Objective:To elucidate the effects of chlorogenic acid(CGA),a bioactive polyphenol compound prevalent in traditional Chinese medicine and various foods,including Lonicera japonica Thunb.(Jin Yin Hua),Eucommia ulmoides...Objective:To elucidate the effects of chlorogenic acid(CGA),a bioactive polyphenol compound prevalent in traditional Chinese medicine and various foods,including Lonicera japonica Thunb.(Jin Yin Hua),Eucommia ulmoides Oliv.(Du Zhong Ye),tea,and coffee,on cardiomyocyte ferroptosis and heart failure.Methods: We assessed the effect of CGA on cardiac function using a mouse model of heart failure induced by transverse aortic constriction(TAC).These indicators included the left ventricular ejection fraction(LVEF),fractional shortening(LVFS),end-systolic volume(LVESV),end-diastolic volume(LVEDV),end-systolic diameter(LVESD),and end-diastolic diameter(LVEDD).An isoprenaline hydrochloride(ISO)-induced H9c2 cardiomyocyte cell model was also established,and the cells were treated with various concentrations of CGA.To assess the effect of CGA on ferroptosis in cardiomyocytes,we measured cell viability and evaluated the levels of intracellular reactive oxygen species(ROS),ferrous ions(Fe^(2+)),and lipid peroxidation using fluorescent staining.To clarify the ferroptosis signaling pathway regulated by CGA,western blotting was used to examine the expression of ferroptosis biomarkers,specifically solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),in H9c2 cardiomyocytes and mouse myocardial tissues.Results: CGA significantly enhanced cardiac performance indices such as LVEF,LVFS,LVESV,LVEDV,LVESD,and LVEDD.H9c2 cardiomyocytes exposed to ISO showed decreased cell viability and increased ROS levels,Fe^(2+)content,and lipid peroxidation levels.However,CGA treatment significantly ameliorated these changes.Additionally,in both H9c2 cardiomyocytes and myocardial tissue obtained from mice with TAC,CGA increased the expression of ferroptosis-related proteins,including SLC7A11 and GPX4.Conclusion: CGA has the potential to enhance cardiac function and diminish lipid peroxidation and ROS levels in cardiomyocytes via the SLC7A11/GPX4 signaling pathway.This process alleviates ferroptosis in cardiomyocytes.These results provide new insights into the clinical use of CGA and the management of heart failure.展开更多
Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failu...Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failure(CHF).Methods:In vitro,the H_(9)C_(2) cell model was induced by ANGII,and cell proliferation and related protein expression were detected by Cell Counting Kit-8 and Western blot.In vivo,A rat model of CHF was prepared by ligation of the left anterior descending coronary artery.The effects of QXHLF on cardiac function in CHF rats were evaluated by cardiac index,hemodynamic changes,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,immunohistochemistry,Western blot and RT-PCR.The expression of pro-apoptotic factors and anti-apoptotic factors,as well as TGFβ1,p-p38,TAK 1 mRNA,and protein,were detected.Results:In vitro,QXHLF has a significant inhibitory effect on the proliferation of H_(9)C_(2) cells.QXHLF can reduce the expression levels of TAK 1,TGFβ1,p-p38,Caspase3 and BAX proteins in H_(9)C_(2) cells,and increase the expression level of BCL_(2) protein.In vivo,QXHLF has the potential to increase left ventricular systolic pressure,m aximum rate of change in left ventricular pressure while decreasing left ventricular end diastolic pressure,and inhibiting the serum levels of brain natriuretic peptide.Moreover,QXHLF exhibits significant improvements in the pathological alterations of myocardial cells and fibers in CHF rats,leading to enhanced myocardial tissue morphology and notable advantages in combating myocardial fibrosis.QXHLF can reduce the levels of BAX and Caspase3 and up-regulate the expression of BCL_(2),thereby inhibiting cardiomyocyte apoptosis.Furthermore,QXHLF demonstrates inhibitory effects on the mRNA and protein expression levels of TGFβ_(1),TAK_(1),and p-p38 in the heart tissue of the CHF rat model.Conclusion:These findings indicate that QXHLF has a therapeutic effect on CHF by inhibiting the p38-MAPK signaling pathway,reducing myocardial fibrosis,preventing apoptosis,inhibiting cell proliferation,and restoring myocardial injury.展开更多
The R F first order second moment method will produce more error for calculating the reliability of welded engineering pipe structures when the failure function is seriously nonlinear and the random variables don...The R F first order second moment method will produce more error for calculating the reliability of welded engineering pipe structures when the failure function is seriously nonlinear and the random variables don′t serve as normal distribution. In order to increase the computing accuracy of reliability, an improved FOSM method is used for calculating the failure probability of welded pipes with flaws in this paper. Because of solving the problems of the linear expansion of failure function at the failure point and constructing equivalent normal variables, the new algorithm can greatly improve the calculating accuracy of probability of the welded pipes with cracks. The examples show that this method is simple, efficient and accurate for reliability safety assessment of the welded pipes with cracks. It can save more time than the Monte Carlo method does, so that the improved FOSM method is recommended for engineering reliability safety assessment of the welded pipes with flaws.展开更多
Stress-induced failure is among the most common causes of instability in Canadian deep underground mines.Open stoping is the most widely practiced underground excavation method in these mines,and creates large stopes ...Stress-induced failure is among the most common causes of instability in Canadian deep underground mines.Open stoping is the most widely practiced underground excavation method in these mines,and creates large stopes which are subjected to stress-induced failure.The probability of failure(POF)depends on many factors,of which the geometry of an open stope is especially important.In this study,a methodology is proposed to assess the effect of stope geometrical parameters on the POF,using numerical modelling.Different ranges for each input parameter are defined according to previous surveys on open stope geometry in a number of Canadian underground mines.A Monte-Carlo simulation technique is combined with the finite difference code FLAC3D,to generate model realizations containing stopes with different geometrical features.The probability of failure(POF)for different categories of stope geometry,is calculated by considering two modes of failure;relaxation-related gravity driven(tensile)failure and rock mass brittle failure.The individual and interactive effects of stope geometrical parameters on the POF,are analyzed using a general multi-level factorial design.Finally,mathematical optimization techniques are employed to estimate the most stable stope conditions,by determining the optimal ranges for each stope’s geometrical parameter.展开更多
Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide. Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells ...Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide. Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression. Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases. Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs. Thus, we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9, Tregs and CHF. Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients. Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA), we found that the HDAC9 mRNA expression level in NYHA grade Ⅱ -Ⅲ group were lower than that in NYHA grade IV group. More importantly, the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF), whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF. The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF. Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.展开更多
The structural system failure probability(SFP) is a valuable tool for evaluating the global safety level of concrete gravity dams.Traditional methods for estimating the failure probabilities are based on defined mathe...The structural system failure probability(SFP) is a valuable tool for evaluating the global safety level of concrete gravity dams.Traditional methods for estimating the failure probabilities are based on defined mathematical descriptions,namely,limit state functions of failure modes.Several problems are to be solved in the use of traditional methods for gravity dams.One is how to define the limit state function really reflecting the mechanical mechanism of the failure mode;another is how to understand the relationship among failure modes and enable the probability of the whole structure to be determined.Performing SFP analysis for a gravity dam system is a challenging task.This work proposes a novel nonlinear finite-element-based SFP analysis method for gravity dams.Firstly,reasonable nonlinear constitutive modes for dam concrete,concrete/rock interface and rock foundation are respectively introduced according to corresponding mechanical mechanisms.Meanwhile the response surface(RS) method is used to model limit state functions of main failure modes through the Monte Carlo(MC) simulation results of the dam-interface-foundation interaction finite element(FE) analysis.Secondly,a numerical SFP method is studied to compute the probabilities of several failure modes efficiently by simple matrix integration operations.Then,the nonlinear FE-based SFP analysis methodology for gravity dams considering correlated failure modes with the additional sensitivity analysis is proposed.Finally,a comprehensive computational platform for interfacing the proposed method with the open source FE code Code Aster is developed via a freely available MATLAB software tool(FERUM).This methodology is demonstrated by a case study of an existing gravity dam analysis,in which the dominant failure modes are identified,and the corresponding performance functions are established.Then,the dam failure probability of the structural system is obtained by the proposed method considering the correlation relationship of main failure modes on the basis of the mechanical mechanism analysis with the MC-FE simulations.展开更多
SoftwareDefined Networks(SDN)introduced better network management by decoupling control and data plane.However,communication reliability is the desired property in computer networks.The frequency of communication link...SoftwareDefined Networks(SDN)introduced better network management by decoupling control and data plane.However,communication reliability is the desired property in computer networks.The frequency of communication link failure degrades network performance,and service disruptions are likely to occur.Emerging network applications,such as delaysensitive applications,suffer packet loss with higher Round Trip Time(RTT).Several failure recovery schemes have been proposed to address link failure recovery issues in SDN.However,these schemes have various weaknesses,which may not always guarantee service availability.Communication paths differ in their roles;some paths are critical because of the higher frequency usage.Other paths frequently share links between primary and backup.Rerouting the affected flows after failure occurrences without investigating the path roles can lead to post-recovery congestion with packet loss and system throughput.Therefore,there is a lack of studies to incorporate path criticality and residual path capacity to reroute the affected flows in case of link failure.This paper proposed Reliable Failure Restoration with Congestion Aware for SDN to select the reliable backup path that decreases packet loss and RTT,increasing network throughput while minimizing post-recovery congestion.The affected flows are redirected through a path with minimal risk of failure,while Bayesian probability is used to predict post-recovery congestion.Both the former and latter path with a minimal score is chosen.The simulation results improved throughput by(45%),reduced packet losses(87%),and lowered RTT(89%)compared to benchmarking works.展开更多
Methodology for the reliability analysis of hydraulic gravity dam is the key technology in current hydropower construction.Reliability analysis for the dynamical dam safety should be divided into two phases:failure mo...Methodology for the reliability analysis of hydraulic gravity dam is the key technology in current hydropower construction.Reliability analysis for the dynamical dam safety should be divided into two phases:failure mode identification and the calculation of the failure probability.Both of them are studied based on the mathematical statistics and structure reliability theory considering two kinds of uncertainty characters(earthquake variability and material randomness).Firstly,failure mode identification method is established based on the dynamical limit state system and verified through example of Koyna Dam so that the statistical law of progressive failure process in dam body are revealed; Secondly,for the calculation of the failure probability,mathematical model and formula are established according to the characteristics of gravity dam,which include three levels,that is element failure,path failure and system failure.A case study is presented to show the practical application of theoretical method and results of these methods.展开更多
Based on Bishop's model and by applying the first and second order mean deviations method, an approximative solution method for the first and second order partial derivatives of functional function was deduced acc...Based on Bishop's model and by applying the first and second order mean deviations method, an approximative solution method for the first and second order partial derivatives of functional function was deduced according to numerical analysis theory. After complicated multi-independent variables implicit functional function was simplified to be a single independent variable implicit function and rule of calculating derivative for composite function was combined with principle of the mean deviations method, an approximative solution format of implicit functional function was established through Taylor expansion series and iterative solution approach of reliability degree index was given synchronously. An engineering example was analyzed by the method. The result shows its absolute error is only 0.78% as compared with accurate solution.展开更多
Engineering structures may be exposed to one or more extreme hazards during their life-cycles.Current structural design specifications usually treat multiple hazards separately in designing structures and there is a l...Engineering structures may be exposed to one or more extreme hazards during their life-cycles.Current structural design specifications usually treat multiple hazards separately in designing structures and there is a limited probabilistic basis on extreme load combinations.Additionally,the performance of engineering structures will be deteriorated by the aggressive environments during their service periods,such as chloride attack,concrete carbonation,and wind-induced fatigue.This study presents a probabilistic methodology to assess the time-dependent failure probability of RC bridges with chloride-induced corrosion under the multiple hazards of earthquakes and strong winds.The loss of cross-section area of reinforcements and the reduction in strength of reinforcing steel and concrete cover induced by the chloride attack are considered.Moreover,the Poisson model is employed to obtain the occurrence probabilities of the individual and concurrent earthquake and strong wind events.The convolution integral is used to determine the joint probability distribution of combined load effects under simultaneous earthquakes and strong winds.Numerical results indicate that the structural failure probability under multiple hazards increases significantly during the bridge′s life-cycle due to the chloride corrosion effect.The contribution of each hazard event on the total structural failure probability varies with time.Thus,neglecting the combined influences of multiple hazards and chloride-induced corrosion may bring erroneous predictions in failure probability estimates of RC bridges.展开更多
The uncertainties of some key influence factors on coal crushing,such as rock strength,pore pressure and magnitude and orientation of three principal stresses,can lead to the uncertainty of coal crushing and make it v...The uncertainties of some key influence factors on coal crushing,such as rock strength,pore pressure and magnitude and orientation of three principal stresses,can lead to the uncertainty of coal crushing and make it very difficult to predict coal crushing under the condition of in-situ reservoir.To account for the uncertainty involved in coal crushing,a deterministic prediction model of coal crushing under the condition of in-situ reservoir was established based on Hoek-Brown criterion.Through this model,key influence factors on coal crushing were selected as random variables and the corresponding probability density functions were determined by combining experiment data and Latin Hypercube method.Then,to analyze the uncertainty of coal crushing,the firstorder second-moment method and the presented model were combined to address the failure probability involved in coal crushing analysis.Using the presented method,the failure probabilities of coal crushing were analyzed for WS5-5 well in Ningwu basin,China,and the relations between failure probability and the influence factors were furthermore discussed.The results show that the failure probabilities of WS5-5 CBM well vary from 0.6 to 1.0; moreover,for the coal seam section at depth of 784.3-785 m,the failure probabilities are equal to 1,which fit well with experiment results; the failure probability of coal crushing presents nonlinear growth relationships with the increase of principal stress difference and the decrease of uniaxial compressive strength.展开更多
Systemreliability sensitivity analysis becomes difficult due to involving the issues of the correlation between failure modes whether using analytic method or numerical simulation methods.A fast conditional reduction ...Systemreliability sensitivity analysis becomes difficult due to involving the issues of the correlation between failure modes whether using analytic method or numerical simulation methods.A fast conditional reduction method based on conditional probability theory is proposed to solve the sensitivity analysis based on the approximate analytic method.The relevant concepts are introduced to characterize the correlation between failure modes by the reliability index and correlation coefficient,and conditional normal fractile the for the multi-dimensional conditional failure analysis is proposed based on the two-dimensional normal distribution function.Thus the calculation of system failure probability can be represented as a summation of conditional probability terms,which is convenient to be computed by iterative solving sequentially.Further the system sensitivity solution is transformed into the derivation process of the failure probability correlation coefficient of each failure mode.Numerical examples results show that it is feasible to apply the idea of failure mode relevancy to failure probability sensitivity analysis,and it can avoid multi-dimension integral calculation and reduce complexity and difficulty.Compared with the product of conditional marginalmethod,a wider value range of correlation coefficient for reliability analysis is confirmed and an acceptable accuracy can be obtained with less computational cost.展开更多
A general failure probability simulation and deviation evaluation methods were presented for fuzzy safety state and fuzzy failure state. And the corresponding number integral method was simultaneously established. As ...A general failure probability simulation and deviation evaluation methods were presented for fuzzy safety state and fuzzy failure state. And the corresponding number integral method was simultaneously established. As the distribution of state variable and the membership of the state variable to the fuzzy safety set were normal, the general failure probability of the single failure mode had precise analytic solution, which was used to verify the precision of the presented methods. The results show that the evaluation of the simulation method convergences to the analytic solution with the number increase of the sampling. The above methods for the single failure mode was extended to the multi-mode by the expansion and probability principles. The presented methods were applied to the engineering problem. For the number of significant mode is not too many, the high precision solution can be given by the presented number simulation and number integral methods, which is illustrated by the engineering examples. In addition, the application scope of the methods was discussed.展开更多
A more accurate determination for the Probability of Failure on Demand(PFD)of the Safety Instrumented System(SIS)contributes to more SIS realiability,thereby ensuring more safety and lower cost.IEC 61508 and ISA TR.84...A more accurate determination for the Probability of Failure on Demand(PFD)of the Safety Instrumented System(SIS)contributes to more SIS realiability,thereby ensuring more safety and lower cost.IEC 61508 and ISA TR.84.02 provide the PFD detemination formulas.However,these formulas suffer from an uncertaity issue due to the inclusion of uncertainty sources,which,including high redundant systems architectures,cannot be assessed,have perfect proof test assumption,and are neglegted in partial stroke testing(PST)of impact on the system PFD.On the other hand,determining the values of PFD variables to achieve the target risk reduction involves daunting efforts and consumes time.This paper proposes a new approach for system PFD determination and PFD variables optimization that contributes to reduce the uncertainty problem.A higher redundant system can be assessed by generalizing the PFD formula into KooN architecture without neglecting the diagnostic coverage factor(DC)and common cause failures(CCF).In order to simulate the proof test effectiveness,the Proof Test Coverage(PTC)factor has been incorporated into the formula.Additionally,the system PFD value has been improved by incorporating PST for the final control element into the formula.The new developed formula is modelled using the Genetic Algorithm(GA)artificial technique.The GA model saves time and effort to examine system PFD and estimate near optimal values for PFD variables.The proposed model has been applicated on SIS design for crude oil test separator using MATLAB.The comparison between the proposed model and PFD formulas provided by IEC 61508 and ISA TR.84.02 showed that the proposed GA model can assess any system structure and simulate industrial reality.Furthermore,the cost and associated implementation testing activities are reduced.展开更多
The zero_failure data research is a new field in the recent years, but it is required urgently in practical projects, so the work has more theory and practical values. In this paper, for zero_failure data (t i,n i...The zero_failure data research is a new field in the recent years, but it is required urgently in practical projects, so the work has more theory and practical values. In this paper, for zero_failure data (t i,n i) at moment t i , if the prior distribution of the failure probability p i=p{T【t i} is quasi_exponential distribution, the author gives the p i Bayesian estimation and hierarchical Bayesian estimation and the reliability under zero_failure date condition is also obtained.展开更多
The current AASHTO load and resistance factor design (LRFD) guidelines are formulated based on bridge reliability, which interprets traditional design safety factors into more rigorously deduced factors based on the...The current AASHTO load and resistance factor design (LRFD) guidelines are formulated based on bridge reliability, which interprets traditional design safety factors into more rigorously deduced factors based on the theory of probability. This is a major advancement in bridge design specifications. However, LRFD is only calibrated for dead and live loads. In cases when extreme loads are significant, they need to be individually assessed. Combining regular loads with extreme loads has been a major challenge, mainly because the extreme loads are time variables and cannot be directly combined with time invariant loads to formulate the probability of structural failure. To overcome these difficulties, this paper suggests a methodology of comprehensive reliability, by introducing the concept of partial failure probability to separate the loads so that each individual load combination under a certain condition can be approximated as time invariant. Based on these conditions, the extreme loads (also referred to as multiple hazard or MH loads) can be broken down into single effects. In Part II of this paper, a further breakdown of these conditional occurrence probabilities into pure conditions is discussed by using a live truck and earthquake loads on a bridge as an example. There are three major steps in establishing load factors from MH load distributions: (1) formulate the failure probabilities; (2) normalize various load distributions; and (3) establish design limit state equations. This paper describes the formulation of the failure probabilities of single and combined loads.展开更多
In this paper, an estimation method for reliability parameter in the case of zero-failuare data-synthetic estimation method is given. For zero-failure data of double-parameter exponential distribution, a hierarchical ...In this paper, an estimation method for reliability parameter in the case of zero-failuare data-synthetic estimation method is given. For zero-failure data of double-parameter exponential distribution, a hierarchical Bayesian estimation of the failure probability is presented. After failure information is introduced, hierarchical Bayesian estimation and synthetic estimation of the failure probability, as well as synthetic estimation of reliability are given. Calculation and analysis are performed regarding practical problems in case that life distribution of an engine obeys double-parameter exponential distribution.展开更多
基金supported by the National Natural Science Foundation of China(82174206)National Natural Science Foundation of China,International(Regional)Cooperation and Exchange Program(82261138556).
文摘Objective:To elucidate the effects of chlorogenic acid(CGA),a bioactive polyphenol compound prevalent in traditional Chinese medicine and various foods,including Lonicera japonica Thunb.(Jin Yin Hua),Eucommia ulmoides Oliv.(Du Zhong Ye),tea,and coffee,on cardiomyocyte ferroptosis and heart failure.Methods: We assessed the effect of CGA on cardiac function using a mouse model of heart failure induced by transverse aortic constriction(TAC).These indicators included the left ventricular ejection fraction(LVEF),fractional shortening(LVFS),end-systolic volume(LVESV),end-diastolic volume(LVEDV),end-systolic diameter(LVESD),and end-diastolic diameter(LVEDD).An isoprenaline hydrochloride(ISO)-induced H9c2 cardiomyocyte cell model was also established,and the cells were treated with various concentrations of CGA.To assess the effect of CGA on ferroptosis in cardiomyocytes,we measured cell viability and evaluated the levels of intracellular reactive oxygen species(ROS),ferrous ions(Fe^(2+)),and lipid peroxidation using fluorescent staining.To clarify the ferroptosis signaling pathway regulated by CGA,western blotting was used to examine the expression of ferroptosis biomarkers,specifically solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),in H9c2 cardiomyocytes and mouse myocardial tissues.Results: CGA significantly enhanced cardiac performance indices such as LVEF,LVFS,LVESV,LVEDV,LVESD,and LVEDD.H9c2 cardiomyocytes exposed to ISO showed decreased cell viability and increased ROS levels,Fe^(2+)content,and lipid peroxidation levels.However,CGA treatment significantly ameliorated these changes.Additionally,in both H9c2 cardiomyocytes and myocardial tissue obtained from mice with TAC,CGA increased the expression of ferroptosis-related proteins,including SLC7A11 and GPX4.Conclusion: CGA has the potential to enhance cardiac function and diminish lipid peroxidation and ROS levels in cardiomyocytes via the SLC7A11/GPX4 signaling pathway.This process alleviates ferroptosis in cardiomyocytes.These results provide new insights into the clinical use of CGA and the management of heart failure.
基金the Science and Technology Research Project of the Education Department of Jilin Province(No.JJKH20220862KJ)the Jilin Province higher education teaching reform research topic(No.20224BRFI7U003M)National Natural Science Foundation of China(No.82074324).
文摘Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failure(CHF).Methods:In vitro,the H_(9)C_(2) cell model was induced by ANGII,and cell proliferation and related protein expression were detected by Cell Counting Kit-8 and Western blot.In vivo,A rat model of CHF was prepared by ligation of the left anterior descending coronary artery.The effects of QXHLF on cardiac function in CHF rats were evaluated by cardiac index,hemodynamic changes,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,immunohistochemistry,Western blot and RT-PCR.The expression of pro-apoptotic factors and anti-apoptotic factors,as well as TGFβ1,p-p38,TAK 1 mRNA,and protein,were detected.Results:In vitro,QXHLF has a significant inhibitory effect on the proliferation of H_(9)C_(2) cells.QXHLF can reduce the expression levels of TAK 1,TGFβ1,p-p38,Caspase3 and BAX proteins in H_(9)C_(2) cells,and increase the expression level of BCL_(2) protein.In vivo,QXHLF has the potential to increase left ventricular systolic pressure,m aximum rate of change in left ventricular pressure while decreasing left ventricular end diastolic pressure,and inhibiting the serum levels of brain natriuretic peptide.Moreover,QXHLF exhibits significant improvements in the pathological alterations of myocardial cells and fibers in CHF rats,leading to enhanced myocardial tissue morphology and notable advantages in combating myocardial fibrosis.QXHLF can reduce the levels of BAX and Caspase3 and up-regulate the expression of BCL_(2),thereby inhibiting cardiomyocyte apoptosis.Furthermore,QXHLF demonstrates inhibitory effects on the mRNA and protein expression levels of TGFβ_(1),TAK_(1),and p-p38 in the heart tissue of the CHF rat model.Conclusion:These findings indicate that QXHLF has a therapeutic effect on CHF by inhibiting the p38-MAPK signaling pathway,reducing myocardial fibrosis,preventing apoptosis,inhibiting cell proliferation,and restoring myocardial injury.
文摘The R F first order second moment method will produce more error for calculating the reliability of welded engineering pipe structures when the failure function is seriously nonlinear and the random variables don′t serve as normal distribution. In order to increase the computing accuracy of reliability, an improved FOSM method is used for calculating the failure probability of welded pipes with flaws in this paper. Because of solving the problems of the linear expansion of failure function at the failure point and constructing equivalent normal variables, the new algorithm can greatly improve the calculating accuracy of probability of the welded pipes with cracks. The examples show that this method is simple, efficient and accurate for reliability safety assessment of the welded pipes with cracks. It can save more time than the Monte Carlo method does, so that the improved FOSM method is recommended for engineering reliability safety assessment of the welded pipes with flaws.
基金funded by a grant from Natural Sciences and Engineering Research Council of Canada (NSERC)the authors would like to acknowledge the Niobec mine (Saint-Honoré, QuébecQuébec)
文摘Stress-induced failure is among the most common causes of instability in Canadian deep underground mines.Open stoping is the most widely practiced underground excavation method in these mines,and creates large stopes which are subjected to stress-induced failure.The probability of failure(POF)depends on many factors,of which the geometry of an open stope is especially important.In this study,a methodology is proposed to assess the effect of stope geometrical parameters on the POF,using numerical modelling.Different ranges for each input parameter are defined according to previous surveys on open stope geometry in a number of Canadian underground mines.A Monte-Carlo simulation technique is combined with the finite difference code FLAC3D,to generate model realizations containing stopes with different geometrical features.The probability of failure(POF)for different categories of stope geometry,is calculated by considering two modes of failure;relaxation-related gravity driven(tensile)failure and rock mass brittle failure.The individual and interactive effects of stope geometrical parameters on the POF,are analyzed using a general multi-level factorial design.Finally,mathematical optimization techniques are employed to estimate the most stable stope conditions,by determining the optimal ranges for each stope’s geometrical parameter.
文摘Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide. Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression. Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases. Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs. Thus, we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9, Tregs and CHF. Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients. Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA), we found that the HDAC9 mRNA expression level in NYHA grade Ⅱ -Ⅲ group were lower than that in NYHA grade IV group. More importantly, the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF), whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF. The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF. Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.
基金Projects(51409167,51139001,51179066)supported by the National Natural Science Foundation of ChinaProjects(201401022,201501036)supported by the Ministry of Water Resources Public Welfare Industry Research Special Fund,ChinaProjects(GG201532,GG201546)supported by the Scientific and Technological Research for Water Conservancy,Henan Province,China
文摘The structural system failure probability(SFP) is a valuable tool for evaluating the global safety level of concrete gravity dams.Traditional methods for estimating the failure probabilities are based on defined mathematical descriptions,namely,limit state functions of failure modes.Several problems are to be solved in the use of traditional methods for gravity dams.One is how to define the limit state function really reflecting the mechanical mechanism of the failure mode;another is how to understand the relationship among failure modes and enable the probability of the whole structure to be determined.Performing SFP analysis for a gravity dam system is a challenging task.This work proposes a novel nonlinear finite-element-based SFP analysis method for gravity dams.Firstly,reasonable nonlinear constitutive modes for dam concrete,concrete/rock interface and rock foundation are respectively introduced according to corresponding mechanical mechanisms.Meanwhile the response surface(RS) method is used to model limit state functions of main failure modes through the Monte Carlo(MC) simulation results of the dam-interface-foundation interaction finite element(FE) analysis.Secondly,a numerical SFP method is studied to compute the probabilities of several failure modes efficiently by simple matrix integration operations.Then,the nonlinear FE-based SFP analysis methodology for gravity dams considering correlated failure modes with the additional sensitivity analysis is proposed.Finally,a comprehensive computational platform for interfacing the proposed method with the open source FE code Code Aster is developed via a freely available MATLAB software tool(FERUM).This methodology is demonstrated by a case study of an existing gravity dam analysis,in which the dominant failure modes are identified,and the corresponding performance functions are established.Then,the dam failure probability of the structural system is obtained by the proposed method considering the correlation relationship of main failure modes on the basis of the mechanical mechanism analysis with the MC-FE simulations.
基金The authors thank the UTM and Deanship of Scientific Research at King Khalid University for funding this work through grant No R.J130000.7709.4J561Large Groups.(Project under grant number(RGP.2/111/43)).
文摘SoftwareDefined Networks(SDN)introduced better network management by decoupling control and data plane.However,communication reliability is the desired property in computer networks.The frequency of communication link failure degrades network performance,and service disruptions are likely to occur.Emerging network applications,such as delaysensitive applications,suffer packet loss with higher Round Trip Time(RTT).Several failure recovery schemes have been proposed to address link failure recovery issues in SDN.However,these schemes have various weaknesses,which may not always guarantee service availability.Communication paths differ in their roles;some paths are critical because of the higher frequency usage.Other paths frequently share links between primary and backup.Rerouting the affected flows after failure occurrences without investigating the path roles can lead to post-recovery congestion with packet loss and system throughput.Therefore,there is a lack of studies to incorporate path criticality and residual path capacity to reroute the affected flows in case of link failure.This paper proposed Reliable Failure Restoration with Congestion Aware for SDN to select the reliable backup path that decreases packet loss and RTT,increasing network throughput while minimizing post-recovery congestion.The affected flows are redirected through a path with minimal risk of failure,while Bayesian probability is used to predict post-recovery congestion.Both the former and latter path with a minimal score is chosen.The simulation results improved throughput by(45%),reduced packet losses(87%),and lowered RTT(89%)compared to benchmarking works.
基金Projects(51021004,51379141)supported by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China
文摘Methodology for the reliability analysis of hydraulic gravity dam is the key technology in current hydropower construction.Reliability analysis for the dynamical dam safety should be divided into two phases:failure mode identification and the calculation of the failure probability.Both of them are studied based on the mathematical statistics and structure reliability theory considering two kinds of uncertainty characters(earthquake variability and material randomness).Firstly,failure mode identification method is established based on the dynamical limit state system and verified through example of Koyna Dam so that the statistical law of progressive failure process in dam body are revealed; Secondly,for the calculation of the failure probability,mathematical model and formula are established according to the characteristics of gravity dam,which include three levels,that is element failure,path failure and system failure.A case study is presented to show the practical application of theoretical method and results of these methods.
基金Project(50378036) supported by the National Natural Science Foundation of ChinaProject(200503) supported by Foundation of Communications Department of Hunan Province, China
文摘Based on Bishop's model and by applying the first and second order mean deviations method, an approximative solution method for the first and second order partial derivatives of functional function was deduced according to numerical analysis theory. After complicated multi-independent variables implicit functional function was simplified to be a single independent variable implicit function and rule of calculating derivative for composite function was combined with principle of the mean deviations method, an approximative solution format of implicit functional function was established through Taylor expansion series and iterative solution approach of reliability degree index was given synchronously. An engineering example was analyzed by the method. The result shows its absolute error is only 0.78% as compared with accurate solution.
基金Supported by:Fundamental Research Funds for the Central Universities under Grant No.2021QN1022。
文摘Engineering structures may be exposed to one or more extreme hazards during their life-cycles.Current structural design specifications usually treat multiple hazards separately in designing structures and there is a limited probabilistic basis on extreme load combinations.Additionally,the performance of engineering structures will be deteriorated by the aggressive environments during their service periods,such as chloride attack,concrete carbonation,and wind-induced fatigue.This study presents a probabilistic methodology to assess the time-dependent failure probability of RC bridges with chloride-induced corrosion under the multiple hazards of earthquakes and strong winds.The loss of cross-section area of reinforcements and the reduction in strength of reinforcing steel and concrete cover induced by the chloride attack are considered.Moreover,the Poisson model is employed to obtain the occurrence probabilities of the individual and concurrent earthquake and strong wind events.The convolution integral is used to determine the joint probability distribution of combined load effects under simultaneous earthquakes and strong winds.Numerical results indicate that the structural failure probability under multiple hazards increases significantly during the bridge′s life-cycle due to the chloride corrosion effect.The contribution of each hazard event on the total structural failure probability varies with time.Thus,neglecting the combined influences of multiple hazards and chloride-induced corrosion may bring erroneous predictions in failure probability estimates of RC bridges.
基金Project(51204201)supported by the National Natural Science Foundation of ChinaProjects(2011ZX05036-001,2011ZX05037-004)supported by the National Science and Technology Major Program of China+1 种基金Project(2010CB226706)supported by the National Basic Research Program of ChinaProject(11CX04050A)supported by the Fundamental Research Funds for the Central Universities of China
文摘The uncertainties of some key influence factors on coal crushing,such as rock strength,pore pressure and magnitude and orientation of three principal stresses,can lead to the uncertainty of coal crushing and make it very difficult to predict coal crushing under the condition of in-situ reservoir.To account for the uncertainty involved in coal crushing,a deterministic prediction model of coal crushing under the condition of in-situ reservoir was established based on Hoek-Brown criterion.Through this model,key influence factors on coal crushing were selected as random variables and the corresponding probability density functions were determined by combining experiment data and Latin Hypercube method.Then,to analyze the uncertainty of coal crushing,the firstorder second-moment method and the presented model were combined to address the failure probability involved in coal crushing analysis.Using the presented method,the failure probabilities of coal crushing were analyzed for WS5-5 well in Ningwu basin,China,and the relations between failure probability and the influence factors were furthermore discussed.The results show that the failure probabilities of WS5-5 CBM well vary from 0.6 to 1.0; moreover,for the coal seam section at depth of 784.3-785 m,the failure probabilities are equal to 1,which fit well with experiment results; the failure probability of coal crushing presents nonlinear growth relationships with the increase of principal stress difference and the decrease of uniaxial compressive strength.
基金This research is supported by National Key Research and Development Project(Grant Number 2019YFD0901002)Also Natural Science Foundation of Liaoning Province(Grant Number 20170540105)Liaoning Province Education Foundation(Grant Number JL201913)are gratefully acknowledged.
文摘Systemreliability sensitivity analysis becomes difficult due to involving the issues of the correlation between failure modes whether using analytic method or numerical simulation methods.A fast conditional reduction method based on conditional probability theory is proposed to solve the sensitivity analysis based on the approximate analytic method.The relevant concepts are introduced to characterize the correlation between failure modes by the reliability index and correlation coefficient,and conditional normal fractile the for the multi-dimensional conditional failure analysis is proposed based on the two-dimensional normal distribution function.Thus the calculation of system failure probability can be represented as a summation of conditional probability terms,which is convenient to be computed by iterative solving sequentially.Further the system sensitivity solution is transformed into the derivation process of the failure probability correlation coefficient of each failure mode.Numerical examples results show that it is feasible to apply the idea of failure mode relevancy to failure probability sensitivity analysis,and it can avoid multi-dimension integral calculation and reduce complexity and difficulty.Compared with the product of conditional marginalmethod,a wider value range of correlation coefficient for reliability analysis is confirmed and an acceptable accuracy can be obtained with less computational cost.
文摘A general failure probability simulation and deviation evaluation methods were presented for fuzzy safety state and fuzzy failure state. And the corresponding number integral method was simultaneously established. As the distribution of state variable and the membership of the state variable to the fuzzy safety set were normal, the general failure probability of the single failure mode had precise analytic solution, which was used to verify the precision of the presented methods. The results show that the evaluation of the simulation method convergences to the analytic solution with the number increase of the sampling. The above methods for the single failure mode was extended to the multi-mode by the expansion and probability principles. The presented methods were applied to the engineering problem. For the number of significant mode is not too many, the high precision solution can be given by the presented number simulation and number integral methods, which is illustrated by the engineering examples. In addition, the application scope of the methods was discussed.
文摘A more accurate determination for the Probability of Failure on Demand(PFD)of the Safety Instrumented System(SIS)contributes to more SIS realiability,thereby ensuring more safety and lower cost.IEC 61508 and ISA TR.84.02 provide the PFD detemination formulas.However,these formulas suffer from an uncertaity issue due to the inclusion of uncertainty sources,which,including high redundant systems architectures,cannot be assessed,have perfect proof test assumption,and are neglegted in partial stroke testing(PST)of impact on the system PFD.On the other hand,determining the values of PFD variables to achieve the target risk reduction involves daunting efforts and consumes time.This paper proposes a new approach for system PFD determination and PFD variables optimization that contributes to reduce the uncertainty problem.A higher redundant system can be assessed by generalizing the PFD formula into KooN architecture without neglecting the diagnostic coverage factor(DC)and common cause failures(CCF).In order to simulate the proof test effectiveness,the Proof Test Coverage(PTC)factor has been incorporated into the formula.Additionally,the system PFD value has been improved by incorporating PST for the final control element into the formula.The new developed formula is modelled using the Genetic Algorithm(GA)artificial technique.The GA model saves time and effort to examine system PFD and estimate near optimal values for PFD variables.The proposed model has been applicated on SIS design for crude oil test separator using MATLAB.The comparison between the proposed model and PFD formulas provided by IEC 61508 and ISA TR.84.02 showed that the proposed GA model can assess any system structure and simulate industrial reality.Furthermore,the cost and associated implementation testing activities are reduced.
文摘The zero_failure data research is a new field in the recent years, but it is required urgently in practical projects, so the work has more theory and practical values. In this paper, for zero_failure data (t i,n i) at moment t i , if the prior distribution of the failure probability p i=p{T【t i} is quasi_exponential distribution, the author gives the p i Bayesian estimation and hierarchical Bayesian estimation and the reliability under zero_failure date condition is also obtained.
基金Federal Highway Administration at the University at Buffalo Under Contract Number DTFH61-08-C-00012
文摘The current AASHTO load and resistance factor design (LRFD) guidelines are formulated based on bridge reliability, which interprets traditional design safety factors into more rigorously deduced factors based on the theory of probability. This is a major advancement in bridge design specifications. However, LRFD is only calibrated for dead and live loads. In cases when extreme loads are significant, they need to be individually assessed. Combining regular loads with extreme loads has been a major challenge, mainly because the extreme loads are time variables and cannot be directly combined with time invariant loads to formulate the probability of structural failure. To overcome these difficulties, this paper suggests a methodology of comprehensive reliability, by introducing the concept of partial failure probability to separate the loads so that each individual load combination under a certain condition can be approximated as time invariant. Based on these conditions, the extreme loads (also referred to as multiple hazard or MH loads) can be broken down into single effects. In Part II of this paper, a further breakdown of these conditional occurrence probabilities into pure conditions is discussed by using a live truck and earthquake loads on a bridge as an example. There are three major steps in establishing load factors from MH load distributions: (1) formulate the failure probabilities; (2) normalize various load distributions; and (3) establish design limit state equations. This paper describes the formulation of the failure probabilities of single and combined loads.
文摘In this paper, an estimation method for reliability parameter in the case of zero-failuare data-synthetic estimation method is given. For zero-failure data of double-parameter exponential distribution, a hierarchical Bayesian estimation of the failure probability is presented. After failure information is introduced, hierarchical Bayesian estimation and synthetic estimation of the failure probability, as well as synthetic estimation of reliability are given. Calculation and analysis are performed regarding practical problems in case that life distribution of an engine obeys double-parameter exponential distribution.