•A modified generalized local model considering multiaxial stress and stress gradient is developed.•A novel probabilistic framework for notch fatigue analysis considering size effects is ...established.•Probabilistic fatigue life prediction of TA19 notched specimens with different scales are conducted.
Structural integrity assessments with discontinuities are critical for ensuring operational life and reliability of engineering components. In this work, through combining with the generalized local model, a probabilistic framework is proposed for fatigue life assessment of notched components under size effects, in which the Smith–Watson–Topper damage parameter is utilized to characterize the multiaxial stress state at the notch tip. In particular, an effective stress concept is introduced to characterize the inhomogeneous stress distribution within the notch region. Finally, experimental data of TA19 notched specimens with different scales are utilized for model validation and comparison, results show that the proposed framework yields acceptable correlations of predicted fatigue lives with experimental ones.
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•Combined critical plane-critical distance approach for notch fatigue analysis under multiaxial loadings is proposed.•Eight life assessment procedures with different coupling sequence of critical ...plane and TCD concepts are explored.•Procedures using the CPA before the TCD own better predictions than that after the TCD.•Procedures regarding the critical distance as a fatigue lifetime related function provides better correlations than others.
Combinations of geometric discontinuities and multiaxial loads appear commonly in engineering components, which raise both stress gradient and multiaxial stress states near the notch root. This work studies the combined critical plane approach with the theory of critical distance for fatigue analysis of notched components under multiaxial loadings. Taking the Fatemi-Socie model for instance, different coupling sequence of critical plane and critical distance concepts is discussed. In particular, the influence of employing the point method and the line method of the theory of critical distance on predicting performance as well as the rationality of regarding the critical distance as a material constant or as a function related to fatigue life are also investigated. Accordingly, 8 life assessment procedures are summarized and the optimal procedure is determined and verified by experimental data of Al 7050-T7451 and GH4169 alloys. Results show that the majority of the predicted points fall within the ±2 scatter band according to experimental results and the procedures which employ the theory of critical distance after using the critical plane approach and regarding the critical distance as a function related to fatigue life provide better accuracy on fatigue life prediction than others.
Heroin use disorder (HUD) is a complex disease resulting from interactions among genetic and other factors (e.g., environmental factors). The mechanism of HUD development remains unknown. Newly ...developed network medicine tools provide a platform for exploring complex diseases at the system level. This study proposes that protein-protein interactions (PPIs), particularly those among proteins encoded by casual or susceptibility genes, are extremely crucial for HUD development. The giant component of our constructed PPI network comprised 111 nodes with 553 edges, including 16 proteins with large degree (k) or high betweenness centrality (BC), which were further identified as the backbone of the network. JUN with the largest degree was suggested to be central to the PPI network associated with HUD. Moreover, PCK1 with the highest BC and MAPK14 with the secondary largest degree and 9
highest BC might be involved in the development HUD and other substance diseases.
•Framework for fatigue reliability analysis under multi-source uncertainties.•Manufacturing errors/tolerances are included for fatigue reliability analysis.•Sensitivity analysis of a turbine bladed ...disk is conducted for fatigue design.•Geometrical uncertainty shows critical influences on fatigue reliability.
Turbine bladed disks normally operate under complex loadings coupling with uncertainties originate from multiple sources, including material variability, load variation and geometrical uncertainty. The influence of these uncertainties on mechanical response of engineering components are critical for their fatigue assessment and reliability evaluation. In this work, a general framework for fatigue reliability analysis is developed by coupling the Latin hypercube sampling with FE analysis to describe the combined effects of multi-source uncertainties. Fatigue reliability analysis of a full-scale bladed disk under multi-source uncertainties was performed as well as sensitivity analysis for fatigue design. In order to describe the manufacturing errors or tolerances, random dimensions are inputted. Comparing the predicted fatigue lifetime distributions with/without geometrical uncertainty, it shows that geometrical uncertainty matters in structural fatigue reliability. Particularly, sensitivity analysis indicates that the geometrical uncertainty exerts more critical influences on the fatigue lifetime and reliability of the turbine bladed disk than others. The sensitivity factors of three typical dimensions emerges the influence of designed sizes and dimensional tolerances on the failure probability, which provides a reference for engineering design.
The hypothalamus plays an important role in regulating body weight through its interactions with multiple brain circuits involved in distinct aspects of feeding behavior. Yet, how hypothalamic gray ...matter volume (GMV) and connectivity may be related to individual differences in body weight remains unclear. We tested the hypothesis that the hypothalamus shows enhanced resting-state functional connectivity (rsFC) with regions of the reward, motivation, and motor circuits in positive correlation with body mass index (BMI) and the opposite with those associated with inhibitory control. We further examined the interdependent relationships between hypothalamic GMV, connectivity, and body weight.
Using seed-based rsFC and voxel-based morphometry analyses, we examined the relationship between the rsFC and GMV of the hypothalamus and BMI in 105 healthy humans. Additionally, we employed mediation analyses to characterize the inter-relationships between hypothalamic connectivity, GMV, and BMI.
A whole-brain multiple regression showed that BMI was positively correlated with hypothalamic rsFC with the insula, thalamus, globus pallidus, and cerebellum, and negatively correlated with hypothalamic rsFC with the superior parietal lobule. Thus, higher BMI was associated with enhanced hypothalamic connectivity with regions involved in motivated feeding and reduced connectivity with those in support of cognitive control of food intake. A second whole-brain multiple regression revealed a positive correlation between hypothalamic GMV and the hypothalamus-posterior insula connectivity. Finally, the relationship between hypothalamic GMV and BMI was significantly and bidirectionally mediated by the hypothalamus-posterior insula connectivity.
The current findings suggest that the hypothalamus differentially interacts with the motivation, motor, and control circuits to regulate BMI. We further found evidence for the interdependence of hypothalamic structure, function, and body weight, which provides potential insights into the brain mechanisms of obesity.
Notch and size effects generally show great influence on the fatigue behavior of engineering structures, which plays a vital role during their structural integrity and reliability evaluations. In ...this study, the influence of notch size effect on fatigue life and critical distance values were investigated. Particularly, a novel method for fatigue life distribution assessment of notched specimens was proposed based on Weibull model and critical distance theory. Experimental data of Al 2024-T351 smooth plate specimens and center hole plate (CHP) specimens with four different notch radii were utilized for model validation and comparison. Results show that all predicted lives of Al 2024-T351 CHP specimens are within the ±2 life scatter bands of experimental ones.
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•Weibull model describes well the dispersity of fatigue lives of Al 2024-T351 alloys.•Influence of notch size effect on critical distance and fatigue strength were characterized.•Proposed model by coupling Weibull with critical distance theories for considering notch size effect.•Proposed model predictions of Al 2024-T351 center hole plate specimens are within ±2 life scatter bands of experimental ones.
Fatigue strength analysis of critical components plays a vital role for ensuring structural integrity and operational reliability of major equipment. In notched components, the concept of cyclic ...plastic zone (CPZ) is commonly utilized for fatigue cracking analysis, in which the CPZ size normally relates to the material strength. In particular, materials with higher yield stress have shown smaller CPZ size and vice versa. According to this, a new approach for determining closed-form stress at the notch tip is proposed by considering the size of cyclic plastic zone, which can be used for the notch tip stress evaluation along the load direction under cyclic loadings. By implementing FE analysis, experimental data of 304 stainless steel, 40Cr steel and Ti-6Al-4V alloy are utilized for model validation and comparison. Results show that the scope of damaged CPZ alters the notch tip stress under fatigue loadings, and the proposed model yields better correlation of fatigue life predictions with experimental results of the three materials than other two models.
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•New closed form notch tip stress calculation method based on cyclic plastic zone•Proposed damage evolution model for notch fatigue life prediction•Notch tip stress relates with both the notch geometry and material property.•Proposed model yields better predictions of three materials than other two models.
The microRNA miR-125b is dysregulated in various human cancers but its underlying mechanisms of action are poorly understood. Here, we report that miR-125b is downregulated in invasive breast cancers ...where it predicts poor patient survival. Hypermethylation of the miR-125b promoter partially accounted for reduction of miR-125b expression in human breast cancer. Ectopic restoration of miR-125b expression in breast cancer cells suppressed proliferation, induced G(1) cell-cycle arrest in vitro, and inhibited tumorigenesis in vivo. We identified the ETS1 gene as a novel direct target of miR-125b. siRNA-mediated ETS1 knockdown phenocopied the effect of miR-125b in breast cell lines and ETS1 overexpression in invasive breast cancer tissues also correlated with poor patient prognosis. Taken together, our findings point to an important role for miR-125b in the molecular etiology of invasive breast cancer, and they suggest miR-125b as a potential theranostic tool in this disease.
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•FeCo-NP (1000A900) is developed for hydrogen capture in NaBH4/EtOH mixture.•Catalyst prepared by self-assembly of N-doped carbon shell and FeCo-alloy core.•This catalyst shows good ...performance for both H2 and O2 capture applications.
Hydrogen energy storage and transportation are critical issues that must be addressed to ensure the development of alternatives to fossil fuel energy in the future. Herein, the poly(Schiff base) strategy is used to explore the carbon substrate, which is enclosed with binary metal Fe and Co as precursors. After the calcination and acid treatment steps, one of the FeCo alloy, termed FeCoNC-1000A900, was assembled with porous carbon skeleton as a shell and enclosed with FeCo alloy as a core. The FeCoNC-1000A900 exhibits outstanding H2 capture properties from NaBH4/EtOH mixtures circumstance owing to its large average particle size of 45 nm and high specific surface area of 462.07 m2/g. Notably, the FeCoNC-1000A900 acquires bi-functional catalysis efficacy, one is for chemoselectivity in the hydrogenation of nitroarene substrates and shows a high turnover frequency in 690 h−1 within the overall conversion yield. The other one is the O2 capture performance toward the oxygen reduction reaction with the excellent onset potential of 0.89 V, the half-wave potential of 0.77 V, and limiting current density of − 5.56 mA cm−2, which are comparable to those of the commercial Pt/C catalyst. In addition, the Tafel slope of 79.6 mV dec−1 is lower than those for other catalysts. Consequently, the development of the novel FeCoNC-1000A900 catalyst has two functional applications.
Objective
To compare the psychiatric service utilization between patients who only received long‐acting injectable antipsychotics (LAIAs) and those who only received oral antipsychotics (OAPs) in the ...maintenance treatment of chronic schizophrenia.
Methods
We constructed a cohort of chronic schizophrenia patients who underwent maintenance treatment from the Taiwan National Health Insurance Research Database in 2011 and followed these patients for 12 months. We included patients who had been diagnosed with schizophrenia for at least 3 years, were not hospitalized in 2011, and had received 1 year of maintenance treatment. Inverse probability of treatment weighting logistic, linear, and negative binomial regression models were used to estimate associated psychiatric services utilization and adjust for covariate imbalances between the LAIAs and OAPs groups.
Results
Among 40,194 patients, 948 (2.36%) received only LAIAs and 39,246 (97.64%) received only OAPs. Compared with those who received only OAPs, the sole LAIAs users were associated with a lower percentage of psychiatric hospitalization (8.4% and 5.8%, respectively; odds ratio: 0.63, p < .01), shorter lengths of hospitalization days (82.8 and 65.9, respectively; coefficient b: −16.87, p = .03), and fewer emergency room visits (2.3 and 1.8, respectively; b: −0.24, p < .01) per patient.
Conclusions
Chronic schizophrenia patients who received only LAIs had a lower risk of disease relapse and a reduction in psychiatric service utilization than those receiving only OAPs.