Pub Date : 2015-07-13DOI: 10.1109/LLS.2015.2449511
Jing Su, M. A. Henson
A critical decision in the mammalian cell cycle is whether to pass through the restriction point (R-point) or enter the cell cycle. In this letter, we modeled the decision-making system of the mammalian cell cycle entry and the simulated circadian regulation of the R-point driven by external epithelial growth factor (EGF) patterns. Our conceptual model replicated key signaling behaviors observed experimentally, suggesting that the proposed network captured the essential system features. The model revealed the dramatic importance of the EGF dynamics on promoting cell proliferation, showed that the EGF signal duration was more important than the signal strength for driving cells past the R-point, and suggested that the loss of circadian control of the cell cycle entry could be associated with cancer development.
{"title":"Circadian Gating of the Mammalian Cell Cycle Restriction Point: A Mathematical Analysis","authors":"Jing Su, M. A. Henson","doi":"10.1109/LLS.2015.2449511","DOIUrl":"https://doi.org/10.1109/LLS.2015.2449511","url":null,"abstract":"A critical decision in the mammalian cell cycle is whether to pass through the restriction point (R-point) or enter the cell cycle. In this letter, we modeled the decision-making system of the mammalian cell cycle entry and the simulated circadian regulation of the R-point driven by external epithelial growth factor (EGF) patterns. Our conceptual model replicated key signaling behaviors observed experimentally, suggesting that the proposed network captured the essential system features. The model revealed the dramatic importance of the EGF dynamics on promoting cell proliferation, showed that the EGF signal duration was more important than the signal strength for driving cells past the R-point, and suggested that the loss of circadian control of the cell cycle entry could be associated with cancer development.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"1 1","pages":"11-14"},"PeriodicalIF":0.0,"publicationDate":"2015-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2015.2449511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62509608","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}
Pub Date : 2015-06-30DOI: 10.1109/LLS.2015.2451291
Burook Misganaw, M. Vidyasagar
In multiclass machine learning problems, one needs to distinguish between the nominal labels that do not have any natural ordering and the ordinal labels that are ordered. Ordinal labels are pervasive in biology, and some examples are given here. In this note, we point out the importance of making use of the order information when it is inherent to the problem. We demonstrate that algorithms that use this additional information outperform the algorithms that do not, on a case study of assigning one of four labels to the ovarian cancer patients on the basis of their time of progression-free survival. As an aside, it is also pointed out that the algorithms that make use of ordering information require fewer data normalizations. This aspect is important in biological applications, where data are plagued by variations in platforms and protocols, batch effects, and so on.
{"title":"Exploiting Ordinal Class Structure in Multiclass Classification: Application to Ovarian Cancer","authors":"Burook Misganaw, M. Vidyasagar","doi":"10.1109/LLS.2015.2451291","DOIUrl":"https://doi.org/10.1109/LLS.2015.2451291","url":null,"abstract":"In multiclass machine learning problems, one needs to distinguish between the nominal labels that do not have any natural ordering and the ordinal labels that are ordered. Ordinal labels are pervasive in biology, and some examples are given here. In this note, we point out the importance of making use of the order information when it is inherent to the problem. We demonstrate that algorithms that use this additional information outperform the algorithms that do not, on a case study of assigning one of four labels to the ovarian cancer patients on the basis of their time of progression-free survival. As an aside, it is also pointed out that the algorithms that make use of ordering information require fewer data normalizations. This aspect is important in biological applications, where data are plagued by variations in platforms and protocols, batch effects, and so on.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"1 1","pages":"15-18"},"PeriodicalIF":0.0,"publicationDate":"2015-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2015.2451291","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62509637","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}
Pub Date : 2015-06-30DOI: 10.1109/LLS.2015.2451291
Burook Misganaw;Mathukumalli Vidyasagar
In multiclass machine learning problems, one needs to distinguish between the nominal labels that do not have any natural ordering and the ordinal labels that are ordered. Ordinal labels are pervasive in biology, and some examples are given here. In this note, we point out the importance of making use of the order information when it is inherent to the problem. We demonstrate that algorithms that use this additional information outperform the algorithms that do not, on a case study of assigning one of four labels to the ovarian cancer patients on the basis of their time of progression-free survival. As an aside, it is also pointed out that the algorithms that make use of ordering information require fewer data normalizations. This aspect is important in biological applications, where data are plagued by variations in platforms and protocols, batch effects, and so on.
{"title":"Exploiting Ordinal Class Structure in Multiclass Classification: Application to Ovarian Cancer","authors":"Burook Misganaw;Mathukumalli Vidyasagar","doi":"10.1109/LLS.2015.2451291","DOIUrl":"https://doi.org/10.1109/LLS.2015.2451291","url":null,"abstract":"In multiclass machine learning problems, one needs to distinguish between the nominal labels that do not have any natural ordering and the ordinal labels that are ordered. Ordinal labels are pervasive in biology, and some examples are given here. In this note, we point out the importance of making use of the order information when it is inherent to the problem. We demonstrate that algorithms that use this additional information outperform the algorithms that do not, on a case study of assigning one of four labels to the ovarian cancer patients on the basis of their time of progression-free survival. As an aside, it is also pointed out that the algorithms that make use of ordering information require fewer data normalizations. This aspect is important in biological applications, where data are plagued by variations in platforms and protocols, batch effects, and so on.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"1 1","pages":"15-18"},"PeriodicalIF":0.0,"publicationDate":"2015-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2015.2451291","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49908372","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}
Pub Date : 2015-06-16DOI: 10.1109/LLS.2015.2446211
Ana Sofia Rufino Ferreira;Justin Hsia;Murat Arcak
We propose a lateral inhibition system and analyze contrasting patterns of gene expression. The system consists of a set of compartments interconnected by channels. Each compartment contains a colony of cells that produce diffusible molecules to be detected by the neighboring colonies. Each cell is equipped with an inhibitory circuit that reduces its production when the detected signal is sufficiently strong. We characterize the parameter range in which steady-state patterns emerge.
{"title":"A Compartmental Lateral Inhibition System to Generate Contrasting Patterns","authors":"Ana Sofia Rufino Ferreira;Justin Hsia;Murat Arcak","doi":"10.1109/LLS.2015.2446211","DOIUrl":"https://doi.org/10.1109/LLS.2015.2446211","url":null,"abstract":"We propose a lateral inhibition system and analyze contrasting patterns of gene expression. The system consists of a set of compartments interconnected by channels. Each compartment contains a colony of cells that produce diffusible molecules to be detected by the neighboring colonies. Each cell is equipped with an inhibitory circuit that reduces its production when the detected signal is sufficiently strong. We characterize the parameter range in which steady-state patterns emerge.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"1 1","pages":"7-10"},"PeriodicalIF":0.0,"publicationDate":"2015-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2015.2446211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49908370","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}
Pub Date : 2015-06-16DOI: 10.1109/LLS.2015.2446211
Ana Sofia Rufino Ferreira, Justin Hsia, M. Arcak
We propose a lateral inhibition system and analyze contrasting patterns of gene expression. The system consists of a set of compartments interconnected by channels. Each compartment contains a colony of cells that produce diffusible molecules to be detected by the neighboring colonies. Each cell is equipped with an inhibitory circuit that reduces its production when the detected signal is sufficiently strong. We characterize the parameter range in which steady-state patterns emerge.
{"title":"A Compartmental Lateral Inhibition System to Generate Contrasting Patterns","authors":"Ana Sofia Rufino Ferreira, Justin Hsia, M. Arcak","doi":"10.1109/LLS.2015.2446211","DOIUrl":"https://doi.org/10.1109/LLS.2015.2446211","url":null,"abstract":"We propose a lateral inhibition system and analyze contrasting patterns of gene expression. The system consists of a set of compartments interconnected by channels. Each compartment contains a colony of cells that produce diffusible molecules to be detected by the neighboring colonies. Each cell is equipped with an inhibitory circuit that reduces its production when the detected signal is sufficiently strong. We characterize the parameter range in which steady-state patterns emerge.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"1 1","pages":"7-10"},"PeriodicalIF":0.0,"publicationDate":"2015-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2015.2446211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62509598","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}
Pub Date : 2015-06-04DOI: 10.1109/LLS.2015.2439498
John H. Abel;Lukas A. Widmer;Peter C. St. John;Jörg Stelling;Francis J. Doyle
In the mammalian suprachiasmatic nucleus (SCN), a population of noisy cell-autonomous oscillators synchronizes to generate robust circadian rhythms at the organism level. Within these cells, two isoforms of Cryptochrome, Cry1 and Cry2 , participate in a negative feedback loop driving oscillation. Previous work has shown that single, dissociated SCN neurons respond differently to Cry1 and Cry2 knockouts. These differences have led to speculation that CRY1 and CRY2 may play different functional roles in the oscillator. To address this proposition, we have developed a new coupled, stochastic model focused on the Period ( Per ) and Cry feedback loop, and incorporating intercellular coupling via vasoactive intestinal peptide. We show that single dissociated Cry1 knockouts display partially rhythmic behavior. Additionally, intrinsic molecular noise and differences in relative abundance, rather than differing functions, are sufficient to explain the range of rhythmicity encountered in Cry knockouts in the SCN. The results further highlight the essential role of stochastic behavior in understanding and accurately modeling the circadian network.
{"title":"A Coupled Stochastic Model Explains Differences in Cry Knockout Behavior","authors":"John H. Abel;Lukas A. Widmer;Peter C. St. John;Jörg Stelling;Francis J. Doyle","doi":"10.1109/LLS.2015.2439498","DOIUrl":"https://doi.org/10.1109/LLS.2015.2439498","url":null,"abstract":"In the mammalian suprachiasmatic nucleus (SCN), a population of noisy cell-autonomous oscillators synchronizes to generate robust circadian rhythms at the organism level. Within these cells, two isoforms of Cryptochrome, \u0000<italic>Cry1</i>\u0000 and \u0000<italic>Cry2</i>\u0000, participate in a negative feedback loop driving oscillation. Previous work has shown that single, dissociated SCN neurons respond differently to \u0000<italic>Cry1</i>\u0000 and \u0000<italic>Cry2</i>\u0000 knockouts. These differences have led to speculation that CRY1 and CRY2 may play different functional roles in the oscillator. To address this proposition, we have developed a new coupled, stochastic model focused on the \u0000<italic>Period</i>\u0000 (\u0000<italic>Per</i>\u0000) and \u0000<italic>Cry</i>\u0000 feedback loop, and incorporating intercellular coupling via vasoactive intestinal peptide. We show that single dissociated \u0000<italic>Cry1</i>\u0000 knockouts display partially rhythmic behavior. Additionally, intrinsic molecular noise and differences in relative abundance, rather than differing functions, are sufficient to explain the range of rhythmicity encountered in \u0000<italic>Cry</i>\u0000 knockouts in the SCN. The results further highlight the essential role of stochastic behavior in understanding and accurately modeling the circadian network.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"1 1","pages":"3-6"},"PeriodicalIF":0.0,"publicationDate":"2015-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2015.2439498","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49908369","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}
Pub Date : 2015-06-04DOI: 10.1109/LLS.2015.2439498
John H. Abel, L. Widmer, Peter C. St. John, J. Stelling, F. Doyle
In the mammalian suprachiasmatic nucleus (SCN), a population of noisy cell-autonomous oscillators synchronizes to generate robust circadian rhythms at the organism level. Within these cells, two isoforms of Cryptochrome, Cry1 and Cry2, participate in a negative feedback loop driving oscillation. Previous work has shown that single, dissociated SCN neurons respond differently to Cry1 and Cry2 knockouts. These differences have led to speculation that CRY1 and CRY2 may play different functional roles in the oscillator. To address this proposition, we have developed a new coupled, stochastic model focused on the Period (Per) and Cry feedback loop, and incorporating intercellular coupling via vasoactive intestinal peptide. We show that single dissociated Cry1 knockouts display partially rhythmic behavior. Additionally, intrinsic molecular noise and differences in relative abundance, rather than differing functions, are sufficient to explain the range of rhythmicity encountered in Cry knockouts in the SCN. The results further highlight the essential role of stochastic behavior in understanding and accurately modeling the circadian network.
{"title":"A Coupled Stochastic Model Explains Differences in Cry Knockout Behavior","authors":"John H. Abel, L. Widmer, Peter C. St. John, J. Stelling, F. Doyle","doi":"10.1109/LLS.2015.2439498","DOIUrl":"https://doi.org/10.1109/LLS.2015.2439498","url":null,"abstract":"In the mammalian suprachiasmatic nucleus (SCN), a population of noisy cell-autonomous oscillators synchronizes to generate robust circadian rhythms at the organism level. Within these cells, two isoforms of Cryptochrome, <italic>Cry1</italic> and <italic>Cry2</italic>, participate in a negative feedback loop driving oscillation. Previous work has shown that single, dissociated SCN neurons respond differently to <italic>Cry1</italic> and <italic>Cry2</italic> knockouts. These differences have led to speculation that CRY1 and CRY2 may play different functional roles in the oscillator. To address this proposition, we have developed a new coupled, stochastic model focused on the <italic>Period</italic> (<italic>Per</italic>) and <italic>Cry</italic> feedback loop, and incorporating intercellular coupling via vasoactive intestinal peptide. We show that single dissociated <italic>Cry1</italic> knockouts display partially rhythmic behavior. Additionally, intrinsic molecular noise and differences in relative abundance, rather than differing functions, are sufficient to explain the range of rhythmicity encountered in <italic>Cry</italic> knockouts in the SCN. The results further highlight the essential role of stochastic behavior in understanding and accurately modeling the circadian network.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"39 1","pages":"3-6"},"PeriodicalIF":0.0,"publicationDate":"2015-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2015.2439498","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62509560","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}
Pub Date : 2015-06-01DOI: 10.1109/LLS.2015.2449511
Jing Su;Michael A. Henson
A critical decision in the mammalian cell cycle is whether to pass through the restriction point (R-point) or enter the cell cycle. In this letter, we modeled the decision-making system of the mammalian cell cycle entry and the simulated circadian regulation of the R-point driven by external epithelial growth factor (EGF) patterns. Our conceptual model replicated key signaling behaviors observed experimentally, suggesting that the proposed network captured the essential system features. The model revealed the dramatic importance of the EGF dynamics on promoting cell proliferation, showed that the EGF signal duration was more important than the signal strength for driving cells past the R-point, and suggested that the loss of circadian control of the cell cycle entry could be associated with cancer development.
{"title":"Circadian Gating of the Mammalian Cell Cycle Restriction Point: A Mathematical Analysis","authors":"Jing Su;Michael A. Henson","doi":"10.1109/LLS.2015.2449511","DOIUrl":"https://doi.org/10.1109/LLS.2015.2449511","url":null,"abstract":"A critical decision in the mammalian cell cycle is whether to pass through the restriction point (R-point) or enter the cell cycle. In this letter, we modeled the decision-making system of the mammalian cell cycle entry and the simulated circadian regulation of the R-point driven by external epithelial growth factor (EGF) patterns. Our conceptual model replicated key signaling behaviors observed experimentally, suggesting that the proposed network captured the essential system features. The model revealed the dramatic importance of the EGF dynamics on promoting cell proliferation, showed that the EGF signal duration was more important than the signal strength for driving cells past the R-point, and suggested that the loss of circadian control of the cell cycle entry could be associated with cancer development.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"1 1","pages":"11-14"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2015.2449511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49908371","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}
Pub Date : 2015-06-01DOI: 10.1109/LLS.2015.2465839
Robert Gooding-Townsend;Steven Ten Holder;Brian Ingalls
Bacterial plasmids employ copy number control systems to ensure that they do not overburden their hosts. Plasmid incompatibility is caused by shared components of copy number control systems, resulting in mutual inhibition of replication. Incompatible plasmids cannot be stably maintained within a host cell. Unilateral incompatibility, in which the plasmid replicons are compatible but one plasmid encodes for the replication inhibitor of the other, leads to rapid displacement of the inhibited plasmid. Thus, we propose that the unilateral incompatibility can be used to eradicate an undesirable plasmid from a population. To investigate this process, we developed deterministic and stochastic models of plasmid dynamics. An analysis of these models provides predictions about the efficacy of plasmid displacement.
{"title":"Displacement of Bacterial Plasmids by Engineered Unilateral Incompatibility","authors":"Robert Gooding-Townsend;Steven Ten Holder;Brian Ingalls","doi":"10.1109/LLS.2015.2465839","DOIUrl":"https://doi.org/10.1109/LLS.2015.2465839","url":null,"abstract":"Bacterial plasmids employ copy number control systems to ensure that they do not overburden their hosts. Plasmid incompatibility is caused by shared components of copy number control systems, resulting in mutual inhibition of replication. Incompatible plasmids cannot be stably maintained within a host cell. Unilateral incompatibility, in which the plasmid replicons are compatible but one plasmid encodes for the replication inhibitor of the other, leads to rapid displacement of the inhibited plasmid. Thus, we propose that the unilateral incompatibility can be used to eradicate an undesirable plasmid from a population. To investigate this process, we developed deterministic and stochastic models of plasmid dynamics. An analysis of these models provides predictions about the efficacy of plasmid displacement.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"1 1","pages":"19-21"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2015.2465839","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49908373","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}
Pub Date : 2015-06-01DOI: 10.1109/LLS.2015.2476536
Francis J. Doyle;Mathukumalli Vidyasagar
We, the editors of the IEEE Life Sciences Letters (LSL), take pleasure in welcoming readers to this, the Inaugural Issue of the journal. LSL is intended to facilitate the rapid review and publication of high-quality contemporary research in the broad areas of personalized medicine, pharmaceutical engineering, synthetic biology, and systems biology. We are fortunate to have four outstanding individuals as Senior Editors, one for each theme area, as well as several Associate Editors.
{"title":"IEEE Life Sciences Letters Inaugural Editorial","authors":"Francis J. Doyle;Mathukumalli Vidyasagar","doi":"10.1109/LLS.2015.2476536","DOIUrl":"https://doi.org/10.1109/LLS.2015.2476536","url":null,"abstract":"We, the editors of the \u0000<italic>IEEE Life Sciences Letters</i>\u0000 (LSL), take pleasure in welcoming readers to this, the Inaugural Issue of the journal. LSL is intended to facilitate the rapid review and publication of high-quality contemporary research in the broad areas of personalized medicine, pharmaceutical engineering, synthetic biology, and systems biology. We are fortunate to have four outstanding individuals as Senior Editors, one for each theme area, as well as several Associate Editors.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"1 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2015.2476536","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49908368","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：