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Sample records for selective isobar suppression

  1. The ILIAS project for selective isobar suppression by laser photodetachment

    NASA Astrophysics Data System (ADS)

    Forstner, Oliver; Andersson, Pontus; Hanstorp, Dag; Lahner, Johannes; Martschini, Martin; Pitters, Johanna; Priller, Alfred; Steier, Peter; Golser, Robin

    2015-10-01

    Laser photodetachment is the process when the extra electron of a negative ion is removed by means of laser radiation. This can happen only if the photon energy is larger than the electron affinity of the ion. The process can be used in mass spectrometry to selectively suppress unwanted isobars, provided that the electron affinity of the unwanted isobar is lower than that of the isobar under investigation. At the Ion Laser InterAction Setup (ILIAS) at the University of Vienna laser photodetachment of negative atomic and molecular ions is studied and its applicability for selective isobar suppression in accelerator mass spectrometry (AMS) is evaluated. The setup provides mass separated beams of negative ions with energies up to 30 keV. Negative ions are produced in a Middleton type cesium sputter ion source, mass selected and overlapped with a strong continuous wave laser beam. In order to extend the interaction time of ions and laser, the ion beam is decelerated to thermal energies in a gas-filled radio frequency quadrupole cooler. For an appropriate choice of the photon energy, unwanted isobars are neutralized while the isobar of interest is unaffected and remains negatively charged. A description of the ILIAS setup and results from the commissioning phase of the RFQ cooler are presented. Up to 8% ion beam transmission could be achieved after a recent redesign of the extraction system. Furthermore first results of photodetachment experiments of 63Cu- within the RFQ cooler are presented.

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

    NASA Astrophysics Data System (ADS)

    Liu, Yuan; Havener, A. C.; Havener, C. C.; Liang, F.; Beene, J. R.

    2004-11-01

    Selectively removing unwanted isobaric negative ions by electron photodetachment with a pulsed laser beam has been reported. However, the fraction of the negative ions removed was very small due to the short laser pulses used. Continuous wave (CW) lasers are desired for this application, but the photon flux available from CW lasers is too low. We have investigated a novel scheme for efficient suppression of isobar contaminants by photodetachment in a gas-filled RF-only quadrupole (RFQ) ion cooler. Simulation studies have shown that the RFQ ion cooler can significantly increase the laser-ion interaction time, thus, high efficiency of photodetachment is possible with commercially available CW lasers. A proof-of-principle experiment of Co^- and Ni^- ions is underway. A CW Nd:YAG laser beam at 1064 nm wavelength is used to selectively remove Co^- ions inside a RFQ ion cooler. A detailed description of the experimental setup and expected photodetachment efficiencies for Co^- and Ni^- ions will be given in this report. 1. D. Berkovits, et al., Nucl. Instrum. Meth. B52 (1990) 378-333.

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

    PubMed

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

    2014-03-01

    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. PMID:24689577

  4. 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; Institute of Applied Physics, TU Darmstadt, Schlossgartenstr. 7, 64289 Darmstadt ; Lassen, Jens Teigelhöfer, Andrea; Department of Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba R3T 2N2

    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.

  5. 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.

  6. 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

  7. 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.

  8. A Radio Frequency Quadrupole Instrument for use with Accelerator Mass Spectrometry: Application to Low Kinetic Energy Reactive Isobar Suppression and Gas--Phase Anion Reaction Studies

    NASA Astrophysics Data System (ADS)

    Eliades, John Alexander

    A radio frequency (rf) quadrupole instrument, currently known as an Isobar Separator for Anions (ISA), has been integrated into an Accelerator Mass Spectrometry (AMS) system to facilitate anion--gas reactions before the tandem accelerator. An AMS Cs+ sputter source provided ≥ 15 keV ions that were decelerated in the prototype ISA to < 20 eV for reaction in a single collision cell and re-accelerated for AMS analysis. Reaction based isobar suppression capabilities were assessed for smaller AMS systems and a new technique for gas--phase reaction studies was developed. Isobar suppression of 36S-- and 12C3-- for 36Cl analysis, and YF3-- and ZrF3-- for 90Sr analysis were studied in NO2 with deceleration to ≤ 12 eV. Observed attenuation cross sections, sigma [x 10--15 cm2], were sigma(S-- + NO2) = 6.6, sigma(C3-- + NO2) = 4.2, sigma(YF3-- + NO 2) = 7.6, sigma(ZrF3-- + NO2) = 19. With 8 mTorr NO2, relative attenuations of S-- /Cl-- ˜ 10--6, C 3--/Cl-- ˜ 10--7 , YF3--/SrF3-- ˜ 5 x 10--5 and ZrF3-- /SrF3-- ˜ 4 x 10--6 were observed with Cl-- ˜ 30% and SrF 3-- > 90% transmission. Current isobar attenuation limits with ≤ 1.75 MV accelerator terminal voltage and ppm impurity levels were calculated to be 36S--/Cl-- ˜ 4 x 10--16, 12C3 --/Cl-- ˜ 1.2 x 10--16, 90YF3--/SrF3-- ˜ 10--15 and 90ZrF3 --/SrF3-- ˜ 10--16 . Using 1.75 MV, four 36Cl reference standards in the range 4 x 10--13 ≤ 36Cl/Cl ≤ 4 x 10 --11 were analyzed with 8 mTorr NO2. The measured 36Cl/Cl ratios plotted very well against the accepted values. A sample impurity content S/Cl ≤ 6 x 10--5 was measured and a background level of 36S--/Cl ≤ 9 x 10--15 was determined. Useful currents of a wide variety of anions are produced in AMS sputter sources and molecules can be identified relatively unambiguously by stripping fragments from tandem accelerators. Reactions involving YF3 --, ZrF3--, S-- and SO-- + NO2 in the ISA analyzed by AMS are described, and some interesting reactants are identified.

  9. Isobar Separator for Anions: Current status

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. Selective Serotonin Reuptake Inhibitor Suppression of HIV Infectivity and Replication

    PubMed Central

    Benton, Tami; Lynch, Kevin; Dubé, Benoit; Gettes, David R.; Tustin, Nancy B.; Lai, Jian Ping; Metzger, David S.; Blume, Joshua; Douglas, Steven D.; Evans, Dwight L.

    2010-01-01

    Objective To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down regulate HIV infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/AIDS. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system. The 5-HT transporter and 5-HT receptors are widely distributed throughout the central nervous and immune systems. Depression has been associated with suppression of natural killer cells (NK) cells and CD8+ lymphocytes, key regulators of HIV infection. Methods Ex-vivo models for acute and chronic HIV infection were used to study the effects of citalopram on HIV viral infection and replication, in 48 depressed and non-depressed women. For both the acute and chronic infection models, HIV reverse transcriptase (RT) activity was measured in the citalopram treatment condition and the control condition. Results The SSRI significantly downregulated the RT response in both the acute and chronic infection models. Specifically, citalopram significantly decreased the acute HIV infectivity of macrophages. Citalopram also significantly decreased HIV viral replication in the latently infected T-cell line and in the latently infected macrophage cell line. There was no difference in down-regulation by depression status. Conclusions These studies suggest that an SSRI enhances NK/CD8 non-cytolytic HIV suppression in HIV/AIDS and decreases HIV viral infectivity of macrophages, ex vivo, suggesting the need for in vivo studies to determine a potential role for agents targeting serotonin in the host defense against HIV. PMID:20947783

  15. Selection of hydrate suppression methods for gas streams

    SciTech Connect

    Behrens, S.D.; Covington, K.K.; Collie, J.T. III

    1999-07-01

    This paper will discuss and compare the methods used to suppress hydrate formation in natural gas streams. Included in the comparison will be regenerated systems using ethylene glycol and non-regenerated systems using methanol. A comparison will be made between the quantities of methanol and ethylene glycol required to achieve a given a suppression. A discussion of BTEX emissions resulting from the ethylene glycol regenerator along with the effect or process variables on these emissions is also given.

  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. Survey of Evaluated Isobaric Analog States

    SciTech Connect

    MacCormick, M.

    2014-06-15

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

  18. 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.

  19. S5FP: Spectrally Selective Suppression with Steady State Free Precession

    PubMed Central

    Derbyshire, J. A.; Herzka, D. A.; McVeigh, E. R.

    2007-01-01

    A method is presented that employs the inherent spectral selectivity of the Steady-State Free Precession (SSFP) pulse sequence to provide a spectral band of suppression. At TE = TR/2, SSFP partitions the magnetization into two phase-opposed spectral components. Z-storing one of these components simultaneously further excites the other, which is then suppressed by gradient crushing and RF spoiling. The Spectrally Selective Suppression with SSFP (S5FP) method is shown to provide significant attenuation of fat signals, while the water signals are essentially unaffected and provide the normal SSFP contrast. Fat suppression is achieved with relatively little temporal overhead (less than 10% reduction in temporal resolution). S5FP was validated using simulations, phantoms, and human studies. Published 2005 Wiley-Liss, Inc.† PMID:16155880

  20. 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

  1. 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

  2. 5-Fluorouracil targets thymidylate synthase in the selective suppression of TH17 cell differentiation

    PubMed Central

    Wang, Juan; Peng, Liang; Zhang, Ruihua; Zheng, Zihan; Chen, Chun; Cheung, Ka Lung; Cui, Miao; Bian, Guanglin; Xu, Feihong; Chiang, David; Hu, Yuan; Chen, Ye; Lu, Geming; Yang, Jianjun; Zhang, Hui; Yang, Jianfei; Zhu, Hongfa; Chen, Shu-hsia; Liu, Kebin; Zhou, Ming-Ming; Sikora, Andrew G.; Li, Liwu; Jiang, Bo; Xiong, Huabao

    2016-01-01

    While it is well established that treatment of cancer patients with 5-Fluorouracil (5-FU) can result in immune suppression, the exact function of 5-FU in the modulation of immune cells has not been fully established. We found that low dose 5-FU selectively suppresses TH17 and TH1 cell differentiation without apparent effect on Treg, TH2, and significantly suppresses thymidylate synthase (TS) expression in TH17 and TH1 cells but has a lesser effect in tumor cells and macrophages. Interestingly, the basal expression of TS varies significantly between T helper phenotypes and knockdown of TS significantly impairs TH17 and TH1 cell differentiation without affecting the differentiation of either Treg or TH2 cells. Finally, low dose 5-FU is effective in ameliorating colitis development by suppressing TH17 and TH1 cell development in a T cell transfer colitis model. Taken together, the results highlight the importance of the anti-inflammatory functions of low dose 5-FU by selectively suppressing TH17 and TH1 immune responses. PMID:27027355

  3. Improvement of non-isobaric model for shock ignition

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  4. Isospin purity in the A=42 isobars

    SciTech Connect

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

    2004-09-13

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

  5. Probing Temperature from Intermediate Mass Fragment by Isobaric Yield Ratio in Heavy-Ion Collisions

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

    A probe to extract the temperature (TIYR) from intermediate-mass fragment has been proposed using the isobaric yield ratio (IYR) difference based on the modified Fisher model. By analyzing the isobaric cross section in the measured 140A MeV 40,48Ca+9Be reactions, the TIYR can well fit the IYR difference for the large mass fragments. Because of the fragments are produced in different colliding regions, it is also suggested to select the fragments according to different mechanisms when using TIYR. Supported by Program for Science & Technology Innovation Talents in Universities of Henan Province under Grant No. 13HASTIT046

  6. 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.

  7. Selective suppression of carrier-driven photochemical etching: Raman spectroscopy as a diagnostic tool

    SciTech Connect

    Ashby, C.I.H.; Myers, D.R.; Vawter, G.A.; Biefeld, R.M.; Klem, J.F.

    1990-01-01

    Carrier-driven photochemical etching of semiconductors can be selectively suppressed by altering the near-surface region to enhance carrier recombination, thereby reducing the supply of carriers that drive the surface etching reaction. Two methods for enhancing recombination and decreasing the etch rate at a given phonon flux include ion implantation and localized Zn diffusion. Raman spectroscopy can be employed to determine whether sufficient alterations of electronic properties has occurred to suppress etching. Carrier-driven photochemical reactions, which require direct participation of free carriers for the chemical reaction to proceed, can be selectively suppressed by increasing the minority carrier recombination rate, thereby reducing the supply of carriers that drive the surface etching reaction. Two methods for enhancing recombination and decreasing the etching quantum yield, which is the number of atoms removed per incident photon, include ion implantation and localized Zn diffusion. For ion implantation, recombination- promoting defect concentrations depend on ion species, fluence, and annealing both during and after the implantation process. Other recombination processes related to carrier scattering from ionized impurities from in-diffusion of dopants or following implant activation can control etching. Raman spectroscopy can be employed to detect changes in electronic properties that correlate with etching suppression. Changes that occur in the LO-phonon lineshape, such as those associated with phonon confinement and ionized impurity scattering, can be diagnostic of the carrier-driven etching behavior following a specific treatment. We have demonstrated two applications of Raman spectroscopy as a diagnostic for suppression of the carrier-driven photochemical etching of GaAs. 12 refs., 3 figs.

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  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. The nest site lottery: how selectively neutral density dependent growth suppression induces frequency dependent selection.

    PubMed

    Argasinski, K; Broom, M

    2013-12-01

    Modern developments in population dynamics emphasize the role of the turnover of individuals. In the new approaches stable population size is a dynamic equilibrium between different mortality and fecundity factors instead of an arbitrary fixed carrying capacity. The latest replicator dynamics models assume that regulation of the population size acts through feedback driven by density dependent juvenile mortality. Here, we consider a simplified model to extract the properties of this approach. We show that at the stable population size, the structure of the frequency dependent evolutionary game emerges. Turnover of individuals induces a lottery mechanism where for each nest site released by a dead adult individual a single newborn is drawn from the pool of newborn candidates. This frequency dependent selection leads towards the strategy maximizing the number of newborns per adult death. However, multiple strategies can maximize this value. Among them, the strategy with the greatest mortality (which implies the greatest instantaneous growth rate) is selected. This result is important for the discussion about universal fitness measures and which parameters are maximized by natural selection. This is related to the fitness measures R0 and r, because the number of newborns per single dead individual equals the lifetime production of newborn R0 in models without aging. We thus have a two-stage procedure, instead of a single fitness measure, which is a combination of R0 and r. According to the nest site lottery mechanism, at stable population size, selection favors strategies with the greatest r, i.e. those with the highest turnover, from those with the greatest R0. PMID:24071631

  11. Noisy Speech Recognition Based on Integration/Selection of Multiple Noise Suppression Methods Using Noise GMMs

    NASA Astrophysics Data System (ADS)

    Kitaoka, Norihide; Hamaguchi, Souta; Nakagawa, Seiichi

    To achieve high recognition performance for a wide variety of noise and for a wide range of signal-to-noise ratio, this paper presents methods for integration of four noise reduction algorithms: spectral subtraction with smoothing of time direction, temporal domain SVD-based speech enhancement, GMM-based speech estimation and KLT-based comb-filtering. In this paper, we proposed two types of combination methods of noise suppression algorithms: selection of front-end processor and combination of results from multiple recognition processes. Recognition results on the CENSREC-1 task showed the effectiveness of our proposed methods.kn-abstract=

  12. 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

  13. Intercellular Redistribution of cAMP Underlies Selective Suppression of Cancer Cell Growth by Connexin26

    PubMed Central

    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. 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

  15. Delta-Isobar magnetic form factor in QCD

    SciTech Connect

    Belyaev, Vladimir

    1993-01-01

    We consider the QCD sum rules approach for Delta-isobar magnetic form factor in the infra-red region $0isobar magnetic moment.

  16. Ubiquitylation of Autophagy Receptor Optineurin by HACE1 Activates Selective Autophagy for Tumor Suppression

    PubMed Central

    Liu, Zhengzhao; Chen, Peng; Gao, Hong; Gu, Yu; Yang, Jiao; Peng, Hong; Xu, Xingxing; Wang, Haifeng; Yang, Meiqiang; Liu, Xiaoying; Fan, Libin; Chen, Shiyao; Zhou, Jian; Sun, Yihong; Ruan, Kangchen; Cheng, Shuqun; Komatsu, Masaaki; White, Eileen; Li, Lin; Ji, Hongbin; Finley, Daniel; Hu, Ronggui

    2014-01-01

    Summary In selective autophagy, receptors are central for cargo selection and delivery. However, it remains yet unclear whether and how multiple autophagy receptors might form complex and function concertedly to control autophagy. Optineurin (OPTN), implicated genetically in glaucoma and amyotrophic lateral sclerosis, was a recently identified autophagy receptor. Here we report that tumor suppressor HACE1, a ubiquitin ligase, ubiquitylates OPTN and promotes its interaction with p62/SQSTM1 to form the autophagy receptor complex, thus accelerating autophagic flux. Interestingly, the K48-linked polyubiquitin chains that HACE1 conjugates onto OPTN might predominantly target OPTN for autophagic degradation. By demonstrating that the HACE1-OPTN axis synergistically suppresses growth and tumorigenicity of lung cancer cells, our findings may open an avenue for developing autophagy-targeted therapeutic intervention into cancer. PMID:25026213

  17. 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

  18. Target effects in isobaric yield ratio differences between projectile fragmentation reactions

    NASA Astrophysics Data System (ADS)

    Ma, Chun-Wang; Zhang, Yan-Li; Qiao, Chun-Yuan; Wang, Shan-Shan

    2015-01-01

    Background: The isobaric yield ratio difference (IBD) between reactions is know to be sensitive to the density difference between projectiles in heavy-ion collisions around the Fermi energy. Purpose: The target effects in the isobaric yield ratio (IYR) and the IBD results have been studied. Methods: The amount of isotopes in the 140 A MeV 48 ,40Ca +181Ta /9Be and 58 ,64Ni +181Ta /9Be reactions have been previously measured with high accuracy. The IYR and IBD results have been obtained from these reactions to study the effects of the light 9Be and heavy 181Ta targets. A ratio (rΔ μ) between the IBD results for the reactions with Ta and Be targets is defined to quantitatively show the target dependence of the IBD results. Results The IYRs for reactions with symmetric projectiles are more easily affected than those for reactions with neutron-rich projectiles. The IBD results are suppressed by using the 181Ta target to different degrees. Conclusions: The IYR and IBD results are influenced by the target used. The IBD for the I =1 isobaric chain is suggested as a probe to study the difference between the neutron and proton densities of the reaction systems.

  19. Selective suppression of human papillomavirus transcription in non-tumorigenic cells by 5-azacytidine.

    PubMed Central

    Rösl, F; Dürst, M; zur Hausen, H

    1988-01-01

    The transcription of human papillomavirus type 18 (HPV 18) is selectively suppressed in non-tumorigenic HeLa x fibroblast or HeLa x keratinocyte cell hybrids by 5-azacytidine. In contrast, viral gene expression is not influenced by 5-azacytidine in both tumorigenic hybrid segregants and in the parental HeLa cells. The suppression mechanism seems to operate at the level of initiation of transcription since nuclear run-on experiments show the absence of elongated nascent viral RNA, whereas the transcription of cellular reference genes remains unaffected. Down-regulation of HPV 18 mRNA correlates directly with cessation of cellular growth and can be abolished using the protein synthesis inhibitor cycloheximide. Furthermore human keratinocytes immortalized by HPV 16 but still retaining the non-tumorigenic phenotype reveal the same inhibitory effect on viral transcription after treatment with 5-azacytidine. These results support a model of a postulated intracellular control mechanism, directed against papillomavirus transcription, which can be induced by 5-azacytidine and appears to correlate with the presence of specific chromosomes in non-tumorigenic cells. Images PMID:2457495

  20. A channel-selection criterion for suppressing reverberation in cochlear implants.

    PubMed

    Kokkinakis, Kostas; Hazrati, Oldooz; Loizou, Philipos C

    2011-05-01

    Little is known about the extent to which reverberation affects speech intelligibility by cochlear implant (CI) listeners. Experiment 1 assessed CI users' performance using Institute of Electrical and Electronics Engineers (IEEE) sentences corrupted with varying degrees of reverberation. Reverberation times of 0.30, 0.60, 0.80, and 1.0 s were used. Results indicated that for all subjects tested, speech intelligibility decreased exponentially with an increase in reverberation time. A decaying-exponential model provided an excellent fit to the data. Experiment 2 evaluated (offline) a speech coding strategy for reverberation suppression using a channel-selection criterion based on the signal-to-reverberant ratio (SRR) of individual frequency channels. The SRR reflects implicitly the ratio of the energies of the signal originating from the early (and direct) reflections and the signal originating from the late reflections. Channels with SRR larger than a preset threshold were selected, while channels with SRR smaller than the threshold were zeroed out. Results in a highly reverberant scenario indicated that the proposed strategy led to substantial gains (over 60 percentage points) in speech intelligibility over the subjects' daily strategy. Further analysis indicated that the proposed channel-selection criterion reduces the temporal envelope smearing effects introduced by reverberation and also diminishes the self-masking effects responsible for flattened formants. PMID:21568424

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

    SciTech Connect

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

    1988-01-01

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

  2. Selective 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.

  3. Selection of Motor Programs for Suppressing Food Intake and Inducing Locomotion in the Drosophila Brain

    PubMed Central

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

    2014-01-01

    Central mechanisms by which specific motor programs are selected to achieve meaningful behaviors are not well understood. Using electrophysiological recordings from pharyngeal nerves upon central activation of neurotransmitter-expressing cells, we show that distinct neuronal ensembles can regulate different feeding motor programs. In behavioral and electrophysiological experiments, activation of 20 neurons in the brain expressing the neuropeptide hugin, a homolog of mammalian neuromedin U, simultaneously suppressed the motor program for food intake while inducing the motor program for locomotion. Decreasing hugin neuropeptide levels in the neurons by RNAi prevented this action. Reducing the level of hugin neuronal activity alone did not have any effect on feeding or locomotion motor programs. Furthermore, use of promoter-specific constructs that labeled subsets of hugin neurons demonstrated that initiation of locomotion can be separated from modulation of its motor pattern. These results provide insights into a neural mechanism of how opposing motor programs can be selected in order to coordinate feeding and locomotive behaviors. PMID:24960360

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

    PubMed

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

    2014-06-01

    Central mechanisms by which specific motor programs are selected to achieve meaningful behaviors are not well understood. Using electrophysiological recordings from pharyngeal nerves upon central activation of neurotransmitter-expressing cells, we show that distinct neuronal ensembles can regulate different feeding motor programs. In behavioral and electrophysiological experiments, activation of 20 neurons in the brain expressing the neuropeptide hugin, a homolog of mammalian neuromedin U, simultaneously suppressed the motor program for food intake while inducing the motor program for locomotion. Decreasing hugin neuropeptide levels in the neurons by RNAi prevented this action. Reducing the level of hugin neuronal activity alone did not have any effect on feeding or locomotion motor programs. Furthermore, use of promoter-specific constructs that labeled subsets of hugin neurons demonstrated that initiation of locomotion can be separated from modulation of its motor pattern. These results provide insights into a neural mechanism of how opposing motor programs can be selected in order to coordinate feeding and locomotive behaviors. PMID:24960360

  5. Isobaric Labeling-Based Relative Quantification in Shotgun Proteomics

    PubMed Central

    2015-01-01

    Mass spectrometry plays a key role in relative quantitative comparisons of proteins in order to understand their functional role in biological systems upon perturbation. In this review, we review studies that examine different aspects of isobaric labeling-based relative quantification for shotgun proteomic analysis. In particular, we focus on different types of isobaric reagents and their reaction chemistry (e.g., amine-, carbonyl-, and sulfhydryl-reactive). Various factors, such as ratio compression, reporter ion dynamic range, and others, cause an underestimation of changes in relative abundance of proteins across samples, undermining the ability of the isobaric labeling approach to be truly quantitative. These factors that affect quantification and the suggested combinations of experimental design and optimal data acquisition methods to increase the precision and accuracy of the measurements will be discussed. Finally, the extended application of isobaric labeling-based approach in hyperplexing strategy, targeted quantification, and phosphopeptide analysis are also examined. PMID:25337643

  6. 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

  7. 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

  8. 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

  9. Activated Drosophila Ras1 is selectively suppressed by isoprenyl transferase inhibitors.

    PubMed Central

    Kauffmann, R C; Qian, Y; Vogt, A; Sebti, S M; Hamilton, A D; Carthew, R W

    1995-01-01

    Ras CAAX (C = cysteine, A = aliphatic amino acid, and X = any amino acid) peptidomimetic inhibitors of farnesyl protein transferase suppress Ras-dependent cell transformation by preventing farnesylation of the Ras oncoprotein. These compounds are potential anticancer agents for tumors associated with Ras mutations. The peptidomimetic FTI-254 was tested for Ras1-inhibiting activity in whole animals by injection of activated Ras1val12 Drosophila larvae. FTI-254 decreased the ability of Ras1val12 to form supernumerary R7 photoreceptor cells in the compound eye of transformed flies. In contrast, it had no effect on the related supernumerary R7 phenotypes of flies transformed with either the activated sevenless receptor tyrosine kinase, Raf kinase, or a chimeric Ras1val12 protein that is membrane associated through myristylation instead of isoprenylation. Therefore, FTI-254 acts as an isoprenylation inhibitor to selectively inhibit Ras1val12 signaling activity in a whole-animal model system. Images Fig. 2 PMID:7479910

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. 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.

  12. Select phytochemicals suppress human T-lymphocytes and mouse splenocytes suggesting their use in autoimmunity and transplantation

    PubMed Central

    Hushmendy, Shazaan; Jayakumar, Lalithapriya; Hahn, Amy B.; Bhoiwala, Devang; Bhoiwala, Dipti L.; Crawford, Dana R.

    2009-01-01

    We have considered a novel “rational” gene targeting approach for treating pathologies whose genetic bases are defined using select phytochemicals. We reason that one such potential application of this approach would be conditions requiring immunosuppression such as autoimmune disease and transplantation, where the genetic target is clearly defined; i.e., interleukin-2 and associated T-cell activation. Therefore, we hypothesized that select phytochemicals can suppress T-lymphocyte proliferation both in vitro and in vivo. The immunosuppressive effects of berry extract, curcumin, quercetin, sulforaphane, epigallocatechin gallate (EGCG), resveratrol, α-tocopherol, vitamin C and sucrose were tested on anti-CD3 plus anti-CD28-activated primary human T-lymphocytes in culture. Curcumin, sulforaphane, quercetin, berry extract and EGCG all significantly inhibited T-cell proliferation, and this effect was not due to toxicity. IL-2 production was also reduced by these agents, implicating this important T-cell cytokine in proliferation suppression. Except for berry extract, these same agents also inhibited mouse splenic T-cell proliferation and IL-2 production. Subsequent in vivo studies revealed that quercetin (but not sulforaphane) modestly suppressed mouse splenocyte proliferation following supplementation of BALB/c mice diets. This effect was especially prominent if corrected for the loss of supplement “recall” as observed in cultured T-cells. These results suggest the potential use of these select phytochemicals for treating autoimmune and transplant patients, and support our strategy of using select phytochemicals to treat genetically-defined pathologies, an approach that we believe is simple, healthy, and cost-effective. PMID:19761891

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

    SciTech Connect

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

    2014-09-15

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

  14. Isobaric yield ratio difference and Shannon information entropy

    NASA Astrophysics Data System (ADS)

    Ma, Chun-Wang; Wei, Hui-Ling; Wang, Shan-Shan; Ma, Yu-Gang; Wada, Ryoichi; Zhang, Yan-Li

    2015-03-01

    The Shannon information entropy theory is used to explain the recently proposed isobaric yield ratio difference (IBD) probe which aims to determine the nuclear symmetry energy. Theoretically, the difference between the Shannon uncertainties carried by isobars in two different reactions (ΔIn21), is found to be equivalent to the difference between the chemical potentials of protons and neutrons of the reactions [the IBD probe, IB- Δ(βμ)21, with β the reverse temperature]. From the viewpoints of Shannon information entropy, the physical meaning of the above chemical potential difference is interpreted by ΔIn21 as denoting the nuclear symmetry energy or density difference between neutrons and protons in reactions more concisely than from the statistical ablation-abrasion model.

  15. Sampling the isothermal-isobaric ensemble by Langevin dynamics

    NASA Astrophysics Data System (ADS)

    Gao, Xingyu; Fang, Jun; Wang, Han

    2016-03-01

    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.

  16. Antitumor activity of YM155, a selective survivin suppressant, in combination with cisplatin in hepatoblastoma.

    PubMed

    Yu, Ying; Zhao, Xiaosu; Zhang, Yu; Kang, Yanling; Wang, Jiaqi; Liu, Yingchun

    2015-07-01

    Cisplatin (CDDP) is a chemotherapeutic drug that is often used for the treatment of hepatoblastoma. However, many patients acquire resistance to therapeutic agents leading to local and distant treatment failure. It has been shown that suppression survivin contributed to the inhibition of tumor growth and enhanced chemotherapeutic sensitivity in several types of cancer. The aim of the present study was to determine whether treatment with sepantronium bromide (YM155), a novel small molecule inhibitor of survivin, enhanced the sensitivity of CDDP to hepatoblastoma cells, leading to the therapeutic efficacy of cisplatin. In vitro and in vivo models were used to examine the anticancer efficacy of YM155, either as a monotherapy or in combination with CDDP to identify more effective therapeutics against hepatoblastoma. The results showed that survivin expression was upregulated in hepatoblastoma tissues and cell lines, and that YM155 inhibited survivin expression in hepatoblastoma cells in a dose-dependent manner. YM155 enhanced sensitivity of CDDP to human HepG2 and HuH-6 hepatoblastoma cells. The YM155 combination with CDDP in hepatoblastoma cells significantly decreased cell proliferation and formation, and induced cell apoptosis than either agent alone. In a mouse xenograft model, YM155 combined with CDDP significantly suppressed tumor growth compared to the monotherapy. Taken together, these findings suggested that the combination of YM155 and CDDP is a promising drug candidate for the treatment of hepatoblastoma. PMID:25955434

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

    PubMed Central

    Starenki, Dmytro

    2015-01-01

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

  18. Isotopic Ratio, Isotonic Ratio, Isobaric Ratio and Shannon Information Uncertainty

    NASA Astrophysics Data System (ADS)

    Ma, Chun-Wang; Wei, Hui-Ling

    2014-11-01

    The isoscaling and the isobaric yield ratio difference (IBD) probes, both of which are constructed by yield ratio of fragment, provide cancelation of parameters. The information entropy theory is introduced to explain the physical meaning of the isoscaling and IBD probes. The similarity between the isoscaling and IBD results is found, i.e., the information uncertainty determined by the IBD method equals to β - α determined by the isoscaling (α (β) is the parameter fitted from the isotopic (isotonic) yield ratio).

  19. 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.

  20. 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. PMID:26253462

  1. 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.

  2. The MR-TOF-MS isobar separator for the TITAN facility at TRIUMF

    NASA Astrophysics Data System (ADS)

    Jesch, Christian; Dickel, Timo; Plaß, Wolfgang R.; Short, Devin; Ayet San Andres, Samuel; Dilling, Jens; Geissel, Hans; Greiner, Florian; Lang, Johannes; Leach, Kyle G.; Lippert, Wayne; Scheidenberger, Christoph; Yavor, Mikhail I.

    2015-11-01

    At TRIUMF's Ion Trap for Atomic and Nuclear Science (TITAN) a multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS) will extend TITAN's capabilities and facilitate mass measurements and in-trap decay spectroscopy of exotic nuclei that so far have not been possible due to strong isobaric contamination. This MR-TOF-MS will also enable mass measurements of very short-lived nuclides (half-life > 1 ms) that are produced in very low quantities (a few detected ions overall). In order to allow the installation of an MR-TOF-MS in the restricted space on the platform, on which the TITAN facility is located, novel mass spectrometric methods have been developed. Transport, cooling and distribution of the ions inside the device is done using a buffer gas-filled RFQ-based ion beam switchyard. Mass selection is achieved using a dynamic retrapping technique after time-of-flight analysis in an electrostatic isochronous reflector system. Only due to the combination of these novel methods the realization of an MR-TOF-MS based isobar separator at TITAN has become possible. The device has been built, commissioned off-line and is currently under installation at TITAN.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  4. Shuttle suppression in room temperature sodium-sulfur batteries using ion selective polymer membranes.

    PubMed

    Bauer, I; Kohl, M; Althues, H; Kaskel, S

    2014-03-25

    A sodiated Nafion-coating on a porous polypropylene backbone was used as a cation selective separator for room temperature sodium-sulfur batteries. The capacity of the cells after 20 cycles could be enhanced by 75% to 350 mA h g(sulfur)(-1) using the new separator. PMID:24522659

  5. 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…

  6. 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

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

    PubMed

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

    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(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. PMID:25979358

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

    PubMed Central

    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 (PDE4H/PDE4L) 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

  9. 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.

  10. 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

  11. Systematic Comparison of Label-Free, Metabolic Labeling, and Isobaric Chemical Labeling for Quantitative Proteomics on LTQ Orbitrap Velos

    SciTech Connect

    Li, Zhou; Adams, Rachel M; Chourey, Karuna; Hurst, Gregory {Greg} B; Hettich, Robert {Bob} L; Pan, Chongle

    2012-01-01

    A variety of quantitative proteomics methods have been developed, including label-free, metabolic labeling, and isobaric chemical labeling using iTRAQ or TMT. Here, these methods were compared in terms of the depth of proteome coverage, quantification accuracy, precision, and reproducibility using a high-performance hybrid mass spectrometer, LTQ Orbitrap Velos. Our results show that (1) the spectral counting method provides the deepest proteome coverage for identification, but its quantification performance is worse than labeling-based approaches, especially the quantification reproducibility; (2) metabolic labeling and isobaric chemical labeling are capable of accurate, precise, and reproducible quantification and provide deep proteome coverage for quantification. Isobaric chemical labeling surpasses metabolic labeling in terms of quantification precision and reproducibility; (3) iTRAQ and TMT perform similarly in all aspects compared in the current study using a CID-HCD dual scan configuration. Based on the unique advantages of each method, we provide guidance for selection of the appropriate method for a quantitative proteomics study.

  12. Isobaric Labeling and Data Normalization without Requiring Protein Quantitation

    PubMed Central

    Kim, Phillip D.; Patel, Bhavinkumar B.; Yeung, Anthony T.

    2012-01-01

    Isobaric multiplexed quantitative proteomics can complement high-resolution sample isolation techniques. Here, we report a simple workflow exponentially modified protein abundance index (emPAI)-MW deconvolution (EMMOL) for normalizing isobaric reporter ratios within and between experiments, where small or unknown amounts of protein are used. EMMOL deconvolutes the isobaric tags for relative and absolute quantification (iTRAQ) data to yield the quantity of each protein of each sample in the pool, a new approach that enables the comparison of many samples without including a channel of reference standard. Moreover, EMMOL allows using a sufficient quantity of control sample to facilitate the peptide fractionation (isoelectric-focusing was used in this report), and mass spectrometry MS/MS sequencing yet relies on the broad dynamic range of iTRAQ quantitation to compare relative protein abundance. We demonstrated EMMOL by comparing four pooled samples with 20-fold range differences in protein abundance and performed data normalization without using prior knowledge of the amounts of proteins in each sample, simulating an iTRAQ experiment without protein quantitation prior to labeling. We used emPAI,1 the target protein MW, and the iTRAQ reporter ratios to calculate the amount of each protein in each of the four channels. Importantly, the EMMOL-delineated proteomes from separate iTRAQ experiments can be assorted for comparison without using a reference sample. We observed no compression of expression in iTRAQ ratios over a 20-fold range for all protein abundances. To complement this ability to analyze minute samples, we report an optimized iTRAQ labeling protocol for using 5 μg protein as the starting material. PMID:22468137

  13. 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

  14. Laser ion source for isobaric heavy ion collider experiment

    NASA Astrophysics Data System (ADS)

    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 96Ru + 96Zr. 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.

  15. 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. PMID:26931981

  16. Test of isospin purity in the A=42 isobaric analogs

    SciTech Connect

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

    2004-07-01

    A careful measurement of the lifetime of the first 2{sub T=1}{sup +} state in {sup 42}Sc has allowed an accurate experimental test of isospin purity in the A=42 isobaric analogs by using the isospin formalism. A lifetime of 69 (18) fs has been determined, giving an isoscalar matrix element of 6.8 (8) W.u. Previous measurements of the lifetimes in the mirror nuclei {sup 42}Ca and {sup 42}Ti provided an isoscalar matrix element of 7.1 (5) W.u. which is very close to the presently measured value for {sup 42}Sc.

  17. CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses

    PubMed Central

    Hammitzsch, Ariane; Tallant, Cynthia; Fedorov, Oleg; O’Mahony, Alison; Brennan, Paul E.; Hay, Duncan A.; Martinez, Fernando O.; Al-Mossawi, M. Hussein; de Wit, Jelle; Vecellio, Matteo; Wells, Christopher; Wordsworth, Paul; Müller, Susanne; Knapp, Stefan; Bowness, Paul

    2015-01-01

    Th17 responses are critical to a variety of human autoimmune diseases, and therapeutic targeting with monoclonal antibodies against IL-17 and IL-23 has shown considerable promise. Here, we report data to support selective bromodomain blockade of the transcriptional coactivators CBP (CREB binding protein) and p300 as an alternative approach to inhibit human Th17 responses. We show that CBP30 has marked molecular specificity for the bromodomains of CBP and p300, compared with 43 other bromodomains. In unbiased cellular testing on a diverse panel of cultured primary human cells, CBP30 reduced immune cell production of IL-17A and other proinflammatory cytokines. CBP30 also inhibited IL-17A secretion by Th17 cells from healthy donors and patients with ankylosing spondylitis and psoriatic arthritis. Transcriptional profiling of human T cells after CBP30 treatment showed a much more restricted effect on gene expression than that observed with the pan-BET (bromo and extraterminal domain protein family) bromodomain inhibitor JQ1. This selective targeting of the CBP/p300 bromodomain by CBP30 will potentially lead to fewer side effects than with the broadly acting epigenetic inhibitors currently in clinical trials. PMID:26261308

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

    NASA Astrophysics Data System (ADS)

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

    2011-05-01

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

  19. 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

  20. 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.

  1. Selective Neural Synchrony Suppression as a Forward Gatekeeper to Piecemeal Conscious Perception.

    PubMed

    Levy, Jonathan; Vidal, Juan R; Fries, Pascal; Démonet, Jean-François; Goldstein, Abraham

    2016-07-01

    The emergence of conscious visual perception is assumed to ignite late (∼250 ms) gamma-band oscillations shortly after an initial (∼100 ms) forward sweep of neural sensory (nonconscious) information. However, this neural evidence is not utterly congruent with rich behavioral data which rather point to piecemeal (i.e., graded) perceptual processing. To address the unexplored neural mechanisms of piecemeal ignition of conscious perception, hierarchical script sensitivity of the putative visual word form area (VWFA) was exploited to signal null (i.e., sensory), partial (i.e., letter-level), and full (i.e., word-level) conscious perception. Two magnetoencephalography experiments were conducted in which healthy human participants viewed masked words (Experiment I: active task, Dutch words; Experiment II: passive task, Hebrew words) while high-frequency (broadband gamma) brain activity was measured. Findings revealed that piecemeal conscious perception did not ignite a linear piecemeal increase in oscillations. Instead, whereas late (∼250 ms) gamma-band oscillations signaled full conscious perception (i.e., word-level), partial conscious perception (i.e., letter-level) was signaled via the inhibition of the early (∼100 ms) forward sweep. This inhibition regulates the downstream broadcast to filter out irrelevant (i.e., masks) information. The findings thus highlight a local (VWFA) gatekeeping mechanism for conscious perception, operating by filtering out and in selective percepts. PMID:26045565

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

    NASA Technical Reports Server (NTRS)

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

    1981-01-01

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

  3. Hard breakup of the deuteron into two Δ -isobars

    NASA Astrophysics Data System (ADS)

    Granados, Carlos; Sargsian, Misak

    2011-04-01

    Photodisintegration of the deuteron into two Δ-isobars at large center of mass angles is studied within the QCD hard rescattering model (HRM). According to the HRM, the reaction proceeds in three main steps: the photon knocks the 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 emerging at large transverse momenta. Within the HRM, the cross section is expressed through the amplitude of pn --> ΔΔ scattering which we evaluated based on the quark-interchange model of hard hadronic scattering. We predict that the cross section of the deuteron breakup to Δ++Δ- is 4-5 times larger than that of the breakup to the Δ+Δ0 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 Δ-isobars are the result of the disintegration of initial ΔΔ components of the deuteron wave function. In this case, the angular distributions and cross sections of the breakup in both Δ++Δ- and Δ+Δ0 channels are expected to be similar. This work was supported by U.S. Department of Energy Grant under contract DE-FG02-01ER41172, and by the FIU DEA program.

  4. Hard breakup of the deuteron into two Δ isobars

    NASA Astrophysics Data System (ADS)

    Granados, Carlos G.; Sargsian, Misak M.

    2011-05-01

    We study high-energy photodisintegration of the deuteron into two Δ 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→ΔΔ 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→ΔΔ scattering. We predict that the cross section of the deuteron breakup to Δ++Δ- is 4-5 times larger than that of the breakup to the Δ+Δ0 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 Δ isobars are the result of the disintegration of the preexisting ΔΔ components of the deuteron wave function. In this case, one expects the angular distributions and cross sections of the breakup in both Δ++Δ- and Δ+Δ0 channels to be similar.

  5. Coumarin sulfonamides derivatives as potent and selective COX-2 inhibitors with efficacy in suppressing cancer proliferation and metastasis.

    PubMed

    Lu, Xiao-Yuan; Wang, Zhong-Chang; Ren, Shen-Zhen; Shen, Fa-Qian; Man, Ruo-Jun; Zhu, Hai-Liang

    2016-08-01

    Cyclooxygenase-2 is frequently overexpression in malignant tumors and the product PGE2 promotes cancer cell progression and metastasis. We designed novel series of coumarin sulfonamides derivatives to improve biological activities of COX-2 inhibition and anticancer. Among them, compound 7t showed most powerful selective inhibitory and antiproliferative activity (IC50=0.09μM for COX-2, IC50=48.20μM for COX-1, IC50=0.36μM against HeLa cells), comparable to the control positive compound Celecoxib (0.31μM, 43.37μM, 7.79μM). Cancer cell apoptosis assay were performed and results indicated that compound 7t effectively fuels HeLa cells apoptosis in a dose and time-dependent manner. Moreover, 7t could significantly suppress cancer cell adhesion, migration and invasion which were essential process of cancer metastasis. Docking simulations results was further indicated that compound 7t could bind well to the COX-2 active site and guided a reasonable design of selective COX-2 inhibitor with anticancer activities in future. PMID:27349331

  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. Selective suppression of bacterial contaminants by process conditions during lignocellulose based yeast fermentations

    PubMed Central

    2011-01-01

    Background Contamination of bacteria in large-scale yeast fermentations is a serious problem and a threat to the development of successful biofuel production plants. Huge research efforts have been spent in order to solve this problem, but additional ways must still be found to keep bacterial contaminants from thriving in these environments. The aim of this project was to develop process conditions that would inhibit bacterial growth while giving yeast a competitive advantage. Results Lactic acid bacteria are usually considered to be the most common contaminants in industrial yeast fermentations. Our observations support this view but also suggest that acetic acid bacteria, although not so numerous, could be a much more problematic obstacle to overcome. Acetic acid bacteria showed a capacity to drastically reduce the viability of yeast. In addition, they consumed the previously formed ethanol. Lactic acid bacteria did not show this detrimental effect on yeast viability. It was possible to combat both types of bacteria by a combined addition of NaCl and ethanol to the wood hydrolysate medium used. As a result of NaCl + ethanol additions the amount of viable bacteria decreased and yeast viability was enhanced concomitantly with an increase in ethanol concentration. The successful result obtained via addition of NaCl and ethanol was also confirmed in a real industrial ethanol production plant with its natural inherent yeast/bacterial community. Conclusions It is possible to reduce the number of bacteria and offer a selective advantage to yeast by a combined addition of NaCl and ethanol when cultivated in lignocellulosic medium such as wood hydrolysate. However, for optimal results, the concentrations of NaCl + ethanol must be adjusted to suit the challenges offered by each hydrolysate. PMID:22185398

  8. 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.

  9. 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...

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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 Central

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

    2015-01-01

    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

  16. 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

  17. 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

  18. 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.

  19. Isobar separation by time-of-flight mass spectrometry for low-energy radioactive ion beam facilities

    NASA Astrophysics Data System (ADS)

    Plaß, Wolfgang R.; Dickel, Timo; Czok, Ulrich; Geissel, Hans; Petrick, Martin; Reinheimer, Katrin; Scheidenberger, Christoph; Yavor, Mikhail I.

    2008-10-01

    A multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS) system for low-energy radioactive ion beam facilities has been developed, which can be used for (i) isobar separation and (ii) direct mass measurements of very short-lived nuclei with half-lives of about 1 ms or longer, and (iii) for identification and diagnosis of the ion beam by mass spectrometry. The system has been designed and simulated, and individual subsystems have been built and characterized experimentally. An injection trap for cooling and bunching of the ion beam has been developed, and cooling times of less than one millisecond have been achieved. The performance of the MR-TOF-MS was characterized using the isobaric doublet of carbon monoxide and nitrogen molecular ions. A mass resolving power of 105 (FWHM) has been obtained even with an uncooled ion population. The separator capabilities of the MR-TOF-MS have been demonstrated by removing either carbon monoxide or nitrogen ions from the beam in a Bradbury-Nielsen Gate after a flight time of 320 μs. The separation power achieved is thus at least 7000 (FWHM) and increases for longer time-of-flight. An energy buncher stage has been designed that compresses the energy spread of the beam after the separation and facilitates efficient injection of the selected ions into an accumulation trap prior to transfer of the ions to experiments downstream of the MR-TOF-MS.

  20. 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

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

    PubMed

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

    2016-05-01

    The human aryl hydrocarbon receptor is a cytosolic signaling molecule which affects immune response and aberrant cell growth. Canonical signaling of the receptor requires the recruitment of coactivators to the promoter region to remodel local chromatin structure. We predicted that interference of this recruitment would block the aryl hydrocarbon receptor function. To prove that, we employed phage display to identify nine peptides of twelve-amino-acid in length which target the C-terminal half of the human aryl hydrocarbon receptor, including the region where coactivators bind. Eight 12mer peptides, in the form of GFP fusion, suppressed the ligand-dependent transcription of six AHR target genes (cyp1a1, cyp1a2, cyp1b1, ugt1a1, nqo1, and ahrr) in different patterns in Hep3B cells, whereas the AHR antagonist CH-223191 suppressed all these target genes similarly. Three of the 12mer peptides (namely 11-3, 1-7, and 7-3) suppressed the 3MC-induced, CYP1A1-dependent EROD activity and the ROS production caused by benzo[a]pyrene. These 12mer peptides suppressed the AHR function synergistically with CH-223191. In conclusion, we provide evidence that targeting the C-terminal half of the human aryl hydrocarbon receptor is a viable, new approach to selectively block the receptor function. PMID:26970402

  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. 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

  4. 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

    2016-06-01

    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

    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

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

    SciTech Connect

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

    1992-07-01

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

  7. Stored waveform inverse fourier-transform (SWIFT) excitation for water-suppressed whole-body slice-selected proton chemical shift spectra at 1.5 tesla

    NASA Astrophysics Data System (ADS)

    Hsu, Annjia T.; Hunter, William W.; Schmalbrock, Petra; Marshall, Alan G.

    Proton NMR spectroscopy for the in vivo study of metabolites in a spatially resolved region with a clinical NMR imaging device must contend with the 70% hydration of normal man. Theoretical and experimental comparisons of several excitation waveforms designed to suppress the H 2O signal in proton NMR spectroscopy and chemical shift imaging have been conducted. In particular, we have compared the 1 overline33 overline1 and 1 overline1 pulse sequences with those obtained via a stored waveform inverse Fourier-transform (SWIFT) time-domain apodized waveform generated by inverse Fourier transformation of a quadratically phase-encoded excitation magnitude spectrum. Theoretical excitation profiles are compared to those measured in a slice selected with a General Electric Signa 1.5 T whole-body imaging system, and demonstrated for a phantom (toluene, dioxane, and dichloromethane). The SWIFT waveform is theoretically and experimentally superior to 1 overline1 and 1 overline33 overline1 for selective suppression of one spectral segment with simultaneous uniform excitation over the rest of the spectral frequency range. SWIFT-excited water-suppressed depth-resolved chemical shift spectra are demonstrated for human brain and human calf muscle of normal volunteers.

  8. Selective PCAF inhibitor ameliorates cognitive and behavioral deficits by suppressing NF-κB-mediated neuroinflammation induced by Aβ in a model of Alzheimer's disease.

    PubMed

    Park, Soo-Yeon; Kim, Mi-Jeong; Kim, Young Jun; Lee, Yoo-Hyun; Bae, Donghyuk; Kim, Sunoh; Na, Younghwa; Yoon, Ho-Geun

    2015-04-01

    Several recent studies have reported an association between neurodegeneration and histone modifications, such as acetylation, deacetylation and methylation. In addition, questions have been raised regarding a potential functional role for the histone acetylation enzymes in β-amyloid (Aβ)-mediated neurotoxicity, particularly the p300/CBP-associated factor (PCAF) enzyme. We recently reported the potential utility of a PCAF inhibitor in the suppression of Aβ-induced neuronal cell death, although the in vivo effectiveness of the PCAF inhibitor remained unclear. In this study, we modified the PCAF inhibitor by chemical derivatization and selected compound C-30-27 as the most potent PCAF inhibitor. We demonstrated that C-30-27 selectively inhibited acetylation-dependent nuclear factor-κB (NF-κB) at Lys-122 and suppressed the NF-κB-mediated inflammatory response induced by lipopolysaccharide (LPS) or Aβ in both BV2 and Neuro-2A (N2A) cells. Finally, we demonstrated that C-30-27 improved cognitive deficits, as well as the capacity for locomotion and the damaged cholinergic system in the Aβ-treated rats. In conclusion, our results demonstrate that this selective PCAF inhibitor has the potential to reduce the neuroinflammatory response induced by Aβ. PMID:25672970

  9. Generation of multiple reporter ions from a single isobaric reagent increases multiplexing capacity for quantitative proteomics.

    PubMed

    Braun, Craig R; Bird, Gregory H; Wühr, Martin; Erickson, Brian K; Rad, Ramin; Walensky, Loren D; Gygi, Steven P; Haas, Wilhelm

    2015-10-01

    Isobaric labeling strategies for mass spectrometry-based proteomics enable multiplexed simultaneous quantification of samples and therefore substantially increase the sample throughput in proteomics. However, despite these benefits, current limits to multiplexing capacity are prohibitive for large sample sizes and impose limitations on experimental design. Here, we introduce a novel mechanism for increasing the multiplexing density of isobaric reagents. We present Combinatorial Isobaric Mass Tags (CMTs), an isobaric labeling architecture with the unique ability to generate multiple series of reporter ions simultaneously. We demonstrate that utilization of multiple reporter ion series improves multiplexing capacity of CMT with respect to a commercially available isobaric labeling reagent with preserved quantitative accuracy and depth of coverage in complex mixtures. We provide a blueprint for the realization of 16-plex reagents with 1 Da spacing between reporter ions and up to 28-plex at 6 mDa spacing using only 5 heavy isotopes per reagent. We anticipate that this improvement in multiplexing capacity will further advance the application of quantitative proteomics, particularly in high-throughput screening assays. PMID:26308379

  10. Linear dependency of full scattering profile isobaric point on tissue diameter.

    PubMed

    Duadi, Hamootal; Feder, Idit; Fixler, Dror

    2014-02-01

    Most methods for measuring light-tissue interaction focus on volume reflectance, while very few measure light transmission. In a previous work, we suggested investigating the influence of blood vessel diameter on photons exiting the tissue at all exit angles to receive the full scattering profile. By this method, we have shown that there is a central angle, i.e., the isobaric point, independent of blood vessel diameter. The vessel diameter changes the effective reduced scattering coefficient. However, both the scattering profile and the value of the isobaric point strongly depend on optical properties and the exact geometry of the tissue. In this study, we investigate the dependency of the isobaric point on tissue diameter and scattering coefficient in both two-dimensional and three-dimensional simulations. We show that the value of this point linearly depends on tissue diameter. The findings of this work solve the dilemma of whether to measure transmission or reflection since the isobaric point reduces by half the total amount of exiting photons. Furthermore, the full scattering profile is sensitive to changes in the scattering properties, but a single isobaric point to these changes is expected. If this point is not found, it is a diagnostic indication of an unexpected change in the tissue. PMID:24522807

  11. 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.

  12. 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.

  13. Biochanin A, a Phytoestrogenic Isoflavone with Selective Inhibition of Phosphodiesterase 4, Suppresses Ovalbumin-Induced Airway Hyperresponsiveness

    PubMed Central

    Ko, Wun-Chang; Lin, Ling-Hung; Shen, Hsin-Yi; Lai, Chi-Yin; Chen, Chien-Ming; Shih, Chung-Hung

    2011-01-01

    The present study investigated the potential of biochanin A, a phytoestrogenic isoflavone of red clover (Triflolium pratense), for use in treating asthma or chronic obstructive pulmonary disease (COPD). Biochanin A (100 μmol/kg, orally (p.o.)) significantly attenuated airway resistance (RL), enhanced pause (Penh), and increased lung dynamic compliance (Cdyn) values induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed an increase in the number of total inflammatory cells, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid (BALF) of the mice. However, it did not influence interferon (IFN)-γ levels. Biochanin A (100 μmol/kg, p.o.) also significantly suppressed the total and ovalbumin (OVA)-specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the total IgG2a level in the serum of these mice. The PDE4H/PDE4L value of biochanin A was calculated as >35. Biochanin A did not influence xylazine/ketamine-induced anesthesia. Biochanin A (10~30 μM) significantly reduced cumulative OVA (10~100 μg/mL)-induced contractions in the isolated guinea pig trachealis, suggesting that it inhibits degranulation of mast cells. In conclusion, red clover containing biochanin A has the potential for treating allergic asthma and COPD. PMID:21437195

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

    NASA Astrophysics Data System (ADS)

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

    1980-09-01

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

  15. 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.

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

    PubMed

    Ishibashi, Y; Matsui, T; Yamagishi, S

    2016-03-01

    Ninety percent of glucose filtered by the glomerulus is reabsorbed by a sodium-glucose cotransporter 2 (SGLT2), which is mainly expressed on S1 and S2 segment of renal proximal tubules. Since SGLT-2-mediated glucose reabsorption is increased under diabetic conditions, selective inhibition of SGLT2 is a potential therapeutic target for the treatment of diabetes. We have recently shown that an inhibitor of SGLT2 has anti-inflammatory and antifibrotic effects on experimental diabetic nephropathy partly by suppressing advanced glycation end products formation and oxidative stress generation in the kidney. However, the direct effects of SGLT2 inhibitor on tubular cell damage remain unclear. In this study, we investigated the effects of tofogliflozin, a highly selective inhibitor of SGLT2 on oxidative stress generation, inflammatory and proapoptotic reactions in cultured human proximal tubular cells exposed to high glucose. Tofogliflozin dose-dependently suppressed glucose entry into tubular cells. High glucose exposure (30 mM) for 4 and 24 h significantly increased oxidative stress generation in tubular cells, which were suppressed by the treatment of tofogliflozin or an antioxidant N-acetylcysteine (NAC). Monocyte chemoattractant protein-1 (MCP-1) gene expression and apoptotic cell death were induced by 4 h- and 8 day-exposure to high glucose, respectively, both of which were also blocked by tofogliflozin or NAC. The present study suggests that SGLT2-mediated glucose entry into tubular cells could stimulate oxidative stress and evoke inflammatory and proapoptotic reactions in this cell type. Blockade of glucose reabsorption in tubular cells by SGLT2 inhibitor might exert beneficial effects on tubulointerstitial damage in diabetic nephropathy. PMID:26158396

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

    PubMed

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

    2016-02-01

    The stress-upregulated catecholamines-activated β1- and β2-adrenergic receptors (β1/2-ARs) have been shown to accelerate the progression of cancers such as colorectal cancer (CRC). We investigated the underlying mechanism of the inhibition of β1/2-ARs signaling for the treatment of CRC and elucidated the significance of β2-AR expression in CRC in vitro and in clinical samples. The impacts of β1/2-AR antagonists in CRC in vitro and CRC-xenograft in vivo were examined. We found that repression of β2-AR but not β1-AR signaling selectively suppressed cell viability, induced G1-phase cell cycle arrest, caused both intrinsic and extrinsic pathways-mediated apoptosis of specific CRC cells and inhibited CRC-xenograft growth in vivo. Moreover, the expression of β2-AR was not consistent with the progression of CRC in vitro or in clinical samples. Our data evidence that the expression profiles, signaling, and blockage of β2-AR have a unique pattern in CRC comparing to other cancers. β2-AR antagonism selectively suppresses the growth of CRC accompanying active β2-AR signaling, which potentially carries wild-type KRAS, in vitro and in vivo via the inhibition of β2-AR transactivated EFGR-Akt/ERK1/2 signaling pathway. Thus, β2-AR blockage might be a potential therapeutic strategy for combating the progressions of β2-AR-dependent CRC. PMID:26189563

  18. Revalidation of the isobaric multiplet mass equation at A = 53, T = 3/2

    NASA Astrophysics Data System (ADS)

    Su, J.; Liu, W. P.; Zhang, N. T.; Shen, Y. P.; Lam, Y. H.; Smirnova, N. A.; MacCormick, M.; Wang, J. S.; Jing, L.; Li, Z. H.; Wang, Y. B.; Guo, B.; Yan, S. Q.; Li, Y. J.; Zeng, S.; Lian, G.; Du, X. C.; Gan, L.; Bai, X. X.; Gao, Z. C.; Zhang, Y. H.; Zhou, X. H.; Tang, X. D.; He, J. J.; Yang, Y. Y.; Jin, S. L.; Ma, P.; Ma, J. B.; Huang, M. R.; Bai, Z.; Zhou, Y. J.; Ma, W. H.; Hu, J.; Xu, S. W.; Ma, S. B.; Chen, S. Z.; Zhang, L. Y.; Ding, B.; Li, Z. H.; Audi, G.

    2016-05-01

    The T = 3 / 2 isobaric analog state (IAS) in 53Co is firmly established through a comprehensive measurement of β-delayed γ and proton decay of 53Ni. The determined excitation energy of 53Co IAS combined with the mass of 53Co generates a precise mass excess of - 38 333.6 (27) keV for the 53Co IAS, which is 70(18) keV lower than the previously adopted value. The new result solves a problem raised by incorrect assignments of the 53Co IAS of unexpected deviation from the isobaric multiplet mass equation (IMME) at A = 53, T = 3 / 2.

  19. Bayesian identification of protein differential expression in multi-group isobaric labelled mass spectrometry data.

    PubMed

    Jow, Howsun; Boys, Richard J; Wilkinson, Darren J

    2014-10-01

    In this paper we develop a Bayesian statistical inference approach to the unified analysis of isobaric labelled MS/MS proteomic data across multiple experiments. An explicit probabilistic model of the log-intensity of the isobaric labels' reporter ions across multiple pre-defined groups and experiments is developed. This is then used to develop a full Bayesian statistical methodology for the identification of differentially expressed proteins, with respect to a control group, across multiple groups and experiments. This methodology is implemented and then evaluated on simulated data and on two model experimental datasets (for which the differentially expressed proteins are known) that use a TMT labelling protocol. PMID:25153608

  20. Technique to select the optimum modulation indices for suppression of undesired signals for simultaneous range and data operations

    NASA Astrophysics Data System (ADS)

    Nguyen, Tien Manh

    An algorithm to search for the optimum set of modulation indices that will optimize a given simultaneous range/command/telemetry communications link is presented. This technique provides a way to suppress the ranging signal in order to limit performance degradation in the data channel due to interference from the ranging channel to a desired level, given a specified ranging accuracy. The link (when optimized) will (1) provide maximum available power to both the data and ranging channels for a specified degradation in the data channel so that it will transmit at the required data rate, (2) achieve a specified ranging accuracy over a maximum distance, under a certain set of conditions, and (3) provide adequate power for carrier tracking without degrading the data-channel thresholds. In addition, both data and ranging channels will fall below the threshold at the same point.

  1. 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.

  2. Proteomic identification and quantification of S-glutathionylation in mouse macrophages using resin-assisted enrichment and isobaric labeling.

    PubMed

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

    2014-02-01

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

  3. High-Throughput Quantitative Proteomics Enabled by Mass Defect-Based 12-Plex DiLeu Isobaric Tags.

    PubMed

    Frost, Dustin C; Li, Lingjun

    2016-01-01

    Isobaric labeling has become a popular technique for high-throughput, mass spectrometry (MS)-based relative quantification of peptides and proteins. However, widespread use of the approach for large-scale proteomics applications has been limited by the high cost of commercial isobaric tags. To address this, we have developed our own N,N-dimethyl leucine (DiLeu) multiplex isobaric tags as a cost-effective alternative that can be synthesized with ease using readily available isotopic reagents. When paired with high-resolution tandem mass (MS(n)) acquisition, mass defect-based DiLeu isobaric tags allow relative quantification of up to twelve samples in a single liquid chromatography (LC)-MS(2) experiment. Herein, we present detailed methods for synthesis of 12-plex DiLeu isobaric tags, labeling of complex protein digest samples, analysis by high-resolution nanoLC-MS(n), and processing of acquired data. PMID:26867744

  4. 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

  5. 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.

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

    PubMed

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

    2016-07-19

    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

  7. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

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

    PubMed

    Fridén, Mikael E; Sjöberg, Per J R

    2014-07-01

    Flavonoids are a class of secondary plant metabolites existing in great variety in nature. Due to this variety, identification can be difficult, especially as overlapping compounds in both chromatographic separations and mass spectrometric detection are common. Methods for distinguishing isobaric flavonoids using MS(2) and MS(3) have been developed. Chromatographic separation of various plant extracts was done with RP-HPLC and detected with positive ESI-MS operated in information-dependent acquisition (IDA) mode. Two methods for the determination of flavonoid identity and substitution pattern, both featuring IDA criteria, were used together with the HPLC equipment. A third method where the collision energy was ramped utilized direct infusion. With the developed strategies, it is possible to differentiate between many isobaric flavonoids. Various classes of flavonoids were found in all of the plant extracts, in the red onion extract 45 components were detected and for 29 of them the aglycone was characterized, while the substituents were tentatively identified for 31 of them. For the strawberry extract, those numbers were 66, 30 and 60, and for the cherry extract 99, 56 and 71. The great variety of flavonoids, several of them isobaric, found in each of the extracts highlights the need for reliable methods for flavonoid characterization. Methods capable of differentiating between most of the isobars analyzed have been developed. PMID:25044850

  10. Paramagnetic NMR relaxation in polymeric matrixes: sensitivity enhancement and selective suppression of embedded species (1H and 13C PSR filter).

    PubMed

    Fernandez-Megia, Eduardo; Correa, Juan; Novoa-Carballal, Ramon; Riguera, Ricardo

    2007-12-12

    A study of the practical applications of the addition of paramagnetic spin relaxation (PSR) ions to a variety of polymers (PLL, PAA, PGA, PVP, and polysaccharides such as hyaluronic acid, chitosan, mannan, and dextran) in solution (D2O and DMSO-d6) is described. Use of Gd(III), Cu(II), and Mn(II) allows a reduction of up to 500% in the 1H longitudinal relaxation times (T1), and so in the time necessary for recording quantitative NMR spectra (sensitivity enhancement) neither an increase of the spectral line width nor chemical shift changes resulted from addition of any of the PSR agents tested. Selective suppression of the 1H and 13C NMR signals of certain components (low MW molecules and polymers) in the spectrum of a mixture was attained thanks to their different sensitivity [transverse relaxation times (T2)] to Gd(III) (PSR filter). Illustration of this strategy with block copolymers (PGA-g-PEG) and mixtures of polymers and low MW molecules (i.e., lactose-hyaluronic acid, dextran-PAA, PVP-glutamic acid) in 1D and 2D NMR experiments (COSY and HMQC) is presented. In those mixtures where PSR and CPMG filters alone failed in the suppression of certain components (i.e., PVP-mannan-hyaluronic acid) due to their similarity of 1H T2 values and sensitivities to Gd(III), use of the PSR filter in combination with CPMG sequences (PSR-CPMG filter) successfully resulted in the sequential suppression of the components (hyaluronic acid first and then mannan). PMID:18004845

  11. Hesperetin-7,3'-O-dimethylether selectively inhibits phosphodiesterase 4 and effectively suppresses ovalbumin-induced airway hyperresponsiveness with a high therapeutic ratio

    PubMed Central

    2011-01-01

    Background Hesperetin was reported to selectively inhibit phosphodiesterase 4 (PDE4). While hesperetin-7,3'-O-dimethylether (HDME) is a synthetic liposoluble hesperetin. Therefore, we were interested in investigating its selectivity on PDE4 and binding ability on high-affinity rolipram-binding sites (HARBs) in vitro, and its effects on ovalbumin-induced airway hyperresponsiveness in vivo, and clarifying its potential for treating asthma and chronic obstructive pulmonary disease (COPD). Methods PDE1~5 activities were measured using a two-step procedure. The binding of HDME on high-affinity rolipram-binding sites was determined by replacing 2 nM [3H]-rolipram. AHR was assessed using the FlexiVent system and barometric plethysmography. Inflammatory cells were counted using a hemocytometer. Cytokines were determined using mouse T helper (Th)1/Th2 cytokine CBA kits, and total immunoglobulin (Ig)E or IgG2a levels were done using ELISA method. Xylazine (10 mg/kg)/ketamine (70 mg/kg)-induced anesthesia was performed. Results HDME revealed selective phosphodiesterase 4 (PDE4) inhibition with a therapeutic (PDE4H/PDE4L) ratio of 35.5 in vitro. In vivo, HDME (3~30 μmol/kg, orally (p.o.)) dose-dependently and significantly attenuated the airway resistance (RL) and increased lung dynamic compliance (Cdyn), and decreased enhanced pause (Penh) values induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in the numbers of 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) of these mice. In addition, HDME (3~30 μmol/kg, p.o.) dose-dependently and significantly suppressed total and ovalbumin-specific immunoglobulin (Ig)E levels in the BALF and serum, and enhanced IgG2a level in the serum of these mice. Conclusions HDME exerted anti-inflammatory effects

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-08-01

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

  14. 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

  15. Slice-selective FID acquisition, localized by outer volume suppression (FIDLOVS) for (1)H-MRSI of the human brain at 7 T with minimal signal loss.

    PubMed

    Henning, Anke; Fuchs, Alexander; Murdoch, James B; Boesiger, Peter

    2009-08-01

    In comparison to 1.5 and 3 T, MR spectroscopic imaging at 7 T benefits from signal-to-noise ratio (SNR) gain and increased spectral resolution and should enable mapping of a large number of metabolites at high spatial resolutions. However, to take full advantage of the ultra-high field strength, severe technical challenges, e.g. related to very short T(2) relaxation times and strict limitations on the maximum achievable B(1) field strength, have to be resolved. The latter results in a considerable decrease in bandwidth for conventional amplitude modulated radio frequency pulses (RF-pulses) and thus to an undesirably large chemical-shift displacement artefact. Frequency-modulated RF-pulses can overcome this problem; but to achieve a sufficient bandwidth, long pulse durations are required that lead to undesirably long echo-times in the presence of short T(2) relaxation times. In this work, a new magnetic resonance spectroscopic imaging (MRSI) localization scheme (free induction decay acquisition localized by outer volume suppression, FIDLOVS) is introduced that enables MRSI data acquisition with minimal SNR loss due to T(2) relaxation and thus for the first time mapping of an extended neurochemical profile in the human brain at 7 T. To overcome the contradictory problems of short T(2) relaxation times and long pulse durations, the free induction decay (FID) is directly acquired after slice-selective excitation. Localization in the second and third dimension and skull lipid suppression are based on a T(1)- and B(1)-insensitive outer volume suppression (OVS) sequence. Broadband frequency-modulated excitation and saturation pulses enable a minimization of the chemical-shift displacement artefact in the presence of strict limits on the maximum B(1) field strength. The variable power RF pulses with optimized relaxation delays (VAPOR) water suppression scheme, which is interleaved with OVS pulses, eliminates modulation side bands and strong baseline distortions. Third

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

    PubMed

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

    2015-01-01

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

  17. 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

  18. 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

  19. Trichostatin A selectively suppresses the cold-induced transcription of the ZmDREB1 gene in maize.

    PubMed

    Hu, Yong; Zhang, Lu; Zhao, Lin; Li, Jun; He, Shibin; Zhou, Kun; Yang, Fei; Huang, Min; Jiang, Li; Li, Lijia

    2011-01-01

    Post-translational modifications of histone proteins play a crucial role in responding to environmental stresses. Histone deacetylases (HDACs) catalyze the removal of an acetyl group from histones and are generally believed to be a transcriptional repressor. In this paper, we report that cold treatment highly induces the up-regulation of HDACs, leading to global deacetylation of histones H3 and H4. Treatment of maize with the HDAC inhibitor trichostatin A (TSA) under cold stress conditions strongly inhibits induction of the maize cold-responsive genes ZmDREB1 and ZmCOR413. However, up-regulation of the ZmICE1 gene in response to cold stress is less affected. The expression of drought and salt induced genes, ZmDBF1 and rab17, is almost unaffected by TSA treatment. Thus, these observations show that HDACs may selectively activate transcription. The time course of TSA effects on the expression of ZmDREB1 and ZmCOR413 genes indicates that HDACs appear to directly activate the ZmDREB1 gene, which in turn modulates ZmCOR413 expression. After cold treatment, histone hyperacetylation and DNA demethylation occurs in the ICE1 binding region, accompanied by an increase in accessibility to micrococcal nuclease (MNase). The two regions adjacent to the ICE1 binding site remain hypoacetylated and methylated. However, during cold acclimation, TSA treatment increases the acetylation status and accessibility of MNase and decreases DNA methylation at these two regions. However, TSA treatment does not affect histone hyperacetylation and DNA methylation levels at the ICE1 binding regions of the ZmDREB1 gene. Altogether, our findings indicate that HDACs positively regulate the expression of the cold-induced ZmDREB1 gene through histone modification and chromatin conformational changes and that this activation is both gene and site selective. PMID:21811564

  20. Moving Stimuli Are Less Effectively Masked Using Traditional Continuous Flash Suppression (CFS) Compared to a Moving Mondrian Mask (MMM): A Test Case for Feature-Selective Suppression and Retinotopic Adaptation

    PubMed Central

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

    2014-01-01

    Continuous flash suppression (CFS) is a powerful interocular suppression technique, which is often described as an effective means to reliably suppress stimuli from visual awareness. Suppression through CFS has been assumed to depend upon a reduction in (retinotopically specific) neural adaptation caused by the continual updating of the contents of the visual input to one eye. In this study, we started from the observation that suppressing a moving stimulus through CFS appeared to be more effective when using a mask that was actually more prone to retinotopically specific neural adaptation, but in which the properties of the mask were more similar to those of the to-be-suppressed stimulus. In two experiments, we find that using a moving Mondrian mask (i.e., one that includes motion) is more effective in suppressing a moving stimulus than a regular CFS mask. The observed pattern of results cannot be explained by a simple simulation that computes the degree of retinotopically specific neural adaptation over time, suggesting that this kind of neural adaptation does not play a large role in predicting the differences between conditions in this context. We also find some evidence consistent with the idea that the most effective CFS mask is the one that matches the properties (speed) of the suppressed stimulus. These results question the general importance of retinotopically specific neural adaptation in CFS, and potentially help to explain an implicit trend in the literature to adapt one’s CFS mask to match one’s to-be-suppressed stimuli. Finally, the results should help to guide the methodological development of future research where continuous suppression of moving stimuli is desired. PMID:24879378

  1. Selective suppression of Notch1 inhibits proliferation of renal cell carcinoma cells through JNK/p38 pathway.

    PubMed

    Wu, Kerong; Hu, Linkun; Hou, Jianquan

    2016-05-01

    The present study was performed to explore the effects of Notch1 inhibition selectively by siRNA on the proliferation and cell cycle of renal carcinoma cells. Human renal carcinoma cell lines, 786-0 and Caki-1, were treated with Si-Notch1 or negative control (NC). RT-PCR and western blotting were used to confirm the efficiency of siRNA on Notch1 expression. MTT, cell cycle analysis, colony formation as well as migration and invasion assays were performed. The expression levels of p38 and SAPK/JNK were measured by western blotting. For both cell lines, as compared with the NC group, the cell growth was markedly reduced, and colony formation was restricted in the Si-Notch1‑treated group. After incubated with Si-Notch1 or NC for 48 h, Si-Notch1-treated cells arrested the cell cycle at G1/S phase. The Si-Notch1 group also had a reduced rate of migration as well as invasion. Moreover, we observed a reduction in p-SAPK/JNK and p-p38 in Si-Notch1 transfected cells. The present study indicated that Notch signaling is important in the tumorigenesis of renal cell carcinoma. Notch1 may be a potential therapeutic regimen towards renal cell carcinoma, and JNK/p38 may serve as an important molecular mechanism for Notch1-mediated carcinogenesis. PMID:26986634

  2. '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.

  3. 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.

  4. 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

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

    DOE PAGESBeta

    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

  6. 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.

  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. 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.

  9. 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.

  10. 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 {ηNN/ 2}/4π ≤ 0.01, and a bound on vector meson exchange models is also obtained.

  11. 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.

  12. 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

  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. 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

  15. [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

  16. 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)

  17. 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.

  18. Delta-Isobar Production in the Hard Photodisintegration of a Deuteron

    NASA Astrophysics Data System (ADS)

    Granados, Carlos; Sargsian, Misak

    2010-02-01

    Hard photodisintegration of the deuteron in delta-isobar production channels is proposed as a useful process in identifying the quark structure of hadrons and of hadronic interactions at large momentum and energy transfer. The reactions are modeled using the hard re scattering model, HRM, following previous works on hard breakup of a nucleon nucleon (NN) system in light nuclei. Here,quantitative predictions through the HRM require the numerical input of fits of experimental NN hard elastic scattering cross sections. Because of the lack of data in hard NN scattering into δ-isobar channels, the cross section of the corresponding photodisintegration processes cannot be predicted in the same way. Instead, the corresponding NN scattering process is modeled through the quark interchange mechanism, QIM, leaving an unknown normalization parameter. The observables of interest are ratios of differential cross sections of δ-isobar production channels to NN breakup in deuteron photodisintegration. Both entries in these ratios are derived through the HRM and QIM so that normalization parameters cancel out and numerical predictions can be obtained. )

  19. 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...

  20. Immune modulation of metalloproteinase production in human macrophages. Selective pretranslational suppression of interstitial collagenase and stromelysin biosynthesis by interferon-gamma.

    PubMed Central

    Shapiro, S D; Campbell, E J; Kobayashi, D K; Welgus, H G

    1990-01-01

    Interferon-gamma (IFN-gamma) is a lymphokine that activates mononuclear phagocytes. To test the hypothesis that IFN-gamma might have important effects upon the ability of human mononuclear phagocytes to degrade extracellular matrix, we have studied the action of this cytokine on the production of metalloproteinases and the counterregulatory tissue inhibitor of metalloproteinases (TIMP) by the human alveolar macrophage. We have found that IFN-gamma potently and selectively suppresses the lipopolysaccharide-induced production of two metalloproteinases--interstitial collagenase and stromelysin--by 50-90% at doses greater than or equal to 10 U/ml. The synthesis of TIMP and 92-kD type IV collagenase was also diminished by IFN-gamma, but these responses required 50- to 100-fold higher concentrations of the cytokine. All doses of IFN-gamma increased total and secreted protein synthesis slightly, indicating a highly specific effect on metalloenzyme biosynthesis. Inhibition of metalloproteinase expression occurred at a pretranslational level, as evidenced by parallel reductions in enzyme biosynthesis and collagenase-specific steady-state mRNA levels. Interestingly, the effect of IFN-gamma on metalloenzyme production was not readily reversible. Therefore, while IFN-gamma activates the macrophage and renders it tumoricidal, this enhanced function appears to be attained at the expense of the cell's capacity to degrade extracellular matrix. Images PMID:2170447

  1. Quantitative analysis of single amino acid variant peptides associated with pancreatic cancer in serum by an isobaric labeling quantitative method.

    PubMed

    Nie, Song; Yin, Haidi; Tan, Zhijing; Anderson, Michelle A; Ruffin, Mack T; Simeone, Diane M; Lubman, David M

    2014-12-01

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

  2. 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.

  3. Isobaric yield ratio difference between the 140 A MeV 58Ni + 9Be and 64Ni +9Be reactions studied by the antisymmetric molecular dynamics model

    NASA Astrophysics Data System (ADS)

    Qiao, C. Y.; Wei, H. L.; Ma, C. W.; Zhang, Y. L.; Wang, S. S.

    2015-07-01

    Background: The isobaric yield ratio difference (IBD) method is found to be sensitive to the density difference of neutron-rich nucleus induced reaction around the Fermi energy. Purpose: An investigation is performed to study the IBD results in the transport model. Methods: The antisymmetric molecular dynamics (AMD) model plus the sequential decay model gemini are adopted to simulate the 140 A MeV 58 ,64Ni +9Be reactions. A relative small coalescence radius Rc= 2.5 fm is used for the phase space at t = 500 fm/c to form the hot fragment. Two limitations on the impact parameter (b 1 =0 -2 fm and b 2 =0 -9 fm) are used to study the effect of central collisions in IBD. Results: The isobaric yield ratios (IYRs) for the large-A fragments are found to be suppressed in the symmetric reaction. The IBD results for fragments with neutron excess I = 0 and 1 are obtained. A small difference is found in the IBDs with the b 1 and b 2 limitations in the AMD simulated reactions. The IBD with b 1 and b 2 are quite similar in the AMD + GEMINI simulated reactions. Conclusions: The IBDs for the I =0 and 1 chains are mainly determined by the central collisions, which reflects the nuclear density in the core region of the reaction system. The increasing part of the IBD distribution is found due to the difference between the densities in the peripheral collisions of the reactions. The sequential decay process influences the IBD results. The AMD + GEMINI simulation can better reproduce the experimental IBDs than the AMD simulation.

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

    NASA Astrophysics Data System (ADS)

    Gautam, Sakshi

    2013-11-01

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

  5. 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.

  6. Coefficients of the isobaric mass equation and their correlations with various nuclear parameters

    SciTech Connect

    Britz, J.; Pape, A.; Antony, M.S.

    1998-05-01

    The coefficients of the isobaric multiplet mass equation M = a + bT{sub z} + cT{sub z}{sup 2} have been calculated for the 430 identified T = 1/2, 1, 3/2, 2 multiplets and correlations of its b, c coefficients with various nuclear parameters have been sought. For most mass numbers A there is a tendency for b to increase, and for c to decrease, with the average excitation energy of the multiplet. There seems to be no separate dependence of b or c on spin, but there could be a dependence of b on parity.

  7. Two-proton decay from Isobaric Analog States of light nuclei

    NASA Astrophysics Data System (ADS)

    Brown, Kyle

    2014-03-01

    Recent experiments at the National Superconducting Cyclotron Laboratory at Michigan State University using the charged-particle array HiRA and the gamma-ray array CAESAR have shed light on a new class of two-proton emitters associated with Isobaric Analog States (IAS). The two-proton decay is to the Isobaric Analog state of the daughter, which then gamma decays. These isospin-allowed transitions occur when one-proton decays are forbidden by either energy or isospin conservation, and when two-proton decay to the ground state is isospin forbidden. Three possible examples of this decay path will be discussed (8BIAS, 12NIAS, and 16FIAS) . The known IAS of 8C in 8B was confirmed to decay by two-proton emission to the 3.56 MeV IAS in 6Li. While the IAS in 8B was previously known, it was measured in this experiment with unbiased statistics and in coincidence with the 3.56 MeV gamma-ray. The IAS in 16F was investigated for the first time in this experiment and is still under investigation. Previous work on the IAS of 12O in 12N at the Cyclotron Institute at Texas A&M will also be presented.

  8. 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.

  9. 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. PMID:24978887

  10. 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.

  11. Two-proton decay of the 6Be ground state and the double isobaric analog of 11Li

    NASA Astrophysics Data System (ADS)

    Charity, R. J.; Elson, J. M.; Komarov, S.; Sobotka, L. G.; Manfredi, J.; Shane, R.; Egorova, I. A.; Grigorenko, L. V.; Hagino, K.; Bazin, D.; Chajecki, Z.; Coupland, D.; Gade, A.; Iwasaki, H.; Kilbrun, M.; Lee, J.; Lukyanov, S. M.; Lynch, W. G.; Mocko, M.; Lobastov, S. P.; Rodgers, A.; Sanetullaev, A.; Tsang, M. B.; Wallace, M. S.; Winkelbauer, J.; Youngs, M.; Hudan, S.; Metelko, C.; Famino, M. A.; Marley, S. T.; Shetty, D. V.; Wuosmaa, A. H.; van Goethem, M. J.; Zhukov, M. V.

    2013-03-01

    Two-proton decay is discussed in a number of light isobaric multiplets. For the lightest two-proton emitter, 6Be, the momentum correlations between the three decay products were measured and found to be consistent with quantum-mechanical three-cluster-model calculations. Two-proton decay was also found for two members of the A=8 and A=11 quintets. Finally, a third member of the A=11 sextet, the double isobaric analog of the halo nucleus 11Li in 11B was observed by its two-proton decay.

  12. 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

  13. 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.

  14. Neutron density distributions of neutron-rich nuclei studied with the isobaric yield ratio difference

    NASA Astrophysics Data System (ADS)

    Ma, Chun-Wang; Bai, Xiao-Man; Yu, Jiao; Wei, Hui-Ling

    2014-09-01

    The isobaric yield ratio difference (IBD) between two reactions of similar experimental setups is found to be sensitive to nuclear density differences between projectiles. In this article, the IBD probe is used to study the density variation in neutron-rich 48Ca . By adjusting diffuseness in the neutron density distribution, three different neutron density distributions of 48Ca are obtained. The yields of fragments in the 80 A MeV 40, 48Ca + 12C reactions are calculated by using a modified statistical abrasion-ablation model. It is found that the IBD results obtained from the prefragments are sensitive to the density distribution of the projectile, while the IBD results from the final fragments are less sensitive to the density distribution of the projectile.

  15. Excitation of Δ and N* resonances in isobaric charge-exchange reactions of heavy nuclei

    NASA Astrophysics Data System (ADS)

    Vidaña, I.; Benlliure, J.; Geissel, H.; Lenske, H.; Scheidenberger, C.; Vargas, J.

    2016-01-01

    We present a model for the study of the excitation of Δ(1232) and N*(1440) resonances in isobaric charge-exchange (AZ, A(Z ± 1)) reactions of heavy nuclei. Quasi-elastic and inelastic elementary processes contributing to the double differential cross sections of the reactions are described in terms of the exchange of virtual pions. The inelastic channel includes processes where the resonances are excited both in the target and in the projectile nucleus. We present results for reactions of 112Sn and 124Sn on different targets. Our results confirm that the position of the Δ peak is insensitive to targets with mass number A ≥ 12, and show that the origin of the Δ peak shift towards low excitation energies, with respect to its position in reactions with a proton target, can be easily explained in terms of the superposition of the different excitation mechanisms contributing to the reaction.

  16. Two-proton decay of the isobaric analogue state of 31Ar

    NASA Astrophysics Data System (ADS)

    Mukha, I.; Axelsson, L.; Äystö, J.; Bergmann, U. C.; Borge, M. J. G.; Fraile, L. M.; Fynbo, H. O. U.; Honkanen, A.; Hornshøj, P.; Jading, Y.; Jonson, B.; Jokinen, A.; Martel, I.; Oinonen, M.; Nilsson, T.; Nyman, G.; Petersen, B.; Riisager, K.; Siiskonen, T.; Smedberg, M. H.; Tengblad, O.; Wenander, F.; Isolde Collaboration

    1998-02-01

    We have studied several two proton branches in the β-decay of 31Ar, the most intensive ones proceeding through the isobaric analogue state (IAS) in 31Cl. The energy and angular correlations of the two protons originating from the IAS have been measured. An indication of non-isotropic emission has been observed in the p+p+ 29P branch. The energy spectra of protons from the IAS 2p-branches seem to be continuous, which is difficult to explain by a sequential emission through a few intermediate levels in 30S. The model of non-sequential or democratic three-particle decay gives the best fit to the present data favoring the IAS spin-parity {5}/{2 +}.

  17. Gamow-Teller strength studied through {Gamma}-excitation of isobaric analog states

    SciTech Connect

    Boswell, M. S.; Young, A. R.; Ejiri, H.

    2013-04-19

    We consider a measurement of isobaric analog states (IAS) of 76As in 76Se as a method for measuring the Gamow-Teller (GT) strength important to constrain and possibly help normalize calculations of double beta ({beta}{beta}) decay matrix elements. We show that photo-nuclear reactions via IAS can provide valuable information about the parent and daughter states of {beta}{beta}-decay not currently available from measurements of charge exchange reactions. Several experiments have been proposed at the HI{open_square} Sfacility at the Triangle Nuclear Research Laboratory in Durham, NC, the first of which will measure the lowest 1{sup -}, 1{sup +} and 2{sup +} IAS in {sup 76}Se.

  18. K--Nucleus Elastic Scattering at IntermediateEnergies in the Isobar-Doorway Model

    NASA Astrophysics Data System (ADS)

    Toyama, F. M.

    1983-11-01

    The differential cross sections for the K--nucleus elastic scattering at about PK = 800 MeV/c are calculated in the phenomenological isobar-doorway model. The many-body corrections on Y* resonances in nuclei are represented by the resonance energy shift Δ E and width-modification factor β. The parametrizations given by Gopal et al. are used for the resonance amplitudes. The effects of Δ E and β on the cross sections are investigated in detail. The results are compared with the available experimental data for the K- elastic scattering on 12C and 40Ca at PK = 800 MeV/c. The calculated cross sections are in good agreement with the data. However, the cross sections are not very sensitive to Δ E and β.

  19. Isobaric yield ratio difference in heavy-ion collisions, and comparison to isoscaling

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

    An isobaric yield ratio difference (IBD) method is proposed to study the ratio of the difference between the chemical potential of neutron and proton to temperature (Δμ/T) in heavy-ion collisions. The Δμ/T determined by the IBD method (IB-Δμ/T) is compared to the results of the isoscaling method (IS-Δμ/T), which uses the isotopic or the isotonic yield ratio. Similar distributions of the IB- and IS-Δμ/T are found in the measured 140A MeV 40,48Ca+9Be and the 58,64Ni+9Be reactions. The IB- and IS-Δμ/T both have a distribution with a plateau in the small mass fragments plus an increasing part in the fragments of relatively larger mass. The IB- and IS-Δμ/T plateaus show dependence on the n/p ratio of the projectile. It is suggested that the height of the plateau is decided by the difference between the neutron density (ρn) and the proton density (ρp) distributions of the projectiles, and the width shows the overlapping volume of the projectiles in which ρn and ρp change very little. The difference between the IB- and IS-Δμ/T is explained by the isoscaling parameters being constrained by the many isotopes and isotones, while the IBD method only uses the yields of two isobars. It is suggested that the IB-Δμ/T is more reasonable than the IS-Δμ/T, especially when the isotopic or isotonic ratio disobeys the isoscaling. As to the question whether the Δμ/T depends on the density or the temperature, the density dependence is preferred since the low density can result in low temperature in the peripheral reactions.

  20. 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.

  1. N, N-Dimethyl Leucines as Novel Isobaric Tandem Mass Tags for Quantitative Proteomics and Peptidomics

    PubMed Central

    Xiang, Feng; Ye, Hui; Chen, Ruibing; Fu, Qiang; Li, Lingjun

    2010-01-01

    Herein we describe the development and application of a set of novel N, N-dimethyl leucine (DiLeu) 4-plex isobaric tandem mass (MS2) tagging reagents with high quantitation efficacy and greatly reduced cost for neuropeptide and protein analysis. DiLeu reagents serve as attractive alternatives for isobaric tag for relative and absolute quantitation (iTRAQ) and tandem mass tags (TMTs) due to their synthetic simplicity, labeling efficiency and improved fragmentation efficiency. DiLeu reagent resembles the general structure of a tandem mass tag in that it contains an amine reactive group (triazine ester) targeting the N-terminus and ε-amino group of the lysine side-chain of a peptide, a balance group, and a reporter group. A mass shift of m/z 145.1 is observed for each incorporated label. Intense a1 reporter ions at m/z 115.1, 116.1, 117.1, and 118.1 are observed for all pooled samples upon MS2. All labeling reagents are readily synthesized from commercially available chemicals with greatly reduced cost. Labels 117 and 118 can be synthesized in one step and labels 115 and 116 can be synthesized in two steps. Both DiLeu and iTRAQ reagents show comparable protein sequence coverage (~43%) and quantitation accuracy (<15%) for tryptically digested protein samples. Furthermore, enhanced fragmentation of DiLeu labeling reagents offers greater confidence in protein identification and neuropeptide sequencing from complex neuroendocrine tissue extracts from a marine model organism, Callinectes sapidus. PMID:20218596

  2. 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

  3. 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

  4. 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

  5. Suppression of growth hormone (GH) secretion by a selective GH-releasing hormone (GHRH) antagonist. Direct evidence for involvement of endogenous GHRH in the generation of GH pulses.

    PubMed Central

    Jaffe, C A; Friberg, R D; Barkan, A L

    1993-01-01

    To study the potential involvement of growth hormone-releasing hormone (GHRH) in the generation of growth hormone (GH) pulses in humans we have used a competitive antagonist to the GHRH receptor, (N-Ac-Tyr1,D-Arg2)GHRH(1-29)NH2(GHRH-Ant). Six healthy young men were given a bolus injection of GHRH-Ant 400 micrograms/kg body wt or vehicle at 2200 h and nocturnal GH concentrations were assessed by every 10-min blood sampling until 0800 h. Integrated total and pulsatile GH secretion were suppressed during GHRH-Ant treatment by 40 +/- 6 (SE) % and 75 +/- 5%, respectively. GHRH-Ant suppressed maximum (7.6 +/- 2.2 vs 1.8 +/- 0.5 micrograms/liter; P < 0.001) and mean (3.3 +/- 1.0 vs 1.1 +/- 0.2 micrograms/liter; P = 0.02) GH pulse amplitudes. There was no change in integrated nonpulsatile GH levels, pulse frequency, or interpulse GH concentration. GHRH-Ant 400 micrograms/kg also suppressed the GH responses to intravenous boluses of GHRH 0.33 micrograms/kg given 1, 6, 12, and 24 h later by 95, 81, 59, and 4%, respectively. In five healthy men, the responses to 10-fold larger GHRH boluses (3.3 micrograms/kg) were suppressed by 82 and 0%, 1 and 6 h after GHRH-Ant 400 micrograms/kg, respectively. These studies provide the first direct evidence that endogenous GHRH participates in the generation of spontaneous GH pulses in humans. PMID:8349808

  6. 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.

  7. 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

  8. 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. PMID:25666619

  9. 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

  10. Capillary electrophoresis-mass spectrometry determination of morphine and its isobaric glucuronide metabolites.

    PubMed

    Isbell, Theresa A; Strickland, Erin C; Hitchcock, Jennifer; McIntire, Gregory; Colyer, Christa L

    2015-02-01

    The determination of morphine and its isobaric metabolites morphine-3-beta-d-glucuronide (M3G) and morphine-6-beta-d-glucuronide (M6G) is useful for therapeutic drug monitoring and forensic identification of drug use. In particular, capillary electrophoresis with mass spectrometry (CE-MS) represents an attractive tool for opioid analysis. Whereas volatile background electrolytes in CE often improve electrospray ionization for coupled MS detection, such electrolytes may reduce CE separation efficiency and resolution. To better understand the effects of background electrolyte (BGE) composition on separation efficiency and detection sensitivity, this work compares and contrasts method development for both volatile (ammonium formate and acetate) and nonvolatile (ammonium phosphate and borate) buffers. Peak efficiencies and migration times for morphine and morphine metabolites were optimal with a 25mM ammonium borate buffer (pH=9.5) although greater sensitivities were achieved in the ammonium formate buffer. Optimized CE methods allowed for the resolution of the isobaric morphine metabolites prior to high mass accuracy, electrospray ionization quadrupole time-of-flight (ESI-QTOF) MS detection applicable to the analysis of urine samples in under seven minutes. Urine sample preparation required only a 10-fold dilution with BGE prior to analysis. Limits of detection (LOD) in normal human urine were found to be 1.0μg/mL for morphine and 2.5μg/mL for each of M3G and M6G by CE-ESI-QTOF-MS. These LODs were comparable to those for CE-UV analysis of opioid standards in buffer, whereas CE-ESI-QTOF-MS analysis of opioid standards in buffer yielded LODs an order of magnitude lower. Patient urine samples (N=12) were analyzed by this new CE-ESI-QTOF-MS method and no significant difference in total morphine content relative to prior liquid chromatography-mass spectrometry (LC-MS) results was found as per a paired-t test at the 99% confidence level. Whereas the LC-MS method applied

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

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

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

  12. Direct atmospheric pressure chemical ionisation ion trap mass spectrometry for aroma analysis: Speed, sensitivity and resolution of isobaric compounds

    NASA Astrophysics Data System (ADS)

    Jublot, Lionel; Linforth, Robert S. T.; Taylor, Andrew J.

    2005-06-01

    Atmospheric pressure chemical ionisation (APCI) sources were developed for real time analysis of volatile release from foods using an ion trap (IT) mass spectrometer (MS). Key objectives were spectral simplicity (minimal fragmentation), response time and signal to noise ratio. The benefits of APCI-IT-MS were assessed by comparing the performance for in vivo and headspace analyses with that obtained using APCI coupled to a quadrupole mass analyser. Using MS-MS, direct APCI-IT-MS was able to differentiate mixtures of some C6 and terpene isobaric aroma compounds. Resolution could be achieved for some compounds by monitoring specific secondary ions. Direct resolution was also achieved with two of the three isobaric compounds released from chocolate with time as the sample was eaten.

  13. 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.

  14. 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

  15. 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.

  16. 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. PMID:23676053

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

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

    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.

  18. 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.

  19. The manometric sorptomat—an innovative volumetric instrument for sorption measurements performed under isobaric conditions

    NASA Astrophysics Data System (ADS)

    Kudasik, Mateusz

    2016-03-01

    The present paper discusses the concept of measuring the process of sorption by means of the volumetric method, developed in such a way as to allow measurements performed under isobaric conditions. On the basis of the concept in question, a prototype of a sorption instrument was built: the manometric sorptomat. The paper provides a detailed description of the idea of the instrument, and of the way it works. In order to evaluate the usefulness of the device in sorption measurements carried out under laboratory conditions, comparative studies were conducted, during which the results of sorption measurements obtained with the developed instrument were compared with the results Mateusz obtained with a reference device. The objects of comparison were the sorption capacities of hard coal samples, calculated on the basis of the established courses of the methane sorption process. The results were regarded as compatible if the compared values fell within the range of the measurement uncertainty of the two devices. For the sake of the comparative studies, fifteen granular samples of hard coal—representing the 0.20-0.25 mm grain fraction and coming from various mines of the Upper Silesian Coal Basin—were used. After comparing the results obtained with the original manometric sorptomat with the results obtained with the gravimetric reference device, it was observed that the compatibility of measurements of sorption capacities was over 90%, based on the defined criterion of the measurement compatibility.

  20. 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.

  1. Search for isobar-analog states of superheavy hydrogen isotopes5-7He

    NASA Astrophysics Data System (ADS)

    Chernyshev, B. A.; Gurov, Yu B.; Korotkova, L. Yu; Kuznetsov, D. S.; Lapushkin, S. V.; Tel'kushev, M. V.; Schurenkova, T. D.

    2016-02-01

    Search for isobar-analog states (IAS) of superheavy hydrogen isotopes 5-7H was performed among the high-excited states of helium isotopes 5-7He. The excited spectra were measured in stopped pion absorption by light nuclei. The experiment was performed at low energy pion channel of LANL with two-arm multilayer semiconductor spectrometer. Excited states of 5-7He were observed in three-body reaction channels on 10,11B nuclei. Several excited levels were observed for the first time. 6He excited state with Ex = 27.0(8) MeV observed in 10B(π-,pt)X channel is an IAS candidate for 6H with Er ∼ 5.5 MeV. 7He excited state with Ex = 24.8(4) MeV observed in 10B(π-,pd)X, nB(π-,pt)X and nB(π-,dd)X channels is an IAS candidate for 7H with Er ∼ 3 MeV.

  2. 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

  3. Analyses of the Kaon - and Electro-Production in the Isobar Model

    NASA Astrophysics Data System (ADS)

    Choi, T. K.; Cheoun, Myung Ki; Kim, K. S.; Yu, B. G.

    2004-06-01

    The SAPHIR cross section data of K+Λ and K+Σ0 reactions are analyzed with new SPring-8(LEPS) data on the beam polarization asymmetry, which are taken into account as new constraints on the Isobar model. The simultaneous fit of model parameters to these data yields the consistent description of both data at the price of worse χ2 value and rather large K* contribution. The role of resonance D13(1895) is obvious in the energy region Eγ ≃ 1.45 GeV and the resonance F15(1650) improves the χ2 fit of cross sections with beam polarization data to a good degree. Analysis of kaon electro-production p(e, e' K+)Λ is also presented by including the contribution of the longitudinal virtual photon. Various electro-magnetic form factors for K, K1 and K* resonances are adopted to compare dependence of the electro-production cross section on these form factors. Our recent progress in this field is also presented.

  4. 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.

  5. Gas-phase ion-molecule reactions for resolution of atomic isobars: AMS and ICP-MS perspectives

    NASA Astrophysics Data System (ADS)

    Bandura, Dmitry R.; Baranov, Vladimir I.; Litherland, A. E.; Tanner, Scott D.

    2006-09-01

    Ion-molecule reactions that can be used for resolution of spectral overlaps of long-lived or stable (T1/2 > 100 years) atomic isobars on the long-lived radio-isotopes (100 < T1/2 < 1012 years) in mass spectrometry are considered. Results for the separations of isobaric overlaps via cation reactions with NO, N2O, O2, CO2, C2H2, CH3F studied with the Inductively Coupled Plasma Dynamic Reaction Cell(TM) Mass Spectrometer (ICP-DRC(TM)-MS) with use of stable isotopes are presented. Overview of potential and reported reactions for separation of 35 isobars is given. Potential for the following isobaric pairs separation is shown (reaction gas and the extent of separation achieved to date in parenthesis): 32Si+/32S+(NO, 5 x 104), 40K+/40Ar+(N2O, 1.9 x 103), 40K+/40Ca+(N2O, 50), 59Ni+/59Co+(N2O, 6), 79Se+/79Br+(O2, 7.2 x 103), 81Kr+/81Br+(C2H2, 1.5 x 104), 93Mo+/93Nb+(N2O, 100), 93Mo+/93Zr+(N2O, 150), 135Cs+/135Ba+(N2O, 8 x 104), 137,138La+/137,138Ba+(O2, 40), 146Sm+/146Nd+(CO2, 1.5 x 105), 176Lu+/176Hf+(NO, 2.8 x 103), 187Re+/187Os+(N2O, 2.8 x 104). Effect of instrumental parameters on reactivity is discussed. The relevance of this work to accelerator mass spectrometry is discussed briefly.

  6. jTraqX: a free, platform independent tool for isobaric tag quantitation at the protein level.

    PubMed

    Muth, Thilo; Keller, Daniela; Puetz, Stephanie Michaela; Martens, Lennart; Sickmann, Albert; Boehm, Andreas M

    2010-03-01

    Many proteomic studies focus on quantitative aspects, using different stable isotope labeling techniques that require specialized software to analyze the generated data. Here we present jTraqX, an easy-to-use tool for processing and visualizing protein quantification data. jTraqX is platform independent and is compatible with all available 4-plex isobaric tags. jTraqX can be freely downloaded at http://sourceforge.net/projects/protms. PMID:20058250

  7. 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

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

    2016-09-01

    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

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

    PubMed Central

    2014-01-01

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

  9. Population Genetics as a Tool to Select Tsetse Control Strategies: Suppression or Eradication of Glossina palpalis gambiensis in the Niayes of Senegal

    PubMed Central

    Solano, Philippe; Kaba, Dramane; Ravel, Sophie; Dyer, Naomi A.; Sall, Baba; Vreysen, Marc J. B.; Seck, Momar T.; Darbyshir, Heather; Gardes, Laetitia; Donnelly, Martin J.; De Meeûs, Thierry; Bouyer, Jérémy

    2010-01-01

    Background The Government of Senegal has initiated the “Projet de lutte contre les glossines dans les Niayes” to remove the trypanosomosis problem from this area in a sustainable way. Due to past failures to sustainably eradicate Glossina palpalis gambiensis from the Niayes area, controversies remain as to the best strategy implement, i.e. “eradication” versus “suppression.” To inform this debate, we used population genetics to measure genetic differentiation between G. palpalis gambiensis from the Niayes and those from the southern tsetse belt (Missira). Methodology/Principal Findings Three different markers (microsatellite DNA, mitochondrial CO1 DNA, and geometric morphometrics of the wings) were used on 153 individuals and revealed that the G. p. gambiensis populations of the Niayes were genetically isolated from the nearest proximate known population of Missira. The genetic differentiation measured between these two areas (θ = 0.12 using microsatellites) was equivalent to a between-taxa differentiation. We also demonstrated that within the Niayes, the population from Dakar – Hann was isolated from the others and had probably experienced a bottleneck. Conclusion/Significance The information presented in this paper leads to the recommendation that an eradication strategy for the Niayes populations is advisable. This kind of study may be repeated in other habitats and for other tsetse species to (i) help decision on appropriate tsetse control strategies and (ii) find other possible discontinuities in tsetse distribution. PMID:20520795

  10. Markedly additive antitumor activity with the combination of a selective survivin suppressant YM155 and alemtuzumab in adult T-cell leukemia.

    PubMed

    Chen, Jing; Pise-Masison, Cynthia A; Shih, Joanna H; Morris, John C; Janik, John E; Conlon, Kevin C; Keating, Anne; Waldmann, Thomas A

    2013-03-14

    Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4(+)CD25(+) lymphocytes caused by human T-cell lymphotropic virus type 1. Currently, there is no accepted curative therapy for ATL. In gene expression profiling, the antiapoptotic protein survivin (BIRC5) demonstrated a striking increase in ATL, and its expression was increased in patient ATL cells resistant to the anti-CD52 monoclonal antibody alemtuzumab (Campath-1H). In this study, we investigated the antitumor activity of a small-molecule survivin suppressant YM155 alone and in combination with alemtuzumab in a murine model of human ATL (MET-1). Both YM155 alone and its combination with alemtuzumab demonstrated therapeutic efficacy by lowering serum soluble IL-2Rα (sIL-2Rα) levels (P < .001) and prolonged the survival of tumor-bearing mice (P < .0001). Moreover, the combination of YM155 with alemtuzumab demonstrated markedly additive antitumor activity by significantly lowering serum sIL-2Rα levels and improving the survival of leukemia-bearing mice compared with monotherapy with either YM155 (P < .001) or alemtuzumab (P < .05). More significantly, all mice that received the combination therapy survived and were tumor free >6 months after treatment. Our data support a clinical trial of the combination of YM155 with alemtuzumab in ATL. This trial was registered at www.clinicaltrials.gov as #NCT00061048. PMID:23321252

  11. Markedly additive antitumor activity with the combination of a selective survivin suppressant YM155 and alemtuzumab in adult T-cell leukemia

    PubMed Central

    Chen, Jing; Pise-Masison, Cynthia A.; Shih, Joanna H.; Morris, John C.; Janik, John E.; Conlon, Kevin C.; Keating, Anne

    2013-01-01

    Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4+CD25+ lymphocytes caused by human T-cell lymphotropic virus type 1. Currently, there is no accepted curative therapy for ATL. In gene expression profiling, the antiapoptotic protein survivin (BIRC5) demonstrated a striking increase in ATL, and its expression was increased in patient ATL cells resistant to the anti-CD52 monoclonal antibody alemtuzumab (Campath-1H). In this study, we investigated the antitumor activity of a small-molecule survivin suppressant YM155 alone and in combination with alemtuzumab in a murine model of human ATL (MET-1). Both YM155 alone and its combination with alemtuzumab demonstrated therapeutic efficacy by lowering serum soluble IL-2Rα (sIL-2Rα) levels (P < .001) and prolonged the survival of tumor-bearing mice (P < .0001). Moreover, the combination of YM155 with alemtuzumab demonstrated markedly additive antitumor activity by significantly lowering serum sIL-2Rα levels and improving the survival of leukemia-bearing mice compared with monotherapy with either YM155 (P < .001) or alemtuzumab (P < .05). More significantly, all mice that received the combination therapy survived and were tumor free >6 months after treatment. Our data support a clinical trial of the combination of YM155 with alemtuzumab in ATL. This trial was registered at www.clinicaltrials.gov as #NCT00061048. PMID:23321252

  12. Background suppression in MAS NMR

    NASA Astrophysics Data System (ADS)

    White, Jeffery L.; Beck, Larry W.; Ferguson, David B.; Haw, James F.

    Pulse sequences for suppressing background signals from spinning modules used in magic-angle spinning NMR are described. These pulse sequences are based on spatially selective composite 90° pulses originally reported by Bax, which provide for no net excitation of spins outside the homogeneous region of the coil. We have achieved essentially complete suppression of background signals originating from our Vespel spinning module (which uses a free-standing coil) in both 1H and 13C spectra without notable loss in signal intensity. Successful modification of both Bloch decay and cross-polarization pulse sequences to include spatially selective pulses was essential to acquire background-free spectra for weak samples. Background suppression was also found to be particularly valuable for both T1 and T1 ϱ, relaxation measurements.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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. PMID:26828203

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

    PubMed

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

    2014-04-01

    Binge eating palatable foods has been shown to have behavioral and neurochemical similarities to drug addiction. GS 455534 is a highly selective reversible aldehyde dehydrogenase 2 inhibitor that has been shown to reduce alcohol and cocaine intake in rats. Given the overlaps between binge eating and drug abuse, we examined the effects of GS 455534 on binge eating and subsequent dopamine release. Sprague-Dawley rats were maintained on a sugar (experiment 1) or fat (experiment 2) binge eating diet. After 25 days, GS 455534 was administered at 7.5 and 15 mg/kg by an intraperitoneal injection, and food intake was monitored. In experiment 3, rats with cannulae aimed at the nucleus accumbens shell were maintained on the binge sugar diet for 25 days. Microdialysis was performed, during which GS 455534 15 mg/kg was administered, and sugar was available. Dialysate samples were analyzed to determine extracellular levels of dopamine. In experiment 1, GS 455534 selectively decreased sugar intake food was made available in the Binge Sugar group but not the Ad libitum Sugar group, with no effect on chow intake. In experiment 2, GS 455534 decreased fat intake in the Binge Fat group, but not the Ad libitum Fat group, however, it also reduced chow intake. In experiment 3, GS 455534 attenuated accumbens dopamine release by almost 50% in binge eating rats compared with the vehicle injection. The findings suggest that selective reversible aldehyde dehydrogenase 2 inhibitors may have the therapeutic potential to reduce binge eating of palatable foods in clinical populations. PMID:24603339

  20. 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

  1. Selective and augmented β-glucuronidase expression combined with DOX-GA3 application elicits the potent suppression of prostate cancer.

    PubMed

    Wang, Longxin; Dong, Jie; Wei, Ming; Wen, Weihong; Gao, Jianping; Zhang, Zhengyu; Qin, Weijun

    2016-03-01

    The present study was carried out to evaluate the specific and amplified β-glucuronidase (βG) expression in prostate cancer cells by using a prostate‑specific antigen (PSA) promoter-controlled bicistronic adenovirus and to evaluate the specific killing of prostate cancer cells after the application of the prodrug DOX‑GA3. Bicistronic adenoviral expression vectors were constructed, and the effectiveness of specific and amplified expression was evaluated using luciferase and EGFP as reporter genes. βG expression was detected in LNCaP cells after they were infected with the βG‑expressing PSA promoter-controlled bicistronic adenovirus. MTT assays were conducted to evaluate the cytoxicity on the infected cells after the application of the prodrug DOX‑GA3. Tumor growth inhibition was also evaluated in nude mice after treatment with the βG‑expressing adenovirus and DOX‑GA3. Selective and amplified expression was observed in the PSA-producing LNCaP cells, but not in the PSA‑non‑producing DU145 cells. Potent cytotoxity and a strong bystander effect were observed in the LNCaP cells after infection with the βG‑expressing adenovirus and the application of DOX‑GA3. Intravenous injection of a GAL4 regulated bicistronic adenovirus vector constructed to express βG under the control of the PSA promoter (Ad/PSAP‑GV16‑βG) and the application of DOX‑GA3 strongly inhibited tumor growth and prolonged the survival time of tumor‑bearing nude mice. Selective and amplified βG expression together with the prodrug DOX‑GA3 had an increased antitumor effect, showing great potential for prostate cancer therapy. PMID:26648021

  2. 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. PMID:20840845

  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. 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

    Fraser, Craig; Dawson, John C; Dowling, Reece; Houston, Douglas R; Weiss, Jason T; Munro, Alison F; Muir, Morwenna; Harrington, Lea; Webster, Scott P; Frame, Margaret C; Brunton, Valerie G; Patton, E Elizabeth; Carragher, Neil O; Unciti-Broceta, Asier

    2016-05-26

    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

  5. A selective inhibitor of the immunoproteasome subunit LMP2 induces apoptosis in PC-3 cells and suppresses tumour growth in nude mice

    PubMed Central

    Wehenkel, M; Ban, J-O; Ho, Y-K; Carmony, K C; Hong, J T; Kim, K B

    2012-01-01

    Background: Although the proteasome is a validated anticancer target, the clinical application of its inhibitors has been limited because of inherent systemic toxicity. To broaden clinical utility of proteasome inhibitors as anticancer agents, it is critical to develop strategies to selectively target proteasomes in cancer cells. The immunoproteasome is an alternative form of the constitutive proteasome that is expressed at high levels in cancer tissues, but not in most normal cells in the body. Methods: To validate the immunoproteasome as a chemotherapeutic target, an immunoproteasome catalytic subunit LMP2-targeting inhibitor and siRNA were used. The sensitivity of PC-3 prostate cancer cells to these reagents was investigated using viability assays. Further, a xenograft model of prostate cancer was studied to test the in vivo effects of LMP2 inhibition. Results: A small molecule inhibitor of the immunoproteasome subunit LMP2, UK-101, induced apoptosis of PC-3 cells and resulted in significant inhibition (∼50–60%) of tumour growth in vivo. Interestingly, UK-101 did not block degradation of IκBα in PC-3 cells treated with TNF-α, suggesting that its mode of action may be different from that of general proteasome inhibitors, such as bortezomib, which block IκBα degradation. Conclusion: These results strongly suggest that the immunoproteasome has important roles in cancer cell growth and thus provide a rationale for targeting the immunoproteasome in the treatment of prostate cancer. PMID:22677907

  6. 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

  7. 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

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

    PubMed

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

    2009-04-01

    Recent studies have demonstrated that glycogen synthase kinase 3beta (GSK-3beta) is overexpressed in human colon and pancreatic carcinomas, contributing to cancer cell proliferation and survival. Here, we report the design, synthesis, and biological evaluation of benzofuran-3-yl-(indol-3-yl)maleimides, potent GSK-3beta inhibitors. Some of these compounds show picomolar inhibitory activity toward GSK-3beta and an enhanced selectivity against cyclin-dependent kinase 2 (CDK-2). Selected GSK-3beta inhibitors were tested in the pancreatic cancer cell lines MiaPaCa-2, BXPC-3, and HupT3. We determined that some of these compounds, namely compounds 5, 6, 11, 20, and 26, demonstrate antiproliferative activity against some or all of the pancreatic cancer cells at low micromolar to nanomolar concentrations. We found that the treatment of pancreatic cancer cells with GSK-3beta inhibitors 5 and 26 resulted in suppression of GSK-3beta activity and a distinct decrease of the X-linked inhibitor of apoptosis (XIAP) expression, leading to significant apoptosis. The present data suggest a possible role for GSK-3beta inhibitors in cancer therapy, in addition to their more prominent applications in CNS disorders. PMID:19338355

  9. BI 5700, a Selective Chemical Inhibitor of IκB Kinase 2, Specifically Suppresses Epithelial-Mesenchymal Transition and Metastasis in Mouse Models of Tumor Progression

    PubMed Central

    Huber, Margit A.; Maier, Harald J.; Alacakaptan, Memetcan; Wiedemann, Eva; Braunger, Jürgen; Boehmelt, Guido; Madwed, Jeffrey B.; Young, Erick R.R.; Marshall, Daniel R.; Pehamberger, Hubert; Wirth, Thomas; Kraut, Norbert; Beug, Hartmut

    2010-01-01

    Increasing evidence suggests that processes termed epithelial-mesenchymal transitions (EMTs) play a key role in therapeutic resistance, tumor recurrence, and metastatic progression. NF-κB signaling has been previously identified as an important pathway in the regulation of EMT in a mouse model of tumor progression. However, it remains unclear whether there is a broad requirement for this pathway to govern EMT and what the relative contribution of IKK family members acting as upstream NF-κB activators is toward promoting EMT and metastasis. To address this question, we have used a novel, small-molecule inhibitor of IκB kinase 2 (IKK2/IKKβ), termed BI 5700. We investigated the role of IKK2 in a number of mouse models of EMT, including TGFβ-induced EMT in the mammary epithelial cell line EpRas, CT26 colon carcinoma cells, and 4T1 mammary carcinoma cells. The latter model was also used to evaluate in vivo activities of BI 5700.We found that BI 5700 inhibits IKK2 with an IC50 of 9 nM and was highly selective as compared to other IKK family members (IKK1, IKKε, and TBK1) and other kinases. BI 5700 effectively blocks NF-κB activity in EpRas cells and prevents TGFβ-induced EMT. In addition, BI 5700 reverts EMT in mesenchymal CT26 cells and prevents EMT in the 4T1 model. Oral application of BI 5700 significantly interferes with metastasis after mammary fat-pad injection of 4T1 cells, yielding fewer, smaller, and more differentiated metastases as compared to vehicle-treated control animals. We conclude that IKK2 is a key regulator of both the induction and maintenance of EMT in a panel of mouse tumor progression models and that the IKK2 inhibitor BI 5700 constitutes a promising candidate for the treatment of metastatic cancers. PMID:21779445

  10. 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

  11. 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. PMID:26517321

  12. Deconstructing Interocular Suppression: Attention and Divisive Normalization

    PubMed Central

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

    2015-01-01

    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. PMID:26517321

  13. 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.

  14. 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

  15. Large-scale identification and analysis of suppressive drug interactions.

    PubMed

    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

    2014-04-24

    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

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

    PubMed Central

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

    2016-01-01

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

  17. Growth hormone suppression test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  18. Dexamethasone suppression test

    MedlinePlus

    Dexamethasone suppression test measures whether adrenocorticotrophic hormone ( ACTH ) secretion by the pituitary can be suppressed. ... During this test, you will receive dexamethasone. This is a strong ... your blood is drawn so that the cortisol level in your blood ...

  19. 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 ...

  20. Growth hormone suppression test

    MedlinePlus

    The growth hormone suppression test determines whether growth hormone production is being suppressed by high blood sugar. ... away. The lab measures the glucose and growth hormone (GH) levels in each sample.

  1. 2p-2p decay of 8C and isospin-allowed 2p decay of the isobaric-analog state in 8B

    NASA Astrophysics Data System (ADS)

    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.; Howard, M. E.

    2010-10-01

    C8 is found to decay to four protons and an α particle in two 2p emission steps. The correlations between the protons in the first step (C8 to Be6) 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 C8 in B8 is also found to decay by 2p emission. This is the first case of isospin-allowed 2p decay between isobaric analog states.

  2. 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.

  3. Selective inhibition of nuclear factor-κB by nuclear factor-κB essential modulator-binding domain peptide suppresses the metastasis of highly metastatic oral squamous cell carcinoma.

    PubMed

    Tanaka, Takuya; Nakayama, Hideki; Yoshitake, Yoshihiro; Irie, Atsushi; Nagata, Masashi; Kawahara, Kenta; Takamune, Yasuo; Yoshida, Ryoji; Nakagawa, Yoshihiro; Ogi, Hidenao; Shinriki, Satoru; Ota, Kazutoshi; Hiraki, Akimitsu; Ikebe, Tetsuro; Nishimura, Yasuharu; Shinohara, Masanori

    2012-03-01

    Nuclear factor-κB (NF-κB) activation contributes to the development of metastasis, thus leading to a poor prognosis in many cancers, including OSCC. However, little in vivo experimental data are available about the effects of NF-κB inhibition on OSCC metastasis. OSCC sublines were established from a GFP-expressing parental cell line, GSAS, and designated GSAS/N3 and N5 according to the in vivo passage number after cervical lymph node metastasis by a serial orthotopic transplantation model. In vitro migration and invasion were assessed in these cells, and the NF-κB activities and expression of NF-κB-regulated metastasis-related molecules were also examined. In in vivo experiments, the metastasis and survival of tumor-engrafted mice were monitored. Furthermore, the effects of a selective NF-κB inhibitor, NEMO-binding domain (NBD) peptide, on metastasis in GSAS/N5-engrafted mice were assessed, and engrafted tongue tumors were immunohistochemically examined. Highly metastatic GSAS/N3 and N5 cells showed an enhanced NF-κB activity, thus contributing to increased migration, invasion, and a poor prognosis compared with the parent cells. Furthermore, the expression levels of NF-κB-regulated metastasis-related molecules, such as fibronectin, β1 integrin, MMP-1, -2, -9, and -14, and VEGF-C, were upregulated in the highly metastatic cells. The NBD peptide suppressed metastasis and tongue tumor growth in GSAS/N5-inoculated mice, and was accompanied by the downregulation of the NF-κB-regulated metastasis-related molecules in engrafted tongue tumors. Our results suggest that the selective inhibition of NF-κB activation by NBD peptide may provide an effective approach for the treatment of highly metastatic OSCC. PMID:22136381

  4. 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

  5. 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

  6. 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

  7. 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?

  8. Identifying separate components of surround suppression

    PubMed Central

    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. PMID:26756172

  9. Physiological consequences of selective suppression of synaptic transmission in developing cerebral cortical networks in vitro: differential effects on intrinsically generated bioelectric discharges in a living 'model' system for slow-wave sleep activity.

    PubMed

    Corner, Michael A; Baker, Robert E; van Pelt, Jaap

    2008-10-01

    Within the context of an updated thorough review of the literature concerning activity-dependent cerebro-cortical development, a survey is made of recent experiments which utilize spontaneous spike-trains as the dependent variable in rodent neocortex cultures when synaptic transmission is interfered with during early ontogeny. Emphasis is placed on the complexity of homeostatic adaptations to reduced as well as intensified firing. Two kinds of adaptation are distinguished: (i) rapid recovery (within several hours) towards baseline levels despite sustained blockade of excitatory synaptic transmission, and (ii) the generation of essentially normal firing patterns in cultures assayed in control medium following development in the presence of excitatory receptor blockers. The former category of homeostatic responses is strongly dependent on the type of preparation, with isolated organotypic explants showing greatly limited plasticity in comparison with co-cultures of matching contralateral pieces of cortical tissue. In such co-cultures, compensatory excitatory drive manifests itself even when all three known types of ionotropic glutamate receptors are chronically blocked, and is then mediated by (muscarinic) cholinergic mechanisms which normally do not contribute measurably to spontaneous activity. The rapid return of high levels of spontaneous firing during sustained selective glutamatergic receptor blockade appears to protect neuronal cultures treated in this way from becoming hyperexcitable. In particular, quasi-epileptiform paroxysmal bursting upon return to control medium, such as appears in preparations where bioelectric activity has been totally suppressed during network formation, fails to appear in chronically receptor blocked cultures. On the contrary, desensitization of blocked glutamate receptors, as a physiological compensation for the up-regulation of non-blocked receptors, could be demonstrated for both the AMPA and the NMDA glutamate receptor sub

  10. Effects of phlorizin on diabetic retinopathy according to isobaric tags for relative and absolute quantification–based proteomics in db/db mice

    PubMed Central

    Zhang, Shi-yang; Li, Bao-ying; Li, Xiao-li; Cheng, Mei; Cai, Qian; Yu, Fei; Wang, Wei-dong; Tan, Min; Yan, Guang; Hu, Shi-lian

    2013-01-01

    Purpose Diabetic retinopathy (DR) is a leading cause of vision loss in working-age people. To retard the development and progression of retina lesions, effective therapeutic strategies directed toward key molecular targets are desired. Phlorizin is effective in treating diabetic complications, but little is known about functional protein changes that may mediate its actions. The aim of this study was to identify retinal proteomic alterations in db/db mice treated with phlorizin. Methods We used C57BLKS/J db/db mice as a type 2 diabetic animal model, while C57BLKS/J db/m mice were selected as the control. Phlorizin (20 mg/kg bodyweight /d) was administrated to db/db mice for ten weeks. Serum fasting blood glucose and advanced glycation end products were determined. Meanwhile, retina cell apoptosis was determined with terminal transferase dUTP nick end labeling. Isobaric tags for relative and absolute quantification and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to identify and profile retinal proteins among control, untreated diabetic, and phlorizin-treated db/db mice. The expression of glial fibrillary acidic protein was measured in retinas using western blotting analysis. Results Phlorizin treatment significantly reduced fasting blood glucose and levels of advanced glycation end products (p<0.05) and remarkably inhibited retina cell apoptosis and the expression of glial fibrillary acidic protein in the retinas of db/db mice. In addition, we identified 1,636 proteins from retina tissue in total, of which 348 proteins were differentially expressed in db/db mice compared with the controls. Only 60 proteins in the retinas of the db/db mice were found to be differentially changed following phlorizin treatment, including 33 proteins that were downregulated and 27 proteins that were upregulated. Most of these differentially changed proteins were involved in oxidative stress, apoptosis, energy metabolism, and signaling transduction