first case of isospin-allowed 2p decay between isobaric analog states.

  14. Short-term selective alleviation of glucotoxicity and lipotoxicity ameliorates the suppressed expression of key β-cell factors under diabetic conditions.

    PubMed

    Shimo, Naoki; Matsuoka, Taka-aki; Miyatsuka, Takeshi; Takebe, Satomi; Tochino, Yoshihiro; Takahara, Mitsuyoshi; Kaneto, Hideaki; Shimomura, Iichiro

    2015-11-27

    Alleviation of hyperglycaemia and hyperlipidemia improves pancreatic β-cell function in type 2 diabetes. However, the underlying molecular mechanisms are still not well clarified. In this study, we aimed to elucidate how the expression alterations of key β-cell factors are altered by the short-term selective alleviation of glucotoxicity or lipotoxicity. We treated db/db mice for one week with empagliflozin and/or bezafibrate to alleviate glucotoxicity and/or liptotoxicity, respectively. The gene expression levels of Pdx1 and Mafa, and their potential targets, insulin 1, Slc2a2, and Glp1r, were higher in the islets of empagliflozin-treated mice, and levels of insulin 2 were higher in mice treated with both reagents, than in untreated mice. Moreover, compared to the pretreatment levels, Mafa and insulin 1 expression increased in empagliflozin-treated mice, and Slc2a2 increased in combination-treated mice. In addition, empagliflozin treatment enhanced β-cell proliferation assessed by Ki-67 immunostaining. Our date clearly demonstrated that the one-week selective alleviation of glucotoxicity led to the better expression levels of the key β-cell factors critical for β-cell function over pretreatment levels, and that the alleviation of lipotoxicity along with glucotoxicity augmented the favorable effects under diabetic conditions. PMID:26471305

  15. Wind-driven spin-up in eddy-resolving ocean models formulated in isopycnic and isobaric coordinates

    NASA Astrophysics Data System (ADS)

    Bleck, Rainer; Boudra, Douglas

    1986-06-01

    Wind-driven spin-up of the four-layer, quasi-isopycnic, eddy-resolving primitive equation model of Bleck and Boudra (1981) is compared with that obtained with a (numerically dissimilar) "pure" isopycnic coordinate model and an isobaric (i.e., quasi-Cartesian) coordinate model. In particular, the onset of hydrodynamic instabilities in the flow forced by a double-gyre wind stress pattern is studied. The spin-up processes associated with the isopycnic and quasi-isopycnic model are found to be similar, whereas the flow pattern produced by the quasi-Cartesian model deviates in the direction of Holland's (1978) and Holland and Lin's (1975a, b) two-layer solutions.

  16. The separation and analysis of symmetric and asymmetric dimethylarginine and other hydrophilic isobaric compounds using aqueous normal phase chromatography.

    PubMed

    Pesek, Joseph J; Matyksa, Maria T; Modereger, Brent; Hasbun, Alejandra; Phan, Vy T; Mehr, Zahra; Guzman, Mariano; Watanable, Seiichiro

    2016-04-01

    Two biologically important compounds with clinical relevance, asymmetric dimethylarginine and symmetric dimethylarginine, are analyzed using aqueous normal phase chromatography on silica hydride-based columns. Two different stationary phases were tested, a commercially available Diamond Hydride™ and a 2-acrylamido-2-methylpropane sulfonic acid experimental column. Two types of analytical protocols were investigated: analysis of the compounds when separation was achieved and analysis of the compounds with partial chromatographic separation. Urine samples from tuberculosis patients were tested for levels of asymmetric and symmetric dimethylarginine. The mass spectrometric technique of in-source fragmentation that can provide data similar to a tandem mass analyzer was evaluated as a means of identification and quantitation of the two compounds when complete separation is not achieved. This same protocol was also evaluated for two other isobaric compounds, glucose-1 and glucose-6 phohsphate, and leucine and isoleucine.

  17. The separation and analysis of symmetric and asymmetric dimethylarginine and other hydrophilic isobaric compounds using aqueous normal phase chromatography.

    PubMed

    Pesek, Joseph J; Matyksa, Maria T; Modereger, Brent; Hasbun, Alejandra; Phan, Vy T; Mehr, Zahra; Guzman, Mariano; Watanable, Seiichiro

    2016-04-01

    Two biologically important compounds with clinical relevance, asymmetric dimethylarginine and symmetric dimethylarginine, are analyzed using aqueous normal phase chromatography on silica hydride-based columns. Two different stationary phases were tested, a commercially available Diamond Hydride™ and a 2-acrylamido-2-methylpropane sulfonic acid experimental column. Two types of analytical protocols were investigated: analysis of the compounds when separation was achieved and analysis of the compounds with partial chromatographic separation. Urine samples from tuberculosis patients were tested for levels of asymmetric and symmetric dimethylarginine. The mass spectrometric technique of in-source fragmentation that can provide data similar to a tandem mass analyzer was evaluated as a means of identification and quantitation of the two compounds when complete separation is not achieved. This same protocol was also evaluated for two other isobaric compounds, glucose-1 and glucose-6 phohsphate, and leucine and isoleucine. PMID:26952368

  18. The selective dopamine uptake inhibitor, D-84, suppresses cocaine self-administration, but does not occasion cocaine-like levels of generalization.

    PubMed

    Batman, Angela M; Dutta, Aloke K; Reith, Maarten E A; Beardsley, Patrick M

    2010-12-01

    A successful replacement pharmacotherapy for treating cocaine dependency would likely reduce cocaine's abuse, support a low abuse liability, overlap cocaine's subjective effects, and have a long duration of action. Inhibitors with varying selectivity at the dopamine transporter (DAT) have approximated these properties. The objective of the present study was to characterize the behavioural effects of an extremely selective DAT inhibitor, (+) trans-4-(2-Benzhydryloxyethyl)-1-(4-fluorobenzyl) piperadin-3-ol (D-84), a 3-hydroxy substituted piperidine derivative of GBR-12935, for its cocaine-like discriminative stimulus effects, its effects on cocaine self-administration, and for its own self-administration. During cocaine discrimination tests, cocaine occasioned the 10 mg/kg cocaine training stimulus with an ED(50) value of 3.13 (1.54-6.34) mg/kg, and reduced response rates with an ED(50) value of 20.39 (7.24-57.44) mg/kg. D-84 incompletely generalized to the cocaine stimulus occasioning a maximal 76% cocaine-lever responding, while reducing response rates with lower potency than cocaine (ED(50)=30.94 (12.34-77.60) mg/kg). Pretreatment with D-84 (9.6-30.4 mg/kg) significantly (P<0.05) reduced cocaine intake at 17.1 mg/kg D-84 when cocaine was self-administered at 0.5 mg/kg/infusion, and at 30.4 mg/kg D-84 when cocaine was self-administered at 0.1, 0.5 .and 1.0 mg/kg/infusion. During self-administration tests with D-84 (0.1-1 mg/kg/infusion), numbers of infusions significantly exceeded vehicle levels at 0.3 mg/kg/infusion. These results show that D-84 pretreatment can decrease cocaine intake especially when high doses of cocaine are being self-administered. This observation, combined with its incomplete generalization to the cocaine discriminative stimulus and its reported long duration of action, provides a profile consistent with a potential replacement therapy for treating cocaine-abusing patients.

  19. Development and characterization of novel 8-plex DiLeu isobaric labels for quantitative proteomics and peptidomics

    PubMed Central

    Frost, Dustin C.; Greer, Tyler; Xiang, Feng; Liang, Zhidan; Li, Lingjun

    2015-01-01

    Rationale Relative quantification of proteins via their enzymatically digested peptide products determines disease biomarker candidate lists in discovery studies. Isobaric label-based strategies using TMT and iTRAQ allow for up to 10 samples to be multiplexed in one experiment, but their expense limits their use. The demand for cost-effective tagging reagents capable of multiplexing many samples led us to develop an 8-plex version of our isobaric labeling reagent, DiLeu. Methods The original 4-plex DiLeu reagent was extended to an 8-plex set by coupling isotopic variants of dimethylated leucine to an alanine balance group designed to offset the increasing mass of the label’s reporter group. Tryptic peptides from a single protein digest, a protein mixture digest, and Saccharomyces cerevisiae lysate digest were labeled with 8-plex DiLeu and analyzed via nanoLC-MS2 on a Q-Exactive Orbitrap mass spectrometer. Characteristics of 8-plex DiLeu-labeled peptides, including quantitative accuracy and fragmentation, were examined. Results An 8-plex set of DiLeu reagents with 1 Da-spaced reporters was synthesized at a yield of 36%. The average cost to label eight 100 μg peptide samples was calculated to be approximately $15. Normalized collision energy tests on the Q-Exactive revealed that a higher-energy collisional dissociation value of 27 generated the optimum number of high-quality spectral matches. Relative quantification of DiLeu-labeled peptides yielded normalized median ratios accurate to within 12% of their expected values. Conclusions Cost-effective 8-plex DiLeu reagents can be synthesized and applied to relative peptide and protein quantification. These labels increase the multiplexing capacity of our previous 4-plex implementation without requiring high-resolution instrumentation to resolve reporter ion signals. PMID:25981542

  20. Selective activation of adenosine A2A receptors on immune cells by a CD73-dependent prodrug suppresses joint inflammation in experimental rheumatoid arthritis.

    PubMed

    Flögel, Ulrich; Burghoff, Sandra; van Lent, Peter L E M; Temme, Sebastian; Galbarz, Lisa; Ding, Zhaoping; El-Tayeb, Ali; Huels, Sandra; Bönner, Florian; Borg, Nadine; Jacoby, Christoph; Müller, Christa E; van den Berg, Wim B; Schrader, Jürgen

    2012-08-01

    Adenosine A(2A) receptor (A(2A)R) agonists are both highly effective anti-inflammatory agents and potent vasodilators. To separate these two activities, we have synthesized phosphorylated A(2A)R agonists (prodrugs) that require the presence of ecto-5'-nucleotidase (CD73) to become activated. In the model of collagen-induced arthritis, 2-(cyclohexylethylthio)adenosine 5'-monophosphate (chet-AMP), but not 2-(cyclohexylethylthio)adenosine (chet-adenosine), potently reduced inflammation as assessed by fluorine-19 ((19)F) magnetic resonance imaging and by histology. The prodrug effect was blunted by inhibition of CD73 and A(2A)R. The selectivity of drug action is due to profound up-regulation of CD73 and adenosine A(2A)R expression in neutrophils and inflammatory monocytes as found in recovered cells from the synovial fluid of arthritic mice. Plasma chet-adenosine was in the subnanomolar range when chet-AMP was applied, whereas concentrations required for vasodilation were about 100 times higher. Thus, chet-AMP is a potent immunosuppressant with negligible vasodilatory activity. These data suggest that phosphorylated A(2A)R agonists may serve as a promising new group of drugs for targeted immunotherapy of inflammation. PMID:22875828

  1. Selective activation of adenosine A2A receptors on immune cells by a CD73-dependent prodrug suppresses joint inflammation in experimental rheumatoid arthritis.

    PubMed

    Flögel, Ulrich; Burghoff, Sandra; van Lent, Peter L E M; Temme, Sebastian; Galbarz, Lisa; Ding, Zhaoping; El-Tayeb, Ali; Huels, Sandra; Bönner, Florian; Borg, Nadine; Jacoby, Christoph; Müller, Christa E; van den Berg, Wim B; Schrader, Jürgen

    2012-08-01

    Adenosine A(2A) receptor (A(2A)R) agonists are both highly effective anti-inflammatory agents and potent vasodilators. To separate these two activities, we have synthesized phosphorylated A(2A)R agonists (prodrugs) that require the presence of ecto-5'-nucleotidase (CD73) to become activated. In the model of collagen-induced arthritis, 2-(cyclohexylethylthio)adenosine 5'-monophosphate (chet-AMP), but not 2-(cyclohexylethylthio)adenosine (chet-adenosine), potently reduced inflammation as assessed by fluorine-19 ((19)F) magnetic resonance imaging and by histology. The prodrug effect was blunted by inhibition of CD73 and A(2A)R. The selectivity of drug action is due to profound up-regulation of CD73 and adenosine A(2A)R expression in neutrophils and inflammatory monocytes as found in recovered cells from the synovial fluid of arthritic mice. Plasma chet-adenosine was in the subnanomolar range when chet-AMP was applied, whereas concentrations required for vasodilation were about 100 times higher. Thus, chet-AMP is a potent immunosuppressant with negligible vasodilatory activity. These data suggest that phosphorylated A(2A)R agonists may serve as a promising new group of drugs for targeted immunotherapy of inflammation.

  2. 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

  3. Deconstructing Interocular Suppression: Attention and Divisive Normalization.

    PubMed

    Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J

    2015-10-01

    In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression.

  4. SIV antigen immunization induces transient antigen-specific T cell responses and selectively activates viral replication in draining lymph nodes in retroviral suppressed rhesus macaques

    PubMed Central

    2011-01-01

    Background HIV infection causes a qualitative and quantitative loss of CD4+ T cell immunity. The institution of anti-retroviral therapy (ART) restores CD4+ T cell responses to many pathogens, but HIV-specific responses remain deficient. Similarly, therapeutic immunization with HIV antigens of chronically infected, ART treated subjects results in poor induction of HIV-specific CD4 responses. In this study, we used a macaque model of ART treatment during chronic infection to study the virologic consequences of SIV antigen stimulation in lymph nodes early after immunization. Rhesus CMV (RhCMV) seropositive, Mamu A*01 positive rhesus macaques were chronically infected with SIVmac251 and treated with ART. The immune and viral responses to SIV gag and RhCMV pp65 antigen immunization in draining lymph nodes and peripheral blood were analyzed. Animals were immunized on contralateral sides with SIV gag and RhCMV pp65 encoding plasmids, which allowed lymph nodes draining each antigen to be obtained at the same time from the same animal for direct comparison. Results We observed that both SIV and RhCMV immunizations stimulated transient antigen-specific T cell responses in draining lymph nodes. The RhCMV-specific responses were potent and sustained (50 days post-immunization) in the periphery, while the SIV-specific responses were transient and extinguished quickly. The SIV antigen stimulation selectively induced transient SIV replication in draining lymph nodes. Conclusions The data are consistent with a model whereby viral replication in response to SIV antigen stimulation limits the generation of SIV antigen-specific responses and suggests a potential mechanism for the early loss and poor HIV-specific CD4+ T cell response observed in HIV-infected individuals. PMID:21752277

  5. Identification of ATR-Chk1 pathway inhibitors that selectively target p53-deficient cells without directly suppressing ATR catalytic activity

    PubMed Central

    Kawasumi, Masaoki; Bradner, James E.; Tolliday, Nicola; Thibodeau, Renee; Sloan, Heather; Brummond, Kay M.; Nghiem, Paul

    2014-01-01

    Resistance to DNA-damaging chemotherapy is a barrier to effective treatment that appears to be augmented by p53 functional deficiency in many cancers. In p53-deficient cells where the G1/S checkpoint is compromised, cell viability after DNA damage relies upon intact intra-S and G2/M checkpoints mediated by the ATR and Chk1 kinases. Thus, a logical rationale to sensitize p53-deficient cancers to DNA-damaging chemotherapy is through the use of ATP-competitive inhibitors of ATR or Chk1. To discover small molecules that may act on uncharacterized components of the ATR pathway, we performed a phenotype-based screen of 9,195 compounds for their ability to inhibit hydroxyurea-induced phosphorylation of Ser345 on Chk1, known to be a critical ATR substrate. This effort led to the identification of four small-molecule compounds, three of which were derived from known bioactive library (anthothecol, dihydrocelastryl, and erysolin) and one of which was a novel synthetic compound termed MARPIN. These compounds all inhibited ATR-selective phosphorylation and sensitized p53-deficient cancer cells to DNA-damaging agents in vitro and in vivo. Notably, these compounds did not inhibit ATR catalytic activity in vitro, unlike typical ATP-competitive inhibitors, but acted in a mechanistically distinct manner to disable ATR-Chk1 function. Our results highlight a set of novel molecular probes to further elucidate druggable mechanisms to improve cancer therapeutic responses produced by DNA-damaging drugs. PMID:25336189

  6. A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3

    PubMed Central

    Zhang, Chenze; Yan, Wenqiang; Li, Bi; Xu, Bing; Gong, Yan; Chu, Fuhao; Zhang, Yuzhong; Yao, Qiuli; Wang, Penglong; Lei, Haimin

    2015-01-01

    A new anticancer ligustrazine derivative, 3β-hydroxyolea-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methylester (T-OA, C38H58O3N2), was previously reported. It was synthesized via conjugating hepatoprotective and anticancer ingredients of traditional Chinese medicine. We found that T-OA exerted its anticancer activity by preventing the expression of nuclear transcription factor NF-κB/p65 and COX-2 in S180 mice. However, the selective cytotoxicity of T-OA on various kinds of cell lines has not been studied sufficiently. In the present study, compared with Cisplatin, T-OA was more toxic to human hepatoma cell line Bel-7402 (IC50 = 6.36 ± 1.56 µM) than other three cancer cell lines (HeLa, HT-29, BGC-823), and no toxicity was observed toward Madin–Darby canine kidney cell line MDCK (IC50 > 150 µM). The morphological changes of Bel-7402 cells demonstrated that T-OA had an apoptosis-inducing effect which had been substantiated using 4ʹ,6-diamidino-2-phenylindole (DAPI) staining, acridine orange (AO)/ethidium bromide (EB) staining, flow cytometry and mitochondrial membrane potential assay. Combining the immumohistochemical staining, we found T-OA could prevent the expression of NF-κB/p65 and COX-2 in Bel-7402 cells. Both of the proteins have been known to play roles in apoptosis and are mainly located in the nuclei. Moreover subcellular localization was performed to reveal that T-OA exerts in nuclei of Bel-7402 cells. The result was in accordance with the effects of down-regulating the expression of NF-κB/p65 and COX-2. PMID:26193270

  7. 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.

  8. 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

  9. Growth hormone suppression test

    MedlinePlus

    GH suppression test; Glucose loading test; Acromegaly - blood test; Gigantism - blood test ... is not changed and stays high during the suppression test, the provider will suspect gigantism or acromegaly. ...

  10. 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 ...

  11. Selective anticancer agents suppress aging in Drosophila

    PubMed Central

    Danilov, Anton; Shaposhnikov, Mikhail; Plyusnina, Ekaterina; Kogan, Valeria; Fedichev, Peter; Moskalev, Alexey

    2013-01-01

    Mutations of the PI3K, TOR, iNOS, and NF-κB genes increase lifespan of model organisms and reduce the risk of some aging-associated diseases. We studied the effects of inhibitors of PI3K (wortmannin), TOR (rapamycin), iNOS (1400W), NF-κB (pyrrolidin dithiocarbamate and QNZ), and the combined effects of inhibitors: PI3K (wortmannin) and TOR (rapamycin), NF-κB (pyrrolidin dithiocarbamates) and PI3K (wortmannin), NF-κB (pyrrolidine dithiocarbamates) and TOR (rapamycin) on Drosophila melanogaster lifespan and quality of life (locomotor activity and fertility). Our data demonstrate that pharmacological inhibition of PI3K, TOR, NF-κB, and iNOS increases lifespan of Drosophila without decreasing quality of life. The greatest lifespan expanding effect was achieved by a combination of rapamycin (5 μM) and wortmannin (5 μM) (by 23.4%). The bioinformatic analysis (KEGG, REACTOME.PATH, DOLite, and GO.BP) showed the greatest aging-suppressor activity of rapamycin, consistent with experimental data. PMID:24096697

  12. Selective anticancer agents suppress aging in Drosophila.

    PubMed

    Danilov, Anton; Shaposhnikov, Mikhail; Plyusnina, Ekaterina; Kogan, Valeria; Fedichev, Peter; Moskalev, Alexey

    2013-09-01

    Mutations of the PI3K, TOR, iNOS, and NF-κB genes increase lifespan of model organisms and reduce the risk of some aging-associated diseases. We studied the effects of inhibitors of PI3K (wortmannin), TOR (rapamycin), iNOS (1400W), NF-κB (pyrrolidin dithiocarbamate and QNZ), and the combined effects of inhibitors: PI3K (wortmannin) and TOR (rapamycin), NF-κB (pyrrolidin dithiocarbamates) and PI3K (wortmannin), NF-κB (pyrrolidine dithiocarbamates) and TOR (rapamycin) on Drosophila melanogaster lifespan and quality of life (locomotor activity and fertility). Our data demonstrate that pharmacological inhibition of PI3K, TOR, NF-κB, and iNOS increases lifespan of Drosophila without decreasing quality of life. The greatest lifespan expanding effect was achieved by a combination of rapamycin (5 μM) and wortmannin (5 μM) (by 23.4%). The bioinformatic analysis (KEGG, REACTOME.PATH, DOLite, and GO.BP) showed the greatest aging-suppressor activity of rapamycin, consistent with experimental data. PMID:24096697

  13. Proteomic Quantification and Site-Mapping of S-Nitrosylated Proteins Using Isobaric iodoTMT Reagents

    PubMed Central

    2015-01-01

    S-Nitrosylation is a redox-based protein post-translational modification in response to nitric oxide signaling and is involved in a wide range of biological processes. Detection and quantification of protein S-nitrosylation have been challenging tasks due to instability and low abundance of the modification. Many studies have used mass spectrometry (MS)-based methods with different thiol-reactive reagents to label and identify proteins with S-nitrosylated cysteine (SNO-Cys). In this study, we developed a novel iodoTMT switch assay (ISA) using an isobaric set of thiol-reactive iodoTMTsixplex reagents to specifically detect and quantify protein S-nitrosylation. Irreversible labeling of SNO-Cys with the iodoTMTsixplex reagents enables immune-affinity detection of S-nitrosylated proteins, enrichment of iodoTMT-labeled peptides by anti-TMT resin, and importantly, unambiguous modification site-mapping and multiplex quantification by liquid chromatography–tandem MS. Additionally, we significantly improved anti-TMT peptide enrichment efficiency by competitive elution. Using ISA, we identified a set of SNO-Cys sites responding to lipopolysaccharide (LPS) stimulation in murine BV-2 microglial cells and revealed effects of S-allyl cysteine from garlic on LPS-induced protein S-nitrosylation in antioxidative signaling and mitochondrial metabolic pathways. ISA proved to be an effective proteomic approach for quantitative analysis of S-nitrosylation in complex samples and will facilitate the elucidation of molecular mechanisms of nitrosative stress in disease. PMID:24926564

  14. Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of Cryptococcus humicola response to aluminum stress.

    PubMed

    Zhang, Jingjing; Zhang, Lei; Qiu, Jinkui; Nian, Hongjuan

    2015-10-01

    Cryptococcus humicola is a highly aluminum (Al) tolerant yeast strain isolated from a tea field. Here the relative changes of protein expression in C. humicola undergoing aluminum stress were analyzed to understand the genetic basis of aluminum tolerance. In this work, iTRAQ-based (isobaric tags for relative and absolute quantification) quantitative proteomic technology was used to detect statistically significant proteins associated with the response to aluminum stress. A total of 625 proteins were identified and were mainly involved in translation/ribosomal structure and biogenesis, posttranslational modification/protein turnover/chaperones, energy production and conversion, and amino acid transport and metabolism. Of these proteins, 59 exhibited differential expression during aluminum stress. Twenty-nine proteins up-regulated by aluminum were mainly involved in translation/ribosomal structure and biogenesis, posttranslational modification/protein turnover and chaperones, and lipid transport and metabolism. Thirty proteins down-regulated by aluminum were mainly associated with energy transport and metabolism, translation/ribosomal structure and biogenesis, posttranslational modification/protein turnover/chaperones, and lipid transport and metabolism. The potential functions of some proteins in aluminum tolerance are discussed. These functional changes may be beneficial for cells to protect themselves from aluminum toxic conditions.

  15. 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.

  16. 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.

  17. 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.

  18. 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. PMID:21318313

  19. Isobaric vapor-liquid equilibria of octane + 1-butanol, + 2-butanol, and + 2-methyl-2-propanol at 101.3 kPa

    SciTech Connect

    Hiaki, T.; Taniguchi, A.; Tsuji, T.; Hongo, M.; Kojima, K.

    1996-09-01

    Isobaric vapor-liquid equilibria were measured for three binary systems of 1-butanol + octane, 2-butanol + octane, and 2-methyl-2-propanol + octane at 101.3 kPa. The measurements were made in an equilibrium still with circulation of both the vapor and liquid phases. Both 1-butanol + octane and 2-butanol + octane form a minimum boiling azeotrope. 2-Methyl-2-propanol + octane is a nonazeotrope. The activity coefficients of three binary systems were best correlated with the Wilson equation.

  20. Effective suppressibility of chaos.

    PubMed

    López, Álvaro G; Seoane, Jesús M; Sanjuán, Miguel A F

    2013-06-01

    Suppression of chaos is a relevant phenomenon that can take place in nonlinear dynamical systems when a parameter is varied. Here, we investigate the possibilities of effectively suppressing the chaotic motion of a dynamical system by a specific time independent variation of a parameter of our system. In realistic situations, we need to be very careful with the experimental conditions and the accuracy of the parameter measurements. We define the suppressibility, a new measure taking values in the parameter space, that allows us to detect which chaotic motions can be suppressed, what possible new choices of the parameter guarantee their suppression, and how small the parameter variations from the initial chaotic state to the final periodic one are. We apply this measure to a Duffing oscillator and a system consisting on ten globally coupled Hénon maps. We offer as our main result tool sets that can be used as guides to suppress chaotic dynamics. PMID:23822472

  1. 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?

  2. Evaluation and Application of Dimethylated Amino Acids as Isobaric Tags for Quantitative Proteomics of the TGF-β/Smad3 Signaling Pathway.

    PubMed

    Yu, Qing; Shi, Xudong; Greer, Tyler; Lietz, Christopher B; Kent, K Craig; Li, Lingjun

    2016-09-01

    Isobaric labeling has become a widespread tool for quantitative proteomic studies. Here, we report the development and evaluation of several dimethylated amino acids as novel isobaric tags for quantitative proteomics. Four-plex dimethylated alanine (DiAla), valine (DiVal), and leucine (DiLeu) have been synthesized, sharing common features of peptide tagging and reporter ion production. DiAla and DiLeu are shown to achieve complete labeling. These two tags' impacts on peptide fragmentation and quantitation are further evaluated using HEK293 cell lysate. DiAla labeling generates more abundant backbone fragmentation whereas DiLeu labeling produces more intense reporter ions. Nonetheless, both tags enable accurate quantitative analysis of HEK293 cell proteomes. DiAla and DiLeu tags are then applied to study the TGF-β/Smad3 pathway with four differentially treated mouse vascular smooth muscle (MOVAS) cells. Our MS data reveal proteome-wide changes of AdSmad3 as compared to the GFP control, consistent with previous findings of causing smooth muscle cell (SMC) dedifferentiation.1 Additionally, the other two novel mutations on the hub protein Smad3, Y226A, and D408H, show compromised TGF-β/Smad3-dependent gene transcription and reversed phenotypic switch. These results are further corroborated with Western blotting and demonstrate that the novel DiAla and DiLeu isobaric tagging reagents provide useful tools for multiplex quantitative proteomics. PMID:27457343

  3. 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.

  4. Identifying separate components of surround suppression.

    PubMed

    Schallmo, Michael-Paul; Murray, Scott O

    2016-01-01

    Surround suppression is a well-known phenomenon in which the response to a visual stimulus is diminished by the presence of neighboring stimuli. This effect is observed in neural responses in areas such as primary visual cortex, and also manifests in visual contrast perception. Studies in animal models have identified at least two separate mechanisms that may contribute to surround suppression: one that is monocular and resistant to contrast adaptation, and another that is binocular and strongly diminished by adaptation. The current study was designed to investigate whether these two mechanisms exist in humans and if they can be identified psychophysically using eye-of-origin and contrast adaptation manipulations. In addition, we examined the prediction that the monocular suppression component is broadly tuned for orientation, while suppression between eyes is narrowly tuned. Our results confirmed that when center and surrounding stimuli were presented dichoptically (in opposite eyes), suppression was orientation-tuned. Following adaptation in the surrounding region, no dichoptic suppression was observed, and monoptic suppression no longer showed orientation selectivity. These results are consistent with a model of surround suppression that depends on both low-level and higher level components. This work provides a method to assess the separate contributions of these components during spatial context processing in human vision.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Cough suppression disorders spectrum.

    PubMed

    Reich, Jerome M

    2014-02-01

    Volitional cough suppression, identified exclusively in females, is an unusual causal mechanism for instances of lobar atalectasis and bronchiectasis. It is a postulated mechanism for the genesis of Lady Windermere Syndrome.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

    2014-12-01

    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. PMID:25403019

  16. 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.

  17. 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

    2014-12-01

    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.

  18. 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.

  19. Evidence for a breakdown of the isobaric multiplet mass equation: A study of the A=35,T=3/2 isospin quartet

    SciTech Connect

    Yazidjian, C.; Beck, D.; Herfurth, F.; Audi, G.; Guenaut, C.; Lunney, D.; Blaum, K.; George, S.; Herlert, A.; Schweikhard, L.; Kellerbauer, A.; Kluge, H.-J.

    2007-08-15

    Mass measurements on radionuclides along the potassium isotope chain have been performed with the ISOLTRAP Penning trap mass spectrometer. For {sup 35}K (T{sub 1/2}=178 ms) to {sup 46}K (T{sub 1/2}=105 s) relative mass uncertainties of 2x10{sup -8} and better have been achieved. The accurate mass determination of {sup 35}K ({delta}m=0.54 keV) has been exploited to test the isobaric multiplet mass equation for the A=35,T=3/2 isospin quartet. The experimental results indicate a deviation from the generally adopted quadratic form.

  20. A high-performance multiple-reflection time-of-flight mass spectrometer and isobar separator for the research with exotic nuclei

    NASA Astrophysics Data System (ADS)

    Dickel, T.; Plaß, W. R.; Becker, A.; Czok, U.; Geissel, H.; Haettner, E.; Jesch, C.; Kinsel, W.; Petrick, M.; Scheidenberger, C.; Simon, A.; Yavor, M. I.

    2015-03-01

    A novel multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS) and isobar separator for the research with exotic nuclides at low-energy rare isotope beam facilities has been developed, commissioned and characterized. It can be used (i) as broadband mass spectrometer with medium resolution, (ii) as highly accurate mass spectrometer for direct mass measurements and (iii) as high-resolution mass separator. The device features a worldwide unique combination of performance characteristics: a mass resolving power of 600,000 (FWHM), a mass measurement accuracy of ~10-7, large ion capacities in excess of 106 ions per second, a transmission efficiency of up to 70%, single-ion sensitivity, and cycle frequencies of up to 400 Hz have been achieved. The spatial separation of close-lying isobars with an intensity ratio of 200:1 and a binding energy difference as small as 4 MeV has been demonstrated. The MR-TOF-MS is ideally suited for experiments with rare and very short-lived nuclei at present and future in-flight, ISOL or IGISOL facilities, such as the FRS Ion-Catcher and SHIP/SHIPTRAP at GSI, TITAN at TRIUMF, IGISOL at the University of Jyväskylä and the Low-Energy Branch of the Super-FRS at FAIR.

  1. Custom 4-Plex DiLeu Isobaric Labels Enable Relative Quantification of Urinary Proteins in Men with Lower Urinary Tract Symptoms (LUTS)

    PubMed Central

    Greer, Tyler; Hao, Ling; Nechyporenko, Anatoliy; Lee, Sanghee; Vezina, Chad M.; Ricke, Will A.; Marker, Paul C.; Bjorling, Dale E.; Bushman, Wade; Li, Lingjun

    2015-01-01

    The relative quantification of proteins using liquid chromatography mass spectrometry (LC-MS) has allowed researchers to compile lists of potential disease markers. These complex quantitative workflows often include isobaric labeling of enzymatically-produced peptides to analyze their relative abundances across multiple samples in a single LC-MS run. Recent efforts by our lab have provided scientists with cost-effective alternatives to expensive commercial labels. Although the quantitative performance of these dimethyl leucine (DiLeu) labels has been reported using known ratios of complex protein and peptide standards, their potential in large-scale proteomics studies using a clinically relevant system has never been investigated. Our work rectifies this oversight by implementing 4-plex DiLeu to quantify proteins in the urine of aging human males who suffer from lower urinary tract symptoms (LUTS). Protein abundances in 25 LUTS and 15 control patients were compared, revealing that of the 836 proteins quantified, 50 were found to be differentially expressed (>20% change) and statistically significant (p-value <0.05). Gene ontology (GO) analysis of the differentiated proteins showed that many were involved in inflammatory responses and implicated in fibrosis. While confirmation of individual protein abundance changes would be required to verify protein expression, this study represents the first report using the custom isobaric label, 4-plex DiLeu, to quantify protein abundances in a clinically relevant system. PMID:26267142

  2. Microstructural Response During Isothermal and Isobaric Loading of a Precipitation-Strengthened Ni-29.7Ti-20Hf High-Temperature Shape Memory Alloy

    NASA Astrophysics Data System (ADS)

    Benafan, O.; Noebe, R. D.; Padula, S. A.; Vaidyanathan, R.

    2012-12-01

    A stable Ni-rich Ni-29.7Ti-20Hf (at. pct) shape memory alloy, with relatively high transformation temperatures, was shown to exhibit promising properties at lower raw material cost when compared to typical NiTi-X (X = Pt, Pd, Au) high-temperature shape memory alloys (HTSMAs). The excellent dimensional stability and high work output for this alloy were attributed to a coherent, nanometer size precipitate phase observed using transmission electron microscopy. To establish an understanding of the role of these precipitates on the microstructure and ensuing stability of the NiTiHf alloy, a detailed study of the micromechanical and microstructural behaviors was performed. In-situ neutron diffraction at stress and temperature was used to obtain quantitative information on phase-specific internal strain, texture, and phase volume fractions during both isothermal and isobaric testing of the alloy. During isothermal testing, the alloy exhibited low isothermal strains due to limited detwinning, consistent with direct measurements of the bulk texture through neutron diffraction. This limited detwinning was attributed to the pinning of twin and variant boundaries by the dispersion of fine precipitates. During isobaric thermal cycling at 400 MPa, the high work output and near-perfect dimensional stability was attributed to the presence of the precipitates that act as homogeneous sources for the nucleation of martensite throughout the material, while providing resistance to irrecoverable processes such as plastic deformation.

  3. 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.

  4. Selective Involvement of the Checkpoint Regulator VISTA in Suppression of B-Cell, but Not T-Cell, Responsiveness by Monocytic Myeloid-Derived Suppressor Cells from Mice Infected with an Immunodeficiency-Causing Retrovirus.

    PubMed

    Green, Kathy A; Wang, Li; Noelle, Randolph J; Green, William R

    2015-09-01

    Inhibition of T-cell responses in tumor microenvironments by myeloid-derived suppressor cells (MDSCs) is widely accepted. We demonstrated augmentation of monocytic MDSCs whose suppression of not only T-cell, but also B-cell, responsiveness paralleled the immunodeficiency during LP-BM5 retrovirus infection. MDSCs inhibited T cells by inducible nitric oxide synthase (iNOS)/nitric oxide (NO), but uniquely, inhibition of B cells was ~50% dependent each on iNOS/NO and the MDSC-expressed negative-checkpoint regulator VISTA. Blockade with a combination of iNOS/NO and VISTA caused additive or synergistic abrogation of MDSC-mediated suppression of B-cell responsiveness.

  5. Photoimmune suppression and photocarcinogenesis.

    PubMed

    Ullrich, Stephen E

    2002-03-01

    The primary cause of non-melanoma skin cancer, the most prevalent form of human neoplasia, is the ultraviolet (UV) radiation found in sunlight. Exposing mice to UV radiation induces skin cancers that are highly antigenic. Upon transfer of an UV-induced skin cancer to a normal syngeneic mouse, the tumor cells are recognized and rapidly destroyed by the immune system of the recipient. This raises the question of how these cancers avoided immune destruction during their development in the UV-irradiated host. This question was answered when it was discovered that in addition to being carcinogenic, UV radiation was also immunosuppressive. Studies with immune suppressed transplantation recipients, and biopsy proven skin cancer patients have confirmed that UV-induced immune suppression is a risk factor for skin cancer development in humans. It is of great importance, therefore, to understand the mechanisms underlying UV-induced immune suppression. The focus of this manuscript will be to use some examples from the more recent scientific literature to review the mechanisms by which UV radiation suppresses the immune response and allows for the progressive outgrowth of antigenic skin tumors. PMID:11861222

  6. 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

    2014-07-01

    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.

  7. Predicting fire suppression in a simulated engine nacelle.

    SciTech Connect

    Keyser, David R.; Hewson, John C.

    2004-06-01

    The Vulcan fire-field model is employed to simulate the evolution of pool fires and the distribution of fire suppressants in a engine nacelle simulator. The objective is to identify conditions for which suppression will and will not be successful in order to (1) provide input on experimental design and (2) to test the model's predictive capabilities through comparison with future test results. Pool fires, where the fuel pool is on the bottom of the nacelle, have been selected for these tests because they have been identified as among the most challenging to suppress. Modeling of the production HFC-125 fire suppression system predicts that all pool fires are extinguished. Removing nozzles and reducing the rate of suppressant injection eventually lead to a predicted failure to suppress the fires. The stability of the fires, and therefore the difficulty in extinguishing them, depends on a variety of additional factors as discussed in the text.

  8. 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.

  9. 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.

  10. Nonsense suppression in archaea

    PubMed Central

    Bhattacharya, Arpita; Köhrer, Caroline; Mandal, Debabrata; RajBhandary, Uttam L.

    2015-01-01

    Bacterial strains carrying nonsense suppressor tRNA genes played a crucial role in early work on bacterial and bacterial viral genetics. In eukaryotes as well, suppressor tRNAs have played important roles in the genetic analysis of yeast and worms. Surprisingly, little is known about genetic suppression in archaea, and there has been no characterization of suppressor tRNAs or identification of nonsense mutations in any of the archaeal genes. Here, we show, using the β-gal gene as a reporter, that amber, ochre, and opal suppressors derived from the serine and tyrosine tRNAs of the archaeon Haloferax volcanii are active in suppression of their corresponding stop codons. Using a promoter for tRNA expression regulated by tryptophan, we also show inducible and regulatable suppression of all three stop codons in H. volcanii. Additionally, transformation of a ΔpyrE2 H. volcanii strain with plasmids carrying the genes for a pyrE2 amber mutant and the serine amber suppressor tRNA yielded transformants that grow on agar plates lacking uracil. Thus, an auxotrophic amber mutation in the pyrE2 gene can be complemented by expression of the amber suppressor tRNA. These results pave the way for generating archaeal strains carrying inducible suppressor tRNA genes on the chromosome and their use in archaeal and archaeviral genetics. We also provide possible explanations for why suppressor tRNAs have not been identified in archaea. PMID:25918386

  11. Nonsense suppression in archaea.

    PubMed

    Bhattacharya, Arpita; Köhrer, Caroline; Mandal, Debabrata; RajBhandary, Uttam L

    2015-05-12

    Bacterial strains carrying nonsense suppressor tRNA genes played a crucial role in early work on bacterial and bacterial viral genetics. In eukaryotes as well, suppressor tRNAs have played important roles in the genetic analysis of yeast and worms. Surprisingly, little is known about genetic suppression in archaea, and there has been no characterization of suppressor tRNAs or identification of nonsense mutations in any of the archaeal genes. Here, we show, using the β-gal gene as a reporter, that amber, ochre, and opal suppressors derived from the serine and tyrosine tRNAs of the archaeon Haloferax volcanii are active in suppression of their corresponding stop codons. Using a promoter for tRNA expression regulated by tryptophan, we also show inducible and regulatable suppression of all three stop codons in H. volcanii. Additionally, transformation of a ΔpyrE2 H. volcanii strain with plasmids carrying the genes for a pyrE2 amber mutant and the serine amber suppressor tRNA yielded transformants that grow on agar plates lacking uracil. Thus, an auxotrophic amber mutation in the pyrE2 gene can be complemented by expression of the amber suppressor tRNA. These results pave the way for generating archaeal strains carrying inducible suppressor tRNA genes on the chromosome and their use in archaeal and archaeviral genetics. We also provide possible explanations for why suppressor tRNAs have not been identified in archaea.

  12. Denervation suppresses gastric tumorigenesis

    PubMed Central

    Kodama, Yosuke; Muthupalani, Sureshkumar; Westphalen, Christoph B.; Andersen, Gøran T.; Flatberg, Arnar; Johannessen, Helene; Friedman, Richard A.; Renz, Bernhard W.; Sandvik, Arne K.; Beisvag, Vidar; Tomita, Hiroyuki; Hara, Akira; Quante, Michael; Li, Zhishan; Gershon, Michael D.; Kaneko, Kazuhiro; Fox, James G.; Wang, Timothy C.; Chen, Duan

    2015-01-01

    The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. We provide evidence that proper innervation is critical at all stages of gastric tumorigenesis. In three separate mouse models of gastric cancer, surgical or pharmacological denervation of the stomach (bilateral or unilateral truncal vagotomy, or local injection of botulinum toxin type A) markedly reduced tumor incidence and progression, but only in the denervated portion of the stomach. Vagotomy or botulinum toxin type A treatment also enhanced the therapeutic effects of systemic chemotherapy and prolonged survival. Denervation-induced suppression of tumorigenesis was associated with inhibition of Wnt signaling and suppression of stem cell expansion. In gastric organoid cultures, neurons stimulated growth in a Wnt-mediated fashion through cholinergic signaling. Furthermore, pharmacological inhibition or genetic knockout of the muscarinic acetylcholine M3 receptor suppressed gastric tumorigenesis. In gastric cancer patients, tumor stage correlated with neural density and activated Wnt signaling, whereas vagotomy reduced the risk of gastric cancer. Together, our findings suggest that vagal innervation contributes to gastric tumorigenesis via M3 receptor–mediated Wnt signaling in the stem cells, and that denervation might represent a feasible strategy for the control of gastric cancer. PMID:25143365

  13. Nonsense suppression in archaea.

    PubMed

    Bhattacharya, Arpita; Köhrer, Caroline; Mandal, Debabrata; RajBhandary, Uttam L

    2015-05-12

    Bacterial strains carrying nonsense suppressor tRNA genes played a crucial role in early work on bacterial and bacterial viral genetics. In eukaryotes as well, suppressor tRNAs have played important roles in the genetic analysis of yeast and worms. Surprisingly, little is known about genetic suppression in archaea, and there has been no characterization of suppressor tRNAs or identification of nonsense mutations in any of the archaeal genes. Here, we show, using the β-gal gene as a reporter, that amber, ochre, and opal suppressors derived from the serine and tyrosine tRNAs of the archaeon Haloferax volcanii are active in suppression of their corresponding stop codons. Using a promoter for tRNA expression regulated by tryptophan, we also show inducible and regulatable suppression of all three stop codons in H. volcanii. Additionally, transformation of a ΔpyrE2 H. volcanii strain with plasmids carrying the genes for a pyrE2 amber mutant and the serine amber suppressor tRNA yielded transformants that grow on agar plates lacking uracil. Thus, an auxotrophic amber mutation in the pyrE2 gene can be complemented by expression of the amber suppressor tRNA. These results pave the way for generating archaeal strains carrying inducible suppressor tRNA genes on the chromosome and their use in archaeal and archaeviral genetics. We also provide possible explanations for why suppressor tRNAs have not been identified in archaea. PMID:25918386

  14. Formation of garnet + corundum during isobaric cooling at UHT conditions: an example from pelitic granulites of the Highland Complex, Sri Lanka

    NASA Astrophysics Data System (ADS)

    Laksthitha Dharmapriya, Prasanna; Galli, Andrea; Prabath Malaviarachchi, Sanjeeva; Su, Ben-Xun

    2014-05-01

    prograde history. Further heating induced a series of biotite-melting reactions which progressively consumed biotite and quartz from the rock matrix and produced garnet-porphyroblasts and spinel. Textural observations coupled with both pseudosections calculated in the CNKFMASHTMnO system and Ti-in-garnet geothermobarometry suggest that peak metamorphic temperature occurred at UHT conditions of 950-975 0C and pressures of 9-9.5 kbar. Peak T was followed by a period of isobaric cooling responsible for the formation of corundum and Grt2 via the reaction Spl + Sil = Grt2 + Crn at around 930 °C, as well as exsolution of rutile needles and apatite rods from Grt1. Modelling of the mode of spinel, sillimanite, corundum and garnet confirms that along an isobaric cooling path at about 920-930 °C and 9-9.5 kbar corundum appears and spinel contemporaneously disappears. At the same PT conditions, our model predicts a decrease of sillimanite and an increase of garnet content. Further isobaric cooling produced a second generation of biotite at the rim of large Grt1-porphyroblasts at ca. 800 °C. Therefore, the investigated granulites provide a rare but meaningful example where garnet + corundum formed along a retrograde metamorphic trajectory under UHT conditions, forcing to consider isobaric cooling at the base of the crust as an alternative process to explain the formation of coexisting garnet + corundum, especially if the studied rock lacks of cordierite or orthopyroxene.

  15. 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.

  16. Isobaric vapor liquid equilibria data for the binary system (glycidyl butyrate + acetone, glycidyl butyrate + carbon tetrachloride, glycidyl butyrate + chloroform) at atmospheric pressure 101 kPa

    NASA Astrophysics Data System (ADS)

    Huang, Qiang; Meng, Qingyi; Ban, Chunlan; Zhang, Rui; Gao, Yingyu

    2016-09-01

    Isobaric vapor liquid equilibria (VLE) for the binary mixtures of glycidyl butyrate(1) + acetone(2), glycidyl butyrate(1) + carbon tetrachloride(2) and glycidyl butyrate(1) + chloroform(2) at 101 kPa were studied. The experimental data were satisfactorily correlated with the models of Wilson, NRTL and UNIQUAC activity coefficients. The activity coefficients for the equilibrium data were obtained by the nonlinear least square method. The average relative deviations between experimental temperatures and calculated temperatures by the Wilson, NRTL and UNIQUAC models were 0.16, 0.16, 0.23% for glycidyl butyrate(1) + chloroform( 2), 0.38, 0.12, 0.27% for glycidylbutyrate(1) + carbon tetrachloride(2), and 0.67, 0.13, 0.54% for glycidyl butyrate(1) + acetone(2). Azeotrope behavior was not found for these systems. The thermodynamic consistency of the correlations was checked by the Herrington's area test.

  17. 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

  18. Novel and cost-effective 6-plex isobaric tagging reagent, DiART, is effective for identification and relative quantification of complex protein mixtures using PQD fragmentation.

    PubMed

    Ramsubramaniam, Nikhil; Tao, Feng; Li, Shuwei; Marten, Mark R

    2013-09-01

    Deuterium isobaric Amine Reactive Tag (DiART) reagents facilitate relative quantification during proteomic analysis in a functionally similar manner to commercially available isobaric tag for relative and absolute quantitation (iTRAQ) and tandem mass tag (TMT) reagents. In contrast to iTRAQ and TMT, DiART reagents incorporate deuterium isotopes which significantly reduce the number of required synthesis steps and hence have potential to significantly reduce reagent production cost. We examined the capability of DiART for performing quantitative proteomic experiments using a linear ion-trap mass spectrometer with Pulsed Q Dissociation (PQD) fragmentation. Using a synthetic peptide tagged with DiART reagent, we observed a precise mass shift of 144.79 Da on the triply charged precursor ion, which shows complete derivatization of the N-terminus and ε-amino group of lysine. A DiART tagged tryptic digest of bovine serum albumin showed a sequence coverage of 57.99% which was very comparable to that showed by iTRAQ, 54.77%. Furthermore, a ten protein mixture tagged with DiART reagents and mixed in 1:1:1:1:1:1 exhibited < 15% error, whereas a linear trend (slope of 1.085) was observed when tagged proteins were mixed in the ratio 2:1:2:4:10:14 and plotted against theoretical ratios. Finally, when complex cell-wall protein mixtures from the model fungus A. nidulans were tagged with DiART reagents and mixed in different ratios, they exhibited similar trends. We conclude that DiART reagents are capable of performing quantitative proteomic experiments using PQD on a linear ion trap mass spectrometer.

  19. Sulfonium Ion Derivatization, Isobaric Stable Isotope Labeling and Data Dependent CID- and ETD-MS/MS for Enhanced Phosphopeptide Quantitation, Identification and Phosphorylation Site Characterization

    PubMed Central

    Lu, Yali; Zhou, Xiao; Stemmer, Paul M.; Reid, Gavin E.

    2014-01-01

    An amine specific peptide derivatization strategy involving the use of novel isobaric stable isotope encoded ‘fixed charge’ sulfonium ion reagents, coupled with an analysis strategy employing capillary HPLC, ESI-MS, and automated data dependent ion trap CID-MS/MS, -MS3, and/or ETD-MS/MS, has been developed for the improved quantitative analysis of protein phosphorylation, and for identification and characterization of their site(s) of modification. Derivatization of 50 synthetic phosphopeptides with S,S′-dimethylthiobutanoylhydroxysuccinimide ester iodide (DMBNHS), followed by analysis using capillary HPLC-ESI-MS, yielded an average 2.5-fold increase in ionization efficiencies and a significant increase in the presence and/or abundance of higher charge state precursor ions compared to the non-derivatized phosphopeptides. Notably, 44% of the phosphopeptides (22 of 50) in their underivatized states yielded precursor ions whose maximum charge states corresponded to +2, while only 8% (4 of 50) remained at this maximum charge state following DMBNHS derivatization. Quantitative analysis was achieved by measuring the abundances of the diagnostic product ions corresponding to the neutral losses of ‘light’ (S(CH3)2) and ‘heavy’ (S(CD3)2) dimethylsulfide exclusively formed upon CID-MS/MS of isobaric stable isotope labeled forms of the DMBNHS derivatized phosphopeptides. Under these conditions, the phosphate group stayed intact. Access for a greater number of peptides to provide enhanced phosphopeptide sequence identification and phosphorylation site characterization was achieved via automated data-dependent CID-MS3 or ETD-MS/MS analysis due to the formation of the higher charge state precursor ions. Importantly, improved sequence coverage was observed using ETD-MS/MS following introduction of the sulfonium ion fixed charge, but with no detrimental effects on ETD fragmentation efficiency. PMID:21952753

  20. Summation of punishment suppression.

    PubMed

    Van Houten, R; Rudolph, R

    1971-01-01

    In two experiments, eight rats were trained to lever press with food on a variable-interval schedule. Bar pressing produced shock on a variable-interval schedule in the presence of two independently presented stimuli, a light and a tone. Two rats in each experiment received alternative presentations of the light and the tone and were consequently always in the presence of a stimulus that signalled variable-interval punishment. The other two rats in each experiment were treated similarly except that they received periods in which neither light nor tone was present. During these periods, bar pressing was not punished. The two stimuli that signalled punishment were then presented simultaneously to evaluate the effect of stimulus compounding on response suppression. The subjects trained without punishment-free periods did not show summation to the compound stimulus; the subjects trained with punishment-free periods showed summation of suppression. The major difference between the two experiments was the longer mean interval of variable-interval punishment used in the second experiment. This manipulation made the summation effect more resistant to extinction and thus increased its magnitude. PMID:16811483

  1. In vivo-selected mutations in methyl-directed mismatch repair suppress the virulence attenuation of Salmonella dam mutant strains following intraperitoneal, but not oral, infection of naïve mice.

    PubMed

    Heithoff, Douglas M; Badie, Golnaz; Julio, Steven M; Enioutina, Elena Y; Daynes, Raymond A; Sinsheimer, Robert L; Mahan, Michael J

    2007-07-01

    Salmonella enterica serovar Typhimurium that lacks the DNA adenine methylase (Dam) ectopically expresses multiple genes that are preferentially expressed during infection, is attenuated for virulence, and confers heightened immunity in vaccinated hosts. The safety of dam mutant Salmonella vaccines was evaluated by screening within infected mice for isolates that have an increased capacity to cause disease relative to the attenuated parental strain. Since dam mutant strains are sensitive to the DNA base analog 2-aminopurine (2-AP), we screened for 2-AP-resistant (2-AP(r)) isolates in systemic tissues of mice infected with dam mutant Salmonella. Such 2-AP(r) derivatives were isolated following intraperitoneal but not oral administration and were shown to be competent for infectivity via intraperitoneal but not oral infection of naïve mice. These 2-AP(r) derivatives were deficient in methyl-directed mismatch repair and were resistant to nitric oxide, yet they retained the bile-sensitive phenotype of the parental dam mutant strain. Additionally, introduction of a mutH null mutation into dam mutant cells suppressed the inherent defects in intraperitoneal infectivity and nitric oxide resistance, as well as overexpression of SpvB, an actin cytotoxin required for Salmonella systemic survival. These data suggest that restoration of intraperitoneal virulence of dam mutant strains is associated with deficiencies in methyl-directed mismatch repair that correlate with the production of systemically related virulence functions.

  2. Isobaric heating and cooling path of the lower crust of a Variscan exotic unit: evidences from P -T estimates in NW Iberian metapelitic granulites

    NASA Astrophysics Data System (ADS)

    Alampi, A.; Gomez Barreiro, J.; Alvarez Valero, A.; Castiñeiras, P.

    2012-12-01

    Allochthonous complexes (AC) in NW Iberia consist of a pile of exotic units characterized by distinct tectonothermal evolution and lithological association, and separated from each other by tectonic contacts, either thrust or extensional detachments. In the Órdenes AC, three groups of units are recognized from bottom to top in the pile: Basal, Ophiolitic and Upper units. Upper units comprise an ensemble of arc-related rocks with a lower section that underwent a high-P and high-T (HP-HT) evolution, and an upper section with an intermediate - pressure (IP) evolution. Extensional detachments have been commonly identifying at the boundary between HP-HT and IP Upper units, like the Fornás and Corredoiras detachments. Pelitic granulites from one IP upper unit, the O Pino unit, have been investigated. Petrologic studies reveal an isobaric tectono-metamorphic crustal evolution throughout a multidisciplinary integration of: (i) detailed microstructural analysis; (ii) EMP mineral chemistry; (iii) mass-balance of the key and representative chemical reactions observed in the microstructures and subsequent interpretation of the reaction sequence; (iv) P-T estimates and paths from phase diagram modeling. Results in the NCKFMASHT system describe an isobaric (c. 7 kbar) continuous heating (and later cooling) evolution ranging from c. 620 to 680 C crossing into the melt-bearing stability fields. These achieved anatectic conditions are evidenced by the presence of both leucosomes (quartz, plagioclase and muscovite) and glass inclusions, mainly in local garnet cores through the dehydration/melting reactions of muscovite first and biotite later. Chemically distinct generations of garnet and plagioclase are evident and stoichiometrically balance each other in continuous reactions. They are consistent with the observations of both a garnet overgrowth and large patches of plagioclase which host euhedral, smaller garnets. In the cooling episode, the newly-grown garnet reacted with melt

  3. 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.

  4. 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.

  5. 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.

  6. Mechanisms of interleukin-10-mediated immune suppression

    PubMed Central

    Akdis, Cezmi A; Blaser, Kurt

    2001-01-01

    Specific immune suppression and induction of anergy are essential processes in the regulation and circumvention of immune defence. Interleukin-10 (IL-10), a suppressor cytokine of T-cell proliferative and cytokine responses, plays a key regulatory role in tolerizing exogenous antigens during specific immunotherapy (SIT) of allergy and natural exposure to antigens. Specific T-cell tolerance is directed against the T-cell epitopes of an antigen and characterized by suppressed proliferative and T helper type 1 (Th1) and type 2 (Th2) cytokine responses. IL-10 elicits tolerance in T cells by selective inhibition of the CD28 co-stimulatory pathway and thereby controls suppression and development of antigen-specific immunity. IL-10 only inhibits T cells stimulated by low numbers of triggered T-cell receptors and which therefore depend on CD28 co-stimulation. T cells receiving a strong signal from the T-cell receptor alone, and thus not requiring CD28 co-stimulation, are not affected by IL-10. IL-10 inhibits CD28 tyrosine phosphorylation, the initial step of the CD28 signalling pathway, and consequently the phosphatidylinositol 3-kinase p85 binding to CD28. Together these results demonstrate that IL-10-induced selective inhibition of the CD28 co-stimulatory pathway acts as a decisive mechanism in determining whether a T cell will contribute to an immune response or become anergic. PMID:11412299

  7. 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.

  8. 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

  9. 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.; Koshchiy, E.; Roeder, B. T.; Alcorta, M.; Chubarian, G.; Davids, B.; Fu, C.; Hooker, J.; et al

    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

  10. 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

    2011-09-01

    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. PMID:21812409

  11. Isobar-model partial-wave analysis of πN-->ππN in the c.m. energy range 1320-1930 MeV

    NASA Astrophysics Data System (ADS)

    Manley, D. Mark; Arndt, Richard A.; Goradia, Yogesh; Teplitz, Vigdor L.

    1984-09-01

    We study the reactions πN-->ππN in the center-of-mass energy range 1320-1930 MeV within the framework of the isobar model. The present analysis includes over 30% more events than the most extensive previous analysis. Data for π-p-->π+π-n, π-p-->π0π-p, π+p-->π0π+p, and π+p-->π+π+n are simultaneously fitted assuming production of ɛ, ρ, Δ(P33) and N*(P11). The cross section for π-p-->π0π0n is predicted and found to be in good agreement with experiment. πN-->πN* amplitudes for I=12 are investigated for the first time. We confirm the existence of a significant πN* decay for the second P33 resonance and determine that πN* is the dominant inelastic channel for the P31 partial wave. The ρN decay of the G17 wave is observed for the first time. Evidence is found for unestablished resonances near 1900 MeV in the S11, P11, P13, and F15 partial waves. We also discuss evidence for a second F35 resonance. Signs of resonant amplitudes determined from this analysis are compared with results of previous analyses and with predictions from several models.

  12. 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.

  13. Nonanesthetics can suppress learning.

    PubMed

    Kandel, L; Chortkoff, B S; Sonner, J; Laster, M J; Eger, E I

    1996-02-01

    Nonanesthetic gases or vapors do not abolish movement in response to noxious stimuli despite partial pressures and affinities for lipids that would, according to the Meyer-Overton hypothesis, predict such abolition. We investigated whether nonanesthetics depress learning and memory (i.e., provide amnesia). To define learning, we used a "fear-potentiated startle paradigm": rats trained to associate light with a noxious stimulus (footshock) will startle more, as measured by an accelerometer, when a startle-eliciting stimulus (e.g., a noise) is paired with light than when the startle-eliciting stimulus is presented alone. We imposed light-shock pairings on 98 rats under three conditions: no anesthesia (control); 0.20, 0.29, and 0.38 times the minimum alveolar anesthetic concentration (MAC) of desflurane; or two nonanesthetics (1,2-dichloroperfluorocyclobutane and perfluoropentane) at partial pressures predicted from their lipid solubilities to be between 0.2 and 1 MAC. Desflurane produced a dose-related depression of learning with abolition of learning at 0.28 MAC. Perfluoropentane at 0.2-predicted MAC had the same effect as 0.28 MAC desflurane. 1,2-Dichloroperfluorocyclobutane at 0.5- to 1-predicted MAC abolished learning. Because nonanesthetics suppress learning but not movement (the two critical components of anesthesia), they may prove useful in discriminating between mechanisms and sites of action of anesthetics. PMID:8561335

  14. Group VIA Phospholipase A2 (iPLA2β) Modulates Bcl-x 5′-Splice Site Selection and Suppresses Anti-apoptotic Bcl-x(L) in β-Cells*

    PubMed Central

    Barbour, Suzanne E.; Nguyen, Phuong T.; Park, Margaret; Emani, Bhargavi; Lei, Xiaoyong; Kambalapalli, Mamatha; Shultz, Jacqueline C.; Wijesinghe, Dayanjan; Chalfant, Charles E.; Ramanadham, Sasanka

    2015-01-01

    Diabetes is a consequence of reduced β-cell function and mass, due to β-cell apoptosis. Endoplasmic reticulum (ER) stress is induced during β-cell apoptosis due to various stimuli, and our work indicates that group VIA phospholipase A2β (iPLA2β) participates in this process. Delineation of underlying mechanism(s) reveals that ER stress reduces the anti-apoptotic Bcl-x(L) protein in INS-1 cells. The Bcl-x pre-mRNA undergoes alternative pre-mRNA splicing to generate Bcl-x(L) or Bcl-x(S) mature mRNA. We show that both thapsigargin-induced and spontaneous ER stress are associated with reductions in the ratio of Bcl-x(L)/Bcl-x(S) mRNA in INS-1 and islet β-cells. However, chemical inactivation or knockdown of iPLA2β augments the Bcl-x(L)/Bcl-x(S) ratio. Furthermore, the ratio is lower in islets from islet-specific RIP-iPLA2β transgenic mice, whereas islets from global iPLA2β−/− mice exhibit the opposite phenotype. In view of our earlier reports that iPLA2β induces ceramide accumulation through neutral sphingomyelinase 2 and that ceramides shift the Bcl-x 5′-splice site (5′SS) selection in favor of Bcl-x(S), we investigated the potential link between Bcl-x splicing and the iPLA2β/ceramide axis. Exogenous C6-ceramide did not alter Bcl-x 5′SS selection in INS-1 cells, and neutral sphingomyelinase 2 inactivation only partially prevented the ER stress-induced shift in Bcl-x splicing. In contrast, 5(S)-hydroxytetraenoic acid augmented the ratio of Bcl-x(L)/Bcl-x(S) by 15.5-fold. Taken together, these data indicate that β-cell apoptosis is, in part, attributable to the modulation of 5′SS selection in the Bcl-x pre-mRNA by bioactive lipids modulated by iPLA2β. PMID:25762722

  15. 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

  16. Inducing amnesia through systemic suppression.

    PubMed

    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

  17. Sound can suppress visual perception.

    PubMed

    Hidaka, Souta; Ide, Masakazu

    2015-05-29

    In a single modality, the percept of an input (e.g., voices of neighbors) is often suppressed by another (e.g., the sound of a car horn nearby) due to close interactions of neural responses to these inputs. Recent studies have also suggested that close interactions of neural responses could occur even across sensory modalities, especially for audio-visual interactions. However, direct behavioral evidence regarding the audio-visual perceptual suppression effect has not been reported in a study with humans. Here, we investigated whether sound could have a suppressive effect on visual perception. We found that white noise bursts presented through headphones degraded visual orientation discrimination performance. This auditory suppression effect on visual perception frequently occurred when these inputs were presented in a spatially and temporally consistent manner. These results indicate that the perceptual suppression effect could occur across auditory and visual modalities based on close and direct neural interactions among those sensory inputs.

  18. 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.

  19. Phospho-iTRAQ data article: Assessing isobaric labels for the large-scale study of phosphopeptide stoichiometry.

    PubMed

    Glibert, Pieter; Meert, Paulien; Van Steendam, Katleen; Martens, Lennart; Deforce, Dieter; Dhaenens, Maarten

    2015-09-01

    The ability to distinguish between phosphopeptides of high and low stoichiometry is essential to discover the true extent of protein phosphorylation. We here extend the strategy whereby a peptide sample is briefly split in two identical parts and differentially labeled preceding the phosphatase treatment of one part (Pflieger et al., 2008. Mol. Cell. Proteomics, 7: 326-46 [1]; Wu et al., 2011. Nat. Methods, 8: 677-83 [2]). Our Phospho-iTRAQ method focuses on the unmodified counterparts of phosphorylated peptides, which thus circumvents the ionization, fragmentation, and phospho-enrichment difficulties that hamper quantitation of stoichiometry in most common phosphoproteomics methods. Since iTRAQ enables multiplexing, simultaneous (phospho)proteome comparison between internal replicates and multiple samples is possible. The technique was validated on multiple instrument platforms by adding internal standards of high stoichiometry to a complex lysate of control and EGF-stimulated HeLa cells. To demonstrate the flexibility of PhosphoiTRAQ with regards to the experimental setup and data mining, the proteome coverage was extended through gel fractionation, while an internal replicate measurement creates more stringent data analysis opportunities. The latter allows other researchers to set their own threshold for selecting potential phosphorylation events in the dataset presented here, depending on the biological question or corroboration under investigation. The latest developments in MS instrumentation promise to further increase the resolution of the stoichiometric measurement of Phospho-iTRAQ in the future. The data accompanying the manuscript on this approach (Glibert et al., 2015, J. Proteome Res. 14: 2015, 839-49 [5]) have been deposited to the ProteomeXchange with identifier PXD001574.

  20. 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.

  1. Menstrual suppression in the adolescent.

    PubMed

    Kantartzis, Kelly L; Sucato, Gina S

    2013-06-01

    Menstrual suppression, the use of contraceptive methods to eliminate or decrease the frequency of menses, is often prescribed for adolescents to treat menstrual disorders or to accommodate patient preference. For young women using hormonal contraceptives, there is no medical indication for menstruation to occur monthly, and various hormonal contraceptives can be used to decrease the frequency of menstruation with different side effect profiles and rates of amenorrhea. This article reviews the different modalities for menstrual suppression, common conditions in adolescents which may improve with menstrual suppression, and strategies for managing common side effects.

  2. 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.

  3. Equation of state of a dense plasma by orbital-free and quantum molecular dynamics: Examination of two isothermal-isobaric mixing rules

    NASA Astrophysics Data System (ADS)

    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 C2H3 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 C2H3 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.

  4. The director and molecular dynamics of the field-induced alignment of a Gay-Berne nematic phase: An isothermal-isobaric nonequilibrium molecular dynamics simulation study

    NASA Astrophysics Data System (ADS)

    Luckhurst, Geoffrey R.; Satoh, Katsuhiko

    2010-05-01

    Isothermal-isobaric molecular dynamics simulations have been performed for the generic Gay-Berne (GB) mesogen, GB(4.4, 20.0, 1, 1), to investigate director and molecular rotational motion during the field-induced alignment of a nematic. The alignment process for the director is discussed within the context of a hydrodynamic analysis based on the Ericksen-Leslie theory and this is found to predict the simulated behavior well. The dependence of the relaxation time for the alignment on the field strength is also in good accord with the theory. The rotational viscosity coefficient estimated from the simulation is smaller than that typically observed for real nematics and the possible reasons for this are discussed. However, the simulation results are found to follow not only the theory but also the experiments, at least qualitatively. No significant variation in the local and long-range structure of the nematic phase is found during the field-induced alignment process. In addition, we have explored the molecular dynamics in the nematic phase in the presence of the field using the first- and second-rank time autocorrelation functions. More importantly we are able to show that the director relaxation time is longer than that for molecular rotation. It is also possible to use the two orientational correlation times to explore the relationship between the rotational viscosity coefficient and the rotational diffusion constant. The diffusion constants determined from the orientational correlation times, based on the short-time expansion of the autocorrelation functions, are found to be significantly different. In consequence it is not possible to test, unambiguously, the relationship between the rotational viscosity coefficient and the rotational diffusion constant. However, it would seem that the second-rank rotational correlation time provides the most reliable route to the rotational viscosity coefficient.

  5. A formula for charmonium suppression

    SciTech Connect

    Pena, C. Blaschke, D.

    2012-07-15

    In this work a formula for charmonium suppression obtained by Matsui in 1989 is analytically generalized for the case of complex cc-barpotential described by a 3-dimensional and isotropic time-dependent harmonic oscillator (THO). It is suggested that under certain scheme the formula can be applied to describe J/{psi} suppression in heavy-ion collisions at CERN-SPS, RHIC, and LHC with the advantage of analytical tractability.

  6. 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

  7. Suppression of phase synchronisation in network based on cat's brain

    NASA Astrophysics Data System (ADS)

    Lameu, Ewandson L.; Borges, Fernando S.; Borges, Rafael R.; Iarosz, Kelly C.; Caldas, Iberê L.; Batista, Antonio M.; Viana, Ricardo L.; Kurths, Jürgen

    2016-04-01

    We have studied the effects of perturbations on the cat's cerebral cortex. According to the literature, this cortex structure can be described by a clustered network. This way, we construct a clustered network with the same number of areas as in the cat matrix, where each area is described as a sub-network with a small-world property. We focus on the suppression of neuronal phase synchronisation considering different kinds of perturbations. Among the various controlling interventions, we choose three methods: delayed feedback control, external time-periodic driving, and activation of selected neurons. We simulate these interventions to provide a procedure to suppress undesired and pathological abnormal rhythms that can be associated with many forms of synchronisation. In our simulations, we have verified that the efficiency of synchronisation suppression by delayed feedback control is higher than external time-periodic driving and activation of selected neurons of the cat's cerebral cortex with the same coupling strengths.

  8. [Aspirin suppresses microsatellite instability].

    PubMed

    Wallinger, S; Dietmaier, W; Beyser, K; Bocker, T; Hofstädter, F; Fishel, R; Rüschoff, J

    1999-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit cancer preventive effects and have been shown to induce regression of adenomas in FAP patients. In order to elucidate the probable underlying mechanism, the effect of NSAIDs on mismatch repair related microsatellite instability was investigated. Six colorectal cancer cell lines all but one deficient for human mismatch repair (MMR) genes were examined for microsatellite instability (MSI) prior and after treatment with Aspirin or Sulindac. For rapid in vitro analysis of MSI a microcloning assay was developed by combining Laser microdissection and random (PEP-) PCR prior to specific MSI-PCR. Effects of NSAIDs on cell cycle and apoptosis were systematically investigated by using flow cytometry and cell-sorting. MSI frequency in cells deficient of MMR genes (hMSH2, hMLH1, hMSH6) was markedly reduced after long-term (> 10 weeks) NSAID treatment. This effect was reversible, time- and concentration dependent. However, in the hPMS2 deficient endometrial cancer cell line (HEC-1-A) the MSI phenotype kept unchanged. According to cell sorting, non-apoptotic cells were stable and apoptotic cells were unstable. These results suggest that aspirin/sulindac induces a genetic selection for microsatellite stability in a subset of MMR-deficient cells and may thus provide an effective prophylactic therapy for HNPCC related colorectal carcinomas.

  9. 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

  10. Odour suppression in binary mixtures.

    PubMed

    Cashion, Larry; Livermore, Andrew; Hummel, Thomas

    2006-10-01

    It has been suggested that odours causing stronger trigeminal activation suppress weaker trigeminal stimuli and that mixed olfactory-trigeminal stimuli suppress odorants that only activate one of these systems. Volunteer normosmic participants (n=20) were exposed to six odorants with varying trigeminal impact to test the hypothesis that more intense "trigeminal" odorants would suppress weaker trigeminal stimuli in binary odour mixtures. It was also hypothesised that stronger trigeminal odorants would dominate six-odour mixtures. The predicted linear pattern of suppression was not seen, with a quadratic model emerging from the data. Stronger trigeminal stimuli failed to dominate six-odour mixtures. Despite the fact that the major hypothesis was not supported, it can be hypothesised from this experiment that the effect of suppression in binary mixtures is reliant upon two major effects: (1) the association formed between odours and the multiple memory systems that they interact with during the encoding and recognition processes, and (2) the balance between activation of the olfactory and trigeminal systems.

  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. Elucidation of complex decay schemes using on-line mass separated sources and a large array of Compton-suppressed germanium detectors

    NASA Astrophysics Data System (ADS)

    Brown, N.; Wood, J. L.; Kulp, W. D.; Furse, D.; Demand, G. A.; Garrett, P. E.; Green, K. L.; Grinyer, G. F.; Leach, K. G.; Phillips, A. A.; Schumaker, M. A.; Svensson, C. E.; Wong, J.; Ball, G. C.; Bandyopadhyay, D. S.; Hackman, G.; Morton, A. C.; Pearson, C. J.; Austin, R. A. E.; Colosimo, S.; Yates, S. W.; Cross, D.

    2008-10-01

    Complex decay scheme construction using beta decay of isotopes produced by spallation and mass separation on-line at TRIUMF-ISAC and studied with the 8π array of 20 Compton-suppressed germanium detectors is described. Results from the analysis of the ^160Yb -> ^160Tm decay will be presented. Emphasis will be placed on the sensitivity to weak decay branches, assignment of γ-ray lines to isobars, and the use of conversion electron coincidences to observe low-energy transitions. The goal of this work is to achieve detailed decay scheme spectroscopy far from stability with the same level of detail as obtained with the 8π array near stabilty in earlier N=90 studies [1] [2]. [1] W.D. Kulp et al., Phys. Rev. C 69, 064309 (2004). [2] W.D. Kulp et al., Phys. Rev. C 76, 034319 (2007).

  13. Aging and repeated thought suppression success.

    PubMed

    Lambert, Ann E; Smyth, Frederick L; Beadel, Jessica R; Teachman, Bethany A

    2013-01-01

    Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility.

  14. 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.

  15. Visual cortex: suppression by depression?

    PubMed

    Mrsic-Flogel, Thomas; Hübener, Mark

    2002-08-20

    The response of a neuron in the visual cortex to an oriented light bar is strongly reduced by concurrent presentation of a stimulus with a different orientation. New data suggest this 'cross-orientation suppression' is caused, not by intracortical inhibition, but by rapid depression of thalamocortical synapses.

  16. Multiple cilia suppress tumour formation.

    PubMed

    Eberhart, Charles

    2016-04-01

    Primary cilia are cellular structures that have important functions in development and disease. The suppression of multiciliate differentiation of choroid plexus precursors, and maintenance of a single primary cilium by Notch1, is now shown to be involved in choroid plexus tumour formation. PMID:27027488

  17. 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.

  18. 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.

  19. High temperature suppression of dioxins.

    PubMed

    Zhan, Ming-Xiu; Chen, Tong; Fu, Jian-Ying; Lin, Xiao-Qing; Lu, Sheng-Yong; Li, Xiao-Dong; Yan, Jian-Hua; Buekens, Alfons

    2016-03-01

    Combined Sulphur-Nitrogen inhibitors, such as sewage sludge decomposition gases (SDG), thiourea and amidosulphonic acid have been observed to suppress the de novo synthesis of dioxins effectively. In this study, the inhibition of PCDD/Fs formation from model fly ash was investigated at unusually high temperatures (650 °C and 850 °C), well above the usual range of de novo tests (250-400 °C). At 650 °C it was found that SDG evolving from dried sewage sludge could suppress the formation of 2,3,7,8-substituted PCDD/Fs with high efficiency (90%), both in weight units and in I-TEQ units. Additionally, at 850 °C, three kinds of sulphur-amine or sulphur-ammonium compounds were tested to inhibit dioxins formation during laboratory-scale tests, simulating municipal solid waste incineration. The suppression efficiencies of PCDD/Fs formed through homogeneous gas phase reactions were all above 85% when 3 wt. % of thiourea (98.7%), aminosulphonic acid (96.0%) or ammonium thiosulphate (87.3%) was added. Differences in the ratio of PCDFs/PCDDs, in weight average chlorination level and in the congener distribution of the 17 toxic PCDD/Fs indicated that the three inhibitors tested followed distinct suppression pathways, possibly in relation to their different functional groups of nitrogen. Furthermore, thiourea reduced the (weight) average chlorinated level. In addition, the thermal decomposition of TUA was studied by means of thermogravimetry-fourier transform infrared spectroscopy (TG-FTIR) and the presence of SO2, SO3, NH3 and nitriles (N≡C bonds) was shown in the decomposition gases; these gaseous inhibitors might be the primary dioxins suppressants.

  20. Apparatus and method for jet noise suppression

    NASA Astrophysics Data System (ADS)

    Maestrello, L.

    1983-08-01

    A method and apparatus for jet noise suppression through control of the static pressure of the jet and control of the rate of entrainment of ambient fluid into the jet downstream of the exhaust nozzle is disclosed. The momentum flux over an extended region of the jet is regulated, affecting Reynolds stresses in the jet and the spreading angle of the jet. Static pressure is controlled through a long hollow, porous nozzle plug centerbody which may be selectively vented to ambient conditions, connected to a vacuum source, or supplied with fluids of various densities for injection into the stream. Sound in the jet may be channeled along the nozzle plug centerbody by injecting coolant such as a cryogenic fluid throughout the center-body into the jet.

  1. 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.

  2. Manipulation of Rhizosphere Bacterial Communities to Induce Suppressive Soils

    PubMed Central

    Mazzola, Mark

    2007-01-01

    Naturally occurring disease-suppressive soils have been documented in a variety of cropping systems, and in many instances the biological attributes contributing to suppressiveness have been identified. While these studies have often yielded an understanding of operative mechanisms leading to the suppressive state, significant difficulty has been realized in the transfer of this knowledge into achieving effective field-level disease control. Early efforts focused on the inundative application of individual or mixtures of microbial strains recovered from these systems and known to function in specific soil suppressiveness. However, the introduction of biological agents into non-native soil ecosystems typically yielded inconsistent levels of disease control. Of late, greater emphasis has been placed on manipulation of the cropping system to manage resident beneficial rhizosphere microorganisms as a means to suppress soilborne plant pathogens. One such strategy is the cropping of specific plant species or genotypes or the application of soil amendments with the goal of selectively enhancing disease-suppressive rhizobacteria communities. This approach has been utilized in a system attempting to employ biological elements resident to orchard ecosystems as a means to control the biologically complex phenomenon termed apple replant disease. Cropping of wheat in apple orchard soils prior to re-planting the site to apple provided control of the fungal pathogen Rhizoctonia solani AG-5. Disease control was elicited in a wheat cultivar-specific manner and functioned through transformation of the fluorescent pseudomonad population colonizing the rhizosphere of apple. Wheat cultivars that induced disease suppression enhanced populations of specific fluorescent pseudomonad genotypes with antagonistic activity toward R. solani AG-5, but cultivars that did not elicit a disease-suppressive soil did not modify the antagonistic capacity of this bacterial community. Alternatively

  3. 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

  4. Legionella pneumophila Suppresses Interleukin-12 Production by Macrophages

    PubMed Central

    Matsunaga, Kazuto; Klein, Thomas W.; Newton, Catherine; Friedman, Herman; Yamamoto, Yoshimasa

    2001-01-01

    In vitro infection of macrophages with Legionella pneumophila induced interleukin-1α (IL-1α), IL-10, monocyte chemotactic protein 1 (MCP-1), and MCP-3 but not IL-12. The lipopolysaccharide (LPS)-induced production of IL-12 was down-regulated by infection with virulent L. pneumophila, but other cytokines were not affected. In contrast, avirulent L. pneumophila or UV-killed, virulent L. pneumophila did not induce any suppression of IL-12. The IL-12 suppression occurred at the level of mRNA accumulation for IL-12 genes in response to LPS stimulation, but the infection induced a marked accumulation of mRNA for both MCP-1 and MCP-3, which are known to suppress IL-12 production in LPS-stimulated macrophages. However, pretreatment of macrophages with MCP-1 did not suppress LPS-induced IL-12 production at the concentrations induced by L. pneumophila infection. These results suggest that L. pneumophila selectively suppresses IL-12 production induced by LPS from macrophages in vitro by an MCP-independent mechanism. PMID:11179377

  5. EBF noise suppression and aerodynamic penalties. [Externally Blown Flaps

    NASA Technical Reports Server (NTRS)

    Mckinzie, L. J., Jr.

    1978-01-01

    Acoustic tests were conducted at model scale to determine the noise produced in the flyover and sideline planes at reduced separation distances between the nozzle exhaust plane and the flaps of an under-the-wing (UTW) externally blown flap (EBF) configuration in its approach attitude. Tests were also made to determine the noise suppression effectiveness of two types of passive devices which were located on the jet impingement surfaces of the configuration. In addition, static aerodynamic performance data were obtained to evaluate the penalties produced by these suppression devices. Broadband low frequency noise reductions were achieved by reducing the separation distance between the nozzle and flaps. However, mid and high frequency noise was produced which exceeded that of the reference configuration. Two passive noise suppression devices located on the flaps produced moderate to large noise reductions at reduced separation distances. Consideration of the static aerodynamic performance data obtained for the configurations tested suggests that specific broadband noise suppression characteristics may be obtained through a trade-off with aerodynamic performance penalties by the careful selection of suppression devices.

  6. Mass-selective operation with REXTRAP

    NASA Astrophysics Data System (ADS)

    Gustafsson, A.; Herlert, A.; Wenander, F.

    2011-01-01

    At the radioactive ion-beam facility REX-ISOLDE more than 60 different types of radionuclide ions have been post-accelerated to energies up to 3.15 MeV/u within the last years. The transmission efficiency of the system has continually increased with gained operation experience. Apart from striving for the highest possible intensity, the beam purity is also of crucial importance for many experiments. For this reason isobaric contaminant suppression in the low energy stage of REX-ISOLDE has been investigated. Until now the Penning trap system REXTRAP was used solely as a device for bunching the incoming quasi-continuous radioactive ion-beam from ISOLDE and reducing the emittance for efficient injection into the REXEBIS charge breeder. The possibility of operating REXTRAP in a mass-resolving mode and injecting bunched beams from the recently installed radiofrequency quadrupole cooler and buncher ISCOOL has been studied in detail. Results related to transmission efficiency,achieved mass-resolving power, and limitations due to space-charge effects are presented.

  7. 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.

  8. Constrained evolvability of interferon suppression in an RNA virus

    PubMed Central

    Garijo, Raquel; Cuevas, José M.; Briz, Álvaro; Sanjuán, Rafael

    2016-01-01

    Innate immunity responses controlled by interferon (IFN) are believed to constitute a major selective pressure shaping viral evolution. Viruses encode a variety of IFN suppressors, but these are often multifunctional proteins that also play essential roles in other steps of the viral infection cycle, possibly limiting their evolvability. Here, we experimentally evolved a vesicular stomatitis virus (VSV) mutant carrying a defect in the matrix protein (M∆51) that abolishes IFN suppression and that has been previously used in the context of oncolytic virotherapy. Serial transfers of this virus in normal, IFN-secreting cells led to a modest recovery of IFN blocking capacity and to weak increases in viral fitness. Full-genome ultra-deep sequencing and phenotypic analysis of population variants revealed that the anti-IFN function of the matrix protein was not restored, and that the Mdelta51 defect was instead compensated by changes in the viral phosphoprotein. We also show that adaptation to IFN-secreting cells can be driven by the selection of fast-growing viruses with no IFN suppression capacity, and that these population variants can be trans-complemented by other, IFN-suppressing variants. Our results thus suggest that virus-virus interactions and alternative strategies of innate immunity evasion can determine the evolution of IFN suppression in a virus. PMID:27098004

  9. Viral vaccines: selected topics.

    PubMed

    Kańtoch, M

    1996-01-01

    Significant role of viruses in pathology, their dominating position in etiology of infectious diseases point at the special position of active prophylactic procedures based on vaccination. The real role and value of viral vaccines of classic and modern generations, the limitation of immune potency in suppression of defence mechanisms, some problems of immunization against virus vertical transmission are presented in the paper. The reader may find tables which cumulate selected but significant patterns of viral vaccines and vaccinations, and selected papers devoted to topics discussed. PMID:9017153

  10. Background Suppression Effects on Signal Estimation

    SciTech Connect

    Burr, Tom

    2008-01-01

    Gamma detectors at border crossings are intended to detect illicit nuclear material. One performance challenge involves the fact that vehicles suppress the natural background, thus potentially reducing detection probability for threat items. Methods to adjust for background suppression have been considered in related but different settings. Here, methods to adjust for background suppression are tested in the context of signal estimation. Adjustment methods include several clustering options. We find that for the small-to-moderate suppression magnitudes exhibited in the analyzed data, suppression adjustment is only moderatel helpful in locating the signal peak, and in estimating its width or magnitude.

  11. 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

  12. Older adults can suppress unwanted memories when given an appropriate strategy.

    PubMed

    Murray, Brendan D; Anderson, Michael C; Kensinger, Elizabeth A

    2015-03-01

    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.

  13. Comparison of Filters Dedicated to Speckle Suppression in SAR Images

    NASA Astrophysics Data System (ADS)

    Kupidura, P.

    2016-06-01

    This paper presents the results of research on the effectiveness of different filtering methods dedicated to speckle suppression in SAR images. The tests were performed on RadarSat-2 images and on an artificial image treated with simulated speckle noise. The research analysed the performance of particular filters related to the effectiveness of speckle suppression and to the ability to preserve image details and edges. Speckle is a phenomenon inherent to radar images - a deterministic noise connected with land cover type, but also causing significant changes in digital numbers of pixels. As a result, it may affect interpretation, classification and other processes concerning radar images. Speckle, resembling "salt and pepper" noise, has the form of a set of relatively small groups of pixels of values markedly different from values of other pixels representing the same type of land cover. Suppression of this noise may also cause suppression of small image details, therefore the ability to preserve the important parts of an image, was analysed as well. In the present study, selected filters were tested, and methods dedicated particularly to speckle noise suppression: Frost, Gamma-MAP, Lee, Lee-Sigma, Local Region, general filtering methods which might be effective in this respect: Mean, Median, in addition to morphological filters (alternate sequential filters with multiple structuring element and by reconstruction). The analysis presented in this paper compared the effectiveness of different filtering methods. It proved that some of the dedicated radar filters are efficient tools for speckle suppression, but also demonstrated a significant efficiency of the morphological approach, especially its ability to preserve image details.

  14. 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.

  15. 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.

  16. 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

  17. Training voluntary motor suppression with real-time feedback of motor evoked potentials

    PubMed Central

    Majid, D. S. Adnan; Lewis, Christina

    2015-01-01

    Training people to suppress motor representations voluntarily could improve response control. We evaluated a novel training procedure of real-time feedback of motor evoked potentials (MEPs) generated by transcranial magnetic stimulation (TMS) over motor cortex. On each trial, a cue instructed participants to use a mental strategy to suppress a particular finger representation without overt movement. A single pulse of TMS was delivered over motor cortex, and an MEP-derived measure of hand motor excitability was delivered visually to the participant within 500 ms. In experiment 1, we showed that participants learned to reduce the excitability of a particular finger beneath baseline (selective motor suppression) within 30 min of practice. In experiment 2, we performed a double-blind study with 2 training groups (1 with veridical feedback and 1 with matched sham feedback) to show that selective motor suppression depends on the veridical feedback itself. Experiment 3 further demonstrated the importance of veridical feedback by showing that selective motor suppression did not arise from mere mental imagery, even when incentivized with reward. Thus participants can use real-time feedback of TMS-induced MEPs to discover an effective mental strategy for selective motor suppression. This high-temporal-resolution, trial-by-trial-feedback training method could be used to help people better control response tendencies and may serve as a potential therapy for motor disorders such as Tourette's and dystonia. PMID:25744889

  18. Training voluntary motor suppression with real-time feedback of motor evoked potentials.

    PubMed

    Majid, D S Adnan; Lewis, Christina; Aron, Adam R

    2015-05-01

    Training people to suppress motor representations voluntarily could improve response control. We evaluated a novel training procedure of real-time feedback of motor evoked potentials (MEPs) generated by transcranial magnetic stimulation (TMS) over motor cortex. On each trial, a cue instructed participants to use a mental strategy to suppress a particular finger representation without overt movement. A single pulse of TMS was delivered over motor cortex, and an MEP-derived measure of hand motor excitability was delivered visually to the participant within 500 ms. In experiment 1, we showed that participants learned to reduce the excitability of a particular finger beneath baseline (selective motor suppression) within 30 min of practice. In experiment 2, we performed a double-blind study with 2 training groups (1 with veridical feedback and 1 with matched sham feedback) to show that selective motor suppression depends on the veridical feedback itself. Experiment 3 further demonstrated the importance of veridical feedback by showing that selective motor suppression did not arise from mere mental imagery, even when incentivized with reward. Thus participants can use real-time feedback of TMS-induced MEPs to discover an effective mental strategy for selective motor suppression. This high-temporal-resolution, trial-by-trial-feedback training method could be used to help people better control response tendencies and may serve as a potential therapy for motor disorders such as Tourette's and dystonia.

  19. Methods of suppressing automotive interference

    NASA Astrophysics Data System (ADS)

    Taggart, H. E.

    1981-11-01

    Automotive manufacturers utilize several techniques to reduce EMI emanating from the vehicle. The techniques include resistor spark plugs, resistor spark plug cables, use of silicone lubricant in the distributor, use of capacitors as filters, placement of grounding straps at key locations, conductive fan belt discharge, and tire static-charge reduction. If even further reduction is needed to obtain the maximum capability of a specific mobile communication system, additional suppression techniques are discussed which are effective at frequencies from approximately 30 to 1000 MHz. Measurement results show that the EMI from a new production-line automobile, measured in accordance with SAE Standard J551g, can be reduced as much as 10 to 15 dB by employing these suppression techniques. The amount of degradation to a mobile narrow-band FM receiver, such as the type used by law enforcement agencies, can be measured using the measurement technique described. This same technique can then be used as a tool to further reduce EMI from the vehicle components.

  20. 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.

  1. Suppressed epidemics in multirelational networks.

    PubMed

    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 ppR. 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.

  2. 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.

  3. Chaos suppression through asymmetric coupling

    NASA Astrophysics Data System (ADS)

    Bragard, J.; Vidal, G.; Mancini, H.; Mendoza, C.; Boccaletti, S.

    2007-12-01

    We study pairs of identical coupled chaotic oscillators. In particular, we have used Roessler (in the funnel and no funnel regimes), Lorenz, and four-dimensional chaotic Lotka-Volterra models. In all four of these cases, a pair of identical oscillators is asymmetrically coupled. The main result of the numerical simulations is that in all cases, specific values of coupling strength and asymmetry exist that render the two oscillators periodic and synchronized. The values of the coupling strength for which this phenomenon occurs is well below the previously known value for complete synchronization. We have found that this behavior exists for all the chaotic oscillators that we have used in the analysis. We postulate that this behavior is presumably generic to all chaotic oscillators. In order to complete the study, we have tested the robustness of this phenomenon of chaos suppression versus the addition of some Gaussian noise. We found that chaos suppression is robust for the addition of finite noise level. Finally, we propose some extension to this research.

  4. 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.

  5. 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

  6. Hiding information by cell suppression.

    PubMed Central

    Vinterbo, S. A.; Ohno-Machado, L.; Dreiseitl, S.

    2001-01-01

    Joining relational data can jeopardize patient confidentiality if disseminated data for research can be joined with publicly available data containing, for example, explicit identifiers. Ambiguity in data hinders the construction of primary keys that are of importance when joining data tables. We define two values to be indiscernible if they are the same or at least one of them is a special value. Two rows in a data table are indiscernible if their corresponding entries are indiscernible. We further define a table to be k-ambiguous if each row is indiscernible from at least k rows in the same table. We present two simple heuristics to make a table k-ambiguous by cell suppression, and compare them on example data. PMID:11825281

  7. Engineered decoherence: Characterization and suppression

    NASA Astrophysics Data System (ADS)

    Hegde, Swathi S.; Mahesh, T. S.

    2014-06-01

    Due to omnipresent environmental interferences, quantum coherences inevitably undergo irreversible transformations over certain time scales, thus leading to the loss of encoded information. This process, known as decoherence, has been a major obstacle in realizing efficient quantum information processors. Understanding the mechanism of decoherence is crucial in developing tools to inhibit it. Here we utilize a method proposed by Teklemariam et al. [Phys. Rev. A 67, 062316 (2003), 10.1103/PhysRevA.67.062316] to engineer artificial decoherence in the system qubits by randomly perturbing their surrounding ancilla qubits. Using a two-qubit nuclear magnetic resonance quantum register, we characterize the artificial decoherence by noise spectroscopy and quantum process tomography. Further, we study the efficacy of dynamical decoupling sequences in suppressing the artificial decoherence. Here we describe the experimental results and their comparisons with theoretical simulations.

  8. 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.

  9. Genetics of barley hooded suppression.

    PubMed Central

    Roig, Cristina; Pozzi, Carlo; Santi, Luca; Müller, Judith; Wang, Yamei; Stile, Maria Rosaria; Rossini, Laura; Stanca, Michele; Salamini, Francesco

    2004-01-01

    The molecular basis of the barley dominant Hooded (K) mutant is a duplication of 305 bp in intron IV of the homeobox gene Bkn3. A chemical mutagenesis screen was carried out to identify genetical factors that participate in Bkn3 intron-mediated gene regulation. Plants from recurrently mutagenized KK seeds were examined for the suppression of the hooded awn phenotype induced by the K allele and, in total, 41 suK (suppressor of K) recessive mutants were identified. Complementation tests established the existence of five suK loci, and alleles suKB-4, suKC-33, suKD-25, suKE-74, and suKF-76 were studied in detail. All K-suppressed mutants showed a short-awn phenotype. The suK loci have been mapped by bulked segregant analysis nested in a standard mapping procedure based on AFLP markers. K suppressor loci suKB, B, E, and F all map in a short interval of chromosome 7H, while the locus suKD is assigned to chromosome 5H. A complementation test between the four suK mutants mapping on chromosome 7H and the short-awn mutant lks2, located nearby, excluded the allelism between suK loci and lks2. The last experiment made clear that the short-awn phenotype of suK mutants is due to a specific dominant function of the K allele, a function that is independent from the control on hood formation. The suK loci are discussed as candidate participants in the regulation of Bkn3 expression. PMID:15166167

  10. Cis-Suppression to Arrest Protein Aggregation in Mammalian Cells

    PubMed Central

    Gregoire, Simpson; Zhang, Shaojie; Costanzo, Joseph; Wilson, Kelly; Fernandez, Erik J.; Kwon, Inchan

    2015-01-01

    Protein misfolding and aggregation are implicated in numerous human diseases and significantly lower production yield of proteins expressed in mammalian cells. Despite the importance of understanding and suppressing protein aggregation in mammalian cells, a protein design and selection strategy to modulate protein misfolding/aggregation in mammalian cells has not yet been reported. In this work, we address the particular challenge presented by mutation-induced protein aggregation in mammalian cells. We hypothesize that an additional mutation(s) can be introduced in an aggregation-prone protein variant, spatially near the original mutation, to suppress misfolding and aggregation (cis-suppression). As a model protein, we chose human copper, zinc superoxide dismutase mutant (SOD1A4V) containing an alanine to valine mutation at residue 4, associated with the familial form of amyotrophic lateral sclerosis. We used the program RosettaDesign to identify Phe20 in SOD1A4V as a key residue responsible for SOD1A4V conformational destabilization. This information was used to rationally develop a pool of candidate mutations at the Phe20 site. After two rounds of mammalian-cell based screening of the variants, three novel SOD1A4V variants with a significantly reduced aggregation propensity inside cells were selected. The enhanced stability and reduced aggregation propensity of the three novel SOD1A4V variants were verified using cell fractionation and in vitro stability assays. PMID:24114411

  11. Suppression of extraneous thermal noise in cavity optomechanics

    NASA Astrophysics Data System (ADS)

    Zhao, Yi; Wilson, Dalziel; Ni, K.-K.; Kimble, H. J.

    2012-06-01

    Extraneous thermal motion can limit displacement sensitivity and radiation pressure effects, such as optical cooling, in a cavity-optomechanical system. Here we present an active noise suppression scheme and its experimental implementation. Our technique involves mapping a measurement of the extraneous noise onto the frequency of the incident laser field to stabilize the associated laser-cavity detuning. The main challenge is to selectively sense and suppress extraneous thermal noise without affecting motion of the oscillator. Our solution is to monitor two modes of the optical cavity, each with different sensitivity to the oscillator's motion but similar sensitivity to the extraneous thermal motion. This information is used to imprint ``anti-noise'' onto the frequency of the incident laser field. In our system, based on a nano-mechanical membrane coupled to a Fabry-P'erot cavity, simulation and experiment demonstrate that extraneous thermal noise can be selectively suppressed without substantially affecting motion of the oscillator and that the associated limit on optical cooling can be reduced. Details of this work are presented in [1].[4pt] [1] Y. Zhao, D. J. Wilson, K.-K. Ni, and H. J. Kimble, Optics Express (in press); arXiv:1112.3362.

  12. 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.

  13. Residual Versus Suppressed-Carrier Coherent Communications

    NASA Astrophysics Data System (ADS)

    Simon, M. K.; Million, S.

    1996-07-01

    This article addresses the issue of when to suppress or not to suppress the transmitted carrier in designing a coherent communication system employing a carrier tracking loop for carrier synchronization. Assuming that a phase-locked loop (PLL) is used whenever there exists a residual carrier and a Costas loop is used whenever the carrier is suppressed, the regions of system parameters that delineate these two options are presented based on the desire to minimize the average probability of error of the system.

  14. 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.

  15. 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. ...

  16. Nitric oxide mediates caerulein-induced suppression of locomotor activity.

    PubMed

    Volke, V; Soosaar, A; Kõks, S; Bourin, M; Männistö, P T; Vasar, E

    1996-08-01

    Caerulein, a non-selective agonist of cholecystokinin (CCK) receptors, is shown to suppress locomotor activity in rodents via stimulation of CCK(A) receptors. In the present study we examined the possible involvement of nitric oxide (NO) in caerulein-induced hypolocomotion in rats. Caerulein (10 microg/kg) markedly decreased the horizontal and vertical components of locomotor activity in rats measured in dark motility boxes. Pretreatment with a nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), at 5 mg/kg i.p., abolished the inhibiting action of caerulein on the horizontal activity, but did not affect the reduced frequency of rearing. The other doses of L-NAME (1, 10 and 20 mg/kg) were ineffective against caerulein. As L-NAME at this dose range does not stimulate locomotor activity, it is likely that NO is involved in the motor suppressant effect of systemically administered caerulein.

  17. Overdrive suppression of implanted pacemakers in patients with AV block.

    PubMed Central

    Grendahl, H; Miller, M; Kjekshus, J

    1978-01-01

    Patients being permanently paced for symptomatic AV block were studied by overdrive suppression of the QRS-inhibited pacemaker, in order to observe the underlying heart rhythm. The chest wall stimulation method was used. In complete AV block the escape rhythm recovery time proved highly reproducible on repeated testing on the same day, and in many patients remained so over months or years. Occasionally, a doubling of the escape rhythm recovery time was seen, suggesting initial exit block of the escape focus. Resetting of the escape rhythm usually followed an exponential curve until stabilisation after about 3 minutes. An early escape rhythm with a recovery time of less than 4 seconds was found on every occasion in 21 of 58 patients with complete AV block, and inconstantly in 23 more; in 14 it was never observed. Accidental pacing failure was seen in 15 patients. The overdrive suppression test was helpful in selecting pacemaker dependent patients. PMID:637960

  18. Photoperiodic Suppression of Drug Reinstatement

    PubMed Central

    Sorg, Barbara A.; Stark, Gemaine; Sergeeva, Anna; Jansen, Heiko T.

    2011-01-01

    The rewarding influence of drugs of abuse varies with time of day and appears to involve interactions between the circadian and the mesocorticolimbic dopamine systems. The circadian system is also intimately involved in measuring daylength. Thus, the present study examined the impact of changing daylength (photoperiod) on cocaine-seeking behaviors. Male Sprague Dawley rats were trained and tested on a 12L:12D light:dark schedule for cocaine-induced reinstatement of conditioned place preference (CPP) at three times of day (Zeitgeber time (ZT): 4, 12, and 20) to determine a preference score. Rats were then shifted to either shorter (6L:18D) or longer (18L:6D) photoperiods and then to constant conditions, re-tested for cocaine-induced reinstatement under each different condition, and then returned to their original photoperiod (12L:12D) and tested once more. Rats exhibited a circadian profile of preference score in constant darkness with a peak at 12h after lights-off. At both ZT4 and ZT20, but not at ZT12, shorter photoperiods profoundly suppressed cocaine reinstatement, which did not recover even after switching back to 12L:12D. In contrast, longer photoperiods did not alter reinstatement. Separate studies showed that the suppression of cocaine reinstatement was not due to repeated testing. In an additional experiment, we examined the photoperiodic regulation of tyrosine hydroxylase (TH) and dopamine transporter (DAT) proteins in drug-naive rats. These results revealed photoperiodic modulation of proteins in the prefrontal cortex and dorsal striatum, but not in the nucleus accumbens or ventral tegmental area. Together, these findings add further support to the circadian genesis of cocaine-seeking behaviors and demonstrate that drug-induced reinstatement is modulated by photoperiod. Furthermore, the results suggest that photoperiod partly contributes to the seasonal expression of certain drug-related behaviors in humans living at different latitudes and thus our

  19. Suppressing Irrelevant Information: Knowledge Activation or Inhibition?

    ERIC Educational Resources Information Center

    McNamara, Danielle S.; McDaniel, Mark A.

    2004-01-01

    In 3 experiments, the authors examined the role of knowledge activation in the suppression of contextually irrelevant meanings for ambiguous homographs. In Experiments 1 and 2, participants with greater baseball knowledge, regardless of reading skill, more quickly suppressed the irrelevant meaning of ambiguous words in baseball-related, but not…

  20. 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,’ ...

  1. 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.

  2. Prolonged over-suppression syndrome.

    PubMed

    Good, A E; Kempers, R D

    1974-07-01

    The syndrome of postpill amenorrhea was investigated retrospectively by studying records of diagnosed cases of amenorrhea (1300) treated or confirmed at the Mayo Clinic. Data are taken from records dating to 1960 (low use of contraceptives) and terminate in 1971. 12 cases are reviewed which were diagnosed as prolonged oversuppression syndrome. No particular oral contraceptive formulation was implicated. 4 of 12 patients had had irregular menstrual cycles before oral contraceptive therapy; whereas 8 had had regular cycles. Bioassay of urinary gonadotropins were consistently in the mid-low normal limits (only 1 determination was available for each patient); some patients had been radioimmunoassayed (single assay) for other pituitary hormones: LH (luteinizing hormone) was at normal basal levels and FSH (follicle stimulating hormone) was also in the normal range. Concentrations of total circulating estrogens were in low or subnormal range in each case. 4 cases had associated galactorrhea, which was attributed to exogenous steroid suppression of the prolactin-inhibiting center of the pituitary. Clomiphene citrate was used to restore functions of the hypothalamic-pituitary axis, and of the 8 receiving clomiphene, 5 responded and 2 conceived.

  3. Vibration suppression of satellites using multifunctional platforms

    NASA Astrophysics Data System (ADS)

    Antin, Nicolas; Russ, Richard; Ma, Kougen; Ghasemi-Nejhad, Mehrdad N.

    2009-03-01

    This research focuses on a finite element analysis of active vibration suppression capabilities of a smart composite platform, which is a structural interface between a satellite main thruster and its structure and possesses simultaneous precision positioning and vibration suppression capabilities for thrust vector control of a satellite. First, the combined system of the smart composite platform and the satellite structure are briefly described followed by the finite element modeling and simulations. The smart platform piezoelectric patches and stacks material properties modeling, for the finite element analysis, are developed consistent with the manufacturer data. Next, a vibration suppression scheme, based on the modal analysis, is presented and used in vibration suppression analysis of satellite structures of the thrust vector under the thruster-firing excitation. The approach introduced here is an effective technique for the design of smart structures with complex geometry to study their MIMO active vibration suppression capabilities.

  4. 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.

  5. Suppressing irrelevant information: knowledge activation or inhibition?

    PubMed

    McNamara, Danielle S; McDaniel, Mark A

    2004-03-01

    In 3 experiments, the authors examined the role of knowledge activation in the suppression of contextually irrelevant meanings for ambiguous homographs. In Experiments 1 and 2, participants with greater baseball knowledge, regardless of reading skill, more quickly suppressed the irrelevant meaning of ambiguous words in baseball-related, but not general-topic, sentences. Experiment 3 demonstrated that participants with greater general knowledge, regardless of reading skill, more quickly suppressed the irrelevant meaning of the ambiguous words in general-topic sentences. As predicted by D. S. McNamara's (1997) knowledge-based account of suppression, ambiguity effects are influenced by greater activation of knowledge related to the intended meaning of the homograph. These results challenge inhibition (e.g. M. A. Gernsbacher, K. R. Varner. & M. Faust, 1990) as the sole mechanism responsible for the suppression of irrelevant information.

  6. 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. PMID:5142387

  7. 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

  8. The system H 2O-NaCl. Part II: Correlations for molar volume, enthalpy, and isobaric heat capacity from 0 to 1000 °C, 1 to 5000 bar, and 0 to 1 XNaCl

    NASA Astrophysics Data System (ADS)

    Driesner, Thomas

    2007-10-01

    A set of correlations for the volumetric properties and enthalpies of phases in the system H 2O-NaCl as a function of temperature, pressure, and composition has been developed that yields accurate values from 0 to 1000 °C, 1 to 5000 bar, and 0 to 1 XNaCl. The volumetric properties of all fluid phases from low-density vapor to hydrous salt melts and single-phase binary fluids at high pressures and temperatures, can be described by a simple equation V(T,P,X)=VO(n1+n2T,P) i.e., for a given pressure and composition, the molar volume of the solution is related to the molar volume of pure water at the same pressure by a linear scaling of temperature. The parameters n1 and n2 are simple functions of pressure and composition. This linear relation could be demonstrated for all ( P, XNaCl) pairs where accurate volumetric data are available over a sufficiently large temperature interval. Extrapolations over as much as 300 °C predict high temperature data within their experimental uncertainty of 1-2%. With a simple fit of parameters n1 and n2, the vast majority of several thousand experimental data points from the literature can be reproduced within experimental error, including dilute solutions in the compressible region. Although a strict theoretical foundation is lacking, this behavior can phenomenologically be rationalized as reflecting the relation between the linear to near-linear isochores of binary fluids to those of pure water. Accordingly, small deviations from linearity that amount to 0.1-0.2% error in molar volume occur only at low temperatures where the pure water isochores behave non-linearly. This effect is accounted for by introducing a deviation function. Given its high accuracy, the formulation for the molar volumes could be integrated along isotherms-isobars to generate data for the specific enthalpy of binary solutions. In order to allow direct computation rather than numerical integration, a correlation scheme was developed that is mathematically similar

  9. 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.

  10. Studies on the mechanism of systemic suppression of contact hypersensitivity by UVB radiation. II. Differences in the suppression of delayed and contact hypersensitivity in mice.

    PubMed

    Kripke, M L; Morison, W L

    1986-05-01

    Exposing mice to UV radiation in the UVB range (280-320 nm) causes a selective immune suppression that contributes to the development of UVB-induced skin cancers. Among the immune responses suppressed by UVB irradiation are contact and delayed hypersensitivity reactions to haptens administered at unexposed sites. In these studies we provide evidence that delayed and contact hypersensitivity to the same hapten are not equivalent reactions and that they are suppressed in UVB-irradiated mice by 2 different mechanisms. This conclusion is based on the findings that: suppression of contact hypersensitivity could not be overcome by immunizing UVB-irradiated mice with hapten-coupled antigen-presenting cells derived from normal donors; and treatment of UVB-irradiated mice with methylprednisolone before immunization prevented the suppression of delayed hypersensitivity but had no effect on the suppression of contact hypersensitivity. The decreased ability to induce contact hypersensitivity in UVB-irradiated mice could be transferred to x-irradiated mice by reconstituting them with spleen cells from UVB-irradiated donors. The induction of hapten-specific suppressor cells, however, required both UVB irradiation and priming with hapten. Based on these results, we postulate that UVB irradiation induces a population of suppressor-inducer cells with specificity for a modified skin antigen and that this antigen serves as a carrier molecule for haptens that induce contact hypersensitivity and for tumor-specific transplantation antigens on UVB-induced tumors. PMID:3745963

  11. Recoil separator ERNA: gas target and beam suppression

    NASA Astrophysics Data System (ADS)

    Gialanella, L.; Schürmann, D.; Strieder, F.; Di Leva, A.; De Cesare, N.; D'Onofrio, A.; Imbriani, G.; Klug, J.; Lubritto, C.; Ordine, A.; Roca, V.; Röcken, H.; Rolfs, C.; Rogalla, D.; Romano, M.; Schümann, F.; Terrasi, F.; Trautvetter, H. P.

    2004-04-01

    For improved cross-section measurements of the reaction 12C(α,γ) 16O in inverted kinematics, a recoil separator ERNA is developed at the 4 MV Dynamitron tandem accelerator in Bochum to detect directly the 16O recoils with high efficiency. The 16O recoils are produced by the 12C projectiles in a windowless 4He gas target. We report on the pressure profile of the gas target, the beam suppression by the separator, and the first observation of the 16O recoils at selected energies.

  12. Simultaneous suppression of water and fat signals in magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Pirogov, Yuri A.; Anisimov, Nikolai V.; Gubskii, Leonid V.

    2002-05-01

    MR diagnostics with obtaining images cleaned of strong signals of water and fat for discovery small tissue contrast variations related with a pathology is discussed. With help of water suppression, one can reveal the pathological changes of brain in small zones near the liquor spaces, particularly disseminated sclerosis cortical plaques, cerebral lesions, subarachnoid hemorrhage. Under the fat suppression T2-weighted images, inflammatory changes in orbits, cranial base, and spine are surely determined. Among several methods of water or fat suppression, one can indicate methods based on frequency selective saturation of fat signals and methods based on inversion-recovery (IR) pulse sequence. Simultaneous suppression of fat and water opens up additional possibilities in medical diagnostics. We realized simultaneous suppression of fat and water signals at the MR scanner Tomikon S50 (Bruker). We used a pulse sequence based on the IR technique, supplemented with special procedure of frequency-selective fat saturation. Sometimes only simultaneous suppression of fat and water signal made possible successful MRI diagnostics.

  13. 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…

  14. 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

  15. Spider mites suppress tomato defenses downstream of jasmonate and salicylate independently of hormonal crosstalk.

    PubMed

    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.

  16. 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

  17. Glyphosate Suppression of an Elicited Defense Response 1

    PubMed Central

    Sharon, Amir; Amsellem, Ziva; Gressel, Jonathan

    1992-01-01

    The major effort in developing pathogenic fungi into potential mycoherbicides is aimed at increasing fungal virulence to weeds without affecting crop selectivity. Specific suppression of biosynthesis of a phytoalexin derived from the shikimate pathway in Cassia obtusifolia L. by a sublethal dose (50 micromolar) of glyphosate increased susceptibility to the mycoherbicide Alternaria cassiae Jurair & Khan. Glyphosate applied with conidia suppressed phytoalexin synthesis beginning at 12 hours, but not an earlier period 8 to 10 hours after inoculation. The phytoalexin synthesis elicited by fungal inoculation was also suppressed by darkness. The magnitudes of virulence of the mycoherbicide in the dark or with glyphosate in the light were both higher than after inoculation in the light with the same concentration of conidia in the absence of glyphosate. Five times less inoculum was needed to cause disease symptoms when applied with glyphosate than without. Glyphosate did not render A. cassiae virulent on soybean (Glycine max), a crop related to the host. These results suggest that a specific inhibition of a weed's elicited defense response can be a safe way to enhance virulence and improve the efficacy of the mycoherbicide. ImagesFigure 1Figure 3Figure 6 PMID:16668691

  18. 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.

  19. Suppression of ventilatory muscle activity in healthy subjects and COPD patients with negative pressure ventilation.

    PubMed

    Gigliotti, F; Duranti, R; Fabiani, A; Schiavina, M; Scano, G

    1991-05-01

    We evaluated the ability of NPV to suppress EMGd and EMGint in seven patients with severe COPD and five normal subjects. Subjects were studied either without (A) or with mouthpiece and nose clip (B). Electromyographic suppression was assessed comparing EMG activity during NPV with the control activity without a mouthpiece and prior to the initiation of the NPV run. In normal subjects, in A, NPV resulted in a partial suppression of EMGd; in B, prior to NPV, EMGd rose compared with A prior to NPV. In patients, in A, NPV resulted in a suppression of both EMGd and EMGint. In B, prior to NPV, both EMGd and EMGint rose compared with A prior to NPV. Thus, it seems that NPV is able to produce a consistent reduction in inspiratory muscle EMG activity. This variable NPV ability would have to be assessed for better selection criteria for patient candidates in a rehabilitation program.

  20. A suppression hierarchy among competing motor programs drives sequential grooming in Drosophila.

    PubMed

    Seeds, Andrew M; Ravbar, Primoz; Chung, Phuong; Hampel, Stefanie; Midgley, Frank M; Mensh, Brett D; Simpson, Julie H

    2014-08-19

    Motor sequences are formed through the serial execution of different movements, but how nervous systems implement this process remains largely unknown. We determined the organizational principles governing how dirty fruit flies groom their bodies with sequential movements. Using genetically targeted activation of neural subsets, we drove distinct motor programs that clean individual body parts. This enabled competition experiments revealing that the motor programs are organized into a suppression hierarchy; motor programs that occur first suppress those that occur later. Cleaning one body part reduces the sensory drive to its motor program, which relieves suppression of the next movement, allowing the grooming sequence to progress down the hierarchy. A model featuring independently evoked cleaning movements activated in parallel, but selected serially through hierarchical suppression, was successful in reproducing the grooming sequence. This provides the first example of an innate motor sequence implemented by the prevailing model for generating human action sequences.

  1. 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

  2. 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

  3. 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.

  4. [Natural selection].

    PubMed

    Mayr, E

    1985-05-01

    Much of the resistance against Darwin's theory of natural selection has been due to misunderstandings. It is shown that natural selection is not a tautology and that it is a two-step process. The first step, the production of variation, is under the control of chance; the second step, selection proper, is an anti-chance process, but subject to many constraints. The target of selection is the individual as a whole, and many neutral mutations can be retained as hitchhikers of successful genotypes. Sexual selection results from selection for pure reproductive success.

  5. 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.

  6. 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.

  7. Quadratic dynamical decoupling with nonuniform error suppression

    SciTech Connect

    Quiroz, Gregory; Lidar, Daniel A.

    2011-10-15

    We analyze numerically the performance of the near-optimal quadratic dynamical decoupling (QDD) single-qubit decoherence errors suppression method [J. West et al., Phys. Rev. Lett. 104, 130501 (2010)]. The QDD sequence is formed by nesting two optimal Uhrig dynamical decoupling sequences for two orthogonal axes, comprising N{sub 1} and N{sub 2} pulses, respectively. Varying these numbers, we study the decoherence suppression properties of QDD directly by isolating the errors associated with each system basis operator present in the system-bath interaction Hamiltonian. Each individual error scales with the lowest order of the Dyson series, therefore immediately yielding the order of decoherence suppression. We show that the error suppression properties of QDD are dependent upon the parities of N{sub 1} and N{sub 2}, and near-optimal performance is achieved for general single-qubit interactions when N{sub 1}=N{sub 2}.

  8. 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)

  9. Suppression of reactions to certain cosmetics.

    PubMed

    Fisher, A A

    1977-08-01

    Reactions to hair dyes and bleaches may be "suppressed" with corticosteroids and antihistamines. Reactions to nail polish may be prevented by a "drying" or "polymerizing" technique. Sensitization to certain perfume ingredients may be inhibited by a "quenching" phenomenon.

  10. Strangeness suppression in the unquenched quark model

    NASA Astrophysics Data System (ADS)

    Bijker, Roelof; García-Tecocoatzi, Hugo; Santopinto, Elena

    2016-07-01

    In this contribution, we discuss the strangeness suppression in the proton in the framework of the unquenched quark model. The theoretical results are in good agreement with the values extracted from CERN and JLab experiments.

  11. Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression.

    PubMed

    Ramos, Gerardo; Kazimi, Nasser; Nghiem, Dat X; Walterscheid, Jeffrey P; Ullrich, Stephen E

    2004-03-15

    Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependent manner. The release of biological response modifiers, particularly prostaglandin E2 (PGE2), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE2 secretion. Jet fuel-induced PGE2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin. PMID:15020195

  12. Morphine suppression of ethanol withdrawal in mice.

    PubMed

    Blum, K; Wallace, J E; Schwerter, H A; Eubanks, J D

    1976-01-15

    The acute administration of morphine, alcohol or dopamine results in a pronounced suppression of the convulsions produced by alcohol in mice. The suppressive action of morphine on alcohol withdrawal in the mouse apparently is not a product of morphine intoxication, but rather to some other specific interaction between alcohol and morphine in the central nervous system. The conclusion suggest that dopamine may play a significant role as a modulator in convulsions produced during alcohol withdrawal.

  13. Neural repetition suppression reflects fulfilled perceptual expectations

    PubMed Central

    Summerfield, Christopher; Monti, Jim M.P.; Trittschuh, Emily H.; Mesulam, M.-Marsel; Egner, Tobias

    2009-01-01

    Stimulus-evoked neural activity is attenuated upon stimulus repetition (‘repetition suppression’), a phenomenon attributed to largely automatic processes in sensory neurons. By manipulating the likelihood of stimulus repetition, we show that repetition suppression in the human brain is reduced when stimulus repetitions are improbable (and thus, unexpected). These data suggest that repetition suppression reflects a relative reduction in top-down perceptual ‘prediction error’ when processing an expected compared to an unexpected stimulus. PMID:19160497

  14. 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.

  15. On the suppression of vaccination dissent.

    PubMed

    Martin, Brian

    2015-02-01

    Dissenters from the dominant views about vaccination sometimes are subject to adverse actions, including abusive comment, threats, formal complaints,censorship, and de registration, a phenomenon that can be called suppression of dissent. Three types of cases are examined: scientists and physicians; a high-profile researcher; and a citizen campaigner. Comparing the methods used in these different types of cases provides a preliminary framework for understanding the dynamics of suppression in terms of vulnerabilities. PMID:24658876

  16. 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.

  17. On the suppression of vaccination dissent.

    PubMed

    Martin, Brian

    2015-02-01

    Dissenters from the dominant views about vaccination sometimes are subject to adverse actions, including abusive comment, threats, formal complaints,censorship, and de registration, a phenomenon that can be called suppression of dissent. Three types of cases are examined: scientists and physicians; a high-profile researcher; and a citizen campaigner. Comparing the methods used in these different types of cases provides a preliminary framework for understanding the dynamics of suppression in terms of vulnerabilities.

  18. 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.

  19. 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

  20. Leptin suppresses sweet taste responses of enteroendocrine STC-1 cells.

    PubMed

    Jyotaki, Masafumi; Sanematsu, Keisuke; Shigemura, Noriatsu; Yoshida, Ryusuke; Ninomiya, Yuzo

    2016-09-22

    Leptin is an important hormone that regulates food intake and energy homeostasis by acting on central and peripheral targets. In the gustatory system, leptin is known to selectively suppress sweet responses by inhibiting the activation of sweet sensitive taste cells. Sweet taste receptor (T1R2+T1R3) is also expressed in gut enteroendocrine cells and contributes to nutrient sensing, hormone release and glucose absorption. Because of the similarities in expression patterns between enteroendocrine and taste receptor cells, we hypothesized that they may also share similar mechanisms used to modify/regulate the sweet responsiveness of these cells by leptin. Here, we used mouse enteroendocrine cell line STC-1 and examined potential effect of leptin on Ca(2+) responses of STC-1 cells to various taste compounds. Ca(2+) responses to sweet compounds in STC-1 cells were suppressed by a rodent T1R3 inhibitor gurmarin, suggesting the involvement of T1R3-dependent receptors in detection of sweet compounds. Responses to sweet substances were suppressed by ⩾1ng/ml leptin without affecting responses to bitter, umami and salty compounds. This effect was inhibited by a leptin antagonist (mutant L39A/D40A/F41A) and by ATP gated K(+) (KATP) channel closer glibenclamide, suggesting that leptin affects sweet taste responses of enteroendocrine cells via activation of leptin receptor and KATP channel expressed in these cells. Moreover, leptin selectively inhibited sweet-induced but not bitter-induced glucagon-like peptide-1 (GLP-1) secretion from STC-1 cells. These results suggest that leptin modulates sweet taste responses of enteroendocrine cells to regulate nutrient sensing, hormone release and glucose absorption in the gut. PMID:27353597

  1. 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

  2. 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.%.

  3. Feature-based attention modulates surround suppression.

    PubMed

    Flevaris, Anastasia V; Murray, Scott O

    2015-01-28

    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.

  4. Contralateral Dpoae Suppression in Humans at Very Low Sound Intensities

    NASA Astrophysics Data System (ADS)

    Janssen, T.; Gehr, D. D.; Kevanishvili, Z.

    2003-02-01

    Different functions are attributed to the olivo-cochlear bundle system (OCBS) such as protecting the ear from acoustic injury, improving signal detection in noise, and mediating selective attention. OCBS reflex strength can be evaluated, in animals as well as in humans, by measuring the degree of suppression of an ipsilateral DPOAE by a contralateral sound. The purpose of the study was to evaluate OCBS reflex strength depending on ipsilateral stimulus level, especially at threshold, by means of extrapolated DPOAE I/O-functions. Additionally, DPOAE was measured at near-to-threshold contralateral stimulus levels when using low-level ipsilateral stimulation for investigating possible enhancement of outer hair cell motion in the presence of low-level contralateral sound. The recording of the 2f1-f2 DPOAE in the presence or absence of contralateral sound was performed in normally hearing human subjects at f2 = 2 kHz. DPOAE I/O-functions were measured in a primary tone level range from L2 = 20 to L2 = 65 dB SPL (L1 = 0.4L2 + 39, f2/f1=1.2). Broad-band noise (BBN), narrow-band noise from 1720 to 2320 Hz (NBN), and pure tones (PT) at f2, 2f1-f2, geometric mean of f1 and f2, and 0.1oct + f2 were used for contralateral stimulation. The contralateral stimulus level (Ls) was decreased from 70 down to 10 dB SPL in 10 dB steps. DPOAE suppression was highest at the lowest primary tone level and was more pronounced for BBN and NBN than for pure tones, suggesting a more diffuse than a strong tonotopic organisation of the OCBS. The contralateral stimulus level at which significant DPOAE suppression occurred (p < 0.05) was different for the different stimuli being 20, 40, and 70 dB SPL for BBN, NBN, and pure-tone (f2), respectively. Significant DPOAE suppression to BBN and NBN occurred at Ls well below audiological middle-ear reflex threshold. DPOAE time course was different for Ls below and above middle-ear reflex threshold. Thus, middle-ear muscle contraction is suggested not to be

  5. 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.

  6. 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

  7. Reported Expressive Suppression in Daily Life Is Associated with Slower Action Planning.

    PubMed

    Niermeyer, Madison A; Franchow, Emilie I; Suchy, Yana

    2016-07-01

    Objectives Growing evidence demonstrates that (a) executive functioning (EF) becomes deleteriously affected by engagement in the emotion regulation strategy known as expressive suppression and (b) EF shows considerable functional and neuroanatomical overlap with motor output. The current study aimed to bridge these two literatures by examining the relationships between naturally occurring expressive suppression and several different aspects of motor output, including action planning, action learning, and motor-control speed and accuracy. In addition, we investigated whether any identified relationships could be explained by EF. Methods Fifty-one healthy young adults completed selected subtests from the Delis-Kaplan Executive Function System as indices of EF, a self-report measure of expressive suppression, and a computerized motor sequencing task (Push Turn Taptap task; PTT) designed to assess action planning, action learning, and motor control speed and accuracy. Results Hierarchical regressions using each aspect of PTT performance as the dependent variable revealed that higher than usual self-reported expressive suppression on the day of testing (relative to the 2 weeks preceding testing) was associated with longer action-planning latencies. This relationship was fully explained by EF. No other PTT variables related to expressive suppression on the day of testing. Conclusions These results suggest that increased expressive suppression in daily life is associated with slower action planning, an aspect of motor output that is reliant on EF, highlighting the importance of factors that lead to intra-individual fluctuations in EF and motor performance. (JINS, 2016, 22, 671-681).

  8. Reported Expressive Suppression in Daily Life Is Associated with Slower Action Planning.

    PubMed

    Niermeyer, Madison A; Franchow, Emilie I; Suchy, Yana

    2016-07-01

    Objectives Growing evidence demonstrates that (a) executive functioning (EF) becomes deleteriously affected by engagement in the emotion regulation strategy known as expressive suppression and (b) EF shows considerable functional and neuroanatomical overlap with motor output. The current study aimed to bridge these two literatures by examining the relationships between naturally occurring expressive suppression and several different aspects of motor output, including action planning, action learning, and motor-control speed and accuracy. In addition, we investigated whether any identified relationships could be explained by EF. Methods Fifty-one healthy young adults completed selected subtests from the Delis-Kaplan Executive Function System as indices of EF, a self-report measure of expressive suppression, and a computerized motor sequencing task (Push Turn Taptap task; PTT) designed to assess action planning, action learning, and motor control speed and accuracy. Results Hierarchical regressions using each aspect of PTT performance as the dependent variable revealed that higher than usual self-reported expressive suppression on the day of testing (relative to the 2 weeks preceding testing) was associated with longer action-planning latencies. This relationship was fully explained by EF. No other PTT variables related to expressive suppression on the day of testing. Conclusions These results suggest that increased expressive suppression in daily life is associated with slower action planning, an aspect of motor output that is reliant on EF, highlighting the importance of factors that lead to intra-individual fluctuations in EF and motor performance. (JINS, 2016, 22, 671-681). PMID:27333538

  9. Why compton-suppressed germanium detector arrays?

    SciTech Connect

    Diamond, R.M.

    1993-10-01

    Nuclear spectroscopic studies have provided a strong incentive to obtain {gamma}-ray detectors with increasingly better energy resolution, higher full-energy peak efficiencies, and greater sensitivity or resolving power. A major step was the introduction of Ge detectors in the early 60`s. But because of the low atomic number of Ge they have a poor response function; a majority of interacting gamma rays of moderate energy Compton scatter out of the detector leaving a large low-energy background. The remedy was to add a Compton-suppression shield made of NaI around the Ge crystal, and if interactions occurred simultaneously in the NaI scintillator and in the Ge detector to veto that event. Efficiencies also increased greatly when an English-Danish collaboration assembled five Ge detectors, each with a NaI suppressor, into the first array at the end of 1980. Obviously, a system of five such detectors gave much better statistics than the usual two bare detectors used for obtaining coincidence data (by a factor of 10). A few years later, another major improvement came with replacement of the NaI suppressors with shields made of the much denser bismuth germanate (BGO) as scintillator, as these could be thinner leading to arrays with of order 20 detectors. Use of such a large number of detectors led to the realization that for cascades of coincident gamma rays, as in going down a band, the improvement in the peak/background ratio observed and already appreciated in going from singles spectra to gated (double-) coincidence spectra continued when doubly-gated triple-coincidence data were compared for the first time to singly-gated double-coincidence ones. The higher-gated spectra were much cleaner and more selective, though with poorer statistics, and the advantages of higher folds and efficiencies led to the proposals for the larger 4{pi} arrays of today, Eurogam and GASP in Europe and Gammasphere in the U.S.

  10. TEOAE suppression in adults with learning disabilities.

    PubMed

    Garinis, Angela C; Glattke, Theodore; Cone-Wesson, Barbara K

    2008-10-01

    The presentation of contralateral noise during the recording of transient evoked otoacoustic emissions (TEOAEs) reduces the amplitude of the TEOAE in normally-hearing adults. This is known as TEOAE suppression. The present study investigated TEOAE suppression in 18 adults with learning disabilities (LDs) compared to 18 adults without LDs. TEOAEs were elicited by 60 dB p.e. SPL clicks and were suppressed by the presentation of 60 dB SPL contralateral broadband noise. Suppression was measured as a change in the overall TEOAE response amplitude, and also analysed in 2-ms epochs representing different TEOAE frequency-response bands. A significant interaction was evident between group type and ear tested. Participants in the control group had right ear dominance for the suppression effect, whereas the left ear was found to be dominant for the LD group. These findings suggest a mechanism of the medial olivary cochlear bundle and efferent auditory pathway that differs in those with LD compared to those with typical learning abilities.

  11. Sexual selection.

    PubMed

    Hosken, David J; House, Clarissa M

    2011-01-25

    Sexual selection is a concept that has probably been misunderstood and misrepresented more than any other idea in evolutionary biology, confusion that continues to the present day. We are not entirely sure why this is, but sexual politics seems to have played its role, as does a failure to understand what sexual selection is and why it was initially invoked. While in some ways less intuitive than natural selection, sexual selection is conceptually identical to it, and evolution via either mechanism will occur given sufficient genetic variation. Recent claims that sexual selection theory is fundamentally flawed are simply wrong and ignore an enormous body of evidence that provides a bedrock of support for this major mechanism of organic evolution. In fact it is partly due to this solid foundation that current research has largely shifted from documenting whether or not sexual selection occurs, to addressing more complex evolutionary questions. PMID:21256434

  12. Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer.

    PubMed

    Yeh, Chao-Chi; Hsu, Chih-Hung; Shao, Yu-Yun; Ho, Wen-Ching; Tsai, Mong-Hsun; Feng, Wen-Chi; Chow, Lu-Ping

    2015-06-01

    Sorafenib has become the standard therapy for patients with advanced hepatocellular carcinoma (HCC). Unfortunately, most patients eventually develop acquired resistance. Therefore, it is important to identify potential biomarkers that could predict the efficacy of sorafenib. To identify target proteins associated with the development of sorafenib resistance, we applied stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomic approach to analyze differences in protein expression levels between parental HuH-7 and sorafenib-acquired resistance HuH-7 (HuH-7(R)) cells in vitro, combined with an isobaric tags for relative and absolute quantitation (iTRAQ) quantitative analysis of HuH-7 and HuH-7(R) tumors in vivo. In total, 2,450 quantified proteins were identified in common in SILAC and iTRAQ experiments, with 81 showing increased expression (>2.0-fold) with sorafenib resistance and 75 showing decreased expression (<0.5-fold). In silico analyses of these differentially expressed proteins predicted that 10 proteins were related to cancer with involvements in cell adhesion, migration, and invasion. Knockdown of one of these candidate proteins, galectin-1, decreased cell proliferation and metastasis in HuH-7(R) cells and restored sensitivity to sorafenib. We verified galectin-1 as a predictive marker of sorafenib resistance and a downstream target of the AKT/mTOR/HIF-1α signaling pathway. In addition, increased galectin-1 expression in HCC patients' serum was associated with poor tumor control and low response rate. We also found that a high serum galectin-1 level was an independent factor associated with poor progression-free survival and overall survival. In conclusion, these results suggest that galectin-1 is a possible biomarker for predicting the response of HCC patients to treatment with sorafenib. As such, it may assist in the stratification of HCC and help direct personalized therapy.

  13. Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer*

    PubMed Central

    Yeh, Chao-Chi; Hsu, Chih-Hung; Shao, Yu-Yun; Ho, Wen-Ching; Tsai, Mong-Hsun; Feng, Wen-Chi; Chow, Lu-Ping

    2015-01-01

    Sorafenib has become the standard therapy for patients with advanced hepatocellular carcinoma (HCC). Unfortunately, most patients eventually develop acquired resistance. Therefore, it is important to identify potential biomarkers that could predict the efficacy of sorafenib. To identify target proteins associated with the development of sorafenib resistance, we applied stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomic approach to analyze differences in protein expression levels between parental HuH-7 and sorafenib-acquired resistance HuH-7 (HuH-7R) cells in vitro, combined with an isobaric tags for relative and absolute quantitation (iTRAQ) quantitative analysis of HuH-7 and HuH-7R tumors in vivo. In total, 2,450 quantified proteins were identified in common in SILAC and iTRAQ experiments, with 81 showing increased expression (>2.0-fold) with sorafenib resistance and 75 showing decreased expression (<0.5-fold). In silico analyses of these differentially expressed proteins predicted that 10 proteins were related to cancer with involvements in cell adhesion, migration, and invasion. Knockdown of one of these candidate proteins, galectin-1, decreased cell proliferation and metastasis in HuH-7R cells and restored sensitivity to sorafenib. We verified galectin-1 as a predictive marker of sorafenib resistance and a downstream target of the AKT/mTOR/HIF-1α signaling pathway. In addition, increased galectin-1 expression in HCC patients' serum was associated with poor tumor control and low response rate. We also found that a high serum galectin-1 level was an independent factor associated with poor progression-free survival and overall survival. In conclusion, these results suggest that galectin-1 is a possible biomarker for predicting the response of HCC patients to treatment with sorafenib. As such, it may assist in the stratification of HCC and help direct personalized therapy. PMID:25850433

  14. Selecting Software.

    ERIC Educational Resources Information Center

    Pereus, Steven C.

    2002-01-01

    Describes a comprehensive computer software selection and evaluation process, including documenting district needs, evaluating software packages, weighing the alternatives, and making the purchase. (PKP)

  15. Glucagon-like peptide-1 receptor agonist administration suppresses both water and saline intake in rats.

    PubMed

    McKay, N J; Daniels, D

    2013-10-01

    Glucagon-like peptide-1 (GLP-1) plays an important role in energy homeostasis. Injections of GLP-1 receptor (GLP-1R) agonists suppress food intake, and endogenous GLP-1 is released when nutrients enter the gut. There is also growing evidence that the GLP-1 system is involved in the regulation of body fluid homeostasis. GLP-1R agonists suppress water intake independent of their effects on food intake. It is unknown, however, whether this suppressive effect of GLP-1R agonists extends to saline intake. Accordingly, we tested the effect of the GLP-1R agonists liraglutide (0.05 μg) and exendin-4 (0.05 μg) on water and saline intake, as stimulated either by angiotensin II (AngII) or by water deprivation with partial rehydration (WD-PR). Each agonist suppressed AngII-induced water intake; however, only exendin-4 suppressed saline intake. WD-PR-induced water and saline intakes were both attenuated by each agonist. Analysis of drinking microstructure after WD-PR found a reliable effect of the agonists on burst number. Furthermore, exendin-4 conditioned a robust taste avoidance to saccharine; however, there was no similar effect of liraglutide. To evaluate the relevance of the conditioned taste avoidance, we tested whether inducing visceral malaise by injection of lithium chloride (LiCl) suppressed fluid intake. Injection of LiCl did not suppress water or saline intakes. Overall, these results indicate that the fluid intake suppression by GLP-1R activation is not selective to water intake, is a function of post-ingestive feedback, and is not secondary to visceral malaise.

  16. Suppression of behavior by timeout punishment when suppression results in loss of positive reinforcement1

    PubMed Central

    Kaufman, Arnold; Baron, Alan

    1968-01-01

    This investigation, using rats as subjects and punishment by timeout for responses maintained on a ratio schedule, sought to determine whether behavior would be suppressed by timeout punishment when such suppression also reduced reinforcement density or frequency. A series of experiments indicated that timeout punishment suppressed responding, with the degree of suppression increasing as a function of the duration of the timeout period. Suppressive effects were found to decrease as a function of increases in deprivation (body weight) and were eliminated when the punished response also was reinforced. It was concluded that timeout can produce aversive effects even when loss of reinforcement results. An alternative interpretation of the findings, based on the effects of extinction periods and delay of reinforcement on chained behavior, was discussed. PMID:5722425

  17. Suppression of behavior by timeout punishment when suppression results in loss of positive reinforcement.

    PubMed

    Kaufman, A; Baron, A

    1968-09-01

    This investigation, using rats as subjects and punishment by timeout for responses maintained on a ratio schedule, sought to determine whether behavior would be suppressed by timeout punishment when such suppression also reduced reinforcement density or frequency. A series of experiments indicated that timeout punishment suppressed responding, with the degree of suppression increasing as a function of the duration of the timeout period. Suppressive effects were found to decrease as a function of increases in deprivation (body weight) and were eliminated when the punished response also was reinforced. It was concluded that timeout can produce aversive effects even when loss of reinforcement results. An alternative interpretation of the findings, based on the effects of extinction periods and delay of reinforcement on chained behavior, was discussed.

  18. Modeling extreme ultraviolet suppression of electrostatic analyzers

    SciTech Connect

    Gershman, Daniel J.; Zurbuchen, Thomas H.

    2010-04-15

    In addition to analyzing energy-per-charge ratios of incident ions, electrostatic analyzers (ESAs) for spaceborne time-of-flight mass spectrometers must also protect detectors from extreme ultraviolet (EUV) photons from the Sun. The required suppression rate often exceeds 1:10{sup 7} and is generally established in tests upon instrument design and integration. This paper describes a novel technique to model the EUV suppression of ESAs using photon ray tracing integrated into SIMION, the most commonly used ion optics design software for such instruments. The paper compares simulation results with measurements taken from the ESA of the Mass instrument flying onboard the Wind spacecraft. This novel technique enables an active inclusion of EUV suppression requirements in the ESA design process. Furthermore, the simulation results also motivate design rules for such instruments.

  19. Semantic and subword priming during binocular suppression.

    PubMed

    Costello, Patricia; Jiang, Yi; Baartman, Brandon; McGlennen, Kristine; He, Sheng

    2009-06-01

    In general, stimuli that are familiar and recognizable have an advantage of predominance during binocular rivalry. Recent research has demonstrated that familiar and recognizable stimuli such as upright faces and words in a native language could break interocular suppression faster than their matched controls. In this study, a visible word prime was presented binocularly then replaced by a high-contrast dynamic noise pattern presented to one eye and either a semantically related or unrelated word was introduced to the other eye. We measured how long it took for target words to break from suppression. To investigate word-parts priming, a second experiment also included word pairs that had overlapping subword fragments. Results from both experiments consistently show that semantically related words and words that shared subword fragments were faster to gain dominance compared to unrelated words, suggesting that words, even when interocularly suppressed and invisible, can benefit from semantic and subword priming.

  20. Modeling extreme ultraviolet suppression of electrostatic analyzers.

    PubMed

    Gershman, Daniel J; Zurbuchen, Thomas H

    2010-04-01

    In addition to analyzing energy-per-charge ratios of incident ions, electrostatic analyzers (ESAs) for spaceborne time-of-flight mass spectrometers must also protect detectors from extreme ultraviolet (EUV) photons from the Sun. The required suppression rate often exceeds 1:10(7) and is generally established in tests upon instrument design and integration. This paper describes a novel technique to model the EUV suppression of ESAs using photon ray tracing integrated into SIMION, the most commonly used ion optics design software for such instruments. The paper compares simulation results with measurements taken from the ESA of the Mass instrument flying onboard the Wind spacecraft. This novel technique enables an active inclusion of EUV suppression requirements in the ESA design process. Furthermore, the simulation results also motivate design rules for such instruments.

  1. Propofol and sevoflurane induce distinct burst suppression patterns in rats

    PubMed Central

    Kenny, Jonathan D.; Westover, M. Brandon; Ching, ShiNung; Brown, Emery N.; Solt, Ken

    2014-01-01

    Burst suppression is an EEG pattern characterized by alternating periods of high-amplitude activity (bursts) and relatively low amplitude activity (suppressions). Burst suppression can arise from several different pathological conditions, as well as from general anesthesia. Here we review current algorithms that are used to quantify burst suppression, its various etiologies, and possible underlying mechanisms. We then review clinical applications of anesthetic-induced burst suppression. Finally, we report the results of our new study showing clear electrophysiological differences in burst suppression patterns induced by two common general anesthetics, sevoflurane and propofol. Our data suggest that the circuit mechanisms that generate burst suppression activity may differ among general anesthetics. PMID:25565990

  2. Evolutionary suppression of erythropoiesis via the modulation of TGF-β signalling in an Antarctic icefish.

    PubMed

    Xu, Qianghua; Cai, Chang; Hu, Xingxing; Liu, Yun; Guo, Yanan; Hu, Peng; Chen, Zuozhou; Peng, Sihua; Zhang, Dongsheng; Jiang, Shouwen; Wu, Zhichao; Chan, Jiulin; Chen, Liangbiao

    2015-09-01

    The Antarctic icefish, a family (Channichthyidae) of teleosts within the perciform suborder Notothenioidei, are the only known vertebrates without oxygen-transporting haemoglobins and that are largely devoid of circulating erythrocytes. To elucidate the evo-devo mechanisms underpinning the suppressed erythropoiesis in the icefish, we conducted comparative studies on the transcriptomes and microRNAomes of the primary haematopoietic tissues between an icefish (Chionodraco hamatus) and two red-blooded notothenioids (Trematomus bernacchii and Gymnodraco acuticeps). We identified substantial remodelling of the haematopoietic programs in the icefish through which erythropoiesis is selectively suppressed. Experimental verification showed that erythropoietic suppression in the icefish may be attributable to the upregulation of TGF-β signalling, which coincides with reductions in multiple transcription factors essential for erythropoiesis and the upregulation of hundreds of microRNAs, the majority (> 80%) of which potentially target erythropoiesis regulating factors. Of the six microRNAs selected for verification, three miRNAs (miR-152, miR-1388 and miR-16b) demonstrated suppressive functions on GATA1 and ALAS2, which are two factors important for erythroid differentiation, resulting in reduced numbers of erythroids in microinjected zebra fish embryos. Codon substitution analyses of the genes of the TGF-β superfamily revealed signs of positive selection in TGF-β1 and endoglin in the lineages leading to Antarctic notothenioids. Both genes are previously known to function in erythropoietic suppression. These findings implied a general trend of erythropoietic suppression in the cold-adapted notothenioid lineages through evolutionary modulation of the multi-functional TGF-β signalling pathway. This trend is more pronounced in the haemoglobin-less icefish, which may pre-emptively hinder the otherwise defective erythroids from production. PMID:26268413

  3. Evolutionary suppression of erythropoiesis via the modulation of TGF-β signalling in an Antarctic icefish.

    PubMed

    Xu, Qianghua; Cai, Chang; Hu, Xingxing; Liu, Yun; Guo, Yanan; Hu, Peng; Chen, Zuozhou; Peng, Sihua; Zhang, Dongsheng; Jiang, Shouwen; Wu, Zhichao; Chan, Jiulin; Chen, Liangbiao

    2015-09-01

    The Antarctic icefish, a family (Channichthyidae) of teleosts within the perciform suborder Notothenioidei, are the only known vertebrates without oxygen-transporting haemoglobins and that are largely devoid of circulating erythrocytes. To elucidate the evo-devo mechanisms underpinning the suppressed erythropoiesis in the icefish, we conducted comparative studies on the transcriptomes and microRNAomes of the primary haematopoietic tissues between an icefish (Chionodraco hamatus) and two red-blooded notothenioids (Trematomus bernacchii and Gymnodraco acuticeps). We identified substantial remodelling of the haematopoietic programs in the icefish through which erythropoiesis is selectively suppressed. Experimental verification showed that erythropoietic suppression in the icefish may be attributable to the upregulation of TGF-β signalling, which coincides with reductions in multiple transcription factors essential for erythropoiesis and the upregulation of hundreds of microRNAs, the majority (> 80%) of which potentially target erythropoiesis regulating factors. Of the six microRNAs selected for verification, three miRNAs (miR-152, miR-1388 and miR-16b) demonstrated suppressive functions on GATA1 and ALAS2, which are two factors important for erythroid differentiation, resulting in reduced numbers of erythroids in microinjected zebra fish embryos. Codon substitution analyses of the genes of the TGF-β superfamily revealed signs of positive selection in TGF-β1 and endoglin in the lineages leading to Antarctic notothenioids. Both genes are previously known to function in erythropoietic suppression. These findings implied a general trend of erythropoietic suppression in the cold-adapted notothenioid lineages through evolutionary modulation of the multi-functional TGF-β signalling pathway. This trend is more pronounced in the haemoglobin-less icefish, which may pre-emptively hinder the otherwise defective erythroids from production.

  4. 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

  5. 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%.

  6. 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%. PMID:26056365

  7. THEORETICAL ISSUES IN J/PSI SUPPRESSION.

    SciTech Connect

    KHARZEEV,D.

    2006-11-14

    Two decades ago Matsui and Satz suggested that Debye screening in the quark-gluon plasma would result in J/{psi} suppression in heavy ion collisions. Much has happened in the subsequent years, and the picture of quark-gluon plasma at present is rapidly evolving - what does it imply for the J/{psi} suppression? What are the recent RHIC and SPS results trying to tell us? What else has to be done? This talk is an attempt to address these questions.

  8. 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.

  9. 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.

  10. Suppression of behavior by intravenous injections of nicotine or by electric shocks in squirrel monkeys: effects of chlordiazepoxide and mecamylamine.

    PubMed

    Goldberg, S R; Spealman, R D

    1983-02-01

    Squirrel monkeys responded under a two-component fixed-ratio schedule of food presentation with both nonpunishment and punishment components. In both components of the multiple schedule, every 30th key-pressing response resulted in food presentation. In the punishment component, the first response in each 30-response fixed ratio also produced either an i.v. injection of nicotine (10-30 micrograms/kg) or an electric shock (1-5 mA). Response-produced nicotine injections or electric shocks functioned similarly to suppress responding by over 70% in the punishment component. Presession treatment with chlordiazepoxide (5.6-10 mg/kg i.m.) markedly increased responding that had been suppressed by either nicotine injection or electric shock. In contrast, presession treatment with the nicotinic antagonist, mecamylamine (0.1-0.3 mg/kg i.m.) increased responding that had been suppressed by nicotine injection but did not increase responding that had been suppressed by electric shock. Thus, chlordiazepoxide appeared to have general rate-increasing effects on suppressed responding, regardless of the nature of the event suppressing responding, whereas mecamylamine appeared to selectively antagonize the suppressant effects of nicotine. Doses of chloridazepoxide and mecamylamine that increased suppressed responding in punishment components either had little effect on or slightly increased responding in nonpunishment components. These results show that under suitable environmental conditions response-produced i.v. injection of nicotine can function effectively as a punisher. PMID:6822959

  11. 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. PMID:27096422

  12. Reappraising suppression: subjective and physiological correlates of experiential suppression in healthy adults

    PubMed Central

    Lemaire, Mathieu; El-Hage, Wissam; Frangou, Sophia

    2014-01-01

    Background: Emotion regulation strategies based on suppressing behavioral expressions of emotion have been considered maladaptive. However, this may not apply to suppressing the emotional experience (experiential suppression). The aim of this study was to define the effect of experiential suppression on subjective and physiological emotional responses. Methods: Healthy adults (N = 101) were characterized in terms of the temperament, personality, and hedonic capacity using the Tridimensional Personality Questionnaire, the Eysenck Personality Questionnaire, the Fawcett–Clark Pleasure Scale, and the State-Trait Anxiety Inventory. Participants were shown positive, negative, and neutral pictures from the International Affective Picture System under two conditions, passive viewing, and experiential suppression. During both conditions, subjective ratings of the intensity and duration of emotional responses and physiological measures of skin conductance (SC) and cardiac inter-beat interval (IBI) to each picture were recorded. Results: Negative pictures elicited the most intense physiological and emotional responses regardless of experimental condition. Ratings of emotional intensity were not affected by condition. In contrast, experiential suppression, compared to passive viewing, was associated with decreased duration of the emotional response, reduced maximum SC amplitude and longer IBIs independent of age, picture valence, personality traits, hedonic capacity, and anxiety. Conclusion: These findings demonstrate that experiential suppression may represent an adaptive emotion regulation mechanism associated with reduced arousal and cardiovascular activation. PMID:24966844

  13. 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…

  14. Emotions shape memory suppression in trait anxiety.

    PubMed

    Marzi, Tessa; Regina, Antonio; Righi, Stefania

    2014-01-01

    The question that motivated this study was to investigate the relation between trait anxiety, emotions and memory control. To this aim, memory suppression was explored in high and low trait anxiety individuals with the Think/No-think paradigm. After learning associations between neutral words and emotional scenes (negative, positive, and neutral), participants were shown a word and were requested either to think about the associated scene or to block it out from mind. Finally, in a test phase, participants were again shown each word and asked to recall the paired scene. The results show that memory control is influenced by high trait anxiety and emotions. Low trait anxiety individuals showed a memory suppression effect, whereas there was a lack of memory suppression in high trait anxious individuals, especially for emotionally negative scenes. Thus, we suggest that individuals with anxiety may have difficulty exerting cognitive control over memories with a negative valence. These findings provide evidence that memory suppression can be impaired by anxiety thus highlighting the crucial relation between cognitive control, emotions, and individual differences in regulating emotions.

  15. Polyphosphate suppresses complement via the terminal pathway

    PubMed Central

    Wat, Jovian M.; Foley, Jonathan H.; Krisinger, Michael J.; Ocariza, Linnette Mae; Lei, Victor; Wasney, Gregory A.; Lameignere, Emilie; Strynadka, Natalie C.; Smith, Stephanie A.; Morrissey, James H.

    2014-01-01

    Polyphosphate, synthesized by all cells, is a linear polymer of inorganic phosphate. When released into the circulation, it exerts prothrombotic and proinflammatory activities by modulating steps in the coagulation cascade. We examined the role of polyphosphate in regulating the evolutionarily related proteolytic cascade complement. In erythrocyte lysis assays, polyphosphate comprising more than 1000 phosphate units suppressed total hemolytic activity with a concentration to reduce maximal lysis to 50% that was 10-fold lower than with monophosphate. In the ion- and enzyme-independent terminal pathway complement assay, polyphosphate suppressed complement in a concentration- and size-dependent manner. Phosphatase-treated polyphosphate lost its ability to suppress complement, confirming that polymer integrity is required. Sequential addition of polyphosphate to the terminal pathway assay showed that polyphosphate interferes with complement only when added before formation of the C5b-7 complex. Physicochemical analyses using native gels, gel filtration, and differential scanning fluorimetry revealed that polyphosphate binds to and destabilizes C5b,6, thereby reducing the capacity of the membrane attack complex to bind to and lyse the target cell. In summary, we have added another function to polyphosphate in blood, demonstrating that it dampens the innate immune response by suppressing complement. These findings further establish the complex relationship between coagulation and innate immunity. PMID:24335501

  16. Visual Blocking: Suppression of Excessive Verbalizations.

    ERIC Educational Resources Information Center

    Zlomke, Lee; And Others

    1986-01-01

    Visual blocking procedures (briefly holding a paper screen in front of a subject's face contingent upon inappropriate behavior) were effective in decreasing inappropriate verbalizations in a moderately retarded 32-year-old male. Followup 4 months later indicated that suppression was maintained in treatment settings but failed to generalize to…

  17. Decoherence suppression in a resonant driving field

    NASA Astrophysics Data System (ADS)

    Minns, R. S.; Kutteruf, M. R.; Commisso, M. A.; Jones, R. R.

    2008-04-01

    Resonant radio frequency (rf) control fields have been employed to suppress decoherence in single quantum bits (qubits) encoded in the probability amplitudes of np fine-structure states in Li Rydberg atoms. As described previously [1], static electric-field tuning of the spin and orbital angular momentum composition of the fine-structure eigenstates enables qubit storage in an approximate decoherence-free subspace in which phase errors due to small stray electric and magnetic fields are strongly suppressed. In addition, it was found that sequences of short electric field pulses could be utilized in a 'bang-bang' dynamic decoupling scheme to improve coherence times. We now show that a continuous resonant rf field can also suppress decoherence in this system. The rf-dressed fine-structure states form a more robust basis in which the energy splitting between the component qubit levels is locked to the drive frequency, and decoherence is essentially eliminated. Measurements of the operational range of rf frequency and field strength required to achieve decoherence suppression are in agreement with the predictions of a two-level model.

  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. Motor induced suppression of auditory cortex

    PubMed Central

    Aliu, Sheye O.; Houde, John F.; Nagarajan, Srikantan S.

    2010-01-01

    Sensory responses to stimuli that are triggered by a self-initiated motor act are suppressed when compared with the response to the same stimuli triggered externally, a phenomenon referred to as motor-induced suppression (MIS) of sensory cortical feedback. Studies in the somatosensory system suggest that such suppression might be sensitive to delays between the motor act and the stimulus-onset, and a recent study in the auditory system suggests that such MIS develops rapidly. In three MEG experiments, we characterize the properties of MIS, by examining the M100 response from the auditory cortex to a simple tone triggered by a button press. In Experiment 1, we found that MIS develops for zero-delays but does not generalize to non-zero delays. In Experiment 2, we found that MIS developed for 100 ms delays within 300 trials and occurs in excess of auditory habituation. In Experiment 3, we found that unlike MIS for zero-delays, MIS for non-zero delays does not exhibit sensitivity to sensory, delay or motor-command changes. These results are discussed in relation to suppression to self-produced speech and a general model of sensory motor control. PMID:18593265

  1. Chlorella suppresses methylmercury transfer to the fetus in pregnant mice.

    PubMed

    Uchikawa, Takuya; Maruyama, Isao; Kumamoto, Shoichiro; Ando, Yotaro; Yasutake, Akira

    2011-10-01

    To investigate the effects of chlorella on methylmercury (MeHg) transfer to the fetus during pregnancy, female C57BL/6N mice (aged 10 weeks) were housed for 7 to 8 weeks, from 4 weeks before mating to birth, with diets containing 0% or 10% chlorella powder (CP) and MeHg-containing drinking water (2 µg Hg/ml). The consumption volume of the MeHg-containing water was limited to 15 ml/mouse/week throughout the experiment. Distilled water and a basal diet (0% CP) was given to control mice. Except for the mating period, during the 5(th) week, mice were housed individually until parturition. Two neonates were randomly selected from each mother mouse within 24 hr after parturition for Hg analysis of the blood, brain, liver, and kidneys. Mother mice were sacrificed on the same day as neonates to obtain tissue samples for Hg analysis. The blood and brain Hg levels of both neonates and mothers in the CP diet group were significantly lower than those in the basal diet group. Although the hepatic and renal Hg levels were not significant in mothers between the two dietary groups, in neonates, the CP diet group showed significantly lower Hg levels in these tissues than the basal diet group. The results obtained here revealed that continuous CP intake suppressed MeHg transfer to the fetus, in addition to effective suppressing MeHg accumulation in brains of the mothers.

  2. 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

  3. 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. PMID:26915998

  4. Intracortical microinjections may cause spreading depression and suppress absence seizures.

    PubMed

    Samotaeva, I S; Tillmanns, N; van Luijtelaar, G; Vinogradova, L V

    2013-01-29

    Intracerebral microinjection is a commonly used technique for local delivery of biologically active agents. However, it is known that mechanical injury of the cortex can induce spreading depression (SD), a wave of transient cellular depolarization. We examined the effects of intracortical microinjections of a new selective I(h) channel antagonist ORG 34167 and of different control treatments (saline and sham microinjections) on spontaneously occurring spike-wave discharges (SWDs) in WAG/Rij rats, a valid genetic model of absence epilepsy. Electroencephalographic (EEG) recording in awake rats has shown that both the drug and control microinjections are followed by long-term (for more than an hour) suppression of SWDs. dc-EEG recording in WAG/Rij rats has revealed that sham microinjections induce SD in 65% (31/48) cases. Number of SWDs decreased substantially for at least 90 min after the sham injections which induced cortical SD but remained unchanged if SD was not triggered by microinjection. These findings suggest that SD induced by intracortical microinjection may contribute to long-term suppression of non-convulsive epileptic activity after this experimental procedure. PMID:23200788

  5. 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.

  6. 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. PMID:26325509

  7. 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.

  8. Neural suppression of irrelevant information underlies optimal working memory performance

    PubMed Central

    Zanto, Theodore P.; Gazzaley, Adam

    2009-01-01

    Our ability to focus attention on task-relevant information and ignore distractions is reflected by differential enhancement and suppression of neural activity in sensory cortex (i.e., top-down modulation). Such selective, goal-directed modulation of activity may be intimately related to memory, such that the focus of attention biases the likelihood of successfully maintaining relevant information by limiting interference from irrelevant stimuli. Despite recent studies elucidating the mechanistic overlap between attention and memory, the relationship between top-down modulation of visual processing during working memory (WM) encoding and subsequent recognition performance has not yet been established. Here, we provide neurophysiological evidence in healthy, young adults that top-down modulation of early visual processing (< 200 ms from stimulus onset) is intimately related to subsequent WM performance, such that the likelihood of successfully remembering relevant information is associated with limiting interference from irrelevant stimuli. The consequences of a failure to ignore distractors on recognition performance was replicated for two types of feature-based memory, motion direction and color. Moreover, attention to irrelevant stimuli was reflected neurally during the WM maintenance period as an increased memory load. These results suggest that neural enhancement of relevant information is not the primary determinant of high-level performance, but rather, optimal WM performance is dependent on effectively filtering irrelevant information through neural suppression to prevent overloading a limited memory capacity. PMID:19279242

  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. 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

  11. Immune Suppression and Immune Activation in Depression

    PubMed Central

    Blume, Joshua; Douglas, Steven D.; Evans, Dwight L.

    2010-01-01

    Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities. Yet the significant associations of findings of both immune suppression and immune activation with depression raise questions concerning the relationship between these two classes of immunological observations. Depressed populations are heterogeneous groups, and there may be differences in the immune profiles of populations that are more narrowly defined in terms of symptom profile and/or demographic features. There have been few reports concurrently investigating markers of immune suppression and immune activation in the same depressed individuals. An emerging preclinical literature suggests that chronic inflammation may directly contribute to the pathophysiology of immune suppression in the context of illnesses such as cancer and rheumatoid arthritis. This literature provides us with specific immunoregulatory mechanisms mediating these relationships that could also explain differences in immune disturbances between subsets of depressed individuals We propose a research agenda emphasizing the assessment of these immunoregulatory mechanisms in large samples of depressed subjects as a means to define the relationships among immune findings (suppression and/or activation) within the same depressed individuals and to characterize subsets of depressed subjects based on shared immune profiles. Such a program of research, building on and integrating our knowledge of the psychoneuroimmunology of depression, could lead to innovation in the assessment and treatment of depression and its medical comorbidities

  12. Lactic Acid Suppresses IL-33-Mediated Mast Cell Inflammatory Responses via Hypoxia-Inducible Factor-1α-Dependent miR-155 Suppression.

    PubMed

    Abebayehu, Daniel; Spence, Andrew J; Qayum, Amina Abdul; Taruselli, Marcela T; McLeod, Jamie J A; Caslin, Heather L; Chumanevich, Alena P; Kolawole, Elizabeth Motunrayo; Paranjape, Anuya; Baker, Bianca; Ndaw, Victor S; Barnstein, Brian O; Oskeritzian, Carole A; Sell, Scott A; Ryan, John J

    2016-10-01

    Lactic acid (LA) is present in tumors, asthma, and wound healing, environments with elevated IL-33 and mast cell infiltration. Although IL-33 is a potent mast cell activator, how LA affects IL-33-mediated mast cell function is unknown. To investigate this, mouse bone marrow-derived mast cells were cultured with or without LA and activated with IL-33. LA reduced IL-33-mediated cytokine and chemokine production. Using inhibitors for monocarboxylate transporters (MCT) or replacing LA with sodium lactate revealed that LA effects are MCT-1- and pH-dependent. LA selectively altered IL-33 signaling, suppressing TGF-β-activated kinase-1, JNK, ERK, and NF-κB phosphorylation, but not p38 phosphorylation. LA effects in other contexts have been linked to hypoxia-inducible factor (HIF)-1α, which was enhanced in bone marrow-derived mast cells treated with LA. Because HIF-1α has been shown to regulate the microRNA miR-155 in other systems, LA effects on miR-155-5p and miR-155-3p species were measured. In fact, LA selectively suppressed miR-155-5p in an HIF-1α-dependent manner. Moreover, overexpressing miR-155-5p, but not miR-155-3p, abolished LA effects on IL-33-induced cytokine production. These in vitro effects of reducing cytokines were consistent in vivo, because LA injected i.p. into C57BL/6 mice suppressed IL-33-induced plasma cytokine levels. Lastly, IL-33 effects on primary human mast cells were suppressed by LA in an MCT-dependent manner. Our data demonstrate that LA, present in inflammatory and malignant microenvironments, can alter mast cell behavior to suppress inflammation. PMID:27559047

  13. 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.

  14. Results from computer program for analyzing scattered light suppression systems for large space telescope

    NASA Technical Reports Server (NTRS)

    Tifft, W. G.; Fannin, B. B.

    1974-01-01

    A computer program was developed which has the ability to analyze the performance of most light suppression systems so as to predict the amount of scattered light which will reach the image plane for various conditions of unwanted light input from the sun, earth, or moon. This program was used to analyze three different configurations of the large space telescope (LST): an LST with a truncated sunshield, an LST with an extended cylindrical sunshield, and an LST with a conical sunshield which is tilted upwards. The computer program gives the user detailed information as to the paths taken by the unwanted stray light to reach the image plane, and pinpoints those portions of the light suppression system which contribute most of the stray light, so that areas requiring improvements are evident. Certain design guide lines were formulated for any light suppression system selected for the LST, and one which meets these requirements (the tilted sunshade) is described in detail.

  15. Method of suppressing formation of contrails and solution therefor

    SciTech Connect

    Singh, S.

    1988-08-30

    This patent describes a method of suppressing the formation of contrails from water vapor in the hot exhaust gases of an engine discharged into a cold temperature atmosphere comprising the steps of providing in relatively sufficient proportions to effect hypernucleation of the water vapor in the hot exhaust gases a solution of a non-corrosive surfactant for reducing the surface energy of the water vapor and a combined carrier and nucleating agent selected from the group of water soluble monohydric, dihydric, trihydric and polyhydric alcohols, and injecting the solution into the hot exhaust gases of the engine, the solution reducing ice particles formed from the water vapor in the cold atmosphere to a size below a humanly visible range.

  16. 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.

  17. FMRI repetition suppression for voices is modulated by stimulus expectations.

    PubMed

    Andics, Attila; Gál, Viktor; Vicsi, Klára; Rudas, Gábor; Vidnyánszky, Zoltán

    2013-04-01

    According to predictive coding models of sensory processing, stimulus expectations have a profound effect on sensory cortical responses. This was supported by experimental results, showing that fMRI repetition suppression (fMRI RS) for face stimuli is strongly modulated by the probability of stimulus repetitions throughout the visual cortical processing hierarchy. To test whether processing of voices is also affected by stimulus expectations, here we investigated the effect of repetition probability on fMRI RS in voice-selective cortical areas. Changing ('alt') and identical ('rep') voice stimulus pairs were presented to the listeners in blocks, with a varying probability of alt and rep trials across blocks. We found auditory fMRI RS in the nonprimary voice-selective cortical regions, including the bilateral posterior STS, the right anterior STG and the right IFC, as well as in the IPL. Importantly, fMRI RS effects in all of these areas were strongly modulated by the probability of stimulus repetition: auditory fMRI RS was reduced or not present in blocks with low repetition probability. Our results revealed that auditory fMRI RS in higher-level voice-selective cortical regions is modulated by repetition probabilities and thus suggest that in audition, similarly to the visual modality, processing of sensory information is shaped by stimulus expectation processes. PMID:23268783

  18. 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.

  19. 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. PMID:26498865

  20. Dermal exposure to jet fuel suppresses delayed-type hypersensitivity: a critical role for aromatic hydrocarbons.

    PubMed

    Ramos, Gerardo; Limon-Flores, Alberto Yairh; Ullrich, Stephen E

    2007-12-01

    Dermal exposure to military (JP-8) and/or commercial (Jet-A) jet fuel suppresses cell-mediated immune reactions. Immune regulatory cytokines and biological modifiers, including platelet activating factor (PAF), prostaglandin E(2), and interleukin-10, have been implicated in the pathway of events leading to immune suppression. It is estimated that approximately 260 different hydrocarbons are found in jet fuel, and the exact identity of the active immunotoxic agent(s) is unknown. The recent availability of synthetic jet fuel (S-8), which is refined from natural gas, and is devoid of aromatic hydrocarbons, made it feasible to design experiments to address this problem. Here we tested the hypothesis that the aromatic hydrocarbons present in jet fuel are responsible for immune suppression. We report that applying S-8 to the skin of mice does not upregulate the expression of epidermal cyclooxygenase-2 (COX-2) nor does it induce immune suppression. Adding back a cocktail of seven of the most prevalent aromatic hydrocarbons found in jet fuel (benzene, toluene, ethylbenzene, xylene, 1,2,4-trimethlybenzene, cyclohexylbenzene, and dimethylnaphthalene) to S-8 upregulated epidermal COX-2 expression and suppressed a delayed-type hypersensitivity (DTH) reaction. Injecting PAF receptor antagonists, or a selective cycloozygenase-2 inhibitor into mice treated with S-8 supplemented with the aromatic cocktail, blocked suppression of DTH, similar to data previously reported using JP-8. These findings identify the aromatic hydrocarbons found in jet fuel as the agents responsible for suppressing DTH, in part by the upregulation of COX-2, and the production of immune regulatory factors and cytokines.

  1. 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.

  2. [The advances of suppression in research of amblyopia].

    PubMed

    Liu, S; Liu, H

    2016-04-11

    Suppression that is the result of interocular competition is an important machanism of amblyopia. The imbalance of suppression may lead the consequence to amblyopia. In the early study, researchers had raised the theory of II. Quadratic Summation which had revealed the relationship of interocular interaction and suppression. In some basic researches, other studies had showed the most possible anatomic location of suppression. Recently, researchers found a new method to quantify the interocular suppression named the noise model. Further studies found a novel disinhibition therapy to treat amblyopia. We summarized the research advances in suppression and disinhibition treatment in amblyopia. (Chin J Ophthalmol, 2016, 52: 305-308). PMID:27094069

  3. Increased photic sensitivity for phase resetting but not melatonin suppression in Siberian hamsters under short photoperiods.

    PubMed

    Glickman, G L; Harrison, E M; Elliott, J A; Gorman, M R

    2014-03-01

    Light regulates a variety of behavioral and physiological processes, including activity rhythms and hormone secretory patterns. Seasonal changes in the proportion of light in a day (photoperiod) further modulate those functions. Recently, short (SP) versus long days (LP) were found to markedly increase light sensitivity for phase shifting in Syrian hamsters. To our knowledge, photoperiod effects on light sensitivity have not been studied in other rodents, nor is it known if they generalize to other circadian responses. We tested whether photic phase shifting and melatonin suppression vary in Siberian hamsters maintained under LP or SP. Select irradiances of light were administered, and shifts in activity were determined. Photic sensitivity for melatonin suppression was examined in a separate group of animals via pulses of light across a 4 log-unit photon density range, with post-pulse plasma melatonin levels determined via RIA. Phase shifting and melatonin suppression were greater at higher irradiances for both LP and SP. The lower irradiance condition was below threshold for phase shifts in LP but not SP. Melatonin suppression did not vary by photoperiod, and the half saturation constant for fitted sigmoid curves was similar under LP and SP. Thus, the photoperiodic modulation of light sensitivity for phase shifting is conserved across two hamster genera. The dissociation of photoperiod effects on photic phase shifting and melatonin suppression suggests that the modulation of sensitivity occurs downstream of the common retinal input pathway. Understanding the mechanistic basis for this plasticity may yield therapeutic targets for optimizing light therapy practices.

  4. Increased photic sensitivity for phase resetting but not melatonin suppression in Siberian hamsters under short photoperiods

    PubMed Central

    Glickman, GL; Harrison, EM; Elliott, JA; Gorman, MR

    2014-01-01

    Light regulates a variety of behavioral and physiological processes, including activity rhythms and hormone secretory patterns. Seasonal changes in the proportion of light in a day (photoperiod) further modulate those functions. Recently, short (SP) versus long days (LP) were found to markedly increase light sensitivity for phase shifting in Syrian hamsters. To our knowledge, photoperiod effects on light sensitivity have not been studied in other rodents nor is it known if they generalize to other circadian responses. We tested whether photic phase shifting and melatonin suppression vary in Siberian hamsters maintained under LP or SP. Select irradiances of light were administered, and shifts in activity were determined. Photic sensitivity for melatonin suppression was examined in a separate group of animals via pulses of light across a 4 log-unit photon density range, with post-pulse plasma melatonin levels determined via RIA. Phase shifting and melatonin suppression were greater at higher irradiances for both LP and SP. The lower irradiance condition was below threshold for phase shifts in LP but not SP. Melatonin suppression did not vary by photoperiod, and the half saturation constant for fitted sigmoid curves was similar under LP and SP. Thus, photoperiodic modulation of light sensitivity for phase shifting is conserved across two hamster genera. The dissociation of photoperiod effects on photic phase shifting and melatonin suppression suggests modulation of sensitivity occurs downstream of the common retinal input pathway. Understanding the mechanistic basis for this plasticity may yield therapeutic targets for optimizing light therapy practices. PMID:24440383

  5. 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

  6. 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. PMID:25567940

  7. Material selection

    SciTech Connect

    Tucker, W.G.

    1990-08-01

    The paper summarizes various criteria that can be used in selecting material used in the construction, furnishing, maintenance, and operation of a building. It also summarizes the types of material and product testing that can be especially useful in the selection process. In broad terms, materials in buildings are classified as building materials, furnishings, maintenance materials, and other contents. At any given time, emissions from materials and products in any of these four categories can dominate the impact on indoor air quality (IAQ) in a building. Responsibility for the selection of these materials may be that of the designer, owner, or occupants. Information on IAQ impacts of materials therefore needs to be developed for a wide range of people.

  8. Suppression of friction by mechanical vibrations.

    PubMed

    Capozza, Rosario; Vanossi, Andrea; Vezzani, Alessandro; Zapperi, Stefano

    2009-08-21

    Mechanical vibrations are known to affect frictional sliding and the associated stick-slip patterns causing sometimes a drastic reduction of the friction force. This issue is relevant for applications in nanotribology and to understand earthquake triggering by small dynamic perturbations. We study the dynamics of repulsive particles confined between a horizontally driven top plate and a vertically oscillating bottom plate. Our numerical results show a suppression of the high dissipative stick-slip regime in a well-defined range of frequencies that depends on the vibrating amplitude, the normal applied load, the system inertia and the damping constant. We propose a theoretical explanation of the numerical results and derive a phase diagram indicating the region of parameter space where friction is suppressed. Our results allow to define better strategies for the mechanical control of friction. PMID:19792738

  9. Mercury vapour suppression by various liquid media.

    PubMed

    Sutow, E J; Foong, W C; Rizkalla, A S; Jones, D W; Power, N L

    1994-09-01

    Fresh and used photographic fixer, Merconvap and water were evaluated for their ability to suppress the vapourization of mercury. Mercury vapour concentration above the four test storage liquids was measured at various times between 10 min and 335 days, using a mercury vapour measuring instrument. The data were analysed using a Student-Newman-Keuls multiple comparison test (P = 0.05). The results showed that fresh and used fixer and Merconvap suppressed the vapourization of mercury to below the detection limit of the measuring instrument (0.01 mg/m3). Water was much less effective compared with the other liquids and showed an increase in mercury vapour concentration with log t. PMID:7996339

  10. Abnormal Grain Growth Suppression in Aluminum Alloys

    NASA Technical Reports Server (NTRS)

    Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)

    2015-01-01

    The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ("IAT") after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions. The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.

  11. Overcoming fixation with repeated memory suppression.

    PubMed

    Angello, Genna; Storm, Benjamin C; Smith, Steven M

    2015-01-01

    Fixation (blocks to memories or ideas) can be alleviated not only by encouraging productive work towards a solution, but, as the present experiments show, by reducing counterproductive work. Two experiments examined relief from fixation in a word-fragment completion task. Blockers, orthographically similar negative primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in both experiments. After priming, but before the fragment completion test, participants repeatedly suppressed half of the blockers using the Think/No-Think paradigm, which results in memory inhibition. Inhibiting blockers did not alleviate fixation in Experiment 1 when conscious recollection of negative primes was not encouraged on the fragment completion test. In Experiment 2, however, when participants were encouraged to remember negative primes at fragment completion, relief from fixation was observed. Repeated suppression may nullify fixation effects, and promote creative thinking, particularly when fixation is caused by conscious recollection of counterproductive information.

  12. Active flutter suppression using dipole filters

    NASA Technical Reports Server (NTRS)

    Srinathkumar, S.; Waszak, Martin R.

    1992-01-01

    By using traditional control concepts of gain root locus, the active suppression of a flutter mode of a flexible wing is examined. It is shown that the attraction of the unstable mode towards a critical system zero determines the degree to which the flutter mode can be stabilized. For control situations where the critical zero is adversely placed in the complex plane, a novel compensation scheme called a 'Dipole' filter is proposed. This filter ensures that the flutter mode is stabilized with acceptable control energy. The control strategy is illustrated by designing flutter suppression laws for an active flexible wing (AFW) wind-tunnel model, where minimal control effort solutions are mandated by control rate saturation problems caused by wind-tunnel turbulence.

  13. Adaptive Suppression of Noise in Voice Communications

    NASA Technical Reports Server (NTRS)

    Kozel, David; DeVault, James A.; Birr, Richard B.

    2003-01-01

    A subsystem for the adaptive suppression of noise in a voice communication system effects a high level of reduction of noise that enters the system through microphones. The subsystem includes a digital signal processor (DSP) plus circuitry that implements voice-recognition and spectral- manipulation techniques. The development of the adaptive noise-suppression subsystem was prompted by the following considerations: During processing of the space shuttle at Kennedy Space Center, voice communications among test team members have been significantly impaired in several instances because some test participants have had to communicate from locations with high ambient noise levels. Ear protection for the personnel involved is commercially available and is used in such situations. However, commercially available noise-canceling microphones do not provide sufficient reduction of noise that enters through microphones and thus becomes transmitted on outbound communication links.

  14. Suppression of Eimeria tenella sporulation by disinfectants.

    PubMed

    You, Myung-Jo

    2014-08-01

    The disinfectant effects (DEs) of 10 types of chemicals, defined by their ability to destroy or inhibit oocysts and consequently prevent sporulation of Eimeria tenella field isolate, were evaluated in vitro. Correct species assignments and sample purities were confirmed by the singular internal transcribed spacer (ITS)-PCR analysis. A total of 18 treatments were performed, and the disinfection suppression levels were 75.9% for 39% benzene + 22% xylene (1:10 dilution), 85.5% for 30% cresol soup (1:1 dilution), and 91.7% for 99.9% acetic acid (1:2 dilution) group. The results indicate that acetic acid, cresol soup, and benzene+xylene are good candidates for suppression of E. tenella oocyst sporulation.

  15. Glucose Suppresses Biological Ferroelectricity in Aortic Elastin

    NASA Astrophysics Data System (ADS)

    Liu, Yuanming; Wang, Yunjie; Chow, Ming-Jay; Chen, Nataly Q.; Ma, Feiyue; Zhang, Yanhang; Li, Jiangyu

    2013-04-01

    Elastin is an intriguing extracellular matrix protein present in all connective tissues of vertebrates, rendering essential elasticity to connective tissues subjected to repeated physiological stresses. Using piezoresponse force microscopy, we show that the polarity of aortic elastin is switchable by an electrical field, which may be associated with the recently discovered biological ferroelectricity in the aorta. More interestingly, it is discovered that the switching in aortic elastin is largely suppressed by glucose treatment, which appears to freeze the internal asymmetric polar structures of elastin, making it much harder to switch, or suppressing the switching completely. Such loss of ferroelectricity could have important physiological and pathological implications from aging to arteriosclerosis that are closely related to glycation of elastin.

  16. Sleep deprivation suppresses aggression in Drosophila

    PubMed Central

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041

  17. Sleep deprivation suppresses aggression in Drosophila.

    PubMed

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness.

  18. System for Suppressing Vibration in Turbomachine Components

    NASA Technical Reports Server (NTRS)

    Morrison, Carlos R. (Inventor); Provenza, Andrew J. (Inventor); Choi, Benjamin B. (Inventor); Bakhle, Milind A. (Inventor); Min, James B (Inventor); Stefko, George L. (Inventor); Kussmann, John A (Inventor); Fougere, Alan J (Inventor)

    2013-01-01

    Disclosed is a system for suppressing vibration and noise mitigation in structures such as blades in turbomachinery. The system includes flexible piezoelectric patches which are secured on or imbedded in turbomachinery blades which, in one embodiment, comprises eight (8) fan blades. The system further includes a capacitor plate coupler and a power transfer apparatus, which may both be arranged into one assembly, that respectively transfer data and power. Each of the capacitive plate coupler and power transfer apparatus is configured so that one part is attached to a fixed member while another part is attached to a rotatable member with an air gap there between. The system still further includes a processor that has 16 channels, eight of which serve as sensor channels, and the remaining eight, serving as actuation channels. The processor collects and analyzes the sensor signals and, in turn, outputs corrective signals for vibration/noise suppression of the turbine blades.

  19. Immersion diuresis without expected suppression of vasopressin

    NASA Technical Reports Server (NTRS)

    Keil, L. C.; Silver, J. E.; Wong, N.; Spaul, W. A.; Greenleaf, J. E.; Kravik, S. E.

    1984-01-01

    There is a shift of blood from the lower parts of the body to the thoracic circulation during bed rest, water immersion, and presumably during weightlessness. On earth, this central fluid shift is associated with a profound diuresis. However, the mechanism involved is not yet well understood. The present investigation is concerned with measurements regarding the plasma vasopressin, fluid, electrolyte, and plasma renin activity (PRA) responses in subjects with normal preimmersion plasma vasopressin (PVP) concentration. In the conducted experiments, PRA was suppressed significantly at 30 min of immersion and had declined by 74 percent by the end of the experiment. On the basis of previously obtained results, it appears that sodium excretion during immersion may be independent of aldosterone action. Experimental results indicate that PVP is not suppressed by water immersion in normally hydrated subjects and that other factors may be responsible for the diuresis.

  20. Suppression of attentional bias in PTSD.

    PubMed

    Constans, Joseph I; McCloskey, Michael S; Vasterling, Jennifer J; Brailey, Kevin; Mathews, Andrew

    2004-05-01

    Sixty combat veterans with posttraumatic stress disorder performed an emotional Stroop task under 1 of 4 contextual conditions designed to test theoretical explanations for an attentional bias suppression effect. Results revealed that when the emotional Stroop task was performed under conditions involving a future threat of either watching a combat video or giving a speech, attentional bias was inhibited. There was limited support for the prediction that the suppression effect was strongest when stressor content matched word content on the Stroop. In contrast to participants in the threat conditions, veterans who believed that they would receive additional compensation for speeded color naming or who believed that they would have no other experimental demands were slower when color naming combat-threat words. Potential theoretical explanations of the findings are discussed.

  1. Adaptive Modal Identification for Flutter Suppression Control

    NASA Technical Reports Server (NTRS)

    Nguyen, Nhan T.; Drew, Michael; Swei, Sean S.

    2016-01-01

    In this paper, we will develop an adaptive modal identification method for identifying the frequencies and damping of a flutter mode based on model-reference adaptive control (MRAC) and least-squares methods. The least-squares parameter estimation will achieve parameter convergence in the presence of persistent excitation whereas the MRAC parameter estimation does not guarantee parameter convergence. Two adaptive flutter suppression control approaches are developed: one based on MRAC and the other based on the least-squares method. The MRAC flutter suppression control is designed as an integral part of the parameter estimation where the feedback signal is used to estimate the modal information. On the other hand, the separation principle of control and estimation is applied to the least-squares method. The least-squares modal identification is used to perform parameter estimation.

  2. Sleep deprivation suppresses aggression in Drosophila.

    PubMed

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. PMID:26216041

  3. Systemic suppression of delayed-type hypersensitivity by supernatants from UV-irradiated keratinocytes

    SciTech Connect

    Rivas, J.M.; Ullrich, S.E. )

    1992-12-15

    Exposing murine keratinocyte cultures to UV radiation causes the release of a suppressive cytokine that mimics the immunosuppressive effects of total-body UV exposure. Injecting supernatants from UV-irradiated keratinocyte cultures into mice inhibits their ability to generate a delayed-type hypersensitivity reaction against allogeneic histocompatibility Ag, and spleen cells from mice injected with supernatant do not respond to alloantigen in the in vitro MLR. A unique feature of the immunosuppression induced by either total-body UV-exposure or injecting the suppressive cytokine from UV-irradiated keratinocytes is the selectivity of suppression. Although cellular immune reactions such as delayed-type hypersensitivity are suppressed antibody production is unaffected. Because the selective nature to the UV-induced immunosuppression is similar to the biologic activity of IL-10, the authors examined the hypothesis that UV exposure of keratinocytes causes the release of IL-10. Keratinocyte monolayers were exposed to UV radiation and at specific times after exposure mRNA was isolated or the culture supernatant from the cells was collected. These data indicate that activated keratinocytes are capable of secreting IL-10 and suggest that the release of IL-10 by UV-irradiated keratinocytes plays an essential role in the induction of systemic immunosuppression after total-body UV exposure. 44 refs., 3 figs., 2 tabs.

  4. Inhibition of Olfactory Receptor Neuron Input to Olfactory Bulb Glomeruli Mediated by Suppression of Presynaptic Calcium Influx

    PubMed Central

    Wachowiak, Matt; McGann, John P.; Heyward, Philip M.; Shao, Zuoyi; Puche, Adam C.; Shipley, Michael T.

    2005-01-01

    We investigated the cellular mechanism underlying presynaptic regulation of olfactory receptor neuron (ORN) input to the mouse olfactory bulb using optical-imaging techniques that selectively report activity in the ORN pre-synaptic terminal. First, we loaded ORNs with calcium-sensitive dye and imaged stimulus-evoked calcium influx in a slice preparation. Single olfactory nerve shocks evoked rapid fluorescence increases that were largely blocked by the N-type calcium channel blocker ω-conotoxin GVIA. Paired shocks revealed a long-lasting suppression of calcium influx with ~40% suppression at 400-ms interstimulus intervals and a recovery time constant of ~450 ms. Blocking activation of postsynaptic olfactory bulb neurons with APV/CNQX reduced this suppression. The GABAB receptor agonist baclofen inhibited calcium influx, whereas GABAB antagonists reduced paired-pulse suppression without affecting the response to the conditioning pulse. We also imaged transmitter release directly using a mouse line that expresses synaptopHluorin selectively in ORNs. We found that the relationship between calcium influx and transmitter release was superlinear and that paired-pulse suppression of transmitter release was reduced, but not eliminated, by APV/CNQX and GABAB antagonists. These results demonstrate that primary olfactory input to the CNS can be presynaptically regulated by GABAergic interneurons and show that one major intracellular pathway for this regulation is via the suppression of calcium influx through N-type calcium channels in the pre-synaptic terminal. This mechanism is unique among primary sensory afferents. PMID:15917320

  5. Fire suppression in human-crew spacecraft

    NASA Technical Reports Server (NTRS)

    Friedman, Robert; Dietrich, Daniel L.

    1991-01-01

    Fire extinguishment agents range from water and foam in early-design spacecraft (Halon 1301 in the present Shuttle) to carbon dioxide proposed for the Space Station Freedom. The major challenge to spacecraft fire extinguishment design and operations is from the micro-gravity environment, which minimizes natural convection and profoundly influences combustion and extinguishing agent effectiveness, dispersal, and post-fire cleanup. Discussed here are extinguishment in microgravity, fire-suppression problems anticipated in future spacecraft, and research needs and opportunities.

  6. Neural-Network Controller For Vibration Suppression

    NASA Technical Reports Server (NTRS)

    Boussalis, Dhemetrios; Wang, Shyh Jong

    1995-01-01

    Neural-network-based adaptive-control system proposed for vibration suppression of flexible space structures. Controller features three-layer neural network and utilizes output feedback. Measurements generated by various sensors on structure. Feed forward path also included to speed up response in case plant exhibits predominantly linear dynamic behavior. System applicable to single-input single-output systems. Work extended to multiple-input multiple-output systems as well.

  7. Currently available cough suppressants for chronic cough.

    PubMed

    Chung, Kian Fan

    2008-01-01

    Chronic cough is a common symptom but only a fraction of patients seek medical attention. Addressing the causes of chronic cough may lead to control of cough; however, this approach is not always successful since there is a certain degree of failure even when the cause(s) of cough are adequately treated; in idiopathic cough, there is no cause to treat. Persistent cough may be associated with deterioration of quality of life, and treatment with cough suppressants is indicated. Currently available cough suppressants include the centrally acting opioids such as morphine, codeine, and dextromethorphan. Peripherally acting antitussives include moguisteine and levodropropizine. Early studies report success in reducing cough in patients with chronic bronchitis or COPD; however, a carefully conducted study showed no effect of codeine on cough of COPD. Success with these cough suppressants can be achieved at high doses that are associated with side effects. Slow-release morphine has been reported to be useful in controlling intractable cough with good tolerance to constipation and drowsiness. There have been case reports of the success of centrally acting drugs such as amitryptiline, paroxetine, gabapentin, and carbamezepine in chronic cough. New opioids such as nociceptin or antagonists of TRPV1 may turn out to be more effective. Efficacy of cough suppressants must be tested in double-blind randomised trials using validated measures of cough in patients with chronic cough not responding to specific treatments. Patients with chronic cough are in desperate need of effective antitussives that can be used either on demand or on a long-term basis.

  8. The retinoblastoma protein: multitasking to suppress tumorigenesis.

    PubMed

    Vormer, Tinke L; Hansen, Jacob B; Te Riele, Hein

    2015-01-01

    Tumor suppressor activity of the retinoblastoma protein pRB is preserved despite loss of interaction with E2F transcription factors (E2F) or proteins harboring a leucine-x-cysteine-x-glutamic acid motif (LxCxE, where x is any amino acid). This indicates that pRB uses several parallel pathways to suppress tumorigenesis, which may also include E2F- and LxCxE-independent interactions. PMID:27308398

  9. The retinoblastoma protein: multitasking to suppress tumorigenesis

    PubMed Central

    Vormer, Tinke L.; Hansen, Jacob B; te Riele, Hein

    2015-01-01

    Tumor suppressor activity of the retinoblastoma protein pRB is preserved despite loss of interaction with E2F transcription factors (E2F) or proteins harboring a leucine-x-cysteine-x-glutamic acid motif (LxCxE, where x is any amino acid). This indicates that pRB uses several parallel pathways to suppress tumorigenesis, which may also include E2F- and LxCxE-independent interactions. PMID:27308398

  10. Currently available cough suppressants for chronic cough.

    PubMed

    Chung, Kian Fan

    2008-01-01

    Chronic cough is a common symptom but only a fraction of patients seek medical attention. Addressing the causes of chronic cough may lead to control of cough; however, this approach is not always successful since there is a certain degree of failure even when the cause(s) of cough are adequately treated; in idiopathic cough, there is no cause to treat. Persistent cough may be associated with deterioration of quality of life, and treatment with cough suppressants is indicated. Currently available cough suppressants include the centrally acting opioids such as morphine, codeine, and dextromethorphan. Peripherally acting antitussives include moguisteine and levodropropizine. Early studies report success in reducing cough in patients with chronic bronchitis or COPD; however, a carefully conducted study showed no effect of codeine on cough of COPD. Success with these cough suppressants can be achieved at high doses that are associated with side effects. Slow-release morphine has been reported to be useful in controlling intractable cough with good tolerance to constipation and drowsiness. There have been case reports of the success of centrally acting drugs such as amitryptiline, paroxetine, gabapentin, and carbamezepine in chronic cough. New opioids such as nociceptin or antagonists of TRPV1 may turn out to be more effective. Efficacy of cough suppressants must be tested in double-blind randomised trials using validated measures of cough in patients with chronic cough not responding to specific treatments. Patients with chronic cough are in desperate need of effective antitussives that can be used either on demand or on a long-term basis. PMID:17909897

  11. Greater magnocellular saccadic suppression in high versus low autistic tendency suggests a causal path to local perceptual style.

    PubMed

    Crewther, David P; Crewther, Daniel; Bevan, Stephanie; Goodale, Melvyn A; Crewther, Sheila G

    2015-12-01

    Saccadic suppression-the reduction of visual sensitivity during rapid eye movements-has previously been proposed to reflect a specific suppression of the magnocellular visual system, with the initial neural site of that suppression at or prior to afferent visual information reaching striate cortex. Dysfunction in the magnocellular visual pathway has also been associated with perceptual and physiological anomalies in individuals with autism spectrum disorder or high autistic tendency, leading us to question whether saccadic suppression is altered in the broader autism phenotype. Here we show that individuals with high autistic tendency show greater saccadic suppression of low versus high spatial frequency gratings while those with low autistic tendency do not. In addition, those with high but not low autism spectrum quotient (AQ) demonstrated pre-cortical (35-45 ms) evoked potential differences (saccade versus fixation) to a large, low contrast, pseudo-randomly flashing bar. Both AQ groups showed similar differential visual evoked potential effects in later epochs (80-160 ms) at high contrast. Thus, the magnocellular theory of saccadic suppression appears untenable as a general description for the typically developing population. Our results also suggest that the bias towards local perceptual style reported in autism may be due to selective suppression of low spatial frequency information accompanying every saccadic eye movement.

  12. Neural Networks for Mindfulness and Emotion Suppression

    PubMed Central

    Katsunuma, Ruri; Oba, Kentaro; Terasawa, Yuri; Motomura, Yuki; Mishima, Kazuo

    2015-01-01

    Mindfulness, an attentive non-judgmental focus on “here and now” experiences, has been incorporated into various cognitive behavioral therapy approaches and beneficial effects have been demonstrated. Recently, mindfulness has also been identified as a potentially effective emotion regulation strategy. On the other hand, emotion suppression, which refers to trying to avoid or escape from experiencing and being aware of one’s own emotions, has been identified as a potentially maladaptive strategy. Previous studies suggest that both strategies can decrease affective responses to emotional stimuli. They would, however, be expected to provide regulation through different top-down modulation systems. The present study was aimed at elucidating the different neural systems underlying emotion regulation via mindfulness and emotion suppression approaches. Twenty-one healthy participants used the two types of strategy in response to emotional visual stimuli while functional magnetic resonance imaging was conducted. Both strategies attenuated amygdala responses to emotional triggers, but the pathways to regulation differed across the two. A mindful approach appears to regulate amygdala functioning via functional connectivity from the medial prefrontal cortex, while suppression uses connectivity with other regions, including the dorsolateral prefrontal cortex. Thus, the two types of emotion regulation recruit different top-down modulation processes localized at prefrontal areas. These different pathways are discussed. PMID:26083379

  13. Suppressing bullfrog larvae with carbon dioxide

    USGS Publications Warehouse

    Gross, Jackson A.; Ray, Andrew; Sepulveda, Adam J.; Watten, Barnaby J.; Densmore, Christine L.; Layhee, Megan J.; Mark Abbey-Lambert,; ,

    2014-01-01

    Current management strategies for the control and suppression of the American Bullfrog (Lithobates catesbeianus = Rana catesbeiana Shaw) and other invasive amphibians have had minimal effect on their abundance and distribution. This study evaluates the effects of carbon dioxide (CO2) on pre- and prometamorphic Bullfrog larvae. Bullfrogs are a model organism for evaluating potential suppression agents because they are a successful invader worldwide. From experimental trials we estimated that the 24-h 50% and 99% lethal concentration (LC50 and LC99) values for Bullfrog larvae were 371 and 549 mg CO2/L, respectively. Overall, larvae that succumbed to experimental conditions had a lower body condition index than those that survived. We also documented sublethal changes in blood chemistry during prolonged exposure to elevated CO2. Specifically, blood pH decreased by more than 0.5 pH units after 9 h of exposure and both blood partial pressure of CO2 (pCO2) and blood glucose increased. These findings suggest that CO2 treatments can be lethal to Bullfrog larvae under controlled laboratory conditions. We believe this work represents the necessary foundation for further consideration of CO2 as a potential suppression agent for one of the most harmful invaders to freshwater ecosystems.

  14. Atomic clocks with suppressed blackbody radiation shift.

    PubMed

    Yudin, V I; Taichenachev, A V; Okhapkin, M V; Bagayev, S N; Tamm, Chr; Peik, E; Huntemann, N; Mehlstäubler, T E; Riehle, F

    2011-07-15

    We develop a concept of atomic clocks where the blackbody radiation shift and its fluctuations can be suppressed by 1-3 orders of magnitude independent of the environmental temperature. The suppression is based on the fact that in a system with two accessible clock transitions (with frequencies ν1 and ν2) which are exposed to the same thermal environment, there exists a "synthetic" frequency ν(syn) ∝ (ν1 - ε12ν2) largely immune to the blackbody radiation shift. For example, in the case of 171Yb+ it is possible to create a synthetic-frequency-based clock in which the fractional blackbody radiation shift can be suppressed to the level of 10(-18) in a broad interval near room temperature (300±15  K). We also propose a realization of our method with the use of an optical frequency comb generator stabilized to both frequencies ν1 and ν2, where the frequency ν(syn) is generated as one of the components of the comb spectrum.

  15. Hypergravity suppresses bone resorption in ovariectomized rats

    NASA Astrophysics Data System (ADS)

    Ikawa, Tesshu; Kawaguchi, Amu; Okabe, Takahiro; Ninomiya, Tadashi; Nakamichi, Yuko; Nakamura, Midori; Uehara, Shunsuke; Nakamura, Hiroaki; Udagawa, Nobuyuki; Takahashi, Naoyuki; Nakamura, Hiroaki; Wakitani, Shigeyuki

    2011-04-01

    The effects of gravity on bone metabolism are unclear, and little has been reported about the effects of hypergravity on the mature skeleton. Since low gravity has been shown to decrease bone volume, we hypothesized that hypergravity increases bone volume. To clarify this hypothesis, adult female rats were ovariectomized and exposed to hypergravity (2.9G) using a centrifugation system. The rats were killed 28 days after the start of loading, and the distal femoral metaphysis of the rats was studied. Bone architecture was assessed by micro-computed tomography (micro-CT) and bone mineral density was measured using peripheral quantitative CT (pQCT). Hypergravity increased the trabecular bone volume of ovariectomized rats. Histomorphometric analyses revealed that hypergravity suppressed both bone formation and resorption and increased bone volume in ovariectomized rats. Further, the cell morphology, activity, proliferation, and differentiation of osteoclasts and osteoblasts exposed to hypergravity were evaluated in vitro. Hypergravity inhibited actin ring formation in mature osteoclasts, which suggested that the osteoclast activity was suppressed. However, hypergravity had no effect on osteoblasts. These results suggest that hypergravity can stimulate an increase in bone volume by suppressing bone resorption in ovariectomized rats.

  16. Suppression of Ostwald Ripening by Chemical Reactions

    NASA Astrophysics Data System (ADS)

    Zwicker, David; Hyman, Anthony A.; Jülicher, Frank

    2015-03-01

    Emulsions consisting of droplets immersed in a fluid are typically unstable and coarsen over time. One important coarsening process is Ostwald ripening, which is driven by the surface tension of the droplets. Ostwald ripening must thus be suppressed to stabilize emulsions, e.g. to control the properties of pharmaceuticals, food, or cosmetics. Suppression of Ostwald ripening is also important in biological cells, which contain stable liquid-like compartments, e.g. germ granules, Cajal-bodies, and centrosomes. Such systems are often driven away from equilibrium by chemical reactions and can thus be called active emulsions. Here, we show that non-equilibrium chemical reactions can suppress Ostwald Ripening, leading to stable, monodisperse emulsions. We derive analytical approximations of the typical droplet size, droplet count, and time scale of the dynamics from a coarse-grained description of the droplet dynamics. We also compare these results to numerical simulations of the continuous concentration fields. Generally, we thus show how chemical reactions can be used to stabilize emulsions and to control their properties in technology and nature.

  17. Suppression of PAI-1 expression through inhibition of the EGFR-mediated signaling cascade in rat kidney fibroblast by ascofuranone.

    PubMed

    Cho, Hyun-Ji; Kang, Jeong-Han; Kim, Teoan; Park, Kwang-Kyun; Kim, Cheorl-Ho; Lee, In-Seon; Min, Kwan-Sik; Magae, Junji; Nakajima, Hiroo; Bae, Young-Seuk; Chang, Young-Chae

    2009-05-15

    Fibrosis in glomerulosclerosis causes progressive loss of renal function. Transforming growth factor (TGF)-beta, one of the major profibrotic cytokines, induces the synthesis of plasminogen activator inhibitor (PAI)-1, a factor that plays a crucial role in the development of fibrosis. Here, we found that an isoprenoid antibiotic, ascofuranone, suppresses expression of profibrotic factors including matrix proteins and PAI-1 induced by TGF-beta in renal fibroblasts. Ascofuranone selectively inhibits phosphorylation of epidermal growth factor receptor (EGFR), and downstream kinases such as Raf-1, MEK-1/2, and ERK-1/2. PAI-1 transcription also is suppressed by treatment with kinase inhibitors for MEK-1/2 or EGFR, and with small interfering RNA for EGFR. Ascofuranone inhibits cellular metalloproteinase activity, and an inhibitor of metalloproteinases suppresses EGFR phosphorylation and PAI-1 transcription. These results suggest that ascofuranone suppresses expression of profibrotic factors through the inhibition of an EGFR-dependent signal transduction pathway activated by metalloproteinases.

  18. Suppression of resonance Raman scattering via ground state depletion towards sub-diffraction-limited label-free microscopy.

    PubMed

    Rieger, Steffen; Fischedick, Markus; Boller, Klaus-Jochen; Fallnich, Carsten

    2016-09-01

    We report on the first experimental demonstration of the suppression of spontaneous Raman scattering via ground state depletion. The concept of Raman suppression can be used to achieve sub-diffraction-limited resolution in label-free microscopy by exploiting spatially selective signal suppression when imaging a sample with a combination of Gaussian- and donut-shaped beams and reconstructing a resolution-enhanced image from this data. Using a nanosecond pulsed laser source with an emission wavelength of 355 nm, the ground state of tris(bipyridine)ruthenium(II) molecules solved in acetonitrile was depleted and the spontaneous Raman scattering at 355 nm suppressed by nearly 50 %. Based on spectroscopic data retrieved from our experiment, we modeled the Raman image of a scattering center in order to demonstrate the applicability of this effect for superresolution Raman microscopy. PMID:27607677

  19. Suppression of resonance Raman scattering via ground state depletion towards sub-diffraction-limited label-free microscopy.

    PubMed

    Rieger, Steffen; Fischedick, Markus; Boller, Klaus-Jochen; Fallnich, Carsten

    2016-09-01

    We report on the first experimental demonstration of the suppression of spontaneous Raman scattering via ground state depletion. The concept of Raman suppression can be used to achieve sub-diffraction-limited resolution in label-free microscopy by exploiting spatially selective signal suppression when imaging a sample with a combination of Gaussian- and donut-shaped beams and reconstructing a resolution-enhanced image from this data. Using a nanosecond pulsed laser source with an emission wavelength of 355 nm, the ground state of tris(bipyridine)ruthenium(II) molecules solved in acetonitrile was depleted and the spontaneous Raman scattering at 355 nm suppressed by nearly 50 %. Based on spectroscopic data retrieved from our experiment, we modeled the Raman image of a scattering center in order to demonstrate the applicability of this effect for superresolution Raman microscopy.

  20. Lexical and Syntactic Influences on Structural Selection in Language Production

    ERIC Educational Resources Information Center

    Frazer, Alexandra Kate

    2016-01-01

    We still know surprisingly little about how grammatical structures are selected for use in sentence production. A major debate concerns whether structural selection is competitive or noncompetitive. Competitive accounts propose that alternative structures or structural components actively suppress one another's activation until one option reaches…