Abstract
Recall from Chap. 1 that it took a visit to Papua New Guinea in the mid-1950s. At that time a rare but fatal disease, kuru, had broken out among the primitive Fore people. In response to what was clearly an unusual happening, the epidemiologist Carleton Gajdusek (1923–2008) traveled to the region at the invitation of the local medical officer, Vincent Zigas. Once he was in the region Gajdusek discovered that the disease was being transmitted by means of funerary cannibalistic feasts involving ingestion of brain tissue.
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Bibliography
Alper, T., Cramp, W. A., Haig, D. A., & Clarke, M. C. (1967). Does the agent of scrapie replicate without nucleic acid? Nature, 214, 764–766.
Alper, T., Haig, D. A., & Clarke, M. C. (1966). The exceptionally small size of the scrapie agent. Biochemical and Biophysical Research Communications, 22, 278–284.
Baron, G. S., Wehrly, K., Dorward, D. W., Chesebro, B., & Caughey, B. (2002). Conversion of raft-associated prion protein to the protease-resistant state requires insertion of PrP-res (PrPSc) into contiguous membranes. The EMBO Journal, 21, 1031–1040.
Basler, K., Oesch, B., Scott, M., Westaway, D., Wälchli, M., Groth, D. F., et al. (1986). Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell, 46, 417–428.
Brandner, S., Isenmann, S., Raeber, A., Fischer, M., Sailer, A., Kobayashi, Y., et al. (1996). Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature, 379, 339–343.
Castilla, J., Saá, P., Hetz, C., & Soto, C. (2005). In vitro generation of infectious scrapie prions. Cell, 121, 195–206.
Chesebro, B., Race, R., Wehrly, K., Nishio, J., Bloom, M., Lechner, D., et al. (1985). Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain. Nature, 315, 331–333.
Chesebro, B., Trifilo, M., Race, R., Meade-White, K., Teng, C., LaCasse, R., et al. (2005). Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science, 308, 1435–1439.
Deleault, N. R., Harris, B. T., Reese, J. R., & Supattapone, S. (2007). Formation of native prions from minimal components in vitro. Proceedings of the National Academy of Sciences of the United States of America, 104, 9741–9746.
Deleault, N. R., Piro, J. R., Walsh, D. J., Wang, F., Ma, J., Geoghegan, J. C., & Supattapone, S. (2012). Isolation of phosphatidylethanolamine as a solitary cofactor for prion formation in the absence of nucleic acids. Proceedings of the National Academy of Sciences of the United States of America, 109, 8546–8551.
Gajdusek, D. C., Gibbs, C. J., Jr., & Alpers, M. (1966). Experimental transmission of a kuru-like syndrome to chimpanzees. Nature, 209, 794–796.
Gajdusek, D. C., & Zigas, V. (1957). Degenerative disease of the central nervous system in New Guinea: Epidemic occurrence of “kuru” in the native population. New England Journal of Medicine, 257, 974–978.
Gibbs, C. J., Jr., Gajdusek, D. C., Asher, D. M., Alpers, M. P., Beck, E., Daniel, P. M., et al. (1968). Creutzfeldt-Jakob disease (spongiform encephalopathy): Transmission to the chimpanzee. Science, 161, 388–389.
Griffith, J. S. (1967). Self-replication and scrapie. Nature, 215, 1043–1044.
Hadlow, W. J. (1959). Scrapie and kuru. Lancet, 2, 289–290.
Kocisko, D. A., Come, J. H., Priola, S. A., Chesebro, B., Raymond, G. J., Lansbury, P. T., et al. (1994). Cell-free formation of protease-resistant prion protein. Nature, 370, 471–474.
Mallucci, G., Dickinson, A., Linehan, J., Klöhn, P. C., Brandner, S., & Collinge, J. (2003). Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science, 302, 871–874.
Makarava, N., Kovacs, G. G., Bocharova, O., Savtchenko, R., Alexeeva, I., Budka, H., et al. (2010). Recombinant prion protein induces a new transmissible prion disease in wild-type animals. Acta Neuropathologica, 119, 177–187.
Oesch, B., Westaway, D., Wälchli, M., McKinley, M. P., Kent, B. H., Aebersold, R., et al. (1985). A cellular gene encoding scrapie PrP 27–30 proteins. Cell, 40, 735–746.
Pan, K. M., Baldwin, M., Nguyen, J., Gasset, M., Serban, A., Groth, D., et al. (1993). Conversion of α-helices into β-sheets features in the formation of the scrapie prion proteins. Proceedings of the National Academy of Sciences of the United States of America, 90, 10962–10966.
Prusiner, S. B. (1982). Novel proteinaceous infectious particles cause scrapie. Science, 216, 136–144.
Prusiner, S. B., McKinley, M. P., Bowman, K. A., Bolton, D. C., Bendheim, P. E., Groth, D. F., et al. (1983). Scrapie prions aggregate to form amyloid-like birefringent rods. Cell, 35, 349–358.
Riek, R., Hornemann, S., Wider, G., Billeter, M., Glockshuber, R., & Wüthrich, K. (1996). NMR structure of the mouse prion protein domain PrP(121–231). Nature, 382, 180–182.
Sandberg, M. K., Al-Doujaily, H., Sharps, B., Clarke, A. R., & Collinge, J. (2011). Prion propagation and toxicity in vivo occur in two distinct mechanistic phases. Nature, 470, 540–542.
Silveira, J. R., Raymond, G. J., Hughson, A. G., Race, R. E., Sim, V. L., Hayes, S. F., et al. (2005). The most infectious prion protein particles. Nature, 437, 257–261.
Wong, C., Xiong, L. W., Horiuchi, M., Raymond, L., Wehrly, K., Chesebro, B., et al. (2001). Sulfated glycans and elevated temperature stimulate PrPSc-dependent cell-free formation of protease-resistant prion protein. The EMBO Journal, 20, 377–386.
Prion Passage from Gut to Brain
Mabbott, N. A., & MacPherson, G. G. (2006). Prions and their lethal journey to the brain. Nature Reviews. Microbiology, 4, 201–211.
Prion Diseases in Animals and Humans
Bruce, M. E., Will, R. G., Ironside, J. W., McConnell, I., Drummond, D., Suttie, A., et al. (1997). Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature, 389, 498–501.
Castilla, J., Gonzalez-Romero, D., Saá, P., Morales, R., de Castro, J., & Soto, C. (2008). Crossing the species barrier by PrPSc replication in vitro generates unique infectious prions. Cell, 134, 757–765.
Chesebro, B. (2003). Introduction to the transmissible spongiform encephalopathies or prion diseases. British Medical Bulletin, 66, 1–20.
Collins, S., McLean, C. A., & Masters, C. L. (2001). Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and kuru: A review of three less common human transmissible spongiform encephalopathies. Journal of Clinical Neuroscience, 8, 387–397.
Hill, A. F., Desbruslais, M., Joiner, S., Sidle, K. C. L., Gowland, I., Collinge, J., et al. (1997). The same prion strain causes vCJD and BSE. Nature, 389, 448–450.
Johnson, C. J., Phillips, K. E., Schramm, P. T., McKenzie, D., Aiken, J. M., & Pedersen, J. A. (2006). Prions adhere to soil minerals and remain infectious. PLoS Pathogens, 2, e32.
Miller, M. W., Williams, E. S., Hobbs, N. T., & Wolfe, L. L. (2004). Environmental sources of prion transmission in mule deer. Emerging Infectious Diseases, 10, 1003–1006.
Raymond, G. J., Bossers, A., Raymond, L. D., O’Rourke, K. I., McHolland, L. E., Bryant, P. K. III, et al. (2000). Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. The EMBO Journal, 19, 4425–4430.
Tamgüney, G., Miller, M. W., Wolfe, L. L., Sirochman, T. M., Glidden, D. V., Palmer, C., et al. (2009). Asymptomatic deer excrete infectious prions in feces. Nature, 461, 529–532.
Vanik, D. L., Surewicz, K. A., & Surewicz, W. K. (2004). Molecular basis of barriers for interspecies transmissibility of mammalian prions. Molecular Cell, 14, 139–145.
Wadsworth, J. D. F., Hill, A., Beck, J. A., & Collinge, J. (2003). Molecular and clinical classification of human prion diseases. British Medical Bulletin, 66, 241–254.
Prion Strains
Beassen, R. A., Kocisko, D. A., Raymond, G. J., Nandan, S., Lansbury, P. T., & Caughey, B. (1995). Non-genetic propagation of strain-specific properties of scrapie prion. Nature, 375, 698–700.
Bessen, R. A., & Marsh, R. F. (1994). Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy. Journal of General Virology, 68, 7859–7868.
Collinge, J., & Clarke, A. R. (2007). A general model of prion strains and their pathogenicity. Science, 318, 930–936.
Jones, E. M., & Surewicz, W. K. (2005). Fibril conformation as the basis of species- and strain-dependent seeding specificity of mammalian prion amyloids. Cell, 121, 163–172.
Legname, G., Baskakov, I. V., Nguyen, H. O. B., Riesner, D., Cohen, F. E., DeArmond, S. J., et al. (2004). Synthetic mammalian prions. Science, 305, 673–676.
Saborio, G. P., Permanne, B., & Soto, C. (2001). Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature, 411, 810–813.
Safar, J., Wille, H., Itri, V., Groth, D., Serban, H., Torchia, M., et al. (1998). Eight prion strains have PrP molecules with different conformations. Nature Medicine, 4, 1157–1165.
Tanaka, M., Chien, P., Naber, N., Cooke, R., & Weissman, J. S. (2004). Conformational variations in an infectious protein determine prion strain differences. Nature, 428, 323–328.
Telling, G. C., Parchi, P., DeArmond, S. J., Cortelli, P., Montagna, P., Gabizon, R., et al. (1996). Evidence for the conformation of the pathogenic isoform of the prion protein enciphering and propagating prion diversity. Science, 274, 2079–2082.
Toyama, B. H., Kelly, M. J. S., Gross, J. D., & Weissman, J. S. (2007). The structural basis of yeast prion strain variants. Nature, 449, 233–237.
Prion Biogenesis, Structure and Function
Bremer, J., Baumann, F., Tiberi, C., Wessig, C., Fischer, H., Schwarz, P., et al. (2010). Axonal prion protein is required for peripheral myelin maintenance. Nature Neuroscience, 13, 310–318.
Collinge, J. (1994). Prion protein is necessary for normal synaptic function. Nature, 370, 295–297.
Khosravani, H., Zhang, Y., Tsutsui, S., Hameed, S., Altier, C., Hamid, J., et al. (2008). Prion protein attenuates excitotoxicity by inhibiting NMDA receptors. Journal of Cell Biology, 181, 551–565.
Le Pichon, C. E., Valley, M. T., Polymenidou, M., Chesler, A. T., Sagdullaev, B. T., Aguzzi, A., et al. (2009). Olfactory behavior and physiology are disrupted in prion protein knockout mice. Nature Neuroscience, 12, 60–69.
Málaga-Trillo, E., Solis, G. P., Schrock, Y., Geiss, C., Luncz, L., Thomanetz, V., et al. (2009). Regulation of embryonic cell adhesion by the prion protein. PLoS Biology, 7, e1000055.
Mouillet-Richard, S., Ermonval, M., Chebassier, C., Laplanche, J. L., Lehrmann, S., Launay, J. M., et al. (2000). Signal transduction through prion protein. Science, 289, 1925–1928.
Santuccione, A., Sytnyk, V., Leshchynsʹka, I., & Schachner, M. (2005). Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth. Journal of Cell Biology, 169, 341–354.
Stahl, N., Baldwin, M. A., Teplow, D. B., Hood, L., Gibson, B. W., Burlingame, A. L., et al. (1993). Structural studies of the scrapie prion protein using mass spectroscopy and amino acid sequencing. Biochemistry, 32, 1991–2002.
Taylor, D. R., & Hooper, N. M. (2006). The prion protein and lipid rafts. Molecular Membrane Biology, 23, 89–99.
Prion Toxicity
Hetz, C., Russelakis-Carneiro, M., Maundrell, K., Castilla, J., & Soto, C. (2003). Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein. The EMBO Journal, 22, 5435–5445.
Kristiansen, M., Deriziotis, P., Dimcheff, D. E., Jachson, G. S., Ovaa, H., Naumann, H., et al. (2007). Disease-associated prion protein oligomers inhibit the 26S proteasome. Molecular Cell, 26, 175–188.
Laurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., & Strittmatter, S. M. (2009). Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers. Nature, 457, 1128–1132.
Moreno, J. A., Radford, H., Peretti, D., Steinert, J. R., Verity, N., Martin, M. G., et al. (2012). Sustained translational repression by eIF2α-P mediates prion neurodegeneration. Nature, 485, 507–511.
Rane, N. S., Kang, S. W., Chakrabarti, O., Feigenbaum, L., & Hedge, R. S. (2008). Reduced translocation of nascent prion protein during ER stress contributes to neurodegeneration. Developmental Cell, 15, 359–370.
Resenberger, U. K., Harmeier, A., Woerner, A. C., Goodman, J. L., Müller, V., Krichnan, R., et al. (2011). The cellular prion protein mediates neurotoxic signaling of β-sheet-rich conformers independent of prion replication. The EMBO Journal, 30, 2057–2070.
Sonati, T., Reimann, R. R., Falsig, J., Baral, P. K., O’Connor, T., Hornemann, S., et al. (2013). The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein. Nature, 501, 102–106.
Um, J. W., Nygaard, H. B., Heiss, J. K., Kostylev, M. A., Stagi, M., Vortmeyer, A., et al. (2012). Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nature Neuroscience, 15, 1227–1235.
Structure of the Prion Amyloid Fibrils
Cobb, N. J., Sönnichsen, F. D., Mchaourab, H., & Surewicz, W. K. (2007). Molecular architecture of human prion protein amyloid: A parallel, in-register β-structure. Proceedings of the National Academy of Sciences of the United States of America, 104, 18946.
DeMarco, M. L., & Daggett, V. (2004). From conversion to aggregation: Protofibril formation of the prion protein. Proceedings of the National Academy of Sciences of the United States of America, 101, 2293–2298.
Govaerts, C., Wille, H., Prusiner, S. B., & Cohen, F. E. (2004). Evidence for assembly of prions with left-handed β-helices into trimers. Proceedings of the National Academy of Sciences of the United States of America, 101, 8342–8347.
Krishnan, R., & Lindquist, S. L. (2005). Structural insights into a yeast prion illuminate nucleation and strain diversity. Nature, 435, 765–772.
Shewmaker, F., Wichner, R. B., & Tycko, R. (2006). Amyloid of the prion domain of Sup35p has an in-register parallel β-sheet structure. Proceedings of the National Academy of Sciences of the United States of America, 103, 19754–19759.
Wickner, R. B., Dyda, F., & Tycko, R. (2008). Amyloid of Rnq1p, the basis of the [PIN+] prion, has a parallel in-register β-sheet structure. Proceedings of the National Academy of Sciences of the United States of America, 105, 2403–2408.
Fungal Prions
Chernoff, Y. O., Lindquist, S. L., Ono, B., Inge-Vechtomov, S. G., & Liebman, S. W. (1995). Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]. Science, 268, 880–884.
Halfmann, R., Jarosz, D. F., Jones, S. K., Chang, A., Lancaster, A. K., & Lindquist, S. (2012). Prions are a common mechanism for phenotypic inheritance in wild yeasts. Nature, 482, 363–368.
Liebman, S. W., & Chernoff, Y. O. (2012). Prions in yeast. Genetics, 191, 1041–1072.
Mukhopadhyay, S., Krishnan, R., Lemke, E. A., Lindquist, S., & Deniz, A. A. (2007). A natively unfolded yeast prion monomer adopts an ensemble of collapsed and rapidly fluctuating structures. Proceedings of the National Academy of Sciences of the United States of America, 104, 2649–2654.
Serio, T. R. (2000). Nucleated conformational conversion and the replication of conformational information by a prion determinant. Science, 289, 1317–1321.
Shorter, J., & Lindquist, S. (2004). Hsp 104 catalyzes formation and elimination of self-replicating Sup35 prion conformers. Science, 304, 1793–1797.
True, H. L., Berlin, I., & Lindquist, S. L. (2004). Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits. Nature, 431, 184–187.
Tuite, M. F., & Serio, T. R. (2010). The prion hypothesis: From biological anomaly to basic regulatory mechanism. Nature Reviews. Molecular Cell Biology, 11, 823–833.
Tyedmers, J., Madariaga, M. L., & Lindquist, S. (2008). Prion switching in response to environmental stress. PLoS Biology, 6, e294.
Wickner, R. B. (1994). [URE3] is an altered URE2 protein: Evidence for a prion analog in Saccharomyces cerevisiae. Science, 264, 566–569.
Beneficial Prions in Higher Organisms
Hou, F., Sun, L., Zheng, H., Skaug, B., Jiang, Q. X., & Chen, Z. J. (2011). MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell, 146, 448–461.
Si, K., Choi, Y. B., White-Grindley, E., Majumdar, A., & Kandel, E. R. (2010). Aplysia CPEB can form prion-like multimers in sensory neurons that contribute to long-term facilitation. Cell, 140, 421–435.
Si, K., Giustetto, M., Etkin, A., Hsu, R., Janisiewicz, A. M., Miniaci, M. C., et al. (2003). A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in Aplysia. Cell, 115, 893–904.
Cell-to-Cell Spread
Braak, H., & Braak, E. (1991). Neuropathological staging of Alzheimer-related changes. Acta Neuropathologica, 82, 239–259.
Braak, H., del Tredici, K., Rüb, U., de Vos, R. A., Jansen Steur, E. N., & Braak, E. (2003). Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging, 24, 197–211.
Fevrier, B., Vilette, D., Archer, F., Loew, D., Faigle, W., Vidal, M., et al. (2004). Cells release prions in association with exosomes. Proceedings of the National Academy of Sciences of the United States of America, 101, 9683–9688.
Gousset, K., Schiff, E., Langevin, C., Marijanovic, Z., Caputo, A., Browman, D. T., et al. (2009). Prions hijack tunneling nanotubes for intercellular spread. Nature Cell Biology, 11, 328–336.
Lundmark, K., Westermark, G. T., Nyström, S., Murphy, C. L., Solomon, A., & Westermark, P. (2002). Transmissibility of systemic amyloidosis by a prion-like mechanism. Proceedings of the National Academy of Sciences of the United States of America, 99, 6979–6984.
Rustom, A., Saffrich, R., Markovic, I., Walther, P., & Gerdes, H. H. (2004). Nanotubular highways for intercellular organelle transport. Science, 303, 1007–1010.
Simons, M., & Raposo, G. (2009). Exosomes—Vesicular carriers for intercellular communication. Current Opinion in Cell Biology, 21, 575–581.
Théry, C., Ostrowski, M., & Segura, E. (2009). Membrane vesicles as conveyors of immune responses. Nature Reviews. Immunology, 9, 581–593.
Lipid Membranes
Karnovsky, M. J., Kleinfeld, A. M., Hoover, R. L., & Klausner, R. D. (1982). The concept of lipid domains in membranes. The Journal of Cell Biology, 94, 1–6.
Simons, K., & Ikonen, E. (1997). Functional rafts in cell membranes. Nature, 387, 569–572.
Simons, K., & van Meer, G. (1988). Lipid sorting in epithelial cells. Biochemistry, 27, 6197–6202.
Singer, S. J., & Nicolson, G. L. (1972). The fluid mosaic model of the structure of cell membranes. Science, 175, 720–731.
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Appendix. Lipid Membrane Composition and Biophysical Properties
Appendix. Lipid Membrane Composition and Biophysical Properties
The mobility properties of the constituents of biological membranes depend both on the amount of cholesterol and the type of lipids present. Membrane lipids consist of a head group, a backbone, and a tail region (Fig. 7.10). Phosphoglycerides contain a glycerol backbone, whereas sphingolipids utilize sphingosine. Lipids found in biological membranes vary in acyl chain length and degree of saturation. Chains possess an even numbers of carbons typically between 14 and 24 with 16, 18, and 20. Chains with one or more doubly bonded carbons are unsaturated. These bonds are rigid and introduce kinks in the chain. These kinks cause irregularities or voids to appear in the array and, consequently, these molecules cannot be packed tightly. In contrast, in a fully saturated acyl chain the carbon–carbon atoms are covalently linked by single bonds. These carbon atoms are able to maximize the number of bonds with hydrogen atoms. As a result the chains can freely rotate about their carbon–carbon bonds and can pack tightly.
Membrane lipid and cholesterol structure. PC phosphatidylcholine (also abbreviated PtdCho), PE phosphatidylethanolamine (PtdEtn), SM sphingomyelin, Chol cholesterol. The inset depicts, in block diagram form, the skeletal structure of the molecules with a typical lipid shown on the left and a smaller cholesterol molecule pictured on the right. (Main figure from van Meer EMBO J. 24: 3159 © 2005 Reprinted with permission from John Wiley and Sons)
Cholesterol plays an important role in determining the fluidity of the membrane compartments. It is smaller than the phospholipids and sphingolipids. As the concentration of cholesterol increases the lipid membrane becomes less like a disordered gel and more like an ordered liquid in which the lipids are more tightly packed together. Three main types of lipid membranes are illustrated in Fig. 7.11. The upper panel depicts a liquid disordered membrane composed of unsaturated and fairly short phosphatidylcholine (or phosphatidylethanolamine) lipid molecules. At the other extreme the bottom panel illustrates the organization of a membrane composed of longer, saturated and fairly straight sphingomyelin molecules plus a considerable amount of cholesterol. This membrane structure is typical of a lipid raft .
Depiction of the lipid phases typical of biological membranes. From top to bottom: liquid-disordered (l d), solid gel (s o), and liquid-ordered (l o) in which there is a high cholesterol content (blue). The chain segment order (S) and diffusion constant (D T) for each of the phases are shown (from van Meer Nat. Rev. Mol. Cell Biol. 9: 112 © 2008 Reprinted by permission from Macmillan Publishers Ltd)
The biophysical properties of these membrane compartments are captured by phase diagrams such as the one shown in Fig. 7.12. This diagram summarizes the possible phases exhibited by mixtures containing various proportions of an unsaturated lipid, a saturated lipid, and cholesterol . In this figure, it can be seen that as the cholesterol content increases the liquid-ordered (l o) phase begins to dominate. Membrane compartments lacking cholesterol but with a high unsaturated lipid content are disordered (l d), while saturated lipids generate gel-like (s o) structures.
Structure of cholesterol and a lipid membrane phase diagram. (a) Rigid structure of the cholesterol molecule. (b) The phases of a hypothetical mixture of cholesterol, an unsaturated lipid Y (e.g., PC) and a saturated lipid Z (e.g., SM) at temperatures near or at the physiological temperature, 37 °C
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Beckerman, M. (2015). Prion Diseases. In: Fundamentals of Neurodegeneration and Protein Misfolding Disorders. Biological and Medical Physics, Biomedical Engineering. Springer, Cham. https://doi.org/10.1007/978-3-319-22117-5_7
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