Aiming at the problem on cooperative air-defense of surface warship formation, this paper maps the cooperative airdefense system of systems （SoS） for surface warship formation （CASoSSWF） to the biological immune s...Aiming at the problem on cooperative air-defense of surface warship formation, this paper maps the cooperative airdefense system of systems （SoS） for surface warship formation （CASoSSWF） to the biological immune system （BIS） according to the similarity of the defense mechanism and characteristics between the CASoSSWF and the BIS, and then designs the models of components and the architecture for a monitoring agent, a regulating agent, a killer agent, a pre-warning agent and a communicating agent by making use of the theories and methods of the artificial immune system, the multi-agent system （MAS）, the vaccine and the danger theory （DT）. Moreover a new immune multi-agent model using vaccine based on DT （IMMUVBDT） for the cooperative air-defense SoS is advanced. The immune response and immune mechanism of the CASoSSWF are analyzed. The model has a capability of memory, evolution, commendable dynamic environment adaptability and self-learning, and embodies adequately the cooperative air-defense mechanism for the CASoSSWF. Therefore it shows a novel idea for the CASoSSWF which can provide conception models for a surface warship formation operation simulation system.展开更多
The biological immune system is a complex adaptive system.There are lots of benefits for building the model of the immune system.For biological researchers,they can test some hypotheses about the infection process or ...The biological immune system is a complex adaptive system.There are lots of benefits for building the model of the immune system.For biological researchers,they can test some hypotheses about the infection process or simulate the responses of some drugs.For computer researchers,they can build distributed,robust and fault tolerant networks inspired by the functions of the immune system.This paper provides a comprehensive survey of the literatures on modelling the immune system.From the methodology perspective,the paper compares and analyzes the existing approaches and models,and also demonstrates the focusing research effort on the future immune models in the next few years.展开更多
Network structures and human behaviors are considered as two important factors in virus defense currently. However, due to ignorance of network security, normal users usually take simple activities, such as reinstalli...Network structures and human behaviors are considered as two important factors in virus defense currently. However, due to ignorance of network security, normal users usually take simple activities, such as reinstalling computer system, or using the computer recovery system to clear virus. How system recovery influences virus spreading is not taken into consideration currently. In this paper, a new virus propagation model considering the system recovery is proposed first, and then in its steady-state analysis, the virus propagation steady time and steady states are deduced. Experiment results show that models considering system recovery can effectively restrain virus propagation. Furthermore, algorithm with system recovery in BA scale-free network is proposed. Simulation result turns out that target immunization strategy with system recovery works better than traditional ones in BA network.展开更多
PSMD14 played a vital role in initiation and progression of hepatocellular carcinoma(HCC).However,PSMD14 and its-related genes for the immune prognostic implications of HCC patients have rarely been analyzed.Messenger...PSMD14 played a vital role in initiation and progression of hepatocellular carcinoma(HCC).However,PSMD14 and its-related genes for the immune prognostic implications of HCC patients have rarely been analyzed.Messenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas(TCGA)and International Cancer Genome Consortium(ICGC)database-Liver Hepatocellular Carcinoma(LIHC).Additionally,we used multi-dimensional bioinformatics analysis to construct and validate a PSMD14-based immune prognostic signature(including RBM45,PSMD1,OLA1,CCT6A,LCAT and IVD)for HCC prognosis prediction.Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group.Calibration curves confirmed the good consistency between the clinical nomogram prediction and the actual observation.Gene set enrichment analyses(GSEA)revealed several significantly enriched pathways,which might help explain the underlying mechanisms.Besides,the rt-PCR further validates the expression of seven immune genes in HCC cells.Our study identified a novel PSMD14-based signature for HCC prognosis prediction,it provided new potential prognostic biomarkers and therapeutic targets for immunotherapy of HCC.展开更多
In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking ...In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.展开更多
Integration of acquired immunity into microbial risk assessment for illness incidence is of no doubt essential for the study of susceptibility to illness.In this study,a probabilistic model was set up as dose response...Integration of acquired immunity into microbial risk assessment for illness incidence is of no doubt essential for the study of susceptibility to illness.In this study,a probabilistic model was set up as dose response for infection and a mathematical derivation was carried out by integrating immunity to obtain probability of illness models.Temporary acquire immunity from epidemiology studies which includes six different Norovirus transmission scenarios such as symptomatic individuals infectious,pre-and post-symptomatic infectiousness(low and high),innate genetic resistance,genogroup 2 type 4 and those with no immune boosting by asymptomatic infection were evaluated.Simulated results on illness inflation factor as a function of dose and exposure indicated that high frequency exposures had immense immunity build up even at high dose levels;hence minimized the probability of illness.Using Norovirus transmission dynamics data,results showed,and immunity included models had a reduction of 2e6 logs of magnitude difference in disease burden for both population and individual probable illness incidence.Additionally,the magnitude order of illness for each dose response remained largely the same for all transmission scenarios;symptomatic infectiousness and no immune boosting after asymptomatic infectiousness also remained the same throughout.With integration of epidemiological data on acquired immunity into the risk assessment,more realistic results were achieved signifying an overestimation of probable risk of illness when epidemiological immunity data are not included.This finding supported the call for rigorous integration of temporary acquired immunity in dose-response in all microbial risk assessments.展开更多
BACKGROUND According to current statistics,renal cancer accounts for 3%of all cancers world-wide.Renal cell carcinoma(RCC)is the most common solid lesion in the kidney and accounts for approximately 90%of all renal ma...BACKGROUND According to current statistics,renal cancer accounts for 3%of all cancers world-wide.Renal cell carcinoma(RCC)is the most common solid lesion in the kidney and accounts for approximately 90%of all renal malignancies.Increasing evi-dence has shown an association between immune infiltration in RCC and clinical outcomes.To discover possible targets for the immune system,we investigated the link between tumor-infiltrating immune cells(TIICs)and the prognosis of RCC.AIM To investigate the effects of 22 TIICs on the prognosis of RCC patients and iden-tify potential therapeutic targets for RCC immunotherapy.METHODS The CIBERSORT algorithm partitioned the 22 TIICs from the Cancer Genome Atlas cohort into proportions.Cox regression analysis was employed to evaluate the impact of 22 TIICs on the probability of developing RCC.A predictive model for immunological risk was developed by analyzing the statistical relationship between the subpopulations of TIICs and survival outcomes.Furthermore,multi-variate Cox regression analysis was used to investigate independent factors for the prognostic prediction of RCC.A value of P<0.05 was regarded as statistically significant.RESULTS Compared to normal tissues,RCC tissues exhibited a distinct infiltration of im-mune cells.An immune risk score model was established and univariate Cox regression analysis revealed a significant association between four immune cell types and the survival risk connected to RCC.High-risk individuals were correlated to poorer outcomes according to the Kaplan-Meier survival curve(P=1E-05).The immunological risk score model was demonstrated to be a dependable predictor of survival risk(area under the curve=0.747)via the receiver operating characteristic curve.According to multivariate Cox regression analysis,the immune risk score model independently predicted RCC patients'prognosis(hazard ratio=1.550,95%CI:1.342–1.791;P<0.001).Finally,we established a nomogram that accurately and comprehensively forecast the survival of patients with RCC.CONCLUSION TIICs play various roles in RCC prognosis.The immunological risk score is an independent predictor of poor survival in kidney cancer cases.展开更多
In this paper,a tumor immune model with time delay is studied.First,the stability of nonnegative equilibria is analyzed.Then the time delay τ is selected as a bifurcation parameter and the existence of Hopf bifurcati...In this paper,a tumor immune model with time delay is studied.First,the stability of nonnegative equilibria is analyzed.Then the time delay τ is selected as a bifurcation parameter and the existence of Hopf bifurcation is proved.Finally,by using the canonical method and the central manifold theory,the criteria for judging the direction and stability of Hopf bifurcation are given.展开更多
Animal models have been extensively used as a gold standard in various biological research,including immu-nological studies.Despite high availability and ease of handling procedure,they inadequately represent complex ...Animal models have been extensively used as a gold standard in various biological research,including immu-nological studies.Despite high availability and ease of handling procedure,they inadequately represent complex interactions and unique cellular properties in humans due to inter-species genetic and microenvironmental differences which have resulted in clinical-stage failures.Organoid technology has gained enormous attention as they provide sophisticated insights about tissue architecture and functionality in miniaturized organs.In this review,we describe the use of organoid system to overcome limitations in animal-based investigations,such as physiological mismatch with humans,costly,time-consuming,and low throughput screening.Immune organoids are one of the specific advancements in organogenesis ex vivo,which can reflect human adaptive immunity with more physiologically relevant aspects.We discuss how immune organoids are established from patient-derived lymphoid tissues,as well as their characteristics and functional features to understand immune mechanisms and responses.Also,some bioengineering perspectives are considered for any potential progress of immuno-engineered organoids.展开更多
The RA mixture is composed of Tripterygium wilfordii (TW) and other Chinese medicinalherbs with effect of expelling Wind, activating blood circulation, invigorating the Kidney and Qi . The authorstreated rheumatoid ar...The RA mixture is composed of Tripterygium wilfordii (TW) and other Chinese medicinalherbs with effect of expelling Wind, activating blood circulation, invigorating the Kidney and Qi . The authorstreated rheumatoid arthritis ( RA) patients with RA mixture and compared it with D-Penicillamine as ocntrol .The two group's therapeutical effect is similar ( P >0. 05) , but side effect occuring ratio in treatment groupwas obviously lower than that of control group ( P<0 . 01 ) . After treatment with RA mixture, the patient's hu-man lymphocytic antigen-degenerative reaction ( HLA-DR+ ) cell, CD4/CD8 ratio were reduced and auto-mixed lymphocytic reaction ( AMLR) level enhanced ( P < 0. 05) . The results of animal experiment showedthat swelling of rheumatoid arthritis model mouse's joint could be reduced by both RA mixture and TW. Com-paring with TW. RA mixture had stronger effect in controlling the inflammation of synovial cell and fibroid de-generation of fibrocytes. At the same time, RA mixture had stronger effect in protecting immune organ fromatrophy and maintaining functions of cellular immunity. All these suggest that RA mixture can reduce the syn-droms of RA by improving distribution of T Iymphocyte subsets and functions of cellular immunity. The Chinesemedicinal herbs for reinforcing Kidney, supplementing Qi , activating blood circulation and expelling evil windin the RA mixture could enhance TW's therapeutical effect and reduce it's side effect.展开更多
文摘Aiming at the problem on cooperative air-defense of surface warship formation, this paper maps the cooperative airdefense system of systems （SoS） for surface warship formation （CASoSSWF） to the biological immune system （BIS） according to the similarity of the defense mechanism and characteristics between the CASoSSWF and the BIS, and then designs the models of components and the architecture for a monitoring agent, a regulating agent, a killer agent, a pre-warning agent and a communicating agent by making use of the theories and methods of the artificial immune system, the multi-agent system （MAS）, the vaccine and the danger theory （DT）. Moreover a new immune multi-agent model using vaccine based on DT （IMMUVBDT） for the cooperative air-defense SoS is advanced. The immune response and immune mechanism of the CASoSSWF are analyzed. The model has a capability of memory, evolution, commendable dynamic environment adaptability and self-learning, and embodies adequately the cooperative air-defense mechanism for the CASoSSWF. Therefore it shows a novel idea for the CASoSSWF which can provide conception models for a surface warship formation operation simulation system.
基金sponsored by the Foundation for the Doctoral Program of Ministry of Education of China under Grant No.20060183041the National Natural Science Foundation of China under Grant No. 60773096 and No. 60773098
文摘The biological immune system is a complex adaptive system.There are lots of benefits for building the model of the immune system.For biological researchers,they can test some hypotheses about the infection process or simulate the responses of some drugs.For computer researchers,they can build distributed,robust and fault tolerant networks inspired by the functions of the immune system.This paper provides a comprehensive survey of the literatures on modelling the immune system.From the methodology perspective,the paper compares and analyzes the existing approaches and models,and also demonstrates the focusing research effort on the future immune models in the next few years.
基金supported by China NSF(61572222, 61272405, 61272033, 61272451, 61472121)Fundamental Research Funds for the Central Universities and the open research fund of Zhejiang Provincial Key Lab of Data StorageTransmission Technology, Hangzhou Dianzi University(No. 201301)
文摘Network structures and human behaviors are considered as two important factors in virus defense currently. However, due to ignorance of network security, normal users usually take simple activities, such as reinstalling computer system, or using the computer recovery system to clear virus. How system recovery influences virus spreading is not taken into consideration currently. In this paper, a new virus propagation model considering the system recovery is proposed first, and then in its steady-state analysis, the virus propagation steady time and steady states are deduced. Experiment results show that models considering system recovery can effectively restrain virus propagation. Furthermore, algorithm with system recovery in BA scale-free network is proposed. Simulation result turns out that target immunization strategy with system recovery works better than traditional ones in BA network.
基金the National Natural Science Foundation of China(81772995 and 81472266)the Excellent Youth Foundation of Jiangsu Province,China(BK20140032)Jiangsu Province’s Key Provincial Talents Program(ZDRCA2016090).
文摘PSMD14 played a vital role in initiation and progression of hepatocellular carcinoma(HCC).However,PSMD14 and its-related genes for the immune prognostic implications of HCC patients have rarely been analyzed.Messenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas(TCGA)and International Cancer Genome Consortium(ICGC)database-Liver Hepatocellular Carcinoma(LIHC).Additionally,we used multi-dimensional bioinformatics analysis to construct and validate a PSMD14-based immune prognostic signature(including RBM45,PSMD1,OLA1,CCT6A,LCAT and IVD)for HCC prognosis prediction.Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group.Calibration curves confirmed the good consistency between the clinical nomogram prediction and the actual observation.Gene set enrichment analyses(GSEA)revealed several significantly enriched pathways,which might help explain the underlying mechanisms.Besides,the rt-PCR further validates the expression of seven immune genes in HCC cells.Our study identified a novel PSMD14-based signature for HCC prognosis prediction,it provided new potential prognostic biomarkers and therapeutic targets for immunotherapy of HCC.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-035National Key Research and Development Project,Grant/Award Number:2022YFA1103803。
文摘In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.
基金This work was supported by DANIDA SaWaFo project with grant number 11-058DHI.
文摘Integration of acquired immunity into microbial risk assessment for illness incidence is of no doubt essential for the study of susceptibility to illness.In this study,a probabilistic model was set up as dose response for infection and a mathematical derivation was carried out by integrating immunity to obtain probability of illness models.Temporary acquire immunity from epidemiology studies which includes six different Norovirus transmission scenarios such as symptomatic individuals infectious,pre-and post-symptomatic infectiousness(low and high),innate genetic resistance,genogroup 2 type 4 and those with no immune boosting by asymptomatic infection were evaluated.Simulated results on illness inflation factor as a function of dose and exposure indicated that high frequency exposures had immense immunity build up even at high dose levels;hence minimized the probability of illness.Using Norovirus transmission dynamics data,results showed,and immunity included models had a reduction of 2e6 logs of magnitude difference in disease burden for both population and individual probable illness incidence.Additionally,the magnitude order of illness for each dose response remained largely the same for all transmission scenarios;symptomatic infectiousness and no immune boosting after asymptomatic infectiousness also remained the same throughout.With integration of epidemiological data on acquired immunity into the risk assessment,more realistic results were achieved signifying an overestimation of probable risk of illness when epidemiological immunity data are not included.This finding supported the call for rigorous integration of temporary acquired immunity in dose-response in all microbial risk assessments.
基金Supported by The Medical Scientific Research Project of the Jiangsu Health Commission,China,No.M2020055The Nanjing Medical Science and Technology Development Project,China,No.YKK22130The Postgraduate Research and Practice Innovation Program of Jiangsu Province,China,No.KYCX23_2105.
文摘BACKGROUND According to current statistics,renal cancer accounts for 3%of all cancers world-wide.Renal cell carcinoma(RCC)is the most common solid lesion in the kidney and accounts for approximately 90%of all renal malignancies.Increasing evi-dence has shown an association between immune infiltration in RCC and clinical outcomes.To discover possible targets for the immune system,we investigated the link between tumor-infiltrating immune cells(TIICs)and the prognosis of RCC.AIM To investigate the effects of 22 TIICs on the prognosis of RCC patients and iden-tify potential therapeutic targets for RCC immunotherapy.METHODS The CIBERSORT algorithm partitioned the 22 TIICs from the Cancer Genome Atlas cohort into proportions.Cox regression analysis was employed to evaluate the impact of 22 TIICs on the probability of developing RCC.A predictive model for immunological risk was developed by analyzing the statistical relationship between the subpopulations of TIICs and survival outcomes.Furthermore,multi-variate Cox regression analysis was used to investigate independent factors for the prognostic prediction of RCC.A value of P<0.05 was regarded as statistically significant.RESULTS Compared to normal tissues,RCC tissues exhibited a distinct infiltration of im-mune cells.An immune risk score model was established and univariate Cox regression analysis revealed a significant association between four immune cell types and the survival risk connected to RCC.High-risk individuals were correlated to poorer outcomes according to the Kaplan-Meier survival curve(P=1E-05).The immunological risk score model was demonstrated to be a dependable predictor of survival risk(area under the curve=0.747)via the receiver operating characteristic curve.According to multivariate Cox regression analysis,the immune risk score model independently predicted RCC patients'prognosis(hazard ratio=1.550,95%CI:1.342–1.791;P<0.001).Finally,we established a nomogram that accurately and comprehensively forecast the survival of patients with RCC.CONCLUSION TIICs play various roles in RCC prognosis.The immunological risk score is an independent predictor of poor survival in kidney cancer cases.
文摘In this paper,a tumor immune model with time delay is studied.First,the stability of nonnegative equilibria is analyzed.Then the time delay τ is selected as a bifurcation parameter and the existence of Hopf bifurcation is proved.Finally,by using the canonical method and the central manifold theory,the criteria for judging the direction and stability of Hopf bifurcation are given.
基金supported by the NUS Presidential Young Professor-ship,Ministry of Education Tier 1,National Medical Research Council Open Fund Young Investigator Research Grant,Manufacturing,Trade and Connectivity Young Investigator Research Grant,iHT OOE award,NUS Healthy Longevity TRP Aged Mice Funding,Joint NCIS Centre Grant and NUS Centre for Cancer Research(N2CR)Seed Funding Programme,TREX Grant,PCM Seed Grant,and PREPARE Strategic Open Grant Call(Vaccines&Therapeutics Co-Operative Programme).
文摘Animal models have been extensively used as a gold standard in various biological research,including immu-nological studies.Despite high availability and ease of handling procedure,they inadequately represent complex interactions and unique cellular properties in humans due to inter-species genetic and microenvironmental differences which have resulted in clinical-stage failures.Organoid technology has gained enormous attention as they provide sophisticated insights about tissue architecture and functionality in miniaturized organs.In this review,we describe the use of organoid system to overcome limitations in animal-based investigations,such as physiological mismatch with humans,costly,time-consuming,and low throughput screening.Immune organoids are one of the specific advancements in organogenesis ex vivo,which can reflect human adaptive immunity with more physiologically relevant aspects.We discuss how immune organoids are established from patient-derived lymphoid tissues,as well as their characteristics and functional features to understand immune mechanisms and responses.Also,some bioengineering perspectives are considered for any potential progress of immuno-engineered organoids.
文摘The RA mixture is composed of Tripterygium wilfordii (TW) and other Chinese medicinalherbs with effect of expelling Wind, activating blood circulation, invigorating the Kidney and Qi . The authorstreated rheumatoid arthritis ( RA) patients with RA mixture and compared it with D-Penicillamine as ocntrol .The two group's therapeutical effect is similar ( P >0. 05) , but side effect occuring ratio in treatment groupwas obviously lower than that of control group ( P<0 . 01 ) . After treatment with RA mixture, the patient's hu-man lymphocytic antigen-degenerative reaction ( HLA-DR+ ) cell, CD4/CD8 ratio were reduced and auto-mixed lymphocytic reaction ( AMLR) level enhanced ( P < 0. 05) . The results of animal experiment showedthat swelling of rheumatoid arthritis model mouse's joint could be reduced by both RA mixture and TW. Com-paring with TW. RA mixture had stronger effect in controlling the inflammation of synovial cell and fibroid de-generation of fibrocytes. At the same time, RA mixture had stronger effect in protecting immune organ fromatrophy and maintaining functions of cellular immunity. All these suggest that RA mixture can reduce the syn-droms of RA by improving distribution of T Iymphocyte subsets and functions of cellular immunity. The Chinesemedicinal herbs for reinforcing Kidney, supplementing Qi , activating blood circulation and expelling evil windin the RA mixture could enhance TW's therapeutical effect and reduce it's side effect.
