Integrated causal inference modeling uncovers novel causal factors and potential therapeutic targets of Qingjin Yiqi granules for chronic fatigue syndrome

Objective:Chronic fatigue syndrome(CFS)is a prevalent symptom of post-coronavirus disease 2019(COVID-19)and is associated with unclear disease mechanisms.The herbal medicine Qingjin Yiqi granules(QJYQ)constitute a clinically approved formula for treating post-COVID-19;however,its potential as a drug target for treating CFS remains largely unknown.This study aimed to identify novel causal factors for CFS and elucidate the potential targets and pharmacological mechanisms of action of QJYQ in treating CFS.Methods:This prospective cohort analysis included 4,212 adults aged≥65 years who were followed up for 7 years with 435 incident CFS cases.Causal modeling and multivariate logistic regression analysis were performed to identify the potential causal determinants of CFS.A proteome-wide,two-sample Mendelian randomization(MR)analysis was employed to explore the proteins associated with the identified causal factors of CFS,which may serve as potential drug targets.Furthermore,we performed a virtual screening analysis to assess the binding affinity between the bioactive compounds in QJYQ and CFS-associated proteins.Results:Among 4,212 participants(47.5%men)with a median age of 69 years(interquartile range:69–70 years)enrolled in 2004,435 developed CFS by 2011.Causal graph analysis with multivariate logistic regression identified frequent cough(odds ratio:1.74,95%confidence interval[CI]:1.15–2.63)and insomnia(odds ratio:2.59,95%CI:1.77–3.79)as novel causal factors of CFS.Proteome-wide MR analysis revealed that the upregulation of endothelial cell-selective adhesion molecule(ESAM)was causally linked to both chronic cough(odds ratio:1.019,95%CI:1.012–1.026,P=2.75 e^(−05))and insomnia(odds ratio:1.015,95%CI:1.008–1.022,P=4.40 e^(−08))in CFS.The major bioactive compounds of QJYQ,ginsenoside Rb2(docking score:−6.03)and RG4(docking score:−6.15),bound to ESAM with high affinity based on virtual screening.Conclusions:Our integrated analytical framework combining epidemiological,genetic,and in silico data provides a novel strategy for elucidating complex disease mechanisms,such as CFS,and informing models of action of traditional Chinese medicines,such as QJYQ.Further validation in animal models is warranted to confirm the potential pharmacological effects of QJYQ on ESAM and as a treatment for CFS.

The Performance of Small Diameter Aluminum Light Support Structures Containing Handholes under Cyclic Fatigue

Aluminum light poles play a pivotal role in modern infrastructure, ensuring proper illumination along highways and in populated areas during nighttime. These poles typically feature handholes near their bases, providing access to electrical wiring for installation and maintenance. While essential for functionality, these handholes introduce a vulnerability to the overall structure, making them a potential failure point. Although prior research and analyses on aluminum light poles have been conducted, the behavior of smaller diameter poles containing handholes remains unexplored. Recognizing this need, a research team at the University of Akron undertook a comprehensive experimental program involving aluminum light poles with handholes containing welded inserts in order to gain a better understanding of their fatigue life, mechanical behavior, and failure mechanisms. The research involved testing seven large-scale aluminum light poles each 8-inch diameter, with two separate handholes. These handholes included a reinforcement that was welded to the poles. Finite Element Analysis (FEA), statistical analysis, and comparison analysis with their large counterparts (10-inch diameter) were used to augment the experimental results. The results revealed two distinct failure modes: progressive crack propagation leading to ultimate failure, and rupture of the pole near the weld initiation/termination site around the handhole. The comparison analysis indicated that the 8-inch diameter specimens exhibited an average fatigue life exceeding that of their 10-inch counterparts by an average of 30.7%. The experimental results were plotted alongside the fatigue detail classifications outlined in the Aluminum Design Manual (ADM), enhancing understanding of the fatigue detail category of the respective poles/handholes.

Ice-Induced Fatigue Analysis by Spectral Approach for Offshore Jacket Platforms with Ice-Breaking Cones

The spectral methods and ice-induced fatigue analysis are discussed based on Miner＇s linear cumulative fatigue hypothesis and S-N curve data. According to the long-term data of full-scale tests on the platforms in the Bohai Sea, the ice force spectrum of conical structures and the fatigue environmental model are established. Moreover, the finite element model of JZ20-2MSW platform, an example of ice-induced fatigue analysis, is built with ANSYS software. The mode analysis and dynamic analysis in frequency domain under all kinds of ice fatigue work conditions are carded on, and the fatigue life of the structure is estimated in detail. The methods in this paper can be helpful in ice-induced fatigue analysis of ice-resistant platforms.

Fatigue Analysis of the Taut-Wire Mooring System Applied for Deep Waters

Precisely predicting the fatigue life of taut-wire mooring systems has become an interesting and important problem for scientists and engineers since there are still difficulties in the inspection and maintenance of mooring lines in a rough sea environment especially in deep waters. In this paper, a comprehensive fatigue analysis is performed for a polyester taut-wire mooring system of an FPSO based on the time domain dynamic theory, rainflow cycle counting method and linear damage accumulation rule of Palmgren-Miner. Three influential factors in the fatigue analysis including the pre-tension, dynamic stiffness and T-N curve are investigated in detail. Two polyester T-N curves, one is from the DNV- 0S-E301 and the other is from the API-RP-2SM, are adopted in the calculation. The fatigue analysis of the mooting system after one-line failure is also carried out. The calculation results indicate that the fatigue life is significantly affected by the T-N curve. The fatigue life decreases with increasing pre-tension, and is largely reduced if taking into account the dynamic stiffness caused by cyclic loading. The analysis also proves that one-line failure has remarkable effects on the fatigue lives of other mooting lines. The present parametric and comparative study is believed to be meaningful to further understanding of the taut-wire mooting system for deepwater applications.

Fatigue Characteristic Analysis of Deepwater Steel Catenary Risers at the Touchdown Point

This paper presents fatigue characteristic analysis of a deepwater steel catenary riser （SCR） under ambient excitations. The SCR involves complex nonlinear dynamic behaviors, especially at the touchdown point （TDP） where the riser first touches the seafloor. Owing to the significant interaction with soil, the touchdown zone is difficnlt to be modeled. Based on Lumped-Mass method and P-y curve, nonlinear springs are used to simulate the SCR-seabed coupled interaction. In case studies, an SCR＇s dynamic features have been obtained by transient analysis and the structure fatigue assessment has been carried out by S-N approach. The comparative analysis shows that the TDP is the key location where soil-riser interaction rises steeply and minimum fatigue life occurs. Parameters such as ocean environment loads, vessel motions, riser material and geometric parameters are discussed. The results indicate that the vessel motion is the principal factor for the structure fatigue life distribution.

Enhanced Multi-Layer Fatigue-Analysis Approach for Unbonded Flexible Risers

This paper proposes an enhanced approach for evaluating the fatigue life of each metallic layer of unbonded flexible risers. Owing to the complex structure of unbonded flexible risers and the nonlinearity of the system, particularly in the critical touchdown zone, the traditional method is insufficient for accurately evaluating the fatigue life of these risers. The main challenge lies in the transposition from global to local analyses, which is a key stage for the fatigue analysis of flexible pipes owing to their complex structure. The new enhanced approach derives a multi-layer stress-decomposition method to meet this challenge. In this study, a numerical model validated experimentally is used to demonstrate the accuracy of the stress-decomposition method. And a numerical case is studied to validate the proposed approach. The results demonstrate that the multi-layer stress-decomposition method is accurate, and the fatigue lives of the metallic layers predicted by the enhanced multi-layer analysis approach are rational. The proposed fatigue-analysis approach provides a practical and reasonable method for predicting fatigue life in the design of unbonded flexible risers.

Study on the application of spectral fatigue analysis

Fatigue failure has long been an important issue for ships and offshore structures. Among the numerous methods for predicting fatigue life, the spectral method is accepted as the most reliable. Although the theory behind spectral analysis is straight-forward, the analysis itself is complicated and time-consuming because it is closely related to critical technical details such as the application of fatigue loading (wave pressures and the inertial forces due to cargoes), the extraction of the stress, and the calculation of stress RAO. Here, four key technical details-loading application, displacement boundary condition, the calculation of stress RAO, and the extraction of the fatigue stress-are discussed thoroughly. For each aspect, a resolution is presented based on the finite element pre-and post-processing software MSC/PATRAN or FE solver MSC/NASTRAN. The resolutions are effective and efficient, which can help engineers perform spectral fatigue analysis accurately and faster.

sEMG Feature Analysis on Forearm Muscle Fatigue During Isometric Contractions

In order to detect and assess the muscle fatigue state with the surface electromyography(sEMG) characteristic parameters,this paper carried out a series of isometric contraction experiments to induce the fatigue on the forearm muscles from four subjects,and recorded the sEMG signals of the flexor carpi ulnaris.sEMG's median frequency(MDF) and mean frequency(MF) were extracted by short term Fourier transform(STFT),and the root mean square(RMS) of wavelet coefficients in the frequency band of 5—45 Hz was obtained by continuous wavelet transform(CWT).The results demonstrate that both MDF and MF show downward trends within 1 min; however,RMS shows an upward trend within the same time.The three parameters are closely correlated with absolute values of mean correlation coefficients greater than 0.8.It is suggested that the three parameters above can be used as reliable indicators to evaluate the level of muscle fatigue during isometric contractions.

Analysis and Comparison of Safety and Fatigue Comfort of Postal Bicycles Based on Finite Element Method and sEMG

The safety and the fatigue comfort were compared between a domestic and a Japanese postal bicycle. Firstly, the fatigue comfort of these two kinds of bicycles was evaluated by surface electromyographic signal (sEMG) experiment, in which human lower limb muscle groups were research objects, and the average EMG (AEMG) index and median frequency (MF) were chosen as the evaluation indexes. Secondly, the safety of these two kinds of bicycle frames was analyzed and compared by using the finite element analysis. The results show that the riding fatigue comfort of the Japanese postal bicycle is better, and the Japanese postal bicycle frame is more safe and reasonable although both the postal bicycles meet the requirement for strength. Finally, based on the above analysis, the frame structure and related parameters of the domestic postal bicycle were improved with reference to the Japanese postal bicycle and biomechanics theory.

Thermal-Mechanical Fatigue Behavior and Life Analysis of Cast Ni-base Superalloy K417

In-phase (IP) and out-of-phase (OP) thermal-mechanical fatigue (TMF) behavior of cast Ni-base superalloy K417 was studied. All experiments were carried out under total strain control with temperature cycling between 400-850℃. Both in-phase and out-of-phase TMF specimens exhibited cyclic hardening followed by cyclic softening at the minimum temperature. Besides, they cyclically hardened in the early stage of life followed by cyclic softening at the maximum temperature. OP TMF life was longer than that of IP TMF. Various damage mechanisms operating in different controlled strain ranges and phasing were discussed. A few life prediction methods for isothermal fatigue were used to handle TMF fatigue and their applicability to superalloy K417 was evaluated. The SEM analysis of the fracture surface showed that transgranular fracture was the principal cracking mode for both IP and OP TMF. Oxidation was the main damage mechanism in causing shorter fatigue life for IP TMF compared with OP TMF.

RELIABILITY ANALYSIS FOR AN AERO ENGINE TURBINE DISK UNDER LOW CYCLE FATIGUE CONDITION

Reliability analysis methods based on the linear damage accumulation law (LDAL) and load-life interference model are studied in this paper. According to the equal probability rule, the equivalent loads are derived, and the reliability analysis method based on load-life interference model and recurrence formula is constructed. In conjunction with finite element analysis (FEA) program, the reliability of an aero engine turbine disk under low cycle fatigue (LCF) condition has been analyzed. The results show the turbine disk is safety and the above reliability analysis methods are feasible.

Multi-Scale Analysis of Fretting Fatigue in Heterogeneous Materials Using Computational Homogenization

This paper deals with modeling of the phenomenon of fretting fatigue in heterogeneous materials using the multi-scale computational homogenization technique and finite element analysis(FEA).The heterogeneous material for the specimens consists of a single hole model(25% void/cell,16% void/cell and 10% void/cell)and a four-hole model(25%void/cell).Using a representative volume element(RVE),we try to produce the equivalent homogenized properties and work on a homogeneous specimen for the study of fretting fatigue.Next,the fretting fatigue contact problem is performed for 3 new cases of models that consist of a homogeneous and a heterogeneous part(single hole cell)in the contact area.The aim is to analyze the normal and shear stresses of these models and compare them with the results of the corresponding heterogeneous models based on the Direct Numerical Simulation(DNS)method.Finally,by comparing the computational time and%deviations,we draw conclusions about the reliability and effectiveness of the proposed method.

Evaluating ultrasound signals of carbon steel fatigue testing using signal analysis approaches

The application of ultrasound techniques to monitor the condition of structures is becoming more prominent because these techniques can detect the early symptoms of defects such as cracks and other defects.The early detection of defects is of vital importance to avoid major failures with catastrophic consequences.An assessment of an ultrasound technique was used to investigate fatigue damage behaviour.Fatigue tests were performed according to the ASTM E466-96 standard with the attachment of an ultrasound sensor to the test specimen.AISI 1045 carbon steel was used due to its wide application in the automotive industry.A fatigue test was performed under constant loading stress at a sampling frequency of 8 Hz.Two sets of data acquisition systems were used to collect the fatigue strain signals and ultrasound signals.All of the signals were edited and analysed using a signal processing approach.Two methods were used to evaluate the signals,the integrated Kurtosis-based algorithm for z-filter technique(I-kaz) and the short-time Fourier transform(STFT).The fatigue damage behaviour was observed from the initial stage until the last stage of the fatigue test.The results of the I-kaz coefficient and the STFT spectrum were used to explain and describe the behaviour of the fatigue damage.I-kaz coefficients were ranged from 60 to 61 for strain signals and ranged from 5 to 76 for ultrasound signals.I-kaz values tend to be high at failure point due to high amplitude of respective signals.STFT spectrogram displays the colour intensity which represents the damage severity of the strain signals.I-kaz technique is found very useful and capable in assessing both stationary and non-stationary signals while STFT technique is suitable only for non-stationary signals by displaying its spectrogram.

Selection Methodology of High-Cycle Fatigue Analysis Approach for Damage Estimation in Welded Structural Joints

The main purpose of this paper is to provide a summarized general guideline to aid decision making of choosing the type of fatigue analysis approach,best suited for modelling and evaluating high-cycle fatigue damage in welded structural joints.It describes how addition of stress concentration and stress direction information into fatigue assessment methodology affect simulated fatigue damage accumulation results and when it is beneficial or necessary to use a particular fatigue damage estimation approach.The focus is on stress-life curve based approaches,particularly when deciding between variants of nominal,hot-spot or multiaxial fatigue assessment approaches for evaluating fatigue damage within welded joint structures.Evaluation is illustrated through application of proposed methodology to choose and perform fatigue assessment for a non-conventional load-bearing tubular joint structure within a floating lemniscate crane upper arm,which has been observed of being prone to aggressive crack propagation within its welds.Damage within the structure is estimated using two non-optimal fatigue analysis approaches to verify applicability of proposed selection methodology.Results are then summarized through comparative assessment and findings are discussed based on what leads to result changes within each fatigue damage analysis approach.

Nonlinear Dynamic Analysis and Fatigue Study of Steep Wave Risers Under Irregular Loads

As a reliable alternative option for traditional steel catenary risers(SCRs),steep wave risers(SWRs)have been widely applied to deepwater oil and gas production.However,the nonlinear dynamic analysis of SWRs is more complicated than that of traditional SCRs due to their special configuration and significant geometric nonlinearity.Moreover,SWRs are highly susceptible to fatigue failure under the combined excitation of irregular waves and top floater motions(TFMs).In this study,considering irregular waves and TFMs,a numerical SWR model with an internal flow is constructed based on the slender rod model and finite element method.The Newmark-βmethod is adopted to solve the dynamic behavior of SWR.Moreover,the Palmgren-Miner rule,a specified S-N curve,and rainflow counting method are applied to estimate the fatigue damage.An efficient numerical computation procedure,i.e.,DRSWR,is programmed with MATLAB in this study.Calculation results are compared with those of OrcaFlex to verify the accuracy of the DRSWR.The nonlinear dynamic response and fatigue damage of an SWR under the combined excitation of irregular waves and TFMs are obtained,and a comprehensive parametric analysis is then conducted.The analysis results show that the buoyancy section undergoes the highest level of stress and fatigue damage under the combined excitation of irregular waves and TFMs.An internal flow with high velocity and high density produces a high level of fatigue damage.The buoyancy factor and length of the buoyancy section should be set moderately to reconcile the reduction of the top tension with increased fatigue life.These results are expected to provide some reference significance for the engineering design of SWR.

Fatigue analysis of closed-cell aluminium foam using different material models

The fatigue analyses of AlSi7 closed-cell aluminium foam were performed using a real porous model and three different homogenised material models:crushable foam model,isotropic hardening model and kinematic hardening model.The numerical analysis using all three homogenised material models is based on the available experimental results previously determined from fatigue tests under oscillating tensile loading with the stress ratio R=0.1.The obtained computational results have shown that both isotropic and kinematic hardening models are suitable to analyse the fatigue behaviour of closed-cell aluminium foam.Besides,the kinematic hardening material model has demonstrated significantly shorter simulation time if compared to the isotropic hardening material model.On the other hand,the crushable foam model is recognized as an inappropriate approach for the fatigue analyses under tension loading conditions.

Optimum Autofrettage Pressure of Hydrogen Valve Using Finite Element and Fatigue Analysis

The presented article shows an estimation method of optimum autofrettage pressure taking into consideration subsequent cyclic loading. An autofrettage process is used in pressure vessel applications for strength improvement. The process relies on applying massive pressure that causes internal portions of the part to yield plastically, resulting in internal compressive residual stresses when pressure is released. Later applied working pressure (much lower than autofrettage pressure) creates stress reduced by the residual compressive stress improving the structural performance of the pressure vessels. The optimum autofrettage pressure is a load that maximizes the fatigue life of the structure at the working load. The estimation method of that pressure of a hydrogen valve is the subject of the presented work. Finite element and fatigue analyses were employed to investigate the presented problem. An automated model was developed to analyze the design for various autofrettage pressures. As the results of the procedure, the optimum autofrettage pressure is determined. The research has shown that the developed method can profitably investigate the complex parts giving the autofrettage load that maximizes the fatigue life. The findings suggest that the technique can be applied to a large group of products subjected to the autofrettage process.

Full－range nonlinear analysis of fatigue behaviors of reinforced concrete structures by finite element method

The offshore reinforced concrete structures are always subject to cyclic load, such as wave load.In this paper a new finite element analysis model is developed to analyze the stress and strain state of reinforced concrete structures including offshore concrete structures, subject to any number of the cyclic load. On the basis of the anal ysis of the experimental data,this model simplifies the number of cycles-total cyclic strain curve of concrete as three straight line segments,and it is assumed that the stress-strain curves of different cycles in each segment are the same, thus the elastoplastic analysis is only needed for the first cycle of each segment, and the stress or strain corresponding to any number of cycles can be obtained by superposition of stress or strain obtained by the above e lastoplastic analysis based on the cyclic numbers in each segment.This model spends less computer time,and can obtain the stress and strain states of the structures after any number of cycles.The endochronic-damage and ideal offshore concrete platform subject to cyclic loading are experimented and analyzed by the finite element method based on the model proposed in this paper. The results between the experiment and the finite element analysis are in good agreement,which demonstrates the validity and accuracy of the proposed model.

Fatigue Analysis of Steel Catenary Risers Based on a Plasticity Model

The most critical issue in the steel catenary riser design is to evaluate the fatigue damage in the touchdown zone accurately. Appropriate modeling of the riser-soil resistance in the touchdown zone can lead to significant cost reduction by optimizing design. This paper presents a plasticity model that can be applied to numerically simulate riser-soil interaction and evaluate dynamic responses and the fatigue damage of a steel catenary riser in the touchdown zone. Utilizing the model, numerous riser-soil elements are attached to the steel catenary riser finite elements, in which each simulates local foundation restraint along the riser touchdown zone. The riser-soil interaction plasticity model accounts for the behavior within an allowable combined loading surface. The model will be represented in this paper, allowing simple numerical implementation. More importantly, it can be incorporated within the structural analysis of a steel catenary riser with the finite element method. The applicability of the model is interpreted theoretically and the results are shown through application to an offshore 8.625 steel catenary riser example. The fatigue analysis results of the liner elastic riser-soil model are also shown. According to the comparison results of the two models, the fatigue life analysis results of the plasticity framework are reasonable and the horizontal effects of the riser-soil interaction can be included.

PROBABILISTIC METHODOLOGY OF LOW CYCLE FATIGUE ANALYSIS

The cyclic stress-strain responses (CSSR), Neuber's rule (NR) and cyclic strain-life relation (CSLR) are treated as probabilistic curves in local stress and strain method of low cycle fatigue analysis. The randomness of loading and the theory of fatigue damage accumulation (TOFDA) are considered. The probabilistic analysis of local stress, local strain and fatigue life are constructed based on the first-order Taylor's series expansions. Through this method proposed fatigue reliability analysis can be accomplished.