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Nitric Oxide as a Mediator of Cerebral Blood-Flow, Synaptic Plasticity, and Superoxide-Mediated Brain Injury

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Book cover Oxygen Free Radicals in Tissue Damage

Abstract

We propose that excessive production of nitric oxide initiated by activation of glutamate receptors after cerebral ischemia potentiates free radical injury to the brain. Nitric oxide, produced by neurons and possibly astrocytes, helps regulate local cerebral blood flow and plays an essential role in synaptic plasticity and normal development of the brain. Nitric oxide itself is a weak oxidizing agent, but after reaction with superoxide (O -2 ), it forms the strong and relatively long-lived oxidant peroxynitrite anion (ONOO-) (Beckman et al., 1990). Peroxynitrite is sufficiently stable even in the presence of physiological concentrations of glutathione and other cellular antioxidants to diffuse for up to several cell diameters. Depending on what peroxynitrite reacts with, it can produce oxidants with the reactivity of hydroxyl radical (HO⋅), nitrogen dioxide (NO2), nitronium ion (NO +2 ), and possibly singlet oxygen. Thus, the conversion of nitric oxide to peroxynitrite and related secondary oxidants may provide a common link between glutamate and free radical-mediated injury. Glutamate antagonists and free radical scavengers can reduce infarct volume by approximately the same extent in rat middle cerebral artery occlusion models of stroke (Oh and Betz, 1991). Recently, nitroarginine, a competitive inhibitor of nitric oxide synthesis, has also been shown to reduce infarct volume in a mouse middle cerebral ischemia model (Nowicki et al., 1991).

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References

  • Albina J, Mills C, Henry WL Jr, Caldwell M (1989): Regulation of macrophage physiology by L-arginine. Role of the oxidative L-arginine deiminase pathway. J Immunol 143:3641–3646.

    Google Scholar 

  • Ando Y, Inoue M, Hirota M, Morino Y, Araki S (1989): Effect of superoxide dismutase derivative on cold-induced brain edema. Brain Res 477:286–291.

    Article  Google Scholar 

  • Araki N, Greenberg J, Uematsu D, Sladky J, Reivich M (1992): Effect of superoxide dismutase on intracellular calcium in stroke. J Cereb Blood Flow Metab 12:43–52.

    Article  Google Scholar 

  • Baum RM (1984): Superoxide theory of oxygen toxicity is center of heated debate. Chem Engin News April 9, 1984:20–28.

    Google Scholar 

  • Beckman JS (1990): Ischemic injury mediator. Nature (Lond) 345: 27–28.

    Article  Google Scholar 

  • Beckman JS (1991): The double edged role of nitric oxide in brain function and superoxide-mediated pathology. J Devl Physiol 15:53–59.

    Google Scholar 

  • Beckman JS, Beckman TW, Chen J, Marshall PM, Freeman BA (1990): Apparent hydroxyl radical production from peroxynitrite: implications for endothelial injury by nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624.

    Article  Google Scholar 

  • Beckman JS, Liu TH, Hogan EL, Lindsay SL, Freeman BA, Hsu CY (1988): Evidence for a role of oxygen radicals in cerebral ischemic injury. In: Cere brovascular Diseases ,Ginsberg WDD, ed. New York: Raven Press.

    Google Scholar 

  • Beckman JS, Minor RM Jr, White CJ, Repine J, Rosen GM, Freeman BA (1988): Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance. J Biol Chem 263:6584–6802.

    Google Scholar 

  • Bernier M, Manning A, Hearse D (1989): Reperfusion arrhythmias: dose-related protection by anti-free radical interventions. Am J Physiol 256:H1344–H1352.

    Google Scholar 

  • Beyer W Jr, Fridovich I, Mullenbach GT, Hallewell R (1987): Examination of the role of arginine-143 in the human copper and zinc superoxide dismutase by site-specific mutagenesis. J Biol Chem 262:11182–11187.

    Google Scholar 

  • Blough NV, Zafiriou OC (1985): Reaction of superoxide with nitric oxide to form peroxonitrite in alkaline aqueous solution. Inorg Chem 24:3504–3505.

    Article  Google Scholar 

  • Böhme G, Bon C, Stutzmann JM, Doble A, Blanchard JC (1991): Possible involvement of nitric oxide in long-term potentiation. Eur J Pharmacol 199:379–381.

    Article  Google Scholar 

  • Bredt D, Hwang P, Glatt C, Lowenstein C, Reed R, Snyder S (1991): Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature 351:714–718.

    Article  Google Scholar 

  • Bredt DS, Snyder HS (1990): Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci USA 87:682–685.

    Article  Google Scholar 

  • Brown TH, Chapman PF, Kairiss EW, Keenan CL (1988): Long-term synaptic potentiation. Science 242:724–728.

    Article  Google Scholar 

  • Brune B, Lapetina EG (1990): Properties of a novel nitric oxide-stimulated ADP-ribosyltransferase. Arch Biochem Biophys 279:286–290.

    Article  Google Scholar 

  • Busse R, Luckhoff A, Bassenge E (1987): Endothelium-derived relaxant factor inhibits platelet activation. Naunyn-Schmiedeberg’s Arch Pharmacol 336:566–571.

    Article  Google Scholar 

  • Cao W, Carney JM, Duchon A, Floyd RA, Chevion M (1988): Oxygen free radical involvement in ischemia and reperfusion injury to brain. Neurosci Lett 88:233–238.

    Article  Google Scholar 

  • Chan P, Chu L, Chen S, Carlson E, Epstein C (1990): Reduced neurotoxicity in transgenic mice overexpressing human copper-zinc-superoxide dismutase. Stroke 21(suppl III):III-80–82.

    Google Scholar 

  • Chan P, Yang G, Chen S, Carlson E, Epstein C (1991): Cold-induced brain edema and infarction are reduced in transgenic mice overexpressing CuZn-superoxide dismutase. Ann Neurol 29:482–486.

    Article  Google Scholar 

  • Chan PH, Longar S, Fishman RA (1987): Protective effects of liposome-entrapped superoxide on post-traumatic brain edema. Ann Neurol 21:540–547.

    Article  Google Scholar 

  • Colton A, Gilbert D (1987): Production of superoxide by a CNS macrophage, the microglia. FEBS Lett 223:284–288.

    Article  Google Scholar 

  • Dawson T, Bredt D, Fotuhi M, Hwang P, Snyder S (1991a): Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 88:7797–7801.

    Article  Google Scholar 

  • Dawson V, Dawson T, London E, Brent D, Snyder S (1991b): Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Natl Acad Sci USA 88:6368–6371.

    Article  Google Scholar 

  • Deguchi T, Yoshioka M (1982): L-Arginine identified as an endogenous activator for soluble guanylate cyclase from neuroblastoma cells. J Biol Chem 257:10147–10151.

    Google Scholar 

  • Demerlè-Pallardy C, Lonchampt M-O, Chabrier P-E, Braquet P (1991): Absence of implication of L-arginine/nitric oxide pathway in neuronal cell injury induced by L-glutamate or hypoxia. Biochem Biophys Res Commun 181:456–464.

    Article  Google Scholar 

  • East S, Garthwaite J (1991): NMDA receptor activation in the rat hippocampus induces cyclic GMP formation through the L-arginine-nitric oxide pathway. Neurosci Lett 123:17–19.

    Article  Google Scholar 

  • Föstermann U, Gorsky L, Pollock J, Schmidt H, Heller M, Murad F (1990): Regional distribution of EDRF/NO-synthesizing enzyme(s) in rat brain. Biochem Biophys Res Commun 168:727–732.

    Article  Google Scholar 

  • Fridovich I (1986): Biological effects of the superoxide radical. Arch Biochem Biophys 247:1–11.

    Article  Google Scholar 

  • Furchgott RF, Vanhoutte PM (1989): Endothelium-derived relaxing and contracting factors. FASEB J 3:2007–2018.

    Google Scholar 

  • Gaily JA, Montague PR, Reeke GN Jr, Edelman GM (1990): The NO hypothesis: possible effects of a short-lived, rapidly diffusible signal in the development and function of the nervous system. Proc Natl Acad Sci USA 87:3547–3551.

    Article  Google Scholar 

  • Garthwaite J, Charles SL, Chess-Williams R (1988): Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature (Lond) 336:385–388.

    Article  Google Scholar 

  • Gehrmann J, Bonnekoh P, Miyazawa T, Hossman K, Kreutzberg G (1992): Immunocytochemical study of an early microglial activation in ischemia. J Cereb Blood Flow Metab 12:257–269.

    Article  Google Scholar 

  • Getzoff ED, Tainer JA, Weiner PK, Kollman PA, Richardson JS, Richardson DC (1983): Electrostatic recognition between superoxide and copper, zinc superoxide dismutase. Nature (Lond) 306:287–290.

    Article  Google Scholar 

  • Goldberg MP, Weiss JH, Pham P-C, Choi DW (1987): N-methyl-D-aspartate receptors mediate hypoxic neuronal injury in cortical culture. J Pharmacol Exp Ther 24:784–791.

    Google Scholar 

  • Granger D, Hibbs J Jr, Perfect J, Durak D (1988): Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages. J Clin Invest 81:1129–1136.

    Article  Google Scholar 

  • Hebb DO (1949): The organization of behavior. New York: Wiley.

    Google Scholar 

  • Hibbs J Jr, Taintor R, Vavrin Z (1987): Macrophage cytotoxicity: Role of Larginine deminiase and imino nitrogen oxidation to nitrite. Science 235:473–235.

    Article  Google Scholar 

  • Hibbs J Jr, Taintor R, Vavrin Z, Rachlin E (1988): Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157:87–94.

    Article  Google Scholar 

  • Hope B, Michael G, Knigge K, Vincent S (1991): Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci USA 88:2811–2814.

    Article  Google Scholar 

  • Hughes M, Nickline H, Sackrule W (1971): The chemistry of peroxynitrites with nucleophiles in alkali, and other nitrite producing reactions. J Chem Soc A 3722–3725.

    Google Scholar 

  • Ignarro LJ (1990): Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol 30:535–560.

    Article  Google Scholar 

  • Imaizumi S, Wollworth V, Fishman RA, Chan PH (1990): Liposome-entrapped superoxide dismutase reduces cerebral infarction in cerebral ischemia in rats. Stroke 21:1312–1317.

    Article  Google Scholar 

  • Ischiropoulos H, Chen J, Tsai JM, Martin J, Smith C, Beckman J (1990): Peroxynitrite (ONOO-) reacts with superoxide dismutase to give the reactive nitronium ion. Free Rad Biol Med 9(S1):131 Abstract.

    Article  Google Scholar 

  • Iyengar R, Stuehr D, Marietta M (1987): Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst. Proc Natl Acad Sei USA 84:6369–6373.

    Article  Google Scholar 

  • Johnston R Jr, Godzik C, Cohn Z (1978): Increased superoxide anion production by immunologically activated and chemically elicited macrophages. J Exp Med 22:115–127.

    Article  Google Scholar 

  • Kinoshita A, Yamada K, Kohmura E, Hayakawa T (1991): Human recombinant superoxide dismutase protects cultured neurons against hypoxic injury. Pathobiology 59:340–344.

    Article  Google Scholar 

  • Kontos HA (1985): Oxygen radicals in cerebral vascular injury. Circ Res 57:508– 516.

    Article  Google Scholar 

  • Kontos HA, Wei EP (1986): Superoxide production in experimental brain injury. J Neurosurg 64:803–807.

    Article  Google Scholar 

  • Kukreja RC, Kontos HA, Hess ML, Ellis EF (1986): PGH synthase and lipoxygenase generate superoxide in the presence of NADH or NADPH. Circ Res 59:612–619.

    Article  Google Scholar 

  • Liu TH, Beckman JS, Freeman BA, Hogan EL, Hsu CY (1989): Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury. Am J Physiol 256:H589–H593.

    Google Scholar 

  • Lynch RE, Fridovich I (1978): Permeation of erythrocyte stroma by superoxide radical. J Biol Chem 253:4697–4699.

    Google Scholar 

  • Marietta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS (1988): Macrophage Oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 27:8706–8711.

    Article  Google Scholar 

  • Matheis G, Sherman M, Buckberg G, Haybron D, Young H, Ignarro L (1992): Role of L-arginine-nitric oxide pathway in myocardial reoxygenation injury. Am J Physiol 262:H616–H620.

    Google Scholar 

  • Mayer B, John M, Böhme E (1990): Purification of a Ca+2/calmodulin-dependent nitric oxide synthase from porcine cerebellum. Cofactor-role of tetrahydro-biopterin. FEBS Lett 277:215–219.

    Article  Google Scholar 

  • Mayer ML, Miller RJ (1990): Excitatory amino acid receptors, second messengers and regulation of intracellular Ca+2 in mammalian neurons. Trends Pharmacol Sci 11:254–260.

    Article  Google Scholar 

  • Mayer ML, Westbrook GL, Gurthie PE (1984): Voltage-dependent block by Mg+2 of NMDA responses in spinal cord neurons. Nature (Lond) 309:261– 277.

    Article  Google Scholar 

  • McCall TB, Boughton-Smith NK, Palmer RMJ, Whittle BJR, Moncada S (1989): Synthesis of nitric oxide from L-arginine by neutrophils. Biochem J 261:293– 296.

    Google Scholar 

  • Ment LA, Steward WB, Duncan CC (1985): Superoxide dismutase protects in a beagle puppy model of neonatal intraventricular hemorrhage. J Neurosurg 62:563–567.

    Article  Google Scholar 

  • Miyamoto M, Murphy T, Schnaar R, Coyle J (1989): Antioxidants protect against glutamate-induced cytotoxicity in a neuronal cell line. J Pharmacol Exp Ther 250:1132–1140.

    Google Scholar 

  • Moncada S, Herman AG, Vanhoutte PM (1987): Endothelium-derived relaxing factor is identified as nitric oxide. Trends Pharmacol Sci 8:365–368.

    Article  Google Scholar 

  • Moncada S, Palmer R, Higgs E (1991): Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142.

    Google Scholar 

  • Mulligan M, Hevel J, Marietta M, Ward P (1991): Tissue injury caused by deposition of immune complexes is L-arginine dependent. Proc Natl Acad Sci USA 88:6338–6342.

    Article  Google Scholar 

  • Murphy S, Minor R Jr, Wel G, Harrison D (1990): Evidence for an astrocyte-derived vasorelaxing factor with properties similar to nitric oxide. J Neu-rochem 55:349–351.

    Article  Google Scholar 

  • Novelli A, Reilly JA, Lysko PG, Henneberry RC (1988): Glutamate becomes neurotoxic with the N-methyl-D-asptarate receptor when intracellular energy levels are reduced. Brain Res 451:205–212.

    Article  Google Scholar 

  • Nowicki J, Duval D, Poignet H, Scatton B (1991): Nitric oxide mediates neuronal death after focal cerebral ischemia in the mouse. Eur J Pharmacol 204:339– 340.

    Article  Google Scholar 

  • Oh S, Betz A (1991): Interaction between ree radicals and excitatory amino acids in the formation of ischemic brain edema in rats. Stroke 22:915–921.

    Article  Google Scholar 

  • Omar B, Gad N, Jordan M, Striplin S, Russell W, Downey J, McCord J (1990): Cardioprotection by Cu,Zn-superoxide dismutase is lost at high doses in the reoxygenated heart. Free Rad Biol Med 9:465–471.

    Article  Google Scholar 

  • Omar BA, McCord J (1990): The cardioprotective effect of Mn-superoxide dismutase is lost at high doses in the postischemic isolate rabbit heart. Free Rad Biol Med 9:473–478.

    Article  Google Scholar 

  • Palmer RMJ, Ashton DS, Moncada S (1988): Arginine is the source of endothe-lial-derived nitric oxide. Nature (Lond) 333:664–666.

    Article  Google Scholar 

  • Palmer RMJ, Ferrige AG, Moncada S (1987): Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature (Lond) 327:523–526.

    Article  Google Scholar 

  • Park CK, Nehls DG, Graham DI, Teasdale GM, McCullough J (1988): Focal cerebral ischemia in the cat: treatment with the glutamate antagonist MK-801 after induction of ischemia. J Cereb Blood Flow Metab 8:757–762.

    Article  Google Scholar 

  • Pollock J, Förstermann J, Mitchell J, Warner T, Schmidt H, Nakane M, Murad F (1991): Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells. Proc Natl Acad Sci USA 88:10480–10484.

    Article  Google Scholar 

  • Radi R, Beckman JS, Bush KM, Freeman BA (1991): Sulfhydryl oxidation by peroxynitrite: the cytotoxic potential of superoxide and nitric oxide. J Biol Chem 266:4244–4250.

    Google Scholar 

  • Radomski M, Palmer R, Moncada S (1990): Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci USA 87:10043–10047.

    Article  Google Scholar 

  • Rothman SM (1984): Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J Neurosci 4:1884–1891.

    Google Scholar 

  • Rubanyi GM, Vanhoutte PM (1986): Superoxide anions and hyperoxia inactive endothelium-derived relaxing factor. Am J Physiol 250:H822–H827.

    Google Scholar 

  • Saez JS, Kessler JA, Bennett MVL, Spray DC (1987): Superoxide dismutase protects cultured neurons against death by starvation. Proc Natl Acad Sci USA 84:3056–3059.

    Article  Google Scholar 

  • Saran M (1990): Reaction of NO with O2-. Implications for the action of endothelium-derived relaxing factor (EDRF). Free Rad Res Commun 10:221– 226.

    Article  Google Scholar 

  • Sawyer DT, Valentine J (1981): How super is superoxide? Acct Chem Res 14:393–400.

    Article  Google Scholar 

  • Schmidt H, Pollock J, Nakane M, Gorsky L (1991): Purification of a soluble isoform of guanylyl cyclase-activating factor synthase. Proc Natl Acad Sci USA 88:365–369.

    Article  Google Scholar 

  • Seisjo BK, Bengtsson F (1989): Calcium fluxes, calcium antagonists, and calciumrelated pathology in brain ischemia, hypoglycemia, and spreading depression: a unifying hypothesis. J Cereb Blood Flow Metab 9:127–140.

    Article  Google Scholar 

  • Shibuki K (1990): An electrochemical microprobe for detecting nitric oxide release in brain tissue. Neurosci Res 9:69–76.

    Article  Google Scholar 

  • Shibuki K, Okada D (1991): Endogenous nitric oxide release required for longterm synaptic depression in the cerebellum. Nature (Lond) 349:326–329.

    Article  Google Scholar 

  • Shulman E, Madison D (1991): A requirement for the intercellular messenger nitric oxide in long-term potentiation. Science 254:1503–1506.

    Article  Google Scholar 

  • Simon RP, Swan JH, Griffins T, Meldrum BS (1984): Blockade of N-methyl-D aspartate receptors may protect against ischemic damage in the brain. Science 226:850–885.

    Article  Google Scholar 

  • Southam E, East S, Garthwaite J (1991): Excitatory amino acid receptors coupled to the nitric oxide/cyclic GMP pathway in rat cerebellum during development. JNeurochem 56:2072–2081.

    Article  Google Scholar 

  • Stuehr D, Kwon N, Nathan C, Griffin O, Feldman P, Wiseman J (1991): NW- hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine. J Biol Chem 266:6259–6263.

    Google Scholar 

  • Stuehr DJ, Nathan C (1989): Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor cells. J Exp Med 169:1543– 1555.

    Article  Google Scholar 

  • Takeuchi Y, Morii H, Tamura M, Hayaishi O, Watanabe Y (1991): A possible mechanism of mitochondrial dysfunction during cerebral ischemia: inhibition of mitochondrial respiration activity by arachidonic acid. Arch Biochem Biophys 289:33–38.

    Article  Google Scholar 

  • Turrens J, Beconi M, Barilla J, Chavez U, McCord J (1991): Mitochondrial generation of oxygen radicals during reoxygenation of ischemic tissues. Free Rad Res Commun 12:681–689.

    Article  Google Scholar 

  • Uemura Y, Kowall N, Beal M (1990): Selective sparing of NADPH-diaphorase somatostatin-neuropeptide Y neurons in ischemic gerbil striatum. Ann Neurol 27:620:625.

    Article  Google Scholar 

  • Wallace GC, Fukuto J (1991): Synthesis and bioactivity of NW-hydroxyarginine: a possible intermediate in the biosynthesis of nitric oxide from arginine. J Med Chem 34:1746–1748.

    Article  Google Scholar 

  • Williams JH, Errington ML, Lynch MA, Bliss TVP (1989): Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus. Nature (Lond) 341:739–742.

    Article  Google Scholar 

  • Yokoyama Y, Beckman JS, Wheat J, Cash TG, Freeman BA, Parks DA (1990): Circulating xanthine oxidase: potential mediator of ischemic injury. Am J Physiol 258:G564–G570.

    Google Scholar 

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Authors
  1. Joseph S. Beckman
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  2. Jun Chen
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  3. Harry Ischiropoulos
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  4. Ling Zhu
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  5. Karl A. Conger
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  6. James H. Halsey Jr
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Editors and Affiliations

  1. Dept. of Physiology, University of Kansas Medical Ctr., Kansas City, KS, 66160-7401, USA

    Merrill Tarr

  2. Ralph L. Smith Research Center, University of Kansas Medical Ctr., Kansas City, KS, 66160-7401, USA

    Fred Samson

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Beckman, J.S., Chen, J., Ischiropoulos, H., Zhu, L., Conger, K.A., Halsey, J.H. (1993). Nitric Oxide as a Mediator of Cerebral Blood-Flow, Synaptic Plasticity, and Superoxide-Mediated Brain Injury. In: Tarr, M., Samson, F. (eds) Oxygen Free Radicals in Tissue Damage. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4615-9840-4_10

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  • DOI: https://doi.org/10.1007/978-1-4615-9840-4_10

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