Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Per...Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.展开更多
Level of repair analysis（LORA） is an important method of maintenance decision for establishing systems of operation and maintenance in the equipment development period. Currently, the research on equipment of repair...Level of repair analysis（LORA） is an important method of maintenance decision for establishing systems of operation and maintenance in the equipment development period. Currently, the research on equipment of repair level focuses on economic analysis models which are used to optimize costs and rarely considers the maintenance time required by the implementation of the maintenance program. In fact, as to the system requiring high mission complete success, the maintenance time is an important factor which has a great influence on the availability of equipment systems. Considering the relationship between the maintenance time and the spares stocks level, it is obvious that there are contradictions between the maintenance time and the cost. In order to balance these two factors, it is necessary to build an optimization LORA model. To this end, the maintenance time representing performance characteristic is introduced, and on the basis of spares stocks which is traditionally regarded as a decision variable, a decision variable of repair level is added, and a multi-echelon multiindenture（MEMI） optimization LORA model is built which takes the best cost-effectiveness ratio as the criterion, the expected number of backorder（EBO） as the objective function and the cost as the constraint. Besides, the paper designs a convex programming algorithm of multi-variable for the optimization model, provides solutions to the non-convex objective function and methods for improving the efficiency of the algorithm. The method provided in this paper is proved to be credible and effective according to the numerical example and the simulation result.展开更多
The network reliability is difficult to be evaluated because of the complex relationship among the network components.It can be quite different for different users running different applications on the same network.Th...The network reliability is difficult to be evaluated because of the complex relationship among the network components.It can be quite different for different users running different applications on the same network.This paper proposes a new concept and a model of application reliability.Different from the existing models that ignores the effects of applications,the proposed application reliability model considers the effects of different applications on the network performance and different types of network faults and makes the analysis of network components relationship possible.This paper also provides a method to evaluate the application reliability when the data flow satisfies Markov properties.Finally,a case study is presented to illustrate the proposed network reliability model and the analysis method.展开更多
The uncertainty analysis is an effective sensitivity analysis method for system model analysis and optimization. However,the existing single-factor uncertainty analysis methods are not well used in the logistic suppor...The uncertainty analysis is an effective sensitivity analysis method for system model analysis and optimization. However,the existing single-factor uncertainty analysis methods are not well used in the logistic support systems with multiple decision-making factors. The multiple transfer parameters graphical evaluation and review technique（MTP-GERT） is used to model the logistic support process in consideration of two important factors, support activity time and support activity resources, which are two primary causes for the logistic support process uncertainty. On this basis,a global sensitivity analysis（GSA） method based on covariance is designed to analyze the logistic support process uncertainty. The aircraft support process is selected as a case application which illustrates the validity of the proposed method to analyze the support process uncertainty, and some feasible recommendations are proposed for aircraft support decision making on carrier.展开更多
The elements of network profile are proposed.Based on the network traffic distribution model,the network profile includes the application request rate,the branch transfer probability,the ratio of application requests,...The elements of network profile are proposed.Based on the network traffic distribution model,the network profile includes the application request rate,the branch transfer probability,the ratio of application requests,and the probability distribution of the requested objects.Based on the evaluation method of network performance reliability,four simulation cases are constructed in OPNET software,and the results show the four elements of profile have impacts on the network reliability.展开更多
Distribution-based degradation models （or graphical approach in some literature） occur in a wide range of applications. However, few of existing methods have taken the validation of the built model into consideratio...Distribution-based degradation models （or graphical approach in some literature） occur in a wide range of applications. However, few of existing methods have taken the validation of the built model into consideration. A validation methodology for distribution-based models is proposed in this paper. Since the model can be expressed as consisting of assumptions of model structures and embedded model parameters, the proposed methodology carries out the validation from these two aspects. By using appropriate statistical techniques, the rationality of degradation distributions, suitability of fitted models and validity of degradation models are validated respectively. A new statistical technique based on control limits is also proposed, which can be implemented in the validation of degradation models＇ validity. The case study on degradation modeling of an actual accelerometer shows that the proposed methodology is an effective solution to the validation problem of distribution-based de qradation models.展开更多
This paper presents a methodology for automatically generating risk scenarios for dynamic reliability applications in which some dynamic characteristics(e.g.,the order,timing and magnitude of events,the value of relev...This paper presents a methodology for automatically generating risk scenarios for dynamic reliability applications in which some dynamic characteristics(e.g.,the order,timing and magnitude of events,the value of relevant process parameters and initial conditions) have a significant influence on the evolution of the system.The main idea of the methodology is:(i) making the system model "express itself" through simulation by having the model driven by an elaborated simulation engine;(ii) exploiting uniform design to pick out a small subset of representative design points from the space of relevant dynamic characteristics;(iii) for each selected design point,employing a depth-first systematic exploration strategy to cover all possible scenario branches at each branch point.A highly dynamic example adapted from the literature(a chemical batch reactor) is studied to test the effectiveness of the proposed methodology.展开更多
A methodology for automatically generating risk scenarios is presented.Its main idea is to let the system model ＂express itself＂ through simulation.This is achieved by having the simulation model driven by an elabor...A methodology for automatically generating risk scenarios is presented.Its main idea is to let the system model ＂express itself＂ through simulation.This is achieved by having the simulation model driven by an elaborated simulation engine,which：（i） manipulates the generation of branch points,i.e.event occurrence times;（ii） employs a depth-first systematic exploration strategy to cover all possible branch paths at each branch point.In addition,a backtracking technique,as an extension,is implemented to recover some missed risk scenarios.A widely discussed dynamic reliability example（a holdup tank） is used to aid in the explanation of and to demonstrate the effectiveness of the proposed methodology.展开更多
A fundamental premise of an accelerated testing is that the failure mechanism under elevated and normal stress levels should remain the same. Thus, verification of the consistency of failure mechanisms is essential du...A fundamental premise of an accelerated testing is that the failure mechanism under elevated and normal stress levels should remain the same. Thus, verification of the consistency of failure mechanisms is essential during an accelerated testing. A new consistency analysis method based on the gray theory is pro- posed for complex products. First of all, existing consistency ana- lysis methods are reviewed with a focus on the comparison of the differences among them. Then, the proposed consistency ana- lysis method is introduced. Two effective gray prediction models, gray dynamic model and new information and equal dimensional （NIED） model, are adapted in the proposed method. The process to determine the dimension of NIED model is also discussed, and a decision rule is expanded. Based on that, the procedure of ap- plying the new consistent analysis method is developed. Finally, a case study of the consistency analysis of a reliability enhancement testing is conducted to demonstrate and validate the proposed method.展开更多
Since the communication principles content are abstract and complex,and systematic,students generally reflect this course is difficult to learn,under stand and master,teachers also feel difficult to teach.Therefore,h...Since the communication principles content are abstract and complex,and systematic,students generally reflect this course is difficult to learn,under stand and master,teachers also feel difficult to teach.Therefore,how to improve the quality of teaching of communication principles curriculum is the key problem in teaching process.The Online to Offline(O2O)hybrid teaching mode can realize classroom flip,further deepen the curriculum reform,make curriculum quality standards,recard and optimize teaching content,refine teaching requirements,improve teaching methods and the construction of curriculum resources,curric ulum construction quality assurance system.It explores the reform of other courses for Communication Engineering Department,provides technical support and accumulates valuable experience for subsequent courses to complete O2O mode teaching.展开更多
The Complementary Metal-Oxide Semiconductor(CMOS)image sensor is a critical component with the function of providing accurate positioning in many space application systems.Under long-time operation in space environmen...The Complementary Metal-Oxide Semiconductor(CMOS)image sensor is a critical component with the function of providing accurate positioning in many space application systems.Under long-time operation in space environments,there are radiation related degradation and var-ious uncertainties affecting the positioning accuracy of CMOS image sensors,which further leads to a reliability reduction of CMOS image sensors.Obviously,the reliability of CMOS image sensors is related to their specified function,degradation,and uncertainties;however,current research has not fully described this relationship.In this paper,a comprehensive approach to reliability modelling of CMOs image sensors is proposed based on the reliability science principles.Firstly,the perfor-mance margin modelling of centroid positioning accuracy is conducted.Then,the degradation model of CMOS image sensors is derived considering the dark current increase induced by the total ionizing dose effects.Finally,various uncertainties are analyzed and quantified,and the measure-ment equation of reliability is proposed.A case study of a CMOS image sensor is conducted to apply the proposed method,and the sensitivity analysis can provide suggestions for design and use of CMOS image sensors to ensure reliability.A simulation study is conducted to present the advantages oftheproposed comprehensive approach.展开更多
Accurately evaluating the lifespan of the Printed Circuit Board(PCB)in airborne equipment is an essential issue for aircraft design and operation in the marine atmospheric environment.This paper presents a novel evalu...Accurately evaluating the lifespan of the Printed Circuit Board(PCB)in airborne equipment is an essential issue for aircraft design and operation in the marine atmospheric environment.This paper presents a novel evaluation method by fusing Accelerated Degradation Testing(ADT)data,degradation data,and life data of small samples based on the uncertainty degradation process.An uncertain life model of PCB in airborne equipment is constructed by employing the uncertain distribution that considers the accelerated factor of multiple environmental conditions such as temperature,humidity,and salinity.In addition,a degradation process model of PCB in airborne equipment is constructed by employing the uncertain process of fusing ADT data and field data,in which the performance characteristics of dynamic cumulative change are included.Based on minimizing the pth sample moments,an integrated method for parameter estimation of the PCB in airborne equipment is proposed by fusing the multi-source data of life,degradation,and ADT.An engineering case illustrates the effectiveness and advantage of the proposed method.展开更多
Osteoarthritis(OA)is one of the most common degenerative joint diseases worldwide,causing pain,disability,and decreased quality of life.The balance between regeneration and inflammation-induced degradation results in ...Osteoarthritis(OA)is one of the most common degenerative joint diseases worldwide,causing pain,disability,and decreased quality of life.The balance between regeneration and inflammation-induced degradation results in multiple etiologies and complex pathogenesis of OA.Currently,there is a lack of effective therapeutic strategies for OA treatment.With the development of CRISPR-based genome,epigenome,and RNA editing tools,OA treatment has been improved by targeting genetic risk factors,activating chondrogenic elements,and modulating inflammatory regulators.Supported by cell therapy and in vivo delivery vectors,genome,epigenome,and RNA editing tools may provide a promising approach for personalized OA therapy.This review summarizes CRISPR-based genome,epigenome,and RNA editing tools that can be applied to the treatment of OA and provides insights into the development of CRISPR-based therapeutics for OA treatment.Moreover,in-depth evaluations of the efficacy and safety of these tools in human OA treatment are needed.展开更多
DearEditor,The CRISPR-mediated genome editing tools,including nucleases,base editors(ABE/CBE),transposases/recombinases,and prime editor(PE),have been extensively applied in basic and clinical researches,although the ...DearEditor,The CRISPR-mediated genome editing tools,including nucleases,base editors(ABE/CBE),transposases/recombinases,and prime editor(PE),have been extensively applied in basic and clinical researches,although the off-target effect remains a major concern(Anzalone et al.,2020).Recently,various methods have been developed to assess the specificity and accuracy of different tools(Zhang et al.,2021),yet each method is designed for limited editing systems,and none of them can simultaneously detect off-target sites in vivo and in vitro.A versatile method for profiling genome-wide off-target effects of various tools remains lacking.展开更多
We consider reliability engineering in modern civil aviation industry, and the related engineering activities and methods. We consider reliability in a broad sense, referring to other system characteristics that are r...We consider reliability engineering in modern civil aviation industry, and the related engineering activities and methods. We consider reliability in a broad sense, referring to other system characteristics that are related to it, like availability, maintainability, safety and durability. We covered the entire lifecycle of the equipment, including reliability requirement identification, reliability analysis and design, verification and validation of reliability requirements(typically involved in the equipment design and development phase), quality assurance(which typically enters in the manufacturing phase), and fault diagnosis and prognosis and maintenance(which are connected to the operation phase). Lessons learnt from reliability engineering practices in civil aviation industry are given, which might serve as reference for reliability managers and engineers, also from other industries with high reliability requirements.展开更多
The second law of thermodynamics implies that any animate and inanimate systems degrade and inevitably stops functioning.It is irreversible over time that can be labeled as‘‘the degradation arrow of time".From ...The second law of thermodynamics implies that any animate and inanimate systems degrade and inevitably stops functioning.It is irreversible over time that can be labeled as‘‘the degradation arrow of time".From perspective of products’reliability design,it is essential to build appropriate models of describing the degradation arrow of time.The current modeling approaches mainly include the model-driven(having assumed forms based on cognitive experience of mankind)and data-driven(using data learning techniques without form hypothesis)approaches.In this paper,we just investigate and review the model-driven degradation approaches,hoping to provide suggestions of the model construction or selection for scholars or engineers.First,for the single mechanism,degradation law models and stochastic process models are classified as separately depicting the tendency and fluctuation of degradation.For the degradation law model,we propose the concept of meta-models as original types for various personal models.For the stochastic process model,two main types including the non-monotonic and monotonical types are presented.Then,four multi-mechanism degradation types are discussed,that are competitive degradation,multi-stage degradation,coexistence of degradation and impact,and coexistence of degradation and failure.Besides,for the multi-performance degradation,independent and coupling models are introduced.The forms,connotations,applicability and insufficiency of these models are described with a series of examples from the literature and our own experiences.The final explicit suggestions about the potential future work are provided for the development of new degradation models.展开更多
A thermal-solid-liquid complex operational environment induces structural interface developing a typical coupling sliding/impact wear behavior.It results in contact damage until systems fail,which may cause significan...A thermal-solid-liquid complex operational environment induces structural interface developing a typical coupling sliding/impact wear behavior.It results in contact damage until systems fail,which may cause significant economic losses and catastrophic consequences.The key point of solving this problem is to reveal the coupling damage mechanism of the sliding/impact behavior in typical systems and life characterization under a complicate evolving environment.This has been a hot topic in the area of mechanical reliability.The main work in this paper can be concluded as follows.Firstly,the main industries in which the"sliding/impact behavior"takes place have been introduced.Then,existing studies on the wear mechanism and degree analysis are presented,which includes surface morphology analysis,wear debris analysis,and wear degree measurement.Meanwhile,existing problems in theoretical modeling and experiments in current research are summarized,so as to point out a bright direction for future research on wear prediction.They include interface contact modeling,mathematic coupling mechanism modeling,wear equation establishment,and wear life characterization,which can provide some new ideas for improving the existing studies on the sliding/impact wear behavior.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignant disease with a unique tumor microenvironment surrounded by an interlaced network of cancer and noncancerous cells.Recent works have revealed that the dy...Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignant disease with a unique tumor microenvironment surrounded by an interlaced network of cancer and noncancerous cells.Recent works have revealed that the dynamic interaction between cancer cells and neuronal cells leads to perineural invasion(PNI),a clinical pathological feature of PDAC.The formation and function of PNI are dually regulated by molecular(e.g.,involving neurotrophins,cytokines,chemokines,and neurotransmitters),metabolic(e.g.,serine metabolism),and cellular mechanisms(e.g.,involving Schwann cells,stromal cells,T cells,and macrophages).Such integrated mechanisms of PNI not only support tumor development,growth,invasion,and metastasis but also mediate the formation of pain,all of which are closely related to poor disease prognosis in PDAC.This review details the modulation,signaling pathways,detection,and clinical relevance of PNI and highlights the opportunities for further exploration that may benefit PDAC patients.展开更多
Innate immunity serves as the rapid and frst-line defense against invading pathogens,and this process can be regulated at various levels,including epigenetic mechanisms.The bromodomain and extraterminal domain(BET)fam...Innate immunity serves as the rapid and frst-line defense against invading pathogens,and this process can be regulated at various levels,including epigenetic mechanisms.The bromodomain and extraterminal domain(BET)family of proteins consists of four conserved mammalian members(BRD2,BRD3,BRD4,and BRDT)that regulate the expression of many immunity-associated genes and pathways.In particular,in response to infection and sterile inflammation,abnormally expressed or dysfunctional BETs are involved in the activation of pattern recognition receptor(e.g,TLR,NLR,and CGAS)pathways,thereby linking chromatin machinery to innate immunity under disease or pathological conditions.Mechanistically,the BET family controls the transcription of a wide range of proinflammatory and immunoregulatory genes by recognizing acetylated histones(mainly H3 and H4)and recruiting transcription factors(e.g.,RELA)and transcription elongation complex(e.g.P-TEFb)to the chromatin,thereby promoting the phosphorylation of RNA polymerase II and subsequent transcription initiation and elongation.This review covers the accumulating data about the roles of the BET family in innate immunity,and discusses the attractive prospect of manipulating the BET family as a new treatment for disease.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82271755,No.81871230)Peking University People's Hospital Scientific Research Development Funds(RZ 2022-06).
文摘Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.
基金supported by the National Natural Science Foundation of China(6110413261304148)
文摘Level of repair analysis（LORA） is an important method of maintenance decision for establishing systems of operation and maintenance in the equipment development period. Currently, the research on equipment of repair level focuses on economic analysis models which are used to optimize costs and rarely considers the maintenance time required by the implementation of the maintenance program. In fact, as to the system requiring high mission complete success, the maintenance time is an important factor which has a great influence on the availability of equipment systems. Considering the relationship between the maintenance time and the spares stocks level, it is obvious that there are contradictions between the maintenance time and the cost. In order to balance these two factors, it is necessary to build an optimization LORA model. To this end, the maintenance time representing performance characteristic is introduced, and on the basis of spares stocks which is traditionally regarded as a decision variable, a decision variable of repair level is added, and a multi-echelon multiindenture（MEMI） optimization LORA model is built which takes the best cost-effectiveness ratio as the criterion, the expected number of backorder（EBO） as the objective function and the cost as the constraint. Besides, the paper designs a convex programming algorithm of multi-variable for the optimization model, provides solutions to the non-convex objective function and methods for improving the efficiency of the algorithm. The method provided in this paper is proved to be credible and effective according to the numerical example and the simulation result.
基金supported by the Beijing Natural Science Foundation(4113074)
文摘The network reliability is difficult to be evaluated because of the complex relationship among the network components.It can be quite different for different users running different applications on the same network.This paper proposes a new concept and a model of application reliability.Different from the existing models that ignores the effects of applications,the proposed application reliability model considers the effects of different applications on the network performance and different types of network faults and makes the analysis of network components relationship possible.This paper also provides a method to evaluate the application reliability when the data flow satisfies Markov properties.Finally,a case study is presented to illustrate the proposed network reliability model and the analysis method.
基金supported by the National Natural Science Foundation of China(71171008)
文摘The uncertainty analysis is an effective sensitivity analysis method for system model analysis and optimization. However,the existing single-factor uncertainty analysis methods are not well used in the logistic support systems with multiple decision-making factors. The multiple transfer parameters graphical evaluation and review technique（MTP-GERT） is used to model the logistic support process in consideration of two important factors, support activity time and support activity resources, which are two primary causes for the logistic support process uncertainty. On this basis,a global sensitivity analysis（GSA） method based on covariance is designed to analyze the logistic support process uncertainty. The aircraft support process is selected as a case application which illustrates the validity of the proposed method to analyze the support process uncertainty, and some feasible recommendations are proposed for aircraft support decision making on carrier.
文摘The elements of network profile are proposed.Based on the network traffic distribution model,the network profile includes the application request rate,the branch transfer probability,the ratio of application requests,and the probability distribution of the requested objects.Based on the evaluation method of network performance reliability,four simulation cases are constructed in OPNET software,and the results show the four elements of profile have impacts on the network reliability.
文摘Distribution-based degradation models （or graphical approach in some literature） occur in a wide range of applications. However, few of existing methods have taken the validation of the built model into consideration. A validation methodology for distribution-based models is proposed in this paper. Since the model can be expressed as consisting of assumptions of model structures and embedded model parameters, the proposed methodology carries out the validation from these two aspects. By using appropriate statistical techniques, the rationality of degradation distributions, suitability of fitted models and validity of degradation models are validated respectively. A new statistical technique based on control limits is also proposed, which can be implemented in the validation of degradation models＇ validity. The case study on degradation modeling of an actual accelerometer shows that the proposed methodology is an effective solution to the validation problem of distribution-based de qradation models.
基金supported by the National Natural Science Foundation of China (70901004)the Fundamental Research Funds for the Central Universities (YWF-10-01-A12)
文摘This paper presents a methodology for automatically generating risk scenarios for dynamic reliability applications in which some dynamic characteristics(e.g.,the order,timing and magnitude of events,the value of relevant process parameters and initial conditions) have a significant influence on the evolution of the system.The main idea of the methodology is:(i) making the system model "express itself" through simulation by having the model driven by an elaborated simulation engine;(ii) exploiting uniform design to pick out a small subset of representative design points from the space of relevant dynamic characteristics;(iii) for each selected design point,employing a depth-first systematic exploration strategy to cover all possible scenario branches at each branch point.A highly dynamic example adapted from the literature(a chemical batch reactor) is studied to test the effectiveness of the proposed methodology.
基金supported by the National Natural Science Foundation of China (70901004)the Fundamental Research Funds for the Central Universities (YWF-10-01-A12)
文摘A methodology for automatically generating risk scenarios is presented.Its main idea is to let the system model ＂express itself＂ through simulation.This is achieved by having the simulation model driven by an elaborated simulation engine,which：（i） manipulates the generation of branch points,i.e.event occurrence times;（ii） employs a depth-first systematic exploration strategy to cover all possible branch paths at each branch point.In addition,a backtracking technique,as an extension,is implemented to recover some missed risk scenarios.A widely discussed dynamic reliability example（a holdup tank） is used to aid in the explanation of and to demonstrate the effectiveness of the proposed methodology.
基金supported by the National Natural Science Foundation of China(61104132)
文摘A fundamental premise of an accelerated testing is that the failure mechanism under elevated and normal stress levels should remain the same. Thus, verification of the consistency of failure mechanisms is essential during an accelerated testing. A new consistency analysis method based on the gray theory is pro- posed for complex products. First of all, existing consistency ana- lysis methods are reviewed with a focus on the comparison of the differences among them. Then, the proposed consistency ana- lysis method is introduced. Two effective gray prediction models, gray dynamic model and new information and equal dimensional （NIED） model, are adapted in the proposed method. The process to determine the dimension of NIED model is also discussed, and a decision rule is expanded. Based on that, the procedure of ap- plying the new consistent analysis method is developed. Finally, a case study of the consistency analysis of a reliability enhancement testing is conducted to demonstrate and validate the proposed method.
文摘Since the communication principles content are abstract and complex,and systematic,students generally reflect this course is difficult to learn,under stand and master,teachers also feel difficult to teach.Therefore,how to improve the quality of teaching of communication principles curriculum is the key problem in teaching process.The Online to Offline(O2O)hybrid teaching mode can realize classroom flip,further deepen the curriculum reform,make curriculum quality standards,recard and optimize teaching content,refine teaching requirements,improve teaching methods and the construction of curriculum resources,curric ulum construction quality assurance system.It explores the reform of other courses for Communication Engineering Department,provides technical support and accumulates valuable experience for subsequent courses to complete O2O mode teaching.
基金the National Natural Science Foundation of China (No.51775020)the Science Challenge Project,China (No.TZ2018007)+1 种基金the National Natural Science Foundation of China (No.62073009)the Fundamental Research Funds for Central Universities,China (No.YWF-19-BJ-J-515).
文摘The Complementary Metal-Oxide Semiconductor(CMOS)image sensor is a critical component with the function of providing accurate positioning in many space application systems.Under long-time operation in space environments,there are radiation related degradation and var-ious uncertainties affecting the positioning accuracy of CMOS image sensors,which further leads to a reliability reduction of CMOS image sensors.Obviously,the reliability of CMOS image sensors is related to their specified function,degradation,and uncertainties;however,current research has not fully described this relationship.In this paper,a comprehensive approach to reliability modelling of CMOs image sensors is proposed based on the reliability science principles.Firstly,the perfor-mance margin modelling of centroid positioning accuracy is conducted.Then,the degradation model of CMOS image sensors is derived considering the dark current increase induced by the total ionizing dose effects.Finally,various uncertainties are analyzed and quantified,and the measure-ment equation of reliability is proposed.A case study of a CMOS image sensor is conducted to apply the proposed method,and the sensitivity analysis can provide suggestions for design and use of CMOS image sensors to ensure reliability.A simulation study is conducted to present the advantages oftheproposed comprehensive approach.
基金supported by the National Natural Science Foundation of China(No.62073009).
文摘Accurately evaluating the lifespan of the Printed Circuit Board(PCB)in airborne equipment is an essential issue for aircraft design and operation in the marine atmospheric environment.This paper presents a novel evaluation method by fusing Accelerated Degradation Testing(ADT)data,degradation data,and life data of small samples based on the uncertainty degradation process.An uncertain life model of PCB in airborne equipment is constructed by employing the uncertain distribution that considers the accelerated factor of multiple environmental conditions such as temperature,humidity,and salinity.In addition,a degradation process model of PCB in airborne equipment is constructed by employing the uncertain process of fusing ADT data and field data,in which the performance characteristics of dynamic cumulative change are included.Based on minimizing the pth sample moments,an integrated method for parameter estimation of the PCB in airborne equipment is proposed by fusing the multi-source data of life,degradation,and ADT.An engineering case illustrates the effectiveness and advantage of the proposed method.
基金supported by the National Natural Science Foundation(32001063 and 82201769)the Guangdong Special Support Program(2019BT02Y276)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2021A1515010759 and 2023A1515010176)the grant from MOE Key Laboratory of Gene Function and Regulation,the Guangzhou Science and Technology Planning Project(202201020411 and 2023A04J1952)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(23ptpy59).
文摘Osteoarthritis(OA)is one of the most common degenerative joint diseases worldwide,causing pain,disability,and decreased quality of life.The balance between regeneration and inflammation-induced degradation results in multiple etiologies and complex pathogenesis of OA.Currently,there is a lack of effective therapeutic strategies for OA treatment.With the development of CRISPR-based genome,epigenome,and RNA editing tools,OA treatment has been improved by targeting genetic risk factors,activating chondrogenic elements,and modulating inflammatory regulators.Supported by cell therapy and in vivo delivery vectors,genome,epigenome,and RNA editing tools may provide a promising approach for personalized OA therapy.This review summarizes CRISPR-based genome,epigenome,and RNA editing tools that can be applied to the treatment of OA and provides insights into the development of CRISPR-based therapeutics for OA treatment.Moreover,in-depth evaluations of the efficacy and safety of these tools in human OA treatment are needed.
基金supported by the Ministry of Science and Technology of China to G.Z.L.(National Science and Technology Major Project,grant nos.2018YFA0109100,2019YFA0802203)National Natural Science Foundation of China to G.z.L.(Grant Nos.31922015,31870808,91753129)+1 种基金Natural Science Foundation of Guangdong Province to G.Z.L.(Grant No.2018B030306044)Guangdong Special Support Program to P.L.(2019BT02Y276).
文摘DearEditor,The CRISPR-mediated genome editing tools,including nucleases,base editors(ABE/CBE),transposases/recombinases,and prime editor(PE),have been extensively applied in basic and clinical researches,although the off-target effect remains a major concern(Anzalone et al.,2020).Recently,various methods have been developed to assess the specificity and accuracy of different tools(Zhang et al.,2021),yet each method is designed for limited editing systems,and none of them can simultaneously detect off-target sites in vivo and in vitro.A versatile method for profiling genome-wide off-target effects of various tools remains lacking.
基金supported by the National Natural Science Foundation of China (Nos. 61573043, 71671009 and 71601010)
文摘We consider reliability engineering in modern civil aviation industry, and the related engineering activities and methods. We consider reliability in a broad sense, referring to other system characteristics that are related to it, like availability, maintainability, safety and durability. We covered the entire lifecycle of the equipment, including reliability requirement identification, reliability analysis and design, verification and validation of reliability requirements(typically involved in the equipment design and development phase), quality assurance(which typically enters in the manufacturing phase), and fault diagnosis and prognosis and maintenance(which are connected to the operation phase). Lessons learnt from reliability engineering practices in civil aviation industry are given, which might serve as reference for reliability managers and engineers, also from other industries with high reliability requirements.
基金co-supported by the National Natural Science Foundation of China(Nos.51675025,and 61573043)。
文摘The second law of thermodynamics implies that any animate and inanimate systems degrade and inevitably stops functioning.It is irreversible over time that can be labeled as‘‘the degradation arrow of time".From perspective of products’reliability design,it is essential to build appropriate models of describing the degradation arrow of time.The current modeling approaches mainly include the model-driven(having assumed forms based on cognitive experience of mankind)and data-driven(using data learning techniques without form hypothesis)approaches.In this paper,we just investigate and review the model-driven degradation approaches,hoping to provide suggestions of the model construction or selection for scholars or engineers.First,for the single mechanism,degradation law models and stochastic process models are classified as separately depicting the tendency and fluctuation of degradation.For the degradation law model,we propose the concept of meta-models as original types for various personal models.For the stochastic process model,two main types including the non-monotonic and monotonical types are presented.Then,four multi-mechanism degradation types are discussed,that are competitive degradation,multi-stage degradation,coexistence of degradation and impact,and coexistence of degradation and failure.Besides,for the multi-performance degradation,independent and coupling models are introduced.The forms,connotations,applicability and insufficiency of these models are described with a series of examples from the literature and our own experiences.The final explicit suggestions about the potential future work are provided for the development of new degradation models.
基金supported by the National Natural Science Foundation of China(No.51675025).
文摘A thermal-solid-liquid complex operational environment induces structural interface developing a typical coupling sliding/impact wear behavior.It results in contact damage until systems fail,which may cause significant economic losses and catastrophic consequences.The key point of solving this problem is to reveal the coupling damage mechanism of the sliding/impact behavior in typical systems and life characterization under a complicate evolving environment.This has been a hot topic in the area of mechanical reliability.The main work in this paper can be concluded as follows.Firstly,the main industries in which the"sliding/impact behavior"takes place have been introduced.Then,existing studies on the wear mechanism and degree analysis are presented,which includes surface morphology analysis,wear debris analysis,and wear degree measurement.Meanwhile,existing problems in theoretical modeling and experiments in current research are summarized,so as to point out a bright direction for future research on wear prediction.They include interface contact modeling,mathematic coupling mechanism modeling,wear equation establishment,and wear life characterization,which can provide some new ideas for improving the existing studies on the sliding/impact wear behavior.
文摘Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignant disease with a unique tumor microenvironment surrounded by an interlaced network of cancer and noncancerous cells.Recent works have revealed that the dynamic interaction between cancer cells and neuronal cells leads to perineural invasion(PNI),a clinical pathological feature of PDAC.The formation and function of PNI are dually regulated by molecular(e.g.,involving neurotrophins,cytokines,chemokines,and neurotransmitters),metabolic(e.g.,serine metabolism),and cellular mechanisms(e.g.,involving Schwann cells,stromal cells,T cells,and macrophages).Such integrated mechanisms of PNI not only support tumor development,growth,invasion,and metastasis but also mediate the formation of pain,all of which are closely related to poor disease prognosis in PDAC.This review details the modulation,signaling pathways,detection,and clinical relevance of PNI and highlights the opportunities for further exploration that may benefit PDAC patients.
基金We thank Dave Primm(Department of Surgery,UTSW)for his critical reading of the manuscriptD.T.is supported by a grant from the U.S.NIH(R01GM127791)R.K.is supported by a grant from the U.S.NIH(R01CA211070).
文摘Innate immunity serves as the rapid and frst-line defense against invading pathogens,and this process can be regulated at various levels,including epigenetic mechanisms.The bromodomain and extraterminal domain(BET)family of proteins consists of four conserved mammalian members(BRD2,BRD3,BRD4,and BRDT)that regulate the expression of many immunity-associated genes and pathways.In particular,in response to infection and sterile inflammation,abnormally expressed or dysfunctional BETs are involved in the activation of pattern recognition receptor(e.g,TLR,NLR,and CGAS)pathways,thereby linking chromatin machinery to innate immunity under disease or pathological conditions.Mechanistically,the BET family controls the transcription of a wide range of proinflammatory and immunoregulatory genes by recognizing acetylated histones(mainly H3 and H4)and recruiting transcription factors(e.g.,RELA)and transcription elongation complex(e.g.P-TEFb)to the chromatin,thereby promoting the phosphorylation of RNA polymerase II and subsequent transcription initiation and elongation.This review covers the accumulating data about the roles of the BET family in innate immunity,and discusses the attractive prospect of manipulating the BET family as a new treatment for disease.
