The Journal of molecular and cellular immunology : JMCI最新文献

{"title":"Induction of antigen presentation ability in purified cultures of astroglia by interferon-gamma.","authors":"M Takiguchi,&nbsp;J A Frelinger","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The role of the immune system in the central nervous system has been elusive. Our original description of Ia bearing cells in the central nervous system was controversial, although it has now been confirmed in a variety of systems in both mouse and humans. The function of Ia bearing cells is however still unclear. Recently, others have shown that astrocytes from rats with EAE could present myelin basic protein to T cell clones; however, no other antigens were tested. We have used the culture systems of McCarthy and DeVellis to produce purified cultures of astrocytes and oligodendroglial cells from newborn mouse brains. Newborn brains were chosen since it is impossible to obtain pure cultures of differentiated brain cells from adult mice. Using these cultures, we showed that astrocyte, but not oligodendrocyte cultures treated with ConA supernatants or recombinant IFN-gamma are able to present antigen to appropriate but not inappropriate T cell hybrids. Untreated cells of either the astrocyte or oligodendroglial cell populations were ineffective at antigen presentation. Concomitant with this increase in antigen presenting ability, follows an increase in both the number and density of MHC class I and class II antigens. Antigen presentation was inhibited by appropriate but not inappropriate anti Ia monoclonal antibodies. Anti class I antibodies were ineffective. Depletion experiments showed that both I-A and I-E molecules are expressed on the antigen presenting cells. Thus, we have been able to show that Ia+ cells derived from pure cultures of astrocytes are able, after induction with IFN-gamma, to present antigen to T cell hybrids. This suggests a possible physiologic role of Ia bearing cells in CNS in initiation of immune responses.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 5","pages":"269-80"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14281070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ontogeny of MHC-linked, T cell-mediated suppression is regulated by the T cell genotype.","authors":"B A Araneo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Regulation of T cell effector functions by major histocompatibility complex (MHC) gene products has been extensively researched. Investigations in this area have established several important concepts of immunobiology. First, genes within the I-region of the MHC profoundly affect development of immune responses through their effects on cell-cell interactions. In the course of analyzing antigen-induced T cell activation, investigators identified specific Ir-genes by demonstrating that certain strains of mice were unable to develop immunity to defined antigens. It is now accepted that immune response defects in murine species are potentiated by cell surface molecules encoded within the I-subregion of the MHC, called Ia. Those molecules coded within the I-A subregion have the potential to be expressed by many different cell types. Second, induction of helper T cell effector function requires recognition of antigen in association with I-region encoded, cell surface molecules. For example, only a single structural combination of antigenic determinant and Ia molecule can deliver the inductive signal(s) to potential helper T cells. This fundamental aspect of helper T cell activation, now documented in numerous experimental systems, is referred to as MHC- or I-region restricted, antigen recognition. MHC-restriction is a characteristic of T cells mediating delayed-type hypersensitivity, help, and cytotoxicity. Third, several lines of evidence have established that T cell recognition of self-MHC molecules is a modifiable phenotype; conferred by a receptor having both variable and constant regions and not encoded by genes in the MHC. The development of both thymic grafted homozygous nu/nu mice and irradiation-induced bone marrow chimeras as experimental models resulted in a better understanding of the mechanism of MHC-restricted, antigen recognition. It was observed that expression of MHC gene products by the host is sufficient to select a new immune response phenotype for cellular interactions. The selection process takes place during T cell maturation, in the absence of antigen and under the dominant influence of the thymus, even though there is ample evidence for selective pressure in the extrathymic environment. For example, the self-MHC recognition repertoire of T cells in P----F1 chimeras undergoes an initial expansion which results in an F1 immune response phenotype. This expansion is followed by an apparent contraction back to the immune response phenotype of the parental donor. The contraction is time dependent and reflects accessory cell turnover in the irradiated host.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 4","pages":"219-31"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13993500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Varieties of idiotype-specific helper T cells--a commentary.","authors":"C A Janeway","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 5","pages":"265-7"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limiting dilution analysis of proliferating and helper T cells in the in vivo immune response to KLH: derepression of helper T cells at moderately increased frequencies.","authors":"B Maier,&nbsp;H J Bühring,&nbsp;M Simon,&nbsp;K Eichmann,&nbsp;I Melchers","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>While it is clear that some T cells have the capacity for almost indefinite proliferation in vitro, it is a controversial issue how much of this proliferative capacity is utilized by T cells in a response to antigen in vivo. In the framework of a strict clonal selection model the functional activities of normal and immune lymphocyte populations are essentially determined by the frequencies of antigen-specific cells which are clonally expanded after recognition of antigen. In contrast, our group has proposed a network model in which the more prominent effect of immunization is a release of antigen-specific T cells from a state of suppression (= derepression) which exists in the non-immune situation and which is generated through interactions between T cells involving their antigen-specific receptors. In this model, derepression is achieved by competition of antigen with the interactions among T cells through which suppression is exerted. To test our model, we analyze in this paper how much of the immune response to keyhole limpet hemocyanin (KLH) in draining lymph nodes is accounted for by an increase in the numbers of KLH-reactive T cells or by their derepression. To this end, we immunize mice subcutaneously with KLH in CFA. For a period of 14 days after immunization draining lymph nodes are removed, and the frequencies of KLH-reactive proliferating T cells and of KLH-reactive helper T cells determined. We find that proliferating T cells increase 5 to 8 fold in frequency from day 1 to 4 after immunization (approximately 1/30,000 to approximately 1/5000) and no evidence for suppression of these T cells in the non-immune situation can be obtained. In contrast, T helper cells are strongly suppressed in non-immune lymph nodes and become derepressed suddenly between days 3 and 4 following immunization. From day 0 to day 3 T helper cell frequencies are in the order of 1/14,000-1/38,000, then increase suddenly approximately 3-6 fold within 1 day from 1/16,000-1/8,000 to 1/3,000-1/5,000 with no further change until day 14. Thus, helper T cell immunity in draining lymph nodes appears to be generated by a combination of increased frequencies of specific T cells with their release from suppression. In addition, we have reasons to suspect that we overestimate the increase in T cell frequencies. We therefore think that derepression is a major factor in the response of T helper cells to antigen.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 5","pages":"293-305"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recycling class I MHC antigens: dynamics of internalization, acidification, and ligand-degradation in murine T lymphoblasts.","authors":"D B Tse,&nbsp;C R Cantor,&nbsp;J McDowell,&nbsp;B Pernis","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have previously shown that activated T lymphocytes spontaneously internalize their own surface class I MHC antigens and that this phenomenon is specific for these cells since it does not occur in B lymphocytes even after activation. The present work was aimed at defining the quantitative aspects of this phenomenon and, in particular, at the elucidation of the route of the internalized class I MHC antigens. We intended to determine if the internalized molecules are delivered to the lysosomal compartment and digested there or if instead they are brought back to the plasma membrane in a recycling pathway similar to that described for various cell surface proteins known to be engaged in the process of receptor-mediated endocytosis. We have devised a flow cytometric assay based on the use of fluorochrome-labeled monoclonal anti-H-2K antibodies to measure the kinetics of H-2K internalization. Comparison of the time necessary for the internalization of one-half of the surface H-2K molecules in activated T lymphocytes, which is approximately 1 hour, with the half-life of these molecules on the same cells, which is 14 hours, clearly indicates that the internalized molecules are not degraded but are instead recycled. The recycling takes place in an endosomal compartment with an average pH of about 5.6. The monoclonal anti-H-2K antibody used in these studies was not eluted from the H-2K molecules at this pH and is recycled along with them. On the other hand, protein A bound to the Fc of the anti-H-2K antibody was eluted at the low pH of the endosomes, delivered to lysosomes, and digested. We have therefore defined a novel phenomenon, namely the recycling of class I MHC antigens, which occurs selectively in T lymphocytes. The features of this phenomenon are similar to the recycling of surface receptors which mediate the endocytosis of a variety of extracellular ligands in different cells. However, no physiological extracellular ligand is known for class I MHC antigens. It is a reasonable speculation that upon activation T lymphocytes recycle their own surface class I MHC antigens as part of the complex machinery whereby these lymphocytes recognize and respond to non-self moieties on the plasma membranes of presentor or target cells.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 6","pages":"315-29"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14633487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of L3T4 in T cell activation: L3T4 may be both an Ia-binding protein and a receptor that transduces a negative signal.","authors":"J P Tite,&nbsp;A Sloan,&nbsp;C A Janeway","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The T cell surface molecules Lyt-2 and L3T4 are strongly correlated with the class of MHC gene product recognized by the T cell bearing them. The L3T4 molecule has been proposed to play a role in enhancing recognition of antigen:Ia by specific T cells. In the present experiments, we have explored the role of L3T4 in T cell activation by examining the effects of the L3T4-specific monoclonal antibody GK1.5 on T cell responses in the presence or absence of class II-MHC gene products. Our studies show that GK1.5 inhibits T cell activation in the absence of class II-MHC gene products, while antibodies to other T cell surface molecules do not transduce negative signals to the same cells. We interpret our results as suggesting a signaling role for L3T4 and, by inference, for Lyt-2 as well. We would propose that L3T4 molecules on the class II-restricted T cell initiate the interaction between the L3T4+ T cell and its class II-MHC gene product bearing target cell (B cell, APC). This initial contact is important in allowing a finite time for antigen, Ia, and the T cell receptor to form an activating complex, which in turn transduces a dominant on signal to the cell. In the absence of specific antigen, or if the class II-bearing cell is of the wrong MHC genotype, so that the antigen:Ia receptor is not aggregated, then the association of L3T4 with class II molecules transduces a net negative signal to the T cell. We suggest that this negative signal is responsible for T cell:target cell deconjugation under these circumstances. Thus, we would propose that L3T4 initiates T cell:Ia-bearing cell interactions and, a finite time later, signals the T cell to discontinue the interaction unless a stimulating level of the antigen:Ia complexes for which the T cell's receptor is specific is present.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 4","pages":"179-90"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14633486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The syngeneic T-T lymphocyte reaction (STTLR). I. Induction of primary T anti-T cell proliferative responses in T cell cultures stimulated with self- and antigen-reactive T cells.","authors":"H Suzuki,&nbsp;B Evavold,&nbsp;T J Swartz,&nbsp;S L Latta,&nbsp;J Quintáns","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The generally accepted \"Gershonian\" view of immunoregulation attributes T cell-mediated regulation of immune responses to the activities of discrete T cell subsets with specialized functions such as help, suppression, and contrasuppression. Several observations made in our laboratory are not compatible with this paradigm. For instance, careful quantitations of carrier-specific T cell help to hapten-specific B cells in an adoptive transfer system yielded complex dose-response curves that could not be explained on the basis of interactions between discrete subsets of helper and suppressor cells. Rather, the results were most easily interpreted according to a model based on the following assumptions: (1) Regulation of helper T cell activity is a dose-dependent, dynamic property of T cell populations that exhibit a high degree of connectivity (self-recognition) and (2) helper T cells have the ability to perform different functions, depending on the current activity of other interacting lymphocytes. A good example of cloned T cells capable of performing multiple immunoregulatory functions was provided by the IEk-specific self-reactive Lbd line which provided help, suppression, and contrasuppression to T cell dependent PFC responses (see Quintáns et al., 1986). Since these effects were strictly dependent on the levels of antigen-specific T cell help, we hypothesized that Lbd cells interacted with other T cells to modulate their function. In this paper, we directly test the hypothesis that activated T cells can interact directly with resting T cells and describe the proliferative component of a syngeneic T cell anti-T cell response induced by antigen and self-reactive helper and cytotoxic T cells. In a follow-up report, we will describe the effector component of the T anti-T cell response.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 6","pages":"331-44"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14634018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional and biochemical evidence for the recognition of T cell receptors by monoclonal antibodies to an immunoglobulin idiotype.","authors":"C Martínez,&nbsp;R Bragado,&nbsp;A de la Hera,&nbsp;M L Toribio,&nbsp;M A Marcos,&nbsp;A Bandeira,&nbsp;P Pereira,&nbsp;A Coutinho","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Sharing of \"idiotypes\" by T and B cells with similar nominal specificities has been extensively reported in functional assays. The recent molecular characterization of T cell receptors has led to the suggestion that such idiotypic mimicries could result from \"network\" selection of available T cell repertoires. Alternatively, the validity of the conclusions taken from those functional assays could be questioned. We have now used an experimental system where recurrent expression of antibody idiotypes by T helper cells requires \"learning\" from the B cell/antibody compartment, and show here that the idiotypic determinants in question are indeed associated with T cell receptor molecules. A monoclonal antibody (F6(51)) directed to an idiotope of the TNP-binding BALB/c myeloma protein MOPC460 specifically inhibits antigen-dependent proliferation and helper activity of BALB/c anti-TNP-BALB/c helper T cells. The anti-idiotypic antibodies also induce IL-2 production by these helper cells and precipitate a surface molecule with characteristics of T cell receptor. We conclude that, in this particular system, T cell receptors and antibodies of similar nominal specificities share idiotypic determinants.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 6","pages":"307-13"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonotypic analysis of the fetal B cell repertoire: evidence for an early and predominant expression of idiotypes associated with the VH 36-60 family.","authors":"J M Teale,&nbsp;J F Kearney","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Determining the mechanisms by which B cells develop that culminates in the generation of a diverse repertoire is critical to our understanding of how the immune response is regulated. The B cell specificity repertoire appears to be developmentally acquired in a predetermined, temporally ordered fashion. Thus, in the Balb/c mouse, the ontogenetic appearance of functional B cells specific for various hapten probes occurs in the order of dinitrophenol (DNP), fluorescein (Fl), and phosphorylcholine (PC). In addition, when the influenza virus hemagglutinin molecule was used as an antigen probe, similar conclusions were drawn regarding a patterned acquisition of the specificity repertoire. More recently, we have used a fetal organ culture system to show that hapten-responsive B cells appear in the same predictable, temporal order in vitro. The importance of these studies was that the effects of environmental influences were minimized in the absence of circulation and cell migration, and therefore the results indicated that the patterned emergence of the specificity repertoire observed was largely the result of genetic regulatory processes. Recent molecular findings may relate to such genetic regulatory processes. The VH genes in Balb/c mice have been grouped into eight families based on sequence homology, and have been mapped relative to the constant region genes. Yancopoulos et al. and Perlmutter et al. have shown that the VH gene segments closest to the JH cluster, the VH1B 7183 family, are preferentially utilized in transformed fetal pre-B cell lines and in fetal B cell hybridomas. This led to the hypothesis that the developmental control of the expression of VH gene segments is related to chromosomal organization. A logical extension of these findings is that the programmed appearance of particular clonotypes in ontogeny may be explained, in part, by the preferential use of particular VH gene segments. However, to what extent the transformed B cell lines represent members of the functional expressed repertoire could not be evaluated. In the studies described herein, the fetal organ culture system was used to assess the early expressed repertoire at the clonotypic level using idiotypic analysis. Anti-DNP secreting clones were derived from fetal organ cultures and tested for the presence of two idiotypes, 36 and MOPC 460 (460). The 36 idiotype is a predominant DNP clonotype of the neonatal repertoire, while the 460 idiotype is a major cross-reactive idiotype of the adult DNP response.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 5","pages":"283-92"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14044312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Responses of B6.C-H-2bm12 to heterologous insulins show no correlation with the putative gene conversion but define Iabm12 as functionally unique.","authors":"T H Hansen,&nbsp;W D Walsh,&nbsp;R J Rubocki,&nbsp;J A Kapp","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The IA mutant mouse strain, B6.C-H-2bm12 (bm12) has been used to address several important questions for the role of Ia molecules in immune responses to foreign antigens. Numerous publications using bm12 mice have led to conclusions concerning (1) the number and relative importance of functional sites on Ia molecules; (2) the effects of qualitative versus quantitative differences in Ia; (3) whether T cells recognize Ia sequence or conformation; and (4) if gene conversion events, such as the one that putatively occurred in bm12, transfer functional Ir gene epitopes. Because of the importance of these conclusions, as well as their controversial nature, we have undertaken a comprehensive and systematic analysis of the aberrant immune response of bm12 mice to heterologous insulin. Responses to beef, horse, and sheep insulin were compared in B6 and bm12 mice by T cell proliferation, enumeration of plaque-forming cells, and quantitation of serum antibody levels. Various doses of antigen were administered and the kinetics of each response was monitored at various times. The findings of these studies suggest (1) B6 and bm12 mice both mount comparably high levels of response to sheep and horse insulins; (2) in contrast to the good response of B6 mice to beef insulin, bm12 mice showed dramatically impaired responses, as evident from both the lower magnitude of the response in all three assays as well as the difference in the kinetics of the response in B6 and bm12 mice; and (3) the response to sheep insulin is controlled by IA and IE encoded genes. These new findings differ from and extend previously published reports using bm12 mice, and therefore have substantive implications on the above stated conclusions regarding recognition of Ia. One such implication is that the bm12 gene conversion did not result in the transfer of a functional epitope for sheep insulin, but rather resulted in the creation of a functionally unique Ia molecule. Furthermore, this critical definition of the Ir gene lesion in bm12 permits us to address mechanistic questions regarding the nature of its Ir gene defect to beef insulin.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"2 6","pages":"359-68"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14281073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}