A fast multipole boundary element method (BEM) is used herein to simulate the two-dimensional interfacial debonding of particulate composites. The behavior of the interface between the inclusion and the matrix is modeled using a nonlinear constitutive relationship. Interface debonding is implemented by decoupling the node pair. In the proposed method, the degree of freedom (DOF) of the interfacial traction changes to that of displacement of the free surface; thus, the number of DOFs of each node pair prior to and after decoupling is the same, which facilitates the simulation better than the finite element method. In simulating the softening stage of the nonlinear interfacial deformation, the stress in the node pair is assumed to be unloaded to zero and then reloaded to a new equilibrium state. A fast multipole expansion technique is applied within the developed BEM to solve the large-scale problem of debonding particulate composites whereby millions of DOFs can be calculated via a step-wise calculation method that provides high precision interface stress results. A comparison of these results with the analytical solution for a single inclusion case demonstrates the high stress accuracy and effectiveness of the developed fast multipole BEM to solve large-scale nonlinear interface problems.
Collocation analysis can be used to extract meaningful linguistic information from large-scale corpus data. This paper reviews the methodological issues one may encounter when performing collocation analysis for discourse studies on Chinese. We propose four crucial aspects to consider in such analyses: (i) the definition of collocates according to various parameters; (ii) the choice of analysis and association measures; (iii) the definition of the search span; and (iv) the selection of corpora for analysis. To illustrate how these aspects can be addressed when applying a Chinese collocation analysis, we conducted a case study of two Chinese causal connectives: yushi ‘that is why’ and yin’er ‘as a result’. The distinctive collocation analysis shows how these two connectives differ in volitionality, an important dimension of discourse relations. The study also demonstrates that collocation analysis, as an explorative approach based on large-scale data, can provide valuable converging evidence for corpus-based studies that have been conducted with laborious manual analysis on limited datasets.
OBJECTIVES: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline recommended 130/80 mm Hg as blood pressure (BP) target goals. However, the generalisability of this recommendation to populations at large with hypertension remains controversial. We assessed the association between BP and cardiovascular diseases (CVDs) mortality using a 20-year follow-up study among Chinese populations. DESIGN: Prospective cohort study. PARTICIPANTS: 7314 participants were followed up for a median of 20 years in Fangshan District, Beijing, China. METHODS: The primary outcome variable was death from cardiovascular causes. The adjusted HR for CVDs mortality associated with baseline BP was calculated using Cox regression analysis. RESULTS: We identified 350 deaths from CVDs (148 stroke, 113 coronary heart disease and 89 other CVDs) during follow-up. Hypertension (defined by systolic BP (SBP)/diastolic BP (DBP) >/=140/90 mm Hg) was significantly associated with mortality due to CVDs (HR=2.49, 95% CI=1.77 to 3.50) among people aged 35-59 years rather than people aged >/=60 years. In addition, there was no significant association between stage 1 hypertension defined by the 2017 ACC/AHA (SBP/DBP of 130-139/80-89 mm Hg) and CVDs mortality when compared with SBP/DBP of <120/80 in neither the participants aged <60 years (HR=0.90, 95% CI=0.54 to 1.50) nor participants aged >/=60 years (HR=1.47, 95% CI=0.94 to 2.29). CONCLUSION: The study revealed hypertension of SBP/DBP>/=140/90 mm Hg was an important risk factor of CVDs mortality, especially among people aged 35-59 years. However, stage 1 hypertension under the definition of 2017 ACC/AHA was not associated with an increased risk of CVDs mortality. This study indicated that whether adopting the new hypertension definition needs further consideration in rural Chinese populations.
Importance: Chronic obstructive pulmonary disease (COPD) is a critical public health burden. The neutrophil to lymphocyte ratio (NLR), an inflammation biomarker, has been associated with COPD morbidity and mortality; however, its associations with lung function decline and COPD development are poorly understood. Objective: To explore the associations of NLR with lung function decline and COPD risks. Design, Setting, and Participants: This longitudinal cohort study included white male veterans in the US with more than 30 years of follow-up to investigate the associations of NLR with lung function, COPD, and hypomethylation of cg05575921, the top DNA methylation marker of lung function changes in response to tobacco smoking. This study included 7466 visits from 1549 participants, each examined up to 13 times between 1982 and 2018. A subgroup of 1411 participants without COPD at baseline were selected to analyze the association of NLR with incident COPD. Data were analyzed from September 2019 to January 2020. Exposures: The primary exposure was NLR, which was estimated using automated whole blood cell counts based on a blood sample collected at each visit. The methylation level of cg05575921 was measured in blood DNA from a subgroup of 1228 visits. Main Outcomes and Measures: The outcomes of interest were lung function, measured as forced respiratory volume in the first second (FEV1) in liters, forced vital capacity (FVC) in liters, percentage of FVC exhaled in the first second (FEV1/FVC), and maximal midexpiratory flow rate (MMEF) in liters per minute and COPD status, defined as meeting the Global Initiative for Chronic Obstructive Lung Diseases stage II (or higher) criteria. Both outcomes were measured as each visit. Results: Among 1549 included men (mean [SD] age, 68.3 [9.3] years) with 7466 visits from 1982 to 2018, a 1-unit increase in NLR was associated with statistically significant mean (SE) decreases of 0.021 (0.004) L in FEV1, 0.016 (0.005) L in FVC, 0.290% (0.005) L in FVC, 0.290% (0.065%) in FEV1/FVC, and 3.65 (0.916) L/min MMEF. Changes in NLR up to approximately 10 years were associated with corresponding longitudinal changes in lung function. Furthermore, this increase in NLR was associated with 9% higher odds of COPD (odds ratio, 1.09 [95% CI, 1.03-1.15]) for all visits and 27% higher risk of incident COPD (odds ratio, 1.07 [95% CI, 1.07-1.51]) for participants without COPD at baseline. Additionally, a 1-unit increase in NLR was associated with a mean (SE) decrease of 0.0048 (0.0021 in cg05575921 hypomethylation, which may mediate the adverse association of NLR-related inflammation on lung function. Conclusions and Relevance: These findings suggest that NLR may be a clinically relevant biomarker associated with high risk of lung function impairment and COPD alone or in combination with DNA methylation profiles.
Current studies indicate that long-term exposure to ambient fine particulate matter (PM2.5) is related with global mortality, yet no studies have explored relationships of PM2.5 and its species with DNAm PhenoAge acceleration (DNAmPhenoAccel), a new epigenetic biomarker of phenotypic age. We identified which PM2.5 species had association with DNAmPhenoAccel in a one-year exposure window in a longitudinal cohort. We collected whole blood samples from 683 elderly men in the Normative Aging Study between 1999 and 2013 (n = 1254 visits). DNAm PhenoAge was calculated using 513 CpGs retrieved from the Illumina Infinium HumanMethylation450 BeadChip. Daily concentrations of PM2.5 species were measured at a fixed air-quality monitoring site and one-year moving averages were computed. Linear mixed-effect (LME) regression and Bayesian kernel machine (BKM) regression were used to estimate the associations. The covariates included chronological age, body mass index (BMI), cigarette pack years, smoking status, estimated cell types, batch effects etc. Benjamini-Hochberg false discovery rate at a 5% false positive threshold was used to adjust for multiple comparison. During the study period, the mean DNAm PhenoAge and chronological age in our subjects were 68 and 73 years old, respectively. Using LME model, only lead and calcium were significantly associated with DNAmPhenoAccel. For example, an interquartile range (IQR, 0.0011 mug/m(3)) increase in lead was associated with a 1.29-year [95% confidence interval (CI): 0.47, 2.11] increase in DNAmPhenoAccel. Using BKM model, we selected PM2.5, lead, and silicon to be predictors for DNAmPhenoAccel. A subsequent LME model showed that only lead had significant effect on DNAmPhenoAccel: 1.45-year (95% CI: 0.46, 2.46) increase in DNAmPhenoAccel following an IQR increase in one-year lead. This is the first study that investigates long-term effects of PM2.5 components on DNAmPhenoAccel. The results demonstrate that lead and calcium contained in PM2.5 was robustly associated with DNAmPhenoAccel.
One-carbon metabolism is an important contributor to aging-related diseases; nevertheless, relationships of one-carbon metabolites with novel DNA methylation-based measures of biological aging remain poorly characterized. We examined relationships of one-carbon metabolites with three DNA methylation-based measures of biological aging: DNAmAge, GrimAge, and PhenoAge. We measured plasma levels of four common one-carbon metabolites (vitamin B6, vitamin B12, folate, and homocysteine) in 715 VA Normative Aging Study participants with at least one visit between 1999 and 2008 (observations = 1153). DNA methylation age metrics were calculated using the HumanMethylation450 BeadChip. We utilized Bayesian Kernel Machine Regression (BKMR) models adjusted for chronological age, lifestyle factors, age-related diseases, and study visits to determine metabolites important to the aging outcomes. BKMR models allowed for the estimation of the relationships of single metabolites and the cumulative metabolite mixture with methylation age. Log vitamin B6 was selected as important to PhenoAge (beta = -1.62-years, 95%CI: -2.28, -0.96). Log folate was selected as important to GrimAge (beta = 0.75-years, 95%CI: 0.41, 1.09) and PhenoAge (beta = 1.62-years, 95%CI: 0.95, 2.29). Compared to a model where each metabolite in the mixture is set to its 50 th percentile, the log cumulative mixture with each metabolite at its 30 th (beta = -0.13-years, 95%CI: -0.26, -0.005) and 40 th percentile (beta = -0.06-years, 95%CI: -0.11, -0.005) was associated with decreased GrimAge. Our results provide novel characterizations of the relationships between one-carbon metabolites and DNA methylation age in a human population study. Further research is required to confirm these findings and establish their generalizability.
We propose an experiment to test the uniform-Berry-curvature picture of composite fermions. We show that the asymmetry of geometrical resonances observed in a periodically modulated composite fermion system can be explained with the uniform-Berry-curvature picture. Moreover, we show that an alternative way of modulating the system, i.e., modulating the external magnetic field, will induce an asymmetry opposite to that of the usual periodic grating modulation which effectively modulates the Chern-Simons field. The experiment can serve as a critical test of the uniform-Berry-curvature picture and probe the dipole structure of composite fermions proposed by Read.