492:
method of hapten conjugation is that there is automated analysis of sample and the testing of sample interactions can be determined in free solution. This method of hapten-protein conjugation is exceptionally effective with conjugates of low epitope densities, where it is otherwise very challenging by the use of other methods to determine their electrical or ionic mobility.
329:. However, to achieve the best and most desirable results, many factors are needed to be taken into the design of hapten conjugates. These include the method of hapten conjugation, the type of carrier used and the hapten density. Variations in these factors could lead to different strengths of immune response toward the newly formed antigenic determinant.
345:), either by itself, or it can be converted to a protein-reactive species for example by air oxidation or cutaneous metabolism. Haptens become fastened to a carrier molecule by a covalent bond. Depending on the haptens being used, other factors in considering the carrier proteins could include their in vivo toxicity, commercial availability and cost.
138:, the small-molecule hapten may also be able to bind to the antibody, but it will usually not initiate an immune response; usually only the hapten-carrier adduct can do this. Sometimes the small-molecule hapten can even block immune response to the hapten-carrier adduct by preventing the adduct from binding to the antibody, a process called
559:
Hapten-specific antibodies are used in broad area of different immunoassays, immunobiosensor technologies and immunoaffinity chromatography purification columns; those antibodies could be used to detect small environmental contaminants, drugs of abuse, vitamins, hormones, metabolites, food toxins and
387:
Most common reaction mechanisms forming covalent bonds and predicted to be involved in sensitization are nucleophilic substitution on a saturated centre, nucleophilic substitution on an unsaturated centre and nucleophilic addition. Other reactions are also possible, such as electrophilic substitution
300:
to crosslink these molecules to carrier proteins suitable for immune recognition. Notably, detection of such small molecules in tissues requires the tissue to be glutaraldehyde-fixed, as the glutaraldehyde covalent-linkage on the molecule of interest often forms a portion of the antibody recognized
491:
with a very high separation capacity. There are numerous advantages to using HPCE as a technique to investigate certain conjugates such as only requiring minute sample sizes (nl). In addition, the sample used does not need to be pure and no type of radiolabeling is needed. A great benefit to this
535:
Haptens are widely used in immunology and related fields. Sensitizing chemicals can cause different forms of allergy, allergic contact dermatitis, or sensitization of the respiratory tract. Interestingly, discrete types of chemicals induce divergent immune responses: contact allergens provoke
115:. The second elicitation phase where the hapten is applied to a different skin area starts with activation of effector T cells followed by T cell-mediated tissue damage and antibody-mediated immune responses. Haptens initially activate innate immune responses by complex mechanisms involving
99:. It consists of two phases: sensitization and elicitation. The sensitization phase where the hapten is applied to the skin for the first time is characterized by the activation of innate immune responses, including migration of dendritic cells to the lymph nodes, priming antigen-specific
744:
Sakamoto, Eri; Katahira, Yasuhiro; Mizoguchi, Izuru; Watanabe, Aruma; Furusaka, Yuma; Sekine, Ami; Yamagishi, Miu; Sonoda, Jukito; Miyakawa, Satomi; Inoue, Shinya; Hasegawa, Hideaki; Yo, Kazuyuki; Yamaji, Fumiya; Toyoda, Akemi; Yoshimoto, Takayuki (12 January 2023).
555:
tests for skin sensitization, hazard identification, and potency evaluation on different drug and cosmetic components are highly preferred in early product development. The ability of a drug to act as a hapten is a clear indication of potential immunogenicity.
433:: A group of compounds with a general formula of R-N=C=N-Râ˛, where R and RⲠare either aliphatic (i.e., diethylcarbodiimide) or aromatic (i.e., diphenylcarbodiimide). Conjugation using a carbodiimide requires the presence of Îą or É-amino and a
441:
residue of the carrier protein while the carboxyl group comes from the hapten. The exact mechanism for this reaction is still unknown. However, two pathways are proposed. The first postulates that an intermediate that can react with an
510:
response. In inhibition, free hapten molecules bind with antibodies toward that molecule without causing the immune response, leaving fewer antibodies left to bind to the immunogenic hapten-protein adduct. An example of a
426:
are to aid the conjugation of haptens to their carriers. The extent of cross-linkage is dependent upon the hapten/carrier to coupling agent ratio, hapten/carrier concentration and the temperature, pH of the environment.
161:-type molecule, which then reacts with skin proteins to form hapten adducts. After a second exposure, the proliferated T-cells become activated, generating an immune reaction that produces typical blisters of a
396:
While selecting a suitable method for hapten conjugation, functional groups on the hapten and its carrier must be identified. Depending on the groups present, one of the two main strategies could be employed:
1009:"Studies on the immune response and preparation of antibodies against a large panel of conjugated neurotransmitters and biogenic amines: specific polyclonal antibody response and tolerance"
468:
of the reaction. Higher pH would give rise to more Schiff base intermediates and subsequently lead to the increase in hapten conjugates' number and size. Overall, cross-linkage involving
956:
Tagliaferro, P; Tandler, C.J; Ramos, A.J; Pecci
Saavedra, J; Brusco, A (1997). "Immunofluorescence and glutaraldehyde fixation. A new procedure based on the Schiff-quenching method".
57:
by itself. The mechanisms of absence of immune response may vary and involve complex immunological interactions, but can include absent or insufficient co-stimulatory signals from
368:
is often to bind to xenobiotics via its substrate-binding pockets and remove the invading chemical from the circulation or tissue, thus acting as a detoxification mechanism.
1289:
Frøkiaer, H.; Sørensen, H.; Sørensen, J. C.; Sørensen, S. (1995-11-24). "Optimization of hapten-protein conjugation by high-performance capillary electrophoresis".
180:
A lot of haptens are comprised in different kinds of drugs, pesticides, hormones, food toxins etc. Most important factor is the molecular mass, which is <1000
293:
364:(HSA) is often the model protein of choice for protein-binding assays. This is a well-characterized protein, and the role of albumin in blood and tissues
1533:
831:"Defining the complementarities between antibodies and haptens to refine our understanding and aid the prediction of a successful binding interaction"
1404:
Divkovic, Maja; Basketter, David A.; Gilmour, Nicola; Panico, Maria; Dell, Anne; Morris, Howard R.; Pease, Camilla K. Smith (2003-01-01).
341:
residues in the reactive side chains to conjugate with the haptens. For protein haptenation to occur, hapten must be electron deficient (
829:
Al
Qaraghuli, Mohammed M.; Palliyil, Soumya; Broadbent, Gillian; Cullen, David C.; Charlton, Keith A.; Porter, Andrew J. (2015-10-24).
484:
620:"Hapten-Induced Contact Hypersensitivity, Autoimmune Reactions, and Tumor Regression: Plausibility of Mediating Antitumor Immunity"
256:
Antibodies have successfully been raised against endogenous & unreactive small molecules such as some neurotransmitters (e.g.
1526:
523:) of the entire dextran complex, which is enough to bind anti-dextran antibodies, but insufficient to result in the formation of
1357:
Hopkins, Josephine E.; Naisbitt, Dean J.; Kitteringham, Neil R.; Dearman, Rebecca J.; Kimber, Ian; Park, B. Kevin (2005-02-01).
1344:
1273:
693:
1211:
Bauminger, Sara; Wilchek, Meir (1980). "[7] the use of carbodiimides in the preparation of immunizing conjugates".
902:
1359:"Selective Haptenation of Cellular or Extracellular Protein by Chemical Allergens: Association with Cytokine Polarization"
162:
120:
1519:
544:, which could be very suitable for modeling how the immune response is polarized towards different types of antigens.
1228:
1080:
1865:
487:(HPCE) is an alternative method in optimizing hapten-protein conjugation. HPCE is predominantly used in separating
1860:
1156:"Hapten-protein binding: from theory to practical application in the in vitro prediction of skin sensitization"
418:
This method mainly applies to nonreactive haptens. Agents with at least two chemically reactive groups such as
1803:
1106:"Synthesis and Characterization of HaptenâProtein Conjugates for Antibody Production against Small Molecules"
87:
Haptens applied on skin, when conjugate with a carrier, could induce contact hypersensitivity, which is a
65:
464:
or
Michael-type double bond addition products. The yield of conjugates can be controlled by varying the
1689:
1333:
Affinity probe capillary electrophoresis evaluation of aptamer binding to
Campylobacter jejuni bacteria
1008:
709:
Shreder, Kevin (March 2000). "Synthetic
Haptens as Probes of Antibody Response and Immunorecognition".
69:
1452:
1331:
Stratis-Cullum, D., McMasters, Sun, Pellegrino, Paul M, & U.S. Army
Research Laboratory. (2009).
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58:
17:
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Although proteins are mostly employed for hapten conjugation, synthetic polypeptides such as
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116:
747:"Chemical- and Drug-Induced Allergic, Inflammatory, and Autoimmune Diseases Via Haptenation"
1855:
1788:
1699:
1623:
1406:"ProteinâHapten Binding: Challenges and Limitations for In Vitro Skin Sensitization Assays"
1104:
Singh, K. V.; Kaur, Jasdeep; Varshney, Grish C.; Raje, Manoj; Suri, C. Raman (2004-01-01).
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in certain individuals. This also appears to be the mechanism by which the anesthetic gas
172:, which is caused by nickel metal ions penetrating the skin and binding to skin proteins.
8:
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Divkovic, Maja; Pease, Camilla K.; Gerberick, G. Frank; Basketter, David A. (May 2005).
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1335:(ARL-TR (Aberdeen Proving Ground, Md.); 5015). Adelphi, MD: Army Research Laboratory.
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79:, who also pioneered the use of synthetic haptens to study immunochemical phenomena.
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412:. This method of conjugation is spontaneous and no cross-linking agents are needed.
325:. They are also vital in the development of sensitive quantitative and qualitative
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Due to their nature and properties, hapten-carrier adducts have been essential in
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Other haptens that are commonly used in molecular biology applications include
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153:. When absorbed through the skin from a poison ivy plant, urushiol undergoes
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214:, a blood pressure-lowering drug that occasionally can produce drug-induced
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450:, the main side product of the reaction at high temperature, has occurred.
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Sheedy, Claudia; Roger MacKenzie, C.; Hall, J. Christopher (2007-07-01).
461:
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and antibodies. They are important in the purification and production of
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In general, carrier proteins should be immunogenic and contain enough
75:
The concept of haptens emerged from the work of
Austrian immunologist
1941:
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Molecule which triggers an immune response when attached to a carrier
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1067:. Methods in Molecular Medicine. Vol. 138. pp. 167â182.
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Lemus, Ranulfo; Karol, Meryl H. (2008). "Conjugation of
Haptens".
1936:
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1453:"Isolation and affinity maturation of hapten-specific antibodies"
1345:
Promiten, drug information from the
Swedish official drug catalog
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50:
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1254:"Conjugation of Peptides to Carrier Proteins via Glutaraldehyde"
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108:
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The
Specificity of Serological Reactions, 2nd Edition, revised
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is formed. The second stating that a rearrangement of an acyl
569:
540:
responses, whereas respiratory allergens stimulate selective
472:
is very stable. However, immunized animals tend to recognize
443:
438:
317:. They have been used to evaluate the properties of specific
82:
1007:
Huisman, Han; Wynveen, Paul; Setter, Peter W. (2010-02-06).
157:
in the skin cells to generate the actual hapten, a reactive
447:
388:(diazonium salts), radical reactions, and ionic reactions.
269:
506:
Hapten inhibition or "semi-hapten" is the inhibition of a
1450:
1215:. Methods in Enzymology. Vol. 70. pp. 151â159.
404:
Used when hapten is a chemical reactive molecule such as
168:
Other example of a hapten-mediated contact dermatitis is
465:
1410:
Journal of Toxicology: Cutaneous and Ocular Toxicology
53:; the carrier may be one that also does not elicit an
1103:
103:, and the generation of antigen-specific effector or
1006:
1260:. Springer Protocols Handbooks. pp. 679â687.
907:Current Opinion in Allergy and Clinical Immunology
1954:
1210:
391:
382:
49:only when attached to a large carrier such as a
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1058:
1056:
1054:
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456:: This method works by the reaction between
683:
668:
617:
482:High performance capillary electrophoresis:
72:(IBD) to induce autoimmune-like responses.
1534:
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485:High performance capillary electrophoresis
83:Immune reaction on a hapten-carrier adduct
1504:at the U.S. National Library of Medicine
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1047:
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437:. The amino group usually comes from the
671:The Specificity of Serological Reactions
900:
708:
14:
1955:
1251:
889:The Specificity of Serologic Reactions
618:Erkes, Dan; Selvan, Senthamil (2014).
175:
1515:
1149:
1147:
476:'s cross-linking bridges as epitopes.
416:Intermediary molecules cross-linkage:
308:
595:"Hapten | biochemistry | Britannica"
501:
226:, as well as the mechanism by which
145:A well-known example of a hapten is
121:damage-associated molecular patterns
803:
163:urushiol-induced contact dermatitis
24:
1144:
187:The first researched haptens were
25:
1979:
1495:
1213:Immunochemical Techniques, Part A
901:Pichler, Werner J. (2003-08-01).
673:. Cambridge: Harvard Univ. Press.
348:The most common carriers include
1469:10.1016/j.biotechadv.2007.02.003
1173:10.1111/j.0105-1873.2005.00683.x
1025:10.1111/j.1471-4159.2009.06492.x
919:10.1097/00130832-200308000-00003
527:and resultant immune responses.
89:type IV delayed hypersensitivity
64:Haptens have been used to study
1444:
1397:
1363:Chemical Research in Toxicology
1350:
1338:
1325:
1282:
1252:Carter, John (1 January 1996).
1245:
1204:
1097:
1000:
958:Journal of Neuroscience Methods
894:
887:Based on K. Landsteiner, 1962,
519:, which is a small fraction (1
496:
1861:Immunoglobulin class switching
1258:The Protein Protocols Handbook
881:
822:
797:
737:
702:
688:. Courier Dover Publications.
677:
662:
624:Journal of Immunology Research
611:
587:
402:Spontaneous chemical reaction:
230:-class drugs cause autoimmune
191:and its carboxyl derivatives (
149:, which is the toxin found in
13:
1:
1266:10.1007/978-1-60327-259-9_117
1221:10.1016/s0076-6879(80)70046-0
1065:Allergy Methods and Protocols
970:10.1016/s0165-0270(97)00126-x
580:
392:Methods of hapten conjugation
383:Mechanisms of protein binding
222:can cause a life-threatening
1303:10.1016/0021-9673(95)00642-X
1073:10.1007/978-1-59745-366-0_14
130:Once the body has generated
68:(ACD) and the mechanisms of
7:
1291:Journal of Chromatography A
964:(2). Elsevier BV: 191â197.
903:"Drug-induced autoimmunity"
563:
530:
332:
66:allergic contact dermatitis
37:, meaning âto fastenâ) are
10:
1984:
1690:Polyclonal B cell response
684:Landsteiner, Karl (1990).
669:Landsteiner, Karl (1945).
560:environmental pollutants.
460:with amine groups to form
70:inflammatory bowel disease
1924:
1882:
1824:
1725:
1655:
1563:
1556:
1013:Journal of Neurochemistry
848:10.1186/s12896-015-0217-x
508:type III hypersensitivity
1506:Medical Subject Headings
1347:Last updated: 2005-02-17
810:pubchem.ncbi.nlm.nih.gov
206:Some haptens can induce
59:antigen-presenting cells
33:(derived from the Greek
764:10.3390/biology12010123
538:type I hypersensitivity
210:disease. An example is
111:and antibody-secreting
1804:Tolerance in pregnancy
1546:adaptive immune system
1457:Biotechnology Advances
1110:Bioconjugate Chemistry
723:10.1006/meth.1999.0929
375:, polysaccharides and
117:inflammatory cytokines
1839:Somatic hypermutation
1673:Polyclonal antibodies
1668:Monoclonal antibodies
1422:10.1081/CUS-120020382
323:monoclonal antibodies
284:), amino acids (e.g.
91:reaction mediated by
1856:Junctional diversity
1624:Antigen presentation
379:could also be used.
373:Poly-L-glutamic acid
134:to a hapten-carrier
1851:V(D)J recombination
1834:Affinity maturation
1586:Antigenic variation
637:10.1155/2014/175265
362:Human serum albumin
294:5-methoxytryptophan
290:5-hydroxytryptophan
216:lupus erythematosus
201:p-aminobenzoic acid
176:Examples of haptens
1160:Contact Dermatitis
599:www.britannica.com
309:Hapten conjugation
1950:
1949:
1878:
1877:
1628:professional APCs
1375:10.1021/tx049688+
1275:978-0-89603-338-2
1122:10.1021/bc034158v
835:BMC Biotechnology
695:978-0-486-66203-9
630:. Hindawi: 1â28.
542:type II responses
502:Hapten inhibition
360:and many others.
140:hapten inhibition
16:(Redirected from
1975:
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1816:Immune privilege
1811:Immunodeficiency
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474:glutaraldehyde
470:glutaraldehyde
458:glutaraldehyde
454:Glutaraldehyde
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435:carboxyl group
424:glutaraldehyde
413:
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350:serum globulin
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298:glutaraldehyde
177:
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170:nickel allergy
105:memory T cells
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1963:Immune system
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1761:Inflammation
1746:Alloimmunity
1741:Autoimmunity
1726:Immunity vs.
1678:Autoantibody
1592:
1576:Superantigen
1460:
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497:Clinical use
481:
462:Schiff bases
431:Carbodiimide
420:carbodiimide
415:
401:
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336:
327:immunoassays
312:
296:), by using
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129:
125:inflammasome
113:plasma cells
86:
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34:
30:
29:
1884:Lymphocytes
1543:Lymphocytic
410:isocyanates
247:digoxigenin
239:fluorescein
212:hydralazine
1968:Immunology
1957:Categories
1925:Substances
1789:Peripheral
1777:Inaction:
1656:Antibodies
1637:Macrophage
1550:complement
815:2023-01-23
806:"Urushiol"
757:(1): 123.
604:2023-01-23
581:References
521:kilodalton
406:anhydrides
339:amino acid
315:immunology
286:tryptophan
274:tryptamine
228:penicillin
208:autoimmune
151:poison ivy
132:antibodies
1942:Cytolysin
1932:Cytokines
1779:Tolerance
1728:tolerance
1647:Immunogen
1477:0734-9750
1430:0731-3829
1383:0893-228X
1311:0021-9673
1182:0105-1873
1130:1043-1802
1041:205621520
978:0165-0270
927:1528-4050
857:1472-6750
841:(1): 99.
804:PubChem.
773:2079-7737
553:in silico
517:dextran 1
377:liposomes
358:ovalbumin
262:glutamate
258:serotonin
224:hepatitis
220:halothane
155:oxidation
1892:Cellular
1736:Immunity
1734:Action:
1717:Paratope
1705:Idiotype
1695:Allotype
1663:Antibody
1617:Mimotope
1581:Allergen
1564:Antigens
1557:Lymphoid
1485:17383141
1438:72917520
1391:15720145
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1091:18612607
1033:19912471
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943:46521947
935:12865767
875:26498921
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731:10694458
656:24949488
564:See also
549:in vitro
531:Research
354:albumins
333:Carriers
319:epitopes
266:dopamine
147:urushiol
1937:Opsonin
1916:NK cell
1904:Humoral
1784:Central
1751:Allergy
1700:Isotype
1600:Epitope
1571:Antigen
1502:Haptens
1319:8520687
1239:6999295
1198:9713648
986:9489897
866:4619568
782:9855847
751:Biology
711:Methods
647:4052058
575:Antigen
366:in vivo
303:epitope
278:glycine
260:(5HT),
189:aniline
159:quinone
109:B cells
93:T cells
51:protein
35:haptein
31:Haptens
18:Haptens
1909:B cell
1897:T cell
1642:B cell
1605:Linear
1593:Hapten
1508:(MeSH)
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243:biotin
199:, and
136:adduct
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1037:S2CID
990:S2CID
939:S2CID
570:Toxin
444:amine
439:lysyl
41:that
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1379:ISSN
1315:PMID
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652:PMID
628:2014
448:urea
408:and
270:GABA
107:and
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1870:HLA
1866:MHC
1465:doi
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1262:doi
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1168:doi
1118:doi
1069:doi
1021:doi
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