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Sample records for peroxynitrite driven nitroxidative

  1. Peroxynitrite scavenging by flavonids.

    NARCIS (Netherlands)

    Haenen, G.R.M.M.; Paquay, J.B.G.; Korthouwer, R.E.M.; Bast, A.

    1997-01-01

    The peroxynitrite scavenging activity of a series of structurally related flavonoids was tested. It was found that flavonoids are excellent scavengers of peroxynitrite. Compared to the known peroxynitrite scavenger ebselen, the most active flavonoids proved to be 10 times more effective. Indications

  2. Imidazoline and imidazolidine nitroxides as controlling agents in nitroxide-mediated pseudoliving radical polymerization

    Science.gov (United States)

    Edeleva, M. V.; Marque, S. R. A.; Bagryanskaya, E. G.

    2018-04-01

    Controlled, or pseudoliving, radical polymerization provides unique opportunities for the synthesis of structurally diverse polymers with a narrow molecular-weight distribution. These reactions occur under relatively mild conditions with broad tolerance to functional groups in the monomers. The nitroxide-mediated pseudoliving radical polymerization is of particular interest for the synthesis of polymers for biomedical applications. This review briefly describes one of the mechanisms of controlled radical polymerization. The studies dealing with the use of imidazoline and imidazolidine nitroxides as controlling agents for nitroxide-mediated pseudoliving radical polymerization of various monomers are summarized and analyzed. The publications addressing the key steps of the controlled radical polymerization in the presence of imidazoline and imidazolidine nitroxides and new approaches to nitroxide-mediated polymerization based on protonation of both nitroxides and monomers are considered. The bibliography includes 154 references.

  3. Cross-talk between lipid and protein carbonylation in a dynamic cardiomyocyte model of mild nitroxidative stress

    Directory of Open Access Journals (Sweden)

    Eva Griesser

    2017-04-01

    Full Text Available Reactive oxygen and nitrogen species (ROS/RNS play an important role in the regulation of cardiac function. Increase in ROS/RNS concentration results in lipid and protein oxidation and is often associated with onset and/or progression of many cardiovascular disorders. However, interplay between lipid and protein modifications has not been simultaneously studied in detail so far. Biomolecule carbonylation is one of the most common biomarkers of oxidative stress. Using a dynamic model of nitroxidative stress we demonstrated rapid changes in biomolecule carbonylation in rat cardiomyocytes. Levels of carbonylated species increased as early as 15 min upon treatment with the peroxynitrite donor, 3-morpholinosydnonimine (SIN-1, and decreased to values close to control after 16 h. Total (lipids+proteins vs. protein-specific carbonylation showed different dynamics, with a significant increase in protein-bound carbonyls at later time points. Treatment with SIN-1 in combination with inhibitors of proteasomal and autophagy/lysosomal degradation pathways allowed confirmation of a significant role of the proteasome in the degradation of carbonylated proteins, whereas lipid carbonylation increased in the presence of autophagy/lysosomal inhibitors. Electrophilic aldehydes and ketones formed by lipid peroxidation were identified and relatively quantified using LC-MS/MS. Molecular identity of reactive species was used for data-driven analysis of their protein targets. Combination of different enrichment strategies with LC-MS/MS analysis allowed identification of more than 167 unique proteins with 332 sites modified by electrophilic lipid peroxidation products. Gene ontology analysis of modified proteins demonstrated enrichment of several functional categories including proteins involved in cytoskeleton, extracellular matrix, ion channels and their regulation. Using calcium mobilization assays, the effect of nitroxidative stress on the activity of several ion

  4. Design concept for α-hydrogen-substituted nitroxides.

    Science.gov (United States)

    Amar, Michal; Bar, Sukanta; Iron, Mark A; Toledo, Hila; Tumanskii, Boris; Shimon, Linda J W; Botoshansky, Mark; Fridman, Natalia; Szpilman, Alex M

    2015-02-06

    Stable nitroxides (nitroxyl radicals) have many essential and unique applications in chemistry, biology and medicine. However, the factors influencing their stability are still under investigation, and this hinders the design and development of new nitroxides. Nitroxides with tertiary alkyl groups are generally stable but obviously highly encumbered. In contrast, α-hydrogen-substituted nitroxides are generally inherently unstable and rapidly decompose. Herein, a novel, concept for the design of stable cyclic α-hydrogen nitroxides is described, and a proof-of-concept in the form of the facile synthesis and characterization of two diverse series of stable α-hydrogen nitroxides is presented. The stability of these unique α-hydrogen nitroxides is attributed to a combination of steric and stereoelectronic effects by which disproportionation is kinetically precluded. These stabilizing effects are achieved by the use of a nitroxide co-planar substituent in the γ-position of the backbone of the nitroxide. This premise is supported by a computational study, which provides insight into the disproportionation pathways of α-hydrogen nitroxides.

  5. The evaluation of new and isotopically labeled isoindoline nitroxides and an azaphenalene nitroxide for EPR oximetry

    Science.gov (United States)

    Khan, Nadeem; Blinco, James P.; Bottle, Steven E.; Hosokawa, Kazuyuki; Swartz, Harold M.; Micallef, Aaron S.

    2011-01-01

    Isoindoline nitroxides are potentially useful probes for viable biological systems, exhibiting low cytotoxicity, moderate rates of biological reduction and favorable Electron Paramagnetic Resonance (EPR) characteristics. We have evaluated the anionic (5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl; CTMIO), cationic (5-(N,N,N-trimethylammonio)-1,1,3,3-tetramethylisoindolin-2-yloxyl iodide, QATMIO) and neutral (1,1,3,3-tetramethylisoindolin-2-yloxyl; TMIO) nitroxides and their isotopically labeled analogues (2H12- and/or 2H12-15N-labeled) as potential EPR oximetry probes. An active ester analogue of CTMIO, designed to localize intracellularly, and the azaphenalene nitroxide 1,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalen-2-yloxyl (TMAO) were also studied. While the EPR spectra of the unlabeled nitroxides exhibit high sensitivity to O2 concentration, deuteration resulted in a loss of superhyperfine features and a subsequent reduction in O2 sensitivity. Labeling the nitroxides with 15N increased the signal intensity and this may be useful in decreasing the detection limits for in vivo measurements. The active ester nitroxide showed approximately 6% intracellular localization and low cytotoxicity. The EPR spectra of TMAO nitroxide indicated an increased rigidity in the nitroxide ring, due to dibenzo-annulation. PMID:21665499

  6. PEROXYNITRITE CHEMISTRY

    Energy Technology Data Exchange (ETDEWEB)

    Lymar, S.V.

    2000-11-29

    This century old area of research has been experiencing a renaissance during the last decade, with the annual number of publications on the subject increasing from only one in 1990 to nearly 200 in the late-1990s. This renewed interest is stimulated by the discovery of biological roles of nitric oxide, distinguished by the 1998 Nobel prize, and the recognition that the conversion of nitric oxide into peroxynitrite may play major roles in human diseases associated with oxidative stress and in cellular defense against invading pathogens. Peroxynitrite (ONOO{sup {minus}})is a structural isomer of nitrate (NO{sub 3}{sup {minus}}) that contains a peroxo bond. The physiological route to ONOO{sup {minus}} is provided by the combination of nitric oxide ({center_dot}NO) with superoxide ({center_dot}O{sub 2}{sup {minus}}), an extremely rapid reaction occurring upon every encounter of these radicals (the upper dot denotes radical species). Both {center_dot}NO and {center_dot}O{sub 2}{sup {minus}} are the oxygen metabolic products simultaneously generated in a number of cell types within a human body. Compared to its precursors, peroxynitrite is a much stronger oxidant capable of oxidizing proteins, nucleic acids, and lipids.

  7. Methamphetamine generates peroxynitrite and produces dopaminergic neurotoxicity in mice: protective effects of peroxynitrite decomposition catalyst.

    Science.gov (United States)

    Imam, S Z; Crow, J P; Newport, G D; Islam, F; Slikker, W; Ali, S F

    1999-08-07

    Methamphetamine (METH)-induced dopaminergic neurotoxicity is believed to be produced by oxidative stress and free radical generation. The present study was undertaken to investigate if METH generates peroxynitrite and produces dopaminergic neurotoxicity. We also investigated if this generation of peroxynitrite can be blocked by a selective peroxynitrite decomposition catalyst, 5, 10,15, 20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) and protect against METH-induced dopaminergic neurotoxicity. Administration of METH resulted in the significant formation of 3-nitrotyrosine (3-NT), an in vivo marker of peroxynitrite generation, in the striatum and also caused a significant increase in the body temperature. METH injection also caused a significant decrease in the concentration of dopamine (DA), 3, 4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) by 76%, 53% and 40%, respectively, in the striatum compared with the control group. Treatment with FeTMPyP blocked the formation of 3-NT by 66% when compared with the METH group. FeTMPyP treatment also provided significant protection against the METH-induced hyperthermia and depletion of DA, DOPAC and HVA. Administration of FeTMPyP alone neither resulted in 3-NT formation nor had any significant effect on DA or its metabolite concentrations. These findings indicate that peroxynitrite plays a role in METH-induced dopaminergic neurotoxicity and also suggests that peroxynitrite decomposition catalysts may be beneficial for the management of psychostimulant abuse. Copyright 1999 Published by Elsevier Science B.V.

  8. Nitrogen, oxygen or sulfur containing heterocyclic compounds as analgesic drugs used as modulators of the nitroxidative stress.

    Science.gov (United States)

    Salat, Kinga; Moniczewski, Andrzej; Librowski, Tadeusz

    2013-03-01

    Numerous lines of evidence suggest that heterocyclic compounds used as analgesic, anti-inflammatory and anti-migraine agents can be potent regulators of the nitroxidative stress and targeting free nitrogen and oxygen radicals is a very promising strategy for future pain management. Both classical analgesics (nonsteroidal anti-inflammatory drugs, opioid drugs) and many analgesic adjuvants, including desipramine, duloxetine, fluoxetine, paroxetine, escitalopram, phenytoin or carbamazepine and α-lipoic acid can modulate the balance between pro-oxidant and antioxidant processes in the mammalian tissues and these properties of drugs such as indomethacin, meloxicam, tenoxicam, valdecoxib or some metabolites of analgesic drugs formed by the activity of tissue peroxidases may contribute to their clinical efficacy and drug-related toxic effects, including gastrointestinal ulcers, hepatic failure, agranulocytosis, aplastic anemia, neutropenia, opiate-induced hyperalgesia and tolerance. The antioxidant capacities of novel heterocyclic compounds, including the compounds acting either by prevention of formation or catalyzed decomposition of peroxynitrite anion (ONOO-), namely the peroxynitrite decomposition catalysts or as superoxide (O2 •-)-scavengers which are the functional mimetics of superoxide dismutase (SOD) enzymes (SODm), as well as the derivatives of 6-nitro-3,4-methylenedioxyphenyl-Nacylhydrazone (LASSBio-881) or γ-butyrolactone (LPP1, BM113, BM113A, BM138 and BM138A) are also discussed as potent and promising future heterocyclic analgesics.

  9. Nitroxide delivery system for Nrf2 activation and skin protection.

    Science.gov (United States)

    Ben Yehuda Greenwald, Maya; Frušić-Zlotkin, Marina; Soroka, Yoram; Sasson, Shmuel Ben; Bianco-Peled, Havazelet; Bitton, Ronit; Kohen, Ron

    2015-08-01

    Cyclic nitroxides are a large group of compounds composed of diverse stable radicals also known as synthetic antioxidants. Although nitroxides are valuable for use in several skin conditions, in in vivo conditions they have several drawbacks, such as nonspecific dispersion in normal tissue, preferential renal clearance and rapid reduction of the nitroxide to the corresponding hydroxylamine. However, these drawbacks can be easily addressed by encapsulating the nitroxides within microemulsions. This approach would allow nitroxide activity and therefore their valuable effects (e.g. activation of the Keap1-Nrf2-EpRE pathway) to continue. In this work, nitroxides were encapsulated in a microemulsion composed of biocompatible ingredients. The nanometric size and shape of the vehicle microemulsion and nitroxide microemulsion displayed high similarity, indicating that the stability of the microemulsions was preserved. Our studies demonstrated that nitroxide microemulsions were more potent inducers of the Keap1-Nrf2-EpRE pathway than the free nitroxides, causing the activation of phase II enzymes. Moreover, microemulsions containing nitroxides significantly reduced UVB-induced cytotoxicity in the skin. Understanding the mechanism of this improved activity may expand the usage of many other Nrf2 modulating molecules in encapsulated form, as a skin protection strategy against oxidative stress-related conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Improved sensitivity for W-band Gd(III)-Gd(III) and nitroxide-nitroxide DEER measurements with shaped pulses

    Science.gov (United States)

    Bahrenberg, Thorsten; Rosenski, Yael; Carmieli, Raanan; Zibzener, Koby; Qi, Mian; Frydman, Veronica; Godt, Adelheid; Goldfarb, Daniella; Feintuch, Akiva

    2017-10-01

    Chirp and shaped pulses have been recently shown to be highly advantageous for improving sensitivity in DEER (double electron-electron resonance, also called PELDOR) measurements due to their large excitation bandwidth. The implementation of such pulses for pulse EPR has become feasible due to the availability of arbitrary waveform generators (AWG) with high sampling rates to support pulse shaping for pulses with tens of nanoseconds duration. Here we present a setup for obtaining chirp pulses on our home-built W-band (95 GHz) spectrometer and demonstrate its performance on Gd(III)-Gd(III) and nitroxide-nitroxide DEER measurements. We carried out an extensive optimization procedure on two model systems, Gd(III)-PyMTA-spacer-Gd(III)-PyMTA (Gd-PyMTA ruler; zero-field splitting parameter (ZFS) D ∼ 1150 MHz) as well as nitroxide-spacer-nitroxide (nitroxide ruler) to evaluate the applicability of shaped pulses to Gd(III) complexes and nitroxides, which are two important classes of spin labels used in modern DEER/EPR experiments. We applied our findings to ubiquitin, doubly labeled with Gd-DOTA-monoamide (D ∼ 550 MHz) as a model for a system with a small ZFS. Our experiments were focused on the questions (i) what are the best conditions for positioning of the detection frequency, (ii) which pump pulse parameters (bandwidth, positioning in the spectrum, length) yield the best signal-to-noise ratio (SNR) improvements when compared to classical DEER, and (iii) how do the sample's spectral parameters influence the experiment. For the nitroxide ruler, we report an improvement of up to 1.9 in total SNR, while for the Gd-PyMTA ruler the improvement was 3.1-3.4 and for Gd-DOTA-monoamide labeled ubiquitin it was a factor of 1.8. Whereas for the Gd-PyMTA ruler the two setups pump on maximum and observe on maximum gave about the same improvement, for Gd-DOTA-monoamide a significant difference was found. In general the choice of the best set of parameters depends on the D

  11. Peroxynitrite efficiently mediates the interconversion of redox intermediates of myeloperoxidase

    International Nuclear Information System (INIS)

    Furtmueller, Paul Georg; Jantschko, Walter; Zederbauer, Martina; Schwanninger, Manfred; Jakopitsch, Christa; Herold, Susanna; Koppenol, Willem H.; Obinger, Christian

    2005-01-01

    Nitric oxide-derived oxidants (e.g., peroxynitrite) are believed to participate in antimicrobial activities as part of normal host defenses but also in oxidative tissue injury in inflammatory disorders. A similar role is ascribed to the heme enzyme myeloperoxidase (MPO), the most abundant protein of polymorphonuclear leukocytes, which are the terminal phagocytosing effector cells of the innate immune system. Concomitant production of peroxynitrite and release of millimolar MPO are characteristic events during phagocytosis. In order to understand the mode of interaction between MPO and peroxynitrite, we have performed a comprehensive stopped-flow investigation of the reaction between all physiological relevant redox intermediates of MPO and peroxynitrite. Both iron(III) MPO and iron(II) MPO are rapidly converted to compound II by peroxynitrite in monophasic reactions with calculated rate constants of (6.8 ± 0.1) x 10 6 M -1 s -1 and (1.3 ± 0.2) x 10 6 M -1 s -1 , respectively (pH 7.0 and 25 deg C). Besides these one- and two-electron reduction reactions of peroxynitrite, which produce nitrogen dioxide and nitrite, a one-electron oxidation to the oxoperoxonitrogen radical must occur in the fast monophasic transition of compound I to compound II mediated by peroxynitrite at pH 7.0 [(7.6 ± 0.1) x 10 6 M -1 s -1 ]. In addition, peroxynitrite induced a steady-state transition from compound III to compound II with a rate of (1.0 ± 0.3) x 10 4 M -1 s -1 . Thus, the interconversion among the various oxidation states of MPO that is prompted by peroxynitrite is remarkable. Reaction mechanisms are proposed and the physiological relevance is discussed

  12. Modulation of oxidative damage by nitroxide free radicals.

    Science.gov (United States)

    Dragutan, Ileana; Mehlhorn, Rolf J

    2007-03-01

    Piperidine nitroxides like 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) are persistent free radicals in non-acidic aqueous solutions and organic solvents that may have value as therapeutic agents in medicine. In biological environments, they undergo mostly reduction to stable hydroxylamines but can also undergo oxidation to reactive oxoammonium compounds. Reactions of the oxoammonium derivatives could have adverse consequences including chemical modification of vital macromolecules and deleterious effects on cell signaling. An examination of their reactivity in aqueous solution has shown that oxoammonium compounds can oxidize almost any organic as well as many inorganic molecules found in biological systems. Many of these reactions appear to be one-electron transfers that reduce the oxoammonium to the corresponding nitroxide species, in contrast to a prevalence of two-electron reductions of oxoammonium in organic solvents. Amino acids, alcohols, aldehydes, phospholipids, hydrogen peroxide, other nitroxides, hydroxylamines, phenols and certain transition metal ions and their complexes are among reductants of oxoammonium, causing conversion of this species to the paramagnetic nitroxide. On the other hand, thiols and oxoammonium yield products that cannot be detected by ESR even under conditions that would oxidize hydroxylamines to nitroxides. These products may include hindered secondary amines, sulfoxamides and sulfonamides. Thiol oxidation products other than disulfides cannot be restored to thiols by common enzymatic reduction pathways. Such products may also play a role in cell signaling events related to oxidative stress. Adverse consequences of the reactions of oxoammonium compounds may partially offset the putative beneficial effects of nitroxides in some therapeutic settings.

  13. Highly efficient and stable catalyst for peroxynitrite decomposition

    Science.gov (United States)

    Yurii V. Geletii; Alan J. Bailey; Jennifer J. Cowan; Ira A. Weinstock; Craig L. Hill

    2001-01-01

    The new cobalt substituted-polyoxometalate K7[CoAlW11O39]•15H2O and the simple CoCl2•6H2O salt are efficient catalysts for peroxynitrite decomposition. These compounds also catalyze the oxidation of ascorbic acid and the nitration of phenol by peroxynitrite.

  14. Fundamentals on the biochemistry of peroxynitrite and protein tyrosine nitration

    Directory of Open Access Journals (Sweden)

    Silvina Bartesaghi

    2018-04-01

    Full Text Available In this review we provide an analysis of the biochemistry of peroxynitrite and tyrosine nitration. Peroxynitrite is the product of the diffusion-controlled reaction between superoxide (O2•- and nitric oxide (•NO. This process is in competition with the enzymatic dismutation of O2•- and the diffusion of •NO across cells and tissues and its reaction with molecular targets (e.g. guanylate cyclase. Understanding the kinetics and compartmentalization of the O2•- / •NO interplay is critical to rationalize the shift of •NO from a physiological mediator to a cytotoxic intermediate. Once formed, peroxynitrite (ONOO- and ONOOH; pKa = 6,8 behaves as a strong one and two-electron oxidant towards a series of biomolecules including transition metal centers and thiols. In addition, peroxynitrite anion can secondarily evolve to secondary radicals either via its fast reaction with CO2 or through proton-catalyzed homolysis. Thus, peroxynitrite can participate in direct (bimolecular and indirect (through secondary radical intermediates oxidation reactions; through these processes peroxynitrite can participate as cytotoxic effector molecule against invading pathogens and/or as an endogenous pathogenic mediator. Peroxynitrite can cause protein tyrosine nitration in vitro and in vivo. Indeed, tyrosine nitration is a hallmark of the reactions of •NO-derived oxidants in cells and tissues and serves as a biomarker of oxidative damage. Protein tyrosine nitration can mediate changes in protein structure and function that affect cell homeostasis. Tyrosine nitration in biological systems is a free radical process that can be promoted either by peroxynitrite-derived radicals or by other related •NO-dependent oxidative processes. Recently, mechanisms responsible of tyrosine nitration in hydrophobic biostructures such as membranes and lipoproteins have been assessed and involve the parallel occurrence and connection with lipid

  15. Method for recovering or recirculating stable nitroxide radicals

    NARCIS (Netherlands)

    Heeres, Andre; Van Doren, Hendrik Arend; Bleeker, Ido Pieter; Gotlieb, Kornelis Fester.

    1996-01-01

    The invention relates fo a method for recovering stable nitroxide radicals, wherein at least a part of a reaction mixt. consisting of a soln. or suspension, or a filtrate or supernatant of a suspension, in which stable nitroxide radicals are present in non-solid form, is subjected to an azeotropic

  16. Cardiolipin modulates allosterically peroxynitrite detoxification by horse heart cytochrome c

    Energy Technology Data Exchange (ETDEWEB)

    Ascenzi, Paolo, E-mail: ascenzi@uniroma3.it [Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, I-00146 Roma (Italy); Ciaccio, Chiara [Department of Experimental Medicine and Biochemical Sciences, University of Roma ' Tor Vergata' , I-00133 Roma (Italy); Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems, I-70126 Bari (Italy); Sinibaldi, Federica; Santucci, Roberto [Department of Experimental Medicine and Biochemical Sciences, University of Roma ' Tor Vergata' , I-00133 Roma (Italy); Coletta, Massimo [Department of Experimental Medicine and Biochemical Sciences, University of Roma ' Tor Vergata' , I-00133 Roma (Italy); Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems, I-70126 Bari (Italy)

    2011-01-07

    Research highlights: {yields} Cardiolipin binding to cytochrome c. {yields} Cardiolipin-dependent peroxynitrite isomerization by cytochrome c. {yields} Cardiolipin-cytochrome c complex plays pro-apoptotic effects. {yields} Cardiolipin-cytochrome c complex plays anti-apoptotic effects. -- Abstract: Upon interaction with bovine heart cardiolipin (CL), horse heart cytochrome c (cytc) changes its tertiary structure disrupting the heme-Fe-Met80 distal bond, reduces drastically the midpoint potential out of the range required for its physiological role, binds CO and NO with high affinity, and displays peroxidase activity. Here, the effect of CL on peroxynitrite isomerization by ferric cytc (cytc-Fe(III)) is reported. In the absence of CL, hexa-coordinated cytc does not catalyze peroxynitrite isomerization. In contrast, CL facilitates cytc-Fe(III)-mediated isomerization of peroxynitrite in a dose-dependent fashion inducing the penta-coordination of the heme-Fe(III)-atom. The value of the second order rate constant for CL-cytc-Fe(III)-mediated isomerization of peroxynitrite (k{sub on}) is (3.2 {+-} 0.4) x 10{sup 5} M{sup -1} s{sup -1}. The apparent dissociation equilibrium constant for CL binding to cytc-Fe(III) is (5.1 {+-} 0.8) x 10{sup -5} M. These results suggest that CL-cytc could play either pro-apoptotic or anti-apoptotic effects facilitating lipid peroxidation and scavenging of reactive nitrogen species, such as peroxynitrite, respectively.

  17. Kinetics of reaction of peroxynitrite with selenium- and sulfur-containing compounds

    DEFF Research Database (Denmark)

    Storkey, Corin; Pattison, David I.; Ignasiak, Marta T.

    2015-01-01

    with peroxynitrite with high rate constants. Low molecular mass selenols react particularly rapidly with peroxynitrite, with second order rate constants k2 in the range 5.1×105-1.9×106 M-1 s-1, and 250-830 fold faster than the corresponding thiols (RSH) and many other endogenous biological targets. Reactions......Peroxynitrite (the physiological mixture of ONOOH and its anion, ONOO-) is a powerful biologically-relevant oxidant capable of oxidizing and damaging a range of important targets including sulfides, thiols, lipids, proteins, carbohydrates and nucleic acids. Excessive production of peroxynitrite...... of peroxynitrite with selenides, including selenosugars are approximately 15-fold faster than their sulfur homologs with k2 approximately 2.5×103 M-1 s-1. The rate constants for diselenides and sulfides were slower with k2 0.72-1.3×103 M-1 s-1 and approximately 2.1×102 M-1 s-1 respectively. These studies...

  18. Nitroxides as antioxidants – possibilities of their application in chemoprevention and radioprotection

    Directory of Open Access Journals (Sweden)

    Sabina Tabaczar

    2011-01-01

    Full Text Available Nitroxides as stabile organic radicals were used initially as spin labels in spectroscopy of electron paramagnetic resonance (EPR with respect to parameters such as pH of an intercellular environment, oxygenation of cells and tissues, fluidity of biological membranes, conformational state and topography of proteins. Nitroxides have also been used in biology and medicine as contrast agents in magnetic resonance imaging (MRI. When their antioxidant activities were discovered, an era of research on the potential utility of these agents began. Nitroxides can modulate the redox state of the cell by participation in oxidation/reduction reactions. Therefore, they are extensively examined in various models of oxidative stress. The antioxidant effect of nitroxides is a result of their ability to catalyze dismutation of superoxide radical (superoxide dismutase-like activity, inhibit lipid peroxidation, prevent Fenton and Haber-Weiss reactions by oxidation of transition metal ions to a higher oxidative state, and confer catalase-like activity on heme proteins. In the present paper the antioxidative mechanisms of nitroxides are presented. The relation between structure, function and the rate of nitroxide reduction inside cells and tissues is also presented. The application of nitroxides in chemoprevention and radioprotection is discussed.

  19. A multipumping flow system for in vitro screening of peroxynitrite scavengers.

    Science.gov (United States)

    Ribeiro, Marta F T; Dias, Ana C B; Santos, João L M; Fernandes, Eduarda; Lima, José L F C; Zagatto, Elias A G

    2007-09-01

    Peroxynitrite anion is a reactive nitrogen species formed in vivo by the rapid, controlled diffusion reaction between nitric oxide and superoxide radicals. By reacting with several biological molecules, peroxynitrite may cause important cellular and tissue deleterious effects, which have been associated with many diseases. In this work, an automated flow-based procedure for the in vitro generation of peroxynitrite and subsequent screening of the scavenging activity of selected compounds is developed. This procedure involves a multipumping flow system (MPFS) and exploits the ability of compounds such as lipoic acid, dihydrolipoic acid, cysteine, reduced glutathione, oxidized glutathione, sulindac, and sulindac sulfone to inhibit the chemiluminescent reaction of luminol with peroxynitrite under physiological simulated conditions. Peroxynitrite was generated in the MPFS by the online reaction of acidified hydrogen peroxide with nitrite, followed by a subsequent stabilization by merging with a sodium hydroxide solution to rapidly quench the developing reaction. The pulsed flow and the timed synchronized insertion of sample and reagent solutions provided by the MPFS ensure the establishment of the reaction zone only inside the flow cell, thus allowing maximum chemiluminescence emission detection. The results obtained for the assayed compounds show that, with the exception of oxidized glutathione, all are highly potent scavengers of peroxynitrite at the studied concentrations.

  20. Nitroxides as redox probes of melanins: dark-induced and photoinduced changes in redox equilibria

    International Nuclear Information System (INIS)

    Sarna, T.; Korytowski, W.; Sealy, R.C.

    1985-01-01

    The interaction of nitroxide free radicals and their reduced products (hydroxylamines) with synthetic and natural melanins has been studied. Electron spin resonance spectroscopy was used to measure changes in radical concentration in the dark and during irradiation with visible or uv light. Some reduction of nitroxide occurs in the dark, and is reversible: the nitroxide can be completely regenerated by the one-electron oxidant ferricyanide. The kinetics of the process depend strongly on radical charge and pH. For positively charged nitroxides the rate is much faster than for either neutral or anionic radicals. At pH 10 the rate is about 20 times faster than at pH 5. Oxidation of hydroxylamine also can occur so that a redox equilibrium is established. The equilibrium constant has been estimated for the reaction between a nitroxide and melanin from autoxidation of 3,4-dihydroxyphenylalanine. Results are also dependent upon the type of melanin used and chemical modification (oxidation or reduction) of the melanin. Redox equilibria are altered during irradiation with either visible or uv light. Rapid oxidation of hydroxylamine to nitroxide is apparent, together with a slower reduction of nitroxide. Action spectra for these processes are related to those for melanin radical production and oxygen consumption in nitroxide-free melanin systems. Reduction of nitroxide is inhibited by oxygen, suggesting a competition between nitroxide and oxygen for photoinduced reducing equivalents

  1. Stability of SG1 nitroxide towards unprotected sugar and lithium salts: a preamble to cellulose modification by nitroxide-mediated graft polymerization

    Directory of Open Access Journals (Sweden)

    Guillaume Moreira

    2013-08-01

    Full Text Available The range of applications of cellulose, a glucose-based polysaccharide, is limited by its inherently poor mechanical properties. The grafting of synthetic polymer chains by, for example, a “grafting from” process may provide the means to broaden the range of applications. The nitroxide-mediated polymerization (NMP method is a technique of choice to control the length, the composition and the architecture of the grafted copolymers. Nevertheless, cellulose is difficult to solubilize in organic media because of inter- and intramolecular hydrogen bonds. One possibility to circumvent this limitation is to solubilize cellulose in N,N-dimethylformamide (DMF or N,N-dimethylacetamide (DMA with 5 to 10 wt % of lithium salts (LiCl or LiBr, and carry out grafted polymerization in this medium. The stability of nitroxides such as SG1 has not been studied under these conditions yet, even though these parameters are of crucial importance to perform the graft modification of polysaccharide by NMP. The aim of this work is to offer a model study of the stability of the SG1 nitroxide in organic media in the presence of unprotected glucose or cellobiose (used as a model of cellulose and in the presence of lithium salts (LiBr or LiCl in DMF or DMA.Contrary to TEMPO, SG1 proved to be stable in the presence of unprotected sugar, even with an excess of 100 molar equivalents of glucose. On the other hand, lithium salts in DMF or DMA clearly degrade SG1 nitroxide as proven by electron-spin resonance measurements. The instability of SG1 in these lithium-containing solvents may be explained by the acidification of the medium by the hydrolysis of DMA in the presence of LiCl. This, in turn, enables the disproportionation of the SG1 nitroxide into an unstable hydroxylamine and an oxoammonium ion.Once the conditions to perform an SG1-based nitroxide-mediated graft polymerization from cellobiose have been established, the next stage of this work will be the modification of

  2. Nitroxides protect horseradish peroxidase from H2O2-induced inactivation and modulate its catalase-like activity.

    Science.gov (United States)

    Samuni, Amram; Maimon, Eric; Goldstein, Sara

    2017-08-01

    Horseradish peroxidase (HRP) catalyzes H 2 O 2 dismutation while undergoing heme inactivation. The mechanism underlying this process has not been fully elucidated. The effects of nitroxides, which protect metmyoglobin and methemoglobin against H 2 O 2 -induced inactivation, have been investigated. HRP reaction with H 2 O 2 was studied by following H 2 O 2 depletion, O 2 evolution and heme spectral changes. Nitroxide concentration was followed by EPR spectroscopy, and its reactions with the oxidized heme species were studied using stopped-flow. Nitroxide protects HRP against H 2 O 2 -induced inactivation. The rate of H 2 O 2 dismutation in the presence of nitroxide obeys zero-order kinetics and increases as [nitroxide] increases. Nitroxide acts catalytically since its oxidized form is readily reduced to the nitroxide mainly by H 2 O 2 . The nitroxide efficacy follows the order 2,2,6,6-tetramethyl-piperidine-N-oxyl (TPO)>4-OH-TPO>3-carbamoyl proxyl>4-oxo-TPO, which correlates with the order of the rate constants of nitroxide reactions with compounds I, II, and III. Nitroxide catalytically protects HRP against inactivation induced by H 2 O 2 while modulating its catalase-like activity. The protective role of nitroxide at μM concentrations is attributed to its efficient oxidation by P940, which is the precursor of the inactivated form P670. Modeling the dismutation kinetics in the presence of nitroxide adequately fits the experimental data. In the absence of nitroxide the simulation fits the observed kinetics only if it does not include the formation of a Michaelis-Menten complex. Nitroxides catalytically protect heme proteins against inactivation induced by H 2 O 2 revealing an additional role played by nitroxide antioxidants in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Genotoxic effect and antigen binding characteristics of SLE auto-antibodies to peroxynitrite-modified human DNA.

    Science.gov (United States)

    Khan, Md Asad; Alam, Khursheed; Mehdi, Syed Hassan; Rizvi, M Moshahid A

    2017-12-01

    Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by auto-antibodies against native deoxyribonucleic acid after modification and is one of the reasons for the development of SLE. Here, we have evaluated the structural perturbations in human placental DNA by peroxynitrite using spectroscopy, thermal denaturation and high-performance liquid chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional oxidative/nitrative agent that is produced both endogenously and exogenously. In experimental animals, the peroxynitrite-modified DNA was found to be highly immunogenic. The induced antibodies showed cross-reactions with different types of DNA and nitrogen bases that were modified with peroxynitrite by inhibition ELISA. The antibody activity was inhibited by approximately 89% with its immunogen as the inhibitor. The antigen-antibodies interaction between induced antibodies with peroxynitrite-modified DNA showed retarded mobility as compared to the native form. Furthermore, significantly increased binding was also observed in SLE autoantibodies with peroxynitrite-modified DNA than native form. Moreover, DNA isolated from lymphocyte of SLE patients revealed significant recognition of anti-peroxynitrite-modified DNA immunoglobulin G (IgG). Our data indicates that DNA modified with peroxynitrite presents unique antigenic determinants that may induce autoantibody response in SLE. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Peroxynitrite modified DNA presents better epitopes for anti-DNA autoantibodies in diabetes type 1 patients.

    Science.gov (United States)

    Tripathi, Prashant; Moinuddin; Dixit, Kiran; Mir, Abdul Rouf; Habib, Safia; Alam, Khursheed; Ali, Asif

    2014-07-01

    Peroxynitrite (ONOO(-)), formed by the reaction between nitric oxide (NO) and superoxide (O2(-)), has been implicated in the etiology of numerous disease processes. Peroxynitrite interacts with DNA via direct oxidative reactions or via indirect radical-mediated mechanism. It can inflict both oxidative and nitrosative damages on DNA bases, generating abasic sites, resulting in the single strand breaks. Plasmid pUC 18 isolated from Escherichiacoli was modified with peroxynitrite, generated by quenched flow process. Modifications incurred in plasmid DNA were characterized by ultraviolet and fluorescence spectroscopy, circular dichroism, HPLC and melting temperature studies. Binding characteristics and specificity of antibodies from diabetes patients were analyzed by direct binding and inhibition ELISA. Peroxynitrite modification of pUC 18 plasmid resulted in the formation of strand breaks and base modification. The major compound formed when peroxynitrite reacted with DNA was 8-nitroguanine, a specific marker for peroxynitrite induced DNA damage in inflamed tissues. The concentration of 8-nitroguanine was found to be 3.8 μM. Sera from diabetes type 1 patients from different age groups were studied for their binding to native and peroxynitrite modified plasmid. Direct binding and competitive-inhibition ELISA results showed higher recognition of peroxynitrite modified plasmid, as compared to the native form, by auto-antibodies present in diabetes patients. The preferential recognition of modified plasmid by diabetes autoantibodies was further reiterated by gel shift assay. Experimentally induced anti-peroxynitrite-modified plasmid IgG was used as a probe to detect nitrosative lesions in the DNA isolated from diabetes patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Electrochemistry of norcocaine nitroxide and related compounds: implications for cocaine hepatotoxicity.

    Science.gov (United States)

    Charkoudian, J C; Shuster, L

    1985-08-15

    Norcocaine nitroxide, a free radical metabolite of cocaine, displays a reversible one-electron cyclic voltammogram which is abolished by the addition of reduced glutathione. The corresponding nitrosonium ion was synthesized. It showed the same electrochemical characteristics as the nitroxide. The spin label 4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl (TEMPOL) and its nitrosonium ion behaved like morcocaine nitroxide and its nitrosonium ion. The nitrosonium ion of TEMPOL caused hemolysis of red blood cells, but TEMPOL did not. These observations suggest that the highly reactive nitrosonium ion may be involved in the production of cocaine-induced hepatic necrosis in mice.

  6. The chemistry of peroxynitrite, a biological toxin

    Directory of Open Access Journals (Sweden)

    W. H. Koppenol

    1998-06-01

    Full Text Available Oxyradicals play a tole in several diseases. While for several decades the hydroxyl radical - produced via the Fenton reaction - has been considered the species that initiates oxyradical damage, new findings suggest that much of this damage can be ascribed to peroxynitrite, O=NOO-, formed from the reaction of the superoxide anion with nitrogen monoxide near activated macrophages. The rate constant for the reaction of this reaction has been investigated by flash photolysis and was found to be significantly higher than previously described in the literature, 1.9 x 10(10 M-1s-1. Studies of the isomerization to nitrate resulted in the discovery of a complex between peroxynitrite and its protonated form with a stability constant of 1 x 10(4 M-1. Some of the harmful reaction of peroxynitrous acid have been ascribed to the hydroxyl radical as a product of homolysis of the O-O bond during the conversion to nitrate. Kinetics of the isomerization reaction as a function of pressure show that the activation volume is only +1.5+1.0 ml mol-1, which is inconsistent with homolysis. Instead, an intermediate, possibly a distorted trans-isomer of O=NOOH could be responsible for the harmful reactions of peroxynitrite.

  7. High-Frequency Electron Paramagnetic Resonance Spectroscopy of Nitroxide-Functionalized Nanodiamonds in Aqueous Solution.

    Science.gov (United States)

    Akiel, R D; Stepanov, V; Takahashi, S

    2017-06-01

    Nanodiamond (ND) is an attractive class of nanomaterial for fluorescent labeling, magnetic sensing of biological molecules, and targeted drug delivery. Many of those applications require tethering of target biological molecules on the ND surface. Even though many approaches have been developed to attach macromolecules to the ND surface, it remains challenging to characterize dynamics of tethered molecule. Here, we show high-frequency electron paramagnetic resonance (HF EPR) spectroscopy of nitroxide-functionalized NDs. Nitroxide radical is a commonly used spin label to investigate dynamics of biological molecules. In the investigation, we developed a sample holder to overcome water absorption of HF microwave. Then, we demonstrated HF EPR spectroscopy of nitroxide-functionalized NDs in aqueous solution and showed clear spectral distinction of ND and nitroxide EPR signals. Moreover, through EPR spectral analysis, we investigate dynamics of nitroxide radicals on the ND surface. The demonstration sheds light on the use of HF EPR spectroscopy to investigate biological molecule-functionalized nanoparticles.

  8. Ferrocene-based diradicals of imino nitroxide, nitronyl nitroxide and verdazyl, and their cations are possible SMM: A quantum chemical study

    Science.gov (United States)

    Pal, Arun K.; Datta, Sambhu N.

    2017-05-01

    Six diradicals designed from imino nitroxide, verdazyl and nitronyl nitroxide monoradicals coupled via the ferrocene moiety and six corresponding triradical cations are quantum chemically investigated. The transoid conformation is employed for considerations of general stability. All biradicals are found as very weakly and antiferromagnetically coupled. This agrees with experiment. The cations have strong antiferromagnetic spin-coupling. The charge and spin population distributions, spin alternation pattern, and the disjoint nature of SOMOs can be used to explain the nature and extent of magnetic interaction. Calculated EPR characteristics identify the neutral species as well as their cations as possible single molecule magnets.

  9. Distance measurements across randomly distributed nitroxide probes from the temperature dependence of the electron spin phase memory time at 240 GHz

    Science.gov (United States)

    Edwards, Devin T.; Takahashi, Susumu; Sherwin, Mark S.; Han, Songi

    2012-10-01

    At 8.5 T, the polarization of an ensemble of electron spins is essentially 100% at 2 K, and decreases to 30% at 20 K. The strong temperature dependence of the electron spin polarization between 2 and 20 K leads to the phenomenon of spin bath quenching: temporal fluctuations of the dipolar magnetic fields associated with the energy-conserving spin "flip-flop" process are quenched as the temperature of the spin bath is lowered to the point of nearly complete spin polarization. This work uses pulsed electron paramagnetic resonance (EPR) at 240 GHz to investigate the effects of spin bath quenching on the phase memory times (TM) of randomly-distributed ensembles of nitroxide molecules below 20 K at 8.5 T. For a given electron spin concentration, a characteristic, dipolar flip-flop rate (W) is extracted by fitting the temperature dependence of TM to a simple model of decoherence driven by the spin flip-flop process. In frozen solutions of 4-Amino-TEMPO, a stable nitroxide radical in a deuterated water-glass, a calibration is used to quantify average spin-spin distances as large as r¯=6.6 nm from the dipolar flip-flop rate. For longer distances, nuclear spin fluctuations, which are not frozen out, begin to dominate over the electron spin flip-flop processes, placing an effective ceiling on this method for nitroxide molecules. For a bulk solution with a three-dimensional distribution of nitroxide molecules at concentration n, we find W∝n∝1/r, which is consistent with magnetic dipolar spin interactions. Alternatively, we observe W∝n for nitroxides tethered to a quasi two-dimensional surface of large (Ø ˜ 200 nm), unilamellar, lipid vesicles, demonstrating that the quantification of spin bath quenching can also be used to discern the geometry of molecular assembly or organization.

  10. Peroxynitrite scavenging activity of herb extracts.

    Science.gov (United States)

    Choi, Hye Rhi; Choi, Jae Sue; Han, Yong Nam; Bae, Song Ja; Chung, Hae Young

    2002-06-01

    Peroxynitrite (ONOO(-)) is a cytotoxicant with strong oxidizing properties toward various cellular constituents, including sulphydryls, lipids, amino acids and nucleotides and can cause cell death, lipid peroxidation, carcinogenesis and aging. The aim of this study was to characterize ONOO(-) scavenging constituents from herbs. Twenty-eight herbs were screened for their ONOO(-) scavenging activities with the use of a fluorometric method. The potency of scavenging activity following the addition of authentic ONOO(-) was in the following order: witch hazel bark > rosemary > jasmine tea > sage > slippery elm > black walnut leaf > Queen Anne's lace > Linden flower. The extracts exhibited dose-dependent ONOO(-) scavenging activities. We found that witch hazel (Hamamelis virginiana L.) bark showed the strongest effect for scavenging ONOO(-) of the 28 herbs. Hamamelitannin, the major active component of witch hazel bark, was shown to have a strong ability to scavenge ONOO(-). It is suggested that hamamelitannin might be developed as an effective peroxynitrite scavenger for the prevention of ONOO(-) involved diseases. Copyright 2002 John Wiley & Sons, Ltd.

  11. Studying mechanism of radical reactions: From radiation to nitroxides as research tools

    Science.gov (United States)

    Maimon, Eric; Samuni, Uri; Goldstein, Sara

    2018-02-01

    Radicals are part of the chemistry of life, and ionizing radiation chemistry serves as an indispensable research tool for elucidation of the mechanism(s) underlying their reactions. The ever-increasing understanding of their involvement in diverse physiological and pathological processes has expanded the search for compounds that can diminish radical-induced damage. This review surveys the areas of research focusing on radical reactions and particularly with stable cyclic nitroxide radicals, which demonstrate unique antioxidative activities. Unlike common antioxidants that are progressively depleted under oxidative stress and yield secondary radicals, nitroxides are efficient radical scavengers yielding in most cases their respective oxoammonium cations, which are readily reduced back in the tissue to the nitroxide thus continuously being recycled. Nitroxides, which not only protect enzymes, cells, and laboratory animals from diverse kinds of biological injury, but also modify the catalytic activity of heme enzymes, could be utilized in chemical and biological systems serving as a research tool for elucidating mechanisms underlying complex chemical and biochemical processes.

  12. Coherence transfer and electron T1-, T2-relaxation in nitroxide spin labels

    DEFF Research Database (Denmark)

    Marsh, Derek

    2017-01-01

    -hyperfine anisotropies of isolated nitroxide spin labels. Results compatible with earlier treatments by Redfield theory are obtained without specifically evaluating matrix elements. Extension to single-transition operators for isolated nitroxides predicts electron coherence transfer by pseudosecular electron...

  13. Simultaneous Introduction of Two Nitroxides in the Reaction: A New Approach to the Synthesis of Heterospin Complexes.

    Science.gov (United States)

    Ovcharenko, Victor; Kuznetsova, Olga; Fursova, Elena; Letyagin, Gleb; Romanenko, Galina; Bogomyakov, Artem; Zueva, Ekaterina

    2017-12-04

    A new approach to the synthesis of multispin compounds has been developed, namely, the simultaneous introduction of two different stable nitroxides (nitronyl nitroxide and imino nitroxide) in a reaction with a metal ion. An important characteristic of the new method is that nitronyl nitroxide and imino nitroxide introduced in the reaction with the metal are the products of different series; i.e., the nitronyl nitroxide molecule differs from the imino nitroxide molecule not only in one additional oxygen molecule per molecule but also in another substituent in the side chain of the organic paramagnet. This possibility was demonstrated on the synthesis of multispin compounds [Ni 2 (A 1 )(L 2 ) 2 (Piv)(MeOH)], [Ni 2 (L 1 )(A 2 ) 2 (Piv)(H 2 O)], [Co 2 (A 1 )(L 2 ) 2 (Piv)(MeOH)], and [Co 3 (L 1 ) 2 (A 2 ) 2 (Piv) 2 ], in which L n and A n differ in the substituent in the phenyl ring. The number of multispin compounds that can be synthesized by the proposed method is almost unlimited. The heterospin complexes of transition metals with coordinated nitronyl nitroxide and imino nitroxide in one molecule contain energy-different exchange interaction channels that differ in both magnitude and sign, as confirmed by the quantum-chemical analysis of exchange channels in [Ni(B 1 )(B 2 ) 2 ](NO 3 ) 2 . The series of mixed-radical complexes may include compounds with nontrivial magnetic properties such as [Co 2 (A 1 )(L 2 ) 2 (Piv)(MeOH)], which experiences bulk magnetic ordering below 3.5 K.

  14. In vivo EPR oximetry using an isotopically-substituted nitroxide: Potential for quantitative measurement of tissue oxygen

    Science.gov (United States)

    Weaver, John; Burks, Scott R.; Liu, Ke Jian; Kao, Joseph P.Y.; Rosen, Gerald M.

    2017-01-01

    Variations in brain oxygen (O2) concentration can have profound effects on brain physiology. Thus, the ability to quantitate local O2 concentrations noninvasively in vivo could significantly enhance understanding of several brain pathologies. However, quantitative O2 mapping in the brain has proven difficult. The electron paramagnetic resonance (EPR) spectra of nitroxides are sensitive to molecular O2 and can be used to estimate O2 concentrations in aqueous media. We recently synthesized labile-ester-containing nitroxides, such as 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl (nitroxide 4), which accumulate in cerebral tissue after in situ hydrolysis, and thus enable spatial mapping of O2 concentrations in the mouse brain by EPR imaging. In an effort to improve O2 quantitation, we prepared 3-acetoxymethox ycarbonyl-2,2,5,5-tetra(2H3)methyl-1-(3,4,4-2H3,1-15N)pyrrolidinyloxyl (nitroxide 2), which proved to be a more sensitive probe than its normo-isotopic version for quantifying O2 in aqueous solutions of various O2 concentrations. We now demonstrate that this isotopically substituted nitroxide is ~2-fold more sensitive in vivo than the normo-isotopic nitroxide 4. Moreover, in vitro and in vivo EPR spectral-spatial imaging results with nitroxide 2 demonstrate significant improvement in resolution, reconstruction and spectral response to local O2 concentrations in cerebral tissue. Thus, isotopic-substituted nitroxides, such as 2, are excellent sensors for in vivo O2 quantitation in tissues, such as the brain. PMID:27567323

  15. Novel Profluorescent Nitroxides for Monitoring Alkyl Radical Reactions During Radiation Degradation

    International Nuclear Information System (INIS)

    George, G.

    2006-01-01

    Hindered amine stabilizers (HAS) are effective at retarding the photo-oxidative and high energy radiation degradation of PP and in certain circumstances, also thermo-oxidative degradation. The effectiveness of HAS as retarders of oxidation relies on the oxidation of the N-C bond by polymer hydroperoxide, ROOH, to form the nitroxyl group -NO which is the scavenger of polymer alkyl radicals, R. This reaction, which produces the alkoxy amine: -NO-R, must be competitive with the reaction of R with oxygen (which gives the chain-carrying peroxy radical, RO 2 ) if this stabilization mechanism is to be important in the inhibition of radiation-induced oxidative degradation of polyolefins by HAS. The rate of this reaction is high and in solution the rate coefficient is from 1 to 9x10 8 l mol - 1 s - 1. The efficient radical trapping by nitroxides has been widely employed in spin-trapping studies by electron spin resonance (esr) spectroscopy]. In addition to the hindered piperidine structure of commercial HAS, more rigid aromatic systems have been studied that are more stable to oxidative degradation and are more efficient at scavenging alkyl radicals. One such family is the iso-indoline nitroxide system, TMDBIO, shown below which, as it contains the phenanthrene fluorophore, is termed phenanthrene nitroxide. This nitroxide only becomes fluorescent when it reacts with alkyl radicals or is reduced and is termed profluorescent. TMDBIO has a vanishingly small fluorescence quantum yield (φ∼10 - 4) due to the enhanced intersystem crossing from the first excited singlet state to the ground state due to electron exchange interactions of the nitroxyl radical. When the nitroxide traps an alkyl radical, R, the resulting alkoxy amine is fluorescent (φ∼10 - 1) and the emission intensity is a measure of the number of reactions that have occurred. This property may be exploited by using quantitative fluorescence spectroscopy to follow the reaction of the nitroxide with alkyl radicals

  16. Clearance and Biodistribution of Liposomally Encapsulated Nitroxides: A Model for Targeted Delivery of Electron Paramagnetic Resonance Imaging Probes to Tumors

    Science.gov (United States)

    Burks, Scott R.; Legenzov, Eric A.; Rosen, Gerald M.

    2011-01-01

    Electron paramagnetic resonance (EPR) imaging using nitroxides as molecular probes is potentially a powerful tool for the detection and physiological characterization of micrometastatic lesions. Encapsulating nitroxides in anti-HER2 immunoliposomes at high concentrations to take advantage of the “self-quenching” phenomenon of nitroxides allows generation of robust EPR signals in HER2-overexpressing breast tumor cells with minimal background from indifferent tissues or circulating liposomes. We investigated the in vivo pharmacological properties of nitroxides encapsulated in sterically stabilized liposomes designed for long circulation times. We show that circulation times of nitroxides can be extended from hours to days; this increases the proportion of liposomes in circulation to enhance tumor targeting. Furthermore, nitroxides encapsulated in sterically stabilized anti-HER2 immunoliposomes can be delivered to HER2-overexpressing tumors at micromolar concentrations, which should be imageable by EPR. Lastly, after in vivo administration, liposomally encapsulated nitroxide signal also appears in the liver, spleen, and kidneys. Although these organs are spatially distinct and would not hinder tumor imaging in our model, understanding nitroxide signal retention in these organs is essential for further improvements in EPR imaging contrast between tumors and other tissues. These results lay the foundation to use liposomally delivered nitroxides and EPR imaging to visualize tumor cells in vivo. PMID:21737567

  17. Cisplatin upregulates mitochondrial nitric oxide synthase and peroxynitrite formation to promote renal injury

    International Nuclear Information System (INIS)

    Jung, Michaela; Hotter, Georgina; Vinas, Jose Luis; Sola, Anna

    2009-01-01

    The mitochondria are a critical target for cisplatin-associated nephrotoxicity. Though nitric oxide formation has been implicated in the toxicity of cisplatin, this formation has not so far been related to a possible activation of mitochondrial nitric oxide synthase (mNOS). We show here that the upregulation of oxide mNOS and peroxynitrite formation in cisplatin treatment are key events that influence the development of the harmful parameters described in cisplatin-associated kidney failure. We confirm this by isolating the mitochondrial fraction of the kidney and across different access routes such as the use of a specific inhibitor of neuronal NOS, L-NPA, a peroxynitrite scavenger, FeTMPyP, and a peroxynitrite donor, SIN-1. The in vitro studies corroborated the information obtained in the in vivo experiments. The administration of cisplatin reveals a clear upregulation in the transcription of neuronal NOS and an increase in the levels of nitrites in the mitochondrial fractions of the kidneys. The upregulated transcription directly affects the cytoskeleton structure and the apoptosis. The inhibition of neuronal NOS reduces the levels of nitrites, cell death, and cytoskeleton derangement. Peroxynitrite is involved in the mechanism promoting the NOS transcription. In addition, in controls SIN-1 imitates the effects of cisplatin. In summary, we demonstrate that upregulation of mNOS in cisplatin treatment is a key component in both the initiation and the spread of cisplatin-associated damage in the kidney. Furthermore, peroxynitrite formation is directly involved in this process

  18. Edaravone, a potent free radical scavenger, reacts with peroxynitrite to produce predominantly 4-NO-edaravone.

    Science.gov (United States)

    Fujisawa, Akio; Yamamoto, Yorihiro

    2016-05-01

    3-Methyl-1-phenyl-2-pyrazolin-5-one (edaravone) is used in clinical treatment of acute brain infarction to rescue the penumbra, based on its ability to prevent lipid peroxidation by scavenging lipid peroxyl radicals. Here, we show that edaravone also reacts with peroxynitrite to yield 4-NO-edaravone as the major product and 4-NO2-edaravone as a minor product. We observed little formation of 3-methyl-1-phenyl-2-pyrazolin-4,5-dione (4-oxoedaravone) and its hydrate, 2-oxo-3-(phenylhydrazono)butanoic acid, which are the major free radical-induced oxidation products of edaravone, suggesting that free radicals are not involved in the reaction with peroxynitrite. The reaction of peroxynitrite with edaravone is approximately 30-fold greater than with uric acid, a physiological peroxynitrite scavenger (reaction rate k = 1.5 × 10 (4)  M(-1) s(-1) vs. 480 M(-1) s(-1)). These results suggest that edaravone functions therapeutically as a scavenger of peroxynitrite as well as lipid peroxyl radicals, which is consistent with a report that edaravone treatment reduced levels of 3-nitrotyrosine in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

  19. Nitroxide-catalyzed selective oxidation of alcohols and polysaccharides

    International Nuclear Information System (INIS)

    Ponedel'kina, I Yu; Khaibrakhmanova, E A; Odinokov, Viktor N

    2010-01-01

    The use of nitroxide radicals in the selective oxidation of alcohols is considered. Attention is focused on the oxidation of polysaccharides as a method of preparation of polyuronic acids, aldehydes and hemiacetals.

  20. Nitrite-reductase and peroxynitrite isomerization activities of Methanosarcina acetivorans protoglobin.

    Directory of Open Access Journals (Sweden)

    Paolo Ascenzi

    Full Text Available Within the globin superfamily, protoglobins (Pgb belong phylogenetically to the same cluster of two-domain globin-coupled sensors and single-domain sensor globins. Multiple functional roles have been postulated for Methanosarcina acetivorans Pgb (Ma-Pgb, since the detoxification of reactive nitrogen and oxygen species might co-exist with enzymatic activity(ies to facilitate the conversion of CO to methane. Here, the nitrite-reductase and peroxynitrite isomerization activities of the CysE20Ser mutant of Ma-Pgb (Ma-Pgb* are reported and analyzed in parallel with those of related heme-proteins. Kinetics of nitrite-reductase activity of ferrous Ma-Pgb* (Ma-Pgb*-Fe(II is biphasic and values of the second-order rate constant for the reduction of NO2- to NO and the concomitant formation of nitrosylated Ma-Pgb*-Fe(II (Ma-Pgb*-Fe(II-NO are k(app1= 9.6 ± 0.2 M(-1 s(-1 and k(app2 = 1.2 ± 0.1 M(-1 s(-1 (at pH 7.4 and 20 °C. The k(app1 and k(app2 values increase by about one order of magnitude for each pH unit decrease, between pH 8.3 and 6.2, indicating that the reaction requires one proton. On the other hand, kinetics of peroxynitrite isomerization catalyzed by ferric Ma-Pgb* (Ma-Pgb*-Fe(III is monophasic and values of the second order rate constant for peroxynitrite isomerization by Ma-Pgb*-Fe(III and of the first order rate constant for the spontaneous conversion of peroxynitrite to nitrate are h(app = 3.8 × 10(4 M(-1 s(-1 and h0 = 2.8 × 10(-1 s(-1 (at pH 7.4 and 20 °C. The pH-dependence of hon and h0 values reflects the acid-base equilibrium of peroxynitrite (pKa = 6.7 and 6.9, respectively; at 20 °C, indicating that HOONO is the species that reacts preferentially with the heme-Fe(III atom. These results highlight the potential role of Pgbs in the biosynthesis and scavenging of reactive nitrogen and oxygen species.

  1. Metabolic Memory Phenomenon and Accumulation of Peroxynitrite in Retinal Capillaries

    Directory of Open Access Journals (Sweden)

    Renu A. Kowluru

    2007-01-01

    Full Text Available Aim. Diabetic retinopathy resists reversal after good glycemic control (GC is reinitiated, and preexisting damage at the time of intervention is considered as the major factor in determining the outcome of the GC. This study is to investigate the role of peroxynitrite accumulation in the retinal capillaries in the failure of retinopathy to reverse after reestablishment of GC, and to determine the effect of this reversal on the activity of the enzyme responsible for scavenging mitochondrial superoxide, MnSOD. Methods. In streptozotocin-diabetic rats, 6 months of poor glycemic control (PC, glycated hemoglobin, GHb>12.0% was followed by 6 additional months of GC (GHb about 6%. The trypsin-digested retinal microvessels were prepared for immunostaining of nitrotyrosine (a measure of peroxynitrite and for counting the number of acellular capillaries (a measure of histopathology. The retina from the other eye was used to quantify nitrotyrosine concentration, MnSOD activity and the total antioxidant capacity. Results. Reversal of hyperglycemia after 6 months of PC had no significant effect on nitrotyrosine concentration in the retina, on the nitrotyrosine-positive retinal capillary cells and on the number of acellular capillaries; the values were similar in PC-GC and PC groups. In the same rats retinal MnSOD activity remained inhibited and the total antioxidant capacity was subnormal 6 months after cessation of PC. Conclusions. Peroxynitrite accumulation in the retinal microvasculature, the site of histopathology, fails to normalize after reversal of hyperglycemia, and superoxide remains inadequately scavenged. This failure of reversal of peroxynitrite accumulation could be, in part, responsible for the resistance of diabetic retinopathy to reverse after termination of PC.

  2. Nitroxide radicals formed in situ as polymer chain growth regulators

    International Nuclear Information System (INIS)

    Kolyakina, Elena V; Grishin, Dmitry F

    2009-01-01

    Published data on controlled synthesis of macromolecules using nitroxide radicals, formed in situ during polymerization, as polymer chain growth regulators are systematized and generalized. The attention is focused on the mechanism of polymer chain growth control during reversibly inhibited radical homopolymerization and the effect of structure of precursors and regulating additives on the polymerization kinetics of monomers of different nature and the molecular-mass characteristics of the polymers thus formed. The key methods for generation of nitroxide radicals directly during polymerization are considered. The prospects for development and practical use of these approaches for the synthesis of new polymeric materials are evaluated.

  3. Development of nitroxide radicals–containing polymer for scavenging reactive oxygen species from cigarette smoke

    International Nuclear Information System (INIS)

    Yoshitomi, Toru; Kuramochi, Kazuhiro; Binh Vong, Long; Nagasaki, Yukio

    2014-01-01

    We developed a nitroxide radicals–containing polymer (NRP), which is composed of poly(4-methylstyrene) possessing nitroxide radicals as a side chain via amine linkage, to scavenge reactive oxygen species (ROS) from cigarette smoke. In this study, the NRP was coated onto cigarette filters and its ROS-scavenging activity from streaming cigarette smoke was evaluated. The intensity of electron spin resonance signals of the NRP in the filter decreased after exposure to cigarette smoke, indicating consumption of nitroxide radicals. To evaluate the ROS-scavenging activity of the NRP-coated filter, the amount of peroxy radicals in an extract of cigarette smoke was measured using UV–visible spectrophotometry and 1,1-diphenyl-2-picrylhydrazyl (DPPH). The absorbance of DPPH at 517 nm decreased with exposure to cigarette smoke. When NRP-coated filters were used, the decrease in the absorbance of DPPH was prevented. In contrast, both poly[4-(cyclohexylamino)methylstyrene]- and poly(acrylic acid)-coated filters, which have no nitroxide radical, did not show any effect, indicating that the nitroxide radicals in the NRP scavenge the ROS in cigarette smoke. As a result, the extract of cigarette smoke passed through the NRP-coated filter has a lower cellular toxicity than smoke passed through poly[4-(cyclohexylamino)methylstyrene]- and poly(acrylic acid)-coated filters. Accordingly, NRP is a promising material for ROS scavenging from cigarette smoke. (papers)

  4. Effect of lycopene and β-carotene on peroxynitrite-mediated cellular modifications

    International Nuclear Information System (INIS)

    Muzandu, Kaampwe; Ishizuka, Mayumi; Sakamoto, Kentaro Q.; Shaban, Zein; El Bohi, Khlood; Kazusaka, Akio; Fujita, Shoichi

    2006-01-01

    Peroxynitrite formed by the reaction of superoxide and nitric oxide is a highly reactive species with a role in various pathological processes such as cancer, chronic inflammation, and cardiovascular and neurological diseases. In the present study, the effect of the carotenoids, lycopene and β-carotene, on peroxynitrite-mediated modifications in plasmid DNA as well as cellular DNA and proteins were investigated. In pUC18 plasmid DNA, these carotenoids strongly inhibited DNA strand breaks caused by peroxynitrite generated from 3-morpholinosydnonimine (SIN-1). SIN-1 was also used to determine effects on DNA damage and protein tyrosine nitration in Chinese hamster lung fibroblasts. SIN-1 dose-dependently increased nitration of proteins in cells above basal levels as determined by Western blotting. This nitration was inhibited in the presence of the uric acid as well as lycopene. Physiological concentrations (0.31-10 μM) of lycopene and β-carotene also had protective effects on DNA damage, as measured by the comet assay. Lycopene significantly reduced DNA damage particularly, in the median range of concentrations (2.5 μM). The protective effects of lycopene and β-carotene could be due to their scavenging of reactive oxygen (ROS) and/or nitrogen species (RNS) as they reduce the amount of intracellular ROS/RNS produced following treatment with SIN-1 by as much as 47.5% and 42.4%, respectively. The results obtained in this study suggest that carotenoids may alleviate some of the deleterious effects of peroxynitrite and possibly other reactive nitrogen species as well in vivo

  5. Peroxynitrite decomposition catalyst prevents apoptotic cell death in a human astrocytoma cell line incubated with supernatants of HIV-infected macrophages

    Directory of Open Access Journals (Sweden)

    Perno Carlo

    2002-09-01

    Full Text Available Abstract Background Oxidative stress has shown to contribute in the mechanisms underlying apoptotic cell death occuring in AIDS-dementia complex. Here we investigated the role of peroxynitrite in apoptosis occurring in astroglial cells incubated with supernatants of HIV-infected human primary macrophages (M/M. Results Flow cytometric analysis (FACS of human cultured astrocytes shortly incubated with HIV-1-infected M/M supernatants showed apoptotic cell death, an effect accompanied by pronounced staining for nitrotyrosine (footprint of peroxynitrite and by abnormal formation of malondialdehyde (MDA. Pretreatment of astrocytes with the peroxynitrite decomposition catalyst FeTMPS antagonized HIV-related astrocytic apoptosis, MDA formation and nitrotyrosine staining. Conclusions Taken together, our results suggest that inibition of peroxynitrite leads to protection against peroxidative stress accompanying HIV-related apoptosis of astrocytes. Overall results support the role of peroxynitrite in HIV-related programmed death of astrocytes and suggest the use of peroxynitrite decomposition catalyst to counteract HIV-1-related neurological disorders.

  6. Carbon dots prepared from citric acid and urea as fluorescent probes for hypochlorite and peroxynitrite

    International Nuclear Information System (INIS)

    Simões, Eliana F. C.; Leitão, João M. M.; Esteves da Silva, Joaquim C. G.

    2016-01-01

    Carbon dots (CDs) were prepared from citric acid and urea, and their fluorescence was found to be quenched by hypochlorite and peroxynitrite. Microwave based synthesis gives CDs with excitation/emission wavelength-dependent quantum yields (8 % at 400/520 nm; 10 % at 360/451 nm; 12 % at 350/420 nm). Quenching of fluorescence depends on pH values, and response is most selective and sensitive to hypochlorite at pH 4, and to peroxynitrite at pH 9. The lower detection limits are 0.5 and 1.5 μM, respectively. The method was successfully applied to quantify hypochlorite and peroxynitrite in standard solutions and in spiked dilute serum samples. (author)

  7. Prevention of dopaminergic neurotoxicity by targeting nitric oxide and peroxynitrite: implications for the prevention of methamphetamine-induced neurotoxic damage.

    Science.gov (United States)

    Imam, S Z; Islam, F; Itzhak, Y; Slikker, W; Ali, S F

    2000-09-01

    Methamphetamine (METH) is a neurotoxic psychostimulant that produces catecholaminergic brain damage by producing oxidative stress and free radical generation. The role of oxygen and nitrogen radicals is well documented as a cause of METH-induced neurotoxic damage. In this study, we have obtained evidence that METH-induced neurotoxicity is the resultant of interaction between oxygen and nitrogen radicals, and it is mediated by the production of peroxynitrite. We have also assessed the effects of inhibitors of neuronal nitric oxide synthase (nNOS) as well as scavenger of nitric oxide and a peroxynitrite decomposition catalyst. Significant protective effects were observed with the inhibitor of nNOS, 7-nitroindazole (7-NI), as well as by the selective peroxynitrite scavenger or decomposition catalyst, 5,10,15,20-tetrakis(2,4,6-trimethyl-3,5-sulfonatophenyl)porphyrinato iron III (FeTPPS). However, the use of a nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), did not provide any significant protection against METH-induced hyperthermia or peroxynitrite generation and the resulting dopaminergic neurotoxicity. In particular, treatment with FeTPPS completely prevented METH-induced hyperthermia, peroxynitrite production, and METH-induced dopaminergic depletion. Together, these data demonstrate that METH-induced dopaminergic neurotoxicity is mediated by the generation of peroxynitrite, which can be selectively protected by nNOS inhibitors or peroxynitrite scavenger or decomposition catalysts.

  8. Spin labelling of human erythrocytes with nitroxide radicals

    International Nuclear Information System (INIS)

    Chagalj, C.; DePaoli, T.C.P.; Hager, A.A.; Palaoro, L.A.; Rubin de Celis, E.; Farach, H.A.; Poole, C.P. jr

    1984-01-01

    Human erythrocytes were labelled with nitroxide, the spin label SYNVAR 101, under various experimantal conditions. A study was made of the influence of antireductants on the labelling efficiency and the kinetics of the radical decay during the labelling process

  9. Nitroxide radicals as contrast substances for magnetic resonance imaging diagnostics. Part 1

    International Nuclear Information System (INIS)

    Zhelev, Z.

    2016-01-01

    In last ten years, there is a significant progress in the selective and localized detection of redox-active compounds in the cells, tissues, and intact organisms. This progress is due to the development of new synthetic and genetically encoded redox-sensitive contrast substances, as well as due to the improvement of the techniques for their imaging: fluorescent, chemiluminescent, magnetic resonance, nuclear, ultrasonic. One of the most attractive redox-sensitive contrast substances are cyclic (stable) nitroxide radicals. They can be visualized and analyzed in vitro and in vivo by a variety of magnetic resonance techniques - electron-paramagnetic resonance imaging (EPRI), magnetic resonance imaging (MRI), Overhauser-enhanced MRI (OMRI). This review describes the merits and demerits of the nitroxide-enhanced EPR and MRI and the perspectives for their application in biomedical studies and clinical practice. The article is intended for a wide range of readers - from students to specialists in the field. Key words: Magnetic Resonance Imaging (MRI). Electron-Paramagnetic Resonance (EPR). Overhauser-Enhanced MRI (O MRI). Nitroxide

  10. Hypoxia-induced dysfunction of rat diaphragm: role of peroxynitrite.

    NARCIS (Netherlands)

    Zhu, X.; Heunks, L.M.A.; Versteeg, E.M.M.; Heijden, E. van der; Ennen, L.; Kuppevelt, A.H.M.S.M. van; Vina, J.; Dekhuijzen, P.N.R.

    2005-01-01

    Oxidants may play a role in hypoxia-induced respiratory muscle dysfunction. In the present study we hypothesized that hypoxia-induced impairment in diaphragm contractility is associated with elevated peroxynitrite generation. In addition, we hypothesized that strenuous contractility of the diaphragm

  11. Nitroxide radicals as research tools: Elucidating the kinetics and mechanisms of catalase-like and "suicide inactivation" of metmyoglobin.

    Science.gov (United States)

    Samuni, Uri; Czapski, Gideon; Goldstein, Sara

    2016-07-01

    Metmyoglobin (MbFe(III)) reaction with H(2)O(2) has been a subject of study over many years. H(2)O(2) alone promotes heme destruction frequently denoted "suicide inactivation," yet the mechanism underlying H(2)O(2) dismutation associated with MbFe(III) inactivation remains obscure. MbFe(III) reaction with excess H(2)O(2) in the absence and presence of the nitroxide was studied at pH 5.3-8.1 and 25°C by direct determination of reaction rate constants using rapid-mixing stopped-flow technique, by following H(2)O(2) depletion, O(2) evolution, spectral changes of the heme protein, and the fate of the nitroxide by EPR spectroscopy. The rates of both H(2)O(2) dismutation and heme inactivation processes depend on [MbFe(III)], [H(2)O(2)] and pH. Yet the inactivation stoichiometry is independent of these variables and each MbFe(III) molecule catalyzes the dismutation of 50±10 H(2)O(2) molecules until it is inactivated. The nitroxide catalytically enhances the catalase-like activity of MbFe(III) while protecting the heme against inactivation. The rate-determining step in the absence and presence of the nitroxide is the reduction of MbFe(IV)O by H(2)O(2) and by nitroxide, respectively. The nitroxide effects on H(2)O(2) dismutation catalyzed by MbFe(III) demonstrate that MbFe(IV)O reduction by H(2)O(2) is the rate-determining step of this process. The proposed mechanism, which adequately fits the pro-catalytic and protective effects of the nitroxide, implies the intermediacy of a compound I-H(2)O(2) adduct, which decomposes to a MbFe(IV)O and an inactivated heme at a ratio of 25:1. The effects of nitroxides are instrumental in elucidating the mechanism underlying the catalysis and inactivation routes of heme proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Polyphenols and Red Wine as Antioxidants against Peroxynitrite and other Oxidants

    Directory of Open Access Journals (Sweden)

    LAURA B VALDEZ

    2004-01-01

    Full Text Available The antioxidant capacity of polyphenols (+-catechin, (--epicatechin and myricetin, and of different types of red wines (Cabernet Sauvignon, Malbec and blended wine was evaluated by three assays. (a NADH oxidation by peroxynitrite (ONOO-: the ONOO- scavenging activity was higher for myricetin (IC50=35 µM than for (+-catechin (IC50=275 µM and (--epicatechin (IC50=313 µM. (b Peroxynitrite initiated chemiluminescence in rat liver homogenate: (--epicatechin (IC50=7.0 µM and (+-catechin (IC50=13 µM were more potent than myricetin (IC50=20 µM in inhibiting the chemiluminescence signal. (c Lucigenin chemiluminescence in aortic rings: (--epicatechin (IC50=15 µM and (+-catechin (IC50=18 µM showed higher antioxidant capacity than myricetin (IC50=32 µM. All the assayed red wines were able to scavenge the oxidants and free radical species that generate the signal in each assay. Cabernet Sauvignon was the red wine with the highest antioxidant capacity in comparison with Malbec and blended wine. It is concluded that the use of sensitive biological systems (as the aortic ring chemiluminescence provides important information in addition to the results from chemical (NADH oxidation by peroxynitrite and biochemical (homogenate chemiluminescence assays and offers advances in the physiological role of polyphenols

  13. Advances in the synthesis of nitroxide radicals for use in biomolecule spin labelling.

    Science.gov (United States)

    Haugland, Marius M; Lovett, Janet E; Anderson, Edward A

    2018-02-05

    EPR spectroscopy is an increasingly useful analytical tool to probe biomolecule structure, dynamic behaviour, and interactions. Nitroxide radicals are the most commonly used radical probe in EPR experiments, and many methods have been developed for their synthesis, as well as incorporation into biomolecules using site-directed spin labelling. In this Tutorial Review, we discuss the most practical methods for the synthesis of nitroxides, focusing on the tunability of their structures, the manipulation of their sidechains into spin labelling handles, and their installation into biomolecules.

  14. Peroxynitrite mediates muscle insulin resistance in mice via nitration of IRβ/IRS-1 and Akt

    International Nuclear Information System (INIS)

    Zhou Jun; Huang Kaixun

    2009-01-01

    Accumulating evidence suggests that peroxynitrite (ONOO - ) is involved in the pathogenesis of insulin resistance. In the current study, we investigated whether insulin resistance in vivo could be mediated by nitration of proteins involved in the early steps of the insulin signal transduction pathway. Exogenous peroxynitrite donated by 3-morpholinosydnonimine hydrochloride (SIN-1) induced in vivo nitration of the insulin receptor β subunit (IRβ), insulin receptor substrate (IRS)-1, and protein kinase B/Akt (Akt) in skeletal muscle of mice and dramatically reduced whole-body insulin sensitivity and muscle insulin signaling. Moreover, in high-fat diet (HFD)-fed insulin-resistant mice, we observed enhanced nitration of IRβ and IRS-1 in skeletal muscle, in parallel with impaired whole-body insulin sensitivity and muscle insulin signaling. Reversal of nitration of these proteins by treatment with the peroxynitrite decomposition catalyst FeTPPS yielded an improvement in whole-body insulin sensitivity and muscle insulin signaling in HFD-fed mice. Taken together, these findings provide new mechanistic insights for the involvement of peroxynitrite in the development of insulin resistance and suggest that nitration of proteins involved in the early steps of insulin signal transduction is a novel molecular mechanism of HFD-induced muscle insulin resistance.

  15. A study of the conformation and stability of nitroxide free radicals

    International Nuclear Information System (INIS)

    Briere, R.

    1969-03-01

    The first part of this study is an application of nuclear magnetic resonance to the determination of the sign and magnitude of the long range nuclear-electron spin-spin couplings in the free radical nitroxide derived from piperidine. It has been shown that the coupling constants of the protons γ to the nitrogen atom have a pronounced spatial dependence as do the protons in the β position, a point which has not been brought out by previous investigations. Conformational analysis of these compounds has been carried out by measurement of the effect of temperature on the NMR spectra at 310 MHz. The synthesis of di-t-Bu nitroxide labelled with C 13 in the α-position made possible the unambiguous determination of the corresponding 13 C nuclear-electron spin-spin coupling constant, a parameter which had not previously been measured. The coupling constants measured in the 2,2,6,6-tetramethyl piperidine series could then be attributed to the 13 C atoms in the β-position and their variation related to the conformations of the heterocycles. This constitutes the second part of the work reported here. The final section is devoted to a study of the decomposition of an unstable nitroxide having a hydrogen atom in the p-position. This decomposition is bimolecular and the primary isotope effect shows that the rupture. of the C-H bond is involved. From this one can conclude that a nitroxide is stable when the different groups attached to the nitrogen atom cannot give rise to a decomposition either intra molecularly, if the molecular geometry is suitable, or inter molecularly by dimerisation through attack on a different center of a neighbouring molecule thus leading to a fragmentation or a disproportionation. (author) [fr

  16. A rigid disulfide-linked nitroxide side chain simplifies the quantitative analysis of PRE data

    Energy Technology Data Exchange (ETDEWEB)

    Fawzi, Nicolas L. [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Fleissner, Mark R. [University of California, Jules Stein Eye Institute and Department of Chemistry and Biochemistry (United States); Anthis, Nicholas J. [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Kalai, Tamas; Hideg, Kalman [University of Pecs, Institute of Organic and Medicinal Chemistry (Hungary); Hubbell, Wayne L., E-mail: hubbellw@jsei.ucla.edu [University of California, Jules Stein Eye Institute and Department of Chemistry and Biochemistry (United States); Clore, G. Marius, E-mail: mariusc@mail.nih.gov [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)

    2011-09-15

    The measurement of {sup 1}H transverse paramagnetic relaxation enhancement (PRE) has been used in biomolecular systems to determine long-range distance restraints and to visualize sparsely-populated transient states. The intrinsic flexibility of most nitroxide and metal-chelating paramagnetic spin-labels, however, complicates the quantitative interpretation of PREs due to delocalization of the paramagnetic center. Here, we present a novel, disulfide-linked nitroxide spin label, R1p, as an alternative to these flexible labels for PRE studies. When introduced at solvent-exposed {alpha}-helical positions in two model proteins, calmodulin (CaM) and T4 lysozyme (T4L), EPR measurements show that the R1p side chain exhibits dramatically reduced internal motion compared to the commonly used R1 spin label (generated by reacting cysteine with the spin labeling compound often referred to as MTSL). Further, only a single nitroxide position is necessary to account for the PREs arising from CaM S17R1p, while an ensemble comprising multiple conformations is necessary for those observed for CaM S17R1. Together, these observations suggest that the nitroxide adopts a single, fixed position when R1p is placed at solvent-exposed {alpha}-helical positions, greatly simplifying the interpretation of PRE data by removing the need to account for the intrinsic flexibility of the spin label.

  17. A rigid disulfide-linked nitroxide side chain simplifies the quantitative analysis of PRE data

    International Nuclear Information System (INIS)

    Fawzi, Nicolas L.; Fleissner, Mark R.; Anthis, Nicholas J.; Kálai, Tamás; Hideg, Kálmán; Hubbell, Wayne L.; Clore, G. Marius

    2011-01-01

    The measurement of 1 H transverse paramagnetic relaxation enhancement (PRE) has been used in biomolecular systems to determine long-range distance restraints and to visualize sparsely-populated transient states. The intrinsic flexibility of most nitroxide and metal-chelating paramagnetic spin-labels, however, complicates the quantitative interpretation of PREs due to delocalization of the paramagnetic center. Here, we present a novel, disulfide-linked nitroxide spin label, R1p, as an alternative to these flexible labels for PRE studies. When introduced at solvent-exposed α-helical positions in two model proteins, calmodulin (CaM) and T4 lysozyme (T4L), EPR measurements show that the R1p side chain exhibits dramatically reduced internal motion compared to the commonly used R1 spin label (generated by reacting cysteine with the spin labeling compound often referred to as MTSL). Further, only a single nitroxide position is necessary to account for the PREs arising from CaM S17R1p, while an ensemble comprising multiple conformations is necessary for those observed for CaM S17R1. Together, these observations suggest that the nitroxide adopts a single, fixed position when R1p is placed at solvent-exposed α-helical positions, greatly simplifying the interpretation of PRE data by removing the need to account for the intrinsic flexibility of the spin label.

  18. A peroxynitrite complex of copper: formation from a copper-nitrosyl complex, transformation to nitrite and exogenous phenol oxidative coupling or nitration.

    Science.gov (United States)

    Park, Ga Young; Deepalatha, Subramanian; Puiu, Simona C; Lee, Dong-Heon; Mondal, Biplab; Narducci Sarjeant, Amy A; del Rio, Diego; Pau, Monita Y M; Solomon, Edward I; Karlin, Kenneth D

    2009-11-01

    Reaction of nitrogen monoxide with a copper(I) complex possessing a tridentate alkylamine ligand gives a Cu(I)-(*NO) adduct, which when exposed to dioxygen generates a peroxynitrite (O=NOO(-))-Cu(II) species. This undergoes thermal transformation to produce a copper(II) nitrito (NO(2) (-)) complex and 0.5 mol equiv O(2). In the presence of a substituted phenol, the peroxynitrite complex effects oxidative coupling, whereas addition of chloride ion to dissociate the peroxynitrite moiety instead leads to phenol ortho nitration. Discussions include the structures (including electronic description) of the copper-nitrosyl and copper-peroxynitrite complexes and the formation of the latter, based on density functional theory calculations and accompanying spectroscopic data.

  19. Relationships between nitric oxide, nitroxyl ion, nitrosonium cation and peroxynitrite.

    Science.gov (United States)

    Hughes, M N

    1999-05-05

    This review is concerned mainly with the three redox-related, but chemically distinct, species NO-, NO. and NO+, with greatest emphasis being placed on the chemistry and biology of the nitroxyl ion. Biochemical routes for the formation of nitroxyl ion and methods for showing the intermediacy of this species are discussed, together with chemical methods for generating nitroxyl ion in solution. Reactions of nitroxyl ion with NO., thiols, iron centres in haem and with dioxygen are reviewed The significance of the reaction between NO- and dioxygen as a source of peroxynitrite is assessed, and attention drawn to the possible significance of the spin state of the nitroxyl ion in this context. The biological significance of nitrosation and the importance of S-nitrosothiols and certain metal nitrosyl complexes as carriers of NO+ at physiological pH is stressed. Some features in the chemistry of peroxynitrite are noted.

  20. Inhibition of peroxynitrite-mediated DNA strand cleavage and hydroxyl radical formation by aspirin at pharmacologically relevant concentrations: Implications for cancer intervention

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wei [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035 (China); Department of Food Science and Technology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Zhu, Hong; Jia, Zhenquan [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); Li, Jianrong [College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035 (China); Misra, Hara P. [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); Zhou, Kequan, E-mail: kzhou@wayne.edu [Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202 (United States); Li, Yunbo, E-mail: yli@vcom.vt.edu [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States)

    2009-12-04

    Epidemiological studies have suggested that the long-term use of aspirin is associated with a decreased incidence of human malignancies, especially colorectal cancer. Since accumulating evidence indicates that peroxynitrite is critically involved in multistage carcinogenesis, this study was undertaken to investigate the ability of aspirin to inhibit peroxynitrite-mediated DNA damage. Peroxynitrite and its generator 3-morpholinosydnonimine (SIN-1) were used to cause DNA strand breaks in {phi}X-174 plasmid DNA. We demonstrated that the presence of aspirin at concentrations (0.25-2 mM) compatible with amounts in plasma during chronic anti-inflammatory therapy resulted in a significant inhibition of DNA cleavage induced by both peroxynitrite and SIN-1. Moreover, the consumption of oxygen caused by 250 {mu}M SIN-1 was found to be decreased in the presence of aspirin, indicating that aspirin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy using 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap demonstrated the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from authentic peroxynitrite, and that aspirin at 0.25-2 mM potently diminished the radical adduct formation in a concentration-dependent manner. Taken together, these results demonstrate for the first time that aspirin at pharmacologically relevant concentrations can inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. These results may have implications for cancer intervention by aspirin.

  1. Inhibition of peroxynitrite-mediated DNA strand cleavage and hydroxyl radical formation by aspirin at pharmacologically relevant concentrations: Implications for cancer intervention

    International Nuclear Information System (INIS)

    Chen, Wei; Zhu, Hong; Jia, Zhenquan; Li, Jianrong; Misra, Hara P.; Zhou, Kequan; Li, Yunbo

    2009-01-01

    Epidemiological studies have suggested that the long-term use of aspirin is associated with a decreased incidence of human malignancies, especially colorectal cancer. Since accumulating evidence indicates that peroxynitrite is critically involved in multistage carcinogenesis, this study was undertaken to investigate the ability of aspirin to inhibit peroxynitrite-mediated DNA damage. Peroxynitrite and its generator 3-morpholinosydnonimine (SIN-1) were used to cause DNA strand breaks in φX-174 plasmid DNA. We demonstrated that the presence of aspirin at concentrations (0.25-2 mM) compatible with amounts in plasma during chronic anti-inflammatory therapy resulted in a significant inhibition of DNA cleavage induced by both peroxynitrite and SIN-1. Moreover, the consumption of oxygen caused by 250 μM SIN-1 was found to be decreased in the presence of aspirin, indicating that aspirin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy using 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap demonstrated the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from authentic peroxynitrite, and that aspirin at 0.25-2 mM potently diminished the radical adduct formation in a concentration-dependent manner. Taken together, these results demonstrate for the first time that aspirin at pharmacologically relevant concentrations can inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. These results may have implications for cancer intervention by aspirin.

  2. Reactions of nitroxide radicals in aqueous solutions exposed to non-thermal plasma: limitations of spin trapping of the plasma induced species

    Science.gov (United States)

    Gorbanev, Yury; Stehling, Nicola; O'Connell, Deborah; Chechik, Victor

    2016-10-01

    Low temperature (‘cold’) atmospheric pressure plasmas have gained much attention in recent years due to their biomedical effects achieved through the interactions of plasma-induced species with the biological substrate. Monitoring of the radical species in an aqueous biological milieu is usually performed via electron paramagnetic resonance (EPR) spectroscopy using various nitrone spin traps, which form persistent radical adducts with the short-lived radicals. However, the stability of these nitroxide radical adducts in the plasma-specific environment is not well known. In this work, chemical transformations of nitroxide radicals in aqueous solutions using a model nitroxide 4-oxo-TEMPO were studied using EPR and LC-MS. The kinetics of the nitroxide decay when the solution was exposed to plasma were assessed, and the reactive pathways proposed. The use of different scavengers enabled identification of the types of reactive species which cause the decay, indicating the predominant nitroxide group reduction in oxygen-free plasmas. The 2H adduct of the PBN spin trap (PBN-D) was shown to decay similarly to the model molecule 4-oxo-TEMPO. The decay of the spin adducts in plasma-treated solutions must be considered to avoid rendering the spin trapping results unreliable. In particular, the selectivity of the decay indicated the limitations of the PTIO/PTI nitroxide system in the detection of nitric oxide.

  3. E. P. R. spectroscopic study of nitroxide mono- and bi-radicals

    International Nuclear Information System (INIS)

    Lemaire, H.

    1966-09-01

    A nitroxide is a molecule containing the group N-O where the oxygen atom made only one bond instead of the usual two. The main advantage of these radicals is their exceptional stability; this allows the study of well defined chemical structures while varying at will the experimental conditions. Studies by electron paramagnetic resonance of nitroxide mono-radicals have given the principal directions and the principal values of the electron-nitrogen nucleus hyperfine tensor and of the anisotropic g-factor tensor. The results were then related to the electronic structure of radicals. An understanding was obtained of the influence of the solvent on the principal values of the tensors, and the marked differences observed in the broadening of hyperfine lines when the medium become viscous. In the nitroxide biradicals, the hyperfine spectra depends not only on the magnetic interactions relative to each monomer, but also on the magnitude of the exchange interaction between the singlet and the triplet states of the dimer; the biradicals studied here are the first organic compounds which show clearly the influence of this exchange on the hyperfine structure. The two unpaired electrons also interact by a magnetic dipolar interaction: in the intermediate case, this can be used to derive the sign of the exchange interaction if the bi-radical is studied in a liquid crystal. Just as for mono-radicals, the hyperfine spectra of bi-radicals show selective broadening in viscous media, which is caused by an overall motional modulation of the anisotropic tensors. This gives another way to determine the sign of the exchange interaction. (author) [fr

  4. Preparation and physico-chemical study of nitroxide radicals. Isotopic marking with carbon 13 and deuterium

    International Nuclear Information System (INIS)

    Chapelet-Letourneux, G.

    1969-01-01

    N-t-butyl-N-phenyl nitroxide is obtained by: a) action of t-butyl-magnesium chloride on nitrobenzene, or of phenyl-magnesium bromide on nitro-t-butane, b) oxidation of N-t-butyl-N-phenylhydroxylamine, c) oxidation of N-t-butylaniline. In these latter two cases, it has been possible to isolate the pure radical and to study it using UV, IR and EPR. It decomposes to give N-t-butylaniline and the N-oxide of N-t-butyl-p-quinon-imine. The action of peracids such as p-nitro-perbenzoic or m-chloro-perbenzoic acids on amines or hydroxylamines leads to the formation of stable or unstable nitroxide radicals easily observable by EPR. Finally, with a view to obtaining definite values for the coupling between the free electron of a nitroxide and carbon 13, the preparation of such radicals marked with 13 C in the α or β position of the nitroxide function has been carried out. The coupling with an α carbon 13 is negative and does not appear to vary with the spin density on the nitrogen. The interaction with the p nuclei of the nitrogen depends on the nature of the substituents: the two benzyl protons have a hyperfine splitting a H which is always less than that of the ethyl. On the other hand, the 13 C coupling is greater in the first case. The usually adopted conformations for the compounds having the carbonyl group cannot account for the observed values of the β couplings. (author) [fr

  5. The LEGO toolbox: Supramolecular building blocks by nitroxide-mediated controlled radical polymerization

    NARCIS (Netherlands)

    Lohmeijer, B.G.G.; Schubert, U.S.

    2005-01-01

    A terpyridine-functionalized alkoxyamine unimolecular initiator was used for the nitroxide-mediated controlled living radical polymerization of n-butylacrylate, N,N-dimethylacrylamide, 4-vinylpyridine, 2-vinylpyridine, and isoprene. For the former three monomers, the kinetics were studied. All

  6. Evidence for Peroxynitrite and Cognates in Whole Smoke

    Directory of Open Access Journals (Sweden)

    Perini FR

    2014-12-01

    Full Text Available The peroxynitrite anion (ONOO-, a major product of the gas-phase interaction between the superoxide radical and nitric oxide, has been detected by ion chromatography (IC for the first time. IC analyses of cigarette whole mainstream smoke collected in deionized water (DiW, using a Dionex 4500i IC, a Dionex AS11 column, an aqueous sodium hydroxide linear gradient with conductivity suppression from 1-20 mMNaOH, and conductivity coupled with diode array detection, revealed an unknown singly charged anion I incompletely resolved from nitrite. Gradient modification produced baseline resolution of I from nitrite and from a number of additional, previously undetected anions associated with smoke samples. Possible candidates for the unexpected smoke sample anion, including bromide, cyanide, and hydrogen hyponitrite were rejected for possible correspondence with the new smoke species on the basis of concentration range and chemical behavior. Chemical, chromatographic, and spectroscopic evidence supported the assignment of this smoke component as ONOO-. Mineral acid immediately destroyed I in the collected aqueous smoke medium. Both the retention time and the ultraviolet spectrum (UV maximum at 302 nm for I were identical to those for synthetic peroxynitrite. The smoke from full flavor [28.5-30.4 mg total particulate matter (TPM] filter cigarettes contained 2.4-3.3 µg/cig of this species. Levels were 4 to 5 times higher, up to 13 µg/cig, in cigarettes with the filters removed.

  7. Nitroxide-mediated homopolymerization and copolymerization of 2-vinylpyridine with styrene

    Czech Academy of Sciences Publication Activity Database

    Lokaj, Jan; Holler, Petr

    2001-01-01

    Roč. 80, č. 11 (2001), s. 2024-2030 ISSN 0021-8995 R&D Projects: GA ČR GA203/99/0572; GA AV ČR KSK2050602 Institutional research plan: CEZ:AV0Z4050913 Keywords : nitroxide-mediated polymerization * pseudoliving mechanism * 2-vinylpyridine polymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.992, year: 2001

  8. Tritiation and Stability Measurements of Nitroxide for Betavoltaic Cells

    Science.gov (United States)

    2016-09-01

    source compounds include low beta-flux power, intrinsic isotope leakage , and beta self-absorption. The figure of merit for a tritiated compound is...graphane, fully hydrogenated graphene. Graphane is not reactive in water or air; it has theoretical higher mechanical and thermal strength than graphene...bonded to the side group of the nitroxide radical TEMPO 6-membered ring. The ester-cleaved product is detectable and is used to assess the specific

  9. Perturbation of nuclear spin polarizations in solid state NMR of nitroxide-doped samples by magic-angle spinning without microwaves

    Energy Technology Data Exchange (ETDEWEB)

    Thurber, Kent R., E-mail: thurberk@niddk.nih.gov; Tycko, Robert [Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520 (United States)

    2014-05-14

    We report solid state {sup 13}C and {sup 1}H nuclear magnetic resonance (NMR) experiments with magic-angle spinning (MAS) on frozen solutions containing nitroxide-based paramagnetic dopants that indicate significant perturbations of nuclear spin polarizations without microwave irradiation. At temperatures near 25 K, {sup 1}H and cross-polarized {sup 13}C NMR signals from {sup 15}N,{sup 13}C-labeled L-alanine in trinitroxide-doped glycerol/water are reduced by factors as large as six compared to signals from samples without nitroxide doping. Without MAS or at temperatures near 100 K, differences between signals with and without nitroxide doping are much smaller. We attribute most of the reduction of NMR signals under MAS near 25 K to nuclear spin depolarization through the cross-effect dynamic nuclear polarization mechanism, in which three-spin flips drive nuclear polarizations toward equilibrium with spin polarization differences between electron pairs. When T{sub 1e} is sufficiently long relative to the MAS rotation period, the distribution of electron spin polarization across the nitroxide electron paramagnetic resonance lineshape can be very different from the corresponding distribution in a static sample at thermal equilibrium, leading to the observed effects. We describe three-spin and 3000-spin calculations that qualitatively reproduce the experimental observations.

  10. Perturbation of nuclear spin polarizations in solid state NMR of nitroxide-doped samples by magic-angle spinning without microwaves

    International Nuclear Information System (INIS)

    Thurber, Kent R.; Tycko, Robert

    2014-01-01

    We report solid state 13 C and 1 H nuclear magnetic resonance (NMR) experiments with magic-angle spinning (MAS) on frozen solutions containing nitroxide-based paramagnetic dopants that indicate significant perturbations of nuclear spin polarizations without microwave irradiation. At temperatures near 25 K, 1 H and cross-polarized 13 C NMR signals from 15 N, 13 C-labeled L-alanine in trinitroxide-doped glycerol/water are reduced by factors as large as six compared to signals from samples without nitroxide doping. Without MAS or at temperatures near 100 K, differences between signals with and without nitroxide doping are much smaller. We attribute most of the reduction of NMR signals under MAS near 25 K to nuclear spin depolarization through the cross-effect dynamic nuclear polarization mechanism, in which three-spin flips drive nuclear polarizations toward equilibrium with spin polarization differences between electron pairs. When T 1e is sufficiently long relative to the MAS rotation period, the distribution of electron spin polarization across the nitroxide electron paramagnetic resonance lineshape can be very different from the corresponding distribution in a static sample at thermal equilibrium, leading to the observed effects. We describe three-spin and 3000-spin calculations that qualitatively reproduce the experimental observations

  11. Perturbation of nuclear spin polarizations in solid state NMR of nitroxide-doped samples by magic-angle spinning without microwaves.

    Science.gov (United States)

    Thurber, Kent R; Tycko, Robert

    2014-05-14

    We report solid state (13)C and (1)H nuclear magnetic resonance (NMR) experiments with magic-angle spinning (MAS) on frozen solutions containing nitroxide-based paramagnetic dopants that indicate significant perturbations of nuclear spin polarizations without microwave irradiation. At temperatures near 25 K, (1)H and cross-polarized (13)C NMR signals from (15)N,(13)C-labeled L-alanine in trinitroxide-doped glycerol/water are reduced by factors as large as six compared to signals from samples without nitroxide doping. Without MAS or at temperatures near 100 K, differences between signals with and without nitroxide doping are much smaller. We attribute most of the reduction of NMR signals under MAS near 25 K to nuclear spin depolarization through the cross-effect dynamic nuclear polarization mechanism, in which three-spin flips drive nuclear polarizations toward equilibrium with spin polarization differences between electron pairs. When T1e is sufficiently long relative to the MAS rotation period, the distribution of electron spin polarization across the nitroxide electron paramagnetic resonance lineshape can be very different from the corresponding distribution in a static sample at thermal equilibrium, leading to the observed effects. We describe three-spin and 3000-spin calculations that qualitatively reproduce the experimental observations.

  12. Modification of HSP proteins and Ca2+ are responsible for the NO-derived peroxynitrite mediated neurological damage in PC12 cell.

    Science.gov (United States)

    Wen, Jun; Li, Hua; Zhang, Yudan; Li, Xia; Liu, Fang

    2015-01-01

    Peroxynitrite as one crucial metabolite of NO-derived agents has been well multi-investigated to inspect its potential role and sought to define its concrete mechanism underlying the memory loss and impaired cognition involved in pathological processes. In this investigation, the cell viability was assessed by the MTT assay. The neurotoxicity of peroxynitrite was analyzed by using immunohistochemical measurements in cultured PC12 cells to explore the underlying mechanisms. The generation of ROS was evaluated by a fluorometry assay by a fluorometry assay. Apoptosis was assayed by annexin V-FITC and PI staining with flow cytometry. [Ca2+]i was examined by using the microspectrofluorometer. Hsp70 was detected by western blot assay. The results revealed that PC12 cells were inhibited by peroxynitrite both in a dose-dependent and time-dependent manner. The level of ROS in PC12 cells exposed to SIN-1 was increased in a dose-dependent manner. The result indicated that the SIN-1 induced apoptosis of PC12 cells in a dose-dependent manner. Quercetin inhibited the viability of PC12 cells in a concentration-dependent manner. [Ca2+]i was increased gradually when cells treated with quercetin alone and also increased with treatment of dantrolene-containing. Hsp70 was significantly decreased in SIN-1-treated group compared with that of control group (P<0.01). In conclusion, Ca2+ homeostasis and chaperone Hsp70 were critically involved in peroxynitrite induced nitrosative stress as protective. Peroxynitrite acts as the pathological agent in learning and memory defects in CNS disorders associated with challenge.

  13. HMGB1-RAGE pathway drives peroxynitrite signaling-induced IBD-like inflammation in murine nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Varun Chandrashekaran

    2017-10-01

    Full Text Available Recent clinical studies found a strong association of colonic inflammation and Inflammatory bowel disease (IBD-like phenotype with NonAlcoholic Fatty liver Disease (NAFLD yet the mechanisms remain unknown. The present study identifies high mobility group box 1 (HMGB1 as a key mediator of intestinal inflammation in NAFLD and outlines a detailed redox signaling mechanism for such a pathway. NAFLD mice showed liver damage and release of elevated HMGB1 in systemic circulation and increased intestinal tyrosine nitration that was dependent on NADPH oxidase. Intestines from NAFLD mice showed higher Toll like receptor 4 (TLR4 activation and proinflammatory cytokine release, an outcome strongly dependent on the existence of NAFLD pathology and NADPH oxidase. Mechanistically intestinal epithelial cells showed the HMGB1 activation of TLR-4 was both NADPH oxidase and peroxynitrite dependent with the latter being formed by the activation of NADPH oxidase. Proinflammatory cytokine production was significantly blocked by the specific peroxynitrite scavenger phenyl boronic acid (FBA, AKT inhibition and NADPH oxidase inhibitor Apocynin suggesting NADPH oxidase-dependent peroxynitrite is a key mediator in TLR-4 activation and cytokine release via an AKT dependent pathway. Studies to ascertain the mechanism of HMGB1-mediated NADPH oxidase activation showed a distinct role of Receptor for advanced glycation end products (RAGE as the use of inhibitors targeted against RAGE or use of deformed HMGB1 protein prevented NADPH oxidase activation, peroxynitrite formation, TLR4 activation and finally cytokine release. Thus, in conclusion the present study identifies a novel role of HMGB1 mediated inflammatory pathway that is RAGE and redox signaling dependent and helps promote ectopic intestinal inflammation in NAFLD.

  14. Cross relaxation in nitroxide spin labels

    DEFF Research Database (Denmark)

    Marsh, Derek

    2016-01-01

    Cross relaxation, and mI-dependence of the intrinsic electron spin-lattice relaxation rate We, are incorporated explicitly into the rate equations for the electron-spin population differences that govern the saturation behaviour of 14N- and 15N-nitroxide spin labels. Both prove important in spin......-label EPR and ELDOR, particularly for saturation recovery studies. Neither for saturation recovery, nor for CW-saturation EPR and CW-ELDOR, can cross relaxation be described simply by increasing the value of We, the intrinsic spin-lattice relaxation rate. Independence of the saturation recovery rates from...... the hyperfine line pumped or observed follows directly from solution of the rate equations including cross relaxation, even when the intrinsic spin-lattice relaxation rate We is mI-dependent....

  15. New Amino-Acid-Based β-Phosphorylated Nitroxides for Probing Acidic pH in Biological Systems by EPR Spectroscopy.

    Science.gov (United States)

    Thétiot-Laurent, Sophie; Gosset, Gaëlle; Clément, Jean-Louis; Cassien, Mathieu; Mercier, Anne; Siri, Didier; Gaudel-Siri, Anouk; Rockenbauer, Antal; Culcasi, Marcel; Pietri, Sylvia

    2017-02-01

    There is increasing interest in measuring pH in biological samples by using nitroxides with pH-dependent electron paramagnetic resonance (EPR) spectra. Aiming to improve the spectral sensitivity (Δa X ) of these probes (i.e., the difference between the EPR hyperfine splitting (hfs) in their protonated and unprotonated forms), we characterized a series of novel linear α-carboxy, α'-diethoxyphosphoryl nitroxides constructed on an amino acid core and featuring an (α or α')-C-H bond. In buffer, the three main hfs (a N , a H , and a P ) of their EPR spectra vary reversibly with pH and, from a P or a H titration curves, a two- to fourfold increase in sensitivity was achieved compared to reference imidazoline or imidazolidine nitroxides. The crystallized carboxylate 10 b (pK a ≈3.6), which demonstrated low cytotoxicity and good resistance to bioreduction, was applied to probe stomach acidity in rats. The results pave the way to a novel generation of highly sensitive EPR pH markers. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Nitroxide-mediated controlled radical polymerisation: towards control of molar mass Controlled Radical Polymerisation

    NARCIS (Netherlands)

    Bon, S.A.F.; Bergman, F.A.C.; Es, van J.J.G.S.; Klumperman, B.; German, A.L.; Matyjaszewski, K.

    1998-01-01

    The mechanism of the TEMPO-mediated controlled radical polymerization of styrene in bulk is discussed. It is shown that the isotropic correlation time (tc) of a nitroxide can be used as a measure of the diffusive rate coefficient of trapping (ketD). A general empirical relationship for the density

  17. Nitroxide-Mediated Radical Polymerization of Styrene Initiated from the Surface of Titanium Oxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    M. Abbasian

    2016-01-01

    Full Text Available Titanium dioxide (TiO2 nanoparticles, with an average size of about 45 nm, were encapsulated by polystyrene using in situ nitroxide mediated radical polymerization   in the presence of 3-aminopropyl triethoxy silane (APTES as a coupling agent and 2, 2, 6, 6-tetramethylpiperidinyl-1-oxy  as a initiator. First, the initiator for NMRP was covalently bonded onto the surface of Titanium dioxide nanoparticles through our novel method. For this purpose, the surface of TiO2 nanoparticle was treated with 3-aminopropyl triethoxy silane, a silane coupling agent, and then these functionalized nanoparticles was reacted with ±-chloro phenyl acetyl chloride. The chlorine groups were converted to nitroxide mediated groups by coupling with 1-hydroxy-2, 2, 6, 6-tetramethyl piperidine. These modified TiO2 nanoparticles were then dispersed in styrene (St monomers to carry out the in situ free radical polymerization.

  18. Anaerobic Nitroxide-Catalyzed Oxidation of Alcohols Using the NO+/NO center dot Redox Pair

    Czech Academy of Sciences Publication Activity Database

    Holan, Martin; Jahn, Ullrich

    2014-01-01

    Roč. 16, č. 1 (2014), s. 58-61 ISSN 1523-7060 R&D Projects: GA ČR GA13-40188S Institutional support: RVO:61388963 Keywords : oxidation * nitroxides * aldehydes * alcohols * ketones * alkyl nitrites Subject RIV: CC - Organic Chemistry Impact factor: 6.364, year: 2014

  19. In vivo evaluation of different alterations of redox status by studying pharmacokinetics of nitroxides using magnetic resonance techniques

    Science.gov (United States)

    Bačić, Goran; Pavićević, Aleksandra; Peyrot, Fabienne

    2015-01-01

    Free radicals, particularly reactive oxygen species (ROS), are involved in various pathologies, injuries related to radiation, ischemia-reperfusion or ageing. Unfortunately, it is virtually impossible to directly detect free radicals in vivo, but the redox status of the whole organism or particular organ can be studied in vivo by using magnetic resonance techniques (EPR and MRI) and paramagnetic stable free radicals – nitroxides. Here we review results obtained in vivo following the pharmacokinetics of nitroxides on experimental animals (and a few in humans) under various conditions. The focus was on conditions where the redox status has been altered by induced diseases or harmful agents, clearly demonstrating that various EPR/MRI/nitroxide combinations can reliably detect metabolically induced changes in the redox status of organs. These findings can improve our understanding of oxidative stress and provide a basis for studying the effectiveness of interventions aimed to modulate oxidative stress. Also, we anticipate that the in vivo EPR/MRI approach in studying the redox status can play a vital role in the clinical management of various pathologies in the years to come providing the development of adequate equipment and probes. PMID:26827126

  20. In vivo evaluation of different alterations of redox status by studying pharmacokinetics of nitroxides using magnetic resonance techniques

    Directory of Open Access Journals (Sweden)

    Goran Bačić

    2016-08-01

    Full Text Available Free radicals, particularly reactive oxygen species (ROS, are involved in various pathologies, injuries related to radiation, ischemia-reperfusion or ageing. Unfortunately, it is virtually impossible to directly detect free radicals in vivo, but the redox status of the whole organism or particular organ can be studied in vivo by using magnetic resonance techniques (EPR and MRI and paramagnetic stable free radicals – nitroxides. Here we review results obtained in vivo following the pharmacokinetics of nitroxides on experimental animals (and a few in humans under various conditions. The focus was on conditions where the redox status has been altered by induced diseases or harmful agents, clearly demonstrating that various EPR/MRI/nitroxide combinations can reliably detect metabolically induced changes in the redox status of organs. These findings can improve our understanding of oxidative stress and provide a basis for studying the effectiveness of interventions aimed to modulate oxidative stress. Also, we anticipate that the in vivo EPR/MRI approach in studying the redox status can play a vital role in the clinical management of various pathologies in the years to come providing the development of adequate equipment and probes.

  1. Photostability enhancement of the pentacene derivative having two nitronyl nitroxide radical substituents.

    Science.gov (United States)

    Shimizu, Akihiro; Ito, Akitaka; Teki, Yoshio

    2016-02-18

    Pentacene derivatives possessing nitronyl nitroxide radical substituents (1a and 1b) were synthesized, and their photochemical properties were evaluated. 1a with two radical substituents showed a remarkable enhancement of photostability compared with pentacene, 6,13-bis(triisopropylsilylethynyl)pentacene and the monoradical, 1b. This is understood due to the presence of the multiple deactivation pathways in the photoexcited states.

  2. Inhibition of nitric oxide synthase expression in activated microglia and peroxynitrite scavenging activity by Opuntia ficus indica var. saboten.

    Science.gov (United States)

    Lee, Ming Hong; Kim, Jae Yeon; Yoon, Jeong Hoon; Lim, Hyo Jin; Kim, Tae Hee; Jin, Changbae; Kwak, Wie-Jong; Han, Chang-Kyun; Ryu, Jae-Ha

    2006-09-01

    Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO-), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. A butanol fraction obtained from 50% ethanol extracts of Opuntia ficus indica var. saboten (Cactaceae) stem (SK OFB901) and its hydrolysis product (SK OFB901H) inhibited the production of NO in LPS-activated microglia in a dose dependent manner (IC50 15.9, 4.2 microg/mL, respectively). They also suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells at higher than 30 microg/mL as observed by western blot analysis and RT-PCR experiment. They also inhibited the degradation of I-kappaB-alpha in activated microglia. Moreover, they showed strong activity of peroxynitrite scavenging in a cell free bioassay system. These results imply that Opuntia ficus indica may have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity. Copyright (c) 2006 John Wiley & Sons, Ltd.

  3. Real-time quantification of oxidative stress and the protective effect of nitroxide antioxidants.

    Science.gov (United States)

    Rayner, Cassie L; Bottle, Steven E; Gole, Glen A; Ward, Micheal S; Barnett, Nigel L

    2016-01-01

    Nitroxides have been exploited as profluorescent probes for the detection of oxidative stress. In addition, they deliver potent antioxidant action and attenuate reactive oxygen species (ROS) in various models of oxidative stress, with these results ascribed to superoxide dismutase or redox and radical-scavenging actions. Our laboratory has developed a range of novel, biostable, isoindoline nitroxide-based antioxidants, DCTEIO and CTMIO. In this study we compared the efficiency of these novel compounds as antioxidant therapies in reducing ROS both in vivo (rat model) and in vitro (661W photoreceptor cells), with the established antioxidant resveratrol. By assessing changes in fluorescence intensity of a unique redox-responsive probe in the rat retina in vivo, we evaluated the ability of antioxidant therapy to (1) ameliorate ROS production and (2) reverse the accumulation of ROS after complete, acute ischemia followed by reperfusion (I/R). I/R injury induced a marked decrease in fluorescence intensity over 60 min of reperfusion, which was successfully ameliorated with each of the antioxidants. DCTEIO and CTMIO reversed the accumulation of ROS when administered intraocularly post ischemic insult, whereas, the effect of resveratrol was not significant. We also investigated our novel agents' capacity to prevent ROS-mediated metabolic dysfunction in the 661W photoreceptor cell line. Cellular stress induced by the oxidant, tert-butyl hydroperoxide, resulted in a loss of spare mitochondrial respiratory capacity (SMRC) and in the extracellular acidification rate in 661W cells. DCTEIO antioxidant administration successfully reduced the loss of SMRC. Together, these findings show we can quantify dynamic changes in cellular oxidative status in vivo and suggest that nitroxide-based antioxidants may provide greater protection against oxidative stress than the current state-of-the-art antioxidant treatments for ROS-mediated diseases. Copyright © 2015 Elsevier Ltd. All rights

  4. Formation of peroxynitrite from the oxidation of hydrogen peroxide by nitrosonium ion (NO+): A pulse radiolysis study

    International Nuclear Information System (INIS)

    Goldstein, S.; Czapski, G.

    1996-01-01

    The rate constant of the reaction of sm-bullet N 3 with sm-bullet NO has been determined to be (4.4 ± 0.5) x 10 9 M -1 s -1 using the pulse radiolysis technique at pH 7.6-8.3 and 21 degrees C. The reaction of sm-bullet 3 with sm-bullet NO takes place through an innersphere electron-transfer mechanism yielding N 3 NO as an intermediate, which subsequently decays to N 2 O and N 2 . Peroxynitrite was formed when H 2 O 2 was added to the sm-bullet N 3 / sm-bullet NO system at pH 5.8-8.3. The maximum yield of peroxynitrite, which was obtained at [H 2 O 2 ] > 0.2 M, was ∼34% of the initially produced sm-bullet N 3 , indicating that N 3 NO does not react directly with H 2 O 2 . The authors conclude that, in the presence of high concentrations of H 2 O 2 , ∼64% of the N 3 NO decomposes into N 2 O and N 2 , whereas the remaining 34% yields NO + or H 2 NO 2 + , which subsequently reacts with H 2 O 2 to form peroxynitrite. The comparison of kinetic results with those obtained previously in the H + /HNO 2 /H 2 O 2 system shows that the nitrosating species in both systems differ. As H 2 NO 2 + is the precursor of NO + in the H + /HNO 2 /H 2 O 2 system, the authors conclude that the reactive intermediate in this system is most probably NO + . From the dependence of the yield of peroxynitrite on [H 2 O 2 ], the ratio between the rate constants of the reactions of NO + with H 2 O 2 and H 2 O was determined to be 65 M -1 . These rate constants were estimated to be k 7 > 3 x 10 8 and k -4 [H 2 O] > 4.6 x 10 6 s -1 , respectively

  5. Silica-Polystyrene Nanocomposite Particles Synthesized by Nitroxide-Mediated Polymerization and Their Encapsulation through Miniemulsion Polymerization

    Directory of Open Access Journals (Sweden)

    Bérangère Bailly

    2006-01-01

    Full Text Available Polystyrene (PS chains with molecular weights comprised between 8000 and 64000 g⋅mol-1 and narrow polydispersities were grown from the surface of silica nanoparticles (Aerosil A200 fumed silica and Stöber silica, resp. through nitroxide-mediated polymerization (NMP. Alkoxyamine initiators based on N-tert-butyl-1-diethylphosphono-2,2-dimethylpropyl nitroxide (DEPN and carrying a terminal functional group have been synthesized in situ and grafted to the silica surface. The resulting grafted alkoxyamines have been employed to initiate the growth of polystyrene chains from the inorganic surface. The maximum grafting density of the surface-tethered PS chains was estimated and seemed to be limited by initiator confinement at the interface. Then, the PS-grafted Stöber silica nanoparticles were entrapped inside latex particles via miniemulsion polymerization. Transmission electron microscopy indicated the successful formation of silica-polystyrene core-shell particles.

  6. Reactivity of Peroxynitrite: Implications for Hanford Waste Management and Remediation

    International Nuclear Information System (INIS)

    Hurst, James K.

    2003-01-01

    The purpose of this grant has been to provide basic chemical research in support of a major project undertaken at Brookhaven National Laboratory (BNL) whose purpose was to provide better understanding of the complex chemical processes occurring an nuclear storage tanks on the Hanford reservation. More specifically, the BNL grant was directed at evaluating the extend of radiation-induced formation of peroxynitrite anion (ONOO) in the tanks and its possible use in was incorporated as a subcontract EMSP 73824, but was later changed to an independent grant to avoid unnecessary duplication of administrative support at both WSU and BNL

  7. Syntheses and study of pyrrolidinic nitroxide free radicals. Preparation of a nitroxide-type stable bi-radical; Synthese et etudes de radicaux libres nitroxydes pyrrolidiniques. Preparation d'un biradical stable du type nitroxyde

    Energy Technology Data Exchange (ETDEWEB)

    Dupeyre, R M [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires, Laboratoire de chimie organique physique

    1967-12-01

    Syntheses and study of pyrrolidinic nitroxide free radicals: These radicals are obtained by oxidation, with hydrogen peroxide, of pyrrolidinic amines prepared from triacetonamine by ring contraction. The U. V,, I. R, and E.P.R. spectral characteristics have been determined. The oxidation of these amines with hydrogen peroxide has led also to rupture of the pentagonal ring; some of the decomposition products have been identified. The high chemical stability of the nitroxide group has made it possible to synthesize and study a stable bi-radical. (author) [French] Syntheses et etudes de radicaux libres nitroxydes pyrrolidiniques: Ces radicaux sont obtenus par oxydation l'eau oxygenee d'amines pyrrolidiniques preparees a partir de la triacetonamine par contraction de cycle. Les caracteristiques spectroscopiques ultra-violettes, infra-rouge et resonance paramagnetique sont determinees. Cependant, 1'oxydation de ces amines a l'eau oxygenee a entraine la coupure du cycle pentagonal et identification de certaines substances de decomposition obtenues. La grande stabilite chimique de groupement nitroxyde a permis la synthese et l'etude d'un biradical stable. (auteur)

  8. Magnetic Properties of linear chain compounds formed by lanthanide (III) ions and nitronyl-nitroxide radicals

    Energy Technology Data Exchange (ETDEWEB)

    Benelli, C.; Caneschi, A.; Gatteschi, D.; Pardi, L. (Florence Univ. (IT)); Rey, P. (CEA Centre d' Etudes Nucleaires de Grenoble, 38 (FR). Dept. de Recherche Fondamentale)

    1988-12-01

    The magnetic properties of novel linear chain compounds containing lanthanide (III) ions (gadolinium, europium) coupled to stable nitronyl-nitroxide radicals are reported. The metal ions and the radicals are regularly alternating along the chain. The magnetic behaviors appears to be dominated by antiferromagnetic interactions between the radicals.

  9. Magnetic Properties of linear chain compounds formed by lanthanide (III) ions and nitronyl-nitroxide radicals

    International Nuclear Information System (INIS)

    Benelli, C.; Caneschi, A.; Gatteschi, D.; Pardi, L.; Rey, P.

    1988-01-01

    The magnetic properties of novel linear chain compounds containing lanthanide (III) ions (gadolinium, europium) coupled to stable nitronyl-nitroxide radicals are reported. The metal ions and the radicals are regularly alternating along the chain. The magnetic behaviors appears to be dominated by antiferromagnetic interactions between the radicals

  10. Interpretation of cw-ESR spectra of p-methyl-thio-phenyl-nitronyl nitroxide in a nematic liquid crystalline phase.

    Science.gov (United States)

    Collauto, Alberto; Zerbetto, Mirco; Brustolon, Marina; Polimeno, Antonino; Caneschi, Andrea; Gatteschi, Dante

    2012-03-07

    In this paper we report on the characterization by continuous wave electron spin resonance spectroscopy (cw-ESR) of a nitronyl nitroxide radical in a nematic phase. A detailed analysis is performed by exploiting an innovative modeling strategy alternative to the usual spectral simulation approach: most of the molecular parameters needed to calculate the spectrum are evaluated a priori and the ESR spectrum is obtained by direct application of the stochastic Liouville equation. Allowing a limited set of fitting parameters it is possible to reproduce satisfactorily ESR spectra in the temperature range 260 K-340 K including the nematic-to-isotropic phase transition (325.1 K). Our results open the way to a more quantitative understanding of the ordering and mobility of nitronyl nitroxide radicals in nanostructured environments.

  11. Inhibition of oxygen-dependent radiation-induced damage by the nitroxide superoxide dismutase mimic, tempol

    International Nuclear Information System (INIS)

    Mitchell, J.B.; DeGraff, W.; Kaufman, D.; Krishna, M.C.; Samuni, A.; Finkelstein, E.; Ahn, M.S.; Hahn, S.M.; Gamson, J.; Russo, A.

    1991-01-01

    Stable nitroxide radicals have been previously shown to function as superoxide dismutase (SOD)2 mimics and to protect mammalian cells against superoxide and hydrogen peroxide-mediated oxidative stress. These unique characteristics suggested that nitroxides, such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), might protect mammalian cells against ionizing radiation. Treating Chinese hamster cells under aerobic conditions with 5, 10, 50, and 100 mM Tempol 10 min prior to X-rays resulted in radiation protection factors of 1.25, 1.30, 2.1, and 2.5, respectively. However, the reduced form of Tempol afforded no protection. Tempol treatment under hypoxic conditions did not provide radioprotection. Aerobic X-ray protection by Tempol could not be attributed to the induction of intracellular hypoxia, increase in intracellular glutathione, or induction of intracellular SOD mRNA. Tempol thus represents a new class of non-thiol-containing radiation protectors, which may be useful in elucidating the mechanism(s) of radiation-induced cellular damage and may have broad applications in protecting against oxidative stress

  12. Inhibition of overexpression of Giα proteins and nitroxidative stress contribute to sodium nitroprusside-induced attenuation of high blood pressure in SHR.

    Science.gov (United States)

    Hossain, Ekhtear; Sarkar, Oli; Li, Yuan; Anand-Srivastava, Madhu B

    2018-03-01

    We earlier showed that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit enhanced expression of Giα proteins which was attributed to the decreased levels of nitric oxide (NO), because elevation of the intracellular levels of NO by NO donors; sodium nitroprusside (SNP) and S-Nitroso-N-acetyl-DL-penicillamine (SNAP), attenuated the enhanced expression of Giα proteins. Since the enhanced expression of Giα proteins is implicated in the pathogenesis of hypertension, the present study was undertaken to investigate if treatment of SHR with SNP could also attenuate the development of high blood pressure (BP) and explore the underlying molecular mechanisms. Intraperitoneal injection of SNP at a concentration of 0.5 mg/kg body weight twice a week for 2 weeks into SHR attenuated the high blood pressure by about 80 mmHg without affecting the BP in WKY rats. SNP treatment also attenuated the enhanced levels of superoxide anion (O 2 - ), hydrogen peroxide (H 2 O 2 ), peroxynitrite (ONOO - ), and NADPH oxidase activity in VSMC from SHR to control levels. In addition, the overexpression of different subunits of NADPH oxidase; Nox-1, Nox-2, Nox-4, P 22phox , and P 47phox , and Giα proteins in VSMC from SHR were also attenuated by SNP treatment. On the other hand, SNP treatment augmented the decreased levels of intracellular NO, eNOS, and cGMP in VSMC from SHR. These results suggest that SNP treatment attenuates the development of high BP in SHR through the elevation of intracellular levels of cGMP and inhibition of the enhanced levels of Giα proteins and nitroxidative stress. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  13. Nitroxide stable radicals interacting as Lewis bases in hydrogen bonds: A search in the Cambridge structural data base for intermolecular contacts

    Science.gov (United States)

    Alkorta, Ibon; Elguero, José; Elguero, Eric

    2017-11-01

    1125 X-ray structures of nitroxide free radicals presenting intermolecular hydrogen bonds have been reported in the Cambridge Structural Database. We will report in this paper a qualitative and quantitative analysis of these bonds. The observation in some plots of an excluded region was statistically analyzed using convex hull and kernel smooting methodologies. A theoretical study at the MP2 level with different basis has been carried out indicating that the nitronyl nitroxide radicals (five electrons) lie just in between nitroso compounds (four electrons) and amine N-oxides (six electrons) as far as hydrogen-bond basicity is concerned.

  14. High-throughput optimization of nitroxide mediated radical polymerizations as basis for the synthesis of temperature-responsive copolymers

    NARCIS (Netherlands)

    Hoogenboom, R.; Becer, C.R.; Eggenhuisen, T.M.; Schubert, U.S.

    2008-01-01

    The development of controlled radical polymn. techniques, namely atom transfer radical polymn. (ATRP), reversible addn. fragmentation transfer (RAFT) and nitroxide mediated radical polymn. (NMP), have opened up unprecedented possibilities for the synthesis of well-defined macromol. architectures

  15. Modification of a single tryptophan residue in human Cu,Zn-superoxide dismutase by peroxynitrite in the presence of bicarbonate.

    Science.gov (United States)

    Yamakura, F; Matsumoto, T; Fujimura, T; Taka, H; Murayama, K; Imai, T; Uchida, K

    2001-07-09

    Human recombinant Cu,Zn-SOD was reacted with peroxynitrite in a reaction mixture containing 150 mM potassium phosphate buffer (pH 7.4) 25 mM sodium bicarbonate, and 0.1 mM diethylenetriamine pentaacetic acid. Disappearance of fluorescence emission at 350 nm, which could be attributed to modification of a single tryptophan residue, was observed in the modified enzyme with a pH optimum of around 8.4. A fluorescence decrease with the same pH optimum was also observed without sodium bicarbonate, but with less efficiency. Amino acid contents of the modified enzyme showed no significant difference in all amino acids except the loss of a single tryptophan residue of the enzyme. The peroxynitrite-modified enzyme showed an increase in optical absorption around 350 nm and 30% reduced enzyme activity based on the copper contents. The modified enzyme showed the same electron paramagnetic resonance spectrum as that of the control enzyme. The modified Cu,Zn-SOD showed a single protein band in sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS--PAGE) and five protein bands in non-denaturing PAGE. From this evidence, we conclude that nitration and/or oxidation of the single tryptophan 32 and partial inactivation of the enzyme activity of Cu,Zn-SOD is caused by a peroxynitrite-carbon dioxide adduct without perturbation of the active site copper integrity.

  16. Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Byoung-Joon Song

    2013-01-01

    Full Text Available Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research.

  17. In situ NMR and modeling studies of nitroxide mediated copolymerization of styrene and n-butyl acrylate

    NARCIS (Netherlands)

    Hlalele, L.; Klumperman, L.

    2011-01-01

    The combination of in situ1H NMR and in situ31P NMR was used to study the nitroxide mediated copolymerization of styrene and n-butyl acrylate. The alkoxyamine MAMA-DEPN was employed to initiate and mediate the copolymerization. The nature of the ultimate/terminal monomer units of dormant polymer

  18. The effect of peroxynitrite decomposition catalyst MnTBAP on aldehyde dehydrogenase-2 nitration by organic nitrates: role in nitrate tolerance.

    Science.gov (United States)

    Mollace, Vincenzo; Muscoli, Carolina; Dagostino, Concetta; Giancotti, Luigino Antonio; Gliozzi, Micaela; Sacco, Iolanda; Visalli, Valeria; Gratteri, Santo; Palma, Ernesto; Malara, Natalia; Musolino, Vincenzo; Carresi, Cristina; Muscoli, Saverio; Vitale, Cristiana; Salvemini, Daniela; Romeo, Francesco

    2014-11-01

    Bioconversion of glyceryl trinitrate (GTN) into nitric oxide (NO) by aldehyde dehydrogenase-2 (ALDH-2) is a crucial mechanism which drives vasodilatory and antiplatelet effect of organic nitrates in vitro and in vivo. Oxidative stress generated by overproduction of free radical species, mostly superoxide anions and NO-derived peroxynitrite, has been suggested to play a pivotal role in the development of nitrate tolerance, though the mechanism still remains unclear. Here we studied the free radical-dependent impairment of ALDH-2 in platelets as well as vascular tissues undergoing organic nitrate ester tolerance and potential benefit when using the selective peroxynitrite decomposition catalyst Mn(III) tetrakis (4-Benzoic acid) porphyrin (MnTBAP). Washed human platelets were made tolerant to nitrates via incubation with GTN for 4h. This was expressed by attenuation of platelet aggregation induced by thrombin (40U/mL), an effect accompanied by GTN-related induction of cGMP levels in platelets undergoing thrombin-induced aggregation. Both effects were associated to attenuated GTN-induced nitrite formation in platelets supernatants and to prominent nitration of ALDH-2, the GTN to NO metabolizing enzyme, suggesting that GTN tolerance was associated to reduced NO formation via impairment of ALDH-2. These effects were all antagonized by co-incubation of platelets with MnTBAP, which restored GTN-induced responses in tolerant platelets. Comparable effect was found under in in vivo settings. Indeed, MnTBAP (10mg/kg, i.p.) significantly restored the hypotensive effect of bolus injection of GTN in rats made tolerants to organic nitrates via chronic administration of isosorbide-5-mononitrate (IS-5-MN), thus confirming the role of peroxynitrite overproduction in the development of tolerance to vascular responses induced by organic nitrates. In conclusion, oxidative stress subsequent to prolonged use of organic nitrates, which occurs via nitration of ALDH-2, represents a key event

  19. A study of nitroxide polyradical/activated carbon composite as the positive electrode material for electrochemical hybrid capacitor

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui-qiao; Zou, Ying; Xia, Yong-yao [Chemistry Department and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200433 (China)

    2007-01-01

    We present a new concept of the hybrid electrochemical capacitor technology in which a poly(2,2,6,6-tetramethylpiperidinyloxy methacrylate) nitroxide polyradical/activated carbon composite (PTMA-AC) is used as the positive electrode material and activated carbon is used as the negative electrode material. On the positive electrode, both reversible reduction and oxidation of nitroxide polyradical and non-faradic ion sorption/de-sorption of activated carbon are involved during charge and discharge process. The capacity of the composite electrode is 30% larger than that of the pure activated carbon electrode. A hybrid capacitor fabricated by the PTMA-AC composite positive electrode and the activated carbon negative electrode shows a good cycling life, it can be charged/discharged for over 1000 cycles with slight capacity loss. The hybrid capacitor also has a good rate capability, it maintains 80% of the initial capacity even at the high discharge current of up to 20C. (author)

  20. Cytochrome P450-2E1 is involved in aging-related kidney damage in mice through increased nitroxidative stress.

    Science.gov (United States)

    Abdelmegeed, Mohamed A; Choi, Youngshim; Ha, Seung-Kwoon; Song, Byoung-Joon

    2017-11-01

    The aim of this study was to investigate the role of cytochrome P450-2E1 (CYP2E1) in aging-dependent kidney damage since it is poorly understood. Young (7 weeks) and aged female (16-17 months old) wild-type (WT) and Cyp2e1-null mice were used. Kidney histology showed that aged WT mice exhibited typical signs of kidney aging such as cell vacuolation, inflammatory cell infiltration, cellular apoptosis, glomerulonephropathy, and fibrosis, along with significantly elevated levels of renal TNF-α and serum creatinine than all other groups. Furthermore, the highest levels of renal hydrogen peroxide, protein carbonylation and nitration were observed in aged WT mice. These increases in the aged WT mice were accompanied by increased levels of iNOS and mitochondrial nitroxidative stress through altered amounts and activities of the mitochondrial complex proteins and significantly reduced levels of the antioxidant glutathione (GSH). In contrast, the aged Cyp2e1-null mice exhibited significantly higher antioxidant capacity with elevated heme oxygenase-1 and catalase activities compared to all other groups, while maintaining normal GSH levels with significantly less mitochondrial nitroxidative stress compared to the aged WT mice. Thus, CYP2E1 is important in causing aging-related kidney damage most likely through increasing nitroxidative stress and that CYP2E1 could be a potential target in preventing aging-related kidney diseases. Published by Elsevier Ltd.

  1. Molecular order and T1-relaxation, cross-relaxation in nitroxide spin labels

    Science.gov (United States)

    Marsh, Derek

    2018-05-01

    Interpretation of saturation-recovery EPR experiments on nitroxide spin labels whose angular rotation is restricted by the orienting potential of the environment (e.g., membranes) currently concentrates on the influence of rotational rates and not of molecular order. Here, I consider the dependence on molecular ordering of contributions to the rates of electron spin-lattice relaxation and cross relaxation from modulation of N-hyperfine and Zeeman anisotropies. These are determined by the averages and , where θ is the angle between the nitroxide z-axis and the static magnetic field, which in turn depends on the angles that these two directions make with the director of uniaxial ordering. For saturation-recovery EPR at 9 GHz, the recovery rate constant is predicted to decrease with increasing order for the magnetic field oriented parallel to the director, and to increase slightly for the perpendicular field orientation. The latter situation corresponds to the usual experimental protocol and is consistent with the dependence on chain-labelling position in lipid bilayer membranes. An altered dependence on order parameter is predicted for saturation-recovery EPR at high field (94 GHz) that is not entirely consistent with observation. Comparisons with experiment are complicated by contributions from slow-motional components, and an unexplained background recovery rate that most probably is independent of order parameter. In general, this analysis supports the interpretation that recovery rates are determined principally by rotational diffusion rates, but experiments at other spectral positions/field orientations could increase the sensitivity to order parameter.

  2. Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction.

    Science.gov (United States)

    Stanyer, Lee; Jorgensen, Wenche; Hori, Osamu; Clark, John B; Heales, Simon J R

    2008-09-01

    The accumulation of oxidatively modified proteins has been shown to be a characteristic feature of many neurodegenerative disorders and its regulation requires efficient proteolytic processing. One component of the mitochondrial proteolytic system is Lon, an ATP-dependent protease that has been shown to degrade oxidatively modified aconitase in vitro and may thus play a role in defending against the accumulation of oxidized matrix proteins in mitochondria. Using an assay system that allowed us to distinguish between basal and ATP-stimulated Lon protease activity, we have shown in isolated non-synaptic rat brain mitochondria that Lon protease is highly susceptible to oxidative inactivation by peroxynitrite (ONOO(-)). This susceptibility was more pronounced with regard to ATP-stimulated activity, which was inhibited by 75% in the presence of a bolus addition of 1mM ONOO(-), whereas basal unstimulated activity was inhibited by 45%. Treatment of mitochondria with a range of peroxynitrite concentrations (10-1000 microM) revealed that a decline in Lon protease activity preceded electron transport chain (ETC) dysfunction (complex I, II-III and IV) and that ATP-stimulated activity was approximately fivefold more sensitive than basal Lon protease activity. Furthermore, supplementation of mitochondrial matrix extracts with reduced glutathione, following ONOO(-) exposure, resulted in partial restoration of basal and ATP-stimulated activity, thus suggesting possible redox regulation of this enzyme complex. Taken together these findings suggest that Lon protease may be particularly vulnerable to inactivation in conditions associated with GSH depletion and elevated oxidative stress.

  3. Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in normal rat kidney (NRK cells

    Directory of Open Access Journals (Sweden)

    Akira Marine

    2014-01-01

    Full Text Available Superoxide is widely regarded as the primary reactive oxygen species (ROS which initiates downstream oxidative stress. Increased oxidative stress contributes, in part, to many disease conditions such as cancer, atherosclerosis, ischemia/reperfusion, diabetes, aging, and neurodegeneration. Manganese superoxide dismutase (MnSOD catalyzes the dismutation of superoxide into hydrogen peroxide which can then be further detoxified by other antioxidant enzymes. MnSOD is critical in maintaining the normal function of mitochondria, thus its inactivation is thought to lead to compromised mitochondria. Previously, our laboratory observed increased mitochondrial biogenesis in a novel kidney-specific MnSOD knockout mouse. The current study used transient siRNA mediated MnSOD knockdown of normal rat kidney (NRK cells as the in vitro model, and confirmed functional mitochondrial biogenesis evidenced by increased PGC1α expression, mitochondrial DNA copy numbers and integrity, electron transport chain protein CORE II, mitochondrial mass, oxygen consumption rate, and overall ATP production. Further mechanistic studies using mitoquinone (MitoQ, a mitochondria-targeted antioxidant and L-NAME, a nitric oxide synthase (NOS inhibitor demonstrated that peroxynitrite (at low micromolar levels induced mitochondrial biogenesis. These findings provide the first evidence that low levels of peroxynitrite can initiate a protective signaling cascade involving mitochondrial biogenesis which may help to restore mitochondrial function following transient MnSOD inactivation.

  4. Spatial profiling of degradation processes in hindered-amine-stabilized polymers by electron spin resonance imaging of nitroxides

    Czech Academy of Sciences Publication Activity Database

    Marek, Antonín; Kaprálková, Ludmila; Pfleger, Jiří; Pospíšil, Jan; Pilař, Jan

    2005-01-01

    Roč. 99, S (2005), s. 195-198 ISSN 0009-2770. [Meeting on Chemistry and Life /3./. Brno, 20.9.2005-22.9.2005] Institutional research plan: CEZ:AV0Z40500505 Keywords : polymer degradation * nitroxides * electron spin resonance imaging Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.445, year: 2005

  5. Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite

    Directory of Open Access Journals (Sweden)

    Takahiro Ueno

    2008-11-01

    Full Text Available Takahiro Ueno1, Hironori Tsuchiya2, Maki Mizogami1, Ko Takakura11Department of Anesthesiology, Asahi University School of Dentistry, Mizuho, Gifu, Japan; 2Department of Dental Basic Education, Asahi University School of Dentistry, Mizuho, Gifu, JapanAbstract: The presence of inflammation decreases local anesthetic efficacy, especially in dental anesthesia. Although inflammatory acidosis is most frequently cited as the cause of such clinical phenomena, this has not been experimentally proved. We verified the acidosis mechanism by studying the drug and membrane lipid interaction under acidic conditions together with proposing an alternative hypothesis. Liposomes and nerve cell model membranes consisting of phospholipids and cholesterol were treated at different pH with lidocaine, prilocaine and bupivacaine (0.05%–0.2%, w/v. Their membrane-interactive potencies were compared by the induced-changes in membrane fluidity. Local anesthetics fluidized phosphatidylcholine membranes with the potency being significantly lower at pH 6.4 than at pH 7.4 (p < 0.01, supporting the acidosis theory. However, they greatly fluidized nerve cell model membranes even at pH 6.4 corresponding to inflamed tissues, challenging the conventional mechanism. Local anesthetics acted on phosphatidylserine liposomes, as well as nerve cell model membranes, at pH 6.4 with almost the same potency as that at pH 7.4, but not on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin liposomes. Since the positively charged anesthetic molecules are able to interact with nerve cell membranes by ion-paring with anionic components like phosphatidylserine, tissue acidosis is not essentially responsible for the local anesthetic failure associated with inflammation. The effects of local anesthetics on nerve cell model membranes were inhibited by treating with peroxynitrite (50 μM, suggesting that inflammatory cells producing peroxynitrite may affect local anesthesia

  6. A perspective on slow-relaxing molecular magnets built from rare-earths and nitronyl-nitroxide building blocks (invited)

    Science.gov (United States)

    Bogani, Lapo

    2011-04-01

    We offer a perspective, accessible to both chemists and physicists, of recent developments in the synthesis and characterization of molecular magnetic materials based on rare-earths and nitronyl-nitroxide radicals. We show both the rationale of the synthetic strategies and the observed behaviors. We highlight the relevance of these findings for synthetic chemists, material scientists, and physicists.

  7. Nitroxides are more efficient inhibitors of oxidative damage to calf skin collagen than antioxidant vitamins.

    Science.gov (United States)

    Venditti, Elisabetta; Scirè, Andrea; Tanfani, Fabio; Greci, Lucedio; Damiani, Elisabetta

    2008-01-01

    Reactive oxygen species generated upon UV-A exposure appear to play a major role in dermal connective tissue transformations including degradation of skin collagen. Here we investigate on oxidative damage to collagen achieved by exposure to (i) UV-A irradiation and to (ii) AAPH-derived radicals and on its possible prevention using synthetic and natural antioxidants. Oxidative damage was identified through SDS-PAGE, circular dichroism spectroscopy and quantification of protein carbonyl residues. Collagen (2 mg/ml) exposed to UV-A and to AAPH-derived radicals was degraded in a time- and dose-dependent manner. Upon UV-A exposure, maximum damage was observable at 730 kJ/m2 UV-A, found to be equivalent to roughly 2 h of sunshine, while exposure to 5 mM AAPH for 2 h at 50 degrees C lead to maximum collagen degradation. In both cases, dose-dependent protection was achieved by incubation with muM concentrations of nitroxide radicals, where the extent of protection was shown to be dictated by their structural differences whereas the vitamins E and C proved less efficient inhibitors of collagen damage. These results suggest that nitroxide radicals may be able to prevent oxidative injury to dermal tissues in vivo alternatively to commonly used natural antioxidants.

  8. Conduction mechanism of nitronyl-nitroxide molecular magnetic compounds

    Science.gov (United States)

    Dotti, N.; Heintze, E.; Slota, M.; Hübner, R.; Wang, F.; Nuss, J.; Dressel, M.; Bogani, L.

    2016-04-01

    We investigate the conduction mechanisms of nitronyl-nitroxide (NIT) molecular radicals, as useful for the creation of nanoscopic molecular spintronic devices, finding that it does not correspond to standard Mott behavior, as previously postulated. We provide a complete investigation using transport measurements, low-energy, sub-THz spectroscopy and introducing differently substituted phenyl appendages. We show that a nontrivial surface-charge-limited regime is present in addition to the standard low-voltage Ohmic conductance. Scaling analysis allows one to determine all the main transport parameters for the compounds and highlights the presence of charge-trapping effects. Comparison among the different compounds shows the relevance of intermolecular stacking between the aromatic ring of the phenyl appendix and the NIT motif in the creation of useful electron transport channels. The importance of intermolecular pathways is further highlighted by electronic structure calculations, which clarify the nature of the electronic channels and their effect on the Mott character of the compounds.

  9. Ability of nitrones of various structures to control the radical polymerization of styrene mediated by in situ formed nitroxides.

    NARCIS (Netherlands)

    Sciannamea, V.; Guerrero-Sanchez, C.A.; Schubert, U.S.; Catala, J.-M.; Jerome, R.; Detrembleur, C.

    2005-01-01

    The ability of several nitrones to control the radical polymerization of styrene at 110 °C has been investigated by high-throughput experimentation. The nitrone/free radical initiator pair dictates the structure of the nitroxide and the alkoxyamine formed in situ, which determines the position of

  10. Synthesis and quaternization of nitroxide-terminated poly(4-vinylpyridine-co-acrylonitrile) macroinitiators and related diblock copolymers

    Czech Academy of Sciences Publication Activity Database

    Poláková, Lenka; Lokaj, Jan; Holler, Petr; Starovoytova, Larisa; Pekárek, Michal; Štěpánek, Petr

    -, 065 (2010), s. 1-10 ISSN 1618-7229 R&D Projects: GA ČR GESON/06/E005; GA ČR GA203/07/0659 Institutional research plan: CEZ:AV0Z40500505 Keywords : 4-vinylpyridine-acrylonitrile copolymers * block copolymers * nitroxide-mediated radical polymerization Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.574, year: 2010 http://www.e-polymers.org/journal/papers/lpolakova_240710.pdf

  11. Synthesis of diblock copolymers comprising poly(2-vinylpyridine-co-acrylonitrile) and polystyrene blocks by nitroxide-mediated radical polymerization

    Czech Academy of Sciences Publication Activity Database

    Lokaj, Jan; Poláková, Lenka; Holler, Petr; Starovoytova, Larisa; Štěpánek, Petr; Diat, O.

    2007-01-01

    Roč. 105, č. 3 (2007), s. 1616-1622 ISSN 0021-8995 R&D Projects: GA ČR GESON/03/E001 Institutional research plan: CEZ:AV0Z40500505 Keywords : 2-vinylpyridine-acrylonitrile copolymers * nitroxide-mediated radical copolymerization * chain extension Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.008, year: 2007

  12. Selective enzymatic degradation of self-assembled particles from amphiphilic block copolymers obtained by the combination of N-carboxyanhydride and nitroxide-mediated polymerization

    NARCIS (Netherlands)

    Habraken, G.J.M.; Peeters, M.; Thornton, P.D.; Koning, C.E.; Heise, A.

    2011-01-01

    Combining controlled radical polymerizations and a controlled polypeptide synthetic technique, such as N-carboxyanhydride (NCA) ring-opening polymerization, enables the generation of well-defined block copolymers to be easily accessible. Here we combine NCA polymerization with the nitroxide-mediated

  13. ¹⁹F magnetic resonance probes for live-cell detection of peroxynitrite using an oxidative decarbonylation reaction.

    Science.gov (United States)

    Bruemmer, Kevin J; Merrikhihaghi, Sara; Lollar, Christina T; Morris, Siti Nur Sarah; Bauer, Johannes H; Lippert, Alexander R

    2014-10-21

    We report a newly discovered oxidative decarbonylation reaction of isatins that is selectively mediated by peroxynitrite (ONOO(-)) to provide anthranilic acid derivatives. We have harnessed this rapid and selective transformation to develop two reaction-based probes, 5-fluoroisatin and 6-fluoroisatin, for the low-background readout of ONOO(-) using (19)F magnetic resonance spectroscopy. 5-fluoroisatin was used to non-invasively detect ONOO(-) formation in living lung epithelial cells stimulated with interferon-γ (IFN-γ).

  14. Intraesophageal administratio (JP4-039) and p53/MDM2/MDM4 Inhibitor (BEB55) ameliorates radiation esophagitisn of GS-Nitroxide

    NARCIS (Netherlands)

    Kim, H.; Bernard, M.; Epperly, M.W.; Shen, H.; Dixon, T.M.; Amoscato, A.A.; Doemling, A.S.; Li, S.; Gao, X.; Wipf, P.

    2011-01-01

    Purpose/Objective(s): To evaluate the esophageal radiation dose modification properties of the GS-nitroxide (JP4-039) and the p53/MDM2/MDM4 inhibitor (BEB55). Materials/Methods: Esophagitis is a significant toxicity of radiation therapy of thoracic cancers. We evaluated radiation dose modification

  15. Synthesis and evaluation of nitroxide-based oligoradicals for low-temperature dynamic nuclear polarization in solid state NMR

    Science.gov (United States)

    Yau, Wai-Ming; Thurber, Kent R.; Tycko, Robert

    2014-07-01

    We describe the synthesis of new nitroxide-based biradical, triradical, and tetraradical compounds and the evaluation of their performance as paramagnetic dopants in dynamic nuclear polarization (DNP) experiments in solid state nuclear magnetic resonance (NMR) spectroscopy with magic-angle spinning (MAS). Under our experimental conditions, which include temperatures in the 25-30 K range, a 9.4 T magnetic field, MAS frequencies of 6.2-6.8 kHz, and microwave irradiation at 264.0 GHz from a 800 mW extended interaction oscillator source, the most effective compounds are triradicals that are related to the previously-described compound DOTOPA-TEMPO (see Thurber et al., 2010), but have improved solubility in glycerol/water solvent near neutral pH. Using these compounds at 30 mM total nitroxide concentration, we observe DNP enhancement factors of 92-128 for cross-polarized 13C NMR signals from 15N,13C-labeled melittin in partially protonated glycerol/water, and build-up times of 2.6-3.8 s for 1H spin polarizations. Net sensitivity enhancements with biradical and tetraradical dopants, taking into account absolute 13C NMR signal amplitudes and build-up times, are approximately 2-4 times lower than with the best triradicals.

  16. Temperature-induced variation in the intrinsic hyperfine separation of a tightly bound nitroxide spin label

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, M.E.

    1979-01-01

    Recently there has been increasing interest in studying the rotational motion of biological molecules by monitoring the electron paramagnetic resonance (EPR) spectra of spin labels which are tightly bound to the molecule of interest. Theoretical studies have shown that in the slow motion region the correlation time may be determined by comparing the apparent hyperfine separation (HFS) in the presence of rotational motion with the rigid limit HFS in the absence of rotational motion. The majority of work to date has assumed the tightly bound nitroxide label to act simply as a reporter group for molecular motion, exhibiting little or no intrinsic environmental or temperature sensitivity. However, we have demonstrated that the rigid limit EPR spectra exhibit a substantial intrinsic temperature dependence, with the rigid limit HFS of MAL-6-labelled carboxyhemoglobin (HbCO) decreasing by nearly 10G over the temperature range -196/sup 0/C to +45/sup 0/C. The steepest temperature dependence was also found to occur over the 0 to 40/sup 0/C temperature range where most biological measurements are made. This strong temperature dependence in the intrinsic HFS was shown to produce substantial errors in correlation time calculations if it was not explicitly recognized and appropriate corrections made. This detailed behavior of this intrinsic temperature dependence suggests that it is most probably produced by equilibrium hydrogen bonding between the nitroxide NO/sup ./ group and an unidentified proton donor within the spin label binding site. (RJC)

  17. Well-defined polyethylene-based graft terpolymers by combining nitroxide-mediated radical polymerization, polyhomologation and azide/alkyne “click” chemistry†

    KAUST Repository

    Alkayal, Nazeeha

    2016-03-30

    Novel well–defined polyethylene–based graft terpolymers were synthesized via the “grafting onto” strategy by combining nitroxide-mediated radical polymerization (NMP), polyhomologation and copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) “click” chemistry. Three steps were involved in this approach: (i) synthesis of alkyne-terminated polyethylene-b-poly(ε-caprolactone) (PE-b-PCL-alkyne) block copolymers (branches) by esterification of PE-b-PCL-OH with 4-pentynoic acid; the PE-b-PCL-OH was obtained by polyhomologation of dimethylsulfoxonium methylide to afford PE-OH, followed by ring opening polymerization of ε-caprolactone using the PE-OH as macroinitiator, (ii) synthesis of random copolymers of styrene (St) and 4-chloromethylstyrene (4-CMS) with various CMS contents, by nitroxide-mediated radical copolymerization (NMP), and conversion of chloride to azide groups by reaction with sodium azide (NaN3) (backbone) and (iii) “click” linking reaction to afford the PE-based graft terpolymers. All intermediates and final products were characterized by high-temperature size exclusion chromatography (HT-SEC), Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy (1H NMR) and differential scanning calorimetry (DSC).

  18. Hypoxia inducible factor-1 alpha stabilization for regenerative therapy in traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Mushfiquddin Khan

    2017-01-01

    Full Text Available Mild traumatic brain injury (TBI, also called concussion, initiates sequelae leading to motor deficits, cognitive impairments and subtly compromised neurobehaviors. While the acute phase of TBI is associated with neuroinflammation and nitroxidative burst, the chronic phase shows a lack of stimulation of the neurorepair process and regeneration. The deficiency of nitric oxide (NO, the consequent disturbed NO metabolome, and imbalanced mechanisms of S-nitrosylation are implicated in blocking the mechanisms of neurorepair processes and functional recovery in the both phases. Hypoxia inducible factor-1 alpha (HIF-1α, a master regulator of hypoxia/ischemia, stimulates the process of neurorepair and thus aids in functional recovery after brain trauma. The activity of HIF-1α is regulated by NO via the mechanism of S-nitrosylation of HIF-1α. S-nitrosylation is dynamically regulated by NO metabolites such as S-nitrosoglutathione (GSNO and peroxynitrite. GSNO stabilizes, and peroxynitrite destabilizes HIF-1α. Exogenously administered GSNO was found not only to stabilize HIF-1α and to induce HIF-1α-dependent genes but also to stimulate the regeneration process and to aid in functional recovery in TBI animals.

  19. Nitroxide-mediated radical ring-opening copolymerization: chain-end investigation and block copolymer synthesis.

    Science.gov (United States)

    Delplace, Vianney; Harrisson, Simon; Tardy, Antoine; Gigmes, Didier; Guillaneuf, Yohann; Nicolas, Julien

    2014-02-01

    Well-defined, degradable copolymers are successfully prepared by nitroxide-mediated radical ring opening polymerization (NMrROP) of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) or methyl methacrylate (MMA), a small amount of acrylonitrile (AN) and cyclic ketene acetals (CKAs) of different structures. Phosphorous nuclear magnetic resonance allows in-depth chain-end characterization and gives crucial insights into the nature of the copoly-mer terminal sequences and the living chain fractions. By using a small library of P(OEGMA-co-AN-co-CKA) and P(MMA-co-AN-co-CKA) as macroinitiators, chain extensions with styrene are performed to furnish (amphiphilic) block copolymers comprising a degradable segment. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. The effect of polyphenolic-polysaccharide conjugates from selected medicinal plants of Asteraceae family on the peroxynitrite-induced changes in blood platelet proteins.

    Science.gov (United States)

    Saluk-Juszczak, Joanna; Pawlaczyk, Izabela; Olas, Beata; Kołodziejczyk, Joanna; Ponczek, Michal; Nowak, Pawel; Tsirigotis-Wołoszczak, Marta; Wachowicz, Barbara; Gancarz, Roman

    2010-12-01

    Lots of plants belonging to Asteraceae family are very popular in folk medicine in Poland. These plants are also known as being rich in acidic polysaccharides, due to the presence of hexuronic acids or its derivatives. Our preliminary experiments have shown that the extract from Conyza canadensis L. possesses various biological activity, including antiplatelet, antiocoagulant and antioxidant properties. The aim of our study was to assess if macromolecular glycoconjugates from selected herbal plants of Asteraceae family: Achillea millefolium L., Arnica montana L., Echinacea purpurea L., Solidago virgaurea L., Chamomilla recutita (L.) Rauschert., and Conyza canadensis L. protect platelet proteins against nitrative and oxidative damage induced by peroxynitrite, which is responsible for oxidative/nitrative modifications of platelet proteins: the formation of 3-nitrotyrosine and carbonyl groups. These modifications may lead to changes of blood platelet functions and can have pathological consequences. The role of these different medicinal plants in the defence against oxidative/nitrative stress in human platelets is still unknown, therefore the oxidative damage to platelet proteins induced by peroxynitrite and protectory effects of tested conjugates by the estimation of carbonyl group level and nitrotyrosine formation (a marker of protein nitration) were studied in vitro. The antioxidative properties of the polyphenolic-polysaccharide conjugates from selected tested medicinal plants were also compared with the action of a well characterized antioxidative commercial polyphenol - resveratrol (3,4',5-trihydroxystilbene). The obtained results demonstrate that the compounds from herbal plants: A. millefolium, A. montana, E. purpurea, C. recutita, S. virgaurea, possess antioxidative properties and protect platelet proteins against peroxynitrite toxicity in vitro, similar to the glycoconjugates from C. canadensis. However, in the comparative studies, the polyphenolic

  1. Redox properties of the nitronyl nitroxide antioxidants studied via their reactions with nitroxyl and ferrocyanide.

    Science.gov (United States)

    Bobko, A A; Khramtsov, V V

    2015-01-01

    Nitronyl nitroxides (NNs) are the paramagnetic probes that are capable of scavenging physiologically relevant reactive oxygen (ROS) and nitrogen (RNS) species, namely superoxide, nitric oxide (NO), and nitroxyl (HNO). NNs are increasingly considered as potent antioxidants and potential therapeutic agents. Understanding redox chemistry of the NNs is important for their use as antioxidants and as paramagnetic probes for discriminative detection of NO and HNO by electron paramagnetic resonance (EPR) spectroscopy. Here we investigated the redox properties of the two most commonly used NNs, including determination of the equilibrium and rate constants of their reduction by HNO and ferrocyanide, and reduction potential of the couple NN/hydroxylamine of nitronyl nitroxide (hNN). The rate constants of the reaction of the NNs with HNO were found to be equal to (1-2) × 10(4) M(-1)s(- 1) being close to the rate constants of scavenging superoxide and NO by NNs. The reduction potential of the NNs and iminonitroxides (INs, product of NNs reaction with NO) were calculated based on their reaction constants with ferrocyanide. The obtained values of the reduction potential for NN/hNN (E'0 ≈ 285 mV) and IN/hIN (E' ≈ 495 mV) are close to the corresponding values for vitamin C and vitamin E, correspondingly. The "balanced" scavenging rates of the NNs towards superoxide, NO, and HNO, and their low reduction potential being thermodynamically close to the bottom of the pecking order of oxidizing radicals, might be important factors contributing into their antioxidant activity.

  2. Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction

    DEFF Research Database (Denmark)

    Stanyer, Lee; Jørgensen, Wenche; Hori, Osamu

    2008-01-01

    shown to degrade oxidatively modified aconitase in vitro and may thus play a role in defending against the accumulation of oxidized matrix proteins in mitochondria. Using an assay system that allowed us to distinguish between basal and ATP-stimulated Lon protease activity, we have shown in isolated non......-synaptic rat brain mitochondria that Lon protease is highly susceptible to oxidative inactivation by peroxynitrite (ONOO(-)). This susceptibility was more pronounced with regard to ATP-stimulated activity, which was inhibited by 75% in the presence of a bolus addition of 1mM ONOO(-), whereas basal unstimulated...... more sensitive than basal Lon protease activity. Furthermore, supplementation of mitochondrial matrix extracts with reduced glutathione, following ONOO(-) exposure, resulted in partial restoration of basal and ATP-stimulated activity, thus suggesting possible redox regulation of this enzyme complex...

  3. Peroxynitrite mediates programmed cell death both in papillar cells and in self-incompatible pollen in the olive (Olea europaea L.)

    Science.gov (United States)

    Serrano, Irene; Romero-Puertas, María C.; Rodríguez-Serrano, María; Sandalio, Luisa M.; Olmedilla, Adela

    2012-01-01

    Programmed cell death (PCD) has been found to be induced after pollination both in papillar cells and in self-incompatible pollen in the olive (Olea europaea L.). Reactive oxygen species (ROS) and nitric oxide (NO) are known to be produced in the pistil and pollen during pollination but their contribution to PCD has so far remained elusive. The possible role of ROS and NO was investigated in olive pollen–pistil interaction during free and controlled pollination and it was found that bidirectional interaction appears to exist between the pollen and the stigma, which seems to regulate ROS and NO production. Biochemical evidence strongly suggesting that both O2˙− and NO are essential for triggering PCD in self-incompatibility processes was also obtained. It was observed for the first time that peroxynitrite, a powerful oxidizing and nitrating agent generated during a rapid reaction between O2˙− and NO, is produced during pollination and that this is related to an increase in protein nitration which, in turn, is strongly associated with PCD. It may be concluded that peroxynitrite mediates PCD during pollen–pistil interaction in Olea europaea L. both in self-incompatible pollen and papillar cells. PMID:22140239

  4. Ferromagnetic interactions in Ru(III)-nitronyl nitroxide radical complex: a potential 2p4d building block for molecular magnets.

    Science.gov (United States)

    Pointillart, Fabrice; Bernot, Kevin; Sorace, Lorenzo; Sessoli, Roberta; Gatteschi, Dante

    2007-07-07

    The reaction between [Ru(salen)(PPh3)Cl] and the 4-pyridyl-substituted nitronyl nitroxide radical (NITpPy) leads to the [Ru(salen)(PPh3)(NITpPy)](ClO4)(H2O)2 complex while the reaction with the azido anion (N3-) leads to the [Ru(salen)(PPh3)(N3)] complex 2 (where salen2- = N,N'-ethan-1,2-diylbis(salicylidenamine) and PPh3 = triphenylphosphine). Both compounds have been characterized by single crystal X-ray diffraction. The two crystal structures are composed by a [Ru(III)(salen)(PPh3)]+ unit where the Ru(III) ion is coordinated to a salen2- ligand and one PPh3 ligand in axial position. In 1 the Ru(III) ion is coordinated to the 4-pyridyl-substituted nitronyl nitroxide radical whereas in 2 the second axial position is occupied by the azido ligand. In both complexes the Ru(III) ions are in the same environment RuO2N3P, in a tetragonally elongated octhaedral geometry. The crystal packing of 1 reveals pi-stacking in pairs. While antiferromagnetic intermolecular interaction (J2 = 5.0 cm(-1)) dominates at low temperatures, ferromagnetic intramolecular interaction (J1 = -9.0 cm(-1)) have been found between the Ru(III) ion and the coordinated NITpPy.

  5. Mononitroxides and proximate dinitroxides derived by oxidation of 2,2,4,4,5,5-hexasubstituted imidazolidines. A new series of nitroxide and dinitroxide spin labels

    International Nuclear Information System (INIS)

    Keana, J.F.W.; Norton, R.S.; Morello, M.; Van Engen, D.; Clardy, J.

    1978-01-01

    The synthesis and some properties of two members of a new series of rigid dinitroxides in which the nitroxide groups are separated from each other by only one carbon atom are reported. The synthesis of reverse intermediate imidazolidine mononitroxides which may have potential as new spin labels is also reported

  6. Stereocontrol of Methyl Methacrylate during Photoinduced Nitroxide-Mediated Polymerization in the Presence of Photosensitive Alkoxyamine

    Directory of Open Access Journals (Sweden)

    Juahui Su

    2016-01-01

    Full Text Available Photosensitive alkoxyamine 2,2,6,6-tetramethyl-1-(1-phenylethoxypiperidin-4-yl quinoline-2-carboxylate (PE-TEMPO-Q was synthesized. Photochemical properties of PE-TEMPO-Q were studied to develop photoinduced nitroxide-mediated polymerization of methyl methacrylate (MMA. Rapid and facile polymerization at ambient temperature with PE-TEMPO-Q as an initiator was confirmed to proceed in a controlled mechanism based on the linear growth in molecular weight combined with relative narrow polydispersity index (1.4–1.8 of the resulting polymers. The stereochemistry of obtained polymers was also investigated, and the syndiotacticity slightly increased compared with the typical photopolymerization. Dual-controlled photopolymerization of MMA was achieved in the presence of synthesized alkoxyamine.

  7. Nuclear spin-lattice relaxation in nitroxide spin-label EPR.

    Science.gov (United States)

    Marsh, Derek

    2016-11-01

    Nuclear relaxation is a sensitive monitor of rotational dynamics in spin-label EPR. It also contributes competing saturation transfer pathways in T 1 -exchange spectroscopy, and the determination of paramagnetic relaxation enhancement in site-directed spin labelling. A survey shows that the definition of nitrogen nuclear relaxation rate W n commonly used in the CW-EPR literature for 14 N-nitroxyl spin labels is inconsistent with that currently adopted in time-resolved EPR measurements of saturation recovery. Redefinition of the normalised 14 N spin-lattice relaxation rate, b=W n /(2W e ), preserves the expressions used for CW-EPR, whilst rendering them consistent with expressions for saturation recovery rates in pulsed EPR. Furthermore, values routinely quoted for nuclear relaxation times that are deduced from EPR spectral diffusion rates in 14 N-nitroxyl spin labels do not accord with conventional analysis of spin-lattice relaxation in this three-level system. Expressions for CW-saturation EPR with the revised definitions are summarised. Data on nitrogen nuclear spin-lattice relaxation times are compiled according to the three-level scheme for 14 N-relaxation: T 1 n =1/W n . Results are compared and contrasted with those for the two-level 15 N-nitroxide system. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Microstructural study of a nitroxide-mediated poly(ethylene oxide)/polystyrene block copolymer (PEO-b-PS) by electrospray tandem mass spectrometry.

    Science.gov (United States)

    Girod, Marion; Phan, Trang N T; Charles, Laurence

    2008-08-01

    Electrospray ionization tandem mass spectrometry has been used to characterize the microstructure of a nitroxide-mediated poly(ethylene oxide)/polystyrene block copolymer, called SG1-capped PEO-b-PS. The main dissociation route of co-oligomers adducted with lithium or silver cation was observed to proceed via the homolytic cleavage of a C-ON bond, aimed at undergoing reversible homolysis during nitroxide mediated polymerization. This cleavage results in the elimination of the terminal SG1 end-group as a radical, inducing a complete depolymerization process of the PS block from the so-formed radical cation. These successive eliminations of styrene molecules allowed a straightforward determination of the PS block size. An alternative fragmentation pathway of the radical cation was shown to provide structural information on the junction group between the two blocks. Proposed dissociation mechanisms were supported by accurate mass measurements. Structural information on the SG1 end-group could be reached from weak abundance fragment ions detected in the low m/z range of the MS/MS spectrum. Amongst fragments typically expected from PS dissociation, only beta ions were produced. Moreover, specific dissociation of the PEO block was not observed to occur in MS/MS, suggesting that these rearrangement reactions do not compete effectively with dissociations of the odd-electron fragment ions. Information about the PEO block length and the initiated end-group were obtained in MS(3) experiments.

  9. Peroxynitrite and Peroxiredoxin in the Pathogenesis of Experimental Amebic Liver Abscess

    Directory of Open Access Journals (Sweden)

    Judith Pacheco-Yepez

    2014-01-01

    Full Text Available The molecular mechanisms by which Entamoeba histolytica causes amebic liver abscess (ALA are still not fully understood. Amebic mechanisms of adherence and cytotoxic activity are pivotal for amebic survival but apparently do not directly cause liver abscess. Abundant evidence indicates that chronic inflammation (resulting from an inadequate immune response is probably the main cause of ALA. Reports referring to inflammatory mechanisms of liver damage mention a repertoire of toxic molecules by the immune response (especially nitric oxide and reactive oxygen intermediates and cytotoxic substances released by neutrophils and macrophages after being lysed by amoebas (e.g., defensins, complement, and proteases. Nevertheless, recent evidence downplays these mechanisms in abscess formation and emphasizes the importance of peroxynitrite (ONOO−. It seems that the defense mechanism of amoebas against ONOO−, namely, the amebic thioredoxin system (including peroxiredoxin, is superior to that of mammals. The aim of the present text is to define the importance of ONOO− as the main agent of liver abscess formation during amebic invasion, and to explain the superior capacity of amoebas to defend themselves against this toxic agent through the peroxiredoxin and thioredoxin system.

  10. Total peroxynitrite scavenging capacity of phenylethanoid and flavonoid glycosides from the flowers of Buddleja officinalis.

    Science.gov (United States)

    Tai, Bui Huu; Jung, Bong Yong; Cuong, Nguyen Manh; Linh, Pham Thuy; Tung, Nguyen Huu; Nhiem, Nguyen Xuan; Huong, Tran Thu; Anh, Ngo Thi; Kim, Jeong Ah; Kim, Sang Kyum; Kim, Young Ho

    2009-12-01

    Nine compounds, including six phenylethanoid glycosides: acteoside (1); bioside (2); echinacoside (3); poliumoside (4); phenylethyl glycoside (5); salidroside (6) and three flavonoids; linarin (7); apigenin (8); isorhoifolin (9), were isolated from the flowers of Buddleja officinalis MAXIM. (Buddlejaceae). Chemical structures were confirmed by (1)H-, and (13)C-NMR, and MS spectral methods and compared with those reported in the literature. Antioxidant activities of the methanol and water extracts, and all isolated compounds were evaluated using the total oxidant scavenging capacity (TOSC) assay against peroxynitrite. Results of the assay showed that the phenylethanoid glycosides, a major class of compounds of the flowers of B. officinalis, possess strong antioxidant activity. Of these, acteoside, echinacoside and poliumoside have 9.9-, 9.8- and 9.5-fold TOSC value, respectively, compared with the positive control, Trolox.

  11. NO, nitrosonium ions, nitroxide ions, nitrosothiols and iron-nitrosyls in biology: a chemist's perspective.

    Science.gov (United States)

    Butler, A R; Flitney, F W; Williams, D L

    1995-01-01

    The multiplicity of biological functions thus far attributed to NO has led to suggestions that some effects might be mediated by other, related species instead. The radical nature of NO cannot account for its cytotoxicity, but its reaction with superoxide to form peroxynitite and highly reactive hydroxyl radicals may be important in this context. The ease with which NO can react with and destroy Fe-S clusters is also an important factor. Nitrosonium and nitroxide ions can be produced in vivo and will react under conditions that are physiologically relevant. Both could, in theory, serve in cell signalling or as cytotoxic agents. More direct experimental evidence for their involvement is needed before we can confidently assign them specific biological roles. In this article, Anthony Butler, Frederick Flitney and Lyn Williams discuss the chemistry of NO and related species.

  12. Quenching of photoluminescence of colloidal ZnO nanocrystals by nitronyl nitroxide radicals

    Energy Technology Data Exchange (ETDEWEB)

    Stroyuk, Oleksandr L., E-mail: stroyuk@inphyschem-nas.kiev.ua [L.V. Pysarzhevsky Institute of Physical Chemistry of National Academy of Sciences of Ukraine, 31 Nauky avenue, 03028 Kyiv (Ukraine); Yakovenko, Anastasiya V.; Raevskaya, Oleksandra E. [L.V. Pysarzhevsky Institute of Physical Chemistry of National Academy of Sciences of Ukraine, 31 Nauky avenue, 03028 Kyiv (Ukraine); Plyusnin, Victor F. [Institute of Chemical Kinetics and Combustion of Siberian Branch of Russian Academy of Sciences, Novosibirsk (Russian Federation)

    2014-11-15

    Quenching of the photoluminescence of colloidal zinc oxide nanocrystals by a series of stable nitronyl nitroxide radicals was studied by means of stationary and time-resolved luminescence spectroscopy. Among the studied radicals the most efficient quenchers of the ZnO luminescence are the carboxyl-substituted species. The meta-substituted radical was found to be a more active quencher, than para-substituted one due to a closer proximity of the radical center to the nanocrystals surface. The PL quenching has a complex dynamic/static character. The dynamic quenching arises from photocatalytic radical reduction by ZnO conduction band electrons, while the static quenching is caused by adsorption of the photoreduction products on the nanocrystal surface. The non-substituted and OH-substituted radicals are inferior to the products of their photoreduction in capability of adsorption of the ZnO surface, and the quenching is dominated by interactions between the nanocrystals and photoreduced hydroxylamines. In case of COOH-substituted radicals, however, the radicals compete with the photoreduction products for the surface sites of ZnO nanocrystals resulting in a dynamic character of photoluminescence quenching.

  13. Smooth transition between SMM and SCM-type slow relaxing dynamics for a 1-D assemblage of {Dy(nitronyl nitroxide)2} units.

    Science.gov (United States)

    Liu, Ruina; Li, Licun; Wang, Xiaoling; Yang, Peipei; Wang, Chao; Liao, Daizheng; Sutter, Jean-Pascal

    2010-04-21

    A model example for size effects on the dynamic susceptibility behavior is provided by the chain compound [{Dy(hfac)(3)NitPhIm(2)}Dy(hfac)(3)] (NitPhIm = 2-[4-(1-imidazole)phenyl]nitronyl nitroxide radical). The Arrhenius plot reveals two relaxation regimes attributed to SMM (Delta = 17.1 K and tau(0) = 17.5 x 10(-6) s) and SCM (Delta = 82.7 K and tau(0) = 8.8 x 10(-8) s) behaviors. The ferromagnetic exchange among the spin carriers has been established for the corresponding Gd derivative.

  14. [Peroxynitrite effect on the haemoglobin oxygen affinity in vitro in presence of different partial pressure of carbon dioxide].

    Science.gov (United States)

    Stepuro, T L; Zinchuk, V V

    2011-08-01

    Peroxynitrite (ONOO-) besides its toxic possesses regulatory action that includes the modulation of oxygen binding properties of blood. The aim of this work was to estimate ONOO- effect on the haemoglobin oxygen affinity (HOA) in vitro in presence of different partial pressure of carbon dioxide (CO2). The ONOO- presence in venous blood in conditions of hypercapnia induced oxyhaemoglobin dissociation curve shift leftward while in hypocapnic conditions the result of a different character was obtained. The revealed effect of ONOO- is realized, possibly, through various modifications ofhaemoglobin whose formation is dependent on the CO2 pressure. The ONOO- influences the HOA in different manner that can be important in regulation of blood oxygenation in lungs and maintenance of oxygen consumption in tissues.

  15. Synthesis, autoxidation and photooxidation of hindered pyrrole derivatives. Hindered pyrrolic nitroxide radicals; Synthese, autoxydation et photoxidation de pyrroles encombres radicaux nitroxydes pyrroliques encombres

    Energy Technology Data Exchange (ETDEWEB)

    Ramasseul, R [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1969-07-01

    2,5-di-t-butyl and 2,3,5-tri-t-butyl pyrrole are prepared from pinacoline and their structure is confirmed by comparison with 2,5-di-t-butyl furan and thiophene (I.R., U.V. and N.M.R. {sup 13}C satellites observation giving J{sub 13{sub C-H}} and J{sub H{sub 3}-H{sub 4}}). The sensitized photooxidation of these hindered pyrroles gives corresponding hydroperoxides which most likely structure is determined using physical and chemical methods. Oxidation of 2,5-di-t-butyl and 2,3,5-tri-t-butyl pyrrole by hydrogen peroxide in presence of inorganic per-acid of by p-nitro-perbenzoic acid does not give the pyrrolic nitroxides in contrast with secondary amines. Some N-hydroxypyrroles are then prepared from pinacoline and ethyl pivaloyl-acetate. Their oxidation by lead dioxide gives the corresponding pyrrolic nitroxides. 2,5-di-t-butyl 3,4-di-ethoxycarbonyl pyrryl 1-oxy is isolated and studied spectroscopically (visible and U.V., E.P.R.). In marked contrast with ordinary nitroxides it does not show solvent effect. It can be compared with 2,4-di-t-butyl cyclopentadienone, a carbon analog. For both, the long wave length transition does not show the usual n - {pi}* behaviour; that is confirmed by E.P.R. Using Huckel method for pyrrolic nitroxide skeleton, it is possible to have a good interpretation of experimental data. (author) [French] Les di-t-butyl 2,5 et tri-t-butyl-2,3,5 pyrrole sont synthetises a partir de la pinacoline et leur structure confirmee par comparaison avec les di-t-butyl-2,5 furanne et thiophene (I.R., U.V. et R.M.N.: observation des satellites {sup 13}C conduisant a la mesure des J{sub 13{sub C-H}} et J{sub H{sub 3}{sub -H{sub 4}}). La photoxydation sensibilisee de ces pyrroles encombres conduit aux hydroperoxydes correspondants dont la structure la plus probable est determinee par les methodes physicochimiques. L'oxydation des di-t-butyl-2,5 et tri-t-butyl-2,3,5 pyrrole par l'eau oxygenee en presence de peracide mineral ou par l'acide p

  16. Studies of a nitroxide radical by EPR in monocrystal: interaction of protons and electronic relaxation

    International Nuclear Information System (INIS)

    Alonso, A.

    1986-01-01

    The ESR spectra of a nitroxide radical, 4-hydroxi-2,2,6,6-tetramethylpiperidine-1-oxyl (TANOL II), introduced as impurity in a diamagnetic host, 4-hydroxi-2,6,6-tetramethylpiperedine (I), were investigated. The use of deuterated radical, 4-hydroxi-2,2,6,6 tetramethylpiperidine-d sub(17) -1, oxyl (PD-TANOL, III) improved the resolution of ESR spectra for most of orientations of magnetic field. The proton interqactions in the neighbourhood of magnetic group N-O were studied and superpyresfine tensors for two strongly coupled protons were determined. In order to study the influence of protons on electronic relaxation of radicals, the relaxation times T sub(1) and T sub(2) were estimated in the temperature range-160 sup(0)C - 25 sup(0)C for several orientations, and comparing data for protonated and deuterated radicals II and III, using the continuous wave saturation method. (author)

  17. Experimental study of living free radical polymerization using trifunctional initiator and polymerization mediated by nitroxide

    International Nuclear Information System (INIS)

    Galhardo, Eduardo; Lona, Liliane M.F.

    2009-01-01

    Controlled free radical polymerization or living free radical polymerization has received increasing attention as a technique for the production of polymers with microstructure highly controlled. In particular, narrow molecular weight distributions are obtained with polydispersity very close to one. In this research it was investigate the controlled polymerization mediated by nitroxide, using a cyclic trifunctional peroxide. As long as we know, there are only publications in literature dealing with NMRP using mono- and bi-functional initiators. It was believed that the trifunctional peroxide can increase the rate of polymerization, since more free radicals are generated, if compared with initiators with lower functionality. Furthermore, the fact of the initiator be cyclic means that branches are not generated in the chains, which theoretically prevents an increase in polydispersity of the polymer. The effect of the dissociation constant of the trifunctional initiator in the velocity of the reaction was analyzed. (author)

  18. Scavenging of peroxynitrite by phycocyanin and phycocyanobilin from Spirulina platensis: protection against oxidative damage to DNA.

    Science.gov (United States)

    Bhat, V B; Madyastha, K M

    2001-07-13

    Peroxynitrite (ONOO(-)) is known to inactivate important cellular targets and also mediate oxidative damage in DNA. The present study has demonstrated that phycocyanin, a biliprotein from spirulina platensis and its chromophore, phycocyanobilin (PCB), efficiently scavenge ONOO(-), a potent physiological inorganic toxin. Scavenging of ONOO(-) by phycocyanin and PCB was established by studying their interaction with ONOO(-) and quantified by using competition kinetics of pyrogallol red bleaching assay. The relative antioxidant ratio and IC(50) value clearly indicate that phycocyanin is a more efficient ONOO(-) scavenger than PCB. The present study has also shown that PCB significantly inhibits the ONOO(-)-mediated single-strand breaks in supercoiled plasmid DNA in a dose-dependent manner with an IC(50) value of 2.9 +/- 0.6 microM. These results suggest that phycocyanin, has the ability to inhibit the ONOO(-)-mediated deleterious biological effects and hence has the potential to be used as a therapeutic agent. Copyright 2001 Academic Press.

  19. A study of the conformation and stability of nitroxide free radicals; Etude de la conformation et de la stabilite de radicaux libres nitroxydes

    Energy Technology Data Exchange (ETDEWEB)

    Briere, R [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1969-03-01

    The first part of this study is an application of nuclear magnetic resonance to the determination of the sign and magnitude of the long range nuclear-electron spin-spin couplings in the free radical nitroxide derived from piperidine. It has been shown that the coupling constants of the protons {gamma} to the nitrogen atom have a pronounced spatial dependence as do the protons in the {beta} position, a point which has not been brought out by previous investigations. Conformational analysis of these compounds has been carried out by measurement of the effect of temperature on the NMR spectra at 310 MHz. The synthesis of di-t-Bu nitroxide labelled with C{sup 13} in the {alpha}-position made possible the unambiguous determination of the corresponding {sup 13}C nuclear-electron spin-spin coupling constant, a parameter which had not previously been measured. The coupling constants measured in the 2,2,6,6-tetramethyl piperidine series could then be attributed to the {sup 13}C atoms in the {beta}-position and their variation related to the conformations of the heterocycles. This constitutes the second part of the work reported here. The final section is devoted to a study of the decomposition of an unstable nitroxide having a hydrogen atom in the p-position. This decomposition is bimolecular and the primary isotope effect shows that the rupture. of the C-H bond is involved. From this one can conclude that a nitroxide is stable when the different groups attached to the nitrogen atom cannot give rise to a decomposition either intra molecularly, if the molecular geometry is suitable, or inter molecularly by dimerisation through attack on a different center of a neighbouring molecule thus leading to a fragmentation or a disproportionation. (author) [French] La premiere partie est une application de la resonance magnetique nucleaire a la determination du signe et de la grandeur des couplages a longue distance dans des radicaux libres nitroxydes piperidiniques. Il est montre que

  20. AN ALTERNATIVE ROUTE TO PRODUCE STANDARDS FOR GEL PERMEATION CHROMATOGRAPHY USING NITROXIDE MEDIATED POLYMERIZATION

    Directory of Open Access Journals (Sweden)

    C. P. R. Malere

    Full Text Available Abstract All over the world standards for Gel Permeation Chromatography (GPC are produced using ionic polymerization. Standards are commercialized in a broad range of molecular weight and their dispersity (Ð must be lower than 1.1. This work proposes the synthesis of polystyrene standards using Nitroxide Mediated Polymerization (NMP, an alternative technique to produce controlled polymers that is much more robust when compared to ionic polymerization. Standards with different ranges of molecular weights were obtained, all of them with very narrow molecular weight distribution (MWD and dispersity (Ð lower than 1.10. In order to do that, several combinations of different initiators were tested. Advanced GPC Triple Detector was used to obtain important properties, such as absolute number and weight average molecular weights, dispersity and intrinsic viscosity. The analytical method used in the characterization of the samples was in-house validated in terms of linearity, accuracy, precision, repeatability and robustness. The validation study demonstrated the quality of the measurements and ensured that the information obtained for a given analyte by the GPC technique is reliable.

  1. Real-time monitoring of drug-induced changes in the stomach acidity of living rats using improved pH-sensitive nitroxides and low-field EPR techniques

    Science.gov (United States)

    Potapenko, Dmitrii I.; Foster, Margaret A.; Lurie, David J.; Kirilyuk, Igor A.; Hutchison, James M. S.; Grigor'ev, Igor A.; Bagryanskaya, Elena G.; Khramtsov, Valery V.

    2006-09-01

    New improved pH-sensitive nitroxides were applied for in vivo studies. An increased stability of the probes towards reduction was achieved by the introduction of the bulky ethyl groups in the vicinity of the paramagnetic N sbnd O fragment. In addition, the range of pH sensitivity of the approach was extended by the synthesis of probes with two ionizable groups, and, therefore, with two p Ka values. Stability towards reduction and spectral characteristics of the three new probes were determined in vitro using 290 MHz radiofrequency (RF)- and X-band electron paramagnetic resonance (EPR), longitudinally detected EPR (LODEPR), and field-cycled dynamic nuclear polarization (FC-DNP) techniques. The newly synthesized probe, 4-[bis(2-hydroxyethyl)amino]-2-pyridine-4-yl-2,5,5-triethyl-2,5-dihydro-1 H-imidazol-oxyl, was found to be the most appropriate for the application in the stomach due to both higher stability and convenient pH sensitivity range from pH 1.8 to 6. LODEPR, FC-DNP and proton-electron double resonance imaging (PEDRI) techniques were used to detect the nitroxide localization and acidity in the rat stomach. Improved probe characteristics allowed us to follow in vivo the drug-induced perturbation in the stomach acidity and its normalization afterwards during 1 h or longer period of time. The results show the applicability of the techniques for monitoring drug pharmacology and disease in the living animals.

  2. Homoleptic Ce(III) and Ce(IV) Nitroxide Complexes: Significant Stabilization of the 4+ Oxidation State

    Energy Technology Data Exchange (ETDEWEB)

    Bogart, Justin A.; Lewis, Andrew J.; Medling, Scott A.; Piro, Nicholas A.; Carroll, Patrick J.; Booth, Corwin H.; Schelter, Eric J.

    2014-06-25

    Electrochemical experiments performed on the complex Ce-IV[2-((BuNO)-Bu-t)py](4), where [2-((BuNO)-Bu-t)py](-) = N-tert-butyl-N-2-pyridylnitroxide, indicate a 2.51 V stabilization of the 4+ oxidation state of Ce compared to [(Bu4N)-Bu-n](2)[Ce(NO3)(6)] in acetonitrile and a 2.95 V stabilization compared to the standard potential for the ion under aqueous conditions. Density functional theory calculations suggest that this preference for the higher oxidation state is a result of the tetrakis(nitroxide) ligand framework at the Ce cation, which allows for effective electron donation into, and partial covalent overlap with, vacant 4f orbitals with delta symmetry. The results speak to the behavior of CeO2 and related solid solutions in oxygen uptake and transport applications, in particular an inherent local character of bonding that stabilizes the 4+ oxidation state. The results indicate a cerium(IV) complex that has been stabilized to an unprecedented degree through tuning of its ligand-field environment.

  3. Peroxynitrite Sensor Based on a Screen Printed Carbon Electrode Modified with a Poly(2,6-dihydroxynaphthalene Film

    Directory of Open Access Journals (Sweden)

    Ioana Silvia Hosu

    2016-11-01

    Full Text Available For the first time the electropolymerization of 2,6-dihydroxynaphthalene (2,6-DHN on a screen printed carbon electrode (SPCE was investigated and evaluated for peroxynitrite (PON detection. Cyclic voltammetry was used to electrodeposit the poly(2,6-DHN on the carbon electrode surface. The surface morphology and structure of poly(2,6-DHN film were investigated by SEM and FTIR analysis, and the electrochemical features by cyclic voltammetry. The poly(2,6-DHN/SPCE sensor showed excellent electrocatalytic activity for PON oxidation in alkaline solutions at very low potentials (0–100 mV vs. Ag/AgCl pseudoreference. An amperometric FIA (flow injection analysis system based on the developed sensor was optimized for PON measurements and a linear concentration range from 2 to 300 μM PON, with a LOD of 0.2 μM, was achieved. The optimized sensor inserted in the FIA system exhibited good sensitivity (4.12 nA·μM−1, selectivity, stability and intra-/inter-electrode reproducibility for PON determination.

  4. Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis.

    Science.gov (United States)

    Shaw, Catherine A; Webb, David J; Rossi, Adriano G; Megson, Ian L

    2009-05-07

    Nitric oxide (NO) can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-). In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMvarphi), and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP) is able to limit apoptosis in this cell type. Characterisation of the NO-related species generated by (Z)-1- [2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO) and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl)-, chloride (GEA-3162) was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR) spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMvarphi. Resultant MDMvarphi were treated for 24 h with DETA/NO (100 - 1000 muM) or GEA-3162 (10 - 300 muM) in the presence or absence of BAY 41-2272 (1 muM), isobutylmethylxanthine (IBMX; 1 muM), 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 muM) or 8-bromo-cGMP (1 mM). Apoptosis in MDMvarphi was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO) had no effect on cell viability, but ONOO- (GEA-3162) caused a concentration-dependent induction of apoptosis in MDMvarphi. Preconditioning of MDMvarphi with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX), or the NO-independent stimulator of soluble guanylate cyclase, BAY 41-2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner. These results

  5. Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Rossi Adriano G

    2009-05-01

    Full Text Available Abstract Background Nitric oxide (NO can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-. In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMϕ, and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP is able to limit apoptosis in this cell type. Methods Characterisation of the NO-related species generated by (Z-1- [2-(2-aminoethyl-N-(2-ammonioethylamino]diazen-1-ium-1,2-diolate (DETA/NO and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl-, chloride (GEA-3162 was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMϕ. Resultant MDMϕ were treated for 24 h with DETA/NO (100 – 1000 μM or GEA-3162 (10 – 300 μM in the presence or absence of BAY 41–2272 (1 μM, isobutylmethylxanthine (IBMX; 1 μM, 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 μM or 8-bromo-cGMP (1 mM. Apoptosis in MDMϕ was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Results Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO had no effect on cell viability, but ONOO- (GEA-3162 caused a concentration-dependent induction of apoptosis in MDMϕ. Preconditioning of MDMϕ with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX, or the NO-independent stimulator of soluble guanylate cyclase, BAY 41–2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner

  6. Preparation and physico-chemical study of nitroxide radicals. Isotopic marking with carbon 13 and deuterium; Preparations et etudes physico-chimiques de radicaux nitroxydes. Marquage isotopique au carbone 13 et au deuterium

    Energy Technology Data Exchange (ETDEWEB)

    Chapelet-Letourneux, G [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1967-07-01

    N-t-butyl-N-phenyl nitroxide is obtained by: a) action of t-butyl-magnesium chloride on nitrobenzene, or of phenyl-magnesium bromide on nitro-t-butane, b) oxidation of N-t-butyl-N-phenylhydroxylamine, c) oxidation of N-t-butylaniline. In these latter two cases, it has been possible to isolate the pure radical and to study it using UV, IR and EPR. It decomposes to give N-t-butylaniline and the N-oxide of N-t-butyl-p-quinon-imine. The action of peracids such as p-nitro-perbenzoic or m-chloro-perbenzoic acids on amines or hydroxylamines leads to the formation of stable or unstable nitroxide radicals easily observable by EPR. Finally, with a view to obtaining definite values for the coupling between the free electron of a nitroxide and carbon 13, the preparation of such radicals marked with {sup 13}C in the {alpha} or {beta} position of the nitroxide function has been carried out. The coupling with an {alpha} carbon 13 is negative and does not appear to vary with the spin density on the nitrogen. The interaction with the p nuclei of the nitrogen depends on the nature of the substituents: the two benzyl protons have a hyperfine splitting a{sub H} which is always less than that of the ethyl. On the other hand, the {sup 13}C coupling is greater in the first case. The usually adopted conformations for the compounds having the carbonyl group cannot account for the observed values of the {beta} couplings. (author) [French] Le N-t-butyl-N-phenyl nitroxyde est obtenu par: a) action du chlorure de t-butylmagnesium sur le nitrobenzene, ou du bromure de phenylmagnesium sur le nitro-t-butane, b) oxydation de la N-t-butyl-N-phenylhydroxylamine, c) oxydation de la N-t-butylaniline. Dans ces deux derniers cas, le radical a pu etre isole pur et etudie par UV, IR et RPE. Il se decompose en N-t-butylaniline et N-oxyde de N-t-butyl-p-quinonimine. L'action de peracides (p-nitroperbenzoique ou m-chloroperbenzoique) sur des amines ou des hydroxylamines conduit a des radicaux nitroxydes

  7. The nitroxide radical TEMPOL prevents obesity, hyperlipidaemia, elevation of inflammatory cytokines, and modulates atherosclerotic plaque composition in apoE(-/-) mice

    DEFF Research Database (Denmark)

    Kim, Christine H. J.; Mitchell, James B.; Bursill, Christina A.

    2015-01-01

    and a decrease in adiponectin. TEMPOL supplementation reversed these effects. When compared to HFD-fed mice, TEMPOL supplementation increased plaque collagen content, decreased lipid content and increased macrophage numbers. CONCLUSIONS: These data indicate that in a well-established model of obesity-associated......OBJECTIVE: The nitroxide compound TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl radical) has been shown to prevent obesity-induced changes in adipokines in cell and animal systems. In this study we investigated whether supplementation with TEMPOL inhibits inflammation and atherosclerosis...... in apoE(-/-) mice fed a high fat diet (HFD). METHODS: ApoE(-/-) mice were fed for 12 weeks on standard chow diet or a high-fat diet. Half the mice were supplemented with 10 mg/g TEMPOL in their food. Plasma samples were analysed for triglycerides, cholesterol, low- and high-density lipoprotein...

  8. Dynamic, in vivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe.

    Science.gov (United States)

    Rayner, Cassie L; Gole, Glen A; Bottle, Steven E; Barnett, Nigel L

    2014-12-01

    Changes to the redox status of biological systems have been implicated in the pathogenesis of a wide variety of disorders including cancer, Ischemia-reperfusion (I/R) injury and neurodegeneration. In times of metabolic stress e.g. ischaemia/reperfusion, reactive oxygen species (ROS) production overwhelms the intrinsic antioxidant capacity of the cell, damaging vital cellular components. The ability to quantify ROS changes in vivo, is therefore essential to understanding their biological role. Here we evaluate the suitability of a novel reversible profluorescent probe containing a redox-sensitive nitroxide moiety (methyl ester tetraethylrhodamine nitroxide, ME-TRN), as an in vivo, real-time reporter of retinal oxidative status. The reversible nature of the probe's response offers the unique advantage of being able to monitor redox changes in both oxidizing and reducing directions in real time. After intravitreal administration of the ME-TRN probe, we induced ROS production in rat retina using an established model of complete, acute retinal ischaemia followed by reperfusion. After restoration of blood flow, retinas were imaged using a Micron III rodent fundus fluorescence imaging system, to quantify the redox-response of the probe. Fluorescent intensity declined during the first 60 min of reperfusion. The ROS-induced change in probe fluorescence was ameliorated with the retinal antioxidant, lutein. Fluorescence intensity in non-Ischemia eyes did not change significantly. This new probe and imaging technology provide a reversible and real-time response to oxidative changes and may allow the in vivo testing of antioxidant therapies of potential benefit to a range of diseases linked to oxidative stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Role of peroxynitrite in the responses induced by heat stress in tobacco BY-2 cultured cells.

    Science.gov (United States)

    Malerba, Massimo; Cerana, Raffaella

    2018-07-01

    Temperatures above the optimum are sensed as heat stress (HS) by all living organisms and represent one of the major environmental challenges for plants. Plants can cope with HS by activating specific defense mechanisms to minimize damage and ensure cellular functionality. One of the most common effects of HS is the overproduction of reactive oxygen and nitrogen species (ROS and RNS). The role of ROS and RNS in the regulation of many plant physiological processes is well established. On the contrary, in plants very little is known about the physiological role of peroxynitrite (ONOO - ), the RNS species generated by the interaction between NO and O 2 - . In this work, the role of ONOO - on some of the stress responses induced by HS in tobacco BY-2 cultured cells has been investigated by measuring these responses both in the presence and in the absence of 2,6,8-trihydroxypurine (urate), a specific scavenger of ONOO - . The obtained results suggest a potential role for ONOO - in some of the responses induced by HS in tobacco cultured cells. In particular, ONOO - seems implicated in a form of cell death showing apoptotic features and in the regulation of the levels of proteins involved in the response to stress.

  10. Chemical modification of polyaniline by N-grafting of polystyrenic chains synthesized via nitroxide-mediated polymerization

    International Nuclear Information System (INIS)

    Hatamzadeh, Maryam; Mahyar, Ali; Jaymand, Mehdi

    2012-01-01

    This study aims to explore an effective route for the preparation of conductive N-substituted polyaniline (PANI) by the incorporation of brominated poly(styrene-co-p-methylstyrene) onto the emeraldine form of polyaniline. For this purpose, at first, poly(styrene-co-p-methylstyrene) was synthesized via nitroxide-mediated polymerization (NMP), and then, N-bromosuccinimide was used as brominating agent to obtain a copolymer with bromine. Thereafter, deprotonated polyaniline was reacted with brominated poly(styrene-co-p-methylstyrene) to prepare the poly(styrene-co-p-methylstyrene)-graft-polyaniline [(PSt-co-PMSt)-g-PANI] terpolymer through N-grafting reaction. The terpolymer was characterized by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Optical properties of (PSt-co-PMSt)-g-PANI in the undoped and doped states were obtained by ultraviolet-visible spectroscopy (UV-Vis), and electrical conductivity at room temperature was measured using samples in which the conductive materials was sandwiched between two Ni electrodes. Moreover, electroactivity of the synthesized terpolymer was verified under cyclic voltammetric conditions on the surface of the working glassy carbon electrode (GCE). The solubility of (PSt-co-PMSt)-g-PANI terpolymer was examined in common organic solvents, such as, tetrahydrofuran (THF), chloroform and xylene. (author)

  11. Correlation between the rate of bioreduction of nitroxide spin label by human tumor cells and their low-dose radiation response

    International Nuclear Information System (INIS)

    Halpern, H.J.; Peric, M.; Nguyen, T.D.; Spencer, D.P.; Bowman, M.K.; Beckett, M.; Weichselbaum, R.R.

    1988-01-01

    The authors discuss a correlation observed between the bioreduction of nitroxide spin label by four human tumor cell lines and a normal tissue fibroblast clone and their low-dose radiation response, specifically their D Q . In measurements of the bioreduction rate of several other cell lines, this correlation appears to persist. In order to define the mechanism of this correlation, they have begun by subtly altering the measurement conditions. The original conditions for measurement involved adding the spin label to cells whose culture medium had been changed (the label was added to the new medium). By delaying the addition of the label to the culture medium, they substantially reduced the variation of the bioreduction rate between the cell lines. This implies that the fresh medium provides a nonspecific irritant or disequilibrium to the cultured cell system to which they response variably by accelerating, among other things, the metabolic process responsible for spin label bioreduction

  12. A novel mitochondria-targeted two-photon fluorescent probe for dynamic and reversible detection of the redox cycles between peroxynitrite and glutathione.

    Science.gov (United States)

    Sun, Chunlong; Du, Wen; Wang, Peng; Wu, Yang; Wang, Baoqin; Wang, Jun; Xie, Wenjun

    2017-12-16

    Redox homeostasis is important for maintenance of normal physiological functions within cells. Redox state of cells is primarily a consequence of precise balance between levels of reducing equivalents and reactive oxygen species. Redox homeostasis between peroxynitrite (ONOO - ) and glutathione (GSH) is closely associated with physiological and pathological processes, such as prolonged relaxation in vascular tissues and smooth muscle preparations, attenuation of hepatic necrosis, and activation of matrix metalloproteinase-2. We report a two-photon fluorescent probe (TP-Se) based on water-soluble carbazole-based compound, which integrates with organic selenium, to monitor changes in ONOO - /GSH levels in cells. This probe can reversibly respond to ONOO - and GSH and exhibits high selectivity, sensitivity, and mitochondrial targeting. The probe was successfully applied to visualize changes in redox cycles during ONOO - outbreak and antioxidant GSH repair in cells. The probe will lead to significant development on redox events involved in cellular redox regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Nitroxide free radical clearance in the live rat monitored by radio-frequency CW-EPR and PEDRI

    International Nuclear Information System (INIS)

    Alecci, Marcello; Seimenis, Ioannis; McCallum, Stephen J.; Lurie, David J.; Foster, Margaret A.

    1998-01-01

    The use of RF (100 to 300 MHz) PEDRI and CW-EPR techniques allows the in vivo study of large animals such as whole rats and rabbits. Recently a PEDRI instrument was modified to also allow CW-EPR spectroscopy with samples of similar size and under the same experimental conditions. In the present study, this CW-EPR and PEDRI apparatus was used to assess the feasibility of the detection of a pyrrolidine nitroxide free radical (2,2,5,5,-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid, PCA) in the abdomen of rats. In particular, we have shown that after the PCA administration (4 mmol kg -1 b.w.): (i) the PCA EPR linewidth does not show line broadening due to concentration effects; (ii) a similar PCA up-take phase is observed by EPR and PEDRI; and (iii) the PCA half-lives in the whole abdomen of rats measured with the CW-EPR (T 1/2 =26±4 min, mean±sd, n=10) and PEDRI (T 1/2 =29±4 min, mean±sd, n=4) techniques were not significantly different (p>0.05). These results show, for the first time, that information about PCA pharmacokinetics obtained by CW-EPR is the same as that from PEDRI under the same experimental conditions. (author)

  14. Intermittent Hypoxia-Induced Carotid Body Chemosensory Potentiation and Hypertension Are Critically Dependent on Peroxynitrite Formation

    Directory of Open Access Journals (Sweden)

    Esteban A. Moya

    2016-01-01

    Full Text Available Oxidative stress is involved in the development of carotid body (CB chemosensory potentiation and systemic hypertension induced by chronic intermittent hypoxia (CIH, the main feature of obstructive sleep apnea. We tested whether peroxynitrite (ONOO−, a highly reactive nitrogen species, is involved in the enhanced CB oxygen chemosensitivity and the hypertension during CIH. Accordingly, we studied effects of Ebselen, an ONOO− scavenger, on 3-nitrotyrosine immunoreactivity (3-NT-ir in the CB, the CB chemosensory discharge, and arterial blood pressure (BP in rats exposed to CIH. Male Sprague-Dawley rats were exposed to CIH (5% O2, 12 times/h, 8 h/day for 7 days. Ebselen (10 mg/kg/day was administrated using osmotic minipumps and BP measured with radiotelemetry. Compared to the sham animals, CIH-treated rats showed increased 3-NT-ir within the CB, enhanced CB chemosensory responses to hypoxia, increased BP response to acute hypoxia, and hypertension. Rats treated with Ebselen and exposed to CIH displayed a significant reduction in 3-NT-ir levels (60.8 ± 14.9 versus 22.9 ± 4.2 a.u., reduced CB chemosensory response to 5% O2 (266.5 ± 13.4 versus 168.6 ± 16.8 Hz, and decreased mean BP (116.9 ± 13.2 versus 82.1 ± 5.1 mmHg. Our results suggest that CIH-induced CB chemosensory potentiation and hypertension are critically dependent on ONOO− formation.

  15. XMCD for monitoring exchange interactions. The role of the Gd 4f and 5d orbitals in metal-nitronyl nitroxide magnetic chains.

    Science.gov (United States)

    Champion, Guillaume; Lalioti, Nikolia; Tangoulis, Vassilis; Arrio, Marie-Anne; Sainctavit, Philippe; Villain, Françoise; Caneschi, Andrea; Gatteschi, Dante; Giorgetti, Christine; Baudelet, François; Verdaguer, Michel; Cartier dit Moulin, Christophe

    2003-07-09

    We report here the X-ray magnetic circular dichroism (XMCD) study at the Gd M(4,5)- and L(2,3)-edges of two linear magnetic chains involving Gd(III) cations bridged by nitronyl nitroxide radicals. This spectroscopy directly probes the magnetic moments of the 4f and 5d orbitals of the gadolinium ions. We compare macroscopic magnetic measurements and local XMCD signals. The M(4,5)-edges results are in agreement with the J values extracted from the fits of the SQUID magnetic measurements. The L(2,3)-edges signals show that the electronic density in the Gd 5d orbitals depends on the neighbors of the gadolinium cations. Nevertheless, the 5d orbitals do not seem to play any role in the superexchange pathway between radicals through the metal ion proposed to explain the particular magnetic exchange interactions between the radicals in these chains.

  16. Peroxynitrite-induced relaxation in isolated rat aortic rings and mechanisms of action

    International Nuclear Information System (INIS)

    Li Jianfeng; Li Wenyan; Altura, Bella T.; Altura, Burton M.

    2005-01-01

    The present study was designed to evaluate the effects of peroxynitrite (ONOO - ), the product of superoxide and nitric oxide, on isolated segments of rat aorta. In the absence of any vasoactive agent, ONOO - (from 10 -8 to 10 -4 M) failed to alter the basal tension. In phenylephrine (PE; 5 x 10 -7 M)-precontracted rat aortic rings (RAR), ONOO - elicited concentration-dependent relaxation at concentrations of from 10 -8 to 10 -4 M. The effective concentrations producing approximately 50% of maximal relaxation (ED 5 ) to ONOO - were 1.84 x 10 -5 M and 1.96 x 10 -5 M in intact and denuded RAR, respectively (P > 0.05). No significant differences in the relaxation responses were found between RAR with or without endothelium (P > 0.05). The presence of either 5 μM methylene blue (MB) or 5 μM 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one (ODQ) significantly inhibited the relaxations induced by ONOO - . Sildenafil (10 -7 M), on the other hand, significantly potentiated the ONOO - -induced relaxations. Tetraethylammonium chloride (T-2265) significantly decreased the ONOO - -induced relaxations in a concentration-dependent manner. However, ONOO - had no effect on RAR precontracted by high KCL (40 mM, n = 6, P > 0.05). Addition of calyculin A also significantly decreased the ONOO - -induced relaxation in a dose-dependent manner. Furthermore, ONOO - significantly inhibited calcium-induced contractions of K + -depolarized aortic rings in a concentration-related manner. Lastly, a variety of other pharmacological agents and antagonists including L-NMMA, L-arginine, indomethacin, atropine, naloxone, diphenhydramine, cimetine, glibenclamide, haloperidol, superoxide dismutase (SOD), and catalase did not influence the relaxant effects of ONOO - on RAR. Our new results suggest that ONOO - -triggered relaxation on rat aortic rings is mediated by elevation of cGMP levels, membrane hyperpolarization via K + -channel activation, activation of myosin phosphatase activity, and

  17. Peroxynitrite-induced relaxation in isolated canine cerebral arteries and mechanisms of action

    International Nuclear Information System (INIS)

    Li Jianfeng; Li Wenyan; Altura, Bella T.; Altura, Burton M.

    2004-01-01

    The present study was undertaken to determine the vascular actions of peroxynitrite (ONOO - ), the product of superoxide and nitric oxide (NO), in isolated canine cerebral arteries and to gain insight into its potential mechanisms of action. In the absence of any vasoactive agent, ONOO - (from 10 -7 to 10 -6 M) was able to reduce the basal tension. In prostaglandin F2α-precontracted canine basilar arterial rings, ONOO - elicited concentration-dependent relaxation at concentrations from 10 -8 to 10 -5 M. The effective concentrations producing approximately 50% maximal relaxation (EC 50 ) to ONOO - were 4.06 x 10 -6 and 4.12 x 10 -6 M in intact and denuded rings, respectively (P > 0.05). No significant differences in relaxation responses were found in ring preparations with or without endothelium (P > 0.05). The presence of either 5 μM methylene blue (MB) or 5 μM 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one (ODQ) significantly inhibited the relaxations induced by ONOO - . Tetraethylammonium chloride (T-2265) significantly decreased the ONOO - -induced relaxations in a concentration-dependent manner. However, ONOO - had no effect on rings precontracted by high KCL (P > 0.05). Addition of low concentrations of calyculin A (50 nM) was able to abolish the ONOO - -induced relaxation. Furthermore, ONOO - significantly inhibited calcium-induced contractions of K + -depolarized canine cerebral rings in a concentration-related manner. Lastly, a variety of pharmacological agents and antagonists including L-NMMA, L-arginine, indomethacin, atropine, naloxone, diphenhydramine, cimetine, glibenclamide, haloperidol, etc., did not influence the relaxant effects of ONOO - on the rings. Our new results suggest that ONOO - -triggered relaxation, on canine cerebral arteries, is mediated by elevation of cyclic guanosine monophosphate (cGMP) levels, membrane hyperpolarization via K+ channel activation, activation of myosin light chain phosphatase activity, and interference with

  18. Grafting of poly[(methyl methacrylate)-block-styrene] onto cellulose via nitroxide-mediated polymerization, and its polymer/clay nanocomposite.

    Science.gov (United States)

    Karaj-Abad, Saber Ghasemi; Abbasian, Mojtaba; Jaymand, Mehdi

    2016-11-05

    For the first time, nitroxide-mediated polymerization (NMP) was used for synthesis of graft and block copolymers using cellulose (Cell) as a backbone, and polystyrene (PSt) and poly(methyl metacrylate) (PMMA) as the branches. For this purpose, Cell was acetylated by 2-bromoisobutyryl bromide (BrBiB), and then the bromine group was converted to 4-oxy-2,2,6,6-tetramethylpiperidin-1-oxyl group by a substitution nucleophilic reaction to afford a macroinitiator (Cell-TEMPOL). The macroinitiator obtained was subsequently used in controlled graft and block copolymerizations of St and MMA monomers to yield Cell-g-PSt and Cell-g-(PMMA-b-PSt). The chemical structures of all samples as representatives were characterized by FTIR and (1)H NMR spectroscopies. In addition, Cell-g-(PMMA-b-PSt)/organophilic montmorillonite nanocomposite was prepared through a solution intercalation method. TEM was used to evaluate the morphological behavior of the polymer-clay system. It was demonstrated that the addition of small percent of organophilic montmorillonite (O-MMT; 3wt.%) was enough to improve the thermal stability of the nanocomposite. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. S-Nitroglutathione, a product of the reaction between peroxynitrite and glutathione that generates nitric oxide.

    Science.gov (United States)

    Balazy, M; Kaminski, P M; Mao, K; Tan, J; Wolin, M S

    1998-11-27

    Peroxynitrite (ONOO-) has been shown in studies on vascular relaxation and guanylate cyclase activation to react with glutathione (GSH), generating an intermediate product that promotes a time-dependent production of nitric oxide (NO). In this study, reactions of ONOO- with GSH produced a new substance, which was characterized by liquid chromatography, ultraviolet spectroscopy, and electrospray tandem mass spectrometry. The mass spectrometric data provided evidence that the product of this reaction was S-nitroglutathione (GSNO2) and that S-nitrosoglutathione (GSNO) was not a detectable product of this reaction. Further evidence was obtained by comparison of the spectral and chromatographic properties with synthetic standards prepared by reaction of GSH with nitrosonium or nitronium borofluorates. Both the synthetic and ONOO-/GSH-derived GSNO2 generated a protonated ion, GSNO2H+, at m/z 353, which was unusually resistant to decomposition under collision activation, and no fragmentation was observed at collision energy of 25 eV. In contrast, an ion at m/z 337 (GSNOH+), generated from the synthetic GSNO, readily fragmented with the abundant loss of NO at 9 eV. Reactions of ONOO- with GSH resulted in the generation of NO, which was detected by the head space/NO-chemiluminescence analyzer method. The generation of NO was inhibited by the presence of glucose and/or CO2 in the buffers employed. Synthetic GSNO2 spontaneously generated NO in a manner that was not significantly altered by glucose or CO2. Thus, ONOO- reacts with GSH to form GSNO2, and GSNO2 decomposes in a manner that generates NO.

  20. Aqueous-phase chemistry and bactericidal effects from an air discharge plasma in contact with water: Evidence for the formation of peroxynitrite through a pseudo-second-order post-discharge reaction of H2O2 and HNO2

    Czech Academy of Sciences Publication Activity Database

    Lukeš, Petr; Doležalová, Eva; Sisrová, Irena; Člupek, Martin

    2014-01-01

    Roč. 23, č. 1 (2014), 015019-015019 ISSN 0963-0252 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M100431203 Program:M Institutional support: RVO:61389021 Keywords : air discharge plasma * plasma–liquid interactions * peroxynitrite * hydrogen peroxide * phenol * bacteria Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 3.591, year: 2014 http://iopscience.iop.org/0963-0252/23/1/015019/pdf/0963-0252_23_1_015019.pdf

  1. E. P. R. spectroscopic study of nitroxide mono- and bi-radicals; Etude par spectroscopie de resonance paramagnetique electronique de monoradicaux et de biradicaux nitroxydes

    Energy Technology Data Exchange (ETDEWEB)

    Lemaire, H [Commissariat a l' Energie Atomique, Grenoble, 38 (France). Centre d' Etudes Nucleaires

    1967-07-01

    A nitroxide is a molecule containing the group N-O where the oxygen atom made only one bond instead of the usual two. The main advantage of these radicals is their exceptional stability; this allows the study of well defined chemical structures while varying at will the experimental conditions. Studies by electron paramagnetic resonance of nitroxide mono-radicals have given the principal directions and the principal values of the electron-nitrogen nucleus hyperfine tensor and of the anisotropic g-factor tensor. The results were then related to the electronic structure of radicals. An understanding was obtained of the influence of the solvent on the principal values of the tensors, and the marked differences observed in the broadening of hyperfine lines when the medium become viscous. In the nitroxide biradicals, the hyperfine spectra depends not only on the magnetic interactions relative to each monomer, but also on the magnitude of the exchange interaction between the singlet and the triplet states of the dimer; the biradicals studied here are the first organic compounds which show clearly the influence of this exchange on the hyperfine structure. The two unpaired electrons also interact by a magnetic dipolar interaction: in the intermediate case, this can be used to derive the sign of the exchange interaction if the bi-radical is studied in a liquid crystal. Just as for mono-radicals, the hyperfine spectra of bi-radicals show selective broadening in viscous media, which is caused by an overall motional modulation of the anisotropic tensors. This gives another way to determine the sign of the exchange interaction. (author) [French] On appelle nitroxyde une molecule contenant le groupement N-O ou l'atome d'oxygene n'a satisfait qu'une seule liaison de valence sur les deux qui lui sont habituelles. L'interet majeur de ces radicaux reside dans leur exceptionnelle stabilite, permettant ainsi de faire varier a loisir les conditions experimentales d'etude de produits

  2. In search of a new class of stable nitroxide: synthesis and reactivity of a peri-substituted N,N-bissulfonylhydroxylamine.

    Science.gov (United States)

    Patel, Bhaven; Carlisle, Julie; Bottle, Steven E; Hanson, Graeme R; Kariuki, Benson M; Male, Louise; McMurtrie, John C; Spencer, Neil; Grainger, Richard S

    2011-04-07

    Acyclic bissulfonylnitroxides have never been isolated, and degrade through fragmentation. In an approach to stabilising a bissulfonylnitroxide radical, the cyclic, peri-substituted N,N-bissulfonylhydroxylamine, 2-hydroxynaphtho[1,8-de][1,3,2]dithiazine 1,1,3,3-tetraoxide (1), has been prepared by formal nitrogen insertion into the sulfur-sulfur bond of a sulfinylsulfone, naphtho[1,8-cd][1,2]dithiole 1,1,2-trioxide. The heterocyclic ring of 1 is shown to adopt a sofa conformation by X-ray crystallography, with a pseudo-axial hydroxyl group. N,N-Bissulfonylhydroxylamine 1 displays high thermal, photochemical and hydrolytic stability compared to acyclic systems. EPR analysis reveals formation of the corresponding bissulfonylnitroxide 2 upon oxidation of 1 with the Ce(IV) salts CAN and CTAN. Although 2 does not undergo fragmentation, it cannot be isolated, since hydrogen atom abstraction to reform 1 occurs in situ. The stability and reactivity of 1 and 2 are compared with the known cyclic benzo-fused N,N-bissulfonylhydroxylamine, N-hydroxy-O-benzenedisulfonimide (6), for which the X-ray data, and EPR of the corresponding nitroxide 10, are also reported for the first time.

  3. Enhanced electrocatalytic activity of graphene-gold nanoparticles hybrids for peroxynitrite electrochemical detection on hemin-based electrode.

    Science.gov (United States)

    Wang, Beibei; Ji, Xueping; Ren, Jujie; Ni, Ruixing; Wang, Lin

    2017-12-01

    A simple, ultrasensitive peroxynitrite anion (ONOO - ) electrochemical sensing platform was developed by immobilizing hemin on a density controllable electrochemically reduced graphene oxide-Au nanoparticles (ERGO-AuNPs) nanohybrids. The ERGO-AuNPs in situ nanohybrids were produced onto a glass carbon electrode (GCE) by one-step electrodeposition, the density of which could be easily controlled by electrodeposited time. The morphology of ERGO-AuNPs nanohybrids was characterized by a scanning electron microscope (SEM). The ERGO-AuNPs nanohybrids showed a high electrocatalytic activity for immobilized-hemin, because the nanostructures hybrids could effectively promote electron transfer rate between hemin and the electrode. Due to nanohybrids-enhanced catalytic effect for hemin, they were firstly selected for use as a highly sensitive electrochemical platform for ONOO - detection. The resulted sensor showed a high electrocatalytic activity toward ONOO - oxidation, being free from the electroactive interferents, including nitrite, nitrate, dopamine and uric acid at an applied potential of 0.7V. The sensor exhibited a high sensitivity of 123.1nAμM -1 and a lower detection limit of 0.1μM, and a wide linear range of 2.4×10 -6 to 5.5×10 -5 M, which could be attributed to the synergy between ERGO and AuNPs in hybrids. The nanohybrids in situ preparation and ONOO - detection methods would be beneficial to developing other sensing interface and have promising applications in biological molecules analysis and clinical diagnostic. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Dynamic changes in the distribution and time course of blood-brain barrier-permeative nitroxides in the mouse head with EPR imaging: visualization of blood flow in a mouse model of ischemia.

    Science.gov (United States)

    Emoto, Miho C; Sato-Akaba, Hideo; Hirata, Hiroshi; Fujii, Hirotada G

    2014-09-01

    Electron paramagnetic resonance (EPR) imaging using nitroxides as redox-sensitive probes is a powerful, noninvasive method that can be used under various physiological conditions to visualize changes in redox status that result from oxidative damage. Two blood-brain barrier-permeative nitroxides, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP) and 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-yloxy (MCP), have been widely used as redox-sensitive probes in the brains of small animals, but their in vivo distribution and properties have not yet been analyzed in detail. In this study, a custom-made continuous-wave three-dimensional (3D) EPR imager was used to obtain 3D EPR images of mouse heads using MCP or HMP. This EPR imager made it possible to take 3D EPR images reconstructed from data from 181 projections acquired every 60s. Using this improved EPR imager and magnetic resonance imaging, the distribution and reduction time courses of HMP and MCP were examined in mouse heads. EPR images of living mice revealed that HMP and MCP have different distributions and different time courses for entering the brain. Based on the pharmacokinetics of the reduction reactions of HMP and MCP in the mouse head, the half-lives of HMP and MCP were clearly and accurately mapped pixel by pixel. An ischemic mouse model was prepared, and the half-life of MCP was mapped in the mouse head. Compared to the half-life in control mice, the half-life of MCP in the ischemic model mouse brain was significantly increased, suggesting a shift in the redox balance. This in vivo EPR imaging method using BBB-permeative MCP is a useful noninvasive method for assessing changes in the redox status in mouse brains under oxidative stress. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Peroxynitrite induces apoptosis of mouse cochlear hair cells via a Caspase-independent pathway in vitro.

    Science.gov (United States)

    Cao, Zhixin; Yang, Qianqian; Yin, Haiyan; Qi, Qi; Li, Hongrui; Sun, Gaoying; Wang, Hongliang; Liu, Wenwen; Li, Jianfeng

    2017-11-01

    Peroxynitrite (ONOO - ) is a potent and versatile oxidant implicated in a number of pathophysiological processes. The present study was designed to investigate the effect of ONOO - on the cultured cochlear hair cells (HCs) of C57BL/6 mice in vitro as well as the possible mechanism underlying the action of such an oxidative stress. The in vitro primary cultured cochlear HCs were subjected to different concentrations of ONOO - , then, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy (TEM), the apoptosis was determined by Terminal deoxynucleotidyl transferase dUNT nick end labeling (TUNEL) assay, the mRNA expressions of Caspase-3, Caspase-8, Caspase-9, Apaf1, Bcl-2, and Bax were analyzed by RT-PCR, and the protein expressions of Caspase-3 and AIF were assessed by immunofluorescence. This work demonstrated that direct exposure of primary cultured cochlear HCs to ONOO - could result in a base-to-apex gradient injury of HCs in a concentration-dependent manner. Furthermore, ONOO - led to much more losses of outer hair cells than inner hair cells mainly through the induction of apoptosis of HCs as evidenced by TEM and TUNEL assays. The mRNA expressions of Caspase-8, Caspase-9, Apaf1, and Bax were increased and, meanwhile, the mRNA expression of Bcl-2 was decreased in response to ONOO - treatment. Of interesting, the expression of Caspase-3 had no significant change, whereas, the expression alteration of AIF was observed. These results suggested that ONOO - can effectively damage the survival of cochlear HCs via triggering the apoptotic pathway. The findings from this work suggest that ONOO - -induced apoptosis is mediated, at least in part, via a Caspase-independent pathway in cochlear HCs.

  6. Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite.

    Science.gov (United States)

    Jones, Charles I; Han, Zhaosheng; Presley, Tennille; Varadharaj, Saradhadevi; Zweier, Jay L; Ilangovan, Govindasamy; Alevriadou, B Rita

    2008-07-01

    Cultured vascular endothelial cell (EC) exposure to steady laminar shear stress results in peroxynitrite (ONOO(-)) formation intramitochondrially and inactivation of the electron transport chain. We examined whether the "hyperoxic state" of 21% O(2), compared with more physiological O(2) tensions (Po(2)), increases the shear-induced nitric oxide (NO) synthesis and mitochondrial superoxide (O(2)(*-)) generation leading to ONOO(-) formation and suppression of respiration. Electron paramagnetic resonance oximetry was used to measure O(2) consumption rates of bovine aortic ECs sheared (10 dyn/cm(2), 30 min) at 5%, 10%, or 21% O(2) or left static at 5% or 21% O(2). Respiration was inhibited to a greater extent when ECs were sheared at 21% O(2) than at lower Po(2) or left static at different Po(2). Flow in the presence of an endothelial NO synthase (eNOS) inhibitor or a ONOO(-) scavenger abolished the inhibitory effect. EC transfection with an adenovirus that expresses manganese superoxide dismutase in mitochondria, and not a control virus, blocked the inhibitory effect. Intracellular and mitochondrial O(2)(*-) production was higher in ECs sheared at 21% than at 5% O(2), as determined by dihydroethidium and MitoSOX red fluorescence, respectively, and the latter was, at least in part, NO-dependent. Accumulation of NO metabolites in media of ECs sheared at 21% O(2) was modestly increased compared with ECs sheared at lower Po(2), suggesting that eNOS activity may be higher at 21% O(2). Hence, the hyperoxia of in vitro EC flow studies, via increased NO and mitochondrial O(2)(*-) production, leads to enhanced ONOO(-) formation intramitochondrially and suppression of respiration.

  7. Controlled and selective placement of boron subphthalocyanines on either chain end of polymers synthesized by nitroxide mediated polymerization

    Directory of Open Access Journals (Sweden)

    Benoît H. Lessard

    2015-10-01

    Full Text Available In previous studies, we synthesized the first organic light emitting diode (OLED using boron subphthalocyanines (BsubPcs based polymers. When designing new polymer materials for organic electronic applications such as OLEDs or organic photovoltaic (OPV devices it is important to consider not only the contribution of each monomer but also the polymer chain ends. In this paper we establish a post-polymerization strategy to couple BsubPcs onto either the α- or the ω-chain end using chemically selective BsubPc derivatives. We outline how the chain ends of two representative polymers, poly(styrene (PS and poly(n-butylacrylate (BA, synthesized by nitroxide mediated polymerization (NMP, using BlocBuilder-MA as the initiating species, can be chemically modified by the incorporation of BsubPc chromophores. The addition of the BsubPc chromophore was confirmed through the use of a photodiode array detector (PDA connected in-line with a gel permeation chromatography (GPC setup. These findings represent the first reported method for the controlled and selective placement of a BsubPc chromophores on either end of a polymer produced by NMP. This strategy will therefore be utilized to make next generation BsubPc polymers for OLEDs and OPV devices. The extremely high molar extinction coefficient of BsubPc also make these polymers ideally suited for dye-labelling of polymers.

  8. Thermally Activated Paramagnets from Diamagnetic Polymers of Biphenyl-3,5-diyl Bis(tert-butyl Nitroxides Carrying Methyl and Fluoro Groups at the 2’- and 5’-Positions

    Directory of Open Access Journals (Sweden)

    Toru Yoshitake

    2016-03-01

    Full Text Available Three new biradicals—2’,5’-dimethyl-, 2’-fluoro-5’-methyl-, and 5’-fluoro-2’-methyl- biphenyl-3,5-diyl bis(tert-butyl nitroxides—were synthesized. The magnetic susceptibility measurements revealed their diamagnetism below and around room temperature. The nitroxide groups are located close to each other in an intermolecular fashion to form a weakly covalent head-to-tail (NO2 ring. Biradical molecules are connected on both radical sites, constructing a diamagnetic chain. The dimethyl derivative underwent a structural phase transition at 83 °C, clarified via differential scanning calorimetry and powder X-ray diffraction, and a paramagnetic solid phase with S = 1 irreversibly appeared. The other analogues exhibited a similar irreversible upsurge of the magnetic susceptibility on heating, but the transition was characterized as the melting.

  9. Protein Tyrosine Nitration: Biochemical Mechanisms and Structural Basis of its Functional Effects

    Science.gov (United States)

    Radi, Rafael

    2012-01-01

    CONSPECTUS The nitration of protein tyrosine residues to 3-nitrotyrosine represents an oxidative postranslational modification that unveils the disruption of nitric oxide (•NO) signaling and metabolism towards pro-oxidant processes. Indeed, excess levels of reactive oxygen species in the presence of •NO or •NO-derived metabolites lead to the formation of nitrating species such as peroxynitrite. Thus, protein 3-nitrotyrosine has been established as a biomarker of cell, tissue and systemic “nitroxidative stress”. Moreover, tyrosine nitration modifies key properties of the amino acid (i.e. phenol group pKa, redox potential, hydrophobicity and volume). Thus, the incorporation of a nitro group (−NO2) to protein tyrosines can lead to profound structural and functional changes, some of which contribute to altered cell and tissue homeostasis. In this Account, I describe our current efforts to define 1) biologically-relevant mechanisms of protein tyrosine nitration and 2) how this modification can cause changes in protein structure and function at the molecular level. First, the relevance of protein tyrosine nitration via free radical-mediated reactions (in both peroxynitrite-dependent or independent pathways) involving the intermediacy of tyrosyl radical (Tyr•) will be underscored. This feature of the nitration process becomes critical as Tyr• can take variable fates, including the formation of 3-nitrotyrosine. Fast kinetic techniques, electron paramagnetic resonance (EPR) studies, bioanalytical methods and kinetic simulations have altogether assisted to characterize and fingerprint the reactions of tyrosine with peroxynitrite and one-electron oxidants and its further evolution to 3-nitrotyrosine. Recent findings show that nitration of tyrosines in proteins associated to biomembranes is linked to the lipid peroxidation process via a connecting reaction that involves the one-electron oxidation of tyrosine by lipid peroxyl radicals (LOO•). Second

  10. Anti-HER2 immunoliposomes for selective delivery of electron paramagnetic resonance imaging probes to HER2-overexpressing breast tumor cells

    Science.gov (United States)

    Burks, Scott R.; Macedo, Luciana F.; Barth, Eugene D.; Tkaczuk, Katherine H.; Martin, Stuart S.; Rosen, Gerald M.; Halpern, Howard J.; Brodie, Angela M.

    2014-01-01

    Electron paramagnetic resonance (EPR) imaging is an emerging modality that can detect and localize paramagnetic molecular probes (so-called spin probes) in vivo. We previously demonstrated that nitroxide spin probes can be encapsulated in liposomes at concentrations exceeding 100 mM, at which nitroxides exhibit a concentration-dependent quenching of their EPR signal that is analogous to the self-quenching of fluorescent molecules. Therefore, intact liposomes encapsulating high concentrations of nitroxides exhibit greatly attenuated EPR spectral signals, and endocytosis of such liposomes represents a cell-activated contrast-generating mechanism. After endocytosis, the encapsulated nitroxide is liberated and becomes greatly diluted in the intracellular milieu. This dequenches the nitroxides to generate a robust intracellular EPR signal. It is therefore possible to deliver a high concentration of nitroxides to cells while minimizing background signal from unendocytosed liposomes. We report here that intracellular EPR signal can be selectively generated in a specific cell type by exploiting its expression of Human Epidermal Growth Factor Receptor 2 (HER2). When targeted by anti-HER2 immunoliposomes encapsulating quenched nitroxides, Hc7 cells, which are novel HER2-overexpressing cells derived from the MCF7 breast tumor cell line, endocytose the liposomes copiously, in contrast to the parent MCF7 cells or control CV1 cells, which do not express HER2. HER2-dependent liposomal delivery enables Hc7 cells to accumulate 750 μM nitroxide intracellularly. Through the use of phantom models, we verify that this concentration of nitroxides is more than sufficient for EPR imaging, thus laying the foundation for using EPR imaging to visualize HER2-overexpressing Hc7 tumors in animals. PMID:20066490

  11. Growth and structure of rapid thermal silicon oxides and nitroxides studied by spectroellipsometry and Auger electron spectroscopy

    Science.gov (United States)

    Gonon, N.; Gagnaire, A.; Barbier, D.; Glachant, A.

    1994-11-01

    Rapid thermal oxidation of Czochralski-grown silicon in either O2 or N2O atmospheres have been studied using spectroellipsometry and Auger electron spectroscopy. Multiwavelength ellipsometric data were processed in order to separately derive the thickness and refractive indexes of rapid thermal dielectrics. Results revealed a significant increase of the mean refractive index as the film thickness falls below 20 nm for both O2 or N2O oxidant species. A multilayer structure including an about 0.3-nm-thick interfacial region of either SiO(x) or nitroxide in the case of O2 and N2O growth, respectively, followed by a densified SiO2 layer, was found to accurately fit the experimental data. The interfacial region together with the densified state of SiO2 close to the interface suggest a dielectric structure in agreement with the continuous random network model proposed for classical thermal oxides. Auger electron spectroscopy analysis confirmed the presence of noncrystalline Si-Si bonds in the interfacial region, mostly in the case of thin oxides grown in O2. It was speculated that the initial fast growth regime was due to a transient oxygen supersaturation in the interfacial region. Besides, the self-limiting growth in N2O was confirmed and explained in agreement with several recently published data, by the early formation of a very thin nitride or oxynitride membrane in the highly densified oxide beneath the interface. The beneficial effect of direct nitrogen incorporation by rapid thermal oxidation in N2O instead of O2 for the electrical behavior of metal-oxide-semiconductor capacitors is likely a better SiO2/Si lattice accommodation through the reduction of stresses and Si-Si bonds in the interfacial region of the dielectric.

  12. Poly(methacrylic acid-ran-2-vinylpyridine Statistical Copolymer and Derived Dual pH-Temperature Responsive Block Copolymers by Nitroxide-Mediated Polymerization

    Directory of Open Access Journals (Sweden)

    Milan Marić

    2017-02-01

    Full Text Available Nitroxide-mediated polymerization using the succinimidyl ester functional unimolecular alkoxyamine initiator (NHS-BlocBuilder was used to first copolymerize tert-butyl methacrylate/2-vinylpyridine (tBMA/2VP with low dispersity (Đ = 1.30–1.41 and controlled growth (linear number average molecular Mn versus conversion, Mn = 3.8–10.4 kg·mol−1 across a wide composition of ranges (initial mol fraction 2VP, f2VP,0 = 0.10–0.90. The resulting statistical copolymers were first de-protected to give statistical polyampholytic copolymers comprised of methacrylic acid/2VP (MAA/2VP units. These copolymers exhibited tunable water-solubility due to the different pKas of the acidic MAA and basic 2VP units; being soluble at very low pH < 3 and high pH > 8. One of the tBMA/2VP copolymers was used as a macroinitiator for a 4-acryloylmorpholine/4-acryloylpiperidine (4AM/4AP mixture, to provide a second block with thermo-responsive behavior with tunable cloud point temperature (CPT, depending on the ratio of 4AM:4AP. Dynamic light scattering of the block copolymer at various pHs (3, 7 and 10 as a function of temperature indicated a rapid increase in particle size >2000 nm at 22–27 °C, corresponding to the 4AM/4AP segment’s thermos-responsiveness followed by a leveling in particle size to about 500 nm at higher temperatures.

  13. Verdazyl-ribose: A new radical for solid-state dynamic nuclear polarization at high magnetic field

    Science.gov (United States)

    Thurber, Kent R.; Le, Thanh-Ngoc; Changcoco, Victor; Brook, David J. R.

    2018-04-01

    Solid-state dynamic nuclear polarization (DNP) using the cross-effect relies on radical pairs whose electron spin resonance (ESR) frequencies differ by the nuclear magnetic resonance (NMR) frequency. We measure the DNP provided by a new water-soluble verdazyl radical, verdazyl-ribose, under both magic-angle spinning (MAS) and static sample conditions at 9.4 T, and compare it to a nitroxide radical, 4-hydroxy-TEMPO. We find that verdazyl-ribose is an effective radical for cross-effect DNP, with the best relative results for a non-spinning sample. Under non-spinning conditions, verdazyl-ribose provides roughly 2× larger 13C cross-polarized (CP) NMR signal than the nitroxide, with similar polarization buildup times, at both 29 K and 76 K. With MAS at 7 kHz and 1.5 W microwave power, the verdazyl-ribose does not provide as much DNP as the nitroxide, with the verdazyl providing less NMR signal and a longer polarization buildup time. When the microwave power is decreased to 30 mW with 5 kHz MAS, the two types of radical are comparable, with the verdazyl-doped sample having a larger NMR signal which compensates for its longer polarization buildup time. We also present electron spin relaxation measurements at Q-band (1.2 T) and ESR lineshapes at 1.2 and 9.4 T. Most notably, the verdazyl radical has a longer T1e than the nitroxide (9.9 ms and 1.3 ms, respectively, at 50 K and 1.2 T). The verdazyl electron spin lineshape is significantly affected by the hyperfine coupling to four 14N nuclei, even at 9.4 T. We also describe 3000-spin calculations to illustrate the DNP potential of possible radical pairs: verdazyl-verdazyl, verdazyl-nitroxide, or nitroxide-nitroxide pairs. These calculations suggest that the verdazyl radical at 9.4 T has a narrower linewidth than optimal for cross-effect DNP using verdazyl-verdazyl pairs. Because of the hyperfine coupling contribution to the electron spin linewidth, this implies that DNP using the verdazyl radical would improve at lower

  14. Verdazyl-ribose: A new radical for solid-state dynamic nuclear polarization at high magnetic field.

    Science.gov (United States)

    Thurber, Kent R; Le, Thanh-Ngoc; Changcoco, Victor; Brook, David J R

    2018-04-01

    Solid-state dynamic nuclear polarization (DNP) using the cross-effect relies on radical pairs whose electron spin resonance (ESR) frequencies differ by the nuclear magnetic resonance (NMR) frequency. We measure the DNP provided by a new water-soluble verdazyl radical, verdazyl-ribose, under both magic-angle spinning (MAS) and static sample conditions at 9.4 T, and compare it to a nitroxide radical, 4-hydroxy-TEMPO. We find that verdazyl-ribose is an effective radical for cross-effect DNP, with the best relative results for a non-spinning sample. Under non-spinning conditions, verdazyl-ribose provides roughly 2× larger 13 C cross-polarized (CP) NMR signal than the nitroxide, with similar polarization buildup times, at both 29 K and 76 K. With MAS at 7 kHz and 1.5 W microwave power, the verdazyl-ribose does not provide as much DNP as the nitroxide, with the verdazyl providing less NMR signal and a longer polarization buildup time. When the microwave power is decreased to 30 mW with 5 kHz MAS, the two types of radical are comparable, with the verdazyl-doped sample having a larger NMR signal which compensates for its longer polarization buildup time. We also present electron spin relaxation measurements at Q-band (1.2 T) and ESR lineshapes at 1.2 and 9.4 T. Most notably, the verdazyl radical has a longer T 1e than the nitroxide (9.9 ms and 1.3 ms, respectively, at 50 K and 1.2 T). The verdazyl electron spin lineshape is significantly affected by the hyperfine coupling to four 14 N nuclei, even at 9.4 T. We also describe 3000-spin calculations to illustrate the DNP potential of possible radical pairs: verdazyl-verdazyl, verdazyl-nitroxide, or nitroxide-nitroxide pairs. These calculations suggest that the verdazyl radical at 9.4 T has a narrower linewidth than optimal for cross-effect DNP using verdazyl-verdazyl pairs. Because of the hyperfine coupling contribution to the electron spin linewidth, this implies that DNP using the verdazyl

  15. Alterations of nitric-oxide synthase and xanthine-oxidase activities of human keratinocytes by ultraviolet-B radiation -potential role for peroxynitrite in skin inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Deliconstantinos, G.; Villiotou, V.; Stavrides, J.C. [Athens Univ. (Greece). School of Medicine

    1996-06-28

    In the present study, we demonstrated that NO synthase (cNOS) and xanthine oxidase (XO) of human keratinocytes can be activated to release NO, superoxide (O-2(-)) and peroxynitrite (ONOO-) following exposure to ultraviolet B (UVB) radiation. We defined that this photo induced response may be involved in the pathogenesis of sunburn erythema and inflammation. Treatment of human keratinocytes with UVB (290-320 nm) radiation (up to 200 mJ/cm(2)) resulted in a dose-dependent increase in NO and ONOO-release that was inhibited by N-monomethyl-L-arginine (L-NMMA). NO and ONOO- release from keratinocytes was accompanied by an increase in intracellular cGMP levels. Treatment of human keratinocyte cytosol with various doses of UVB (up to 100 mJ/cm(2)) resulted in an increase in XO activity that was inhibited by oxypurinol. In in vivo experiments, when experimental animals were subjected to UVB radiation, a protection factor (PF) of 6.5 {+-} 1.8 was calculated when an emulsified cream formulation containing nitro-L-arginine (L-NA) (2%) and L-NMMA (2%) was applied to their skin. The present study indicates that UVB radiation acts as a potent stimulator of cNOS and XO activities in human keratinocytes. NO and ONOO- may exert cytotoxic effects in keratinocytes themselves, as well as in their neighbouring endothelial and smooth muscle cells. This may be a major part of the integrated response leading to erythema production and the inflammation process. (UK).

  16. Alterations of nitric-oxide synthase and xanthine-oxidase activities of human keratinocytes by ultraviolet-B radiation -potential role for peroxynitrite in skin inflammation

    International Nuclear Information System (INIS)

    Deliconstantinos, G.; Villiotou, V.; Stavrides, J.C.

    1996-01-01

    In the present study, we demonstrated that NO synthase (cNOS) and xanthine oxidase (XO) of human keratinocytes can be activated to release NO, superoxide (O-2(-)) and peroxynitrite (ONOO-) following exposure to ultraviolet B (UVB) radiation. We defined that this photo induced response may be involved in the pathogenesis of sunburn erythema and inflammation. Treatment of human keratinocytes with UVB (290-320 nm) radiation (up to 200 mJ/cm(2)) resulted in a dose-dependent increase in NO and ONOO-release that was inhibited by N-monomethyl-L-arginine (L-NMMA). NO and ONOO- release from keratinocytes was accompanied by an increase in intracellular cGMP levels. Treatment of human keratinocyte cytosol with various doses of UVB (up to 100 mJ/cm(2)) resulted in an increase in XO activity that was inhibited by oxypurinol. In in vivo experiments, when experimental animals were subjected to UVB radiation, a protection factor (PF) of 6.5 ± 1.8 was calculated when an emulsified cream formulation containing nitro-L-arginine (L-NA) (2%) and L-NMMA (2%) was applied to their skin. The present study indicates that UVB radiation acts as a potent stimulator of cNOS and XO activities in human keratinocytes. NO and ONOO- may exert cytotoxic effects in keratinocytes themselves, as well as in their neighbouring endothelial and smooth muscle cells. This may be a major part of the integrated response leading to erythema production and the inflammation process. (UK)

  17. In vivo EPR imaging of differential tumor targeting using cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl

    Science.gov (United States)

    Redler, Gage; Barth, Eugene D.; Bauer, Kenneth S.; Kao, Joseph P.Y.; Rosen, Gerald M.; Halpern, Howard J.

    2015-01-01

    Purpose EPR spectroscopy promises quantitative images of important physiologic markers of animal tumors and normal tissues, such as pO2, pH, and thiol redox status. These parameters of tissue function are conveniently reported by tailored nitroxides. For defining tumor physiology, it is vital that nitroxides are selectively localized in tumors relative to normal tissue. Furthermore, these paramagnetic species should be specifically taken up by cells of the tumor, thereby reporting on both the site of tumor formation and the physiological status of the tissue. This study investigates the tumor localization of the novel nitroxide, cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl 3 relative to the corresponding di-acid 4. Methods We obtained images of nitroxide 3 infused intravenously into C3H mice bearing 0.5-cm3 FSa fibrosarcoma on the leg, and compared these with images of similar tumors infused with nitroxide 4. Results The ratio of spectral intensity from within the tumor-bearing region to that of normal tissue was higher in the mice injected with 3 relative to 4. Conclusion This establishes the possibility of tumor imaging with a nitroxide with intracellular distribution and provides the basis for EPR images of animal models to investigate the relationship between crucial aspects of tumor microenvironment and malignancy and its response to therapy. PMID:23776127

  18. The synthesis and spectroscopic study of stable free radicals related to piperidine-n-oxyl, including a stable bi-radical

    International Nuclear Information System (INIS)

    Briere, R.

    1965-07-01

    A new synthesis of di-tert-butyl nitroxide using the reaction between tert-butyl magnesium chloride and nitro-tert-butane is presented in the first section. Synthesis and investigation of stable free piperidine-N-oxyl radicals are described in the second section. All these nitroxides have been characterised by their I. R., U. V. and E. P. R. absorption spectra. The final section contains a description of the synthesis of a stable bi-radical of the nitroxide type by condensation of 2,2, 6, 6-tetramethyl-piperid-4-one-l-oxyl with hydrazine. (author) [fr

  19. Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants

    International Nuclear Information System (INIS)

    Dairou, Julien; Petit, Emile; Ragunathan, Nilusha; Baeza-Squiban, Armelle; Marano, Francelyne; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2009-01-01

    Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and β-naphthylamine (β-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating that inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H 2 O 2 or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.

  20. Reaction between peroxynitrite and boronates: EPR spin-trapping, HPLC analyses, and quantum mechanical study of the free radical pathway

    Science.gov (United States)

    Sikora, Adam; Zielonka, Jacek; Lopez, Marcos; Dybala-Defratyka, Agnieszka; Joseph, Joy; Marcinek, Andrzej; Kalyanaraman, Balaraman

    2013-01-01

    Recently we showed that peroxynitrite (ONOO−) reacts directly and rapidly with aromatic and aliphatic boronic acids (k ≈ 106 M−1s−1). Product analyses and substrate consumption data indicated that ONOO− reacts stoichiometrically with boronates, yielding the corresponding phenols as the major product (~85–90%), and the remaining products (10–15%) were proposed to originate from free radical intermediates (phenyl and phenoxyl radicals). Here we investigated in detail the minor, free radical pathway of boronate reaction with ONOO−. The electron paramagnetic resonance (EPR) spin-trapping technique was used to characterize the free radical intermediates formed from the reaction between boronates and ONOO−. Using 2-methyl-2-nitrosopropane (MNP) and 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO) spin traps, phenyl radicals were trapped and detected. Although phenoxyl radicals were not detected, the positive effects of molecular oxygen, and inhibitory effects of hydrogen atom donors (acetonitrile, and 2-propanol) and general radical scavengers (GSH, NADH, ascorbic acid and tyrosine) on the formation of phenoxyl radical-derived nitrated product, suggest that phenoxyl radical was formed as the secondary species. We propose that the initial step of the reaction involves the addition of ONOO− to the boron atom in boronates. The anionic intermediate undergoes both heterolytic (major pathway) and homolytic (minor pathway) cleavage of the peroxy (O-O) bond to form phenol and nitrite as a major product (via a non-radical mechanism), or a radical pair PhB(OH)2O•−…•NO2 as a minor product. It is conceivable that phenyl radicals are formed by the fragmentation of PhB(OH)2O•− radical anion. According to the DFT quantum mechanical calculations, the energy barrier for the dissociation of PhB(OH)2O•− radical anion to form phenyl radicals is only a few kcal/mol, suggesting rapid and spontaneous fragmentation of PhB(OH)2O•− radical anion

  1. Effects-Driven IT Development

    DEFF Research Database (Denmark)

    Hertzum, Morten; Simonsen, Jesper

    2010-01-01

    We present effects-driven IT development as an instrument for pursuing and reinforcing Participatory Design (PD) when it is applied in commercial information technology (IT) projects. Effects-driven IT development supports the management of a sustained PD process throughout design and organizatio......We present effects-driven IT development as an instrument for pursuing and reinforcing Participatory Design (PD) when it is applied in commercial information technology (IT) projects. Effects-driven IT development supports the management of a sustained PD process throughout design...

  2. Uric acid in multiple sclerosis

    NARCIS (Netherlands)

    Koch, M; De Keyser, J

    Peroxynitrite, a reactive oxidant formed by the reaction of nitric oxide with superoxide at sites of inflammation in multiple sclerosis (MS), is capable of damaging tissues and cells. Uric acid, a natural scavenger of peroxynitrite, reduces inflammatory demyelination in experimental allergic

  3. Light-Driven Alignment

    CERN Document Server

    Antonyuk, Boris P

    2009-01-01

    This book deals with influencing the properties of solids by light-driven electron transport. The theoretical basis of these effects, light-driven ordering and self-organisation, as well as optical motors are presented. With light as a tool, new ways to produce materials are opened.

  4. Model Driven Engineering

    Science.gov (United States)

    Gaševic, Dragan; Djuric, Dragan; Devedžic, Vladan

    A relevant initiative from the software engineering community called Model Driven Engineering (MDE) is being developed in parallel with the Semantic Web (Mellor et al. 2003a). The MDE approach to software development suggests that one should first develop a model of the system under study, which is then transformed into the real thing (i.e., an executable software entity). The most important research initiative in this area is the Model Driven Architecture (MDA), which is Model Driven Architecture being developed under the umbrella of the Object Management Group (OMG). This chapter describes the basic concepts of this software engineering effort.

  5. L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction

    NARCIS (Netherlands)

    Maarsingh, H.; Bossenga, B. E.; Bos, I. S. T.; Volders, H. H.; Zaagsma, J.; Meurs, H.

    Peroxynitrite has been shown to be crucially involved in airway hyperresponsiveness (AHR) after the late asthmatic reaction (LAR). Peroxynitrite production may result from simultaneous synthesis of nitric oxide (NO) and superoxide by inducible NO-synthase (iNOS) at low L-arginine concentrations.

  6. Data-Driven and Expectation-Driven Discovery of Empirical Laws.

    Science.gov (United States)

    1982-10-10

    occurred in small integer proportions to each other. In 1809, Joseph Gay- Lussac found evidence for his law of combining volumes, which stated that a...of Empirical Laws Patrick W. Langley Gary L. Bradshaw Herbert A. Simon T1he Robotics Institute Carnegie-Mellon University Pittsburgh, Pennsylvania...Subtitle) S. TYPE OF REPORT & PERIOD COVERED Data-Driven and Expectation-Driven Discovery Interim Report 2/82-10/82 of Empirical Laws S. PERFORMING ORG

  7. Emotion-driven level generation

    OpenAIRE

    Togelius, Julian; Yannakakis, Georgios N.

    2016-01-01

    This chapter examines the relationship between emotions and level generation. Grounded in the experience-driven procedural content generation framework we focus on levels and introduce a taxonomy of approaches for emotion-driven level generation. We then review four characteristic level generators of our earlier work that exemplify each one of the approaches introduced. We conclude the chapter with our vision on the future of emotion-driven level generation.

  8. Analogy between optically driven injection-locked laser diodes and driven damped linear oscillators

    International Nuclear Information System (INIS)

    Murakami, Atsushi; Shore, K. Alan

    2006-01-01

    An analytical study of optically driven laser diodes (LDs) has been undertaken to meet the requirement for a theoretical treatment for chaotic drive and synchronization occurring in the injection-locked LDs with strong injection. A small-signal analysis is performed for the sets of rate equations for the injection-locked LDs driven by a sinusoidal optical signal. In particular, as a model of chaotic driving signals from LD dynamics, an optical signal caused by direct modulation to the master LD is assumed, oscillating both in field amplitude and phase as is the case with chaotic driving signals. Consequently, we find conditions that allow reduction in the degrees of freedom of the driven LD. Under these conditions, the driven response is approximated to a simple form which is found to be equivalent to driven damped linear oscillators. The validity of the application of this theory to previous work on the synchronization of chaos and related phenomena occurring in the injection-locked LDs is demonstrated

  9. Evaluation of Respondent-Driven Sampling

    Science.gov (United States)

    McCreesh, Nicky; Frost, Simon; Seeley, Janet; Katongole, Joseph; Tarsh, Matilda Ndagire; Ndunguse, Richard; Jichi, Fatima; Lunel, Natasha L; Maher, Dermot; Johnston, Lisa G; Sonnenberg, Pam; Copas, Andrew J; Hayes, Richard J; White, Richard G

    2012-01-01

    Background Respondent-driven sampling is a novel variant of link-tracing sampling for estimating the characteristics of hard-to-reach groups, such as HIV prevalence in sex-workers. Despite its use by leading health organizations, the performance of this method in realistic situations is still largely unknown. We evaluated respondent-driven sampling by comparing estimates from a respondent-driven sampling survey with total-population data. Methods Total-population data on age, tribe, religion, socioeconomic status, sexual activity and HIV status were available on a population of 2402 male household-heads from an open cohort in rural Uganda. A respondent-driven sampling (RDS) survey was carried out in this population, employing current methods of sampling (RDS sample) and statistical inference (RDS estimates). Analyses were carried out for the full RDS sample and then repeated for the first 250 recruits (small sample). Results We recruited 927 household-heads. Full and small RDS samples were largely representative of the total population, but both samples under-represented men who were younger, of higher socioeconomic status, and with unknown sexual activity and HIV status. Respondent-driven-sampling statistical-inference methods failed to reduce these biases. Only 31%-37% (depending on method and sample size) of RDS estimates were closer to the true population proportions than the RDS sample proportions. Only 50%-74% of respondent-driven-sampling bootstrap 95% confidence intervals included the population proportion. Conclusions Respondent-driven sampling produced a generally representative sample of this well-connected non-hidden population. However, current respondent-driven-sampling inference methods failed to reduce bias when it occurred. Whether the data required to remove bias and measure precision can be collected in a respondent-driven sampling survey is unresolved. Respondent-driven sampling should be regarded as a (potentially superior) form of convenience

  10. Evaluation of respondent-driven sampling.

    Science.gov (United States)

    McCreesh, Nicky; Frost, Simon D W; Seeley, Janet; Katongole, Joseph; Tarsh, Matilda N; Ndunguse, Richard; Jichi, Fatima; Lunel, Natasha L; Maher, Dermot; Johnston, Lisa G; Sonnenberg, Pam; Copas, Andrew J; Hayes, Richard J; White, Richard G

    2012-01-01

    Respondent-driven sampling is a novel variant of link-tracing sampling for estimating the characteristics of hard-to-reach groups, such as HIV prevalence in sex workers. Despite its use by leading health organizations, the performance of this method in realistic situations is still largely unknown. We evaluated respondent-driven sampling by comparing estimates from a respondent-driven sampling survey with total population data. Total population data on age, tribe, religion, socioeconomic status, sexual activity, and HIV status were available on a population of 2402 male household heads from an open cohort in rural Uganda. A respondent-driven sampling (RDS) survey was carried out in this population, using current methods of sampling (RDS sample) and statistical inference (RDS estimates). Analyses were carried out for the full RDS sample and then repeated for the first 250 recruits (small sample). We recruited 927 household heads. Full and small RDS samples were largely representative of the total population, but both samples underrepresented men who were younger, of higher socioeconomic status, and with unknown sexual activity and HIV status. Respondent-driven sampling statistical inference methods failed to reduce these biases. Only 31%-37% (depending on method and sample size) of RDS estimates were closer to the true population proportions than the RDS sample proportions. Only 50%-74% of respondent-driven sampling bootstrap 95% confidence intervals included the population proportion. Respondent-driven sampling produced a generally representative sample of this well-connected nonhidden population. However, current respondent-driven sampling inference methods failed to reduce bias when it occurred. Whether the data required to remove bias and measure precision can be collected in a respondent-driven sampling survey is unresolved. Respondent-driven sampling should be regarded as a (potentially superior) form of convenience sampling method, and caution is required

  11. From current-driven to neoclassically driven tearing modes.

    Science.gov (United States)

    Reimerdes, H; Sauter, O; Goodman, T; Pochelon, A

    2002-03-11

    In the TCV tokamak, the m/n = 2/1 island is observed in low-density discharges with central electron-cyclotron current drive. The evolution of its width has two distinct growth phases, one of which can be linked to a "conventional" tearing mode driven unstable by the current profile and the other to a neoclassical tearing mode driven by a perturbation of the bootstrap current. The TCV results provide the first clear observation of such a destabilization mechanism and reconcile the theory of conventional and neoclassical tearing modes, which differ only in the dominant driving term.

  12. Discovery Driven Growth

    DEFF Research Database (Denmark)

    Bukh, Per Nikolaj

    2009-01-01

    Anmeldelse af Discovery Driven Growh : A breakthrough process to reduce risk and seize opportunity, af Rita G. McGrath & Ian C. MacMillan, Boston: Harvard Business Press. Udgivelsesdato: 14 august......Anmeldelse af Discovery Driven Growh : A breakthrough process to reduce risk and seize opportunity, af Rita G. McGrath & Ian C. MacMillan, Boston: Harvard Business Press. Udgivelsesdato: 14 august...

  13. What we learn from surveillance testing of standby turbine driven and motor driven pumps

    International Nuclear Information System (INIS)

    Christie, B.

    1996-01-01

    This paper describes a comparison of the performance information collected by the author and the respective system engineers from five standby turbine driven pumps at four commercial nuclear electric generating units in the United States and from two standby motor driven pumps at two of these generating units. Information was collected from surveillance testing and from Non-Test actuations. Most of the performance information (97%) came from surveillance testing. open-quotes Conditional Probabilitiesclose quotes of the pumps ability to respond to a random demand were calculated for each of the seven standby pumps and compared to the historical record of the Non-Test actuations. It appears that the Conditional Probabilities are comparable to the rate of success for Non-Test actuations. The Conditional Probabilities of the standby motor driven pumps (approximately 99%) are better than the Conditional Probabilities of the standby turbine driven pumps (82%-96% range). Recommendations were made to improve the Conditional Probabilities of the standby turbine driven pumps

  14. What we learn from surveillance testing of standby turbine driven and motor driven pumps

    Energy Technology Data Exchange (ETDEWEB)

    Christie, B.

    1996-12-01

    This paper describes a comparison of the performance information collected by the author and the respective system engineers from five standby turbine driven pumps at four commercial nuclear electric generating units in the United States and from two standby motor driven pumps at two of these generating units. Information was collected from surveillance testing and from Non-Test actuations. Most of the performance information (97%) came from surveillance testing. {open_quotes}Conditional Probabilities{close_quotes} of the pumps ability to respond to a random demand were calculated for each of the seven standby pumps and compared to the historical record of the Non-Test actuations. It appears that the Conditional Probabilities are comparable to the rate of success for Non-Test actuations. The Conditional Probabilities of the standby motor driven pumps (approximately 99%) are better than the Conditional Probabilities of the standby turbine driven pumps (82%-96% range). Recommendations were made to improve the Conditional Probabilities of the standby turbine driven pumps.

  15. Using Two Different Approaches to Assess Dietary Patterns: Hypothesis-Driven and Data-Driven Analysis

    Directory of Open Access Journals (Sweden)

    Ágatha Nogueira Previdelli

    2016-09-01

    Full Text Available The use of dietary patterns to assess dietary intake has become increasingly common in nutritional epidemiology studies due to the complexity and multidimensionality of the diet. Currently, two main approaches have been widely used to assess dietary patterns: data-driven and hypothesis-driven analysis. Since the methods explore different angles of dietary intake, using both approaches simultaneously might yield complementary and useful information; thus, we aimed to use both approaches to gain knowledge of adolescents’ dietary patterns. Food intake from a cross-sectional survey with 295 adolescents was assessed by 24 h dietary recall (24HR. In hypothesis-driven analysis, based on the American National Cancer Institute method, the usual intake of Brazilian Healthy Eating Index Revised components were estimated. In the data-driven approach, the usual intake of foods/food groups was estimated by the Multiple Source Method. In the results, hypothesis-driven analysis showed low scores for Whole grains, Total vegetables, Total fruit and Whole fruits, while, in data-driven analysis, fruits and whole grains were not presented in any pattern. High intakes of sodium, fats and sugars were observed in hypothesis-driven analysis with low total scores for Sodium, Saturated fat and SoFAA (calories from solid fat, alcohol and added sugar components in agreement, while the data-driven approach showed the intake of several foods/food groups rich in these nutrients, such as butter/margarine, cookies, chocolate powder, whole milk, cheese, processed meat/cold cuts and candies. In this study, using both approaches at the same time provided consistent and complementary information with regard to assessing the overall dietary habits that will be important in order to drive public health programs, and improve their efficiency to monitor and evaluate the dietary patterns of populations.

  16. Input-driven versus turnover-driven controls of simulated changes in soil carbon due to land-use change

    Science.gov (United States)

    Nyawira, S. S.; Nabel, J. E. M. S.; Brovkin, V.; Pongratz, J.

    2017-08-01

    Historical changes in soil carbon associated with land-use change (LUC) result mainly from the changes in the quantity of litter inputs to the soil and the turnover of carbon in soils. We use a factor separation technique to assess how the input-driven and turnover-driven controls, as well as their synergies, have contributed to historical changes in soil carbon associated with LUC. We apply this approach to equilibrium simulations of present-day and pre-industrial land use performed using the dynamic global vegetation model JSBACH. Our results show that both the input-driven and turnover-driven changes generally contribute to a gain in soil carbon in afforested regions and a loss in deforested regions. However, in regions where grasslands have been converted to croplands, we find an input-driven loss that is partly offset by a turnover-driven gain, which stems from a decrease in the fire-related carbon losses. Omitting land management through crop and wood harvest substantially reduces the global losses through the input-driven changes. Our study thus suggests that the dominating control of soil carbon losses is via the input-driven changes, which are more directly accessible to human management than the turnover-driven ones.

  17. Knowledge-Driven Versus Data-Driven Logics

    Czech Academy of Sciences Publication Activity Database

    Dubois, D.; Hájek, Petr; Prade, H.

    2000-01-01

    Roč. 9, č. 1 (2000), s. 65-89 ISSN 0925-8531 R&D Projects: GA AV ČR IAA1030601 Grant - others:CNRS(FR) 4008 Institutional research plan: AV0Z1030915 Keywords : epistemic logic * possibility theory * data-driven reasoning * deontic logic Subject RIV: BA - General Mathematics

  18. Synchrotron-driven spallation sources

    CERN Document Server

    Bryant, P J

    1996-01-01

    The use of synchrotrons for pulsed neutron spallation sources is an example of scientific and technological spin-off from the accelerator development for particle physics. Accelerator-driven sources provide an alternative to the continuous-flux, nuclear reactors that currently furnish the majority of neutrons for research and development. Although the present demand for neutrons can be adequately met by the existing reactors, this situation is unlikely to continue due to the increasing severity of safety regulations and the declared policies of many countries to close down their reactors within the next decade or so. Since the demand for neutrons as a research tool is, in any case,expected to grow, there has been a corresponding interest in sources that are synchrotron-driven or linac-driven with a pulse compression ring and currently several design studies are being made. These accelerator-driven sources also have the advantage of a time structure with a high peak neutron flux. The basic requirement is for a...

  19. Coherent states of the driven Rydberg atom: Quantum-classical correspondence of periodically driven systems

    International Nuclear Information System (INIS)

    Vela-Arevalo, Luz V.; Fox, Ronald F.

    2005-01-01

    A methodology to calculate generalized coherent states for a periodically driven system is presented. We study wave packets constructed as a linear combination of suitable Floquet states of the three-dimensional Rydberg atom in a microwave field. The driven coherent states show classical space localization, spreading, and revivals and remain localized along the classical trajectory. The microwave strength and frequency have a great effect in the localization of Floquet states, since quasienergy avoided crossings produce delocalization of the Floquet states, showing that tuning of the parameters is very important. Using wavelet-based time-frequency analysis, the classical phase-space structure is determined, which allows us to show that the driven coherent state is located in a large regular region in which the z coordinate is in resonance with the external field. The expectation values of the wave packet show that the driven coherent state evolves along the classical trajectory

  20. The interaction between stimulus-driven and goal-driven orienting as revealed by eye movements

    NARCIS (Netherlands)

    Schreij, D.B.B.; Los, S.A.; Theeuwes, J.; Enns, J.T.; Olivers, C.N.L.

    2014-01-01

    It is generally agreed that attention can be captured in a stimulus-driven or in a goal-driven fashion. In studies that investigated both types of capture, the effects on mean manual response time (reaction time [RT]) are generally additive, suggesting two independent underlying processes. However,

  1. Data Driven Economic Model Predictive Control

    Directory of Open Access Journals (Sweden)

    Masoud Kheradmandi

    2018-04-01

    Full Text Available This manuscript addresses the problem of data driven model based economic model predictive control (MPC design. To this end, first, a data-driven Lyapunov-based MPC is designed, and shown to be capable of stabilizing a system at an unstable equilibrium point. The data driven Lyapunov-based MPC utilizes a linear time invariant (LTI model cognizant of the fact that the training data, owing to the unstable nature of the equilibrium point, has to be obtained from closed-loop operation or experiments. Simulation results are first presented demonstrating closed-loop stability under the proposed data-driven Lyapunov-based MPC. The underlying data-driven model is then utilized as the basis to design an economic MPC. The economic improvements yielded by the proposed method are illustrated through simulations on a nonlinear chemical process system example.

  2. Data-Driven Problems in Elasticity

    Science.gov (United States)

    Conti, S.; Müller, S.; Ortiz, M.

    2018-01-01

    We consider a new class of problems in elasticity, referred to as Data-Driven problems, defined on the space of strain-stress field pairs, or phase space. The problem consists of minimizing the distance between a given material data set and the subspace of compatible strain fields and stress fields in equilibrium. We find that the classical solutions are recovered in the case of linear elasticity. We identify conditions for convergence of Data-Driven solutions corresponding to sequences of approximating material data sets. Specialization to constant material data set sequences in turn establishes an appropriate notion of relaxation. We find that relaxation within this Data-Driven framework is fundamentally different from the classical relaxation of energy functions. For instance, we show that in the Data-Driven framework the relaxation of a bistable material leads to material data sets that are not graphs.

  3. Current-driven turbulence in plasmas

    International Nuclear Information System (INIS)

    Kluiver, H. de.

    1977-10-01

    Research on plasma heating in linear and toroidal systems using current-driven turbulence is reviewed. The motivation for this research is presented. Relations between parameters describing the turbulent plasma state and macroscopic observables are given. Several linear and toroidal devices used in current-driven turbulence studies are described, followed by a discussion of special diagnostic methods used. Experimental results on the measurement of electron and ion heating, anomalous plasma conductivity and associated turbulent fluctuation spectra are reviewed. Theories on current-driven turbulence are discussed and compared with experiments. It is demonstrated from the experimental results that current-driven turbulence occurs not only for extreme values of the electric field but also for an experimentally much more accessible and wide range of parameters. This forms a basis for a discussion on possible future applications in fusion-oriented plasma research

  4. Water-driven micromotors.

    Science.gov (United States)

    Gao, Wei; Pei, Allen; Wang, Joseph

    2012-09-25

    We demonstrate the first example of a water-driven bubble-propelled micromotor that eliminates the requirement for the common hydrogen peroxide fuel. The new water-driven Janus micromotor is composed of a partially coated Al-Ga binary alloy microsphere prepared via microcontact mixing of aluminum microparticles and liquid gallium. The ejection of hydrogen bubbles from the exposed Al-Ga alloy hemisphere side, upon its contact with water, provides a powerful directional propulsion thrust. Such spontaneous generation of hydrogen bubbles reflects the rapid reaction between the aluminum alloy and water. The resulting water-driven spherical motors can move at remarkable speeds of 3 mm s(-1) (i.e., 150 body length s(-1)), while exerting large forces exceeding 500 pN. Factors influencing the efficiency of the aluminum-water reaction and the resulting propulsion behavior and motor lifetime, including the ionic strength and environmental pH, are investigated. The resulting water-propelled Al-Ga/Ti motors move efficiently in different biological media (e.g., human serum) and hold considerable promise for diverse biomedical or industrial applications.

  5. Convenient biosynthetic preparation of isomeric spin-labelled radioactive phosphatidic acids

    Energy Technology Data Exchange (ETDEWEB)

    Stuhne, L.; Stanacev, N.Z. (Toronto Univ., Ontario (Canada). Dept. of Clinical Biochemistry)

    1982-11-01

    A convenient method for the enzymatic preparation of sn-3-(2-/sup 3/H)phosphatidic acids carrying also 5-, 12-, or 16-nitroxide stearic acids, from sn-3-(2-/sup 3/H) glycerophosphate and isolated guinea pig liver microsomes, is described in detail. The procedure allows a simultaneous preparation of three spin-labelled sn-3-(2-/sup 3/H)phosphatidic acids of yields 3-3.5..mu..mol of each compound which is >99% pure in respect to the radioactivity and which contains 25 mol% of spin-labelled fatty acids. These phosphatidic acids were approximately equally distributed between the primary and the secondary hydroxyl when 12- or 16-nitroxide stearic acids were used or predominantly (75%) associated with the secondary hydroxyl of sn-3-(2-/sup 3/H)phosphatidic acid when 5-nitroxide stearic acid was present in the incubation mixture.

  6. Nitroxydes chiraux à squelette imidazolidin-4-one comme catalyseurs d'oxydation énantiosélective d'alcools par O2

    OpenAIRE

    Carbo Lopez , Marta

    2014-01-01

    The aim of this thesis was to evaluate the use of chiral nitroxides containing an imidazolidin-4-one squeletton as enantioselective catalysts for the aerobic oxidation of alcohols. In this view, several nitroxides with different α substituents have been synthesized to investigate the influence of these groups. Several co-catalysts reported in the literature have been tested for the oxidation reactions that take place at room temperature and atmospheric pressure. These catalytic systems can be...

  7. Heat-driven spin torques in antiferromagnets

    Science.gov (United States)

    Białek, Marcin; Bréchet, Sylvain; Ansermet, Jean-Philippe

    2018-04-01

    Heat-driven magnetization damping, which is a linear function of a temperature gradient, is predicted in antiferromagnets by considering the sublattice dynamics subjected to a heat-driven spin torque. This points to the possibility of achieving spin torque oscillator behavior. The model is based on the magnetic Seebeck effect acting on sublattices which are exchange coupled. The heat-driven spin torque is estimated and the feasibility of detecting this effect is discussed.

  8. Reaction-based Indicator displacement Assay (RIA) for the selective colorimetric and fluorometric detection of peroxynitrite† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4sc03983a Click here for additional data file.

    Science.gov (United States)

    Sun, Xiaolong; Lacina, Karel; Ramsamy, Elena C.; Flower, Stephen E.; Fossey, John S.; Qian, Xuhong

    2015-01-01

    Using the self-assembly of aromatic boronic acids with Alizarin Red S (ARS), we developed a new chemosensor for the selective detection of peroxynitrite. Phenylboronic acid (PBA), benzoboroxole (BBA) and 2-(N,N-dimethylaminomethyl)phenylboronic acid (NBA) were employed to bind with ARS to form the complex probes. In particular, the ARS–NBA system with a high binding affinity can preferably react with peroxynitrite over hydrogen peroxide and other ROS/RNS due to the protection of the boron via the solvent-insertion B–N interaction. Our simple system produces a visible colorimetric change and on–off fluorescence response towards peroxynitrite. By coupling a chemical reaction that leads to an indicator displacement, we have developed a new sensing strategy, referred to herein as RIA (Reaction-based Indicator displacement Assay). PMID:28706677

  9. Role of compressibility on driven magnetic reconnection

    International Nuclear Information System (INIS)

    Sato, T.; Hayashi, T.; Watanabe, K.; Horiuchi, R.; Tanaka, M.; Sawairi, N.; Kusano, K.

    1991-08-01

    Whether it is induced by an ideal (current driven) instability or by an external force, plasma flow causes a change in the magnetic field configuration and often gives rise to a current intensification locally, thereby a fast driven reconnection being driven there. Many dramatic phenomena in magnetically confined plasmas such as magnetospheric substorms, solar flares, MHD self-organization and tokamak sawtooth crash, may be attributed to this fast driven reconnection. Using a fourth order MHD simulation code it is confirmed that compressibility of the plasma plays a crucial role in leading to a fast (MHD time scale) driven reconnection. This indicates that the incompressible representation is not always applicable to the study of a global dynamical behavior of a magnetically confined plasma. (author)

  10. Into the Surge of Network-driven Innovation

    DEFF Research Database (Denmark)

    Østergaard, Claus Møller; Rosenstand, Claus Andreas Foss; Gertsen, Frank

    2013-01-01

    this is examined from the 1880’s up until today. The contribution of the paper is a societal perspective on innovation, where the difference between industrial society and knowledge society leads into the surge of network-driven innovation. Network-driven innovation is unfolded on top of the known cost- driven...

  11. Economics-driven software architecture

    CERN Document Server

    Mistrik, Ivan; Kazman, Rick; Zhang, Yuanyuan

    2014-01-01

    Economics-driven Software Architecture presents a guide for engineers and architects who need to understand the economic impact of architecture design decisions: the long term and strategic viability, cost-effectiveness, and sustainability of applications and systems. Economics-driven software development can increase quality, productivity, and profitability, but comprehensive knowledge is needed to understand the architectural challenges involved in dealing with the development of large, architecturally challenging systems in an economic way. This book covers how to apply economic consider

  12. Data-driven batch schuduling

    Energy Technology Data Exchange (ETDEWEB)

    Bent, John [Los Alamos National Laboratory; Denehy, Tim [GOOGLE; Arpaci - Dusseau, Remzi [UNIV OF WISCONSIN; Livny, Miron [UNIV OF WISCONSIN; Arpaci - Dusseau, Andrea C [NON LANL

    2009-01-01

    In this paper, we develop data-driven strategies for batch computing schedulers. Current CPU-centric batch schedulers ignore the data needs within workloads and execute them by linking them transparently and directly to their needed data. When scheduled on remote computational resources, this elegant solution of direct data access can incur an order of magnitude performance penalty for data-intensive workloads. Adding data-awareness to batch schedulers allows a careful coordination of data and CPU allocation thereby reducing the cost of remote execution. We offer here new techniques by which batch schedulers can become data-driven. Such systems can use our analytical predictive models to select one of the four data-driven scheduling policies that we have created. Through simulation, we demonstrate the accuracy of our predictive models and show how they can reduce time to completion for some workloads by as much as 80%.

  13. Measurement of rotational dynamics by the simultaneous nonlinear analysis of optical and EPR data.

    OpenAIRE

    Hustedt, E J; Cobb, C E; Beth, A H; Beechem, J M

    1993-01-01

    In the preceding companion article in this issue, an optical dye and a nitroxide radical were combined in a new dual function probe, 5-SLE. In this report, it is demonstrated that time-resolved optical anisotropy and electron paramagnetic resonance (EPR) data can be combined in a single analysis to measure rotational dynamics. Rigid-limit and rotational diffusion models for simulating nitroxide EPR data have been incorporated into a general non-linear least-squares procedure based on the Marq...

  14. Design Driven Testing Test Smarter, Not Harder

    CERN Document Server

    Stephens, M

    2010-01-01

    The groundbreaking book Design Driven Testing brings sanity back to the software development process by flipping around the concept of Test Driven Development (TDD) - restoring the concept of using testing to verify a design instead of pretending that unit tests are a replacement for design. Anyone who feels that TDD is "Too Damn Difficult" will appreciate this book. Design Driven Testing shows that, by combining a forward-thinking development process with cutting-edge automation, testing can be a finely targeted, business-driven, rewarding effort. In other words, you'll learn how to test

  15. The SimpleMix study with biphasic insulin aspart 30: a randomized controlled trial investigating patient-driven titration versus investigator-driven titration.

    Science.gov (United States)

    Gao, Yan; Luquez, Cecilia; Lynggaard, Helle; Andersen, Henning; Saboo, Banshi

    2014-12-01

    The study aimed to confirm the efficacy, through non-inferiority, of patient-driven versus investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) in terms of glycemic control assessed by HbA1c change. SimpleMix was a 20 week, open-label, randomized, two-armed, parallel-group, multicenter study in five countries (Argentina, China, India, Poland, and the UK). Patients with type 2 diabetes were randomized into either patient-driven or investigator-driven BIAsp 30 titration groups. Non-inferiority of patient-driven vs. investigator-driven titration based on change in HbA1c from baseline to week 20 could not be demonstrated. Mean (SE) estimated change from baseline to week 20 was -0.72 (0.08)% in the patient-driven group and -0.97 (0.08)% in the investigator-driven group; estimated difference 0.25% (95% CI: 0.04; 0.46). Estimated mean change (SE) in fasting plasma glucose from baseline to week 20 was similar between groups: -0.94 (0.21) mmol/L for patient-driven and -1.07 (0.22) mmol/L for investigator-driven (difference non-significant). Both treatment arms were well tolerated, and hypoglycemic episode rates were similar between groups, with a rate ratio of 0.77 (95% CI: 0.54; 1.09; p = 0.143) for all hypoglycemic episodes and 0.78 (95% CI: 0.42; 1.43; p = 0.417) for nocturnal hypoglycemic episodes. Non-inferiority of patient-driven versus investigator-driven titration with regard to change from baseline to end-of-treatment HbA1c could not be confirmed. It is possible that a clinic visit 12 weeks after intensification of treatment with BIAsp 30 in patients with type 2 diabetes inadequately treated with basal insulin may benefit patient-driven titration of BIAsp 30. A limitation of the study was the relatively small number of patients recruited in each country, which does not allow country-specific analyses to be performed. Overall, treatment with BIAsp 30 was well tolerated in both treatment groups.

  16. Stability analysis of hybrid-driven underwater glider

    Science.gov (United States)

    Niu, Wen-dong; Wang, Shu-xin; Wang, Yan-hui; Song, Yang; Zhu, Ya-qiang

    2017-10-01

    Hybrid-driven underwater glider is a new type of unmanned underwater vehicle, which combines the advantages of autonomous underwater vehicles and traditional underwater gliders. The autonomous underwater vehicles have good maneuverability and can travel with a high speed, while the traditional underwater gliders are highlighted by low power consumption, long voyage, long endurance and good stealth characteristics. The hybrid-driven underwater gliders can realize variable motion profiles by their own buoyancy-driven and propeller propulsion systems. Stability of the mechanical system determines the performance of the system. In this paper, the Petrel-II hybrid-driven underwater glider developed by Tianjin University is selected as the research object and the stability of hybrid-driven underwater glider unitedly controlled by buoyancy and propeller has been targeted and evidenced. The dimensionless equations of the hybrid-driven underwater glider are obtained when the propeller is working. Then, the steady speed and steady glide path angle under steady-state motion have also been achieved. The steady-state operating conditions can be calculated when the hybrid-driven underwater glider reaches the desired steady-state motion. And the steadystate operating conditions are relatively conservative at the lower bound of the velocity range compared with the range of the velocity derived from the method of the composite Lyapunov function. By calculating the hydrodynamic coefficients of the Petrel-II hybrid-driven underwater glider, the simulation analysis has been conducted. In addition, the results of the field trials conducted in the South China Sea and the Danjiangkou Reservoir of China have been presented to illustrate the validity of the analysis and simulation, and to show the feasibility of the method of the composite Lyapunov function which verifies the stability of the Petrel-II hybrid-driven underwater glider.

  17. Profit-driven and demand-driven investment growth and fluctuations in different accumulation regimes

    OpenAIRE

    Giovanni Dosi; Mauro Sodini; Maria Enrica Virgillito

    2013-01-01

    The main task of this work is to develope a model able to encompass, at the same time, Keynesian, demand-driven, and Marxian, profit-driven determinants of fluctuations. Our starting point is the Goodwin's model (1967), rephrased in discrete time and extended by means of a coupled dynamics structure. The model entails the combined interaction of a demand effect, which resembles a rudimentary first approximation to an accelerator, and of a hysteresis effect in wage formation in turn affecting ...

  18. Non-driven micromechanical gyroscopes and their applications

    CERN Document Server

    Zhang, Fuxue; Wang, Guosheng

    2018-01-01

    This book comprehensively and systematically introduces readers to the theories, structures, performance and applications of non-driven mechanical and non-driven micromechanical gyroscopes. The book is divided into three parts, the first of which mainly addresses mathematic models, precision, performance and operating error in non-driven mechanical gyroscopes. The second part focuses on the operating theory, error, phase shift and performance experiments involving non-driven micromechanical gyroscopes in rotating flight carriers, while the third part shares insights into the application of non-driven micromechanical gyroscopes in control systems for rotating flight carriers. The book offers a unique resource for all researchers and engineers who are interested in the use of inertial devices and automatic control systems for rotating flight carriers.  It can also serve as a reference book for undergraduates, graduates and instructors in related fields at colleges and universities.

  19. Temporal Data-Driven Sleep Scheduling and Spatial Data-Driven Anomaly Detection for Clustered Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Gang Li

    2016-09-01

    Full Text Available The spatial–temporal correlation is an important feature of sensor data in wireless sensor networks (WSNs. Most of the existing works based on the spatial–temporal correlation can be divided into two parts: redundancy reduction and anomaly detection. These two parts are pursued separately in existing works. In this work, the combination of temporal data-driven sleep scheduling (TDSS and spatial data-driven anomaly detection is proposed, where TDSS can reduce data redundancy. The TDSS model is inspired by transmission control protocol (TCP congestion control. Based on long and linear cluster structure in the tunnel monitoring system, cooperative TDSS and spatial data-driven anomaly detection are then proposed. To realize synchronous acquisition in the same ring for analyzing the situation of every ring, TDSS is implemented in a cooperative way in the cluster. To keep the precision of sensor data, spatial data-driven anomaly detection based on the spatial correlation and Kriging method is realized to generate an anomaly indicator. The experiment results show that cooperative TDSS can realize non-uniform sensing effectively to reduce the energy consumption. In addition, spatial data-driven anomaly detection is quite significant for maintaining and improving the precision of sensor data.

  20. Automated Testing of Event-Driven Applications

    DEFF Research Database (Denmark)

    Jensen, Casper Svenning

    may be tested by selecting an interesting input (i.e. a sequence of events), and deciding if a failure occurs when the selected input is applied to the event-driven application under test. Automated testing promises to reduce the workload for developers by automatically selecting interesting inputs...... and detect failures. However, it is non-trivial to conduct automated testing of event-driven applications because of, for example, infinite input spaces and the absence of specifications of correct application behavior. In this PhD dissertation, we identify a number of specific challenges when conducting...... automated testing of event-driven applications, and we present novel techniques for solving these challenges. First, we present an algorithm for stateless model-checking of event-driven applications with partial-order reduction, and we show how this algorithm may be used to systematically test web...

  1. Nitro-Oxidative Stress after Neuronal Ischemia Induces Protein Nitrotyrosination and Cell Death

    Directory of Open Access Journals (Sweden)

    Marta Tajes

    2013-01-01

    Full Text Available Ischemic stroke is an acute vascular event that obstructs blood supply to the brain, producing irreversible damage that affects neurons but also glial and brain vessel cells. Immediately after the stroke, the ischemic tissue produces nitric oxide (NO to recover blood perfusion but also produces superoxide anion. These compounds interact, producing peroxynitrite, which irreversibly nitrates protein tyrosines. The present study measured NO production in a human neuroblastoma (SH-SY5Y, a murine glial (BV2, a human endothelial cell line (HUVEC, and in primary cultures of human cerebral myocytes (HC-VSMCs after experimental ischemia in vitro. Neuronal, endothelial, and inducible NO synthase (NOS expression was also studied up to 24 h after ischemia, showing a different time course depending on the NOS type and the cells studied. Finally, we carried out cell viability experiments on SH-SY5Y cells with H2O2, a prooxidant agent, and with a NO donor to mimic ischemic conditions. We found that both compounds were highly toxic when they interacted, producing peroxynitrite. We obtained similar results when all cells were challenged with peroxynitrite. Our data suggest that peroxynitrite induces cell death and is a very harmful agent in brain ischemia.

  2. Dynamical critical phenomena in driven-dissipative systems.

    Science.gov (United States)

    Sieberer, L M; Huber, S D; Altman, E; Diehl, S

    2013-05-10

    We explore the nature of the Bose condensation transition in driven open quantum systems, such as exciton-polariton condensates. Using a functional renormalization group approach formulated in the Keldysh framework, we characterize the dynamical critical behavior that governs decoherence and an effective thermalization of the low frequency dynamics. We identify a critical exponent special to the driven system, showing that it defines a new dynamical universality class. Hence critical points in driven systems lie beyond the standard classification of equilibrium dynamical phase transitions. We show how the new critical exponent can be probed in experiments with driven cold atomic systems and exciton-polariton condensates.

  3. Recent advances in laser-driven neutron sources

    Science.gov (United States)

    Alejo, A.; Ahmed, H.; Green, A.; Mirfayzi, S. R.; Borghesi, M.; Kar, S.

    2016-11-01

    Due to the limited number and high cost of large-scale neutron facilities, there has been a growing interest in compact accelerator-driven sources. In this context, several potential schemes of laser-driven neutron sources are being intensively studied employing laser-accelerated electron and ion beams. In addition to the potential of delivering neutron beams with high brilliance, directionality and ultra-short burst duration, a laser-driven neutron source would offer further advantages in terms of cost-effectiveness, compactness and radiation confinement by closed-coupled experiments. Some of the recent advances in this field are discussed, showing improvements in the directionality and flux of the laser-driven neutron beams.

  4. Applications of laser-driven particle acceleration

    CERN Document Server

    Parodi, Katia; Schreiber, Jorg

    2018-01-01

    The first book of its kind to highlight the unique capabilities of laser-driven acceleration and its diverse potential, Applications of Laser-Driven Particle Acceleration presents the basic understanding of acceleration concepts and envisioned prospects for selected applications. As the main focus, this new book explores exciting and diverse application possibilities, with emphasis on those uniquely enabled by the laser driver that can also be meaningful and realistic for potential users. A key aim of the book is to inform multiple, interdisciplinary research communities of the new possibilities available and to inspire them to engage with laser-driven acceleration, further motivating and advancing this developing field. Material is presented in a thorough yet accessible manner, making it a valuable reference text for general scientific and engineering researchers who are not necessarily subject matter experts. Applications of Laser-Driven Particle Acceleration is edited by Professors Paul R. Bolton, Katia ...

  5. Consistent data-driven computational mechanics

    Science.gov (United States)

    González, D.; Chinesta, F.; Cueto, E.

    2018-05-01

    We present a novel method, within the realm of data-driven computational mechanics, to obtain reliable and thermodynamically sound simulation from experimental data. We thus avoid the need to fit any phenomenological model in the construction of the simulation model. This kind of techniques opens unprecedented possibilities in the framework of data-driven application systems and, particularly, in the paradigm of industry 4.0.

  6. Proposal of laser-driven automobile

    Science.gov (United States)

    Yabe, Takashi; Oozono, Hirokazu; Taniguchi, Kazumoto; Ohkubo, Tomomasa; Miyazaki, Sho; Uchida, Shigeaki; Baasandash, Choijil

    2004-09-01

    We propose an automobile driven by piston motion, which is driven by water-laser coupling. The automobile can load a solar-pumped fiber laser or can be driven by ground-based lasers. The vehicle is much useful for the use in other planet in which usual combustion engine cannot be used. The piston is in a closed system and then the water will not be exhausted into vacuum. In the preliminary experiment, we succeeded to drive the cylindrical piston of 0.2g (6mm in diameter) on top of water placed inside the acrylic pipe of 8 mm in inner diameter and the laser is incident from the bottom and focused onto the upper part of water by the lens (f=8mm) attached to the bottom edge.

  7. Data-driven architectural production and operation

    NARCIS (Netherlands)

    Bier, H.H.; Mostafavi, S.

    2014-01-01

    Data-driven architectural production and operation as explored within Hyperbody rely heavily on system thinking implying that all parts of a system are to be understood in relation to each other. These relations are increasingly established bi-directionally so that data-driven architecture is not

  8. Non-inductively driven currents in JET

    International Nuclear Information System (INIS)

    Challis, C.D.; Cordey, J.G.; Hamnen, H.; Stubberfield, P.M.; Christiansen, J.P.; Lazzaro, E.; Muir, D.G.; Stork, D.; Thompson, E.

    1989-01-01

    Neutral beam heating data from JET have been analysed in detail to determine what proportion of the current is driven non-inductively. It is found that in low density limiter discharges, currents of the order of 0.5 MA are driven, while in H-mode plasmas currents of the order of 0.7 MA are measured. These measured currents are found to be in reasonable agreement with theoretical predictions based on neoclassical models. In low density plasmas the beam driven current is large while the neoclassical bootstrap current dominates H-mode plasmas. (author). 19 refs, 11 figs

  9. BRAHMMA - accelerator driven subcritical facility

    International Nuclear Information System (INIS)

    Roy, Tushar; Shukla, Shefali; Shukla, M.; Ray, N.K.; Kashyap, Y.S.; Patel, T.; Gadkari, S.C.

    2017-01-01

    Accelerator Driven Subcritical systems are being studied worldwide for their potential in burning minor actinides and reducing long term radiotoxicity of spent nuclear fuels. In order to pursue the physics studies of Accelerator Driven Subcritical systems, a thermal subcritical assembly BRAHMMA (BeOReflectedAndHDPeModeratedMultiplying Assembly) has been developed at Purnima Labs, BARC. The facility consists of two major components: Subcritical core and Accelerator (DT/ DD Purnima Neutron Generator)

  10. Comments to accelerator-driven system

    International Nuclear Information System (INIS)

    Taka aki, Matsumoto

    2003-01-01

    Accelerator-driven system (ADS) that was a subcritical nuclear reactor driven by a high power proton accelerator was recently studied by several large organisations over the world. This paper described two comments for ADS: philosophical and technological ones. The latter was made from a view point of micro ball lightning (BL) that was newly discovered by the author. Negative and positive aspects of micro BL for ADS were discussed. (author)

  11. Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells.

    Science.gov (United States)

    Bauer, Georg

    2015-12-01

    Tumor cells generate extracellular superoxide anions and are protected against intercellular apoptosis-inducing HOCl- and NO/peroxynitrite signaling through the expression of membrane-associated catalase. This enzyme decomposes H2O2 and thus prevents HOCl synthesis. It efficiently interferes with NO/peroxynitrite signaling through oxidation of NO and decomposition of peroxynitrite. The regulatory potential of catalase at the crosspoint of ROS and RNS chemical biology, as well as its high local concentration on the outside of the cell membrane of tumor cells, establish tight control of intercellular signaling and thus prevent tumor cell apoptosis. Therefore, inhibition of catalase or its inactivation by singlet oxygen reactivate intercellular apoptosis-inducing signaling. Nitric oxide and peroxynitrite are connected with catalase in multiple and meaningful ways, as (i) NO can be oxidated by compound I of catalase, (ii) NO can reversibly inhibit catalase, (iii) peroxynitrite can be decomposed by catalase and (iv) the interaction between peroxynitrite and H2O2 leads to the generation of singlet oxygen that inactivates catalase. Therefore, modulation of the concentration of free NO through addition of arginine, inhibition of arginase, induction of NOS expression or inhibition of NO dioxygenase triggers an autoamplificatory biochemical cascade that is based on initial formation of singlet oxygen, amplification of superoxide anion/H2O2 and NO generation through singlet oxygen dependent stimulation of the FAS receptor and caspase-8. Finally, singlet oxygen is generated at sufficiently high concentration to inactivate protective catalase and to reactivate intercellular apoptosis-inducing ROS signaling. This regulatory network allows to establish several pathways for synergistic interactions, like the combination of modulators of NO metabolism with enhancers of superoxide anion generation, modulators of NO metabolism that act at different targets and between modulators of

  12. Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells

    Science.gov (United States)

    Bauer, Georg

    2015-01-01

    Tumor cells generate extracellular superoxide anions and are protected against intercellular apoptosis-inducing HOCl- and NO/peroxynitrite signaling through the expression of membrane-associated catalase. This enzyme decomposes H2O2 and thus prevents HOCl synthesis. It efficiently interferes with NO/peroxynitrite signaling through oxidation of NO and decomposition of peroxynitrite. The regulatory potential of catalase at the crosspoint of ROS and RNS chemical biology, as well as its high local concentration on the outside of the cell membrane of tumor cells, establish tight control of intercellular signaling and thus prevent tumor cell apoptosis. Therefore, inhibition of catalase or its inactivation by singlet oxygen reactivate intercellular apoptosis-inducing signaling. Nitric oxide and peroxynitrite are connected with catalase in multiple and meaningful ways, as (i) NO can be oxidated by compound I of catalase, (ii) NO can reversibly inhibit catalase, (iii) peroxynitrite can be decomposed by catalase and (iv) the interaction between peroxynitrite and H2O2 leads to the generation of singlet oxygen that inactivates catalase. Therefore, modulation of the concentration of free NO through addition of arginine, inhibition of arginase, induction of NOS expression or inhibition of NO dioxygenase triggers an autoamplificatory biochemical cascade that is based on initial formation of singlet oxygen, amplification of superoxide anion/H2O2 and NO generation through singlet oxygen dependent stimulation of the FAS receptor and caspase-8. Finally, singlet oxygen is generated at sufficiently high concentration to inactivate protective catalase and to reactivate intercellular apoptosis-inducing ROS signaling. This regulatory network allows to establish several pathways for synergistic interactions, like the combination of modulators of NO metabolism with enhancers of superoxide anion generation, modulators of NO metabolism that act at different targets and between modulators of

  13. Test-driven modeling of embedded systems

    DEFF Research Database (Denmark)

    Munck, Allan; Madsen, Jan

    2015-01-01

    To benefit maximally from model-based systems engineering (MBSE) trustworthy high quality models are required. From the software disciplines it is known that test-driven development (TDD) can significantly increase the quality of the products. Using a test-driven approach with MBSE may have...... a similar positive effect on the quality of the system models and the resulting products and may therefore be desirable. To define a test-driven model-based systems engineering (TD-MBSE) approach, we must define this approach for numerous sub disciplines such as modeling of requirements, use cases...... suggest that our method provides a sound foundation for rapid development of high quality system models....

  14. An RCT Investigating Patient-Driven Versus Physician-Driven Titration of BIAsp 30 in Patients with Type 2 Diabetes Uncontrolled Using NPH Insulin.

    Science.gov (United States)

    Chraibi, Abdelmjid; Al-Herz, Shoorook; Nguyen, Bich Dao; Soeatmadji, Djoko W; Shinde, Anil; Lakshmivenkataraman, Balasubramanian; Assaad-Khalil, Samir H

    2017-08-01

    The aim of this study was to confirm the efficacy of patient-driven titration of BIAsp 30 in terms of glycemic control, by comparing it to physician-driven titration of BIAsp 30, in patients with type 2 diabetes in North Africa, the Middle East, and Asia. A 20-week, open-label, randomized, two-armed, parallel-group, multicenter study in Egypt, Indonesia, Morocco, Saudi Arabia, and Vietnam. Patients (n = 155) with type 2 diabetes inadequately controlled using neutral protamine Hagedorn (NPH) insulin were randomized to either patient-driven or physician-driven BIAsp 30 titration. The noninferiority of patient-driven compared to physician-driven titration with respect to the reduction in HbA1c was confirmed. The estimated mean change in HbA1c from baseline to week 20 was -1.27% in the patient-driven arm and -1.04% in the physician-driven arm, with an estimated treatment difference of -0.23% (95% confidence interval: -0.54; 0.08). After 20 weeks of treatment, the proportions of patients achieving the target of HbA1c titration arms; the proportions of patients achieving the target of ≤6.5% were also similar. Both titration algorithms were well tolerated, and hypoglycemic episode rates were similar in both arms. Patient-driven titration of BIAsp 30 can be as effective and safe as physician-driven titration in non-Western populations. Overall, the switch from NPH insulin to BIAsp 30 was well tolerated in both titration arms and led to improved glycemic control. A limitation of the study was the relatively small number of patients recruited in each country. ClinicalTrials.gov NCT01589653. Novo Nordisk A/S, Denmark.

  15. Solar-driven refrigeration technologies; Koeltechnologieen op zonne-energie

    Energy Technology Data Exchange (ETDEWEB)

    De Cillis, S.; Infante Ferreira, C.A. [Technische Universiteit Delft, Delft (Netherlands); Krieg, J. [Unilever Foods and Health Research Institute, Vlaardingen (Netherlands)

    2005-12-01

    A review is presented of solar driven refrigeration technologies. A subdivision is made between electric driven and thermal driven systems. Their potential and stage of development are discussed. The electric driven systems include Stirling, thermo-acoustic, thermoelectric, electrochemical and membrane assisted absorption systems. The thermal driven systems include absorption and adsorption systems. A model is used to compare the performance of the different solutions. [Dutch] Dit artikel geeft een overzicht van zon-aangedreven koeltechnologieen. Er wordt onderscheid gemaakt tussen elektrisch en thermisch aangedreven systemen. Hun potentieel en niveau van ontwikkeling worden besproken. De elektrisch aangedreven systemen omvatten Stirling, thermo-akoestisch, thermo-elektrisch, elektrochemisch en membraanondersteund absorptiesystemen.De warmte-aangedreven systemen omvatten absorptie en adsorptie. Er wordt gebruik gemaakt van een model om de prestaties van de verschillende alternatieven onderling te vergelijken.

  16. Electromagnetic Properties Analysis on Hybrid-driven System of Electromagnetic Motor

    Science.gov (United States)

    Zhao, Jingbo; Han, Bingyuan; Bei, Shaoyi

    2018-01-01

    The hybrid-driven system made of permanent-and electromagnets applied in the electromagnetic motor was analyzed, equivalent magnetic circuit was used to establish the mathematical models of hybrid-driven system, based on the models of hybrid-driven system, the air gap flux, air-gap magnetic flux density, electromagnetic force was proposed. Taking the air-gap magnetic flux density and electromagnetic force as main research object, the hybrid-driven system was researched. Electromagnetic properties of hybrid-driven system with different working current modes is studied preliminary. The results shown that analysis based on hybrid-driven system can improve the air-gap magnetic flux density and electromagnetic force more effectively and can also guarantee the output stability, the effectiveness and feasibility of the hybrid-driven system are verified, which proved theoretical basis for the design of hybrid-driven system.

  17. Just-in-time Database-Driven Web Applications

    Science.gov (United States)

    2003-01-01

    "Just-in-time" database-driven Web applications are inexpensive, quickly-developed software that can be put to many uses within a health care organization. Database-driven Web applications garnered 73873 hits on our system-wide intranet in 2002. They enabled collaboration and communication via user-friendly Web browser-based interfaces for both mission-critical and patient-care-critical functions. Nineteen database-driven Web applications were developed. The application categories that comprised 80% of the hits were results reporting (27%), graduate medical education (26%), research (20%), and bed availability (8%). The mean number of hits per application was 3888 (SD = 5598; range, 14-19879). A model is described for just-in-time database-driven Web application development and an example given with a popular HTML editor and database program. PMID:14517109

  18. Natriuretic peptide receptor-C activation attenuates angiotensin II-induced enhanced oxidative stress and hyperproliferation of aortic vascular smooth muscle cells.

    Science.gov (United States)

    Madiraju, Padma; Hossain, Ekhtear; Anand-Srivastava, Madhu B

    2018-02-07

    We showed previously that natriuretic peptide receptor-C (NPR-C) agonist, C-ANP 4-23 , attenuated the enhanced expression of Giα proteins in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) through the inhibition of enhanced oxidative stress. Since the enhanced levels of endogenous angiotensin II (Ang II) contribute to the overexpression of Giα proteins and augmented oxidative stress in VSMC from SHR, the present study was undertaken to investigate if C-ANP 4-23 could also attenuate angiotensin II (Ang II)-induced oxidative stress and associated signaling. Ang II treatment of aortic VSMC augmented the levels of superoxide anion (O 2 - ), NADPH oxidase activity, and the expression of NADPH oxidase subunits and C-ANP 4-23 treatment attenuated all these to control levels. In addition, Ang II-induced enhanced levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyl content were also attenuated toward control levels by C-ANP 4-23 treatment. On the other hand, Ang II inhibited the levels of nitric oxide (NO) and augmented the levels of peroxynitrite (OONO - ) in VSMC which were restored to control levels by C-ANP 4-23 treatment. Furthermore, C-ANP 4-23 treatment attenuated Ang II-induced enhanced expression of Giα proteins, phosphorylation of p38, JNK, and ERK 1,2 as well as hyperproliferation of VSMC as determined by DNA synthesis, and metabolic activity. These results indicate that C-ANP 4-23 , via the activation of NPR-C, attenuates Ang II-induced enhanced nitroxidative stress, overexpression of Giα proteins, increased activation of the p38/JNK/ERK 1,2 signaling pathways, and hyperproliferation of VSMC. It may be suggested that C-ANP 4-23 could be used as a therapeutic agent in the treatment of vascular remodeling associated with hypertension and atherosclerosis.

  19. Bending of Euler-Bernoulli nanobeams based on the strain-driven and stress-driven nonlocal integral models: a numerical approach

    Science.gov (United States)

    Oskouie, M. Faraji; Ansari, R.; Rouhi, H.

    2018-04-01

    Eringen's nonlocal elasticity theory is extensively employed for the analysis of nanostructures because it is able to capture nanoscale effects. Previous studies have revealed that using the differential form of the strain-driven version of this theory leads to paradoxical results in some cases, such as bending analysis of cantilevers, and recourse must be made to the integral version. In this article, a novel numerical approach is developed for the bending analysis of Euler-Bernoulli nanobeams in the context of strain- and stress-driven integral nonlocal models. This numerical approach is proposed for the direct solution to bypass the difficulties related to converting the integral governing equation into a differential equation. First, the governing equation is derived based on both strain-driven and stress-driven nonlocal models by means of the minimum total potential energy. Also, in each case, the governing equation is obtained in both strong and weak forms. To solve numerically the derived equations, matrix differential and integral operators are constructed based upon the finite difference technique and trapezoidal integration rule. It is shown that the proposed numerical approach can be efficiently applied to the strain-driven nonlocal model with the aim of resolving the mentioned paradoxes. Also, it is able to solve the problem based on the strain-driven model without inconsistencies of the application of this model that are reported in the literature.

  20. Extracellular localization of catalase is associated with the transformed state of malignant cells.

    Science.gov (United States)

    Böhm, Britta; Heinzelmann, Sonja; Motz, Manfred; Bauer, Georg

    2015-12-01

    Oncogenic transformation is dependent on activated membrane-associated NADPH oxidase (NOX). However, the resultant extracellular superoxide anions are also driving the NO/peroxynitrite and the HOCl pathway, which eliminates NOX-expressing transformed cells through selective apoptosis induction. Tumor progression is dependent on dominant interference with intercellular apoptosis-inducing ROS signaling through membrane-associated catalase, which decomposes H2O2 and peroxynitrite and oxidizes NO. Particularly, the decomposition of extracellular peroxynitrite strictly requires membrane-associated catalase. We utilized small interfering RNA (siRNA)-mediated knockdown of catalase and neutralizing antibodies directed against the enzyme in combination with challenging H2O2 or peroxynitrite to determine activity and localization of catalase in cells from three distinct steps of multistage oncogenesis. Nontransformed cells did not generate extracellular superoxide anions and only showed intracellular catalase activity. Transformed cells showed superoxide anion-dependent intercellular apoptosis-inducing ROS signaling in the presence of suboptimal catalase activity in their membrane. Tumor cells exhibited tight control of intercellular apoptosis-inducing ROS signaling through a high local concentration of membrane-associated catalase. These data demonstrate that translocation of catalase to the outside of the cell membrane is already associated with the transformation step. A strong local increase in the concentration of membrane-associated catalase is achieved during tumor progression and is controlled by tumor cell-derived H2O2 and by transglutaminase.

  1. Disentangling Competition Among Platform Driven Strategic Groups

    DEFF Research Database (Denmark)

    Kazan, Erol; Tan, Chee-Wee; Lim, Eric

    2015-01-01

    In platform-driven markets, competitive advantage is derived from superior platform design and configurations. For this reason, platform owners strive to create unique and inimitable platform configurals to maintain and extend their competitiveness within network economies. To disentangle firm...... competition within platform-driven markets, we opted for the UK mobile payment market as our empirical setting. By embracing the theoretical lens of strategic groups and digital platforms, this study supplements prior research by deriving a taxonomy of platform-driven strategic groups that is grounded...

  2. Strategy-driven talent management a leadership imperative

    CERN Document Server

    Silzer, Rob

    2009-01-01

    A Publication of the Society for Industrial and Organizational Psychology Praise for Strategy-Driven Talent Management ""Silzer and Dowell''s Strategy-Driven Talent Management provides a comprehensive overview of the different elements of the best talent management processes used in organizations today. This is a valuable resource for leaders and managers, HR practitioners and anyone involved in developing leadership talent.""-Ed Lawler, Professor, School of Business, University of Southern California ""Talent is the key to successful execution of a winning business strategy. Strategy-Driven T

  3. Beyond Solar Fuels: Renewable Energy-Driven Chemistry.

    Science.gov (United States)

    Lanzafame, Paola; Abate, Salvatare; Ampelli, Claudio; Genovese, Chiara; Passalacqua, Rosalba; Centi, Gabriele; Perathoner, Siglinda

    2017-11-23

    The future feasibility of decarbonized industrial chemical production based on the substitution of fossil feedstocks (FFs) with renewable energy (RE) sources is discussed. Indeed, the use of FFs as an energy source has the greatest impact on the greenhouse gas emissions of chemical production. This future scenario is indicated as "solar-driven" or "RE-driven" chemistry. Its possible implementation requires to go beyond the concept of solar fuels, in particular to address two key aspects: i) the use of RE-driven processes for the production of base raw materials, such as olefins, methanol, and ammonia, and ii) the development of novel RE-driven routes that simultaneously realize process and energy intensification, particularly in the direction of a significant reduction of the number of the process steps. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. On fusion driven systems (FDS) for transmutation

    Energy Technology Data Exchange (ETDEWEB)

    Aagren, O (Uppsala Univ., Aangstroem laboratory, div. of electricity, Uppsala (Sweden)); Moiseenko, V.E. (Inst. of Plasma Physics, National Science Center, Kharkov Inst. of Physics and Technology, Kharkov (Ukraine)); Noack, K. (Forschungszentrum Dresden-Rossendorf (Germany))

    2008-10-15

    This report gives a brief description of ongoing activities on fusion driven systems (FDS) for transmutation of the long-lived radioactive isotopes in the spent nuclear waste from fission reactors. Driven subcritical systems appears to be the only option for efficient minor actinide burning. Driven systems offer a possibility to increase reactor safety margins. A comparatively simple fusion device could be sufficient for a fusion-fission machine, and transmutation may become the first industrial application of fusion. Some alternative schemes to create strong fusion neutron fluxes are presented

  5. On fusion driven systems (FDS) for transmutation

    International Nuclear Information System (INIS)

    Aagren, O; Moiseenko, V.E.; Noack, K.

    2008-10-01

    This report gives a brief description of ongoing activities on fusion driven systems (FDS) for transmutation of the long-lived radioactive isotopes in the spent nuclear waste from fission reactors. Driven subcritical systems appears to be the only option for efficient minor actinide burning. Driven systems offer a possibility to increase reactor safety margins. A comparatively simple fusion device could be sufficient for a fusion-fission machine, and transmutation may become the first industrial application of fusion. Some alternative schemes to create strong fusion neutron fluxes are presented

  6. Information-Driven Inspections

    International Nuclear Information System (INIS)

    Laughter, Mark D.; Whitaker, J. Michael; Lockwood, Dunbar

    2010-01-01

    New uranium enrichment capacity is being built worldwide in response to perceived shortfalls in future supply. To meet increasing safeguards responsibilities with limited resources, the nonproliferation community is exploring next-generation concepts to increase the effectiveness and efficiency of safeguards, such as advanced technologies to enable unattended monitoring of nuclear material. These include attribute measurement technologies, data authentication tools, and transmission and security methods. However, there are several conceptual issues with how such data would be used to improve the ability of a safeguards inspectorate such as the International Atomic Energy Agency (IAEA) to reach better safeguards conclusions regarding the activities of a State. The IAEA is pursuing the implementation of information-driven safeguards, whereby all available sources of information are used to make the application of safeguards more effective and efficient. Data from continuous, unattended monitoring systems can be used to optimize on-site inspection scheduling and activities at declared facilities, resulting in fewer, better inspections. Such information-driven inspections are the logical evolution of inspection planning - making use of all available information to enhance scheduled and randomized inspections. Data collection and analysis approaches for unattended monitoring systems can be designed to protect sensitive information while enabling information-driven inspections. A number of such inspections within a predetermined range could reduce inspection frequency while providing an equal or greater level of deterrence against illicit activity, all while meeting operator and technology holder requirements and reducing inspector and operator burden. Three options for using unattended monitoring data to determine an information-driven inspection schedule are to (1) send all unattended monitoring data off-site, which will require advances in data analysis techniques to

  7. Molecular dynamics for irradiation driven chemistry

    DEFF Research Database (Denmark)

    Sushko, Gennady B.; Solov'yov, Ilia A.; Solov'yov, Andrey V.

    2016-01-01

    A new molecular dynamics (MD) approach for computer simulations of irradiation driven chemical transformations of complex molecular systems is suggested. The approach is based on the fact that irradiation induced quantum transformations can often be treated as random, fast and local processes...... that describe the classical MD of complex molecular systems under irradiation. The proposed irradiation driven molecular dynamics (IDMD) methodology is designed for the molecular level description of the irradiation driven chemistry. The IDMD approach is implemented into the MBN Explorer software package...... involving small molecules or molecular fragments. We advocate that the quantum transformations, such as molecular bond breaks, creation and annihilation of dangling bonds, electronic charge redistributions, changes in molecular topologies, etc., could be incorporated locally into the molecular force fields...

  8. Second-Order Multiagent Systems with Event-Driven Consensus Control

    Directory of Open Access Journals (Sweden)

    Jiangping Hu

    2013-01-01

    Full Text Available Event-driven control scheduling strategies for multiagent systems play a key role in future use of embedded microprocessors of limited resources that gather information and actuate the agent control updates. In this paper, a distributed event-driven consensus problem is considered for a multi-agent system with second-order dynamics. Firstly, two kinds of event-driven control laws are, respectively, designed for both leaderless and leader-follower systems. Then, the input-to-state stability of the closed-loop multi-agent system with the proposed event-driven consensus control is analyzed and the bound of the inter-event times is ensured. Finally, some numerical examples are presented to validate the proposed event-driven consensus control.

  9. User-driven innovation of an outpatient department

    DEFF Research Database (Denmark)

    Broberg, Ole; Edwards, Kasper

    2012-01-01

    This paper presents experiences from a user-driven innovation process of an outpatient department in a hospital. The mixing of methods from user-driven innovation and participatory design contributed to develop an innovative concept of the spatial and organizational design of an outpatient...

  10. Recyclable crosslinked polymer networks with full property recovery made via one-step controlled radical polymerization

    Science.gov (United States)

    Jin, Kailong; Li, Lingqiao; Torkelson, John

    Rubber tires illustrate well the issues ranging from economic loss to environmental problems and sustainability issues that arise with spent, covalently crosslinked polymers. A nitroxide-mediated polymerization (NMP) strategy has been developed that allows for one-step synthesis of recyclable crosslinked polymers from monomers or polymers that contain carbon-carbon double bonds amenable to radical polymerization. Resulting materials possess dynamic alkoxyamine crosslinks that undergo reversible decrosslinking as a function of temperature. Using polybutadiene as starting material, and styrene, an appropriate nitroxide molecule and bifunctional initiator for initial crosslinking, a model for tire rubber can be produced by reaction at temperatures comparable to those employed in tire molding. Upon cooling, the crosslinks are made permanent due to the extraordinarily strong temperature dependence of the reverisible nitroxide capping and uncapping reaction. Based on thermomechanical property characterization, when the original crosslinked model rubber is chopped into bits and remolded in the melt state, a well-consolidated material is obtained which exhibits full recovery of properties reflecting crosslink density after multiple recycling steps.

  11. Distance-driven projection and backprojection in three dimensions

    International Nuclear Information System (INIS)

    De Man, Bruno; Basu, Samit

    2004-01-01

    Projection and backprojection are operations that arise frequently in tomographic imaging. Recently, we proposed a new method for projection and backprojection, which we call distance-driven, and that offers low arithmetic cost and a highly sequential memory access pattern. Furthermore, distance-driven projection and backprojection avoid several artefact-inducing approximations characteristic of some other methods. We have previously demonstrated the application of this method to parallel and fan beam geometries. In this paper, we extend the distance-driven framework to three dimensions and demonstrate its application to cone beam reconstruction. We also present experimental results to demonstrate the computational performance, the artefact characteristics and the noise-resolution characteristics of the distance-driven method in three dimensions

  12. User-driven innovation in tourism

    DEFF Research Database (Denmark)

    Hjalager, Anne-Mette; Nordin, Sara

    2011-01-01

    This literature study reviews user-driven innovation and establishes a typology of its forms in a tourism context. Sixteen methods are distinguishable. They comprise situations where users are actively involved and methods where information is collected without direct user involvement. The nature...... and intensity of the dialogue between companies and their customers are addressed. Drawing on this existing research, the article concludes that there is still little comprehensive follow-up on user-driven innovation in tourism and its impact on quality improvements and assurance. Key areas for future studies...

  13. Limits on the generalizability of context-driven control.

    Science.gov (United States)

    Hutcheon, Thomas G; Spieler, Daniel H

    2017-07-01

    Context-driven control refers to the fast and flexible weighting of stimulus dimensions that may be applied at the onset of a stimulus. Evidence for context-driven control comes from interference tasks in which participants encounter a high proportion of incongruent trials at one location and a high proportion of congruent trials at another location. Since the size of the congruency effect varies as a function of location, this suggests that stimulus dimensions are weighted differently based on the context in which they appear. However, manipulations of condition proportion are often confounded by variations in the frequency with which particular stimuli are encountered. To date, there is limited evidence for the context-driven control in the absence of stimulus frequency confounds. In the current paper, we attempt to replicate and extend one such finding [Crump, M. J. C., & Milliken, B. (2009). The flexibility of context-specific control: Evidence for context-driven generalization of item-specific control settings. The Quarterly Journal of Experimental Psychology, 62, 1523-1532]. Across three experiments we fail to find evidence for context-driven control in the absence of stimulus frequency confounds. Based on these results, we argue that consistency in the informativeness of the irrelevant dimension may be required for context-driven control to emerge.

  14. Regulation of ETG turbulence by TEM driven zonal flows

    Science.gov (United States)

    Asahi, Yuuichi; Ishizawa, Akihiro; Watanabe, Tomohiko; Tsutsui, Hiroaki; Tsuji-Iio, Shunji

    2013-10-01

    Anomalous heat transport driven by electron temperature gradient (ETG) turbulence is investigated by means of gyrokinetic simulations. It is found that the ETG turbulence can be suppressed by zonal flows driven by trapped electron modes (TEMs). The TEMs appear in a statistically steady state of ETG turbulence and generate zonal flows, while its growth rate is much smaller than those of ETGs. The TEM-driven zonal flows with lower radial wave numbers are more strongly generated than those driven by ETG modes, because of the higher zonal flow response to a density source term. An ExB shearing rate of the TEM-driven zonal flows is strong enough to suppress the long-wavelength ETG modes which make the main contribution to the turbulent transport.

  15. Data-driven storytelling

    CERN Document Server

    Hurter, Christophe; Diakopoulos, Nicholas ed.; Carpendale, Sheelagh

    2018-01-01

    This book is an accessible introduction to data-driven storytelling, resulting from discussions between data visualization researchers and data journalists. This book will be the first to define the topic, present compelling examples and existing resources, as well as identify challenges and new opportunities for research.

  16. Data-driven modeling of nano-nose gas sensor arrays

    DEFF Research Database (Denmark)

    Alstrøm, Tommy Sonne; Larsen, Jan; Nielsen, Claus Højgård

    2010-01-01

    We present a data-driven approach to classification of Quartz Crystal Microbalance (QCM) sensor data. The sensor is a nano-nose gas sensor that detects concentrations of analytes down to ppm levels using plasma polymorized coatings. Each sensor experiment takes approximately one hour hence...... the number of available training data is limited. We suggest a data-driven classification model which work from few examples. The paper compares a number of data-driven classification and quantification schemes able to detect the gas and the concentration level. The data-driven approaches are based on state...

  17. Data–driven modeling of nano-nose gas sensor arrays

    DEFF Research Database (Denmark)

    Alstrøm, Tommy Sonne; Larsen, Jan; Nielsen, Claus Højgård

    2010-01-01

    We present a data-driven approach to classification of Quartz Crystal Microbalance (QCM) sensor data. The sensor is a nano-nose gas sensor that detects concentrations of analytes down to ppm levels using plasma polymorized coatings. Each sensor experiment takes approximately one hour hence...... the number of available training data is limited. We suggest a data-driven classification model which work from few examples. The paper compares a number of data-driven classification and quantification schemes able to detect the gas and the concentration level. The data-driven approaches are based on state...

  18. Model-Driven Theme/UML

    Science.gov (United States)

    Carton, Andrew; Driver, Cormac; Jackson, Andrew; Clarke, Siobhán

    Theme/UML is an existing approach to aspect-oriented modelling that supports the modularisation and composition of concerns, including crosscutting ones, in design. To date, its lack of integration with model-driven engineering (MDE) techniques has limited its benefits across the development lifecycle. Here, we describe our work on facilitating the use of Theme/UML as part of an MDE process. We have developed a transformation tool that adopts model-driven architecture (MDA) standards. It defines a concern composition mechanism, implemented as a model transformation, to support the enhanced modularisation features of Theme/UML. We evaluate our approach by applying it to the development of mobile, context-aware applications-an application area characterised by many non-functional requirements that manifest themselves as crosscutting concerns.

  19. The wicked problems of supplier-driven innovation

    DEFF Research Database (Denmark)

    Christensen, Poul Rind; Munksgaard, Kristin Balslev; Bang, Anne Louise

    2017-01-01

    Suppliers stand in the wake of a new diversified strategic momentum in the global production network, where innovation is growing in importance. The term “supplier-driven innovation” is coined in contrast to the current hype on user-driven innovation; this paper aims to discuss the wicked problems...

  20. Resonances in a periodically driven bosonic system

    NARCIS (Netherlands)

    Quelle, Anton; de Morais Smith, Cristiane

    2017-01-01

    Periodically driven systems are a common topic in modern physics. In optical lattices specifically, driving is at the origin of many interesting phenomena. However, energy is not conserved in driven systems, and under periodic driving, heating of a system is a real concern. In an effort to better

  1. Dynamic Data-Driven UAV Network for Plume Characterization

    Science.gov (United States)

    2016-05-23

    AFRL-AFOSR-VA-TR-2016-0203 Dynamic Data-Driven UAV Network for Plume Characterization Kamran Mohseni UNIVERSITY OF FLORIDA Final Report 05/23/2016...AND SUBTITLE Dynamic Data-Driven UAV Network for Plume Characterization 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA9550-13-1-0090 5c.  PROGRAM ELEMENT...studied a dynamic data driven (DDD) approach to operation of a heterogeneous team of unmanned aerial vehicles ( UAVs ) or micro/miniature aerial

  2. Shock propagation in locally driven granular systems

    Science.gov (United States)

    Joy, Jilmy P.; Pathak, Sudhir N.; Das, Dibyendu; Rajesh, R.

    2017-09-01

    We study shock propagation in a system of initially stationary hard spheres that is driven by a continuous injection of particles at the origin. The disturbance created by the injection of energy spreads radially outward through collisions between particles. Using scaling arguments, we determine the exponent characterizing the power-law growth of this disturbance in all dimensions. The scaling functions describing the various physical quantities are determined using large-scale event-driven simulations in two and three dimensions for both elastic and inelastic systems. The results are shown to describe well the data from two different experiments on granular systems that are similarly driven.

  3. Solar-Driven Air-Conditioning Cycles: A Review

    Directory of Open Access Journals (Sweden)

    A. M. Abu-Zour

    2007-12-01

    Full Text Available Most conventional cooling/refrigeration systems are driven by fossil fuel combustion, and therefore give rise to emission of environmentally damaging pollutants. In addition, many cooling systems employ refrigerants, which are also harmful to the environment in terms of their Global Warming Potential (GWP and Ozone Depletion Potential (ODP. Development of a passive or hybrid solar-driven air-conditioning system is therefore of interest as exploitation of such systems would reduce the demand for grid electricity particularly at times of peak load. This paper presents a review of various cooling cycles and summarises work carried out on solar-driven air-conditioning systems.

  4. Data-driven methods towards learning the highly nonlinear inverse kinematics of tendon-driven surgical manipulators.

    Science.gov (United States)

    Xu, Wenjun; Chen, Jie; Lau, Henry Y K; Ren, Hongliang

    2017-09-01

    Accurate motion control of flexible surgical manipulators is crucial in tissue manipulation tasks. The tendon-driven serpentine manipulator (TSM) is one of the most widely adopted flexible mechanisms in minimally invasive surgery because of its enhanced maneuverability in torturous environments. TSM, however, exhibits high nonlinearities and conventional analytical kinematics model is insufficient to achieve high accuracy. To account for the system nonlinearities, we applied a data driven approach to encode the system inverse kinematics. Three regression methods: extreme learning machine (ELM), Gaussian mixture regression (GMR) and K-nearest neighbors regression (KNNR) were implemented to learn a nonlinear mapping from the robot 3D position states to the control inputs. The performance of the three algorithms was evaluated both in simulation and physical trajectory tracking experiments. KNNR performed the best in the tracking experiments, with the lowest RMSE of 2.1275 mm. The proposed inverse kinematics learning methods provide an alternative and efficient way to accurately model the tendon driven flexible manipulator. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Test Driven Development: Performing Art

    Science.gov (United States)

    Bache, Emily

    The art of Test Driven Development (TDD) is a skill that needs to be learnt, and which needs time and practice to master. In this workshop a select number of conference participants with considerable skill and experience are invited to perform code katas [1]. The aim is for them to demonstrate excellence and the use of Test Driven Development, and result in some high quality code. This would be for the benefit of the many programmers attending the conference, who could come along and witness high quality code being written using TDD, and get a chance to ask questions and provide feedback.

  6. Test-driven development with Mockito

    CERN Document Server

    Acharya, Sujoy

    2013-01-01

    This book is a hands-on guide, full of practical examples to illustrate the concepts of Test Driven Development.If you are a developer who wants to develop software following Test Driven Development using Mockito and leveraging various Mockito features, this book is ideal for you. You don't need prior knowledge of TDD, Mockito, or JUnit.It is ideal for developers, who have some experience in Java application development as well as a basic knowledge of unit testing, but it covers the basic fundamentals of TDD and JUnit testing to get you acquainted with these concepts before delving into them.

  7. Suppression of magnetic islands by rf-driven currents

    International Nuclear Information System (INIS)

    Reiman, A.H.

    1982-06-01

    The quasilinear theory for the saturation of nonlinear tearing modes is modified to include rf driven currents. It is shown that the presence of lower hybrid driven currents can strongly suppress the growth of magnetic islands

  8. Light-field-driven currents in graphene

    Science.gov (United States)

    Higuchi, Takuya; Heide, Christian; Ullmann, Konrad; Weber, Heiko B.; Hommelhoff, Peter

    2017-10-01

    The ability to steer electrons using the strong electromagnetic field of light has opened up the possibility of controlling electron dynamics on the sub-femtosecond (less than 10-15 seconds) timescale. In dielectrics and semiconductors, various light-field-driven effects have been explored, including high-harmonic generation, sub-optical-cycle interband population transfer and the non-perturbative change of the transient polarizability. In contrast, much less is known about light-field-driven electron dynamics in narrow-bandgap systems or in conductors, in which screening due to free carriers or light absorption hinders the application of strong optical fields. Graphene is a promising platform with which to achieve light-field-driven control of electrons in a conducting material, because of its broadband and ultrafast optical response, weak screening and high damage threshold. Here we show that a current induced in monolayer graphene by two-cycle laser pulses is sensitive to the electric-field waveform, that is, to the exact shape of the optical carrier field of the pulse, which is controlled by the carrier-envelope phase, with a precision on the attosecond (10-18 seconds) timescale. Such a current, dependent on the carrier-envelope phase, shows a striking reversal of the direction of the current as a function of the driving field amplitude at about two volts per nanometre. This reversal indicates a transition of light-matter interaction from the weak-field (photon-driven) regime to the strong-field (light-field-driven) regime, where the intraband dynamics influence interband transitions. We show that in this strong-field regime the electron dynamics are governed by sub-optical-cycle Landau-Zener-Stückelberg interference, composed of coherent repeated Landau-Zener transitions on the femtosecond timescale. Furthermore, the influence of this sub-optical-cycle interference can be controlled with the laser polarization state. These coherent electron dynamics in

  9. Taylor dispersion in wind-driven current

    Science.gov (United States)

    Li, Gang; Wang, Ping; Jiang, Wei-Quan; Zeng, Li; Li, Zhi; Chen, G. Q.

    2017-12-01

    Taylor dispersion associated with wind-driven currents in channels, shallow lakes and estuaries is essential to hydrological environmental management. For solute dispersion in a wind-driven current, presented in this paper is an analytical study of the evolution of concentration distribution. The concentration moments are intensively derived for an accurate presentation of the mean concentration distribution, up to the effect of kurtosis. The vertical divergence of concentration is then deduced by Gill's method of series expansion up to the fourth order. Based on the temporal evolution of the vertical concentration distribution, the dispersion process in the wind-driven current is concretely characterized. The uniform shear leads to a special symmetrical distribution of mean concentration free of skewness. The non-uniformity of vertical concentration is caused by convection and smeared out gradually by the effect of diffusion, but fails to disappear even at large times.

  10. Proliferation Potential of Accelerator-Driven Systems: Feasibility Calculations

    International Nuclear Information System (INIS)

    Riendeau, C.D.; Moses, D.L.; Olson, A.P.

    1998-01-01

    Accelerator-driven systems for fissile materials production have been proposed and studied since the early 1950s. Recent advances in beam power levels for small accelerators have raised the possibility that such use could be feasible for a potential proliferator. The objective of this study is to review the state of technology development for accelerator-driven spallation neutron sources and subcritical reactors. Energy and power requirements were calculated for a proton accelerator-driven neutron spallation source and subcritical reactors to produce a significant amount of fissile material--plutonium

  11. The association of graduated driver licensing with miles driven and fatal crash rates per miles driven among adolescents.

    Science.gov (United States)

    Zhu, Motao; Cummings, Peter; Zhao, Songzhu; Coben, Jeffrey H; Smith, Gordon S

    2015-04-01

    Graduated driver licensing (GDL) laws are associated with reduced crash rates per person-year among adolescents. It is unknown whether adolescents crash less per miles driven or drive less under GDL policies. We used data from the US National Household Travel Survey and Fatality Analysis Reporting System for 1995-1996, 2001-2002 and 2008-2009. We compared adolescents subject to GDL laws with those not by estimating adjusted IRRs for being a driver in a crash with a death per person-year (aIRRpy) and per miles driven (aIRRm), and adjusted miles driven ratios (aMR) controlling for changes in rates over time. Comparing persons subject to GDL policies with those not, 16 year olds had fewer fatal crashes per person-year (aIRRpy 0.63, 95% CI 0.47 to 0.91), drove fewer miles (aMR 0.79, 95% CI 0.63 to 0.98) and had lower crash rates per miles driven (aIRRm 0.83, 95% CI 0.65 to 1.06). For age 17, the aIRRpy was 0.83 (95% CI 0.60 to 1.17), the aMR 0.80 (95% CI 0.63 to 1.03) and the aIRRm 1.03 (95% CI 0.80 to 1.35). For age 18, the aIRRpy was 0.93 (95% CI 0.72 to 1.19), the aMR 0.92 (95% CI 0.77 to 1.09) and the aIRRm 1.01 (95% CI 0.84 to 1.23). If these associations are causal, GDL laws reduced crashes per person-year by about one-third among 16 year olds; half the reduction was due to fewer crashes per miles driven and half to less driving. For ages 17 and 18, there was no evidence of reduced crash rates per miles driven. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Orientation of Steel Fibers in Magnetically Driven Concrete and Mortar.

    Science.gov (United States)

    Xue, Wen; Chen, Ju; Xie, Fang; Feng, Bing

    2018-01-22

    The orientation of steel fibers in magnetically driven concrete and magnetically driven mortar was experimentally studied in this paper using a magnetic method. In the magnetically driven concrete, a steel slag was used to replace the coarse aggregate. In the magnetically driven mortar, steel slag and iron sand were used to replace the fine aggregate. A device was established to provide the magnetic force. The magnetic force was used to rotate the steel fibers. In addition, the magnetic force was also used to vibrate the concrete and mortar. The effect of magnetic force on the orientation of steel fibers was examined by comparing the direction of fibers before and after vibration. The effect of magnetically driven concrete and mortar on the orientation of steel fibers was also examined by comparing specimens to normal concrete and mortar. It is shown that the fibers could rotate about 90° in magnetically driven concrete. It is also shown that the number of fibers rotated in magnetically driven mortar was much more than in mortar vibrated using a shaking table. A splitting test was performed on concrete specimens to investigate the effect of fiber orientation. In addition, a flexural test was also performed on mortar test specimens. It is shown that the orientation of the steel fibers in magnetically driven concrete and mortar affects the strength of the concrete and mortar specimens.

  13. The Hypothesis-Driven Physical Examination.

    Science.gov (United States)

    Garibaldi, Brian T; Olson, Andrew P J

    2018-05-01

    The physical examination remains a vital part of the clinical encounter. However, physical examination skills have declined in recent years, in part because of decreased time at the bedside. Many clinicians question the relevance of physical examinations in the age of technology. A hypothesis-driven approach to teaching and practicing the physical examination emphasizes the performance of maneuvers that can alter the likelihood of disease. Likelihood ratios are diagnostic weights that allow clinicians to estimate the post-probability of disease. This hypothesis-driven approach to the physical examination increases its value and efficiency, while preserving its cultural role in the patient-physician relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. THE DOMINANCE OF NEUTRINO-DRIVEN CONVECTION IN CORE-COLLAPSE SUPERNOVAE

    International Nuclear Information System (INIS)

    Murphy, Jeremiah W.; Dolence, Joshua C.; Burrows, Adam

    2013-01-01

    Multi-dimensional instabilities have become an important ingredient in core-collapse supernova (CCSN) theory. Therefore, it is necessary to understand the driving mechanism of the dominant instability. We compare our parameterized three-dimensional CCSN simulations with other buoyancy-driven simulations and propose scaling relations for neutrino-driven convection. Through these comparisons, we infer that buoyancy-driven convection dominates post-shock turbulence in our simulations. In support of this inference, we present four major results. First, the convective fluxes and kinetic energies in the neutrino-heated region are consistent with expectations of buoyancy-driven convection. Second, the convective flux is positive where buoyancy actively drives convection, and the radial and tangential components of the kinetic energy are in rough equipartition (i.e., K r ∼ K θ + K φ ). Both results are natural consequences of buoyancy-driven convection, and are commonly observed in simulations of convection. Third, buoyant driving is balanced by turbulent dissipation. Fourth, the convective luminosity and turbulent dissipation scale with the driving neutrino power. In all, these four results suggest that in neutrino-driven explosions, the multi-dimensional motions are consistent with neutrino-driven convection.

  15. Semantic Web and Model-Driven Engineering

    CERN Document Server

    Parreiras, Fernando S

    2012-01-01

    The next enterprise computing era will rely on the synergy between both technologies: semantic web and model-driven software development (MDSD). The semantic web organizes system knowledge in conceptual domains according to its meaning. It addresses various enterprise computing needs by identifying, abstracting and rationalizing commonalities, and checking for inconsistencies across system specifications. On the other side, model-driven software development is closing the gap among business requirements, designs and executables by using domain-specific languages with custom-built syntax and se

  16. Patient safety and technology-driven medication

    DEFF Research Database (Denmark)

    Orbæk, Janne; Gaard, Mette; Keinicke Fabricius, Pia

    2015-01-01

    ways of educating nursing students in today's medication administration. AIM: To explore nursing students' experiences and competences with the technology-driven medication administration process. METHODS: 16 pre-graduate nursing students were included in two focus group interviews which were recorded...... for the technology-driven medication process, nursing students face difficulties in identifying and adopting best practices. The impact of using technology on the frequency, type and severity of medication errors; the technologies implications on nursing professionalism and the nurses ability to secure patient...

  17. Science-Driven Computing: NERSC's Plan for 2006-2010

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Horst D.; Kramer, William T.C.; Bailey, David H.; Banda,Michael J.; Bethel, E. Wes; Craw, James M.; Fortney, William J.; Hules,John A.; Meyer, Nancy L.; Meza, Juan C.; Ng, Esmond G.; Rippe, Lynn E.; Saphir, William C.; Verdier, Francesca; Walter, Howard A.; Yelick,Katherine A.

    2005-05-16

    NERSC has developed a five-year strategic plan focusing on three components: Science-Driven Systems, Science-Driven Services, and Science-Driven Analytics. (1) Science-Driven Systems: Balanced introduction of the best new technologies for complete computational systems--computing, storage, networking, visualization and analysis--coupled with the activities necessary to engage vendors in addressing the DOE computational science requirements in their future roadmaps. (2) Science-Driven Services: The entire range of support activities, from high-quality operations and user services to direct scientific support, that enable a broad range of scientists to effectively use NERSC systems in their research. NERSC will concentrate on resources needed to realize the promise of the new highly scalable architectures for scientific discovery in multidisciplinary computational science projects. (3) Science-Driven Analytics: The architectural and systems enhancements and services required to integrate NERSC's powerful computational and storage resources to provide scientists with new tools to effectively manipulate, visualize, and analyze the huge data sets derived from simulations and experiments.

  18. Mathematical modeling of compression processes in air-driven boosters

    International Nuclear Information System (INIS)

    Li Zeyu; Zhao Yuanyang; Li Liansheng; Shu Pengcheng

    2007-01-01

    The compressed air in normal pressure is used as the source of power of the air-driven booster. The continuous working of air-driven boosters relies on the difference of surface area between driven piston and driving piston, i.e., the different forces acting on the pistons. When the working surface area of the driving piston for providing power is greater than that of the driven piston for compressing gas, the gas in compression chamber will be compressed. On the basis of the first law of thermodynamics, the motion regulation of piston is analyzed and the mathematical model of compression processes is set up. Giving a calculating example, the vary trends of gas pressure and pistons' move in working process of booster have been gotten. The change of parameters at different working conditions is also calculated and compared. And the corresponding results can be referred in the design of air-driven boosters

  19. Kaehler-driven tribrid inflation

    International Nuclear Information System (INIS)

    Antusch, Stefan; Nolde, David

    2012-01-01

    We discuss a new class of tribrid inflation models in supergravity, where the shape of the inflaton potential is dominated by effects from the Kaehler potential. Tribrid inflation is a variant of hybrid inflation which is particularly suited for connecting inflation with particle physics, since the inflaton can be a D-flat combination of charged fields from the matter sector. In models of tribrid inflation studied so far, the inflaton potential was dominated by either loop corrections or by mixing effects with the waterfall field (as in 'pseudosmooth' tribrid inflation). Here we investigate the third possibility, namely that tribrid inflation is dominantly driven by effects from higher-dimensional operators of the Kaehler potential. We specify for which superpotential parameters the new regime is realized and show how it can be experimentally distinguished from the other two (loop-driven and p seudosmooth ) regimes

  20. Effects-Driven IT Development

    DEFF Research Database (Denmark)

    Hertzum, Morten; Simonsen, Jesper

    2011-01-01

    For customers information technology (IT) is a means to an end. This tight association between IT systems and their use is, however, often absent during their development and implementation, resulting in systems that may fail to produce desired ends. Effects-driven IT development aims to avoid...... change that realize the specified effects, and (c) measuring the absence or presence of the specified effects during pilot use of the system while also remaining alert to the emergence of beneficial but hitherto unspecified effects. In this paper we explore effects-driven IT development and discuss...... the possibilities and challenges involved in making it an instrument for managing IT projects. Two main challenges are that effects must be measured while development is still ongoing, making pilot implementations a central activity, and that vendor and customer must extend their collaboration, particularly...

  1. Plasmon-driven sequential chemical reactions in an aqueous environment.

    Science.gov (United States)

    Zhang, Xin; Wang, Peijie; Zhang, Zhenglong; Fang, Yurui; Sun, Mengtao

    2014-06-24

    Plasmon-driven sequential chemical reactions were successfully realized in an aqueous environment. In an electrochemical environment, sequential chemical reactions were driven by an applied potential and laser irradiation. Furthermore, the rate of the chemical reaction was controlled via pH, which provides indirect evidence that the hot electrons generated from plasmon decay play an important role in plasmon-driven chemical reactions. In acidic conditions, the hot electrons were captured by the abundant H(+) in the aqueous environment, which prevented the chemical reaction. The developed plasmon-driven chemical reactions in an aqueous environment will significantly expand the applications of plasmon chemistry and may provide a promising avenue for green chemistry using plasmon catalysis in aqueous environments under irradiation by sunlight.

  2. Model-driven software engineering

    NARCIS (Netherlands)

    Amstel, van M.F.; Brand, van den M.G.J.; Protic, Z.; Verhoeff, T.; Hamberg, R.; Verriet, J.

    2014-01-01

    Software plays an important role in designing and operating warehouses. However, traditional software engineering methods for designing warehouse software are not able to cope with the complexity, size, and increase of automation in modern warehouses. This chapter describes Model-Driven Software

  3. Data-driven architectural design to production and operation

    NARCIS (Netherlands)

    Bier, H.H.; Mostafavi, S.

    2015-01-01

    Data-driven architectural production and operation explored within Hyperbody rely heavily on system thinking implying that all parts of a system are to be understood in relation to each other. These relations are established bi-directionally so that data-driven architecture is not only produced

  4. Optical modeling of induction-linac driven free-electron lasers

    International Nuclear Information System (INIS)

    Scharlemann, E.T.; Fawley, W.M.

    1986-01-01

    The free-electron laser (FEL) simulation code FRED, developed at Lawrence Livermore National Laboratory (LLNL) primarily to model single-pass FEL amplifiers driven by induction linear accelerators, is described. The main emphasis is on the modeling of optical propagation in the laser and on the differences between the requirements for modeling rf-linac-driven vs. induction-linac-driven FELs. Examples of optical guiding and mode cleanup are presented for a 50 μm FEL

  5. Stakeholder-Driven Quality Improvement: A Compelling Force for Clinical Practice Guidelines.

    Science.gov (United States)

    Rosenfeld, Richard M; Wyer, Peter C

    2018-01-01

    Clinical practice guideline development should be driven by rigorous methodology, but what is less clear is where quality improvement enters the process: should it be a priority-guiding force, or should it enter only after recommendations are formulated? We argue for a stakeholder-driven approach to guideline development, with an overriding goal of quality improvement based on stakeholder perceptions of needs, uncertainties, and knowledge gaps. In contrast, the widely used topic-driven approach, which often makes recommendations based only on randomized controlled trials, is driven by epidemiologic purity and evidence rigor, with quality improvement a downstream consideration. The advantages of a stakeholder-driven versus a topic-driven approach are highlighted by comparisons of guidelines for otitis media with effusion, thyroid nodules, sepsis, and acute bacterial rhinosinusitis. These comparisons show that stakeholder-driven guidelines are more likely to address the quality improvement needs and pressing concerns of clinicians and patients, including understudied populations and patients with multiple chronic conditions. Conversely, a topic-driven approach often addresses "typical" patients, based on research that may not reflect the needs of high-risk groups excluded from studies because of ethical issues or a desire for purity of research design.

  6. Patron-driven acquisitions history and best practices

    CERN Document Server

    2011-01-01

    About 40 percent of the books academic libraries purchase in traditional ways never circulate and another 40 percent circulate fewer than three times. By contrast, patron-driven acquisition allows a library to borrow or buy books only when a patron needs them. In a typical workflow, the library imports bibliographic records into its catalogue at no cost. When a patron finds a patron-driven record in the course of research, a short-term loan can allow him to borrow the book, and the transaction charge to the library will be a small percentage of the list price. Typically, a library will automatically buy a book on a third or fourth use. The contributions in this volume, written by experts, describe the genesis and brief history of patron-driven acquisitions, its current status, and its promise.

  7. Educational Accountability: A Qualitatively Driven Mixed-Methods Approach

    Science.gov (United States)

    Hall, Jori N.; Ryan, Katherine E.

    2011-01-01

    This article discusses the importance of mixed-methods research, in particular the value of qualitatively driven mixed-methods research for quantitatively driven domains like educational accountability. The article demonstrates the merits of qualitative thinking by describing a mixed-methods study that focuses on a middle school's system of…

  8. Collision and recombination driven instabilities in variable charged ...

    Indian Academy of Sciences (India)

    The dust-acoustic instability driven by recombination of electrons and ions on the surface of charged and variably-charged dust grains as well as by collisions in dusty plasmas with significant pressure of background neutrals have been theoretically investigated. The recombination driven instability is shown to be dominant ...

  9. A Consumer-Driven Approach To Increase Suggestive Selling.

    Science.gov (United States)

    Rohn, Don; Austin, John; Sanford, Alison

    2003-01-01

    Discussion of the effectiveness of behavioral interventions in improving suggestive selling behavior of sales staff focuses on a study that examined the efficacy of a consumer-driven approach to improve suggestive selling behavior of three employees of a fast food franchise. Reports that consumer-driven intervention increased suggestive selling…

  10. The Structural Consequences of Big Data-Driven Education.

    Science.gov (United States)

    Zeide, Elana

    2017-06-01

    Educators and commenters who evaluate big data-driven learning environments focus on specific questions: whether automated education platforms improve learning outcomes, invade student privacy, and promote equality. This article puts aside separate unresolved-and perhaps unresolvable-issues regarding the concrete effects of specific technologies. It instead examines how big data-driven tools alter the structure of schools' pedagogical decision-making, and, in doing so, change fundamental aspects of America's education enterprise. Technological mediation and data-driven decision-making have a particularly significant impact in learning environments because the education process primarily consists of dynamic information exchange. In this overview, I highlight three significant structural shifts that accompany school reliance on data-driven instructional platforms that perform core school functions: teaching, assessment, and credentialing. First, virtual learning environments create information technology infrastructures featuring constant data collection, continuous algorithmic assessment, and possibly infinite record retention. This undermines the traditional intellectual privacy and safety of classrooms. Second, these systems displace pedagogical decision-making from educators serving public interests to private, often for-profit, technology providers. They constrain teachers' academic autonomy, obscure student evaluation, and reduce parents' and students' ability to participate or challenge education decision-making. Third, big data-driven tools define what "counts" as education by mapping the concepts, creating the content, determining the metrics, and setting desired learning outcomes of instruction. These shifts cede important decision-making to private entities without public scrutiny or pedagogical examination. In contrast to the public and heated debates that accompany textbook choices, schools often adopt education technologies ad hoc. Given education

  11. Entropy-driven phase transitions

    NARCIS (Netherlands)

    Frenkel, D.

    1999-01-01

    Increase in visible order can be associated with an increase in microscopic disorder. This phenomenon leads to many counter-intuitive phenomena such as entropy driven crystallization and phase separation. I devote special attention to the entropic depletion interaction as a means to tune the range

  12. A mobile design lab for user-driven innovation

    DEFF Research Database (Denmark)

    Christiansen, Ellen; Kanstrup, Anne Marie

    2007-01-01

    The paper presents the history and conceptual foundation for the Mobile Design Lab, ment to support both designers and users in the acts of user-driven innovation. The Mobile Design Lab is based on Vygotsky's theory of tool- and language-mediation, and was created in 2004 to support research...... and teaching of user driven innovation. Being itself an example of user-driven innovation it has taken shape of HCI design research projekcts, in which we have been involved since 2004. The first challenge was to get 'out of the lab', the next to get 'out of the head', and finally we are currently working...

  13. Scaling up nanoscale water-driven energy conversion into evaporation-driven engines and generators

    Science.gov (United States)

    Chen, Xi; Goodnight, Davis; Gao, Zhenghan; Cavusoglu, Ahmet H.; Sabharwal, Nina; Delay, Michael; Driks, Adam; Sahin, Ozgur

    2015-06-01

    Evaporation is a ubiquitous phenomenon in the natural environment and a dominant form of energy transfer in the Earth's climate. Engineered systems rarely, if ever, use evaporation as a source of energy, despite myriad examples of such adaptations in the biological world. Here, we report evaporation-driven engines that can power common tasks like locomotion and electricity generation. These engines start and run autonomously when placed at air-water interfaces. They generate rotary and piston-like linear motion using specially designed, biologically based artificial muscles responsive to moisture fluctuations. Using these engines, we demonstrate an electricity generator that rests on water while harvesting its evaporation to power a light source, and a miniature car (weighing 0.1 kg) that moves forward as the water in the car evaporates. Evaporation-driven engines may find applications in powering robotic systems, sensors, devices and machinery that function in the natural environment.

  14. Technologies using accelerator-driven targets under development at BNL

    International Nuclear Information System (INIS)

    Van Tuyle, G.J.

    1994-01-01

    Recent development work conducted at Brookhaven National Laboratory on technologies which use particle accelerator-driven targets is summarized. These efforts include development of the Spallation-Induced Lithium Conversion (SILC) Target for the Accelerator Production of Tritium (APT), the Accelerator-Driven Assembly for Plutonium Transformation (ADAPT) Target for the Accelerator-Based Conversion (ABC) of excess weapons plutonium. The PHOENIX Concept for the accelerator-driven transmutation of minor actinides and fission products from the waste stream of commercial nuclear power plants, and other potential applications

  15. Efficiency of wave-driven rigid body rotation toroidal confinement

    Science.gov (United States)

    Rax, J. M.; Gueroult, R.; Fisch, N. J.

    2017-03-01

    The compensation of vertical drifts in toroidal magnetic fields through a wave-driven poloidal rotation is compared with compensation through the wave driven toroidal current generation to support the classical magnetic rotational transform. The advantages and drawbacks associated with the sustainment of a radial electric field are compared with those associated with the sustainment of a poloidal magnetic field both in terms of energy content and power dissipation. The energy content of a radial electric field is found to be smaller than the energy content of a poloidal magnetic field for a similar set of orbits. The wave driven radial electric field generation efficiency is similarly shown, at least in the limit of large aspect ratio, to be larger than the efficiency of wave-driven toroidal current generation.

  16. User-driven sampling strategies in image exploitation

    Science.gov (United States)

    Harvey, Neal; Porter, Reid

    2013-12-01

    Visual analytics and interactive machine learning both try to leverage the complementary strengths of humans and machines to solve complex data exploitation tasks. These fields overlap most significantly when training is involved: the visualization or machine learning tool improves over time by exploiting observations of the human-computer interaction. This paper focuses on one aspect of the human-computer interaction that we call user-driven sampling strategies. Unlike relevance feedback and active learning sampling strategies, where the computer selects which data to label at each iteration, we investigate situations where the user selects which data is to be labeled at each iteration. User-driven sampling strategies can emerge in many visual analytics applications but they have not been fully developed in machine learning. User-driven sampling strategies suggest new theoretical and practical research questions for both visualization science and machine learning. In this paper we identify and quantify the potential benefits of these strategies in a practical image analysis application. We find user-driven sampling strategies can sometimes provide significant performance gains by steering tools towards local minima that have lower error than tools trained with all of the data. In preliminary experiments we find these performance gains are particularly pronounced when the user is experienced with the tool and application domain.

  17. Equilibrium of current driven rotating liquid metal

    International Nuclear Information System (INIS)

    Velikhov, E.P.; Ivanov, A.A.; Zakharov, S.V.; Zakharov, V.S.; Livadny, A.O.; Serebrennikov, K.S.

    2006-01-01

    In view of great importance of magneto-rotational instability (MRI) as a fundamental mechanism for angular momentum transfer in magnetized stellar accretion disks, several research centers are involved in experimental study of MRI under laboratory conditions. The idea of the experiment is to investigate the rotation dynamics of well conducting liquid (liquid metal) between two cylinders in axial magnetic field. In this Letter, an experimental scheme with immovable cylinders and fluid rotation driven by radial current is considered. The analytical solution of a stationary flow was found taking into account the external current. Results of axially symmetric numerical simulations of current driven fluid dynamics in experimental setup geometry are presented. The analytical solution and numerical simulations show that the current driven fluid rotation in axial magnetic field provides the axially homogeneous velocity profile suitable for MRI study in classical statement

  18. Pressure Driven Poiseuille Flow

    DEFF Research Database (Denmark)

    Stotz, Ingo Leonardo; Iaffaldano, Giampiero; Davies, D. Rhodri

    2018-01-01

    The Pacific plate is thought to be driven mainly by slab pull, associated with subduction along the Aleutians–Japan, Marianas–Izu–Bonin and Tonga–Kermadec trenches. This implies that viscous flow within the sub–Pacific asthenosphere is mainly generated by overlying plate motion (i.e. Couette flow...

  19. Understanding Climate Change and Manifestation of its Driven ...

    African Journals Online (AJOL)

    This article examines the nature and manifestation of climate change driven impacts on the agrarian districts of Kongwa and Bahi in the semi arid areas of Dodoma region in Tanzania. A Survey of 398 households in the study area was undertaken to elicit information on the nature and manifestation of climate change driven ...

  20. Ponderomotive force effects on temperature-gradient-driven instabilities

    International Nuclear Information System (INIS)

    Sundaram, A.K.; Hershkowitz, N.

    1992-01-01

    The modification of temperature-gradient-driven instabilities due to the presence of nonuniform radio-frequency fields near the ion cyclotron frequency is investigated in the linear regime. Employing the fluid theory, it is shown that the induced field line compression caused by ion cyclotron range of frequencies (ICRF) fields makes the net parallel compressibility positive, and thus provides a stabilizing influence on the ion-temperature-gradient-driven mode for an appropriately tailored profile of radio-frequency (rf) pressure. Concomitantly, the radial ponderomotive force generates an additional contribution via coupling between the perturbed fluid motion and the equilibrium ponderomotive force and this effect plays the role of dissipation to enhance or decrease the growth of temperature-gradient-driven modes depending upon the sign of rf pressure gradients. For decreased growth of temperature-gradient-driven instabilities, the plasma density gradients and rf pressure gradients must have opposite signs while enhancement in growth arises when both gradients have the same sign. Finally, the kinetic effects associated with these modes are briefly discussed

  1. Behavioural Motives of Acquisition of Solar-driven Equipment

    Directory of Open Access Journals (Sweden)

    Shkurupska Iryna O.

    2013-12-01

    Full Text Available The article identifies needs of the target group, namely structure of motives, which justify making a decision to buy, in order to create efficient marketing strategy of an enterprise, which sell solar-driven equipment in Ukraine. There are five segments in the domestic market of helio-systems: individual consumers, recreation industry, agrarian industry, construction and social spheres. The article allocates 15 motives of acquisition of the solar-driven equipment for these segments, the most important of which are price, availability of solar energy, alternative price and energy saving. Besides, the structure of such motives is determined for each segment individually. In order to choose specific marketing instruments in the policy of promotion of solar-driven equipment, the article identifies differences in the form of goals of use and motives of acquisition between the specified consumer segments. The article reveals certain barriers that interfere with acquisition of solar-driven equipment – low level of trust into helio-systems, conservatism of consumers, absence of free applications for consumers – overcoming which is only possible with the help of certain marketing actions.

  2. Turbulent mixed buoyancy driven flow and heat transfer in lid driven enclosure

    International Nuclear Information System (INIS)

    Mishra, Ajay Kumar; Sharma, Anil Kumar

    2015-01-01

    Turbulent mixed buoyancy driven flow and heat transfer of air in lid driven rectangular enclosure has been investigated for Grashof number in the range of 10 8 to 10 11 and for Richardson number 0.1, 1 and 10. Steady two dimensional Reynolds-Averaged-Navier-Stokes equations and conservation equations of mass and energy, coupled with the Boussinesq approximation, are solved. The spatial derivatives in the equations are discretized using the finite-element method. The SIMPLE algorithm is used to resolve pressure-velocity coupling. Turbulence is modeled with the k-ω closure model with physical boundary conditions along with the Boussinesq approximation, for the flow and heat transfer. The predicted results are validated against benchmark solutions reported in literature. The results include stream lines and temperature fields are presented to understand flow and heat transfer characteristics. There is a marked reduction in mean Nusselt number (about 58%) as the Richardson number increases from 0.1 to 10 for the case of Ra=10 10 signifying the effect of reduction of top lid velocity resulting in reduction of turbulent mixing. (author)

  3. Leidenfrost Driven Waste-Water Separator

    Data.gov (United States)

    National Aeronautics and Space Administration — A Leidenfrost Driven Waste-Water Separator (LDS) is proposed in response to TA 6.1: Environmental Control and Life Support Systems and Habitation Systems. The LDS...

  4. Problems in the neutron dynamics of source-driven systems

    International Nuclear Information System (INIS)

    Ravetto, P.

    2001-01-01

    The present paper presents some neutronic features of source-driven neutron multiplying systems, with special regards to dynamics, discussing the validity and limitations of classical methods, developed for systems in the vicinity of criticality. Specific characteristics, such as source dominance and the role of delayed neutron emissions are illustrated. Some dynamic peculiarities of innovative concepts proposed for accelerator-driven systems, such as fluid-fuel, are also discussed. The second portion of the work formulates the quasi-static methods for source-driven systems, evidencing its novel features and presenting some numerical results. (author)

  5. 2nd International Conference on Cable-Driven Parallel Robots

    CERN Document Server

    Bruckmann, Tobias

    2015-01-01

    This volume presents the outcome of the second forum to cable-driven parallel robots, bringing the cable robot community together. It shows the new ideas of the active researchers developing cable-driven robots. The book presents the state of the art, including both summarizing contributions as well as latest research and future options. The book cover all topics which are essential for cable-driven robots: Classification Kinematics, Workspace and Singularity Analysis Statics and Dynamics Cable Modeling Control and Calibration Design Methodology Hardware Development Experimental Evaluation Prototypes, Application Reports and new Application concepts

  6. Fenton-Driven Regeneration of MTBE-spent Granular Activated Carbon

    Science.gov (United States)

    Fenton-driven regeneration of Methyl tert-butyl ether (MTBE)-spent granular activated carbon (GAC) involves the combined, synergistic use of two treatment technologies: adsorption of organic chemicals onto activated carbon and Fenton-driven oxidation regeneration of the spent-GAC...

  7. Customer Driven Uniform Manufacture (CDUM) Program. Customer Driven Uniform Management Apparel Research

    Science.gov (United States)

    2008-11-13

    ABSTRACT (Maximum 200 Words) The DLA and DSCP sponsored Customer Driven Uniform Manufacturing (CDUM) program’s primary goals are to reduce total...functions that make decisions or consume apparel items. PDIT’s CDUM assignments were to create the web accessible database, create decision support tools...Manufacturing Monitoring Processes ....................................................40  Figure 32 – Assign Contract to Buyer

  8. The Exploration of Design Driven Innovation as a Dynamic Capability

    Directory of Open Access Journals (Sweden)

    Philips Kembaren

    2012-01-01

    Full Text Available Innovation enables companies to attain consistent organic growth that brings benefits to stakeholders. Designthinking approach in innovation has been emergent to be an alternative to technological development path inorder to generate competitive and successful product or service in the market place. Design driven innovationcombines functional and semantic dimensions of products or services in the marketplace. Previous researchhas recently revealed practices of design driven innovation in various industries. However, little is known tothe extent that companies in Indonesia practicing design driven innovation. A theoretical framework withperspective from dynamic capability theoretical lens and guided by Dubin’s theory building methodology isproposed to explain the constructs and role of design in the process of innovation. The research is expected tocontribute a new construct to the existing framework, namely construct that related to how we could assessthe value of the design-driven innovation output, perceived by the costumers.Keywords: design driven innovation, dynamic capabilities, theory building

  9. Work(er)-Driven Innovation

    Science.gov (United States)

    Smith, Raymond

    2017-01-01

    Purpose: The focus on innovation as a foundational element of enhanced organisational performance has led to the promoting and valuing of greater levels of employee participation in innovation processes. An emergent concept of employee-driven innovation could be argued to have hindered understandings of the creative and transformative nature of…

  10. Examples of Entropy-driven Ordering

    Indian Academy of Sciences (India)

    driven Ordering. Orientational ordering of long objects. Entropy of sliding increases. Freezing in hard-sphere systems. Vibrational entropy increases. Phase separation in hard-sphere binary mixtures with disparate sizes. More room for smaller ...

  11. Quantification of superoxide radical production in thylakoid membrane using cyclic hydroxylamines.

    Science.gov (United States)

    Kozuleva, Marina; Klenina, Irina; Mysin, Ivan; Kirilyuk, Igor; Opanasenko, Vera; Proskuryakov, Ivan; Ivanov, Boris

    2015-12-01

    Applicability of two lipophilic cyclic hydroxylamines (CHAs), CM-H and TMT-H, and two hydrophilic CHAs, CAT1-H and DCP-H, for detection of superoxide anion radical (O2(∙-)) produced by the thylakoid photosynthetic electron transfer chain (PETC) of higher plants under illumination has been studied. ESR spectrometry was applied for detection of the nitroxide radical originating due to CHAs oxidation by O2(∙-). CHAs and corresponding nitroxide radicals were shown to be involved in side reactions with PETC which could cause miscalculation of O2(∙-) production rate. Lipophilic CM-H was oxidized by PETC components, reducing the oxidized donor of Photosystem I, P700(+), while at the same concentration another lipophilic CHA, TMT-H, did not reduce P700(+). The nitroxide radical was able to accept electrons from components of the photosynthetic chain. Electrostatic interaction of stable cation CAT1-H with the membrane surface was suggested. Water-soluble superoxide dismutase (SOD) was added in order to suppress the reaction of CHA with O2(∙-) outside the membrane. SOD almost completely inhibited light-induced accumulation of DCP(∙), nitroxide radical derivative of hydrophilic DCP-H, in contrast to TMT(∙) accumulation. Based on the results showing that change in the thylakoid lumen pH and volume had minor effect on TMT(∙) accumulation, the reaction of TMT-H with O2(∙-) in the lumen was excluded. Addition of TMT-H to thylakoid suspension in the presence of SOD resulted in the increase in light-induced O2 uptake rate, that argued in favor of TMT-H ability to detect O2(∙-) produced within the membrane core. Thus, hydrophilic DCP-H and lipophilic TMT-H were shown to be usable for detection of O2(∙-) produced outside and within thylakoid membranes. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Data-driven workflows for microservices

    DEFF Research Database (Denmark)

    Safina, Larisa; Mazzara, Manuel; Montesi, Fabrizio

    2016-01-01

    Microservices is an architectural style inspired by service-oriented computing that has recently started gainingpopularity. Jolie is a programming language based on the microservices paradigm: the main building block of Jolie systems are services, in contrast to, e.g., functions or objects....... The primitives offered by the Jolie language elicit many of the recurring patterns found in microservices, like load balancers and structured processes. However, Jolie still lacks some useful constructs for dealing with message types and data manipulation that are present in service-oriented computing......). We show the impact of our implementation on some of the typical scenarios found in microservice systems. This shows how computation can move from a process-driven to a data-driven approach, and leads to the preliminary identification of recurring communication patterns that can be shaped as design...

  13. Theoretical thermodynamic analysis of Rankine power cycle with thermal driven pump

    International Nuclear Information System (INIS)

    Lakew, Amlaku Abie; Bolland, Olav; Ladam, Yves

    2011-01-01

    Highlights: → The work is focused on theoretical aspects of thermal driven pump (TDP) Rankine cycle. → The mechanical pump is replaced by thermal driven pump. → Important parameters of thermal driven pump Rankine cycle are investigated. → TDP Rankine cycle produce more power but it requires additional low grade heat. - Abstract: A new approach to improve the performance of supercritical carbon dioxide Rankine cycle which uses low temperature heat source is presented. The mechanical pump in conventional supercritical carbon dioxide Rankine cycle is replaced by thermal driven pump. The concept of thermal driven pump is to increase the pressure of a fluid in a closed container by supplying heat. A low grade heat source is used to increase the pressure of the fluid instead of a mechanical pump, this increase the net power output and avoid the need for mechanical pump which requires regular maintenance and operational cost. The thermal driven pump considered is a shell and tube heat exchanger where the working fluid is contained in the tube, a tube diameter of 5 mm is chosen to reduce the heating time. The net power output of the Rankine cycle with thermal driven pump is compared to that of Rankine cycle with mechanical pump and it is observed that the net power output is higher when low grade thermal energy is used to pressurize the working fluid. The thermal driven pump consumes additional heat at low temperature (60 o C) to pressurize the working fluid.

  14. Overview of nonlinear theory of kinetically driven instabilities

    International Nuclear Information System (INIS)

    Berk, H.L.; Breizman, B.N.

    1998-09-01

    An overview is presented of the theory for the nonlinear behavior of instabilities driven by the resonant wave particle interaction. The approach should be applicable to a wide variety of kinetic systems in magnetic fusion devices and accelerators. Here the authors emphasize application to Alfven were driven instability, and the principles of the theory are used to interpret experimental data

  15. Curvature driven instabilities in toroidal plasmas

    International Nuclear Information System (INIS)

    Andersson, P.

    1986-11-01

    The electromagnetic ballooning mode, the curvature driven trapped electron mode and the toroidally induced ion temperature gradient mode have been studies. Eigenvalue equations have been derived and solved both numerically and analytically. For electromagnetic ballooning modes the effects of convective damping, finite Larmor radius, higher order curvature terms, and temperature gradients have been investigated. A fully toroidal fluid ion model has been developed. It is shown that a necessary and sufficient condition for an instability below the MHD limit is the presence of an ion temperature gradient. Analytical dispersion relations giving results in good agreement with numerical solutions are also presented. The curvature driven trapped electron modes are found to be unstable for virtually all parameters with growth rates of the order of the diamagnetic drift frequency. Studies have been made, using both a gyrokinetic ion description and the fully toroidal ion model. Both analytical and numerical results are presented and are found to be in good agreement. The toroidally induced ion temperature gradients modes are found to have a behavior similar to that of the curvature driven trapped electron modes and can in the electrostatic limit be described by a simple quadratic dispersion equation. (author)

  16. Lithium ion beam driven hohlraums for PBFA II

    International Nuclear Information System (INIS)

    Dukart, R.J.

    1994-01-01

    In our light ion inertial confinement fusion (ICF) program, fusion capsules are driven with an intense x-ray radiation field produced when an intense beam of ions penetrates a radiation case and deposits energy in a foam x-ray conversion region. A first step in the program is to generate and measure these intense fields on the Particle Beam Fusion Accelerator II (PBFA II). Our goal is to generate a 100-eV radiation temperature in lithium ion beam driven hohlraums, the radiation environment which will provide the initial drive temperature for ion beam driven implosion systems designed to achieve high gain. In this paper, we describe the design of such hohlraum targets and their predicted performance on PBFA II as we provide increasing ion beam intensities

  17. Magnetically driven oscillator and resonance: a teaching tool

    Science.gov (United States)

    Erol, M.; Çolak, İ. Ö.

    2018-05-01

    This paper reports a simple magnetically driven oscillator, designed and resolved in order to achieve a better student understanding and to overcome certain instructional difficulties. The apparatus is mainly comprised of an ordinary spring pendulum with a neodymium magnet attached to the bottom, a coil placed in the same vertical direction, an ordinary function generator, an oscilloscope and a smartphone. Driven oscillation and resonance is basically managed by applying a sinusoidal voltage to the coil and tuning the driving frequency to the natural frequency of the pendulum. The resultant oscillation is recorded by a smartphone video application and analyzed via a video analysis programme. The designed apparatus can easily be employed in basic physics laboratories to achieve an enhanced and deeper understanding of driven oscillation and resonance.

  18. Measurement of beam driven hydrodynamic turbulence

    International Nuclear Information System (INIS)

    Norem, J.; Black, E.; Bandura, L.; Errede, D.; Cummings, M. A. C.

    2003-01-01

    Cooling intense muon beams in liquid hydrogen absorbers introduces kW of heating to the cold fluid, which will drive turbulent flow. The amount of turbulence may be sufficient to help cool the liquid, but calculations are difficult. We have used a 20 MeV electron beam in a water tank to look at the scale of the beam driven convection and turbulence. The density and flow measurements are made with schlieren and Ronchi systems. We describe the optical systems and the turbulence measured. These data are being used to calibrate hydrodynamic calculations of convection driven and forced flow cooling in muon cooling absorbers

  19. Voltage-driven quantum oscillations in graphene

    International Nuclear Information System (INIS)

    Yampol'skii, V A; Savel'ev, S; Nori, Franco

    2008-01-01

    We predict unusual (for non-relativistic quantum mechanics) electron states in graphene, which are localized within a finite-width potential barrier. The density of localized states in the sufficiently high and/or wide graphene barrier exhibits a number of singularities at certain values of the energy. Such singularities provide quantum oscillations of both the transport (e.g. conductivity) and thermodynamic properties of graphene-when increasing the barrier height and/or width, similarly to the well-known Shubnikov-de-Haas (SdH) oscillations of conductivity in pure metals. However, here the SdH-like oscillations are driven by an electric field instead of the usual magnetically driven SdH-oscillations

  20. Envisioning the future of collaborative model-driven software engineering

    NARCIS (Netherlands)

    Di Ruscio, Davide; Franzago, Mirco; Malavolta, Ivano; Muccini, Henry

    2017-01-01

    The adoption of Model-driven Software Engineering (MDSE) to develop complex software systems in application domains like automotive and aerospace is being supported by the maturation of model-driven platforms and tools. However, empirical studies show that a wider adoption of MDSE technologies is

  1. Light-driven solute transport in Halobacterium halobium

    Science.gov (United States)

    Lanyi, J. K.

    1979-01-01

    The cell membrane of Halobacterium halobium exhibits differential regions which contain crystalline arrays of a single kind of protein, termed bacteriorhodopsin. This bacterial retinal-protein complex resembles the visual pigment and, after the absorption of protons, translocates H(+) across the cell membrane, leading to an electrochemical gradient for protons between the inside and the outside of the cell. Thus, light is an alternate source of energy in these bacteria, in addition to terminal oxidation. The paper deals with work on light-driven transport in H. halobium with cell envelope vesicles. The discussion covers light-driven movements of H(+), Na(+), and K(+); light-driven amino acid transport; and apparent allosteric control of amino acid transport. The scheme of energy coupling in H. halobium vesicles appears simple, its quantitative details are quite complex and reveal regulatory phenomena. More knowledge is required of the way the coupling components are regulated by the ion gradients present.

  2. Test-driven development with Django

    CERN Document Server

    Harvey, Kevin

    2015-01-01

    This book is for Django developers with little or no knowledge of test-driven development or testing in general. Familiarity with the command line, setting up a Python virtual environment, and starting a Django project are assumed.

  3. Manganese superoxide dismutase (MnSOD catalyzes NO-dependent tyrosine residue nitration

    Directory of Open Access Journals (Sweden)

    SRDJAN STOJANOVIC

    2005-04-01

    Full Text Available The peroxynitrite-induced nitration of manganese superoxide dismutase (MnSOD tyrosine residue, which causes enzyme inactivation, is well established. This led to suggestions that MnSOD nitration and inactivation in vivo, detected in various diseases associated with oxidative stress and overproduction of nitric monoxide (NO, conditions which favor peroxynitrite formation, is also caused by peroxynitrite. However, our previous in vitro study demonstrated that exposure of MnSOD to NO led to NO conversion into nitrosonium (NO+ and nitroxyl (NO– species, which caused enzyme modifications and inactivation. Here it is reported that MnSOD is tyrosine nitrated upon exposure to NO, as well as that MnSOD nitration contributes to inactivation of the enzyme. Collectively, these observations provide a compelling argument supporting the generation of nitrating species in MnSOD exposed to NO and shed a new light on MnSOD tyrosine nitration and inactivation in vivo. This may represent a novel mechanism by which MnSOD protects cell from deleterious effects associated with overproduction of NO. However, extensive MnSOD modification and inactivation associated with prolonged exposure to NO will amplify the toxic effects caused by increased cell superoxide and NO levels.

  4. Aqueous reactive species induced by a PCB surface micro-discharge air plasma device: a quantitative study

    Science.gov (United States)

    Chen, Chen; Li, Fanying; Chen, Hai-Lan; Kong, Michael G.

    2017-11-01

    This paper presents a quantitative investigation on aqueous reactive species induced by air plasma generated from a printed circuit board surface micro-discharge (SMD) device. Under the conditions amenable for proliferation of mammalian cells, concentrations of ten types of reactive oxygen and nitrogen species (RONS) in phosphate buffering solution (PBS) are measured by chemical fluorescent assays and electron spin resonance spectroscopy (ESR). Results show that concentrations of several detected RNS (NO2- , NO3- , peroxynitrites, and NO2\\centerdot ) are higher than those of ROS (H2O2, O2\\centerdot - , and 1O2) in the air plasma treated solution. Concentrations of NO3- can reach 150 times of H2O2 with 60 s plasma treatment. For short-lived species, the air plasma generates more copious peroxynitrite than other RONS including NO2\\centerdot , O2\\centerdot - , 1O2, and N{{O}\\centerdot } in PBS. In addition, the existence of reaction between H2O2 and NO2- /HNO2 to produce peroxynitrite is verified by the chemical scavenger experiments. The reaction relations between detected RONS are also discussed.

  5. Research on accelerator-driven transmutation and studies of experimental facilities

    Energy Technology Data Exchange (ETDEWEB)

    Takizuka, Takakazu [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-11-01

    JAERI is carrying out R and Ds on accelerator-driven transmutation systems under the national OMEGA Program that aims at development of the technology to improve efficiency and safety in the final disposal of radioactive waste. Research facilities for accelerator-driven transmutation experiments are proposed to construct within the framework of the planned JAERI Neutron Science Project. This paper describes the features of the proposed accelerator-driven transmutation systems and their technical issues to be solved. A research facility plan under examination is presented. The plan is divided in two phases. In the second phase, technical feasibility of accelerator-driven systems will be demonstrated with a 30-60 MW experimental integrated system and with a 7 MW high-power target facility. (author)

  6. Heat driven pulse pump

    Science.gov (United States)

    Benner, Steve M (Inventor); Martins, Mario S. (Inventor)

    2000-01-01

    A heat driven pulse pump includes a chamber having an inlet port, an outlet port, two check valves, a wick, and a heater. The chamber may include a plurality of grooves inside wall of the chamber. When heated within the chamber, a liquid to be pumped vaporizes and creates pressure head that expels the liquid through the outlet port. As liquid separating means, the wick, disposed within the chamber, is to allow, when saturated with the liquid, the passage of only liquid being forced by the pressure head in the chamber, preventing the vapor from exiting from the chamber through the outlet port. A plurality of grooves along the inside surface wall of the chamber can sustain the liquid, which is amount enough to produce vapor for the pressure head in the chamber. With only two simple moving parts, two check valves, the heat driven pulse pump can effectively function over the long lifetimes without maintenance or replacement. For continuous flow of the liquid to be pumped a plurality of pumps may be connected in parallel.

  7. Integrated Optoelectronic Networks for Application-Driven Multicore Computing

    Science.gov (United States)

    2017-05-08

    AFRL-AFOSR-VA-TR-2017-0102 Integrated Optoelectronic Networks for Application- Driven Multicore Computing Sudeep Pasricha COLORADO STATE UNIVERSITY...AND SUBTITLE Integrated Optoelectronic Networks for Application-Driven Multicore Computing 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA9550-13-1-0110 5c...and supportive materials with innovative architectural designs that integrate these components according to system-wide application needs. 15

  8. The synthesis and spectroscopic study of stable free radicals related to piperidine-n-oxyl, including a stable bi-radical; Syntheses et etudes spectroscopiques de radicaux libres piperidiniques et d'un biradical stable, du type nitroxyde

    Energy Technology Data Exchange (ETDEWEB)

    Briere, R [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires, Laboratoire de chimie organique physique

    1967-06-01

    A new synthesis of di-tert-butyl nitroxide using the reaction between tert-butyl magnesium chloride and nitro-tert-butane is presented in the first section. Synthesis and investigation of stable free piperidine-N-oxyl radicals are described in the second section. All these nitroxides have been characterised by their I. R., U. V. and E. P. R. absorption spectra. The final section contains a description of the synthesis of a stable bi-radical of the nitroxide type by condensation of 2,2, 6, 6-tetramethyl-piperid-4-one-l-oxyl with hydrazine. (author) [French] La premiere partie expose une nouvelle methode de synthase du di-t-butyl nitroxyde, par action d'halogenures de t-butyl magnesium sur le nitro-t-butane (Rdt maximum 45 pour cert, purete 86 pour cent). Une etude de radicaux. libres stables pipericliniques est faite dans une seconde partie. Ces composes sont obtenus par oxydation de derives de la triacetonamine. Les caracteristiques spectroscopiques ultra-violette, infra-rouge, et paramagnetique electronique de ces radicaux sont donnees. La grande inertie chimique du groupement nitroxyde a permis la syn-these d'un biradical stable par formation d'azine d'une cetone radicalaire, ce qui fait 1'objet de la troisieme partie. (auteur)

  9. Driven self-assembly of hard nanoplates on soft elastic shells

    International Nuclear Information System (INIS)

    Zhang Yao-Yang; Hua Yun-Feng; Deng Zhen-Yu

    2015-01-01

    The driven self-assembly behaviors of hard nanoplates on soft elastic shells are investigated by using molecular dynamics (MD) simulation method, and the driven self-assembly structures of adsorbed hard nanoplates depend on the shape of hard nanoplates and the bending energy of soft elastic shells. Three main structures for adsorbed hard nanoplates, including the ordered aggregation structures of hard nanoplates for elastic shells with a moderate bending energy, the collapsed structures for elastic shells with a low bending energy, and the disordered aggregation structures for hard shells, are observed. The self-assembly process of adsorbed hard nanoplates is driven by the surface tension of the elastic shell, and the shape of driven self-assembly structures is determined on the basis of the minimization of the second moment of mass distribution. Meanwhile, the deformations of elastic shells can be controlled by the number of adsorbed rods as well as the length of adsorbed rods. This investigation can help us understand the complexity of the driven self-assembly of hard nanoplates on elastic shells. (paper)

  10. Investigation of Current Driven Loudspeakers

    DEFF Research Database (Denmark)

    Schneider, Henrik; Agerkvist, Finn T.; Knott, Arnold

    2015-01-01

    Current driven loudspeakers have previously been investigated but the literature is limited and the advantages and disadvantages are yet to be fully identified. This paper makes use of a non-linear loudspeaker model to analyse loudspeakers with distinct non-linear characteristics under voltage an......” woofer where a copper ring in the pole piece has not been implemented to compensate for eddy currents. However the drive method seems to be irrelevant for a 5” woofer where the compliance, force factor as well as the voice coil inductance has been optimized for linearity.......Current driven loudspeakers have previously been investigated but the literature is limited and the advantages and disadvantages are yet to be fully identified. This paper makes use of a non-linear loudspeaker model to analyse loudspeakers with distinct non-linear characteristics under voltage...

  11. Kähler-driven tribrid inflation

    Science.gov (United States)

    Antusch, Stefan; Nolde, David

    2012-11-01

    We discuss a new class of tribrid inflation models in supergravity, where the shape of the inflaton potential is dominated by effects from the Kähler potential. Tribrid inflation is a variant of hybrid inflation which is particularly suited for connecting inflation with particle physics, since the inflaton can be a D-flat combination of charged fields from the matter sector. In models of tribrid inflation studied so far, the inflaton potential was dominated by either loop corrections or by mixing effects with the waterfall field (as in "pseudosmooth" tribrid inflation). Here we investigate the third possibility, namely that tribrid inflation is dominantly driven by effects from higher-dimensional operators of the Kähler potential. We specify for which superpotential parameters the new regime is realized and show how it can be experimentally distinguished from the other two (loop-driven and "pseudosmooth") regimes.

  12. Discovery and analysis of e-mail-driven business processes

    NARCIS (Netherlands)

    Stuit, Marco; Wortmann, Hans

    E-mail is used as the primary tool for business communication and collaboration. This paper presents a novel e-mail interaction mining method to discover and analyze e-mail-driven business processes. An e-mail-driven business process is perceived as a human collaboration process that consists of

  13. Torque Control of Underactuated Tendon-driven Robotic Fingers

    Science.gov (United States)

    Abdallah, Muhammad E. (Inventor); Ihrke, Chris A. (Inventor); Reiland, Matthew J. (Inventor); Wampler, Charles W. (Inventor); Diftler, Myron A. (Inventor); Platt, Robert (Inventor); Bridgwater, Lyndon (Inventor)

    2013-01-01

    A robotic system includes a robot having a total number of degrees of freedom (DOF) equal to at least n, an underactuated tendon-driven finger driven by n tendons and n DOF, the finger having at least two joints, being characterized by an asymmetrical joint radius in one embodiment. A controller is in communication with the robot, and controls actuation of the tendon-driven finger using force control. Operating the finger with force control on the tendons, rather than position control, eliminates the unconstrained slack-space that would have otherwise existed. The controller may utilize the asymmetrical joint radii to independently command joint torques. A method of controlling the finger includes commanding either independent or parameterized joint torques to the controller to actuate the fingers via force control on the tendons.

  14. Role of oxidative metabolites of cocaine in toxicity and addiction: oxidative stress and electron transfer.

    Science.gov (United States)

    Kovacic, Peter

    2005-01-01

    Cocaine is one of the principal drugs of abuse. Although impressive advances have been made, unanswered questions remain concerning mechanism of toxicity and addiction. Discussion of action mode usually centers on receptor binding and enzyme inhibition, with limited attention to events at the molecular level. This review provides extensive evidence in support of the hypothesis that oxidative metabolites play important roles comprising oxidative stress (OS), reactive oxygen species (ROS), and electron transfer (ET). The metabolites include norcocaine and norcocaine derivatives: nitroxide radical, N-hydroxy, nitrosonium, plus cocaine iminium and formaldehyde. Observed formation of ROS is rationalized by redox cycling involving several possible ET agents. Three potential ones are present in the form of oxidative metabolites, namely, nitroxide, nitrosonium, and iminium. Most attention has been devoted to the nitroxide-hydroxylamine couple which has been designated by various investigators as the principal source of ROS. The proximate ester substituent is deemed important for intramolecular stabilization of reactive intermediates. Reduction potential of nitroxide is in accord with plausibility of ET in the biological milieu. Toxicity by cocaine, with evidence for participation of OS, is demonstrated for many body components, including liver, central nervous system, cardiovascular system, reproductive system, kidney, mitochondria, urine, and immune system. Other adverse effects associated with ROS comprise teratogenesis and apoptosis. Examples of ROS generated are lipid peroxides and hydroxyl radical. Often observed were depletion of antioxidant defenses, and protection by added antioxidants, such as, thiol, salicylate, and deferoxamine. Considerable evidence supports the contention that oxidative ET metabolites of cocaine are responsible for much of the observed OS. Quite significantly, the pro-oxidant, toxic effects, including generation of superoxide and lipid peroxyl

  15. Effectiveness of User- and Expert-Driven Web-based Hypertension Programs: an RCT.

    Science.gov (United States)

    Liu, Sam; Brooks, Dina; Thomas, Scott G; Eysenbach, Gunther; Nolan, Robert P

    2018-04-01

    The effectiveness of self-guided Internet-based lifestyle counseling (e-counseling) varies, depending on treatment protocol. Two dominant procedures in e-counseling are expert- and user-driven. The influence of these procedures on hypertension management remains unclear. The objective was to assess whether blood pressure improved with expert-driven or user-driven e-counseling over control intervention in patients with hypertension over a 4-month period. This study used a three-parallel group, double-blind randomized controlled design. In Toronto, Canada, 128 participants (aged 35-74 years) with hypertension were recruited. Participants were recruited using online and poster advertisements. Data collection took place between June 2012 and June 2014. Data were analyzed from October 2014 to December 2016. Controls received a weekly e-mail newsletter regarding hypertension management. The expert-driven group was prescribed a weekly exercise and diet plan (e.g., increase 1,000 steps/day this week). The user-driven group received weekly e-mail, which allowed participants to choose their intervention goals (e.g., [1] feel more confident to change my lifestyle, or [2] self-help tips for exercise or a heart healthy diet). Primary outcome was systolic blood pressure measured at baseline and 4-month follow-up. Secondary outcomes included cholesterol, 10-year Framingham cardiovascular risk, daily steps, and dietary habits. Expert-driven groups showed a greater systolic blood pressure decrease than controls at follow-up (expert-driven versus control: -7.5 mmHg, 95% CI= -12.5, -2.6, p=0.01). Systolic blood pressure reduction did not significantly differ between user- and expert-driven. Expert-driven compared with controls also showed a significant improvement in pulse pressure, cholesterol, and Framingham risk score. The expert-driven intervention was significantly more effective than both user-driven and control groups in increasing daily steps and fruit intake. It may be

  16. The Arizona Universities Library Consortium patron-driven e-book model

    Directory of Open Access Journals (Sweden)

    Jeanne Richardson

    2013-03-01

    Full Text Available Building on Arizona State University's patron-driven acquisitions (PDA initiative in 2009, the Arizona Universities Library Consortium, in partnership with the Ingram Content Group, created a cooperative patron-driven model to acquire electronic books (e-books. The model provides the opportunity for faculty and students at the universities governed by the Arizona Board of Regents (ABOR to access a core of e-books made accessible through resource discovery services and online catalogs. These books are available for significantly less than a single ABOR university would expend for the same materials. The patron-driven model described is one of many evolving models in digital scholarship, and, although the Arizona Universities Library Consortium reports a successful experience, patron-driven models pose questions to stakeholders in the academic publishing industry.

  17. Plasma-driven liners

    International Nuclear Information System (INIS)

    Kilic, H.; Linhart, J.G.; Bortolotti, A.; Nardi, V.

    1992-01-01

    The deposition of thermal energy by laser or ion beams in an ablator is capable of producing a very large acceleration of the adjacent pusher - for power densities of 100 Terrawatts/cm 2 , ablator pressure in the range of 10 Mbar is attainable. In the case of a plasma drive such driving pressures and accelerations are not directly possible. When a snowplough (SP) is used to accelerate a thin liner, the driving pressure is that of the magnetic piston pushing the SP, i.e. at most 0.1 Mbar. However, the initial radius r 0 of the liner can be a few centimeters, instead of 1 (mm) as in the case in direct pellet implosions. In order to compete with the performance of the beam-driven liners, the plasma drive must demonstrate that a) thin liner retains a high density during the implosion (lasting a fraction of a μsec); b) radial compression ratio r 0 /r min of the order of 100 can be attained. It is also attractive to consider the staging of two or more liners in order to get sharpening and amplifications of the pressure and/or radiation pulse. If a) and b) are verified then the final pressures produced will be comparable with those of the beam-driven implosions. (author) 5 refs., 3 figs

  18. Analysis of directly driven ICF targets

    International Nuclear Information System (INIS)

    Velarde, G.; Aragones, J.M.; Gago, J.A.

    1986-01-01

    The current capabilities at DENIM for the analysis of directly driven targets are presented. These include theoretical, computational and applied physical studies and developments of detailed simulation models for the most relevant processes in ICF. The simulation of directly driven ICF targets is carried out with the one-dimensional NORCLA code developed at DENIM. This code contains two main segments: NORMA and CLARA, able to work fully coupled and in an iterative manner. NORMA solves the hydrodynamic equations in a lagrangian mesh. It has modular programs couple to it to treat the laser or particle beam interaction with matter. Equations of state, opacities and conductivities are taken from a DENIM atomic data library, generated externally with other codes that will also be explained in this work. CLARA solves the transport equation for neutrons, as well as for charged particles, and suprathermal electrons using discrete ordinates and finite element methods in the computational procedure. Parametric calculations of multilayered single-shell targets driven by heavy ion beams are also analyzed. Finally, conclusions are focused on the ongoing developments in the areas of interest such as: radiation transport, atomic physics, particle in cell method, charged particle transport, two-dimensional calculations and instabilities. (author)

  19. Mixed signals: The effect of conflicting reward- and goal-driven biases on selective attention

    OpenAIRE

    Preciado, Daniel; Munneke, Jaap; Theeuwes, Jan

    2017-01-01

    Attentional selection depends on the interaction between exogenous (stimulus-driven), endogenous (goal-driven), and selection history (experience-driven) factors. While endogenous and exogenous biases have been widely investigated, less is known about their interplay with value-driven attention. The present study investigated the interaction between reward-history and goal-driven biases on perceptual sensitivity (d?) and response time (RT) in a modified cueing paradigm presenting two coloured...

  20. Magnon-driven quantum dot refrigerators

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuan; Huang, Chuankun; Liao, Tianjun; Chen, Jincan, E-mail: jcchen@xmu.edu.cn

    2015-12-18

    Highlights: • A three-terminal quantum dot refrigerator is proposed. • The effects of magnetic field, applied voltage, and polarization are considered. • The region that the system can work as a refrigerator is determined. • Two different magnon-driven quantum dot refrigerators are compared. - Abstract: A new model of refrigerator consisting of a spin-splitting quantum dot coupled with two ferromagnetic reservoirs and a ferromagnetic insulator is proposed. The rate equation is used to calculate the occupation probabilities of the quantum dot. The expressions of the electron and magnon currents are obtained. The region that the system can work in as a refrigerator is determined. The cooling power and coefficient of performance (COP) of the refrigerator are derived. The influences of the magnetic field, applied voltage, and polarization of two leads on the performance are discussed. The performances of two different magnon-driven quantum dot refrigerators are compared.

  1. Resonances in a periodically driven bosonic system

    Science.gov (United States)

    Quelle, Anton; Smith, Cristiane Morais

    2017-11-01

    Periodically driven systems are a common topic in modern physics. In optical lattices specifically, driving is at the origin of many interesting phenomena. However, energy is not conserved in driven systems, and under periodic driving, heating of a system is a real concern. In an effort to better understand this phenomenon, the heating of single-band systems has been studied, with a focus on disorder- and interaction-induced effects, such as many-body localization. Nevertheless, driven systems occur in a much wider context than this, leaving room for further research. Here, we fill this gap by studying a noninteracting model, characterized by discrete, periodically spaced energy levels that are unbounded from above. We couple these energy levels resonantly through a periodic drive, and discuss the heating dynamics of this system as a function of the driving protocol. In this way, we show that a combination of stimulated emission and absorption causes the presence of resonant stable states. This will serve to elucidate the conditions under which resonant driving causes heating in quantum systems.

  2. Resonances in a periodically driven bosonic system.

    Science.gov (United States)

    Quelle, Anton; Smith, Cristiane Morais

    2017-11-01

    Periodically driven systems are a common topic in modern physics. In optical lattices specifically, driving is at the origin of many interesting phenomena. However, energy is not conserved in driven systems, and under periodic driving, heating of a system is a real concern. In an effort to better understand this phenomenon, the heating of single-band systems has been studied, with a focus on disorder- and interaction-induced effects, such as many-body localization. Nevertheless, driven systems occur in a much wider context than this, leaving room for further research. Here, we fill this gap by studying a noninteracting model, characterized by discrete, periodically spaced energy levels that are unbounded from above. We couple these energy levels resonantly through a periodic drive, and discuss the heating dynamics of this system as a function of the driving protocol. In this way, we show that a combination of stimulated emission and absorption causes the presence of resonant stable states. This will serve to elucidate the conditions under which resonant driving causes heating in quantum systems.

  3. Theory of radiatively driven stellar winds. I. A physical interpretation

    International Nuclear Information System (INIS)

    Abbott, D.C.

    1980-01-01

    This series of papers extends the line-driven wind theory of Castor, Abbott, and Klein (CAK). The present paper develops a physical interpretation of line-driven flows using analytic methods. Numerical results will follow in two subsequent papers

  4. Electromagnetic cold-test characterization of the quad-driven stripline kicker

    International Nuclear Information System (INIS)

    Dunlap, J E; Nelson, S D.

    1998-01-01

    The first kicker concept design for beam deflection was constructed to allow stripline plates to be driven; thus directing, or kicking, the electron beam into two subsequent beam lines. This quad-driven stripline kicker is an eight port electromagnetic network and consists of two actively driven plates and two terminated plates. Electromagnetic measurements performed on the bi-kicker and quad-kicker were designed to determine: (1) the quality of the fabrication of the kicker, including component alignments; (2) quantification of the input feed transition regions from the input coax to the driven kicker plates; (3) identification of properties of the kicker itself without involving the effects of the electron beam; (4) coupling between a line current source and the plates of the kicker; and (5) the effects on the driven current to simulate an electron beam through the body of the kicker. Included in this are the angular variations inside the kicker to examine modal distributions. The goal of the simulated beam was to allow curved path and changing radius studies to be performed electromagnetically. The cold test results produced were then incorporated into beam models

  5. Data-Driven Methods to Diversify Knowledge of Human Psychology

    OpenAIRE

    Jack, Rachael E.; Crivelli, Carlos; Wheatley, Thalia

    2017-01-01

    open access article Psychology aims to understand real human behavior. However, cultural biases in the scientific process can constrain knowledge. We describe here how data-driven methods can relax these constraints to reveal new insights that theories can overlook. To advance knowledge we advocate a symbiotic approach that better combines data-driven methods with theory.

  6. Pulsed power driven hohlraum research at Sandia National Laboratories

    International Nuclear Information System (INIS)

    Leeper, R.J.; Alberts, T.E.; Allshouse, G.A.

    1996-01-01

    Three pulsed power driven hohlraum concepts are being investigated at Sandia for application to inertial fusion research. These hohlraums are driven by intense proton and Li ion beams as well as by two different types of z-pinch x-ray sources. Research on these hohlraum systems will continue on Sandia's PBFA II-Z facility

  7. Real-space renormalization group approach to driven diffusive systems

    Energy Technology Data Exchange (ETDEWEB)

    Hanney, T [SUPA and School of Physics, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JZ (United Kingdom); Stinchcombe, R B [Theoretical Physics, 1 Keble Road, Oxford, OX1 3NP (United Kingdom)

    2006-11-24

    We introduce a real-space renormalization group procedure for driven diffusive systems which predicts both steady state and dynamic properties. We apply the method to the boundary driven asymmetric simple exclusion process and recover exact results for the steady state phase diagram, as well as the crossovers in the relaxation dynamics for each phase.

  8. Real-space renormalization group approach to driven diffusive systems

    International Nuclear Information System (INIS)

    Hanney, T; Stinchcombe, R B

    2006-01-01

    We introduce a real-space renormalization group procedure for driven diffusive systems which predicts both steady state and dynamic properties. We apply the method to the boundary driven asymmetric simple exclusion process and recover exact results for the steady state phase diagram, as well as the crossovers in the relaxation dynamics for each phase

  9. Combining environment-driven adaptation and task-driven optimisation in evolutionary robotics.

    Science.gov (United States)

    Haasdijk, Evert; Bredeche, Nicolas; Eiben, A E

    2014-01-01

    Embodied evolutionary robotics is a sub-field of evolutionary robotics that employs evolutionary algorithms on the robotic hardware itself, during the operational period, i.e., in an on-line fashion. This enables robotic systems that continuously adapt, and are therefore capable of (re-)adjusting themselves to previously unknown or dynamically changing conditions autonomously, without human oversight. This paper addresses one of the major challenges that such systems face, viz. that the robots must satisfy two sets of requirements. Firstly, they must continue to operate reliably in their environment (viability), and secondly they must competently perform user-specified tasks (usefulness). The solution we propose exploits the fact that evolutionary methods have two basic selection mechanisms-survivor selection and parent selection. This allows evolution to tackle the two sets of requirements separately: survivor selection is driven by the environment and parent selection is based on task-performance. This idea is elaborated in the Multi-Objective aNd open-Ended Evolution (monee) framework, which we experimentally validate. Experiments with robotic swarms of 100 simulated e-pucks show that monee does indeed promote task-driven behaviour without compromising environmental adaptation. We also investigate an extension of the parent selection process with a 'market mechanism' that can ensure equitable distribution of effort over multiple tasks, a particularly pressing issue if the environment promotes specialisation in single tasks.

  10. Combining environment-driven adaptation and task-driven optimisation in evolutionary robotics.

    Directory of Open Access Journals (Sweden)

    Evert Haasdijk

    Full Text Available Embodied evolutionary robotics is a sub-field of evolutionary robotics that employs evolutionary algorithms on the robotic hardware itself, during the operational period, i.e., in an on-line fashion. This enables robotic systems that continuously adapt, and are therefore capable of (re-adjusting themselves to previously unknown or dynamically changing conditions autonomously, without human oversight. This paper addresses one of the major challenges that such systems face, viz. that the robots must satisfy two sets of requirements. Firstly, they must continue to operate reliably in their environment (viability, and secondly they must competently perform user-specified tasks (usefulness. The solution we propose exploits the fact that evolutionary methods have two basic selection mechanisms-survivor selection and parent selection. This allows evolution to tackle the two sets of requirements separately: survivor selection is driven by the environment and parent selection is based on task-performance. This idea is elaborated in the Multi-Objective aNd open-Ended Evolution (monee framework, which we experimentally validate. Experiments with robotic swarms of 100 simulated e-pucks show that monee does indeed promote task-driven behaviour without compromising environmental adaptation. We also investigate an extension of the parent selection process with a 'market mechanism' that can ensure equitable distribution of effort over multiple tasks, a particularly pressing issue if the environment promotes specialisation in single tasks.

  11. Developmental Trajectories of Boys’ Driven Exercise and Fasting During the Middle School Years

    Science.gov (United States)

    Davis, Heather A.; Guller, Leila; Smith, Gregory T.

    2016-01-01

    Boys appear to engage in eating disorder behavior, particularly nonpurging compensatory behaviors such as driven exercise and fasting, at higher rates than previously thought. Little is known about the development of these behaviors in adolescent boys. In a sample of 631 non-binge eating and non-purging boys studied once in 5th grade and 6 times over the 3 years of middle school (grades 6 through 8), we found that (a) for some youth, driven exercise and fasting were present from grade 6; (b) different boys progressed along different trajectories of engagement in driven exercise and fasting, with some boys engaging in no driven exercise or fasting (65.8% and 83.5%, respectively), some boys engaging in driven exercise and fasting throughout middle school (25.2% and 16.5%, respectively), and other boys discontinuing engagement in driven exercise (9%); (c) 5th grade depression, eating expectancies, and thinness expectancies predicted subsequent trajectory group membership; and (d) boys engaging in driven exercise and fasting in 8th grade remained distressed. Boys’ engagement in driven exercise and fasting behavior merits the attention of researchers and clinicians. PMID:26707543

  12. Curvature-driven instabilities in a hot-electron plasma: radial analysis

    International Nuclear Information System (INIS)

    Berk, H.L.; Van Dam, J.W.; Rosenbluth, M.N.; Spong, D.A.

    1981-12-01

    The theory of unfavorable curvature-driven instabilities is developed for a plasma interacting with a hot electron ring whose drift frequencies are larger than the growth rates predicted from conventional magnetohydrodynamic theory. A z-pinch model is used to emphasize the radial structure of the problem. Stability criteria are obtained for the five possible modes of instability: the conventional hot electron interchange, a high-frequency hot electron interchange (at frequencies larger than the ion cyclotron frequency), a compressional instability, a background pressure-driven interchange, and an interacting pressure-driven interchange

  13. High-explosive driven crowbar switch

    International Nuclear Information System (INIS)

    Dike, R.S.; Kewish, R.W. Jr.

    1976-01-01

    The disclosure relates to a compact explosive driven switch for use as a low resistance, low inductance crowbar switch. A high-explosive charge extrudes a deformable conductive metallic plate through a polyethylene insulating layer to achieve a hard current contact with a supportive annular conductor

  14. Failure-probability driven dose painting

    DEFF Research Database (Denmark)

    Vogelius, Ivan R; Håkansson, Katrin; Due, Anne K

    2013-01-01

    To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study...

  15. Predicting when precipitation-driven synthesis is feasible : application to biocatalysis

    NARCIS (Netherlands)

    Ulijn, R.V.; Janssen, A.E.M.; Moore, B.D.; Halling, P.J.

    2001-01-01

    Precipitation-driven synthesis offers the possibility of obtaining high reaction yields using very low volume reactors and is finding increasing applications in biocatalysis. Here, a model that allows straightforward prediction of when such a precipitation-driven reaction will be thermodynamically

  16. Interaction-driven versus disorder-driven transport in ultra-dilute GaAs two-dimensional hole systems

    Science.gov (United States)

    Huang, Jian; Pfeiffer, L. N.; West, K. W.

    2012-02-01

    It is well-known that the insulating behavior in the two-dimensional metal-to-insulator transition demonstrates a finite temperature conduction via hopping. Recently, however, some very strongly interacting higher purity two-dimensional electron systems at temperatures T->0 demonstrate certain nonactivated insulating behaviors that are absent in more disordered systems. Through measuring in dark the T-dependence of the conductivity of ultra-high quality 2D holes with charge densities down to 7x10^8 cm-2, an approximate power-law behavior is identified. Moreover, for the lowest charge densities, the exponent exhibits a linearly decreasing density-dependence which suggests an interaction-driven nature. Such an electron state is fragile to even a slight increase of disorder which causes a crossover from nonactivated to activated conduction. The non-activated conduction may well be an universal interaction-driven signature of an electron state of strongly correlated (semiquantum) liquid.

  17. Efficacy of ACA strategies in biography-driven science teaching: an investigation

    Science.gov (United States)

    MacDonald, Grizelda L.; Miller, Stuart S.; Murry, Kevin; Herrera, Socorro; Spears, Jacqueline D.

    2013-12-01

    This study explored the biography-driven approach to teaching culturally and linguistically diverse students in science education. Biography-driven instruction (BDI) embraces student diversity by incorporating students' sociocultural, linguistic, cognitive, and academic dimensions of their biographies into the learning process (Herrera in Biography-driven culturally responsive teaching. Teachers College Press, New York, 2010). Strategies have been developed (Herrera, Kavimandan and Holmes in Crossing the vocabulary bridge: differentiated strategies for diverse secondary classrooms. Teachers College Press, New York, 2011) that provide teachers with instructional routines that facilitate BDI. Using systematic classroom observations we empirically demonstrate that these activate, connect, affirm, strategies are likely to be effective in increasing teachers' biography-driven practices. Implications for theory and practice are discussed.

  18. On stability of accelerator driven systems

    International Nuclear Information System (INIS)

    Makai, Mihaly

    2003-01-01

    An unsolved problem of energy production in nuclear reactors is the waste management. A large portion of the nuclear waste is the spent fuel. At present, two possibilities are seen. The first one is to 'wrap up' all the radioactive waste safely and to bury it at a remote quiet place where it can rest undisturbed until its activity decreases to a tolerable level. The second one is to exploit the excitation energy still present in the nuclear waste. In order to release that energy, the spent fuel is bombarded by high energy particles obtained from an accelerator. The resulting system is called accelerator driven system (ADS). In an ADS, the spent fuel forms a subcritical reactor, which is driven by an external source. (author)

  19. Nova-driven winds in globular clusters

    International Nuclear Information System (INIS)

    Scott, E.H.; Durisen, R.H.

    1978-01-01

    Recent sensitive searches for Hα emission from ionized intracluster gas in globular clusters have set upper limits that conflict with theoretical predictions. We suggest that nova outbursts heat the gas, producing winds that resolve this discrepancy. The incidence of novae in globular clusters, the conversion of kinetic energy of the nova shell to thermal energy of the intracluster gas, and the characteristics of the resultant winds are discussed. Calculated emission from the nova-driven models does not conflict with any observations to date. Some suggestions are made concerning the most promising approaches for future detection of intracluster gas on the basis of these models. The possible relationship of nova-driven winds of globular cluster X-ray sources is also considered

  20. Spectrum of resistivity gradient driven turbulence

    International Nuclear Information System (INIS)

    Terry, P.W.; Diamond, P.H.; Shaing, K.C.; Garcia, L.; Carreras, B.A.

    1986-01-01

    The resistivity fluctuation correlation function and electrostatic potential spectrum of resistivity gradient driven turbulence are calculated analytically and compared to the results of three dimensional numerical calculations. Resistivity gradient driven turbulence is characterized by effective Reynolds' numbers of order unity. Steady-state solution of the renormalized spectrum equations yields an electrostatic potential spectrum (circumflex phi 2 )/sub ktheta/ approx. k/sub theta//sup -3.25/. Agreement of the analytically calculated potential spectrum and mean-square radial velocity with the results of multiple helicity numerical calculations is excellent. This comparison constitutes a quantitative test of the analytical turbulence theory used. The spectrum of magnetic fluctuations is also calculated, and agrees well with that obtained from the numerical computations. 13 refs., 8 figs

  1. Test and Behaviour Driven Development with Python

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    Experience has taught us that bugs are impossible to avoid when programming. Specially on continuous delivery processes where there are new versions that refactor or incorporate new modules to the project. Although, there are different tools which help us to ensure code quality by enabling developers to catch bugs while still in the development stage. In this talk, I will talk about Test-driven development(TDD) and Behaviour-Driven development (BDD) methodologies focused on web development. Also, I will present an overview of unit testing tools as Selenium or Behave, which help us to produce working software, with fewer bugs, quickly and consistently.

  2. Model-driven Service Engineering with SoaML

    Science.gov (United States)

    Elvesæter, Brian; Carrez, Cyril; Mohagheghi, Parastoo; Berre, Arne-Jørgen; Johnsen, Svein G.; Solberg, Arnor

    This chapter presents a model-driven service engineering (MDSE) methodology that uses OMG MDA specifications such as BMM, BPMN and SoaML to identify and specify services within a service-oriented architecture. The methodology takes advantage of business modelling practices and provides a guide to service modelling with SoaML. The presentation is case-driven and illuminated using the telecommunication example. The chapter focuses in particular on the use of the SoaML modelling language as a means for expressing service specifications that are aligned with business models and can be realized in different platform technologies.

  3. Large Field Visualization with Demand-Driven Calculation

    Science.gov (United States)

    Moran, Patrick J.; Henze, Chris

    1999-01-01

    We present a system designed for the interactive definition and visualization of fields derived from large data sets: the Demand-Driven Visualizer (DDV). The system allows the user to write arbitrary expressions to define new fields, and then apply a variety of visualization techniques to the result. Expressions can include differential operators and numerous other built-in functions, ail of which are evaluated at specific field locations completely on demand. The payoff of following a demand-driven design philosophy throughout becomes particularly evident when working with large time-series data, where the costs of eager evaluation alternatives can be prohibitive.

  4. Constellations-driven innovation

    DEFF Research Database (Denmark)

    Hansbøl, Mikala

    2011-01-01

    The paper presents a science and technology studies and actor-network-theory inspired approach to understanding the development and ongoing re-didactication and re-design of a Danish developed presentation tool called the Theme Board (Tematavlen.dk). It is argued that this approach provides a par...... a particularly useful point of departure for engaging in researching innovation and didactic design of digital teaching and learning instruments such as the Theme Board that are programmed and serviced 'in the sky'. I call this approach: constellation-driven innovations....

  5. Laser-driven polarized sources of hydrogen and deuterium

    International Nuclear Information System (INIS)

    Young, L.; Holt, R.J.; Green, M.C.; Kowalczyk, R.S.

    1988-01-01

    A novel laser-driven polarized source of hydrogen and deuterium which operates on the principle of spin exchange optical pumping is described. The advantages of this method over conventional polarized sources for internal target experiments are presented. Technological difficulties which prevent ideal source operation are outlined along with proposed solutions. At present, the laser-driven polarized hydrogen source delivers 8 /times/ 10 16 atoms/s with a polarization (P/sub z/) of 24%. 9 refs., 2 figs

  6. Population death sequences and Cox processes driven by interacting Feller diffusions

    CERN Document Server

    Wei Gang; Feng Jian Feng

    2002-01-01

    We carry out a complete study on the relationship between Cox processes driven by interacting Feller diffusions and death sequences of immigration-emigration linked population networks. It is first proved that the Cox process driven by a Feller diffusion is equivalent to the death sequence of a birth and death process. The conclusion is then generalized to the case of Cox processes driven by interacting Feller diffusions and death sequences of interacting populations.

  7. Population death sequences and Cox processes driven by interacting Feller diffusions

    International Nuclear Information System (INIS)

    Wei Gang; Clifford, Peter; Feng Jianfeng

    2002-01-01

    We carry out a complete study on the relationship between Cox processes driven by interacting Feller diffusions and death sequences of immigration-emigration linked population networks. It is first proved that the Cox process driven by a Feller diffusion is equivalent to the death sequence of a birth and death process. The conclusion is then generalized to the case of Cox processes driven by interacting Feller diffusions and death sequences of interacting populations

  8. Population death sequences and Cox processes driven by interacting Feller diffusions

    Energy Technology Data Exchange (ETDEWEB)

    Wei Gang [Department of Mathematics, Baptist University, Hong Kong (China); Clifford, Peter [Department of Statistics, 1 South Parks Road, Oxford (United Kingdom); Feng Jianfeng [COGS, Sussex University, Brighton (United Kingdom)

    2002-11-08

    We carry out a complete study on the relationship between Cox processes driven by interacting Feller diffusions and death sequences of immigration-emigration linked population networks. It is first proved that the Cox process driven by a Feller diffusion is equivalent to the death sequence of a birth and death process. The conclusion is then generalized to the case of Cox processes driven by interacting Feller diffusions and death sequences of interacting populations.

  9. Sumoylation of IkB attenuates NF-kB-induced nitrosative stress at rostral ventrolateral medulla and cardiovascular depression in experimental brain death.

    Science.gov (United States)

    Tsai, Ching-Yi; Li, Faith C H; Wu, Carol H Y; Chang, Alice Y W; Chan, Samuel H H

    2016-09-22

    Small ubiquitin-related modifier (SUMO) is a group of proteins that participates in post-translational modifications. One known SUMO target is the transcription factor nuclear factor-kB (NF-kB) that plays a pivotal role in many disease processes; sumoylation inactivates NF-kB by conjugation with inhibitors of NF-kB (IkB). Our laboratory demonstrated previously that transcriptional upregulation of nitric oxide synthase II (NOS II) by NF-kB, leading to nitrosative stress by the formation of peroxynitrite in the rostral ventrolateral medulla (RVLM), underpins the defunct brain stem cardiovascular regulation that precedes brain death. Based on an experimental endotoxemia model, this study evaluated the hypothesis that sumoylation plays a pro-life role in brain death by interacting with the NF-kB/NOS II/peroxynitrite signaling pathway in the RVLM. In Sprague-Dawley rats, intravenous administration of Escherichia coli lipopolysaccharide (LPS; 10 mg kg -1 ) elicited an augmentation of SUMO-1 and ubiquitin-conjugase 9 (Ubc9) mRNA or protein levels, alongside SUMO-1-conjugated proteins in the RVLM. Immunoneutralization of SUMO-1 or Ubc9 in the RVLM significantly potentiated the already diminished sumoylation of IkBα and intensified NF-kB activation and NOS II/peroxynitrite expression in this brain stem substrate, together with exacerbated fatality, cardiovascular depression and reduction of an experimental index of a life-and-death signal detected from arterial pressure that disappears in comatose patients signifying failure of brain stem cardiovascular regulation before brain death. We conclude that sumoylation of IkB in the RVLM ameliorates the defunct brain stem cardiovascular regulation that underpins brain death in our experimental endotoxemia modal by reducing nitrosative stress via inhibition of IkB degradation that diminishes the induction of the NF-kB/NOS II/peroxynitrite signaling cascade.

  10. X-Ray-Driven Gamma Emission

    International Nuclear Information System (INIS)

    Carroll, J. J.; Karamian, S. A.; Rivlin, L. A.; Zadernovsky, A. A.

    2001-01-01

    X-ray-driven gamma emission describes processes that may release nuclear energy in a 'clean' way, as bursts of incoherent or coherent gamma rays without the production of radioactive by-products. Over the past decade, studies in this area, as a part of the larger field of quantum nucleonics, have gained tremendous momentum. Since 1987 it has been established that photons could trigger gamma emission from a long-lived metastable nuclear excited state of one nuclide and it appears likely that triggering in other isotopes will be demonstrated conclusively in the near future. With these experimental results have come new proposals for the creation of collective and avalanche-like incoherent gamma-ray bursts and even for the ultimate light source, a gamma-ray laser. Obviously, many applications would benefit from controlled bursts of gamma radiation, whether coherent or not. This paper reviews the experimental results and concepts for the production of gamma rays, driven by externally produced X-rays

  11. Transmutation of fission products in reactors and accelerator-driven systems

    International Nuclear Information System (INIS)

    Janssen, A.J.

    1994-01-01

    Energy flows and mass flows in several scenarios are considered. Economical and safety aspects of the transmutation scenarios are compared. It is difficult to find a sound motivation for the transmutation of fission products with accelerator-driven systems. If there would be any hesitation in transmuting fission products in nuclear reactors, there would be an even stronger hesitation to use accelerator-driven systems, mainly because of their lower energy efficiency and their poor cost effectiveness. The use of accelerator-driven systems could become a 'meaningful' option only if nuclear energy would be banished completely. (orig./HP)

  12. Analysis of a simple pendulum driven at its suspension point

    International Nuclear Information System (INIS)

    Yoshida, S; Findley, T

    2005-01-01

    To familiarize undergraduate students with the dynamics of a damped driven harmonic oscillator, a simple pendulum was set up and driven at its suspension point under different damping conditions. From the time domain analysis, the decay constant was estimated and used to predict the frequency response. The simple pendulum was then driven at a series of frequencies near the resonance. By measuring the maximum amplitude at each driving frequency, the frequency response was determined. With one free parameter, which was determined under the first damping condition, the predicted frequency responses showed good agreement with the measured frequency responses under all damping conditions

  13. Perceived Effectiveness of Community-driven Development ...

    African Journals Online (AJOL)

    Perceived Effectiveness of Community-driven Development Approach of Community and Social ... African Journal of Sustainable Development ... that CSDP in Oyo state be scaled up and the CDD approach be adopted for rural development.

  14. Thermochemical performance analysis of solar driven CO_2 methane reforming

    International Nuclear Information System (INIS)

    Fuqiang, Wang; Jianyu, Tan; Huijian, Jin; Yu, Leng

    2015-01-01

    Increasing CO_2 emission problems create urgent challenges for alleviating global warming, and the capture of CO_2 has become an essential field of scientific research. In this study, a finite volume method (FVM) coupled with thermochemical kinetics was developed to analyze the solar driven CO_2 methane reforming process in a metallic foam reactor. The local thermal non-equilibrium (LTNE) model coupled with radiative heat transfer was developed to provide more temperature information. A joint inversion method based on chemical process software and the FVM coupled with thermochemical kinetics was developed to obtain the thermochemical reaction parameters and guarantee the calculation accuracy. The detailed thermal and thermochemical performance in the metal foam reactor was analyzed. In addition, the effects of heat flux distribution and porosity on the solar driven CO_2 methane reforming process were analyzed. The numerical results can serve as theoretical guidance for the solar driven CO_2 methane reforming application. - Highlights: • Solar driven CO_2 methane reforming process in metal foam reactor is analyzed. • FVM with chemical reactions was developed to analyze solar CO_2 methane reforming. • A joint inversion method was developed to obtain thermochemical reaction parameters. • Results can be a guidance for the solar driven CO_2 methane reforming application.

  15. Numerical Study on Blast Wave Propagation Driven by Unsteady Ionization Plasma

    International Nuclear Information System (INIS)

    Ogino, Yousuke; Sawada, Keisuke; Ohnishi, Naofumi

    2008-01-01

    Understanding the dynamics of laser-produced plasma is essential for increasing the available thrust and energy conversion efficiency from a pulsed laser to a blast wave in a gas-driven laser-propulsion system. The performance of a gas-driven laser-propulsion system depends heavily on the laser-driven blast wave dynamics as well as on the ionizing and/or recombining plasma state that sustains the blast wave. In this study, we therefore develop a numerical simulation code for a laser-driven blast wave coupled with time-dependent rate equations to explore the formation of unsteady ionizing plasma produced by laser irradiation. We will also examine the various properties of blast waves and unsteady ionizing plasma for different laser input energies

  16. Typology of customer driven manufacturing

    NARCIS (Netherlands)

    Wortmann, J.C.; Wortmann, J.C.; Muntslag, D.R.; Timmermans, P.J.M.

    1997-01-01

    The aim of this chapter has been to introduce a variety of customer driven manufacturing situations. This variety has been placed in a two-dimensional grid, which constitutes a typology. For some of these types, production management issues were discussed in section 6.3. It was concluded that an

  17. High glucose modifies transient receptor potential canonical type 6 channels via increased oxidative stress and syndecan-4 in human podocytes

    DEFF Research Database (Denmark)

    Thilo, Florian; Lee, Marlene; Xia, Shengqiang

    2014-01-01

    oxidative stress and syndecan-4 (SDC-4) in human podocytes. Human podocytes were exposed to control conditions (5.6 mmol/L D-glucose), high glucose (30 mmol/L D-glucose or L-glucose), 100 μmol/L peroxynitrite, or high glucose and the superoxide dismutase mimetic tempol (100 μmol/L). TRPC6 and SDC-4...... transcripts and protein expression were measured using RT-PCR and in-cell Western assay. Intracellular reactive oxygen species (ROS) and cytosolic calcium were measured using fluorescent dye techniques. High D-glucose increased TRPC6 transcripts to 8.66±4.08 (p....44±0.07 (poxidative stress using peroxynitrite significantly increased TRPC6 transcripts to 4.29±1.26 (p

  18. Design Driven Innovation Practices in Design-preneur led Creative Industry

    Directory of Open Access Journals (Sweden)

    Philips Kembaren

    2014-09-01

    Full Text Available Design driven innovation has emerged to be an alternative way to generate sustainable competitive products or services. Previous research has recently revealed succesful practices of design driven innovation in various industries. However, little has been known about the creative companies that practice design driven innovation, especially in developing countries. This research investigates the existence and practices of design-driven innovation in the Indonesian creative industry. Based on interviews with the design-preneurs of the creative industry, one of the results of this study reveals how the Indonesian creative industry creates new meanings that are embedded into new products. Based on the identification, a framework to create new meaningsis resulted which consists of a set of key processes, such as sensing, sensemaking, specifying, setting up and storytelling. The practical contribution of this research is that this identified framework can be adopted by any creative companies interested in improving their innovation capability.

  19. A Business Ecosystem Driven Market Analysis

    DEFF Research Database (Denmark)

    Ma, Zheng; Billanes, Joy Dalmacio; Jørgensen, Bo Nørregaard

    2017-01-01

    Due to the huge globally emerging market of the bright green buildings, this paper aims to develop a business-ecosystem driven market analysis approach for the investigation of the bright green building market. This paper develops a five-steps business-ecosystem driven market analysis (definition...... of the business domain, stakeholder listing, integration of the value chain, relationship mapping, and ego innovation ecosystem mapping.). This paper finds the global-local matters influence the market structure, which the technologies for building energy technology are developed and employed globally......, and the market demand is comparatively localized. The market players can be both local and international stakeholders who involve and collaborate for the building projects. This paper also finds that the building extensibility should be considered into the building design due to the gap between current market...

  20. Defining and Supporting Narrative-driven Recommendation

    DEFF Research Database (Denmark)

    Bogers, Toine; Koolen, Marijn

    2017-01-01

    Research into recommendation algorithms has made great strides in recent years. However, these algorithms are typically applied in relatively straightforward scenarios: given information about a user's past preferences, what will they like in the future? Recommendation is often more complex......: evaluating recommended items never takes place in a vacuum, and it is often a single step in the user's more complex background task. In this paper, we define a specific type of recommendation scenario called narrative-driven recommendation, where the recommendation process is driven by both a log...... of the user's past transactions as well as a narrative description of their current interest(s). Through an analysis of a set of real-world recommendation narratives from the LibraryThing forums, we demonstrate the uniqueness and richness of this scenario and highlight common patterns and properties...

  1. Authoring Data-Driven Videos with DataClips.

    Science.gov (United States)

    Amini, Fereshteh; Riche, Nathalie Henry; Lee, Bongshin; Monroy-Hernandez, Andres; Irani, Pourang

    2017-01-01

    Data videos, or short data-driven motion graphics, are an increasingly popular medium for storytelling. However, creating data videos is difficult as it involves pulling together a unique combination of skills. We introduce DataClips, an authoring tool aimed at lowering the barriers to crafting data videos. DataClips allows non-experts to assemble data-driven "clips" together to form longer sequences. We constructed the library of data clips by analyzing the composition of over 70 data videos produced by reputable sources such as The New York Times and The Guardian. We demonstrate that DataClips can reproduce over 90% of our data videos corpus. We also report on a qualitative study comparing the authoring process and outcome achieved by (1) non-experts using DataClips, and (2) experts using Adobe Illustrator and After Effects to create data-driven clips. Results indicated that non-experts are able to learn and use DataClips with a short training period. In the span of one hour, they were able to produce more videos than experts using a professional editing tool, and their clips were rated similarly by an independent audience.

  2. Phase transformations and systems driven far from equilibrium

    International Nuclear Information System (INIS)

    Ma, E.; Atzmon, M.; Bellon, P.; Trivedi, R.

    1998-01-01

    This volume compiles invited and contributed papers that were presented at Symposium B of the 1997 Materials Research Society Fall Meeting, Phase Transformations and Systems Driven Far From Equilibrium, which was held December 1--5, in Boston, Massachusetts. While this symposium followed the tradition of previous MRS symposia on the fundamental topic of phase transformations, this year the emphasis was on materials systems driven far from equilibrium. The central theme of the majority of the work presented is the understanding of the thermodynamics and kinetics of phase transformations, with significant coverage of metastable materials and externally forced transformations driven, for example, by energy beams or mechanical deformation. The papers are arranged in seven sections: solidification theory and experiments; nucleation; solid state transformations and microstructural evolution; beam-induced transformations; amorphous solids; interfacial and thin film transformations; and nanophases and mechanical alloying. One hundred three papers have been processed separately for inclusion on the data base

  3. Keldysh field theory for driven open quantum systems.

    Science.gov (United States)

    Sieberer, L M; Buchhold, M; Diehl, S

    2016-09-01

    Recent experimental developments in diverse areas-ranging from cold atomic gases to light-driven semiconductors to microcavity arrays-move systems into the focus which are located on the interface of quantum optics, many-body physics and statistical mechanics. They share in common that coherent and driven-dissipative quantum dynamics occur on an equal footing, creating genuine non-equilibrium scenarios without immediate counterpart in equilibrium condensed matter physics. This concerns both their non-thermal stationary states and their many-body time evolution. It is a challenge to theory to identify novel instances of universal emergent macroscopic phenomena, which are tied unambiguously and in an observable way to the microscopic drive conditions. In this review, we discuss some recent results in this direction. Moreover, we provide a systematic introduction to the open system Keldysh functional integral approach, which is the proper technical tool to accomplish a merger of quantum optics and many-body physics, and leverages the power of modern quantum field theory to driven open quantum systems.

  4. Performance-Driven Interface Contract Enforcement for Scientific Components

    Energy Technology Data Exchange (ETDEWEB)

    Dahlgren, Tamara Lynn [Univ. of California, Davis, CA (United States)

    2008-01-01

    Performance-driven interface contract enforcement research aims to improve the quality of programs built from plug-and-play scientific components. Interface contracts make the obligations on the caller and all implementations of the specified methods explicit. Runtime contract enforcement is a well-known technique for enhancing testing and debugging. However, checking all of the associated constraints during deployment is generally considered too costly from a performance stand point. Previous solutions enforced subsets of constraints without explicit consideration of their performance implications. Hence, this research measures the impacts of different interface contract sampling strategies and compares results with new techniques driven by execution time estimates. Results from three studies indicate automatically adjusting the level of checking based on performance constraints improves the likelihood of detecting contract violations under certain circumstances. Specifically, performance-driven enforcement is better suited to programs exercising constraints whose costs are at most moderately expensive relative to normal program execution.

  5. Peroxynitrite-mediated oxidation of plasma fibronectin

    DEFF Research Database (Denmark)

    Degendorfer, Georg; Chuang, Christine Y; Kawasaki, Hiroaki

    2016-01-01

    Fibronectin is a large dimeric glycoprotein present in both human plasma and in basement membranes. The latter are specialized extracellular matrices underlying endothelial cells in the artery wall. Peroxynitrous acid (ONOOH) a potent oxidizing and nitrating agent, is formed in vivo from superoxide...... and nitric oxide radicals by stimulated macrophages and other cells. Considerable evidence supports ONOOH involvement in human atherosclerotic lesion development and rupture, possibly via extracellular matrix damage. Here we demonstrate that Tyr and Trp residues on human plasma fibronectin are highly...

  6. Statistical Transmutation in Floquet Driven Optical Lattices.

    Science.gov (United States)

    Sedrakyan, Tigran A; Galitski, Victor M; Kamenev, Alex

    2015-11-06

    We show that interacting bosons in a periodically driven two dimensional (2D) optical lattice may effectively exhibit fermionic statistics. The phenomenon is similar to the celebrated Tonks-Girardeau regime in 1D. The Floquet band of a driven lattice develops the moat shape, i.e., a minimum along a closed contour in the Brillouin zone. Such degeneracy of the kinetic energy favors fermionic quasiparticles. The statistical transmutation is achieved by the Chern-Simons flux attachment similar to the fractional quantum Hall case. We show that the velocity distribution of the released bosons is a sensitive probe of the fermionic nature of their stationary Floquet state.

  7. Periodically Driven Array of Single Rydberg Atoms

    Science.gov (United States)

    Basak, Sagarika; Chougale, Yashwant; Nath, Rejish

    2018-03-01

    An array of single Rydberg atoms driven by a temporally modulated atom-field detuning is studied. The periodic modulation effectively modifies the Rabi coupling, leading to unprecedented dynamics in the presence of Rydberg-Rydberg interactions, in particular, blockade enhancement, antiblockades, and state-dependent population trapping. Interestingly, the Schrieffer-Wolf transformation reveals a fundamental process in Rydberg gases, correlated Rabi coupling, which stems from the extended nature of the Rydberg-Rydberg interactions. Also, the correlated coupling provides an alternative depiction for the Rydberg blockade, exhibiting a nontrivial behavior in the presence of periodic modulation. The dynamical localization of a many-body configuration in a driven Rydberg lattice is discussed.

  8. The User-Driven Creative Academy

    DEFF Research Database (Denmark)

    Nielsen, Louise Møller; Poulsen, Søren Bolvig

    2016-01-01

    Users have always been a point of focus in design, but in the beginning of the new millennium userdriven approaches and user-oriented projects were taken to a new level of recognition. As part of this development, the User Driven Creative Academy (U-CrAc) was created at Aalborg University...

  9. Managing Innovation Probabilities: Core-driven vs. Bottleneck-removing Innovations

    OpenAIRE

    Tsutomu Harada

    2015-01-01

    This paper provides a simplified framework of focusing devices that generate different patterns of innovation, i.e., core-driven and bottleneck-removing innovations, and discusses the managerial implications. We show that core-driven innovation should be undertaken when technology components are independent (independent technology system), while bottleneck-removing innovation should be pursued when they are interdependent (interdependent technology system). Different types of focusing device ...

  10. Antioxidant potential of Aesculus hippocastanum extract and escin against reactive oxygen and nitrogen species.

    Science.gov (United States)

    Vašková, J; Fejerčáková, A; Mojžišová, G; Vaško, L; Patlevič, P

    2015-01-01

    Antioxidant, anti-inflammatory and venoconstrictor properties have been attributed to extracts from Aesculus hippocastanum. These unusual and diverse properties may be possibly basically linked with ability to scavenge free radicals. The scavenging capacity of dry horse chestnut extract of and escin have been investigated in vitro against superoxide anion radicals, hydroxyl radicals, nitrites and peroxynitrite. In general, the activity of the whole extract against superoxide radicals did not exceed 15% at pH 7.4, but the highest inhibition (46.11%) was recorded against hydroxyl radicals at a concentration of 100 µg.ml-1; however, the activity against other radicals was lower. Escin demonstrated a better ability to counteract nitric oxide oxidation products, nitrites. However, the efficiency of the whole extract completely disappeared as the concentration increased. Both extracts showed very low activity towards peroxynitrite. Escin was even able to induce peroxynitrite formation at the lower concentrations used. Whole extract showed better antiradical properties compared to its main active ingredient, escin, probably due to potential synergistic interaction with a mixture of compounds present in the plant extract. These findings can be the basis of both the presentation of side-effects and the persistence of disease in spite of ongoing treatment.

  11. Role of nitric oxide and superoxide in Giardia lamblia killing

    Directory of Open Access Journals (Sweden)

    P.D. Fernandes

    1997-01-01

    Full Text Available Giardia lamblia trophozoites were incubated for 2 h with activated murine macrophages, nitric oxide (NO donors or a superoxide anion generator (20 mU/ml xanthine oxidase plus 1 mM xanthine. Activated macrophages were cytotoxic to Giardia trophozoites (~60% dead trophozoites. This effect was inhibited (>90% by an NO synthase inhibitor (200 µM and unaffected by superoxide dismutase (SOD, 300 U/ml. Giardia trophozoites were killed by the NO donors, S-nitroso-acetyl-penicillamine (SNAP and sodium nitroprusside (SNP in a dose-dependent manner (LD50 300 and 50 µM, respectively. A dual NO-superoxide anion donor, 3-morpholino-sydnonimine hydrochloride (SIN-1, did not have a killing effect in concentrations up to 1 mM. However, when SOD (300 U/ml was added simultaneously with SIN-1 to Giardia, a significant trophozoite-killing effect was observed (~35% dead trophozoites at 1 mM. The mixture of SNAP or SNP with superoxide anion, which yields peroxynitrite, abolished the trophozoite killing induced by NO donors. Authentic peroxynitrite only killed trophozoites at very high concentrations (3 mM. These results indicate that NO accounts for Giardia trophozoite killing and this effect is not mediated by peroxynitrite

  12. Concurrent targeting of nitrosative stress-PARP pathway corrects functional, behavioral and biochemical deficits in experimental diabetic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Negi, Geeta; Kumar, Ashutosh [Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062 (India); Sharma, Shyam S., E-mail: sssharma@niper.ac.in [Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062 (India)

    2010-01-01

    Peroxynitrite mediated nitrosative stress, an indisputable initiator of DNA damage and overactivation of poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated after sensing DNA damage, are two crucial pathogenetic mechanisms in diabetic neuropathy. The intent of the present study was to investigate the effect of combination of a peroxynitrite decomposition catalyst (PDC), FeTMPyP and a PARP inhibitor, 4-ANI against diabetic peripheral neuropathy. The end points of evaluation of the study included motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) for evaluating nerve functions; thermal hyperalgesia and mechanical allodynia for assessing nociceptive alterations, malondialdehyde and peroxynitrite levels to detect oxidative stress-nitrosative stress; NAD concentration in sciatic nerve to assess overactivation of PARP. Additionally immunohistochemical studies for nitrotyrosine and Poly(ADP-ribose) (PAR) was also performed. Treatment with the combination of FeTMPyP and 4-ANI led to significant improvement in nerve functions and pain parameters and also attenuated the oxidative-nitrosative stress markers. Further, the combination also reduced the overactivation of PARP as evident from increased NAD levels and decreased PAR immunopositivity in sciatic nerve microsections. Thus, it can be concluded that treatment with the combination of a PDC and PARP inhibitor attenuates alteration in peripheral nerves in diabetic neuropathy (DN).

  13. Mixed signals: The effect of conflicting reward- and goal-driven biases on selective attention.

    Science.gov (United States)

    Preciado, Daniel; Munneke, Jaap; Theeuwes, Jan

    2017-07-01

    Attentional selection depends on the interaction between exogenous (stimulus-driven), endogenous (goal-driven), and selection history (experience-driven) factors. While endogenous and exogenous biases have been widely investigated, less is known about their interplay with value-driven attention. The present study investigated the interaction between reward-history and goal-driven biases on perceptual sensitivity (d') and response time (RT) in a modified cueing paradigm presenting two coloured cues, followed by sinusoidal gratings. Participants responded to the orientation of one of these gratings. In Experiment 1, one cue signalled reward availability but was otherwise task irrelevant. In Experiment 2, the same cue signalled reward, and indicated the target's most likely location at the opposite side of the display. This design introduced a conflict between reward-driven biases attracting attention and goal-driven biases directing it away. Attentional effects were examined comparing trials in which cue and target appeared at the same versus opposite locations. Two interstimulus interval (ISI) levels were used to probe the time course of attentional effects. Experiment 1 showed performance benefits at the location of the reward-signalling cue and costs at the opposite for both ISIs, indicating value-driven capture. Experiment 2 showed performance benefits only for the long ISI when the target was at the opposite to the reward-associated cue. At the short ISI, only performance costs were observed. These results reveal the time course of these biases, indicating that reward-driven effects influence attention early but can be overcome later by goal-driven control. This suggests that reward-driven biases are integrated as attentional priorities, just as exogenous and endogenous factors.

  14. International conference on sub-critical accelerator driven systems. Proceedings

    International Nuclear Information System (INIS)

    Litovkina, L.P.; Titarenko, Yu.E.

    1999-01-01

    The International Meeting on Sub-Critical Accelerator Driven Systems was organized by the State Scientific Center - Institute for Theoretical and Experimental Physics with participation of Atomic Ministry of RF. The Meeting objective was to analyze the recent achievements and tendencies of the accelerator-driven systems development. The Meeting program covers a broad range of problems including the accelerator-driven systems (ADS) conceptual design; analyzing the ADS role in nuclear fuel cycle; accuracy of modeling the main parameters of ADS; conceptual design of high-current accelerators. Moreover, the results of recent experimental and theoretical studies on nuclear data accumulation to support the ADS technologies are presented. About 70 scientists from the main scientific centers of Russia, as well as scientists from USA, France, Belgium, India, and Yugoslavia, attended the meeting and presented 44 works [ru

  15. Managing business compliance using model-driven security management

    Science.gov (United States)

    Lang, Ulrich; Schreiner, Rudolf

    Compliance with regulatory and governance standards is rapidly becoming one of the hot topics of information security today. This is because, especially with regulatory compliance, both business and government have to expect large financial and reputational losses if compliance cannot be ensured and demonstrated. One major difficulty of implementing such regulations is caused the fact that they are captured at a high level of abstraction that is business-centric and not IT centric. This means that the abstract intent needs to be translated in a trustworthy, traceable way into compliance and security policies that the IT security infrastructure can enforce. Carrying out this mapping process manually is time consuming, maintenance-intensive, costly, and error-prone. Compliance monitoring is also critical in order to be able to demonstrate compliance at any given point in time. The problem is further complicated because of the need for business-driven IT agility, where IT policies and enforcement can change frequently, e.g. Business Process Modelling (BPM) driven Service Oriented Architecture (SOA). Model Driven Security (MDS) is an innovative technology approach that can solve these problems as an extension of identity and access management (IAM) and authorization management (also called entitlement management). In this paper we will illustrate the theory behind Model Driven Security for compliance, provide an improved and extended architecture, as well as a case study in the healthcare industry using our OpenPMF 2.0 technology.

  16. Progress and prospects of ion-driven fast ignition

    International Nuclear Information System (INIS)

    Fernandez, Juan C.; Albright, Brian J.; Flippo, Kirk A.; Gautier, D. Cort; Hegelich, Bjoern M.; Schmitt, Mark J.; Yin Lin; Honrubia, J.J.; Temporal, M.

    2009-01-01

    Fusion fast ignition (FI) initiated by laser-driven ion beams is a promising concept examined in this paper. FI based on a beam of quasi-monoenergetic ions (protons or heavier ions) has the advantage of a more localized energy deposition, which minimizes the required total beam energy, bringing it close to the ∼10 kJ minimum required for fuel densities ∼500 g cm -3 . High-current, laser-driven ion beams are most promising for this purpose. Because they are born neutralized in picosecond timescales, these beams may deliver the power density required to ignite the compressed DT fuel, ∼10 kJ/10 ps into a spot 20 μm in diameter. Our modelling of ion-based FI include high fusion gain targets and a proof of principle experiment. That modelling indicates the concept is feasible, and provides confirmation of our understanding of the operative physics, a firmer foundation for the requirements, and a better understanding of the optimization trade space. An important benefit of the scheme is that such a high-energy, quasi-monoenergetic ignitor beam could be generated far from the capsule (≥1 cm away), eliminating the need for a reentrant cone in the capsule to protect the ion-generation laser target, a tremendous practical benefit. This paper summarizes the ion-based FI concept, the integrated ion-driven FI modelling, the requirements on the ignitor beam derived from that modelling, and the progress in developing a suitable laser-driven ignitor ion beam.

  17. Ion-temperature-gradient-driven modes in bi-ion magnetoplasma

    Energy Technology Data Exchange (ETDEWEB)

    Batool, Nazia; Mirza, Arshad M [Theoretical Plasma Physics Group, Department of Physics, Quaid-i-Azam University, Islamabad 45320 (Pakistan); Qamar, Anisa [Department of Physics, Peshawar University, NWFP 25120 (Pakistan)], E-mail: nazia.batool@ncp.edu.pk

    2008-12-15

    The toroidal ion-temperature-gradient (ITG)-driven electrostatic drift waves are investigated for bi-ion plasmas with equilibrium density, temperature and magnetic field gradients. Using Braginskii's transport equations for the ions and Boltzmann distributed electrons, the mode coupling equations are derived. New ITG-driven modes are shown to exist. The results of the present study should be helpful to understand several wave phenomena in space and tokamak plasmas.

  18. Driven Quantum Dynamics: Will It Blend?

    Directory of Open Access Journals (Sweden)

    Leonardo Banchi

    2017-10-01

    Full Text Available Randomness is an essential tool in many disciplines of modern sciences, such as cryptography, black hole physics, random matrix theory, and Monte Carlo sampling. In quantum systems, random operations can be obtained via random circuits thanks to so-called q-designs and play a central role in condensed-matter physics and in the fast scrambling conjecture for black holes. Here, we consider a more physically motivated way of generating random evolutions by exploiting the many-body dynamics of a quantum system driven with stochastic external pulses. We combine techniques from quantum control, open quantum systems, and exactly solvable models (via the Bethe ansatz to generate Haar-uniform random operations in driven many-body systems. We show that any fully controllable system converges to a unitary q-design in the long-time limit. Moreover, we study the convergence time of a driven spin chain by mapping its random evolution into a semigroup with an integrable Liouvillian and finding its gap. Remarkably, we find via Bethe-ansatz techniques that the gap is independent of q. We use mean-field techniques to argue that this property may be typical for other controllable systems, although we explicitly construct counterexamples via symmetry-breaking arguments to show that this is not always the case. Our findings open up new physical methods to transform classical randomness into quantum randomness, via a combination of quantum many-body dynamics and random driving.

  19. Wind driven mobile charging of automobile battery- A case study ...

    African Journals Online (AJOL)

    This paper deals with implementation of mobile wind driven generator technology to produce electricity in charging of two wheeler (12V) automobile battery. The use of PWM methodology with pulse charging method at a constant rate has been adopted for this purpose. The low speed PMSG driven by wind at speed of ...

  20. Patterns, principles, and practices of domain-driven design

    CERN Document Server

    Millett, Scott

    2015-01-01

    Methods for managing complex software construction following the practices, principles and patterns of Domain-Driven Design with code examples in C# This book presents the philosophy of Domain-Driven Design (DDD) in a down-to-earth and practical manner for experienced developers building applications for complex domains. A focus is placed on the principles and practices of decomposing a complex problem space as well as the implementation patterns and best practices for shaping a maintainable solution space. You will learn how to build effective domain models through the use of tactical pat

  1. Laser-driven acceleration with Bessel beam

    International Nuclear Information System (INIS)

    Imasaki, Kazuo; Li, Dazhi

    2005-01-01

    A new approach of laser-driven acceleration with Bessel beam is described. Bessel beam, in contrast to the Gaussian beam, shows diffraction-free'' characteristics in its propagation, which implies potential in laser-driven acceleration. But a normal laser, even if the Bessel beam, laser can not accelerate charged particle efficiently because the difference of velocity between the particle and photon makes cyclic acceleration and deceleration phase. We proposed a Bessel beam truncated by a set of annular slits those makes several special regions in its travelling path, where the laser field becomes very weak and the accelerated particles are possible to receive no deceleration as they undergo decelerating phase. Thus, multistage acceleration is realizable with high gradient. In a numerical computation, we have shown the potential of multistage acceleration based on a three-stage model. (author)

  2. Challenges of Data-driven Healthcare Management

    DEFF Research Database (Denmark)

    Bossen, Claus; Danholt, Peter; Ubbesen, Morten Bonde

    This paper describes the new kind of data-work involved in developing data-driven healthcare based on two cases from Denmark: The first case concerns a governance infrastructure based on Diagnose-Related Groups (DRG), which was introduced in Denmark in the 1990s. The DRG-system links healthcare...... activity and financing and relies of extensive data entry, reporting and calculations. This has required the development of new skills, work and work roles. The second case concerns a New Governance project aimed at developing new performance indicators for healthcare delivery as an alternative to DRG....... Here, a core challenge is select indicators and actually being able to acquire data upon them. The two cases point out that data-driven healthcare requires more and new kinds of work for which new skills, functions and work roles have to be developed....

  3. Source driven breeding thermal power reactors

    International Nuclear Information System (INIS)

    Greenspan, E.; Schneider, A.; Misulovin, A.; Gilai, D.; Levin, P.; Ben-Gurion Univ. of the Negev, Beersheba

    1978-03-01

    Improvements in the performance of fission power reactors made possible by designing them subcritical driven by D-T neutron sources are investigated. Light-water thermal systems are found to be most promising, neutronically and energetically, for the source driven mode of operation. The range of performance characteristics expected from breeding Light Water Hybrid Reactors (LWHR) is defined. Several promising types of LWHR blankets are identified. Options opened for the nuclear energy strategy by four types of the LWHRs are examined, and the potential contribution of these LWHRs to the nuclear energy economy are discussed. The power systems based on these LWHRs are found to enable a high utilization of the energy content of the uranium resources in all forms available - including depleted uranium and spent fuel from LWRs, while being free from the need for uranium enrichment and plutonium separation capabilities. (author)

  4. Light-driven robotics for nanoscopy

    DEFF Research Database (Denmark)

    Glückstad, Jesper; Palima, Darwin

    2013-01-01

    The science fiction inspired shrinking of macro-scale robotic manipulation and handling down to the micro- and nanoscale regime opens new doors for exploiting the forces and torques of light for micro- and nanoscopic probing, actuation and control. Advancing light-driven micro-robotics requires...... and matter for robotically probing at the smallest biological length scales....

  5. Working memory-driven attention improves spatial resolution: Support for perceptual enhancement.

    Science.gov (United States)

    Pan, Yi; Luo, Qianying; Cheng, Min

    2016-08-01

    Previous research has indicated that attention can be biased toward those stimuli matching the contents of working memory and thereby facilitates visual processing at the location of the memory-matching stimuli. However, whether this working memory-driven attentional modulation takes place on early perceptual processes remains unclear. Our present results showed that working memory-driven attention improved identification of a brief Landolt target presented alone in the visual field. Because the suprathreshold target appeared without any external noise added (i.e., no distractors or masks), the results suggest that working memory-driven attention enhances the target signal at early perceptual stages of visual processing. Furthermore, given that performance in the Landolt target identification task indexes spatial resolution, this attentional facilitation indicates that working memory-driven attention can boost early perceptual processing via enhancement of spatial resolution at the attended location.

  6. Accelerator-driven X-ray Sources

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Dinh Cong [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-11-09

    After an introduction which mentions x-ray tubes and storage rings and gives a brief review of special relativity, the subject is treated under the following topics and subtopics: synchrotron radiation (bending magnet radiation, wiggler radiation, undulator radiation, brightness and brilliance definition, synchrotron radiation facilities), x-ray free-electron lasers (linac-driven X-ray FEL, FEL interactions, self-amplified spontaneous emission (SASE), SASE self-seeding, fourth-generation light source facilities), and other X-ray sources (energy recovery linacs, Inverse Compton scattering, laser wakefield accelerator driven X-ray sources. In summary, accelerator-based light sources cover the entire electromagnetic spectrum. Synchrotron radiation (bending magnet, wiggler and undulator radiation) has unique properties that can be tailored to the users’ needs: bending magnet and wiggler radiation is broadband, undulator radiation has narrow spectral lines. X-ray FELs are the brightest coherent X-ray sources with high photon flux, femtosecond pulses, full transverse coherence, partial temporal coherence (SASE), and narrow spectral lines with seeding techniques. New developments in electron accelerators and radiation production can potentially lead to more compact sources of coherent X-rays.

  7. Quantum correlations and limit cycles in the driven-dissipative Heisenberg lattice

    Science.gov (United States)

    Owen, E. T.; Jin, J.; Rossini, D.; Fazio, R.; Hartmann, M. J.

    2018-04-01

    Driven-dissipative quantum many-body systems have attracted increasing interest in recent years as they lead to novel classes of quantum many-body phenomena. In particular, mean-field calculations predict limit cycle phases, slow oscillations instead of stationary states, in the long-time limit for a number of driven-dissipative quantum many-body systems. Using a cluster mean-field and a self-consistent Mori projector approach, we explore the persistence of such limit cycles as short range quantum correlations are taken into account in a driven-dissipative Heisenberg model.

  8. Concept evaluation of nuclear fusion driven symbiotic energy systems

    International Nuclear Information System (INIS)

    Renier, J.P.; Hoffman, T.J.

    1979-01-01

    This paper analyzes systems based on D-T and semi-catalyzed D-D fusion-powered U233 breeders. Two different blanket types were used: metallic thorium pebble-bed blankets with a batch reprocessing mode and a molten salt blanket with on-line continuous or batch reprocessing. All fusion-driven blankets are assumed to have spherical geometries, with a 85% closure. Neutronics depletion calculations were performed with a revised version of the discrete ordinates code XSDRN-PM, using multigroup (100 neutron, 21 gamma-ray groups) coupled cross-section libraries. These neutronics calculations are coupled with a scenario optimization and cost analysis code. Also, the fusion burn was shaped so as to keep the blanket maximum power density below a preset value, and to improve the performance of the fusion-driven systems. The fusion-driven symbiotes are compared with LMFBR-driven energy systems. The nuclear fission breeders that were used as drivers have parameters characteristic of heterogeneous, oxide LMFBRs. They are net plutonium users - the plutonium is obtained from the discharges of LWRs - and U233 is bred in the fission breeder thorium blankets. The analyses of the symbiotic energy systems were performed at equilibrium, at maximum rate of grid expansion, and for a given nuclear power demand

  9. Investigation toward laser driven IFE power plant

    International Nuclear Information System (INIS)

    Nakai, S.; Kozaki, Y.; Izawa, Y.

    2001-01-01

    Inertial fusion energy (IFE) is becoming feasible due to the increasing understanding of implosion physics. Reactor technology issues have begun to be developed. Based on the conceptual design of Laser Driven IFE Power Plant, the technical and physical issues have been examined. R and D on key issues that affect the feasibility of power plant have been proceeded taking into account the collaboration in the field of laser driver, fuel pellet, reaction chamber and system design. It is concluded that the technical feasibility of IFE power plant seems to be reasonably high. Coordination and collaboration scheme of reactor technology experts in Japan on Laser Driven IFE Power Plant is being proceeded. (author)

  10. User Driven Innovation in the Building Process

    DEFF Research Database (Denmark)

    Christiansson, Per; Sørensen, Kristian Birch; Rødtness, Mette

    2008-01-01

    During the late years there has been an ever-increasing focus on the possibilities to change the building process to raise quality on the final building products as well as the activities of actors involved in the building process. One reason for this interest is the new opportunities evolving du...... building design. A general methodological framework and meta ontology for Virtual Innovation in Construction is presented as well as findings from implementation of the method....... to introduction of advanced information and communication technology (ICT). The paper focuses on creative changes of the building process powered by user driven innovation activities. An overview of existing user driven innovation methodologies is given as well experiences from the ongoing Virtual Innovation...

  11. Theory of ion-temperature-gradient-driven turbulence in tokamaks

    International Nuclear Information System (INIS)

    Lee, G.S.; Diamond, P.H.

    1986-01-01

    An analytic theory of ion-temperature-gradient-driven turbulence in tokamaks is presented. Energy-conserving, renormalized spectrum equations are derived and solved in order to obtain the spectra of stationary ion-temperature-gradient-driven turbulence. Corrections to mixing-length estimates are calculated explicitly. The resulting anomalous ion thermal diffusivity chi/sub i/ = 0.4[(π/2)ln(1 + eta/sub i/)] 2 [(1 + eta/sub i/)/tau] 2 rho/sub s/ 2 c/sub s//L/sub s/ is derived and is found to be consistent with experimentally-deduced thermal diffusivities. The associated electron thermal diffusivity and particle and heat-pinch velocities are also calculated. The effect of impurity gradients on saturated ion-temperature-gradient-driven turbulence is discussed and a related explanation of density profile steepening during Z-mode operation is proposed. 35 refs., 4 figs

  12. Interfacial waves generated by electrowetting-driven contact line motion

    Science.gov (United States)

    Ha, Jonghyun; Park, Jaebum; Kim, Yunhee; Shin, Bongsu; Bae, Jungmok; Kim, Ho-Young

    2016-10-01

    The contact angle of a liquid-fluid interface can be effectively modulated by the electrowetting-on-dielectric (EWOD) technology. Rapid movement of the contact line can be achieved by swift changes of voltage at the electrodes, which can give rise to interfacial waves under the strong influence of surface tension. Here we experimentally demonstrate EWOD-driven interfacial waves of overlapping liquids and compare their wavelength and decay length with the theoretical results obtained by a perturbation analysis. Our theory also allows us to predict the temporal evolution of the interfacial profiles in either rectangular or cylindrical containers, as driven by slipping contact lines. This work builds a theoretical framework to understand and predict the dynamics of capillary waves of a liquid-liquid interface driven by EWOD, which has practical implications on optofluidic devices used to guide light.

  13. A hot air driven thermoacoustic-Stirling engine

    Energy Technology Data Exchange (ETDEWEB)

    Tijani, M.E.H.; Spoelstra, S. [ECN Biomass and Energy Efficiency, Petten (Netherlands)

    2012-09-15

    Significant energy savings can be obtained by implementing a thermally driven heat pump into industrial or domestic applications. Such a thermally driven heat pump uses heat from a high-temperature source to drive the system which upgrades an abundantly available heat source (industrial waste heat, air, water, geothermal). A way to do this is by coupling a thermoacoustic engine with a thermoacoustic heat pump. The engine is driven by a burner and produces acoustic power and heat at the required temperature. The acoustic power is used to pump heat in the heat pump to the required temperature. This system is attractive since it uses a noble gas as working medium and has no moving mechanical parts. This paper deals with the first part of this system: the engine. In this study, hot air is used to simulate the flue gases originating from a gas burner. This is in contrast with a lot of other studies of thermoacoustic engines that use an electrical heater as heat source. Using hot air resembles to a larger extent the real world application. The engine produces about 300W of acoustic power with a performance of 41% of the Carnot efficiency at a hot air temperature of 620C.

  14. PC driven integrated vacuum system

    International Nuclear Information System (INIS)

    Curuia, M.; Culcer, M.; Brandea, I.; Anghel, M.

    2001-01-01

    The paper presents a integrated vacuum system which was designed and manufactured in our institute. The main parts of this system are the power supply unit for turbo-melecular pumps and the vacuummeter. Both parts of the system are driven by means of a personal computer using a serial communication, according to the RS 232 hardware standard.(author)

  15. Privacy driven internet ecosystem

    OpenAIRE

    Trinh, Tuan Anh; Gyarmati, Laszlo

    2012-01-01

    The dominant business model of today's Internet is built upon advertisements; users can access Internet services while the providers show ads to them. Although significant efforts have been made to model and analyze the economic aspects of this ecosystem, the heart of the current status quo, namely privacy, has not received the attention of the research community yet. Accordingly, we propose an economic model of the privacy driven Internet ecosystem where privacy is handled as an asset that c...

  16. Biomarkers derived from heterolytic and homolytic cleavage of allylic hydroperoxides resulting from alkenone autoxidation

    Digital Repository Service at National Institute of Oceanography (India)

    Rontania, J.F.; Harji, R.; Volkmanc, J.K.

    Laboratory incubation of alkenone mixtures with tert-butyl hydroperoxide and di-tert-butyl nitroxide (radical initiator) in hexane, as a means to simulate alkenone autoxidation processes, rapidly led to the formation of allylic hydroperoxides, whose...

  17. Data Driven Constraints for the SVM

    DEFF Research Database (Denmark)

    Darkner, Sune; Clemmensen, Line Katrine Harder

    2012-01-01

    We propose a generalized data driven constraint for support vector machines exemplified by classification of paired observations in general and specifically on the human ear canal. This is particularly interesting in dynamic cases such as tissue movement or pathologies developing over time. Assum...

  18. Making a case for a development-driven approach to law as a ...

    African Journals Online (AJOL)

    driven approach to law as a linchpin for the post-2015 development agenda. KEYWORDS: Law, development, development-driven law, development law, development goals, development strategy, Millennium Development Goals, Millennium ...

  19. Flux-driven simulations of turbulence collapse

    Energy Technology Data Exchange (ETDEWEB)

    Park, G. Y.; Kim, S. S.; Jhang, Hogun; Rhee, T. [National Fusion Research Institute, Daejeon 305-333 (Korea, Republic of); Diamond, P. H. [National Fusion Research Institute, Daejeon 305-333 (Korea, Republic of); CASS and Department of Physics, University of California, San Diego, La Jolla, California 92093-0429 (United States); Xu, X. Q. [Lawrence Livermore National Laboratory, Livermore, California 94551 (United States)

    2015-03-15

    Using three-dimensional nonlinear simulations of tokamak turbulence, we show that an edge transport barrier (ETB) forms naturally once input power exceeds a threshold value. Profiles, turbulence-driven flows, and neoclassical coefficients are evolved self-consistently. A slow power ramp-up simulation shows that ETB transition is triggered by the turbulence-driven flows via an intermediate phase which involves coherent oscillation of turbulence intensity and E×B flow shear. A novel observation of the evolution is that the turbulence collapses and the ETB transition begins when R{sub T} > 1 at t = t{sub R} (R{sub T}: normalized Reynolds power), while the conventional transition criterion (ω{sub E×B}>γ{sub lin} where ω{sub E×B} denotes mean flow shear) is satisfied only after t = t{sub C} ( >t{sub R}), when the mean flow shear grows due to positive feedback.

  20. Surface-Plasmon-Driven Hot Electron Photochemistry.

    Science.gov (United States)

    Zhang, Yuchao; He, Shuai; Guo, Wenxiao; Hu, Yue; Huang, Jiawei; Mulcahy, Justin R; Wei, Wei David

    2017-11-30

    Visible-light-driven photochemistry has continued to attract heightened interest due to its capacity to efficiently harvest solar energy and its potential to solve the global energy crisis. Plasmonic nanostructures boast broadly tunable optical properties coupled with catalytically active surfaces that offer a unique opportunity for solar photochemistry. Resonant optical excitation of surface plasmons produces energetic hot electrons that can be collected to facilitate chemical reactions. This review sums up recent theoretical and experimental approaches for understanding the underlying photophysical processes in hot electron generation and discusses various electron-transfer models on both plasmonic metal nanostructures and plasmonic metal/semiconductor heterostructures. Following that are highlights of recent examples of plasmon-driven hot electron photochemical reactions within the context of both cases. The review concludes with a discussion about the remaining challenges in the field and future opportunities for addressing the low reaction efficiencies in hot-electron-induced photochemistry.

  1. Vlasov dynamics of periodically driven systems

    Science.gov (United States)

    Banerjee, Soumyadip; Shah, Kushal

    2018-04-01

    Analytical solutions of the Vlasov equation for periodically driven systems are of importance in several areas of plasma physics and dynamical systems and are usually approximated using ponderomotive theory. In this paper, we derive the plasma distribution function predicted by ponderomotive theory using Hamiltonian averaging theory and compare it with solutions obtained by the method of characteristics. Our results show that though ponderomotive theory is relatively much easier to use, its predictions are very restrictive and are likely to be very different from the actual distribution function of the system. We also analyse all possible initial conditions which lead to periodic solutions of the Vlasov equation for periodically driven systems and conjecture that the irreducible polynomial corresponding to the initial condition must only have squares of the spatial and momentum coordinate. The resulting distribution function for other initial conditions is aperiodic and can lead to complex relaxation processes within the plasma.

  2. Thermo-driven microcrawlers fabricated via a microfluidic approach

    International Nuclear Information System (INIS)

    Wang Wei; Yao Chen; Zhang Maojie; Ju Xiaojie; Xie Rui; Chu Liangyin

    2013-01-01

    A novel thermo-driven microcrawler that can transform thermal stimuli into directional mechanical motion is developed by a simple microfluidic approach together with emulsion-template synthesis. The microcrawler is designed with a thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel body and a bell-like structure with an eccentric cavity. The asymmetric shrinking–swelling circulation of the microcrawlers enables a thermo-driven locomotion responding to repeated temperature changes, which provides a novel model with symmetry breaking principle for designing biomimetic soft microrobots. The microfluidic approach offers a novel and promising platform for design and fabrication of biomimetic soft microrobots. (paper)

  3. Laser driven white light source for BRDF measurement

    DEFF Research Database (Denmark)

    Amdemeskel, Mekbib Wubishet; Thorseth, Anders; Dam-Hansen, Carsten

    2017-01-01

    In this paper, we will present a setup with laser driven light source (LDLS) for measuring a 2D bidirectional reflectance distribution function (BRDF). We have carried out measurements to acquire the BRDF of different samples based on our setup: which consists of a new laser driven broadband light...... source (UV-VIS-NIR), spectroradiometer and sample holder stepper motor in a dark UV-protected environment. Here, we introduced a special kind of light source which has a bright, stable, broad spectral range and well collimated light output to give a very good angular resolution. The experimental results...

  4. Combustion-Driven Oscillation in Process Heaters

    Energy Technology Data Exchange (ETDEWEB)

    Seebold, J.G. [Chevron Corporation (Retired), 198 James Avenue, Atherton, CA 94027 (United States)

    2005-10-15

    At this moment in thousands of process heaters all over the world there are, to borrow a phrase from the late Carl Sagan, 'billions and billions' of Btu/hr beneficially being released entirely free of pulsation. On those few occasions, perhaps a dozen and a half in my career, when I would get the inevitable 'Why me?' call, I have generally responsed with something like, 'Consider yourself lucky, you have a rare scientific curiosity on your hands'. Reflecting on the solutions ultimately found, I'm reminded that many years ago my friend Abbott Putnam shared with me an early AGA (American Gas Association) field-service bulletin that included a prescription for eliminating combustion-driven oscillations in home heating units; viz., 'Drill a hole; if that doesn't work, drill another hole' or words to that effect. Many times have I wished that I still had a copy of that bulletin and in this paper we will have occasion, once again, to reflect upon the value of that advice. In this paper we will discuss an instance that arose in a pioneering installation of a breakthrough development of 'extremely', to distinguish it from 'ultra', low-NOx lean premix burner technology. We will illustrate how, when and under what circumstances combustion-driven oscillation can arise; we will touch on the many alternatives for its elimination that were considered and investigated; and we will discuss three practical alternatives for eliminating combustion-driven oscillations.

  5. The Permanent Magnet Operating Mechanism of Double Coil Parallel Driven at a High Speed

    Directory of Open Access Journals (Sweden)

    WEI Xau-Lao

    2017-02-01

    Full Text Available Abstract:Operating mechanism is the main part of breaker,and the quality of breaker will directly influence the safe operation of power system. Because of the continuous improvement requirements of switch,in order to mak this actuator faster and more powerful closing,this paper proposes a double coil parallel driven permanent magnet actuator at a high speed. This paper expounds the working principle of single and double coil parallel driven permanent magnet actuator. It uses Ansoft building model and contrasts test results. In prance we designed and produced the single and double coil parallel driven permanent magnet actuator for experimental study. The simulation and experiment results show that double coil parallel driven permanent magnet actuator,compared with single coil parallel driven permanent magnet actuator,has a better and faster action performance. Thus,the double coil parallel driven permanent magnet actuator achieves a kind of optimization.

  6. Flexural Behavior of GFRP Tubes Filled with Magnetically Driven Concrete.

    Science.gov (United States)

    Xie, Fang; Chen, Ju; Dong, Xinlong; Feng, Bing

    2018-01-08

    Experimental investigation of GFRP (glass fiber reinforced polymer) tubes that were filled with magnetically driven concrete was carried out to study the flexural behavior of specimens under bending. Specimens having different cross section and lengths were tested. The test specimens were fabricated by filling magnetically driven concrete into the GFRP tubes and the concrete was vibrated using magnetic force. Specimens vibrated using vibrating tube were also tested for comparison. In addition, specimens having steel reinforcing bars and GFRP bars were both tested to study the effect of reinforcing bars on the magnetically driven concrete. The load-displacement curves, load-strain curves, failure mode, and ultimate strengths of test specimens were obtained. Design methods for the flexural stiffness of test specimens were also discussed in this study.

  7. Neutron Transport Methods for Accelerator-Driven Systems

    International Nuclear Information System (INIS)

    Nicholas Tsoulfanidis; Elmer Lewis

    2005-01-01

    The objective of this project has been to develop computational methods that will enable more effective analysis of Accelerator Driven Systems (ADS). The work is centered at the University of Missouri at Rolla, with a subcontract at Northwestern University, and close cooperation with the Nuclear Engineering Division at Argonne National Laboratory. The work has fallen into three categories. First, the treatment of the source for neutrons originating from the spallation target which drives the neutronics calculations of the ADS. Second, the generalization of the nodal variational method to treat the R-Z geometry configurations frequently needed for scoping calculations in Accelerator Driven Systems. Third, the treatment of void regions within variational nodal methods as needed to treat the accelerator beam tube

  8. Data-driven regionalization of housing markets

    NARCIS (Netherlands)

    Helbich, M.; Brunauer, W.; Hagenauer, J.; Leitner, M.

    2013-01-01

    This article presents a data-driven framework for housing market segmentation. Local marginal house price surfaces are investigated by means of mixed geographically weighted regression and are reduced to a set of principal component maps, which in turn serve as input for spatial regionalization. The

  9. IMPROVING BANDWIDTH OF FLIPPED VOLTAGE FOLLOWER USING GATE-BODY DRIVEN TECHNIQUE

    Directory of Open Access Journals (Sweden)

    VANDANA NIRANJAN

    2017-01-01

    Full Text Available In this paper, a new approach to enhance the bandwidth of flipped voltage follower is explored. The proposed approach is based on gate-body driven technique. This technique boosts the transconductance in a MOS transistor as both gate and body/bulk terminals are tied together and used as signal input. This novel technique appears as a good solution to merge the advantages of gate-driven and bulk-driven techniques and suppress their disadvantages. The gate-body driven technique utilizes body effect to enable low voltage low power operation and improves the overall performance of flipped voltage follower, providing it with low output impedance, high input impedance and bandwidth extension ratio of 2.614. The most attractive feature is that bandwidth enhancement has been achieved without use of any passive component or extra circuitry. Simulations in PSpice environment for 180 nm CMOS technology verified the predicted theoretical results. The improved flipped voltage follower is particularly interesting for high frequency low noise signal processing applications.

  10. Maximum Principle for General Controlled Systems Driven by Fractional Brownian Motions

    International Nuclear Information System (INIS)

    Han Yuecai; Hu Yaozhong; Song Jian

    2013-01-01

    We obtain a maximum principle for stochastic control problem of general controlled stochastic differential systems driven by fractional Brownian motions (of Hurst parameter H>1/2). This maximum principle specifies a system of equations that the optimal control must satisfy (necessary condition for the optimal control). This system of equations consists of a backward stochastic differential equation driven by both fractional Brownian motions and the corresponding underlying standard Brownian motions. In addition to this backward equation, the maximum principle also involves the Malliavin derivatives. Our approach is to use conditioning and Malliavin calculus. To arrive at our maximum principle we need to develop some new results of stochastic analysis of the controlled systems driven by fractional Brownian motions via fractional calculus. Our approach of conditioning and Malliavin calculus is also applied to classical system driven by standard Brownian motions while the controller has only partial information. As a straightforward consequence, the classical maximum principle is also deduced in this more natural and simpler way.

  11. A systematic review of fantasy driven vs. contact driven internet-initiated sexual offences: Discrete or overlapping typologies?

    Science.gov (United States)

    Broome, Laura Jayne; Izura, Cristina; Lorenzo-Dus, Nuria

    2018-05-01

    Within the literature individuals who use the internet to facilitate the sexual abuse of a minor are generally classified as being fantasy or contact driven. Classification is based upon the intended location for sexual climax: fantasy driven individuals aim to reach sexual climax online, whereas contact driven individuals target minors to achieve physical sex offline. This review systematically investigates whether there is an empirical basis for the distinction between these two proposed discrete types. Comparison of tactics and behaviour are considered to examine whether the contact vs. fantasy distinction is useful. A two-stage literature selection process, considered against pre-determined inclusion criteria, identified a total of twenty-two studies. As methodological heterogeneity limited the ability to conduct pooled analysis, a narrative synthesis of data employing an interpretive approach was conducted. This showed that the contact and fantasy distinction is ambiguous, given that both groups engage in online behaviours that provide them with online sexual gratification that can also lead to offline contact. Furthermore, no clear pattern of behaviour was found to define contact and fantasy individuals idiosyncratically. The European Online Grooming Project typology is thus proposed as a better representation of this behaviour; intimacy seeking, adaptable and hypersexualized groups. The distinction between these groups focuses primarily on the intensity of the relationship, acknowledging that sexual abuse can occur with or without offline contact. This review also highlights the need for larger, methodologically robust studies that examine the behaviour of online child sexual offenders. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Convergence of service, policy, and science toward consumer-driven mental health care.

    Science.gov (United States)

    Carroll, Christopher D; Manderscheid, Ronald W; Daniels, Allen S; Compagni, Amelia

    2006-12-01

    A common theme is emerging in sentinel reports on the United States health care system. Consumer relevance and demands on service systems and practices are influencing how mental health care is delivered and how systems will be shaped in the future. The present report seeks to assemble a confluence of consumer-driven themes from noteworthy reports on the state of the mental health system in the U.S. It also explores innovative efforts, promising practices, collaborative efforts, as well as identification of barriers to consumer-directed care, with possible solutions. The report reviews the relevant public mental health policy and data used in published work. The findings indicate an increasing public and private interest in promoting consumer-driven care, even though historical systems of care predominate, and often create, barriers to wide-spread redesign of a consumer-centered mental health care system. Innovative consumer-driven practices are increasing as quality, choice, and self-determination become integral parts of a redesigned U.S. mental health care system. The use of consumer-driven approaches in mental health is limited at best. These programs challenge industry norms and traditional practices. Limitations include the need for additional and thorough evaluations of effectiveness (cost and clinical) and replicability of consumer-directed programs. Consumer-driven services indicate that mental health consumers are expecting to be more participative in their mental health care. This expectation will influence how traditional mental health services and providers become more consumer-centric and meet the demand. Public and private interest in consumer-driven health care range from creating cost-conscious consumers to individualized control of recovery. The health care sector should seek to invest more resources in the provision of consumer-driven health care programs. The results of this study have implications and are informative for other countries where

  13. Electron heating of voltage-driven and matched dual frequency discharges

    International Nuclear Information System (INIS)

    Lieberman, M A; Lichtenberg, A J

    2010-01-01

    In a dual frequency capacitive sheath, a high frequency uniform sheath motion is coupled with a low frequency Child law sheath motion. For current-driven high and low frequency sheaths, the high frequency sheath motion generates most of the ohmic and stochastic heating of the discharge electrons. The low frequency motion, in addition to its primary purpose of establishing the ion bombarding energy, also increases the heating by widening the sheath width and transporting the oscillating electrons to regions of lower plasma density, and hence higher sheath velocity. In this work, we show that for voltage-driven high and low frequency sheaths, increasing the low frequency voltage reduces the heating, due to the reduced high frequency current that flows through the sheath under voltage-driven conditions. We determine the dependence of the heating on various parameters and compare the results with the current-driven case. Particle-in-cell simulations are used to confirm this result. Discharges generally employ a matching network to maximize the power transmitted to the plasma. We obtain analytic expressions for the effect of the low frequency source under matched conditions and, again, find that the low frequency source reduces the heating.

  14. Characterization of diagnostic hole-closure in Z-pinch driven hohlraums

    International Nuclear Information System (INIS)

    Baker, K. L.; Porter, J. L.; Ruggles, L. E.; Chandler, G. A.; Deeney, Chris; Vargas, M.; Moats, Ann; Struve, Ken; Torres, J.; McGurn, J. S.

    2000-01-01

    In this article we investigate the partial closure of diagnostic holes in Z-pinch driven hohlraums. These hohlraums differ from current laser-driven hohlraums in a number of ways such as their larger size, greater x-ray drive energy, and lower temperature. Although the diameter of the diagnostic holes on these Z-pinch driven hohlraums can be much greater than their laser-driven counterparts, 4 mm in diameter or larger, radiation impinges on the wall material surrounding the hole for the duration of the Z pinch, nearly 100 ns. This incident radiation causes plasma to ablate from the hohlraum walls surrounding the diagnostic hole and partially obscure this diagnostic hole. This partial obscuration reduces the effective area over which diagnostics view the hohlraum's radiation. This reduction in area can lead to an underestimation of the wall temperature when nonimaging diagnostics such as x-ray diodes and bolometers are used to determine power and later to infer a wall temperature. In this article we describe the techniques used to characterize the hole-closure in these hohlraums and present the experimental measurements of this process. (c) 2000 American Institute of Physics

  15. Characterization of diagnostic hole-closure in Z-pinch driven hohlraums

    Energy Technology Data Exchange (ETDEWEB)

    Baker, K. L. [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States); Porter, J. L. [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States); Ruggles, L. E. [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States); Chandler, G. A. [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States); Deeney, Chris [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States); Vargas, M. [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States); Moats, Ann [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States); Struve, Ken [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States); Torres, J. [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States); McGurn, J. S. [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States)] (and others)

    2000-02-01

    In this article we investigate the partial closure of diagnostic holes in Z-pinch driven hohlraums. These hohlraums differ from current laser-driven hohlraums in a number of ways such as their larger size, greater x-ray drive energy, and lower temperature. Although the diameter of the diagnostic holes on these Z-pinch driven hohlraums can be much greater than their laser-driven counterparts, 4 mm in diameter or larger, radiation impinges on the wall material surrounding the hole for the duration of the Z pinch, nearly 100 ns. This incident radiation causes plasma to ablate from the hohlraum walls surrounding the diagnostic hole and partially obscure this diagnostic hole. This partial obscuration reduces the effective area over which diagnostics view the hohlraum's radiation. This reduction in area can lead to an underestimation of the wall temperature when nonimaging diagnostics such as x-ray diodes and bolometers are used to determine power and later to infer a wall temperature. In this article we describe the techniques used to characterize the hole-closure in these hohlraums and present the experimental measurements of this process. (c) 2000 American Institute of Physics.

  16. Evanescent-wave proton postaccelerator driven by intense THz pulse

    OpenAIRE

    L. Pálfalvi; J. A. Fülöp; Gy. Tóth; J. Hebling

    2014-01-01

    Hadron therapy motivates research dealing with the production of particle beams with ∼100  MeV/nucleon energy and relative energy fluctuation on the order of 1%. Laser-driven accelerators produce ion beams with only tens of MeV/nucleon energy and an extremely broad spectra. Here, a novel method is proposed for postacceleration and monochromatization of particles, leaving the laser-driven accelerator, by using intense THz pulses. It is based on further developing the idea of using the evanesce...

  17. Influence of helical external driven current on nonlinear resistive tearing mode evolution and saturation in tokamaks

    Science.gov (United States)

    Zhang, W.; Wang, S.; Ma, Z. W.

    2017-06-01

    The influences of helical driven currents on nonlinear resistive tearing mode evolution and saturation are studied by using a three-dimensional toroidal resistive magnetohydrodynamic code (CLT). We carried out three types of helical driven currents: stationary, time-dependent amplitude, and thickness. It is found that the helical driven current is much more efficient than the Gaussian driven current used in our previous study [S. Wang et al., Phys. Plasmas 23(5), 052503 (2016)]. The stationary helical driven current cannot persistently control tearing mode instabilities. For the time-dependent helical driven current with f c d = 0.01 and δ c d < 0.04 , the island size can be reduced to its saturated level that is about one third of the initial island size. However, if the total driven current increases to about 7% of the total plasma current, tearing mode instabilities will rebound again due to the excitation of the triple tearing mode. For the helical driven current with time dependent strength and thickness, the reduction speed of the radial perturbation component of the magnetic field increases with an increase in the driven current and then saturates at a quite low level. The tearing mode is always controlled even for a large driven current.

  18. Foundations of Torey Hayden’s Relationship-Driven Classroom Practice with Troubled Children

    Directory of Open Access Journals (Sweden)

    Mike Marlowe

    2012-06-01

    Full Text Available This paper discusses the relationship-driven classroom practice of Torey Hayden, a teacher of children with emotional and behavioral difficulties, and author of eight books chronicling her day-to-day work in special education and child psychology. Seven philosophical principles which underpin and inform all action taken in her relationship-driven classroom model are delineated: 1 relationships are a process, not a goal; 2 there is a difference between a person and the person’s actions; 3 no one chooses to be unhappy; 4 misbehavior is a teaching opportunity; 5 everyone can change; 6 personal change is very difficult; and 7 the world is complex. A consilience of evidence supporting the use of a relationship-driven methodology with troubled children is presented. Final thoughts on Hayden’s relationship-driven classroom are offered.

  19. Dynamic posturography using a new movable multidirectional platform driven by gravity.

    NARCIS (Netherlands)

    Commissaris, D.A.C.M.; Nieuwenhuijzen, P.H.J.A.; Overeem, S.; Vos, A. de; Duysens, J.E.J.; Bloem, B.R.

    2002-01-01

    Human upright balance control can be quantified using movable platforms driven by servo-controlled torque motors (dynamic posturography). We introduce a new movable platform driven by the force of gravity acting upon the platform and the subject standing on it. The platform consists of a 1 m2 metal

  20. Dynamic posturography using a new movable multidirectional platform driven by gravity

    NARCIS (Netherlands)

    Commissaris, D.A.C.M.; Nieuwenhuijzen, P.H.J.A.; Overeem, S.; Vos, A. de; Duysens, J.E.J.; Bloem, B.R.

    2002-01-01

    Human upright balance control can be quantified using movable platforms driven by servo-controlled torque motors (dynamic posturography). We introduce a new movable platform driven by the force of gravity acting upon the platform and the subject standing on it. The platform consists of a 1 m(2)

  1. Functionality-driven fractionation of lupin seeds

    NARCIS (Netherlands)

    Berghout, J.A.M.

    2015-01-01

    Functionality-driven fractionation of lupin seeds

    The growth in the world population requires an increase in the production of protein-rich foods from plant-based materials. Lupin seeds have potential to become a novel plant protein source for food products because they are rich

  2. Scripted Bodies and Spline Driven Animation

    DEFF Research Database (Denmark)

    Erleben, Kenny; Henriksen, Knud

    2002-01-01

    In this paper we will take a close look at the details and technicalities in applying spline driven animation to scripted bodies in the context of dynamic simulation. The main contributions presented in this paper are methods for computing velocities and accelerations in the time domain...

  3. Off-equatorial current-driven instabilities ahead of approaching dipolarization fronts

    Science.gov (United States)

    Zhang, Xu; Angelopoulos, V.; Pritchett, P. L.; Liu, Jiang

    2017-05-01

    Recent kinetic simulations have revealed that electromagnetic instabilities near the ion gyrofrequency and slightly away from the equatorial plane can be driven by a current parallel to the magnetic field prior to the arrival of dipolarization fronts. Such instabilities are important because of their potential contribution to global electromagnetic energy conversion near dipolarization fronts. Of the several instabilities that may be consistent with such waves, the most notable are the current-driven electromagnetic ion cyclotron instability and the current-driven kink-like instability. To confirm the existence and characteristics of these instabilities, we used observations by two Time History of Events and Macroscale Interactions during Substorms satellites, one near the neutral sheet observing dipolarization fronts and the other at the boundary layer observing precursor waves and currents. We found that such instabilities with monochromatic signatures are rare, but one of the few cases was selected for further study. Two different instabilities, one at about 0.3 Hz and the other at a much lower frequency, 0.02 Hz, were seen in the data from the off-equatorial spacecraft. A parallel current attributed to an electron beam coexisted with the waves. Our instability analysis attributes the higher-frequency instability to a current-driven ion cyclotron instability and the lower frequency instability to a kink-like instability. The current-driven kink-like instability we observed is consistent with the instabilities observed in the simulation. We suggest that the currents needed to excite these low-frequency instabilities are so intense that the associated electron beams are easily thermalized and hence difficult to observe.

  4. Present status of laser driven fusion--fission energy systems

    International Nuclear Information System (INIS)

    Maniscalco, J.A.; Hansen, L.F.

    1978-01-01

    The potential of laser fusion driven hybrids to produce fissile fuel and/or electricity has been investigated in the laser program at the Lawrence Livermore Laboratory (LLL) for several years. Our earlier studies used neutronic methods of analysis to estimate hybrid performance. The results were encouraging, but it was apparent that a more accurate assessment of the hybrid's potential would require studies which treat the engineering, environmental, and economic issues as well as the neutronic aspects. More recently, we have collaborated with Bechtel and Westinghouse Corporations in two engineering design studies of laser fusion driven hybrid power plants. With Bechtel, we have been engaged in a joint effort to design a laser fusion driven hybrid which emphasizes fissile fuel production while the primary objective of our joint effort with Westinghouse has been to design a hybrid which emphasizes power production. The hybrid designs which have resulted from these two studies are briefly described and analyzed by considering their most important operational parameters

  5. An experimental platform for pulsed-power driven magnetic reconnection

    Science.gov (United States)

    Hare, J. D.; Suttle, L. G.; Lebedev, S. V.; Loureiro, N. F.; Ciardi, A.; Chittenden, J. P.; Clayson, T.; Eardley, S. J.; Garcia, C.; Halliday, J. W. D.; Robinson, T.; Smith, R. A.; Stuart, N.; Suzuki-Vidal, F.; Tubman, E. R.

    2018-05-01

    We describe a versatile pulsed-power driven platform for magnetic reconnection experiments, based on the exploding wire arrays driven in parallel [Suttle et al., Phys. Rev. Lett. 116, 225001 (2016)]. This platform produces inherently magnetised plasma flows for the duration of the generator current pulse (250 ns), resulting in a long-lasting reconnection layer. The layer exists for long enough to allow the evolution of complex processes such as plasmoid formation and movement to be diagnosed by a suite of high spatial and temporal resolution laser-based diagnostics. We can access a wide range of magnetic reconnection regimes by changing the wire material or moving the electrodes inside the wire arrays. We present results with aluminium and carbon wires, in which the parameters of the inflows and the layer that forms are significantly different. By moving the electrodes inside the wire arrays, we change how strongly the inflows are driven. This enables us to study both symmetric reconnection in a range of different regimes and asymmetric reconnection.

  6. Controlling chaos in the current-driven ion acoustic instability

    International Nuclear Information System (INIS)

    Fukuyama, T.; Taniguchi, K.; Kawai, Y.

    2002-01-01

    Control of intermittent chaos caused by the current-driven ion acoustic instability is attempted and the controlling mechanism is investigated. When a small negative dc voltage is applied to the chaotic system as a perturbation, the system changes from a chaotic state to a periodic state while maintaining the instability, indicating that the chaotic state caused by the ion acoustic instability is well controlled by applying a small negative dc voltage. A hysteresis structure is observed on the V-I curve of the mesh grid to which the negative dc voltage to control is applied. Furthermore, when a negative dc voltage is applied to the state which shows a laminar structure existing under same experimental conditions, the system becomes chaotic via a bifurcation. Driven-chaos is excited when a negative dc voltage is applied to the laminar state. Applying a small negative dc voltage leads to controlling intermittent chaos while exciting driven-chaos

  7. Exploring Techniques of Developing Writing Skill in IELTS Preparatory Courses: A Data-Driven Study

    Science.gov (United States)

    Ostovar-Namaghi, Seyyed Ali; Safaee, Seyyed Esmail

    2017-01-01

    Being driven by the hypothetico-deductive mode of inquiry, previous studies have tested the effectiveness of theory-driven interventions under controlled experimental conditions to come up with universally applicable generalizations. To make a case in the opposite direction, this data-driven study aims at uncovering techniques and strategies…

  8. Selfconsistent RF driven and bootstrap currents

    International Nuclear Information System (INIS)

    Peysson, Y.

    2002-01-01

    This important problem selfconsistent calculations of the bootstrap current with RF, taking into account possible synergistic effects, is addressed for the case of lower hybrid (LH) and electron cyclotron (EC) current drive by numerically solving the electron drift kinetic equation. Calculations are performed using a new, fast, and fully implicit code which solves the 3-D relativistic Fokker-Planck equation with quasilinear diffusion. These calculations take into account the perturbations to the electron distribution due to radial drifts induced by magnetic field gradient and curvature. While the synergism between bootstrap and LH-driven current does not seem to exceed 15%, it can reach 30-40% with the EC-driven current for some plasma parameters. In addition, considerable current can be generated by judiciously using ECCD with the Okhawa effect. This is in contrast to the usual ECCD which tries to avoid it. A detailed analysis of the numerical results is presented using a simplified analytical model which incorporates the underlying physical processes. (author)

  9. A charge-driven molecular water pump.

    Science.gov (United States)

    Gong, Xiaojing; Li, Jingyuan; Lu, Hangjun; Wan, Rongzheng; Li, Jichen; Hu, Jun; Fang, Haiping

    2007-11-01

    Understanding and controlling the transport of water across nanochannels is of great importance for designing novel molecular devices, machines and sensors and has wide applications, including the desalination of seawater. Nanopumps driven by electric or magnetic fields can transport ions and magnetic quanta, but water is charge-neutral and has no magnetic moment. On the basis of molecular dynamics simulations, we propose a design for a molecular water pump. The design uses a combination of charges positioned adjacent to a nanopore and is inspired by the structure of channels in the cellular membrane that conduct water in and out of the cell (aquaporins). The remarkable pumping ability is attributed to the charge dipole-induced ordering of water confined in the nanochannels, where water can be easily driven by external fields in a concerted fashion. These findings may provide possibilities for developing water transport devices that function without osmotic pressure or a hydrostatic pressure gradient.

  10. Noise-driven phenomena in hysteretic systems

    CERN Document Server

    Dimian, Mihai

    2014-01-01

    Noise-Driven Phenomena in Hysteretic Systems provides a general approach to nonlinear systems with hysteresis driven by noisy inputs, which leads to a unitary framework for the analysis of various stochastic aspects of hysteresis. This book includes integral, differential and algebraic models that are used to describe scalar and vector hysteretic nonlinearities originating from various areas of science and engineering. The universality of the authors approach is also reflected by the diversity of the models used to portray the input noise, from the classical Gaussian white noise to its impulsive forms, often encountered in economics and biological systems, and pink noise, ubiquitous in multi-stable electronic systems. The book is accompanied by HysterSoft© - a robust simulation environment designed to perform complex hysteresis modeling – that can be used by the reader to reproduce many of the results presented in the book as well as to research both disruptive and constructive effects of noise in hysteret...

  11. Distributed simulation a model driven engineering approach

    CERN Document Server

    Topçu, Okan; Oğuztüzün, Halit; Yilmaz, Levent

    2016-01-01

    Backed by substantive case studies, the novel approach to software engineering for distributed simulation outlined in this text demonstrates the potent synergies between model-driven techniques, simulation, intelligent agents, and computer systems development.

  12. Universality in driven-dissipative quantum many-body systems

    International Nuclear Information System (INIS)

    Sieberer, L.M.

    2015-01-01

    Recent experimental investigations of condensation phenomena in driven-dissipative quantum many-body systems raise the question of what kind of novel universal behavior can emerge under non-equilibrium conditions. We explore various aspects of universality in this context. Our results are of relevance for a variety of open quantum systems on the interface of quantum optics and condensed matter physics, ranging from exciton-polariton condensates to cold atomic gases. In Part I we characterize the dynamical critical behavior at the Bose-Einstein condensation phase transition in driven open quantum systems in three spatial dimensions. Although thermodynamic equilibrium conditions are emergent at low frequencies, the approach to this thermalized low-frequency regime is described by a critical exponent which is specific to the non-equilibrium transition, and places the latter beyond the standard classification of equilibrium dynamical critical behavior. Our theoretical approach is based on the functional renormalization group within the framework of Keldysh non-equilibrium field theory, which is equivalent to a microscopic description of the open system dynamics in terms of a many-body quantum master equation. Universal behavior in the coherence properties of driven-dissipative condensates in reduced dimensions is investigated in Part II. We show that driven two-dimensional Bose systems cannot exhibit algebraic order as in thermodynamic equilibrium, unless they are sufficiently anisotropic. However, we find evidence that even isotropic systems may have a finite superfluidity fraction. In one-dimensional systems, non-equilibrium conditions are traceable in the behavior of the autocorrelation function. We obtain these results by mapping the long-wavelength condensate dynamics onto the Kardar-Parisi-Zhang equation. In Part III we show that systems in thermodynamic equilibrium have a specific symmetry, which makes them distinct from generic driven open systems. The novel

  13. Event-driven simulation of neural population synchronization facilitated by electrical coupling.

    Science.gov (United States)

    Carrillo, Richard R; Ros, Eduardo; Barbour, Boris; Boucheny, Christian; Coenen, Olivier

    2007-02-01

    Most neural communication and processing tasks are driven by spikes. This has enabled the application of the event-driven simulation schemes. However the simulation of spiking neural networks based on complex models that cannot be simplified to analytical expressions (requiring numerical calculation) is very time consuming. Here we describe briefly an event-driven simulation scheme that uses pre-calculated table-based neuron characterizations to avoid numerical calculations during a network simulation, allowing the simulation of large-scale neural systems. More concretely we explain how electrical coupling can be simulated efficiently within this computation scheme, reproducing synchronization processes observed in detailed simulations of neural populations.

  14. Calibration of Resistance Factors Needed in the LRFD Design of Driven Piles

    Science.gov (United States)

    2009-05-01

    This research project presents the calibration of resistance factors for the Load and Resistance Factor Design (LRFD) method of driven : piles driven into Louisiana soils based on reliability theory. Fifty-three square Precast-Prestressed-Concrete (P...

  15. Laser-driven ion acceleration: methods, challenges and prospects

    Science.gov (United States)

    Badziak, J.

    2018-01-01

    The recent development of laser technology has resulted in the construction of short-pulse lasers capable of generating fs light pulses with PW powers and intensities exceeding 1021 W/cm2, and has laid the basis for the multi-PW lasers, just being built in Europe, that will produce fs pulses of ultra-relativistic intensities ~ 1023 - 1024 W/cm2. The interaction of such an intense laser pulse with a dense target can result in the generation of collimated beams of ions of multi-MeV to GeV energies of sub-ps time durations and of extremely high beam intensities and ion fluencies, barely attainable with conventional RF-driven accelerators. Ion beams with such unique features have the potential for application in various fields of scientific research as well as in medical and technological developments. This paper provides a brief review of state-of-the art in laser-driven ion acceleration, with a focus on basic ion acceleration mechanisms and the production of ultra-intense ion beams. The challenges facing laser-driven ion acceleration studies, in particular those connected with potential applications of laser-accelerated ion beams, are also discussed.

  16. Developing a theory driven text messaging intervention for addiction care with user driven content.

    Science.gov (United States)

    Muench, Frederick; Weiss, Rebecca A; Kuerbis, Alexis; Morgenstern, Jon

    2013-03-01

    The number of text messaging interventions designed to initiate and support behavioral health changes have been steadily increasing over the past 5 years. Messaging interventions can be tailored and adapted to an individual's needs in their natural environment-fostering just-in-time therapies and making them a logical intervention for addiction continuing care. This study assessed the acceptability of using text messaging for substance abuse continuing care and the intervention preferences of individuals in substance abuse treatment in order to develop an interactive mobile text messaging intervention. Fifty individuals enrolled in intensive outpatient substance abuse treatment completed an assessment battery relating to preferred logistics of mobile interventions, behavior change strategies, and types of messages they thought would be most helpful to them at different time points. Results indicated that 98% participants were potentially interested in using text messaging as a continuing care strategy. Participants wrote different types of messages that they perceived might be most helpful, based on various hypothetical situations often encountered during the recovery process. Although individuals tended to prefer benefit driven over consequence driven messages, differences in the perceived benefits of change among individuals predicted message preference. Implications for the development of mobile messaging interventions for the addictions are discussed. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  17. From design education to user-driven innovation and back again

    DEFF Research Database (Denmark)

    Tollestrup, Christian; Eriksen, Kaare

    2012-01-01

    Can distilled design methods for non-designers to user-driven innovation inform design education of Industrial Designers? In 2010 a project on employee driven innovation in the Hospital Sector with Aalborg University and Aalborg Hospital provided 35 participants from all over the hospital...... of potentials and problems to systematic ideation. This paper compares the use these methods in the two settings and especially the problem framing is problematic for both employees and students. For each method strengths and weakness in both situations are outlined. Finally it is concluded that the experiment...... of taking the tools made for employee-driven innovation back into the education stage without any change and without the full-facilitated support from the project setting shows that introducing tools without the mind-set is challenging the very value of these tools....

  18. Proton-driven Plasma Wakefield Acceleration

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    The construction of ever larger and costlier accelerator facilities has a limited future, and new technologies will be needed to push the energy frontier. Plasma wakefield acceleration is a rapidly developing field and is a promising candidate technology for future high energy colliders. We focus on the recently proposed idea of proton-driven plasma wakefield acceleration and describe the current status and plans for this approach.

  19. Tongue-Driven Wheelchair Out-Maneuvers the Competition

    Science.gov (United States)

    ... 2, 2014 Tongue-Driven Wheelchair Out-Maneuvers the Competition Researchers funded by the National Institute of Biomedical ... significant step towards vastly improving the independence and quality of life of individuals with tetraplegia, and is ...

  20. Symmetry breaking in clogging for oppositely driven particles

    Science.gov (United States)

    Glanz, Tobias; Wittkowski, Raphael; Löwen, Hartmut

    2016-11-01

    The clogging behavior of a symmetric binary mixture of colloidal particles that are driven in opposite directions through constrictions is explored by Brownian dynamics simulations and theory. A dynamical state with a spontaneously broken symmetry occurs where one species is flowing and the other is blocked for a long time, which can be tailored by the size of the constrictions. Moreover, we find self-organized oscillations in clogging and unclogging of the two species. Apart from statistical physics, our results are of relevance for fields like biology, chemistry, and crowd management, where ions, microparticles, pedestrians, or other particles are driven in opposite directions through constrictions.

  1. Hysteretic behavior of spin-crossover noise driven system

    Energy Technology Data Exchange (ETDEWEB)

    Gudyma, Iurii [Department of General Physics, Chernivtsi National University, Chernivtsi 58012 (Ukraine); Maksymov, Artur, E-mail: maxyartur@gmail.com [Department of General Physics, Chernivtsi National University, Chernivtsi 58012 (Ukraine); Advanced Materials Research Institute, University of New Orleans, LA 70148 (United States); Dimian, Mihai [Department of Electrical and Computer Engineering, Howard University, Washington DC, 20059 (United States); Faculty of Electrical Engineering and Computer Science, Stefan cel Mare University, Suceava 720229 (Romania)

    2016-04-01

    The influence of white Gaussian noise on hysteretic behavior of spin-crossover system is analyzed in the framework of stochastic Langevin dynamics. Various stochastic simulations are performed and several important properties of spin-transition in spin-crossover system driven by noise are reproduced. The numerical results are tested against the stationary probability function and the associated dynamic potential obtained from Fokker–Planck equation corresponding to spin-crossover Langevin dynamics. The dependence of light-induced optical hysteresis width and non-hysteretic transition curve slope on the noise intensity is illustrated. The role of low-spin and high-spin phase stabilities in the hysteretic behavior of noise-driven spin-crossover system is discussed.

  2. Laser-driven particle acceleration towards radiobiology and medicine

    CERN Document Server

    2016-01-01

    This book deals with the new method of laser-driven acceleration for application to radiation biophysics and medicine. It provides multidisciplinary contributions from world leading scientist in order to assess the state of the art of innovative tools for radiation biology research and medical applications of ionizing radiation. The book contains insightful contributions on highly topical aspects of spatio-temporal radiation biophysics, evolving over several orders of magnitude, typically from femtosecond and sub-micrometer scales. Particular attention is devoted to the emerging technology of laser-driven particle accelerators and their applicatio to spatio-temporal radiation biology and medical physics, customization of non-conventional and selective radiotherapy and optimized radioprotection protocols.

  3. Electrostatically Driven Nanoballoon Actuator.

    Science.gov (United States)

    Barzegar, Hamid Reza; Yan, Aiming; Coh, Sinisa; Gracia-Espino, Eduardo; Dunn, Gabriel; Wågberg, Thomas; Louie, Steven G; Cohen, Marvin L; Zettl, Alex

    2016-11-09

    We demonstrate an inflatable nanoballoon actuator based on geometrical transitions between the inflated (cylindrical) and collapsed (flattened) forms of a carbon nanotube. In situ transmission electron microscopy experiments employing a nanoelectromechanical manipulator show that a collapsed carbon nanotube can be reinflated by electrically charging the nanotube, thus realizing an electrostatically driven nanoballoon actuator. We find that the tube actuator can be reliably cycled with only modest control voltages (few volts) with no apparent wear or fatigue. A complementary theoretical analysis identifies critical parameters for nanotube nanoballoon actuation.

  4. A refinement driven component-based design

    DEFF Research Database (Denmark)

    Chen, Zhenbang; Liu, Zhiming; Ravn, Anders Peter

    2007-01-01

    the work on the Common Component Modelling Example (CoCoME). This gives evidence that the formal techniques developed in rCOS can be integrated into a model-driven development process and shows where it may be integrated in computer-aided software engineering (CASE) tools for adding formally supported...

  5. Model Driven Architecture: Foundations and Applications

    NARCIS (Netherlands)

    Rensink, Arend

    The OMG's Model Driven Architecture (MDA) initiative has been the focus of much attention in both academia and industry, due to its promise of more rapid and consistent software development through the increased use of models. In order for MDA to reach its full potential, the ability to manipulate

  6. Stimulus-driven capture and contingent capture

    NARCIS (Netherlands)

    Theeuwes, J.; Olivers, C.N.L.; Belopolsky, A.V.

    2010-01-01

    Whether or not certain physical events can capture attention has been one of the most debated issues in the study of attention. This discussion is concerned with how goal-directed and stimulus-driven processes interact in perception and cognition. On one extreme of the spectrum is the idea that

  7. Static Checking of Interrupt-driven Software

    DEFF Research Database (Denmark)

    Brylow, Dennis; Damgaard, Niels; Palsberg, Jens

    2001-01-01

    at the assembly level. In this paper we present the design and implementation of a static checker for interrupt-driven Z86-based software with hard real-time requirements. For six commercial microcontrollers, our checker has produced upper bounds on interrupt latencies and stack sizes, as well as verified...

  8. Nitric oxide-induced calcium release: activation of type 1 ryanodine receptor by endogenous nitric oxide.

    Science.gov (United States)

    Kakizawa, Sho; Yamazawa, Toshiko; Iino, Masamitsu

    2013-01-01

    Ryanodine receptors (RyRs), located in the sarcoplasmic/endoplasmic reticulum (SR/ER) membrane, are required for intracellular Ca2+ release that is involved in a wide range of cellular functions. In addition to Ca2+-induced Ca2+ release in cardiac cells and voltage-induced Ca2+ release in skeletal muscle cells, we recently identified another mode of intracellular Ca2+ mobilization mediated by RyR, i.e., nitric oxide-induced Ca2+ release (NICR), in cerebellar Purkinje cells. NICR is evoked by neuronal activity, is dependent on S-nitrosylation of type 1 RyR (RyR1) and is involved in the induction of long-term potentiation (LTP) of cerebellar synapses. In this addendum, we examined whether peroxynitrite, which is produced by the reaction of nitric oxide with superoxide, may also have an effect on the Ca2+ release via RyR1 and the cerebellar LTP. We found that scavengers of peroxynitrite have no significant effect either on the Ca2+ release via RyR1 or on the cerebellar LTP. We also found that an application of a high concentration of peroxynitrite does not reproduce neuronal activity-dependent Ca2+ release in Purkinje cells. These results support that NICR is induced by endogenous nitric oxide produced by neuronal activity through S-nitrosylation of RyR1.

  9. A perspective on the structural studies of inner membrane electrochemical potential-driven transporters.

    Science.gov (United States)

    Lemieux, M Joanne

    2008-09-01

    Electrochemical potential-driven transporters represent a vast array of proteins with varied substrate specificities. While diverse in size and substrate specificity, they are all driven by electrochemical potentials. Over the past five years there have been increasing numbers of X-ray structures reported for this family of transporters. Structural information is available for five subfamilies of electrochemical potential-driven transporters. No structural information exists for the remaining 91 subfamilies. In this review, the various subfamilies of electrochemical potential-driven transporters are discussed. The seven reported structures for the electrochemical potential-driven transporters and the methods for their crystallization are also presented. With a few exceptions, overall crystallization trends have been very similar for the transporters despite their differences in substrate specificity and topology. Also discussed is why the structural studies on these transporters were successful while others are not as fruitful. With the plethora of transporters with unknown structures, this review provides incentive for crystallization of transporters in the remaining subfamilies for which no structural information exists.

  10. Shear-driven phase transformation in silicon nanowires.

    Science.gov (United States)

    Vincent, L; Djomani, D; Fakfakh, M; Renard, C; Belier, B; Bouchier, D; Patriarche, G

    2018-03-23

    We report on an unprecedented formation of allotrope heterostructured Si nanowires by plastic deformation based on applied radial compressive stresses inside a surrounding matrix. Si nanowires with a standard diamond structure (3C) undergo a phase transformation toward the hexagonal 2H-allotrope. The transformation is thermally activated above 500 °C and is clearly driven by a shear-stress relief occurring in parallel shear bands lying on {115} planes. We have studied the influence of temperature and axial orientation of nanowires. The observations are consistent with a martensitic phase transformation, but the finding leads to clear evidence of a different mechanism of deformation-induced phase transformation in Si nanowires with respect to their bulk counterpart. Our process provides a route to study shear-driven phase transformation at the nanoscale in Si.

  11. Hysteresis in pressure-driven DNA denaturation.

    Directory of Open Access Journals (Sweden)

    Enrique Hernández-Lemus

    Full Text Available In the past, a great deal of attention has been drawn to thermal driven denaturation processes. In recent years, however, the discovery of stress-induced denaturation, observed at the one-molecule level, has revealed new insights into the complex phenomena involved in the thermo-mechanics of DNA function. Understanding the effect of local pressure variations in DNA stability is thus an appealing topic. Such processes as cellular stress, dehydration, and changes in the ionic strength of the medium could explain local pressure changes that will affect the molecular mechanics of DNA and hence its stability. In this work, a theory that accounts for hysteresis in pressure-driven DNA denaturation is proposed. We here combine an irreversible thermodynamic approach with an equation of state based on the Poisson-Boltzmann cell model. The latter one provides a good description of the osmotic pressure over a wide range of DNA concentrations. The resulting theoretical framework predicts, in general, the process of denaturation and, in particular, hysteresis curves for a DNA sequence in terms of system parameters such as salt concentration, density of DNA molecules and temperature in addition to structural and configurational states of DNA. Furthermore, this formalism can be naturally extended to more complex situations, for example, in cases where the host medium is made up of asymmetric salts or in the description of the (helical-like charge distribution along the DNA molecule. Moreover, since this study incorporates the effect of pressure through a thermodynamic analysis, much of what is known from temperature-driven experiments will shed light on the pressure-induced melting issue.

  12. On the Use of Client-Driven Projects in the Mathematics Classroom

    Science.gov (United States)

    Maki, Dan; Winston, Wayne; Shafii-Mousavi, Morteza; Kochanowski, Paul; Lang, Chris; Ernstberger, Kathy; Hodgson, Ted

    2006-01-01

    In this article, we discuss the use of client-driven projects--projects that are posed by business, government, and non-profit organizations and based upon real problems facing the organization. Although client-driven projects have long been used in business and engineering education, their use in the mathematics classroom is rare. Client-driven…

  13. Heat Driven Cooling in District Energy Systems; Vaermedriven Kyla

    Energy Technology Data Exchange (ETDEWEB)

    Rydstrand, Magnus; Martin, Viktoria; Westermark, Mats [Royal Inst. of Technology, Stockholm (Sweden). Dept. of Chemical Engineering and Technology

    2004-07-01

    This report is reviewing different heat driven technologies for the production of cooling. It is shown that the supply of cooling gives the highest fuel utilization if heat from CHP production is used for the production of cooling instead of maximizing the electricity output in a condensing plant. High fuel utilization is reached since the direct production of cooling from heat is a thermodynamic shortcut as compared to the production of electricity as an intermediate product before cooling is produced. At direct production of cooling from heat it is possible to obtain 70 percent of the obtainable cooling of an ideal process. If electricity is produced from heat, 70 percent electricity could be obtained as compared to an ideal process. If this electricity would be used for the production of cooling 70 percent of the obtainable cooling in an ideal process would the result. The total production of cooling from heat with electricity as an intermediate product would therefore give 50 percent cooling as compared to an ideal process. Hence, heat driven cooling will give more cooling for a given fuel input. In the review of the different heat driven cooling options it was found that there are many alternatives suitable for different applications. Absorption cooling is suitable for water distributed cooling if the latent cooling load is low. Desiccant cooling is believed to have a large market in climates (applications) with high latent cooling loads. In the energy efficiency evaluation it is found that the highest fuel utilization is given for a central production of electricity using either district heating or district cooling as the energy carrier to supply cooling. In fact the potential of district heating as the energy carrier is thought to be the largest in large cities with humid climates. Further it is found that the chiller heat sink can contribute significantly to the cost in many applications, especially if water and/or electricity consumption are issues with

  14. Studies of the hydroxyborohydride and triborohydride ions

    International Nuclear Information System (INIS)

    Reed, J.

    1977-10-01

    Results of the following studies are reported: chemical synthesis of hydroxytrihydroborate and peroxynitrite; the reduction of organic compounds with the hydroxyborohydride ion; and a kinetic study of the hydrolysis of the octahydrotriborate ions

  15. Current and noise in driven heterostructures

    Energy Technology Data Exchange (ETDEWEB)

    Kaiser, Franz

    2009-02-18

    In this thesis we consider the electron transport in nanoscale systems driven by an external energy source. We introduce a tight-binding Hamiltonian containing an interaction term that describes a very strong Coulomb repulsion between electrons in the system. Since we deal with time-dependent situations, we employ a Floquet theory to take into account the time periodicity induced by different external oscillating fields. For the two-level system, we even provide an analytical solution for the eigenenergies with arbitrary phase shift between the levels for a cosine-shaped driving. To describe time-dependent driven transport, we derive a master equation by tracing out the influence of the surrounding leads in order to obtain the reduced density operator of the system. We generalise the common master equation for the reduced density operator to perform an analysis of the noise characteristics. The concept of Full Counting Statistics in electron transport gained much attention in recent years proven its value as a powerful theoretical technique. Combining its advantages with the master equation approach, we find a hierarchy in the moments of the electron number in one lead that allows us to calculate the first two cumulants. The first cumulant can be identified as the current passing through the system, while the noise of this transmission process is reflected by the second cumulant. Moreover, in combination with our Floquet approach, the formalism is not limited to static situations, which we prove by calculating the current and noise characteristics for the non-adiabatic electron pump. We study the influence of a static energy disorder on the maximal possible current for different realisations. Further, we explore the possibility of non-adiabatically pumping electrons in an initially symmetric system if random fluctuations break this symmetry. Motivated by recent and upcoming experiments, we use our extended Floquet model to properly describe systems driven by

  16. Mastering Technologies in Design-Driven Innovation

    DEFF Research Database (Denmark)

    Dell'era, Claudio; Marchesi, Alessio; Verganti, Roberto

    2010-01-01

    Only a few companies have mastered the design-driven approach to innovation. This paper examines what it means to make design a central part of the business process, able to add value to products and create new markets. More specifically, it focuses on the interplay between the functional and sem...

  17. Persistence of Value-Driven Attentional Capture

    Science.gov (United States)

    Anderson, Brian A.; Yantis, Steven

    2013-01-01

    Stimuli that have previously been associated with the delivery of reward involuntarily capture attention when presented as unrewarded and task-irrelevant distractors in a subsequent visual search task. It is unknown how long such effects of reward learning on attention persist. One possibility is that value-driven attentional biases are plastic…

  18. Laser-driven wakefield electron acceleration and associated radiation sources

    International Nuclear Information System (INIS)

    Davoine, X.

    2009-10-01

    The first part of this research thesis introduces the basic concepts needed for the understanding of the laser-driven wakefield acceleration. It describes the properties of the used laser beams and plasmas, presents some notions about laser-plasma interactions for a better understanding of the physics of laser-driven acceleration. The second part deals with the numerical modelling and the presentation of simulation tools needed for the investigation of laser-induced wakefield acceleration. The last part deals with the optical control of the injection, a technique analogous to the impulsion collision scheme

  19. Nonlinearly driven oscillations in the gyrotron traveling-wave amplifier

    International Nuclear Information System (INIS)

    Chiu, C. C.; Pao, K. F.; Yan, Y. C.; Chu, K. R.; Barnett, L. R.; Luhmann, N. C. Jr.

    2008-01-01

    By delivering unprecedented power and gain, the gyrotron traveling-wave amplifier (gyro-TWT) offers great promise for advanced millimeter wave radars. However, the underlying physics of this complex nonlinear system is yet to be fully elucidated. Here, we report a new phenomenon in the form of nonlinearly driven oscillations. A zero-drive stable gyro-TWT is shown to be susceptible to a considerably reduced dynamic range at the band edge, followed by a sudden transition into driven oscillations and then a hysteresis effect. An analysis of this unexpected behavior and its physical interpretation are presented.

  20. Fast Mechanically Driven Daughter Cell Separation Is Widespread in Actinobacteria

    Directory of Open Access Journals (Sweden)

    Xiaoxue Zhou

    2016-08-01

    Full Text Available Dividing cells of the coccoid Gram-positive bacterium Staphylococcus aureus undergo extremely rapid (millisecond daughter cell separation (DCS driven by mechanical crack propagation, a strategy that is very distinct from the gradual, enzymatically driven cell wall remodeling process that has been well described in several rod-shaped model bacteria. To determine if other bacteria, especially those in the same phylum (Firmicutes or with similar coccoid shapes as S. aureus, might use a similar mechanically driven strategy for DCS, we used high-resolution video microscopy to examine cytokinesis in a phylogenetically wide range of species with various cell shapes and sizes. We found that fast mechanically driven DCS is rather rare in the Firmicutes (low G+C Gram positives, observed only in Staphylococcus and its closest coccoid relatives in the Macrococcus genus, and we did not observe this division strategy among the Gram-negative Proteobacteria. In contrast, several members of the high-G+C Gram-positive phylum Actinobacteria (Micrococcus luteus, Brachybacterium faecium, Corynebacterium glutamicum, and Mycobacterium smegmatis with diverse shapes ranging from coccoid to rod all undergo fast mechanical DCS during cell division. Most intriguingly, similar fast mechanical DCS was also observed during the sporulation of the actinobacterium Streptomyces venezuelae.

  1. LASNEX simulations of the classical and laser-driven Rayleigh-Taylor instability

    International Nuclear Information System (INIS)

    Mikaelian, K.O.

    1990-01-01

    We present the results of two-dimensional LASNEX simulations of the classical and laser-driven Rayleigh-Taylor instability. Our growth rates and eigenmodes for classical two- and three-fluid problems agree closely with the exact analytic expressions. We illustrate in several examples how perturbations feed through from one interface to another. For targets driven by a 1/4-μm laser at I=2x10 14 W/cm 2 our growth rates are 40--80 % of the classical case rates for wavelengths between 5 and 100 μm. We find that radiation transport has a stabilizing effect on the Rayleigh-Taylor instability, particularly at high intensities. A brief comparison with a laser-driven experiment is also presented

  2. Variation in polydispersity in pump- and pressure-driven micro-droplet generators

    Science.gov (United States)

    Zeng, Wen; Jacobi, Ian; Li, Songjing; Stone, Howard A.

    2015-11-01

    The polydispersity of droplets produced in a typical T-junction microfluidic channel under both syringe-pump-driven and pressure-driven flow configurations is measured quantitatively. Both flow systems exhibit high-frequency flow fluctuations that result in an intrinsic polydispersity due to the mechanism of droplet generation. In addition to this intrinsic polydispersity, the syringe-pump-driven device also exhibits low-frequency fluctuations due to mechanical oscillations of the pump, which overwhelm the high-frequency flow fluctuations and produce a signficantly heightened level of polydispersity. The quantitative difference in polydispersity between the two configurations and time-resolved measurements of individual droplet sizes are presented in order to enable the design of better flow control systems for droplet production.

  3. The role of protozoa-driven selection in shaping human genetic variability.

    Science.gov (United States)

    Pozzoli, Uberto; Fumagalli, Matteo; Cagliani, Rachele; Comi, Giacomo P; Bresolin, Nereo; Clerici, Mario; Sironi, Manuela

    2010-03-01

    Protozoa exert a strong selective pressure in humans. The selection signatures left by these pathogens can be exploited to identify genetic modulators of infection susceptibility. We show that protozoa diversity in different geographic locations is a good measure of protozoa-driven selective pressure; protozoa diversity captured selection signatures at known malaria resistance loci and identified several selected single nucleotide polymorphisms in immune and hemolytic anemia genes. A genome-wide search enabled us to identify 5180 variants mapping to 1145 genes that are subjected to protozoa-driven selective pressure. We provide a genome-wide estimate of protozoa-driven selective pressure and identify candidate susceptibility genes for protozoa-borne diseases. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. Soft X-Ray Measurements of Z-Pinch-Driven Vacuum Hohlraums

    International Nuclear Information System (INIS)

    Baker, K.L.; Porter, J.L.; Ruggles, L.E.; Chandler, G.A.; Deeney, Chris; Varas, M.; Moats, Ann; Struve, Ken; Torres, J.; McGurn, J.; Simpson, W.W.; Fehl, D.L.; Chrien, R.E.; Matuska, W.; Idzorek, G.C.

    1999-01-01

    This article reports the experimental characterization of a z-pinch driven-vacuum hohlraum. The authors have measured soft x-ray fluxes of 5 x 10 12 W/cm 2 radiating from the walls of hohlraums which are 2.4--2.5 cm in diameter by 1 cm tall. The x-ray source used to drive these hohlraums was a z-pinch consisting of a 300 wire tungsten array driven by a 2 MA, 100 ns current pulse. In this hohlraum geometry, the z-pinch x-ray source can produce energies in excess of 800 kJ and powers in excess of 100 TW to drive these hohlraums. The x-rays released in these hohlraums represent greater than a factor of 25 in energy and more than a factor of three in x-ray power over previous laboratory-driven hohlraums

  5. Functional Domain Driven Design

    OpenAIRE

    Herrera Guzmán, Sergio

    2016-01-01

    Las tecnologías están en constante expansión y evolución, diseñando nuevas técnicas para cumplir con su fin. En el desarrollo de software, las herramientas y pautas para la elaboración de productos software constituyen una pieza en constante evolución, necesarias para la toma de decisiones sobre los proyectos a realizar. Uno de los arquetipos para el desarrollo de software es el denominado Domain Driven Design, donde es importante conocer ampliamente el negocio que se desea modelar en form...

  6. Segmentation-DrivenTomographic Reconstruction

    DEFF Research Database (Denmark)

    Kongskov, Rasmus Dalgas

    such that the segmentation subsequently can be carried out by use of a simple segmentation method, for instance just a thresholding method. We tested the advantages of going from a two-stage reconstruction method to a one stage segmentation-driven reconstruction method for the phase contrast tomography reconstruction......The tomographic reconstruction problem is concerned with creating a model of the interior of an object from some measured data, typically projections of the object. After reconstructing an object it is often desired to segment it, either automatically or manually. For computed tomography (CT...

  7. A universal piezo-driven ultrasonic cell microinjection system.

    Science.gov (United States)

    Huang, Haibo; Mills, James K; Lu, Cong; Sun, Dong

    2011-08-01

    Over the past decade, the rapid development of biotechnologies such as gene injection, in-vitro fertilization, intracytoplasmic sperm injection (ICSI) and drug development have led to great demand for highly automated, high precision equipment for microinjection. Recently a new cell injection technology using piezo-driven pipettes with a very small mercury column was proposed and successfully applied in ICSI to a variety of mammal species. Although this technique significantly improves the survival rates of the ICSI process, shortcomings due to the toxicity of mercury and damage to the cell membrane due to large lateral tip oscillations of the injector pipette may limit its application. In this paper, a new cell injection system for automatic batch injection of suspended cells is developed. A new design of the piezo-driven cell injector is proposed for automated suspended cell injection. This new piezo-driven cell injector design relocates the piezo oscillation actuator to the injector pipette which eliminates the vibration effect on other parts of the micromanipulator. A small piezo stack is sufficient to perform the cell injection process. Harmful lateral tip oscillations of the injector pipette are reduced substantially without the use of a mercury column. Furthermore, ultrasonic vibration micro-dissection (UVM) theory is utilized to analyze the piezo-driven cell injection process, and the source of the lateral oscillations of the injector pipette is investigated. From preliminary experiments of cell injection of a large number of zebrafish embryos (n = 200), the injector pipette can easily pierce through the cell membrane at a low injection speed and almost no deformation of the cell wall, and with a high success rate(96%) and survival rate(80.7%) This new injection approach shows good potential for precision injection with less damage to the injected cells.

  8. Prophylactic antioxidants and phenolics of seagrass and seaweed ...

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    KEY WORDS: Antioxidant; Total Phenols; Total Flavonoids; FRAP; TEAC; Seagrass;. Seaweed; Seasonal ... ozone (O3) and peroxynitrite (ONOO−) are not free radicals but can ... oxygen during respiration and from the synthesis of complex ...

  9. Investigation toward laser driven IFE (inertial fusion energy) power plant

    International Nuclear Information System (INIS)

    Nakai, S.; Kozaki, Y.; Izawa, Y.; Yamanaka, M.; Kanabe, T.; Kato, Y.; Norimatsu, T.; Nagai, K.; Nakatsuka, M.; Jitsuno, T.; Yamanaka, T.

    2000-01-01

    Based on the conceptual design of Laser Driven IFE Power Plant, the technical and physical issues have been examined. R and D on key issues which affect the feasibility of power plant has been performed taking into account the collaboration in the field of laser driver, fuel pellet, reaction chamber and system design. The coordination and collaboration organization of reactor technology experts in Japan on Laser Driven IFE Power Plant are reviewed. (authors)

  10. ONTOLOGY-DRIVEN TOOL FOR UTILIZING PROGRAMMING STYLES

    Directory of Open Access Journals (Sweden)

    Nikolay Sidorov

    2017-07-01

    Full Text Available Activities of a programmer will be more effective and the software will be more understandable when within the process of software development, programming styles (standards are used, providing clarity of software texts. Purpose: In this research, we present the tool for the realization of new ontology-based methodology automated reasoning techniques for utilizing programming styles. In particular, we focus on representing programming styles in the form of formal ontologies, and study how description logic reasoner can assist programmers in utilizing programming standards. Our research hypothesis is as follows: ontological representation of programming styles can provide additional benefits over existing approaches in utilizing programmer of programming standards. Our research goal is to develop a tool to support the ontology-based utilizing programming styles. Methods: ontological representation of programming styles; object-oriented programming; ontology-driven utilizing of programming styles. Results: the architecture was obtained and the tool was developed in the Java language, which provide tool support of ontology-driven programming styles application method. On the example of naming of the Java programming language standard, features of implementation and application of the tool are provided. Discussion: application of programming styles in coding of program; lack of automated tools for the processes of programming standards application; tool based on new method of ontology-driven application of programming styles; an example of the implementation of tool architecture for naming rules of the Java language standard.

  11. Data-Driven Learning of Q-Matrix

    Science.gov (United States)

    Liu, Jingchen; Xu, Gongjun; Ying, Zhiliang

    2012-01-01

    The recent surge of interests in cognitive assessment has led to developments of novel statistical models for diagnostic classification. Central to many such models is the well-known "Q"-matrix, which specifies the item-attribute relationships. This article proposes a data-driven approach to identification of the "Q"-matrix and estimation of…

  12. 30 CFR 77.407 - Power-driven pulleys.

    Science.gov (United States)

    2010-07-01

    ... equipment especially designed for hand feeding. (b) Pulleys of conveyors shall not be cleaned manually while the conveyor is in motion. ... for Mechanical Equipment § 77.407 Power-driven pulleys. (a) Belts, chains, and ropes shall not be...

  13. Speech-driven environmental control systems--a qualitative analysis of users' perceptions.

    Science.gov (United States)

    Judge, Simon; Robertson, Zoë; Hawley, Mark; Enderby, Pam

    2009-05-01

    To explore users' experiences and perceptions of speech-driven environmental control systems (SPECS) as part of a larger project aiming to develop a new SPECS. The motivation for this part of the project was to add to the evidence base for the use of SPECS and to determine the key design specifications for a new speech-driven system from a user's perspective. Semi-structured interviews were conducted with 12 users of SPECS from around the United Kingdom. These interviews were transcribed and analysed using a qualitative method based on framework analysis. Reliability is the main influence on the use of SPECS. All the participants gave examples of occasions when their speech-driven system was unreliable; in some instances, this unreliability was reported as not being a problem (e.g., for changing television channels); however, it was perceived as a problem for more safety critical functions (e.g., opening a door). Reliability was cited by participants as the reason for using a switch-operated system as back up. Benefits of speech-driven systems focused on speech operation enabling access when other methods were not possible; quicker operation and better aesthetic considerations. Overall, there was a perception of increased independence from the use of speech-driven environmental control. In general, speech was considered a useful method of operating environmental controls by the participants interviewed; however, their perceptions regarding reliability often influenced their decision to have backup or alternative systems for certain functions.

  14. Effects-Driven IT Development: Status 2004-2011

    DEFF Research Database (Denmark)

    Hertzum, Morten; Simonsen, Jesper

    2011-01-01

    that the desired effects can be specified and measured, though we have mixed experiences with ensuring that effects are measured. An effects hierarchy has been devised and appears suitable for working with effects at different levels of abstraction. A key challenge with which we still have insufficient experience...... the benefits of the deployed system. Effects-driven IT development aims to counter this risk by providing an instrument for managing IT projects through a sustained focus on the effects desired from the use of the IT system. A sustained focus on effects entails that the specification, realization......, and assessment of effects become central systems-development activities. In this chapter, we describe the six empirical projects we have conducted in our work on effects-driven IT development during the period 2004–2011 and we discuss the experiences gained so far. The empirical projects indicate...

  15. Radiation-driven winds in x-ray binaries

    International Nuclear Information System (INIS)

    Friend, D.B.; Castor, J.I.

    1982-01-01

    We discuss the properties of a radiation-driven stellar wind in an X-ray binary system. The Castor, Abbott, Klein line-driven wind model is used, but the effects of the compact companion (gravity and continuum radiation pressure) and the centrifugal force due to orbital motion are included. These forces destroy the spherical symmetry of the wind and can make the mass loss and accretion strong functions of the size of the primary relative to its critical potential lobe. We in most systems the wind alone could power the X-ray emission. It also appears that, in the evolution of these systems, there would be a continuous transition from wind accretion to critical potential lobe overflow. The model is also used to make a prediction about the nature of a suspected binary system which is not known to be an X-ray emitter

  16. Recent Progress in Energy-Driven Water Splitting.

    Science.gov (United States)

    Tee, Si Yin; Win, Khin Yin; Teo, Wee Siang; Koh, Leng-Duei; Liu, Shuhua; Teng, Choon Peng; Han, Ming-Yong

    2017-05-01

    Hydrogen is readily obtained from renewable and non-renewable resources via water splitting by using thermal, electrical, photonic and biochemical energy. The major hydrogen production is generated from thermal energy through steam reforming/gasification of fossil fuel. As the commonly used non-renewable resources will be depleted in the long run, there is great demand to utilize renewable energy resources for hydrogen production. Most of the renewable resources may be used to produce electricity for driving water splitting while challenges remain to improve cost-effectiveness. As the most abundant energy resource, the direct conversion of solar energy to hydrogen is considered the most sustainable energy production method without causing pollutions to the environment. In overall, this review briefly summarizes thermolytic, electrolytic, photolytic and biolytic water splitting. It highlights photonic and electrical driven water splitting together with photovoltaic-integrated solar-driven water electrolysis.

  17. Dynamic Systems Driven by Non-Poissonian Impulses

    DEFF Research Database (Denmark)

    Nielsen, Søren R.K.; Iwankiewicz, R.

    interarrival times. The moment equations for the augmented Poisson driven system are derived and closed by an ordinary cumulant neglect closure at the order N=4. The obtained moments are compared with these obtained by Monte Carlo simulations for both the original process with lognormally distributed......Dynamic systems under random trains of impulses driven by renewal point processes are studied. Then the system state variables no longer form a Markov vector as it is in the case of Poisson impulses. A general format is given for the replacing an ordinary renewal process by an equivalent Poisson...... process at the expense of the introduction of auxiliary state variables. A technique is devised for truncating the hierarchy of stochastic equations governing the auxiliary state variables. For the generalized Erlang process, suitable for approximating a wide class of renewal processes, the technique...

  18. Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

    Directory of Open Access Journals (Sweden)

    Turgut Topal

    2007-08-01

    Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull. 2007; 6(4: 227-232

  19. Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

    Directory of Open Access Journals (Sweden)

    Turgut Topal

    2007-08-01

    Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull 2007; 6(4.000: 227-232

  20. A Model-Driven Development Method for Management Information Systems

    Science.gov (United States)

    Mizuno, Tomoki; Matsumoto, Keinosuke; Mori, Naoki

    Traditionally, a Management Information System (MIS) has been developed without using formal methods. By the informal methods, the MIS is developed on its lifecycle without having any models. It causes many problems such as lack of the reliability of system design specifications. In order to overcome these problems, a model theory approach was proposed. The approach is based on an idea that a system can be modeled by automata and set theory. However, it is very difficult to generate automata of the system to be developed right from the start. On the other hand, there is a model-driven development method that can flexibly correspond to changes of business logics or implementing technologies. In the model-driven development, a system is modeled using a modeling language such as UML. This paper proposes a new development method for management information systems applying the model-driven development method to a component of the model theory approach. The experiment has shown that a reduced amount of efforts is more than 30% of all the efforts.