記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1128/JVI.03425-12

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

After entry into target cells, retroviruses encounter the host restriction factors such as Fv1 and TRIM5 alpha. While it is clear that these factors target retrovirus capsid proteins (CA), recognition remains poorly defined in the absence of structural information. To better understand the binding interaction between TRIM5 alpha and CA, we selected a panel of novel N-tropic murine leukaemia virus (N-MLV) escape mutants by a serial passage of replication competent N-MLV in rhesus macaque TRIM5 alpha (rhTRIM5 alpha)-positive cells using a small percentage of unrestricted cells to allow multiple rounds of virus replication. The newly identified mutations, many of which involve changes in charge, are distributed over the outer 'top' surface of NMLV CA, including the N-terminal beta-hairpin, and map up to 29 A(o) apart. Biological characterisation with a number of restriction factors revealed that only one of the new mutations affects restriction by human TRIM5 alpha, indicating significant differences in the binding interaction between N-MLV and the two TRIM5 alpha s, whereas three of the mutations result in dual sensitivity to Fv1(n) and Fv1(b). Structural studies of two mutants show that no major changes in the overall CA conformation are associated with escape from restriction. We conclude that interactions involving much, if not all, of the surface of CA are vital for TRIM5 alpha binding.

DOI： 10.1371/journal.ppat.1002011

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DOI： 10.1371/journal.ppat.1002011

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC MICROBIOLOGY  

Foamy viruses (FVs) are unconventional retroviruses with a replication strategy that is significantly different from orthoretroviruses and bears some homology to that of hepadnaviruses. Although some cellular proteins, such as APOBEC3, have been reported to block FVs, no restriction by Trim5 alpha has been described to date. The sensitivity of three FV isolates of human-chimpanzee or prototypic (PFV), macaque (SFVmac), and feline (FFV) origin to a variety of primate Trim5 alpha s was therefore tested. PFV and SFVmac were restricted by Trim5 alpha s from most New World monkeys, but not from other primates, whereas FFV-based vectors were restricted by Trim5 alpha s from the great apes gorilla and orangutan. Trim5 alpha s from Old World monkeys did not restrict any FV isolate tested. Capuchin Trim5 alpha was unique, as it restricted SFVmac and FFV but not PFV. Trim5 alpha specificity for FVs was determined by the B30.2 domain, interestingly involving, in some instances, the same residues of the variable regions previously implicated as major determinants for human immunodeficiency virus type 1 restriction. FVs with chimeric Gags were made to map the viral determinants of sensitivity to restriction. The N-terminal half of the Gag molecule was found to contain the regions that control susceptibility. This region most likely corresponds to the capsid of conventional retroviruses. Due to their unique replication strategy, FVs should provide a valuable new system to examine the mechanism of retroviral restriction by Trim5 alpha.

DOI： 10.1128/JVI.02462-07

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC MICROBIOLOGY  

Recent studies have revealed the contribution of TRIM alpha to retrovirus restriction in cells from a variety of primate species. TRIM5 alpha consists of a tripartite motif (the RBCC domain) followed by a B30.2 domain. The B30.2 domain is thought to be involved in determination of restriction specificity and contains three variable regions. To investigate the relationship between the phylogeny of primate TRIM5 alpha and retrovirus restriction specificity, a series of chimeric TRIM5 alpha consisting of the human RBCC domain followed by the B30.2 domain from various primates was constructed. These constructs showed restriction profiles largely consistent with the origin of the B30.2 domain. Restriction specificity was further investigated with a variety of TRIM5 alpha s containing mixed or mutated B30.2 domains. This study revealed the importance of all three variable regions for determining restriction specificity. Based on the molecular structures of other PRYSPRY domains solved recently, a model for the molecular structure of the B30.2 domain of TRIM5 alpha was developed. The model revealed that the variable regions of the B30.2 domain are present as loops located on one side of the B30.2 core structure. It is hypothesized that these three loops form a binding surface for virus and that evolutionary changes in any one of the loops can alter restriction specificity.

DOI： 10.1128/JVI.006880-06

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SOC GENERAL MICROBIOLOGY  

In order to understand primate lentivirus; evolution, characterization of additional simian immunodeficiency virus (SIV) strains is essential. Here, an SIV from a black mangabey (Lophocebus aterrimus) originating from the Democratic Republic of Congo was analysed phylogenetically. The monkey had cross-reactive antibodies against human immunodeficiency virus type 1 (HIV-1) and HIV-2. The viral pol region sequence was amplified by nested PCR and sequence analysis confirmed that it was related to known SIV sequences. This is the first report to characterize genetically an SIV from the monkey genus Lophocebus. Phylogenetic analysis of the pol region revealed that this novel SIV, designated SIVbkm, fell into the SIVsyk and SIVgsn virus group, containing viruses isolated from the genus Cercopithecus, and suggests that cross-species transmission has occurred between species of the genera Lophocebus, and Cercopithecus.

DOI： 10.1099/vir.0.80697-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MARY ANN LIEBERT INC  

Seven isolates of human T cell leukemia virus type 1 (HTLV-1) were taken in southern India and phylogenetically analyzed to gain new insights into the origin and dissemination of HTLV-1 in the subcontinent. The new Indian HTLV-1s were found to be members of subgroup A (Transcontinental subgroup) of the Cosmopolitan group. They formed three different clusters ( South African/Caribbean, Middle Eastern, and East Asian clusters). These results demonstrate that Indian HTLV-1s are genetically heterogeneous and include the most divergent strain of subgroup A. On the basis of these results, we speculate that subgroup A HTLV-1s may have been present for thousands of years in India.

DOI： 10.1089/aid.2005.21.325

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CENTER ACADEMIC PUBL JAPAN  

We previously reported that a nef-deleted SHIV (SHIV-NI) is nonpathogenic and gave macaques protection from challenge infection with pathogenic SHIV-C2/1. To investigate whether IFN-gamma augments the immune response induced by this vaccination, we examined the antiviral and adjuvant effect of recombinant human IFN-gamma (rIFN-gamma) in vaccinated and unvaccinated monkeys. Nine monkeys were vaccinated with nef-deleted nonpathogenic SHIV-NI. Four of them were administered with rIFN-gamma and the other five monkeys were administered with placebo. After the challenge with pathogenic SHIV-C2/1, CD4(+) T-cell counts were maintained similarly in monkeys of both groups, while those of the unvaccinated monkeys decreased dramatically at 2 weeks after challenge. However, the peaks of plasma viral load were reduced to 100-fold in SHIV-NI vaccinated monkeys combined with rIFN-gamma compared with those in SHIV-NI vaccinated monkeys without rIFN-gamma. The peaks of plasma viral load were inversely correlated with the number of SIV Gag-specific IFN-gamma-producing cells. In SHIV-NI-vaccinated monkeys with rIFN-gamma, the number of SIV Gag-specific IFN-gamma-producing cells of PBMCs increased 2-fold compared with those in SHIV-NI-vaccinated monkeys without rIFN-gamma, and the NK activity and MIP-1 alpha production of PBMCs were also enhanced. Thus, vaccination of SHIV-NI in combination with rIFN-gamma was more effective in modulating the antiviral immune system into a Th1 type response than SHIV-NI vaccination alone. These results suggest that IFN-gamma augmented the anti-viral effect by enhancing innate immunity and shifting the immune response to Th1.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER-VERLAG WIEN  

To detect the major sites of viral replication in immunodeficiency virus-infected individuals, we quantified proviral DNA and infectious viruses using quantitative PCR and a plaque assay, respectively, in various tissues of SHIVKU-2-infected monkeys in the early and AIDS stages of infection. Compared the quantity of infectious virus among PBMC and the lymphoid tissues, the mesenteric lymph node had the largest number of infectious viruses at the AIDS stage more than at the early stage of infection. These results suggested that the gastrointestinal tract was a major site of viral replication. In the brain, proviral DNA was detected at the early and AIDS stage of infection, but infectious viruses were detected at only the AIDS stage. Moreover, we analyzed the nucleotide sequences of the env V3 region in infectious virus clones isolated from each plaque. The viruses in the lymphoid tissues of the monkey that developed AIDS diverged from the inoculated virus and had the same three amino acid substitutions. However, the viruses in the brain were almost identical to the inoculated virus, suggesting that the virus entered the brain early after infection and persisted without replication and genetic diversion until the AIDS stage.

DOI： 10.1007/s00705-003-0252-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

To clarify the relationship between the amino acid variations of the gp120 of human immunodeficiency virus type 1 (HIV-1) and the chemokine receptors that are used as the second receptor for HIV, we evaluated amino acid site variation of gp120 between the X4 strains (use CXCR4) and the R5 strains (use CCR5) from 21 sequences of subtype B. Our analysis showed that residues 306 and 322 in the V3 loop and residue 440 in the C4 region were associated with usage of the second receptor. The polymorphism at residue 440 is clearly associated with the usage of the second receptor: The amino acid at position 440 was a basic amino acid in the R5 strains, and a nonbasic and smaller amino acid in the X4 strains, while the V3 loop of the X4 strains was more basic than that of the R5 strains. This suggests that residue 440 in the C4 region, which is close to the V3 loop in the three-dimensional structure, is critical in determining which second receptor is used. Analysis of codon frequency suggests that, in almost all cases, the difference at residue 440 between basic amino acids in the R5 strains and nonbasic amino acids in the X4 strains could be due to a single nucleotide change. These findings predict that the evolutionary changes in amino acid residue 440 may be correlated with evolutionary changes in the V3 loop. One possibility is that a change in electric charge at residue 440 compensates for a change in electric charge in the V3 loop. The amino acid polymorphism at position 440 can be useful to predict the cell tropism of a strain of HIV-1 subtype B.

DOI： 10.1007/s00239-003-2555-x

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC MICROBIOLOGY  

Simian T-cell leukemia viruses (STLVs) are the simian counterparts of human T-cell leukemia viruses (HTLVs). A novel, divergent type of STLV (STLV-L) from captive baboons was reported in 1994, but its natural prevalence remained unclear. We investigated the prevalence of STLV-L in 519 blood samples from wild-living nonhuman primates in Ethiopia. Seropositive monkeys having cross-reactive antibodies against HTLV were found among 22 out of 40 hamadryas baboons, 8 of 96 anubis baboons, 24 of 50 baboons that are hybrids between hamadryas and anubis baboons, and 41 of 177 grivet monkeys, but not in 156 gelada baboons. A Western blotting assay showed that sera obtained from seropositive hamadryas and hybrid baboons exhibited STLV-L-like reactivity. A PCR assay successfully amplified STLV sequences, which were subsequently sequenced and confirmed as being closely related to STLV-L. Surprisingly, further PCR showed that nearly half of the hamadryas (20 out of 40) and hybrid (19 out of 50) baboons had STLV-L DNA sequences. In contrast, most of the seropositive anubis baboons and grivet monkeys carried typical STLV-1 but not STLV-L. These observations demonstrate that STLV-L naturally prevails among hamadryas and hybrid baboons at significantly high rates. STLV-1 and -2, the close relative of STLV-L, are believed to have jumped across simian-human barriers, which resulted in widespread infection of HTLV-1 and -2. Further studies are required to know if STLV-L is spreading into human populations.

DOI： 10.1128/JVI.76.4.1642-1648.2002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Mary Ann Liebert  

We found a novel primate lentivirus in mandrill (Mandrillus sphinx). To clarify the evolutionary relationships and transmission patterns of human/simian immunodeficiency virus (HIV/SIV), we screened blood samples from 30 wild-born healthy Cameroonian mandrills. Five (16.7%) of them were seropositive for SIV. Three SIV strains were isolated from the five seropositive mandrills by cocultivation of their peripheral blood mononuclear cells (PBMCs) with PBMCs of rhesus macaques, a human T cell line (M8166), and/or a cynomolgus macaque T cell line (HSC-F). One of the newly isolated SIV strains was intravenously inoculated into two rhesus macaques and resulted in chronic infection. In the SIV-infected macaques at 45 weeks after inoculation, we observed a mild decline in the number of peripheral CD4+lymphocytes, lymphadenopathy, and blastic follicular dendritic cells with mild follicular hyperplasia in the peripheral lymph nodes. A phylogenetic analysis based on the pol sequence showed that the newly found SIVs from Cameroonian mandrills did not cluster with SIVmndGB1, which is the former representative strain of SIVmnd. The SIVmnds from Cameroon formed a new, independent lineage that branched before the root of the HIV-1/SIVcpz lineage with 996 of 1000 bootstrap replications. They clustered host specifically, and exhibited about 16.9% diversity at the level of nucleotide sequence among Cameroonian SIVmnd strains. These results indicate that the SIVmnds isolated in Cameroon are a novel type of SIVmnd and have infected Cameroonian mandrills for a long time. We therefore designated the Cameroonian SIVmnd as SIVmnd type 2 and redesignated SIVmndGB1 as SIVmnd type 1. To date, M. sphinx is the only primate species other than humans that is naturally infected with two different types of SIV. © 2001 Mary Ann Liebert, Inc.

DOI： 10.1089/088922201316912754

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MARY ANN LIEBERT INC PUBL  

Human T cell leukemia virus type 1 (HTLV-1) is endemic among three ethnically distinguishable populations in Japan (the Ainu, Ryukyuans, and Wajin), which, together, account for most of the population in Japan. While much is known about the phylogeny of the Ryukyuan and Wajin strains of HTLV-1, only one Ainu strain has been phylogenetically analyzed. We report here a new HTLV-1 strain from the Ainu, The new isolate (U8306), as well as the previously reported isolate, are members of the Cosmopolitan group and further belong to the Transcontinental subgroup. This subgroup also predominates among the Ryukyuans, whereas the Japanese subgroup is the major subgroup among the Wajin, The predominance of subgroup A in the Ainu and Ryukyuans suggests that they share a common origin of HTLV-1.

DOI： 10.1089/088922201750237068

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記述言語：日本語   出版者・発行元：(一社)日本エイズ学会  

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記述言語：日本語   出版者・発行元：(一社)日本エイズ学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SOC GENERAL MICROBIOLOGY  

Human T-cell leukaemia virus type I (HTLV-I) is endemic in Melanesia, one of the three ethnogeographic regions of the Pacific; in the other two regions, Polynesia and Micronesia, the incidence of the virus is relatively low. In an effort to gain new insights into the prevalence of HTLVI in the Pacific region, we did a seroepidemiological survey on Easter island, which is located on the eastern edge of Polynesia, Of 138 subjects surveyed, including 108 Papa Nui (the native inhabitants of this island), we identified one HTLV-I-seropositive Papa Nui, The new HTLV-I isolate derived from this carrier (E-12) was phylogenetically analysed to ascertain the origin and past dissemination of HTLV-I in the island, The analysis demonstrated that isolate E-12 belongs to subgroup A of the Cosmopolitan group, and that it differs from HTLV-ls found in Melanesia, which are highly divergent variants, In subgroup A, E-12 grouped with South American HTLV-ls including those from Amerindians, This result suggests that this isolate originated in South America rather than in Melanesia.

DOI： 10.1099/0022-1317-80-8-1995

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC  

To better understand the origin of human T-cell leukemia virus type I (HTLV-I) in South America, we conducted a phylogenetic study on 27 new HTLV-Is in Brazil. These were obtained from Brazilians of various ethnic origins, such as Japanese immigrants, whites, blacks, and mulattos. We amplified and sequenced proviral DNAs of a part of the long terminal repeats. Phylogenetic trees revealed that all but 6 of the new isolates were not only similar to each other but also similar to HTLV-Is of other South American countries, including those from Amerindians. However, the isolates differed from the HTLV-Is of Africa and Japan. The other six isolates were from Japanese immigrants and were phylogenetically almost identical to HTLV-Is in Japan but different from the majority of South American HTLV-Is, including the other new Brazilian HTLV-Is. These findings indicate that the recent introduction of HTLV-I from Japan is limited to Japanese immigrants. In addition, the results do not support the prevailing hypothesis that HTLV-Is in South America were introduced by blacks who were brought from Africa as slaves. Rather, these results suggest that the majority of HTLV-Is prevailing in South America have spread from Amerindians, some of whom are likely to have possessed this human retrovirus from the beginning of their settlement in South America. (C) 1999 Academic Press.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MARY ANN LIEBERT INC PUBL  

DOI： 10.1089/088922299310557

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

To understand the origin and past dissemination of human T-cell leukemia/lymphotropic virus type I (HTLV-I) in Latin America, we conducted a phylogenetic study of five new HTLV-I isolates from Argentina. We sequenced partial fragments of long terminal repeats (LTR) of the new HTLV-ls, and then the sequences were subjected to a phylogenetic analysis for comparison with other HTLV-ls of various geographical origins. Our results indicated that all the isolates were members of the Cosmopolitan group. Furthermore, most (four out of five isolates) of the new HTLV-ls belonged to the Transcontinental (A) subgroup, the most widespread subgroup of the four subgroups in the Cosmopolitan group. In this subgroup, they were closely related to HTLV-ls found in other South American countries including those of Amerindians, and were different from those found in Africa. In contrast, the remaining one HTLV-I (ARGMF) did not show any clear similarity to known HTLV-I isolates belonging to the Cosmopolitan group. The close similarity of South American HTLV-ls strongly suggests a common origin of the virus in this continent. Our results do not support the proposed idea of recent introduction of HTLV-I into South America as a consequence of the slave trade from Africa, where phylogenetically different HTLV-ls predominate. (C) 1998 Wiley-Liss, Inc.

DOI： 10.1002/(SICI)1096-9071(199806)55:2<152::AID-JMV12>3.0.CO;2-K

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

Our previous analysis of an HTLV-I isolate (CMR229) from a Cameroonian Pygmy demonstrated that the isolate is distinct from typical HTLV-Is of the ''Central African group,'' which has a close similarity to HTLV-I-related simian viruses (STLV-I) in Africa. In this study, we analyzed six new HTLV-Is from Cameroon consisting of three isolates from the Pygmy and three from the Bantu to examine further the genetic features of HTLV-I in Cameroon, especially in the Pygmy. A phylogenetic tree based on the long terminal repeats (LTR) region showed that all the new HTLV-Is belong to the Central African group. On the other hand, an env-based analysis of CMR229 confirmed the previous finding derived from LTR-based analysis that CMR229 has a similarity to African STLV-Is, but is distinct from the typical Central African group of HTLV-I. This suggests that multiple interspecies transmissions from non-human primates to humans have occurred in Central Africa, resulting in the presence of two distinct HTLV-I strains in this area. In addition, it seems likely that the Pygmy harbors the heterogeneous HTLV-I strains from which the main HTLV-I population spread into the Bantu.

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：日本語   会議種別：ポスター発表  

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記述言語：日本語   会議種別：口頭発表（一般）  

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記述言語：日本語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

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記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

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記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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記述言語：英語   会議種別：ポスター発表  

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記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

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記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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記述言語：日本語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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記述言語：英語  

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記述言語：英語   会議種別：ポスター発表  

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