Abstract
Heat and alkali treatment of proteins catalyzes formation of crosslinked amino-acid side chains such as lysinoalanine, ornithino- alanine and lanthionine, and concurrent racemization of L-isomers of all amino acid residues to D-analogues. Factors that favor these transformations include high pH and temperature, long exposure, and certain inductive or steric properties of the various amino acid side chains. Factors that minimize crosslink formation include the presence of certain additives, such as cysteine or sulfite ions, and acylation of ε-NH2 groups of lysine side chains. Free and protein-bound lysinoalanine and D-serine induce nephrocytomegaly in rat kidney tissues. The presence of lysinoalanine and D-amino acid residues along a protein chain decreases its digestibility and nutritional quality. Understanding the factors that govern the formation of potentially harmful unnatural amino acid residues in food proteins and the toxic and nutritionally antagonistic action of these compounds in animals should lead to better and safer foods.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Alworth, W. L. (1972). “Stereochemistry and Its Application in Biochemisty,” Wiley, Interscience, New York.
Asquith, R. S. and Otterburn, M. S. (1977). Cystine-alkali reaction in relation to protein crossi inking. In “Protein Crossi inking: Nutritional and Medical Consequences,” M. Friedman, Ed., Plenum Press, New York, pp. 93–121.
Bada, J. L. (1972). Kinetics of racemization of amino acids as a function of pH. J. Amer. Chem. Soc., 94, 1371–1372.
Bada, J. L. and Shou, M. Y. (1980). Kinetics and mechanism of amino acid racemization in aqueous solution and in bones. In “Biologeochemistry of Amino Acids,” P. E. Hare, Ed., John Wiley amp Sons, Inc., p. 235.
Berg, C. P. (1959). Utilization of D-amino acids. In “Protein and Amino Acid Nutrition,” A. A. Albanese, Ed., Academic Press, N. Y., pp. 57–96.
Bohak, Z. (1964). N-Epsilon-(DL–2-amino–2-carboxyethyl)-L-lysine (lysinoalanine), a new amino acid formed on alkaline treatment of proteins. J. Biol. Chem., 239, 2878–2887.
Brunner, J. R. (1977). Milk proteins. In “Food Proteins,” J. R. Whitaker, S. R. Tannenbaum, Eds., Avi, Westport, CT., p. 175.
Bunjapamai, S., Mahoney; R. R. and Fagerson, I. S. (1982). Determination of D-amino acids in some processed foods and effect of racemization on in vitro digestibility of casein. J. Food Sci., 47, 1229–1234.
Cavins, J. F. and Friedman, M. (1967). New amino acids derived from reactions of e-amino groups in proteins with a,03b2-unsaturated compounds. Biochemistry, 6, 3766–3770.
Charton, M. (1964). Definition of “inductive substituent constants.” J. Org. Chem., 29, 1222.
Cheftel, J. C. (1979). Proteins and amino acids. In “Nutritional and Safety Aspects of Food Processing”, S. R. Tannenbaum, Ed., Marcel Dekker, New York, pp. 154–215.
Dakin, H. D. (1912–1913). The racemization of proteins and their derivatives resulting from tautomeric change. J. Biol. Chem., 13, 357–362.
Dakin, H. D. and Dudley, H. W. (1913). The action of enzymes on racemized proteins and their fate in the animal body. J. Biol. Chem., 15, 271–276.
Darge, W. and Thiemann, W. (1971). Hydrolysis and racemization of oligopeptides studied by optical rotation measurement and ion exchange chromatography. In “First European Biophysics Congress Proceedings”, E. Broda, AT Locker, and H. Springer-Lederer, Eds., Baden, Vol. 1, 133–137.
de Groot, A. P. and Slump, P. (1969). Effects of severe alkali treatmeent of proteins on amino acid composition and nutritive value. J. Nutr., 98, 45–56.
de Groot, A. P., Slump, P., Feron, V. J. and Van Beek, L. (1976). Effects of alkali-treated proteins. Feeding studies with free and protein-bound lysinoalanine in rats and other animals. J. Nutr., 106, 1527–1538.
de Groot, A. P., Slump, P., Van Beek, L. and Feron, V. J. (1976). Severe alkali treatment of proteins, Evaluation of Proteins for Humans, C. Bodwell, Ed., Avi Publishing Co., Westport, CT.
de Koning, P. J. and van Rooijen, P. J. (1982). Aspects of the for-mation of lysionalanine in milk and milk products. J. Dairy Res. 49, 725–736.
Erbersdobler, H. F., von Wangenheim, B., Hänichen, T. (1978). Adverse effects of Maillard products - especially of fructoselysine in the organism. Paper presented at X I Internat. Congress of Nutrition, Rio de Janeiro, Brazil, and Private Communication.
Engelsma, J. W., Muelen, J. D. v. d., Slump, P. and Haagsma, N. (1979). The oxidation of lysinoalanine by L-amino acid oxidase. Identification of Products. Food Sci. & Technol. 203–207.
Exner, O. (1978). A critical compilation of substiuent constants. In “Correlation Analysis in Chemistry.” N. B. Chapman and J. Shorter, Eds., Plenum Press, New York, pp. 439–540.
Feron, V. J., van Beek, L., Slump, P. and Beems, R. B. (1977). Toxicologicai aspects of alkali treatment of food proteins. In “Biological Aspects of New Protein Food”, Pergamon Press, Oxford England, J. Adler Nissen, Ed., pp. 139–147.
Finch, L. R. and Hird, F. J. R. (1960). The uptake of amino acids by isolated segments of rat intestine. II. A survey of affinity for uptake from rates of uptake and competition of uptake., Biochim. Biophys. Acta, 43, 278–287.
Finley, J. W., Snow, J. T., Johnston, P. H. and Friedman, M. (1978a). Inhibitory effect of mercaptoamino acid on lysinoalanine formation during alkali treatment of proteins. In “Protein Crosslinking: Nutritional and Medical Consequences”, M. Friedman, Ed., Plenum Press, New York, pp. 85–92.
Finley, J. W., Snow, J. T., Johnston, P. H., and Friedman, M. (1978b). Inhibition of lysinoalanine formation in food proteins. J.. Food Sci., 43: 619–621.
Finot, P.-A. (1983). Lysinoalanine in food proteins. Nutrition Abstracts and Reviews, Clin. Nutr., 53, 67–80.
Finot, P.-A., Bujard, E., and Arnaud, M. (1977). Metabolic transit of lysinoalanine (LAL) bound to protein and of free radioactive [C]-lysinoalanine. In: “Protein Crosslinking — Nutritional and Medical Consequences,” M. Friedman, Ed., Plenum Press, N.Y., pp. 51–71.
Freimuth, U., Krause, W. and Doss, A. (1978). On the alkali treat-ment of proteins. II. Enzymatic hydrolysis of al kali-treated ß- casein and acid casein. Nahrung, 22, 557–568. (German).
Friedman, M. (1982a). Lysinoalanine formation in soybean proteins: kinetics and mechanisms. In “Food Protein Deterioration Mechanisms and Functionality”, J. P. Cherry (Ed.), ACS Symposium Series, Washington, D. C. 206; 231–273.
Friedman, M. (1982b). Chemically reactive and unreactive lysine as an index of browning. Diabetes, 31, 5–14.
Friedman, M. (1980). Inhibition of lanthionine formation during alkaline treatment of keratinous fibers. U. S. Patent 4, 212, 800.
Friedman, M. (1978a). Wheat gluten-alkali reactions. (1978 a). In “Proceedings of the 10th National Conference on Wheat Utilization Research”, U. S. Department of Agriculture, Science and Education Administration, Western Regional Research Center, Berkeley, Cali-fornia 94710, ARM-W–4, pp. 81–100.
Friedman, M. (1978b). Inhibition of lysinoalanine synthesis by protein acylation. in “Nutritional Improvement of Food and Feed Proteins”, M. Friedman, Ed., Plenum Press, New York, pp. 613- 648.
Friedman, M. (1977). Crosslinking amino acids-stereochemistry and namenclature. In “Protein Crosslinking: Nutritional and Medical Consequences”, W. Friedman, Ed., Plenum Press, New York, pp. 1–27.
Friedman, M. and Gumbmann, M. R. (1982). Bioavailability of D-amino acids in mice. Fed. Proc. 41, 392.
Friedman, M. and Gumbmann, M. R. (1981). Bioavailability of some lysine derivatives in mice. J. Nutrition, 111, 1362–1369.
Friedman, M., and Gumbmann, M. R. (1979). Biological availability of epsilon-N-methyl-L-lysine, 1-N-methyl-L-histidine, and 3-N- methyl-L-histidine in mice. Nutrition Reports International, 19, 437–443.
Friedman, M. and Masters, P. M. (1982). Kinetics of racemization of amino acid residues in casein. J. Food Sci., 47, 760–764.
Friedman, M., and Wall, J. S. (1964), Application of a Hammett- Taft relation to kinetics of alkylation of amino J. Amer. Chem. Soc., 86, 37735–3741.
Friedman, M., and Wall, J. S. (1966). Additive linear free energy relationships in reaction kinetics of amino groups with a-, 3-unsaturated compounds. J. Org. Chem., 31, 2888–2874.
Friedman, M., Gumbmann, M. R. and Savoie, L. (1982a). The nutri-tional value of lysinoalanine as a source of lysine for mice. Nutrition Reports International, 26, 939–947.
Friedman, M., Wehr, C. M., Schade, J. E. and MacGregor, J. T. (1982b). Inactivation of aflatoxin Bi mutagenicity by thiols. Food and Chemical Toxicology, 20: 887–892.
Friedman, M., Zahnley, J. C. and Masters, P. M. (1981). Relationship between in vitro digestibility of casein and its content of lysinoalanine and D-ami no acids. J. Food Sci. 46, 127–131 and 134.
Friedman, M., Finley, J. W. and Yeh, Lai-Sue. (1977). Reactions of proteins with dehydrolanines. In “Protein Crosslinking: Nutritional and Medical Consequences”, M. Friedman, Ed., Plenum Press, New York, pp. 213–224.
Friedman, M. Cavins, J. F., and Wall, J. S. (1965). Relative nucí eophilie reactivities of amino groups and mercaptide ions in addition reactions with a, e-unsaturated compounds. J. Amer. Chem. Soc., 87, 3572–3682.
Fritsch, R. J., Hoffman, H. and Klostermeyer, H. (1983). Formation of lysinoalanine during heat treatment of milk. Z. Lemensm. Unters. Forsch. 176, 341–345.
Ganóte, C. E., Peterson, D. R. and Carone, F. A. (1974). The nature of D-serine induced nephrotoxicity. Am. J. Pathol., 77, 269–176.
Gauthier, S. F., Vachon, C., Jones, J. D. and Savoie, L. (1982). Assessment of protein digestibility by vitro enzymatic hydrolysis with simultaneous dialysis. J. Nutr., 112, 1717–1725.
Gee, M., Huxsoll, C. C. and Graham, R. P. (1974). Acidification of dry caustic peeling by lactic acid fermentation. Am. Potato J. 51, 126–131.
Gibson, 0. H. and Wiseman, G. (1951). Selective absorption of stereoisomers of amino acids from loops of the small intestine of the rat. Biochem. J., 48, 426–429.
Goldblatt, L. A. (1969). “Aflatoxin: Scientific Background, Control, and Implications”, Academic Press, New York.
Gross, E. (1977). a, e-Unsaturated and related amino acids in peptides and proteins. Adv. Exp. Med. Biol., 86A, 131–153.
Gould, D. H. and MacGregor, J. T. (1977). Biological effects of alkali-treated protein and lysinoalanine: an overview. In “Protein Crosslinking: Nutritional and Medical Consequences,” M. Friedman, Ed., Part B, Plenum Press, N. Y., pp. 29–48.
Hayase, F., Kato, H., and Fujimaki, M. (1975). Racemization of amino acid residues in proteins and poly(L-amino acids) during roasting. J. Agric. Food Chem., 23, 491–494.
Hayashi, R. (1982). Lysinoalanine as a metal chelator. An implication for toxicity. J. Biol. Chem., 257, 13,896–13, 898.
Hayashi, R. and Kameda, I. (1980). Decreased proteolysis of alkali - treated protein: consequences of racemization in food processing. J. Food Sci., 45, 1430–1431.
Hewitt, D., Ford, J. E. and Porter, J. W. G. (1979). Nutritional quality of spun soya-bean protein: comparison of biological and microbiological tests. Qualitas Plantarum, 29, 253–260.
Horn, M. J., Jones, D. B., Ringel, S. J. (1941). Isolation of a new sulfur-containing amino acid (lanthionine) from sodium carbonate treated wool. J. Biol. Chem., 138, 141–149.
Kaltenbach, J. P., Ganote, G. E. and Carone, F. A. (1979). Renal tubular necrosis induced by compounds structurally related to D- serine. Exp, and Mol. Pathol., 30, 209–214.
Karayiannis, N. (1976). Lysinoalanine Formation in Alkali Treated Proteins and their Biological Effects, Ph.D. Thesis. University of California, Berkeley.
Karayiannis, N. I., MacGregor, J. T. and Bjeldanes, L. F. (1979a). Lysinoalanine formation in alkali-treated proteins and model compounds. Food Cosmet. Toxicol., 17, 585–590.
Karayiannis, N. I., MacGregor, J. T. and Bjeldanes, L. F. (1979b). Biological effects of alkali-treated soy protein and lactalbumin in the rat and mouse. Food and Cosm. Toxicol., 17, 509–604.
Karayiannis, N. I., Panopoulos, N. J., Bjeldanes, L. F. and Mac-Gregor, J. T. (1979c). Lysinoalanine utilization by Erwinia Chrysanthemi and Escherichia Coli. Food Cosmet. Toxicol., 17, 319
Kies, C, Fox, H. and Aprahamian, S. (1975). Comparative value of L-, DL-, and D-methionine supplementation of an oat-based diet for humans. J. Nutr., 105, 809–814.
Kossel, A., and Weiss, F. (1909). Ober Einwirkung von Alkalien auf Proteinstoffe. Z. Physiol. Chem., 59, 492–498.
Leegwater, D. C. and Tas, A. C. (1980). Identification of an enzymic oxidation product of lysinoalanine. Lebensm.-Wiss. Technol., 13, 87–91.
Leegwater, D. C. (1978). The nephrotoxicity of lysinoalanine in the rat. Food Cosmet. Toxicol., 16, 405.
Levene, P. A. and Bass, L. W. (1927). Studies on racemi zation. V. The action of alkali on gelatin. J. Biol. Chem., 74, 715–725.
Levene, P. A. and Bass, L. W. (1928). Studies on racemization. VII. The action of alkali on casein. J. Biol. Chem., 78, 145–157.
Levene, P. A. and Bass, L. W. (1929). Studies on racemization. VIII. The action of alkali on proteins: racemization and hydrolysis. J. Biol. Chem., 82, 171–190.
Liardon, R. and Hurrell, R. F. (1983). Amino acid racemization in heated and alkali-treated proteins. J. Agric. Food Chem., 31, 432–437.
Masri, M. S. and Friedman, M. (1982). Transformation of dehydro- alanine to S-03b2-(2-pyridylethyl)-L-cysteine side chains. Biochem. Biophys. Res. Commun., 104, 321–325.
Masters, P. M. and Friedman, M. (1980). Amino acid racemization in alkali-treated food proteins—chemistry, toxicology, and nutritional consequences. In “Chemical Deterioration of Proteins”, J. R. Whitaker and M. Fujimaki, Eds. ACS Symposium Series, Washington, D. C. 123, 165–194.
Masters, P. M. and Friedman, M. (1979). Racemization of amino acids in alkali-treated food proteins. J. Agric. Food Chem., 27, 507–511.
Meister, A. (1965). “Biochemistry of the Amino Acids,” Vol. I, Academic Press, N.Y., pp. 338–369.
Munro, H. N. (1978). Nutritional consequences of excess amino acid intake. In “Nutritional Improvement of Food and Feed Proteins”, M. Friedman, Ed., Plenum Press, New York, pp. 119–129.
Newberne, P. M. and Young, V. R. (1966). Effects of diets marginal in methionine and choline with and without vitamin B12 on rat liver and kidney. J. Nutr., 89, 69–79.
Newberne, P. M., Rogers, A. E. and Wogan, G. N. (1968). Hepatorenal lesions in rats fed a low lipotrope diet and exposed to aflatoxin. J. Nutr., 94, 331–343.
Nicolet, B. H. (1931). The mechanism or sulfur lability in cysteine and its derivatives. I. Some thio ethers readily split by alkali. J. Am. Chem. Soc., 53, 3066–3072.
Nicolet, B. H. (1932). The mechanism of sulfur lability in cystein and its derivatives. II. The addition of mereaptan to benzoyl aminocinnamic acid derivatives. J. Biol. Chem., 95, 389–392.
Nicolet, B. H., Shinn, L. A., and Saidel, L. J. (1942). The lability toward alkali of serine and threonine in proteins, and some of its consequences. J. Biol. Chem., 142, 609–613.
O’Donovan, C. J. (1976). Recent studies of lysinoalanine in alkali -treated proteins. Fd. Cosmet. Toxicol., 14, 483–489.
Patchornik, A. and Sokolovsky, M. (1964a). Chemical interactions between lysine and dehydroalanine in modified bovine pancreatic ribonuclease. J. Am. Chem. Soc., 86, 1860–1861.
Patchornik, A. and Sokolovsky, M. (1964b). Nonenzymatic cleavages of peptide chains at the cysteine and serine residues through their conversion into dehydroalanine residues. J. Am. Chem. Soc., 86, 1206–1212.
Provansal, M. M. P., Cuq, J. L. A. and Cheftel, J. C. (1975). Chemical and nutritional modifications of sunflower proteins due to alkaline processing. Formation of amino acid crosslinks and isomerization of lysine residues. J. Ag. Food Chem., 23, 938–943.
Reyniers, J. P., (1979). Renal toxicity of lysinoalanine and its potential catabolites in germfree and conventional animals. Diss. Abstr. Int. B. 39 (10), 1820.
Reyniers, J. P., Woodard, J. C. and Alvarez, M. R. (1974). Nuclear cytochemical alterations in «-protein induced nephrocytomegalia. Lab. Invest., 30, 582–588.
Robbins, K. R. and Ballew, J. E. (1982). Effect of alkaline treat-ment of soy protein on sulfur amino acid bioavailability. J. Food Sci. 47, 2070–2071.
Robbins, K. R., Baker, D. H. and Finley, J. W. (1980). Studies on the utilization of lysinoalanine and lanthionine. J. Nutr., 110, 907–914.
Rose, W. C. (1949). Amino acid requirements of man. Fed. Proc. 8, 546–552.
Rosenhagen, M. and Segal, S. (1974). Stereospecificity of amino acid uptake by rat and human kidney cortex slices. Am. J. Physiol., 227, 843–847.
Sanderson, J., Wall, J. S. Donaldson, G. L. and Cavins, J. F. (1978) Effect of alkaline processing of corn on its amino acids. Cereal Chem., 55, 204–213.
Saunders, R. M., Connor, M. A., Edwards, R. H. and Kohler, G. O. (1975). Preparation of protein concentrates from wheat shorts and wheat millrun by a wet alkaline process. Cereal Chem., 52, 93–101.
Smith, G. G., Williams, K. M. and Wonnacot, D. M. (1978). Factors affecting the rate of racemization of amino acids and their sig-nificance of geochronology. J. Org. Chem., 43, 1–5.
Snow, J. T., Finley, J. W. and Friedman, M. (1976). Relative re-activities of sulfhydryl groups with N-acetyl dehydroalanine and N-acetyldehydroalanine methyl ester. Int. J. Petide Protein Res., 7, 461–466.
Stegink, L. D. (1977). D-Amino acids. In “Clinical Nutrition Up-date: Amino Acids,” American Medical Association, Chicago, Illinois, p. 198.
Steining J. and Montag, A. Studies on the alteration of lysine of food proteins. II. Formation of lysinoalanine. Z. Lebensm. Unter. Forsch. 175, 8–12. (German).
Sternberg, M. and Kim, C. Y. (1979). Growth response of mice and Tetrahymena piriformis to lysinoalanine-supplement wheat gluten. J. Agric. Food Chem., 27, 1130.
Sternberg, M. and Kim, C. Y. (1977). Lysinoalanine formation in protein food ingredients. In “Protein Crosslinking: Nutritional and Medical Consequences”, IT. Friedman, Ed., Plenum Press, New York, pp. 73–84.
Sternberg, M., Kim, C. Y., and Schwende, F. J. (1975). Lysinoalanine: presence in foods and food ingredients. Science, 190, 992–994.
Struthers, B. J., Brielmaier, J. R., Raymond, M. L., Dahlgren, R. R. and Hopkins, D. T. (1980). Excretion and tissue distribution of radioactive lysinoalanine. J. Nutr., 110, 2065–2077.
Struthers, B. J., Dahlgren, R. R., Hopkins, D. T. and Raymond, M. L. (1979). Lysinoalanine: biological effects and significance. In In Soy Protein and Human Nutrition: H. L. Wilcke, D. T. Hopkins, and D. H. Waggle, Eds., Academic Press, New York, pp. 235–260.
Taft, R. Jr. (1956). In “Steric Effects in Organic Chemistry,” M. S. Newman, Ed., John Wiley and Sons, Inc. New York, N.Y., Chapter 13.
Tannenbaum, S. R., Ahern, M., and Bates, R. P. (1970). Solubilization of fish protein concentrate. 1. An alkaline process. Food Tech., 24, 96–99.
Tas, A. C. and Kleipool, R. J. C. (1979). The stereoisomers of lysinoalanine. Lebensm. Wiss. und Technol., 9 360–362.
Van Beek, L., Feron, V. J. and de Groot, A. P. (1974). Nutritional effects of alkali-treated soy protein in rats. J. Nutr., 104, 1630–1636.
Wachstein, M. (1974). Nephrotoxic action of D,L-serine in the rat. Arch. Pathol., 43, 503–514.
Whitaker, J. R. and Feeney, R. E. (1977). Behaviour of 0-glycosyl and 0-phosphoryl proteins in alkaline solution. In “Protein Crosslinking: Nutritional and Medical Consequences”, Friedman, Ed., Plenum Press, New York, pp. 155–175.
Woodard, J. C. (1969). On the pathogenesis of alpha protein-induced nephrocytomegalia. Lab. Invest., 20, 9–16.
Woodard, J. C. and Alvarez, M. R. (1967). Renal lesions in rats fed diets containing alpha protein. Arch. Path., 84, 153–162.
Woodard, J. C., and Short, D. D. (1973). Toxicity of alkali- treated soy protein in rats. J. Nutr., 103, 569–574.
Woodard, J. C. and Short, D. D. (1977). Renal toxicity of Lysino-alanine in rats. Food Cosmet. Toxicol., 15, 117–119.
Woodard, J. C., Short, D. D., Alvarez, M. R. and Reyniers, J. (1975). Biologic effects of N-e-(DL–2-amino–2-carboxyethyl)-L-lysine, lysinoalanine. “Protein Nutritional Quality of Foods and Feeds” M. Friedman, Ed., Marcel Dekker, New York, pp. 595–616.
Wretlind, J. A. J. (1952). The effect of D-amino acids on the stereonaturalization of D-methionine. Acta Physiol. Scand., 25, 267–275.
Wu, Y. V., Sexson, K. R., Cluskey, J. E. and Inglett, G. E. (1977). Protein isolates from high protein oats preparation. Composition and properties. J. Food Sci., 42, 1383–1386.
Zezulka, A. Y. and Calloway, D. H. (1976). Nitrogen retention in men fed isolated soybean protein supplemented with L-methionine, D-methionine, N-acetyl-L-methionine, or inorganic sulfate. J. Nutr., 106, 1286–1291.
Zumberge, J. E. The effect of D-glucose on aspartic acid racemization. Paper presented at the Carnegie Institution of Washington Conference: Advances in the Biogeochemistry of Amino Acids, Warrenton, Virginia, Oct. 29-Nov. 1,. 1978.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1984 Plenum Press, New York
About this chapter
Cite this chapter
Friedman, M., Gumbmann, M.R., Masters, P.M. (1984). Protein-Alkali Reactions: Chemistry, Toxicology, and Nutritional Consequences. In: Friedman, M. (eds) Nutritional and Toxicological Aspects of Food Safety. Advances in Experimental Medicine and Biology, vol 177. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4790-3_18
Download citation
DOI: https://doi.org/10.1007/978-1-4684-4790-3_18
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-4792-7
Online ISBN: 978-1-4684-4790-3
eBook Packages: Springer Book Archive