Trends in Glycoscience and Glycotechnology
Online ISSN : 1883-2113
Print ISSN : 0915-7352
Volume 9 , Issue 45
Showing 1-20 articles out of 20 articles from the selected issue
  • Samuel H. Barondes, [in Japanese]
    1997 Volume 9 Issue 45 Pages 1-7
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Galectins, the large and growing class of β-galactosidebinding proteins that are the subject of this special issue, were discovered in the context of prior studies of soluble lectins in plant seeds and in cellular slime molds. In this paper I will describe how the early work on galectins evolved from these antecedents as well as from an interest in the mechanism of neuronal recognition; and I will share a few personal reminiscences.
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  • Hakon Leffler, [in Japanese]
    1997 Volume 9 Issue 45 Pages 9-19
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Galectins are a family of proteins defined by their affinity for β-galactosides and by conserved sequence elements. Ten galectins from mammals are known, as well as many from other phyla including birds, amphibians, fish, nematodes, sponges and fungi. Galectins are unusual among lectins in that they are cytosolic proteins. From the cytosol they may be secreted by non-classical pathways, but they may also be targeted to the nucleus or specific sub-cytosolic sites. Their function in the extracellular compartment has attracted most attention; there they are thought to act by cross-linking β-galactoside containing glycoconjugates, resulting in modulation of cell adhesion and cell signaling. However, they may also have functions in the cytosol and nucleus. Their non-classical secretory pathways per se, of which little is known in general, is another area of great interest. Although first discovered based on their β-galactoside binding activity, with the definition of characteristic sequence elements and the advent of molecular biological techniques, galectins are now being discovered in a variety of other interesting ways. Galectins, galectin inhibitors, or anti-galectin antibodies may possibly be used in therapy and diagnosis of cancer and inflammatory disorders.
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  • Karen E. Pace, Linda G. Baum, [in Japanese]
    1997 Volume 9 Issue 45 Pages 21-29
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Galectin-1, a member of the galectin family of β-galactoside binding proteins, is produced by many types of normal and neoplastic cells. Galectin-1 has been proposed to have a variety of functions, such as mediating cell-cell interactions and influencing cell growth.
    Recently, we have identified a possible additional function for galectin-1 as a mediator of T cell apoptosis, or physiologic cell death. Apoptosis is a crucial mechanism for the production of immunocompetent T cells in thymus and for the termination of an immune response in peripheral lymphoid organs. In the immune system, galectin-1 is expressed in human thymus, lymph node, and spleen. The presence of galectin-1 within lymphoid organs, and the ability of galectin-1 to induce apoptosis of thymocytes and activated T cells suggests galectin-1 may play an important role in maintaining central and peripheral immune tolerance to self antigens.
    Susceptibility of T cells to galectin-1 may be modulated by regulating the expression of cell surface glycoprotein counter-receptors for galectin-1. CD45, a cell surface glycoprotein counter-receptor for galectin-1, appears to be essential for triggering galectin-1 induced apoptosis. However, T cell susceptibility to galectin-1 may be further modulated by the glycosylation state of CD45, or by the presence of other galectin-1 counter-receptors, such as CD43.
    Galectin-1 may also play a role in regulating the immune system in nonlymphoid organs. Galectin-1 is expressed in many immune privileged sites and tissues, such as placenta, prostate, and cornea. An immune privileged site or tissue is a region of the body where the immune response is tempered in order to protect critical organs, such as the cornea, from damage induced by the inflammatory response of activated T cells. Apoptosis has been shown to be an important mechanism for preserving immune privilege. Expression of galectin-1 in immune privileged tissues may contribute to the maintenance of immune privilege by inducing apoptosis of infiltrating activated T cells. We hypothesize that the expression of galectin-1 in lymphoid organs and in immune privileged sites may play a significant role in modulating the immune response.
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  • Céline Colnot, Marie-Anne Ripoche, Deborah Fowlis, Virginetta C ...
    1997 Volume 9 Issue 45 Pages 31-40
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Galectins are members of a family of carbohydrate-recognizing molecules specific for β-galactosides, distinguishable from all other animal lectins by their low molecular weight, ranging from 14kDal to 36kDal, and their variable subcellular location. Ten members of this gene family have now been identified.
    Studies of the spatio-temporal distribution of various galectins during embryogenesis have shown that these molecules present very dynamic patterns of expression, suggesting roles in several developmental processes.
    In an attempt to elucidate the potential functions of these proteins during embryogenesis, we have generated mutants with targeted deletions of galectin-1 and galectin-3 genes. Animals homozygous for either of these mutations are viable and fertile. Despite the coexpression of galectins-1 and -3 on the surface of the embryo at the time of uterine implantation, double homozygote embryos also implant successfully and the combined loss of galectins-1 and 3 does not lead to any overt phenotype. Detailed analysis of these animals is in progress.
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  • Brian Key, Adam C. Puche, [in Japanese]
    1997 Volume 9 Issue 45 Pages 41-45
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    The olfactory nervous system is responsible for the detection of odors. Primary sensory olfactory neurons are located in a neuroepithelial sheet lining the nasal cavity. The axons from these neurons converge on to discrete loci or glomeruli in the olfactory bulb. Each glomerulus consists of the termination of thousands of primary axons on the dendrites of second-order olfactory neurons. What are the molecular mechanisms which guide growing olfactory axons to select sites in the olfactory bulb? We have shown that subpopulations of these axons differentially express cell surface carbohydrates and that these different subpopulations target and terminate in particular regions of the olfactory bulb. Interestingly, the olfactory neurons and glial components in the olfactory pathway between the nose and brain express galectin-1. By using in vitro assays of neurite outgrowth we found that both galectin-1 and it's ligands were capable of specifically stimulating neurite elongation. Examination of the olfactory system in galectin-1 null mutants revealed that a subpopulation of axons failed to navigate to their target site in the olfactory bulb. This is the first phenotypic effect observed in galectin-1 null mutants and indicates that galectin-1 has a role in the growth and/or guidance of a subpopulation of axons in the olfactory system during development.
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  • Moonjae Cho, Richard D. Cummings, [in Japanese]
    1997 Volume 9 Issue 45 Pages 47-56
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Galectin-1 is a member of the galectin-1 family of lectins that is able to form a homodimer of 14kDa subunits and each subunit has a single carbohydrate-binding site. The lectin is unusual in that it is synthesized in the cytosol of mammalian cells where it accumulates in a monomeric form. The lectin is actively, but slowly secreted (t1/2≈20h), and the secreted form requires glycoconjugate ligands to properly fold and acquire stability. The functional lectin exists in a monomer-dimer equilibrium with a Kd of -7μM and the equilibration rate is rather slow (t1/2≈10h). To explore the mechanism of dimerization and functional differences between monomeric and dimeric forms of the galectin-1, specific mutations were made in the extreme N-terminus involved in subunit interactions. Two of these mutants, termed N-Gal-1 and V5D-Gal-1, are functional monomers at low concentrations (<60μM), but they dimerize at high concentrations. The dimeric forms of native and mutated galectin-1 can be covalently cross-linked to generate nondissociable forms of galectin-1 that are extremely potent agglutinins. In contrast, the monomeric forms lack agglutinating activity, but they can compete with the dimeric forms of the lectin and block binding of the dimers.
    Galectin-1 binds to lactose Galβ1→4Glc and N-acetyllactosamine Galβ1→4GlcNAc with relatively low affinity (Kd in the range of 90-100μM), but the lectin binds to glycoproteins containing polylactosamine sequences [→3Galβ1→4GlcNAcβ1→]n with high affinity (Kd≈1μM). The lectin does not require terminal non-reducing galactose residues in polylactosamines for recognition. Polylactosamine sequences are selectively expressed on glycoproteins, such as laminin and lysosome-associated membrane proteins (LAMPs). The glycoproteins selectively recognized by galectin-1 may serve as potential ligands through which the lectin promotes cellular adhesion and cell signaling.
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  • Douglas N.W. Cooper, [in Japanese]
    1997 Volume 9 Issue 45 Pages 57-67
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Galectin-1 is a homodimeric lectin which is expressed at high levels in skeletal and smooth muscle, peripheral nerves, and some tumor cells. It has particular affinity for polylactosamine oligosaccharides. This review discusses the evidence that galectin-1 is secreted by unorthodox mechanisms and then binds to polylactosamine chains on laminin in the extracellular matrix and integrins, LAMPs, or lactosamine-containing glycolipids on cell surfaces. Depending on which matrix and cell surface receptors are expressed, galectin-1 can either promote or inhibit cell adhesion, migration, and neurite elongation. In this way galectin-1 is suspected to participate in regulating changes in cell interactions during normal development and tumor metastasis.
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  • Shiro Akahani, Hidenori Inohara, Pratima Nangia-Makker, Avraham Raz
    1997 Volume 9 Issue 45 Pages 69-75
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Galectin-3, previously described as IgE binding-protein, CBP35, CBP30, Mac-2, L-29, L-31, L34 and other names, is one of endogenous β-galactoside-binding proteins which is expressed broadly in normal and neoplastic cells. Although biological functions of galectin-3 remain largely in veil, a numerous number of trials to clarify them have been made, resulting in the elucidation of a possible involvement of galectin-3 in biological phenomena including cell growth and adhesion. It has been shown that galectin-3 expression correlates with neoplastic transformation in some type of cells. However, inconsistent and varying amounts of galectin-3 expression in tumors of the same origin reflect heterogenicity of tumor cells, and thus assume no relevance of galectin-3 in the definitive diagnosis of malignancy. In this regard northworthy is the recent findings showing that expression of galectin-3 is uniformly elevated with neoplastic progression in certain malignancies, and therefore, galectin-3 is expected to serve as a reliable tumor marker. Here we describe the evidence for galectin-3 to play a key role in tumor metastasis.
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  • Ronald J. Patterson, Sue F. Dagher, Anandita Vyakarnam, John L. Wang, ...
    1997 Volume 9 Issue 45 Pages 77-85
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    We describe a novel activity for nuclear galectins-1 and -3. Data presented indicate that these galectins are required factors in the splicing of pre-messenger RNA. Addition of saccharide ligands with high affinity for galectins inhibits pre-mRNA splicing in an in vitro assay using nuclear extracts isolated from HeLa cells. Depletion of the galectins from nuclear extracts by lactose-agarose affinity chromatography results in a splicing-deficient extract whereas depletion using a control saccharide affinity matrix does not affect splicing. The splicing activity of the galectin-depleted extract can be reconstituted by the addition of either recombinant galectin-1 or -3, suggesting that galectin splicing activity is functionally redundant. We further discuss this redundancy of galectin function in splicing, the nature of potential nuclear ligands for the galectins and several possible mechanisms of galectin action in the splicing pathway.
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  • Michael A. Gitt, Elizabeth T. Jordan, Hakon Leffler, [in Japanese]
    1997 Volume 9 Issue 45 Pages 87-93
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    There are now 10 known mammalian galectins. Here we describe the discovery and characterization of five of them. Galectin-2 is a 14kDa subunit dimeric galectin related to galectin-1 and is expressed in intestinal epithelial cells. Galectin-5 is a 15kDa monomeric galectin expressed in erythrocytes. Galectin-9 is a newly discovered 36kDa protein expressed in many tissues; it has two carbohydrate recognition domains (CRDs) with the C-terminal CRD very similar to galectin-5. Galectin-4 and -6 are two closely related bi-CRD galectins of 36 and 34kDa, respectively, which are expressed in epithelial cells of the alimentary tract.
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  • Thierry Magnaldo, Michel Darmon, [in Japanese]
    1997 Volume 9 Issue 45 Pages 95-102
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Galectin-7 is a 14kDA member of the lectin family recently cloned in the human. In human epidermis galectin-7 mRNA and protein were found to be present in all viable cell layers of the epithelium, showing that the expression of this marker was independant of the stage of differentiation of the keratinocyte. Studies with cultured keratinocytes showed that galectin-7 expression was not influenced by the calcium concentration and the resulting modulation of stratification, a result correlating with its pan-epidermal expression. Moreover, a model of reconstructed epidermis allowed us to show that galectin-7 expression is reduced but not suppressed when the metaplasia of epidermis into oral epithelium is induced by retinoic acid. This result suggested to us that galectin-7 could be a marker of both keratinized and non-keratinized stratified epithelia. To check this hypothesis the distribution of galectin-7 in human, rat and mouse epithelia was studied with a specific antiserum raised against a synthetic peptide. Moreover the rat cDNA was cloned and the distribution of galectin-7 mRNA was also studied in the rat. Galectin-7 was found to be expressed in interfollicular epidermis and the outer root sheath of the hair follicle, but not in the hair matrix, nor in the sebaceous glands. It was also present in esophagus and oral epithelia, cornea, Hassal corpuscles of the thymus, but not in simple and transitional epithelia. Galectin-7 can thus be considered as a marker of all subtypes of keratinocytes. Moreover this marker does not seem to be influenced by the stage of differentiation. In that respect it differs from keratins K5-K14 which are transcribed only in the basal layer and from involucrin which is synthesized only in the suprabasal layers. Galectin-7 also differs from desmosomal proteins, which are present in all types of epithelia and in myocardium.
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  • Yaron R. Hadari, Miri Eisenstein, Rina Zakut, Yehiel Zick, [in Japanes ...
    1997 Volume 9 Issue 45 Pages 103-112
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    We have recently cloned and expressed a novel mammalian lectin of the galectin family and named it galectin-8 [Hadari et al. (1995) J. Biol. Chem. 270, 3447-3453], Galectin-8 is a 35kDa protein, made of two domains of -140 amino-acids, each containing a single carbohydrate recognition domain (CRD). These domains are joined by a -30 amino acids ‘link peptide’. Galectin-8 is a widely expressed protein present in liver, heart, muscle, kidney and brain. Native galectin-8 exists as a monomer, that is tightly associated to yet undefined cellular constituent. A conserved Arg residue which forms part of the sugar-binding site of all galectins, including the C-terminal CRD of galectin-8, is replaced with Ile90 at the N-terminal CRD of galectin-8. This substitution markedly changes the predicted surface of the N-terminal CRD, creating an extended hydrophobic pocket that can accommodate hydrophobic glycoconjugates. As such, the two CRDs of galectin-8 are expected to be structurally different and to interact with two different types of carbohydrates. Hence, galectin-8 is a naturally-occurring, ubiquitous, bifunctional mammalian lectin that might complex glycoconjugates of different types.
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  • Jun Hirabayashi, Yoichiro Arata, Ken-ichi Kasai
    1997 Volume 9 Issue 45 Pages 113-122
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    The finding of Caenorhabditis elegans galectin (32kDa) demonstrated, for the first time; the presence of the “tandem-repeat type” of galectin, which consists of two homologous domains (ca. 16kDa). Its N- and C-terminal half domains show relatively low sequence similarity to each other (ca. 30% identity), though most (but not all) of the amino acids involved in the carbohydrate binding are conserved. The nematode 32kDa galectin shows strong hemagglutinating activity, but its saccharide specificity is rather complex. The individual half domains have considerably distinct features in the binding to asialofetuin-agarose. Though the endogenous ligand for them is not known, these observations imply that the 32-kDa nematode galectin functions as a possible “heterobifunctional crosslinker”. Since this galectin is localized most abundantly in the adult cuticle, it possibly plays a role in the formation of tight and insoluble epidermal layers. A recently isolated novel nematode galectin (16-kDa) forms a non-covalent dimer, and exhibits significant hemagglutinating activity, which is inhibitable by lactose. The current progress in the C. elegans genome project has revealed the presence of a number of galectin-related genes, and at least four other tandem-repeat-type galectins (40-75% identical to the 32-kDa galectin) have been proved to be expressed. Two closely related genes encoding CRDs (carbohydrate-recognition domains) having a somewhat longer C-terminal tail have also been predicted. Because the complete genome sequence of C. elegans (1 x 108bp) will be obtained in the near future, galectin research utilizing this model animal will hopefully provide us with new concepts about both the biological and evolutionary significance of multivalent galectin-carbohydrate interactions.
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  • Werner E.G. Müller, Barbara Blumbach, Claudia Wagner-Hülsman ...
    1997 Volume 9 Issue 45 Pages 123-130
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    With the marine sponge Geodia cydonium as a model system for cell reaggregation it was previously shown that cell-cell interactions require an aggregation factor. Recently it was found that this complex molecule is linked to the plasma membrane-bound aggregation receptor via a lectin, which turned out to be a β-galactoside-binding galectin. The cDNA encoding this molecule has been isolated and characterized; the deduced as sequence comprises high sequence similarity to other members of the family of galectins. Hence, it is shown that sponges [Porifera], the phylogenetically oldest metazoan phylum already possess galectins.
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  • Gerardo R. Vasta, Hafiz Ahmed, L. Mario Amzel, Mario A. Bianchet, [in ...
    1997 Volume 9 Issue 45 Pages 131-144
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Galectins appear to be ubiquitous in homeotherm vertebrates and presumably mediate several biological processes related to cell-cell and cell-extracellular matrix interactions. However, the detailed mechanisms of their function(s), as well as the stability of their binding activity in the extracellular environment, still remain unclear. Further, although their presence has been reported in poikilotherm vertebrates and invertebrates, very little is known about their molecular properties, nature of their endogenous carbohydrate ligands, biological role(s), and the overall evolutionary history of the galectin family in these taxa. Among amphibian species, galectins have been isolated from the toad Bufo arenarum, the frogs Rana tigerina and R. catesbeiana, the African clawed frog Xenopus laevis and the axolotl Ambystoma mexicanum, but only those from X. laevis and B. arenarum have been characterized in detail. Our recent work on a galectin from toad (B. arenarum) ovary suggest that it is closer in primary and three-dimensional structure and carbohydrate specificity, to the bovine galectin-1 than to the galectin from X. laevis, a species considered as exhibiting archaic features. This observation raises several questions: How prevalent are galectin-1-like lectins in oocytes from extant species within the “modern” amphibian taxa such as Bufo sp. (Neobatrachia), as compared to the “primitive” groups that include Xenopus sp. (Archaeobatrachia)? Is the presence or absence of these lectins the result of the species' life history or environmental factors? Or does it truly reveal the fact that galectin-1-like lectins arising in the Neobatrachia have merited such striking evolutionary conservation throughout the vertebrate lineages in structure and specificity, due to their involvement in a critical biological function? In contrast with X. laevis, where galectins are mainly confined to adult skin, in the toad B. arenarum galectins are detected in oocytes and further post-fertilization stages, raising the possibility that although present in phylogenetically related taxa, they might mediate mechanisms associated with substantially different biological functions, such as host defense in X. laevis vs. developmental processes in B. arenarum. In homeotherm vertebrates galectin-1 is expressed at the earliest in the blastula stage and has been postulated to participate in trophoblast implantation on the endometrium, whereas galectin activity in B. arenarum can be detected in oocytes, fertilized eggs and stages prior to blastula. It is possible that it mediates attachment of the protective jelly coat that is typical of egg masses of Bufo sp., and further participates in cell-cell or cell-intercellular matrix interactions in the developing embryo. Our preliminary work suggests that amphibian species may constitute useful models for gaining insight in the phylogenetic and functional aspects of galectins.
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  • Yuri D. Lobsanov, James M. Rini, [in Japanese]
    1997 Volume 9 Issue 45 Pages 145-154
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    The x-ray crystal structures of galectins-1 and -2 and their carbohydrate complexes have provided the galectin fold, the nature of their dimeric structure, and the molecular basis for carbohydrate-binding. Detailed analysis of the carbohydrate binding site has further provided the structural basis for its ability to bind poly-N-lactosaminyl glycan structures, and an explanation for some of the carbohydrate binding specificity differences shown by members of the galectin family. Sequence data in conjunction with recent x-ray crystallographic analysis of carbohydrate recognition domains from galectins-3 and -4, suggest that the galectin CRDs can be separated into the galectin-1/galectin-2 and galectin-3/galectin-4 subtypes. These two groups represent galectins whose CRDs are found in fundamentally different tertiary/quaternary organizations.
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  • C. Fred Brewer, [in Japanese]
    1997 Volume 9 Issue 45 Pages 155-165
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    The multivalent binding activities of lectins including certain galectins lead to the formation of type-1 and type-2 cross-linked complexes with multivalent carbohydrates and glycoconjugates. Type-1 complexes occur between divalent lectins and divalent carbohydrates or glycoconjugates which yield 1-dimensional cross-linked complexes. This type of complex has been observed between galectin-1 from bovine heart muscle and a bivalent N-linked biantennary complex glycopeptide (Bourne et al., 1994). Type-2 interactions occur between lectins and carbohydrates or glycoconjugates where one of the two molecules possesses a valency greater than two. In this case, 2- and 3-dimensional cross-linking occurs which may be homogeneous if crystal packing interactions are present. Evidence indicates that calf spleen galectin-1 undergo type-2 cross-linking interactions with ASF (Gupta and Brewer, 1994). The flexibility of certain galectins such as galectin-1 to form type-1 and type-2 cross-linked complexes with carbohydrates and glycoconjugates may relate to the biological activities of this animal lectin, and to the activities of other members of the galectin family.
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  • K. Kasai
    1997 Volume 9 Issue 45 Pages 167-170
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
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  • Jun Hirabayashi
    1997 Volume 9 Issue 45 Pages 181-182
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
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  • Yoichiro Arata
    1997 Volume 9 Issue 45 Pages 183-184
    Published: January 02, 1997
    Released: January 05, 2010
    JOURNALS FREE ACCESS
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