Summary
The enzyme peroxidase has acquired popularity with plant scientists partly because its activity is inversely related to growth rate, perhaps as a consequence of the enzyme’s IAA oxidase activity, and partly because its “isozymes” vary with the developmental state of the tissue studied. The changes in both activity and “isozyme” patterns could be accounted for by de novo synthesis of the enzyme or by post-synthesis alterations of existing enzyme molecules. The paucity of information on the structural nature of peroxidase “isozymes” has hampered a distinction being made in most physiological studies between synthesis and post-synthesis mechanisms of change. This leaves the basic question of peroxidase regulation unanswered.
Analogies between peroxidase and other hemoproteins like hemoglobin and leghemoglobin lead to the suggestion that heme might function in regulating apoperoxidase synthesis. Investigations with peanut cells in suspension culture indicate that the heme of peroxidase is drawn from a cellular heme pool. Whereas peroxidase activity in these cells exhibits a phytochrome-mediated light response, the heme pool responds otherwise to light. The lack of parallels in the response of peroxidase and the heme pool to light argue for a lack of heme involvement in at least the lightmediated changes in peroxidase activity although the role of heme in establishing the baseline levels of peroxidase in the dark has yet to be explored.
The use of a peroxidase-specific mRNA is proposed to facilitate studies of the mechanisms of change in activity and “isozyme” pattern and to facilitate identification of the factors involved in the regulation of peroxidase synthesis.
Resumé
L’enzyme appelée peroxydase a acquis une popularité auprès des botanistes à cause de son activité qui est inversement proportionnelle au taux de croissance, ceci etant probablement une conséquence de l’activité enzymatique de l’oxydase AIA, d’autre part a cause de ses differents “Isoenzymes” dont le nombre varie selon l’état de développement du tissu etudié. Les changements au niveau de son activité enzymatique et de son nombre d’isoenzymes pourraient être dûs à la synthèse de novo de l’enzyme ou à des alterations des molécules enzymatiques existantes. Le manque d’information concernant la structure des “isoenzymes” de la peroxydase a gêné une distinction, faite dans la plupart des études physiologiques, entre les mécanismes de changement au cours de la synthèse et ceux après la synthèse. Ceci laisse la question fondamentale du mécanisme de régulation de la peroxydase sans réponse.
Des analogies entre la peroxydase et d’autres hemoprotéines comme l’hemoglobine et la leg-hemoglobine conduisent a suggérer que l’heme pourrait intervenir dans la régulation de la synthèse de l’apoperoxydase. Des investigations faites avec des cellules d’arachide en culture liquide, indiquent que l’heme de la peroxydase provient d’un pool hemique cellulaire. Différemment a celle du pool hemique, la réponse à la lumiere de l’activité peroxydasique se fait par l’intermediaire du phytochrome. Le manque de parallele entre la réponse de la peroxydase et celle du, pool hemique a la lumière indiquerait que l’heme ne serait pas impliqué dans les changements de l’activité peroxydasique interverant sous l’effet de la lumière. Cependant le rôle de l’heme, lors de l’étude de la réponse de l’activité peroxydasique à l’obscurité rstera etre déterminé.
L’utilisation d’un mRNA specifique de la peroxydase est proposée pour faciliter les études des mecanismes de changement au niveau de l’activité et au niveau du nombre d’isoenzymes et pour faciliter l’identification des facteurs intervenant dans la régulation de la synthèse de la peroxydase.
Zusammenfassung
Peroxidase ist bei Pflanzenwissenschaftlern deshalb beliebt geworden, weil einerseits bei diesem Enzym eine entgegengesetzte Wechselwirkung zur Wachstumsrate besteht (wahrscheinlich als Konsequenz der IAA Oxidase Aktivität des Enzyms) und andererseits, weil ihre “Isoenzyme” mit dem Wachstumsstadium des untersuchten Gewebes wechseln. Die Veränderung in Aktivität und “Isoenzym” —Muster kann durch de novo—Synthese des Enzyms oder durch nach-synthetische Veränderungen bestehender Enzym-Moleküle erklärt werden. Da die Struktur von Peroxidase “Isoenzymen” kaum beschrieben ist, ist in den meisten physiologischen Untersuchungen eine Unterscheidung erschwert zwischen der Synthese und dem nach-synthetischen Veränderungs-mechanismus. Dies lässt die Grundfrage der Peroxidase Regulation unbeantwortet.
Analogien zwischen Peroxidase und anderen Hamoproteinen wie Hamoglobin und Leghamoglobin lassen erwarten, dass die Regulation von Apoperoxidase Synthese eine Häm Funktion ist. Experimente mit Erdnusszellen in Suspensionskultur zeigen, dass das Häm der Peroxidase einem zellulären Pool entzogen wird. Während Peroxidase Aktivität in diesen Zellen eine Phytochrom-vermittelte Lichtreaktion zeigen, reagiert der Häm Pool insgesamt anders zu Licht. Mangel an Parallelen in der Reaktion der Peroxidase und dem Häm Pool zu Licht argumentieren dagegen, dass das Häm in der Licht-vermittelten Veränderung in der Peroxidase Aktivität eine grosse Rolle spielt, obwohl die Rolle des Häm in der Bestimmung des Grundniveaus der Peroxidase im Dunkeln noch zu untersuchen ist.
Es wird vorgeschlagen, Peroxidase-spezifisches mRNS zu benutzen, um den Mechanismus der Veränderung in Aktivität und “Isoenzym” Muster zu untersuchen, und um die Bestimmung der Faktoren zu erleichtern, die in der Regulation von Peroxidase Synthese am Werk sind.
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Literature Cited
Alibert, G., R. Ranjeva andA. M. Boudet. 1977. Organization subcellulaire des voies de synthèse de composés phenoliques. Physiol. Vég.15: 279–301.
Anstine, W., J. V. Jacobsen, J. G. Scandalios andJ. E. Varner. 1970. Deuterium oxide as a density label of peroxidases in germinating barley embryos. Plant Physiol.45: 148–152.
Baumann, I., G. Baumann andG. Gunther. 1977. Effect of 3 amino-l,2,4-triazole (Amitrole) on cytoplasmic and chloroplast rRNA of oat seedlings. Biochem. Physiol. Pflanzen171: 157–163.
Bastin, M. 1968. Effect of wounding on the synthesis of phenols, phenol oxidase and peroxidase in tuber tissue of Jerusalem artichoke. Can. J. Biochem.46: 1339–1343.
Birecka, H. andA. W. Galston. 1970. Peroxidase ontogeny in dwarf pea stem as affected by gibberellin and decapitation. J. Exp. Bot.21: 735–745.
— andA. Miller. 1974. Cell wall and protoplast isoperoxidase in relation to injury, indole acetic acid and ethylene effects. Plant Physiol.53: 569–574.
Bradbeer, J. W., Y. E. Atkinson, T. Börner andR. Hagemann. 1979. Cytoplasmic synthesis of plastid polypeptides may be controlled by plastid-synthesized RNA. Nature279: 816–817.
Brownlee, C. andR. E. Kendrick. 1979a. Ion fluxes and phytochrome protons in mung bean hypocotyl segments. I. Fluxes of potassium. Plant Physiol.64: 206–210.
——. 1979b. Ion fluxes and phytochrome protons in mung bean hypocotyl segments. II. Fluxes of chloride, protons and orthophosphate in apical and subhook segments. Plant Physiol.64: 211–213.
Cairns, E., R. B. van Huystee andW. L. Cairns. 1979. Peanut and horse radish peroxidase isozymes. Intraspecies and interspecies immunological relatedness. Physiol. Plant.49: 78–82.
Castelfranco, P. A. andO. T. G. Jones. 1975. Protoheme turnover and chlorophyll synthesis in greening barley leaves. Plant Physiol.55: 485–490.
Catedral, F. andJ. M. Daly. 1976. Partial characterization of peroxidase isoenzymes from rust affected wheat leaves. Phytochemistry15: 627–631.
Chang, J. Y. andW. A. Schroeder. 1973. Reaction of 3 amino-l,2,4-triazole with lactoperoxidase. Arch. Biochem. Biophys.156: 475–479.
Clemens, M. J. 1976. Functional relationships between a reticulocyte polypeptide-chain initiation factor (IF-MP) and the translation inhibitor involved in regulation of protein synthesis by haemin. Eur. J. Biochem.66: 413–422.
Cutting, J. A. andH. M. Schulman. 1971. The biogenesis of leghemoglobin. The determinant in theRhizobium-legume symbiosis for leghemoglobin specificity. Biochem. Biophys. Acta229: 58–62.
Dabney, B. J. andA. L. Beaudet. 1977. Increase in globin chains and globin mRNA in erythroleukemia cells in response to hemin. Arch. Biochem. Biophys.179: 106–122.
Dalton, C. C. andH. E. Street. 1976. The role of the gas phase in the greening and growth of illuminated cell suspension cultures of spinach (Spinacia oleracea L.). In vitro12: 485–473.
Derbyshire, B. 1973. The glycoprotein nature of Indole acetic acid oxidase/peroxidase fraction and their development in pea roots. Physiol. Plant.29: 293–297.
Daussant, J., J. Roussaux andP. Manigault. 1971. Characterizations immunochémiques de deux auxine oxydases extraites de tumeurs vegetables. F.E.B.S. Lett.14: 245–250.
Dunford, H. B. andJ. S. Stillman. 1976. On the function and mechanism of action of peroxidase. Coordination Chemistry Reviews19: 187–251.
Enzyme Nomenclature. 1972. Recommendations of the International Union of Pure and Applied Chemistry and the International Union of Biochemistry. Elsevier Scientific Publishing Co., Amsterdam.
Evans, J. J. andN. A. Alldridge. 1965. The distribution of peroxidase in extreme dwarf and normal tomato. Phytochemistry4: 499–503.
Feierabend, J. andB. Schubert. 1978. Comparative investigation of the action of several chlorosis-inducing herbicides on the biogenesis of chloroplasts and leaf microbodies. Plant Physiol.61: 1017–1022.
Fieldes, M. A. andH. Tyson. 1973. Total phenolic content and peroxidase isozymes inLinum usitatissimum. Phytochemistry12: 2133–2143.
Freeling, M. andD. Schwartz. 1973. Genetic relationships between the multiple alcohol dehydrogenases of maize. Biochem. Gen.8: 27–36.
Galston, A. W. andP. J. Davies. 1969. Hormonal regulation in higher plants. Science163: 1288–1297.
——. (eds.). 1970. Control mechanisms in plant development. Prentice-Hall Inc., Englewood Cliffs, NJ. P. 149–163.
Gardiner, M. G. andR. Cleland. 1974. Peroxidase isoenzymes of theAvena coleoptile. Phytochemistry13: 1707–1711.
Gaspar, T., A. Berville andE. Darimont. 1974. Peroxidase activity and isoperoxidase pattern of a commercial cytochrome c compared with a maize mitochondrial fraction. Plant Biochem. J.1: 59–63.
Granick, S. andS. I. Beale. 1978. Hemes, chlorophylls and related compounds: Biosynthesis and metabolic regulation. A. Meister (ed.).In: Advances in Enzymology 46: 33–203. J. Wiley and Sons, New York.
Hare, R. C. 1964. Indole acetic acid oxidase. Bot. Rev.30: 129–165.
Harkin, J. M. andJ. R. Obst. 1973. Lignification in trees: indication of exclusive peroxidase participation. Science180: 296–298.
Hendry, G. A. F. andA. K. Stobart. 1977. Haem and chlorophyll formation in etiolated and greening leaves of barley. Phytochemistry16: 1545–1548.
——. 1978. The effect of haem on chlorophyll synthesis in barley leaves. Phytochemistry17: 73–77.
Hinnman, R. L. andJ. Lang. 1965. Peroxidase catalyzed oxidation of indole 3-acetic acid. Biochemistry4: 144–158.
Hopkins, W. G. 1972. Independence of phytochrome destruction and physiological response inAvena andPisum segment elongation. Can. J. Bot.50: 1–7.
Huner, N. P. A. andF. D. H. Macdowall. 1979a. Changes in the net charge and subunit properties of ribulose biphosphate carboxylase-oxygenase during cold hardening of Puma rye. Can. J. Biochem.57: 155–164.
——. 1979b. The effects of low temperature acclimation of winter rye on catalytic properties of its ribulose biphosphate carboxylase-oxygenase. Can. J. Biochem.57: 1036–1041.
Ibrahim, N. G., S. T. Hoffstein andM. L. Freedman. 1979. Induction of liver cell oxygenase in iron-overloaded rats. Biochem. J.180: 257–263.
Ida, S., I. Kitamura, H. Nikaido andY. Morita. 1972. Studies on respiratory enzymes in rice kernel. IX. Peroxidase isoenzymes of rice embryo. Agric. Biol. Chem.36: 611–620.
Jennings, A. C. andH. E. Street. 1974. Changes in peroxidase isoenzyme activities in batch cultured sycamore cells—problems of assay by gel electrophoresis. Plant Science Letters3: 357–363.
Kacperska-Palacz, A. andM. Uliasz. 1974. Cold-induced changes in peroxidase activities in winter rape leaves. Physiol. Vég.12: 561–570.
Keilin, D. andE. F. Hartree. 1951. Purification of horse radish peroxidase and comparison of its properties with those of catalase and methaemoglobin. Biochem. J.49: 88–104.
Khan, A. A., Th. Gaspar, C. H. Roe, M. Bouchet andM. Dubucq. 1972. Synthesis of isoperoxidases in lentil embryonic axis. Phytochemistry11: 2963–2969.
Kobrehel, K. 1978. Identification of chromosome segments controlling the synthesis of peroxidases in wheat seeds and in transfer lines withAgropyron elongatum. Can. J. Bot.56: 1091–1094.
Kossatz, V. C. andR. B. van Huystee. 1976. The specific activities of peroxidase and ALA dehydratase during the growth cycle of peanut suspension culture. Can. J. Bot.54: 2089–2094.
Lam, T. H. andM. Shaw. 1970. Removal of phenolics from plant extracts by grinding with anion exchange resins. Biochem. Biophys. Res. Commun.39: 965–968.
Lavee, S. andM. Hoffman. 1971. The effect of potassium ions on peroxidase activity and its isozyme composition as related to apple callus growth in vitro. Bot. Gaz.132: 232–237.
Legrand, B., T. Gaspar, C. Penel andH. Grepin. 1976. Light and hormonal control of phenolic inhibitors of peroxidase inCichorium intybus L. Plant Biochem. J.3: 119–127.
Leshem, Y. andA. W. Galston. 1971. Repression of isoperoxidase formation in excised tobacco pith by exogeneous auxin controlled RNA. Phytochemistry10: 2869–2878.
Lobarzewski, J. 1977. Hemoproteid peroxidase fromInonotus radiatus. Acta Microbiol. Polonica26: 179–184.
Mäder, M., P. Münch andM. Bopp. 1975. Regulation und Bedeutung der Peroxidase-Musteränderungen in sprossdifferenzierden Kalluskulturen vonNicotiana tabacum L. Planta123: 257–265.
Marcus, A. 1971. Enzyme induction in plants. Ann. Rev. Plant Physiol.22: 313–336.
Mazza, G., C. Charles, M. Bouchet, J. Ricard andJ. Reynaud. 1968. Isolement, purification et propriétes physico-chimiques des peroxidase de navet. Biochim. Biophys. Acta167: 89–98.
Moustafa, E. 1963. Peroxidase isozymes in root nodules of various leguminous plants. Nature199: 1189.
Müller, H. P. 1969. Enzyme distribution in some radiation induced mutants ofPisum sativum with different internode length. Phytochemistry8: 1869–1871.
Nash, D. T. andM. E. Davies. 1972. Some aspects of growth and metabolism of Paul’s Scarlet rose cell suspension. J. Exp. Bot.23: 75–91.
——. 1975. Isoenzyme changes during the growth cycle of Paul’s Scarlet rose cell suspension. Phytochemistry14: 2113–2118.
Nelson, C. E., E. V. Sitzman, C. H. Kang andE. Margoliash. 1977. Preparation of cytochrome C peroxidase from Baker’s yeast. Anal. Biochem.83: 622–631.
Penel, C., E. Darimont, B. Legrand, T. Gaspar andH. Greppin. 1977. Influence des traitments subis par les extraits végétaux sur le nombre et l’activité des peroxidases. Compt. Rend. Acad. Sci. (Paris)284: 679–682.
— andH. Greppin. 1974. Variation de la photostimulation de l’activité des peroxydases basiques chez l’epinard. Plant Science Letters3: 75–80.
——. 1979a. Effect of calcium on subcellular distribution of peroxidases. Phytochemistry18: 29–33.
——. 1979b. Effect of far red and red light on a pelletable peroxidase activity in extracts from spinach leaves. Physiol. Plant.46: 208–210.
—— andJ. Boissard. 1976. In vitro photo modulation of a peroxidase activity through membrane bound phytochrome. Plant Science Letters6: 117–121.
Penon, P. J.-P. Cecchini, R. Miassod, J. Ricard, M. Teissere andM.-H. Pinna. 1970. Peroxidases associated with lentil root ribosomes. Phytochemistry9: 73–86.
Ramaiah, P. K., D. J. Durzan andA. J. Mia. 1971. Amino acids, soluble proteins, and isoenzyme patterns of peroxidase during germination of jack pine. Can. J. Bot.49: 2151–2161.
Ricard, J. andD. Job. 1974. Reaction mechanism of indole 3-acetate degradation by peroxidase. A stop flow low temperature spectroscopy study. Eur. J. Biochem.44: 359–374.
Ridge, J. andD. J. Osborne. 1970. Regulation of peroxidase activity by ethylene inPisum sativum: Requirements for protein and RNA synthesis. J. Exp. Bot.21: 720–734.
Rosner, A., J. Gressel andK. M. Jacob. 1977. Discoordination of ribosomal RNA metabolism during metabolic shifts to Spirodella. Biochim. Biophys. Acta474: 386–397.
Rychter, A. andS. Lewak. 1971. Apple embryo peroxidases. Phytochemistry10: 2609–2613.
Saunders, B. C., A. G. Holmes-Siedle andB. P. Stark. 1964. Peroxidase—The properties and uses of a versatile enzyme and some related catalysts. Butterworth, London. p. 40.
Scandalios, J. G. 1974. Isozymes in development and differentiation. Ann. Rev. Plant Physiol.25: 225–258.
— andJ. C. Sorenson. 1977. Isozymes in plant tissue culture.In: J. Reinert and Y. P. S. Bajaj (eds.). Applied and fundamental aspects of plant cell. Tissue and organ culture. Springer-Verlag, Berlin, p. 722.
Schneider, E. A. andF. Whightman. 1974. Metabolism of auxin in higher plants. Ann. Rev. Plant Physiol.25: 487–513.
Schonbaum, G. R. and B. Chance. 1970. Catalase.In: P. D. Boyer (ed.). The enzymes. XIII part C. p. 384.
Schopfer, P. andC. Plachy. 1973. Die organspezifische Photodetermination der Entwicklung von Peroxydaseaktivität in Senfkeimling durch Phytochrome. 1. Kinetische Analyse. Z. Naturforsch.28c: 296–301.
Schröder, J., B. Betz andK. Hahlbrock. 1976. Light-induced enzyme synthesis in cell suspension cultures ofPetroselinum hortense. Eur. J. Biochem.67: 527–541.
Shannon, L. M., E. Kay andJ. Y. Lew. 1966. Peroxidase isozymes from horseradish roots. I. Isolation and physical properties. J. Biol. Chem.241: 2166–2172.
—,I. Uritani andH. Imaseki. 1971.De novo synthesis of peroxidase isozymes in sweet potato slices. Plant Physiol.47: 493–498.
Shih, J. H.C., L. M. Shannon, E. Kay andJ. Y. Lew. 1971. Peroxidase isozymes from horseradish roots. III. Structural relationship. Jour. Biol. Chem.246: 4546–4551.
Sidloi-Lumbroso, R., L. Kleiman, andH. M. Schulman. 1978. Biochemical evidence that leghaemoglobin genes are present in the soyabean but not inRhizobium genome. Nature273: 558–560.
Siegel, B. Z. andA. W. Galston. 1966. Biosynthesis of deuterated isoperoxidases in rye plants grown in D2O. Proc. Natl. Acad. Sci. (Wash.)56: 1040–1042.
Smith, A. K. andJ. J. Rackis. 1957. Phytin elimination in soyabean protein isolation. J. Am. Chem. Soc.79: 633–637.
Smith, H. 1977. Regulation of enzyme synthesis and activity in higher plants. Academic Press, New York.
—,E. Ellen Billett andA. B. Giles. 1977. The photo control of gene expression in higher plants.In: H. Smith (ed.). Regulation of enzyme synthesis and activity in higher plants. Academic Press, New York. P. 93–127.
Srivastava, O. P. 1976. Study of peroxidase isozymes from culture medium of peanut cell suspension. Ph.D. Thesis, University of Western Ontario, London, Ontario, Canada.
— andR. B. van Huystee. 1973. Evidence for close association of peroxidase, polyphenol oxidase and IAA oxidase isozymes of peanut cell suspension culture medium. Can. J. Bot.51: 2207–2215.
——. 1977a. An interrelationship among peroxidase, IAA-oxidase and polyphenol oxidase from peanut cells. Can. J. Bot.55: 2630–2635.
——. 1977b. IAA oxidase and polyphenol oxidase activities of peanut peroxidase isozymes. Phytochemistry16: 1527–1530.
——. 1977c. Interactions among phenolics and peroxidase isozymes. Bot. Gaz.138: 457–464.
——. 1977d. Spectral and molecular properties of peanut peroxidase isozymes. Phytochemistry16: 1657–1659.
Stafford, H. A. 1960. Differences between lignin-like polymers formed by peroxidation of eugenol and ferulic acid in leaf segments ofPhleum. Plant Physiol.25: 459–486.
—. 1974. The metabolism of aromatic compounds. Ann. Rev. Plant Physiol.25: 459–486.
Stonier, T., S. Stasinos andK. B. S. Murthy Reddy. 1979. The masking of peroxidasecatalyzed oxidation of IAA inVigna. Phytochemistry18: 25–28.
Thomas, P. andH. Delincée. 1979. Effect of gamma irradiation on peroxidase isoenzymes during suberization of wounded potato tubers. Phytochemistry18: 917–921.
Thorpe, T. A. andTh. Gaspar. 1978. Changes in isoperoxidases during shoot formation in tobacco callus. In vitro14: 522–526.
Troxler, R. F. andG. D. Offner. 1979. Aminolevulinic acid synthesis in aCyanidium caldarium mutant unable to make chlorophyll a and phycobiliproteins. Arch. Biochem. Biophys.195: 53–65.
van Hoof, P. andT. Gaspar. 1973. Controle auxinique des peroxidases de racines excisées deMaìs en culture stérile. Compt. Rend. Acad. Sci. (Paris)277: 933–936.
van Huystee, R. B. 1976a. A study of peroxidase synthesis by means of double labelling and affinity chromatography. Can. J. Bot.54: 876–880.
—. 1976b. Immunological studies on proteins released by a peanut (Arachis hypogaea L.) suspension culture. Bot. Gaz.137: 325–329.
—. 1977a. Porphyrin and peroxidase synthesis in cultured peanut cells. Can. J. Bot.55: 1340–1344.
—. 1977b. Porphyrin metabolism in peanut cells cultured in sucrose containing medium. Acta Horticulturae78: 83–87.
—. 1977c. Relationship of the heme moiety of peroxidase and the free heme pool in cultured peanut cells. Z. Pflanzenphysiol.84: 427–433.
— andG. Turcon. 1973. Rapid release of peroxidase by peanut cells in suspension culture. Can. J. Bot.51: 1169–1175.
Verma, D. P. S. andA. K. Bal. 1976. Intracellular site of synthesis and localization of leghemoglobin in root nodules. Proc. Natl. Acad. Sci.73: 3843–3847.
—,G. A. Maclachlan, H. Byrne andD. Ewings. 1975. Regulation and in vitro translation of messenger ribonucleic acid for cellulase from auxin treated pea epicotyls. Jour. Biol. Chem.250: 1019–1026.
—,D. T. Nash andH. M. Schulman. 1974. Isolation and in vitro translation of soybean leghemoglobin mRNA. Nature251: 74–77.
— andR. B. van Huystee. 1970. Relationship between peroxidase, catalase and protein synthesis during cellular development in cell cultures of peanut. Can. J. Biochem.48: 444–449.
Wangenheim, K.-H.v. 1976. A mechanism for the endocellular control of cell differentiation and cell proliferation. J. Theor. Biol.59: 205–222.
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van Huystee, R.B., Cairns, W.L. Appraisal of studies on induction of peroxidase and associated porphyrin metabolism. Bot. Rev 46, 429–446 (1980). https://doi.org/10.1007/BF02860533
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DOI: https://doi.org/10.1007/BF02860533