230 research outputs found

    Probabilistic optimization of fatigue maintenance for welded components in steel bridges based on LEFM and LCCM

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    In this paper a probabilistic-based method for fatigue maintenance optimization of steel bridgeā€™s welded joints, combined with linear elastic fracture mechanics (LEFM), the structure reliability, and life cycle cost method(LCCM) is proposed. The probabilistic analysis method can be used with the fatigue maintenance of steel bridges. Weld cracks are classified by its size and maintenance decisions, and are made according to its size classification. Maintenance cost is divided into inspection, repair and failure costs, according to the life cycle cost method. The maintenance optimization strategy is transformed to minimize the expected lifetime total costs with the constraints of the minimum acceptable reliability index to attain the most cost-optimal inspection and repair for the balanced costs between risk and safety. An example concerning the transverse stiffeners of welded components in the main girder of suspension bridge is investigated through the research of some parameters sensitivity. Among all the parameters, the inspection cost is the most remarkable. The optimal time interval of repair will delay based on the increase of the inspection cost. The optimal time interval of repair will advance based on the increase of repair cost. A discount rate can drastically change the value of the total cost, but when the probability of failure is very small, the increase of failure cost has little effect on the optimal time interval of repair. The method presented in this paper can be conducted using the similar maintenance of steel structures

    Therapeutic Potential of Metformin in Diabetes Mellitus-Related Cardiovascular Complications

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    The diabetic population continues to grow worldwide, resulting in many chronic cardiovascular complications, including atherosclerosis and diabetic cardiomyopathy, as well as an increase in the incidence of heart failure. Metformin, as the first-line oral therapy for type 2 diabetes, lowers blood glucose and reduces the incidence of diabetes mellitus (DM)-related cardiovascular events, such as myocardial infarction. The cardiovascular protective effect of metformin is due not only to the relief of insulin resistance and the improvement of glucose and lipid metabolism but also to the inhibition of oxidation and inflammation. Metformin exerts its multiple effects primarily through AMPK-dependent and AMPK-independent mechanisms. This chapter reviews the beneficial effects of metformin on DM-related cardiovascular complications and dissects the potential molecular mechanisms

    Increasing Interest in Inclusive Education in the Context of Action Plan for the Development and Enhancement of Special Education during the Fourteenth Five-Year Period in China: An Analysis of Baidu Index Data

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    Objective: Current evidence shows that public interest in inclusive education has been rising since the implementation of Action Plan for the development and enhancement of special education during the Fourteenth Five-Year period in China. The aim of this study was to quantify recent trends in public interest and related online search behavior for inclusive education in the context of this Action Plan. Methods: Baidu Index, a database of search engines with massive information, was employed. By searching for the keyword inclusive education, and using content analysis to understand the data information related to inclusive education. This study also extracted the search trend data of Chinese netizens on the related terms "Law on the Protection of Persons with Disabilities " and "Regulation on the Education of Persons with Disabilities" from January 1, 2022 to October 27, 2022. Finally, it compares the search trend of public search interests of inclusive education with related terms. Results: The public's interest in "inclusive education" and the related terms "Law on the Protection of Persons with Disabilities " and "Regulation on the Education of Persons with Disabilities" has been on the rise since the implementation of the Action Plan. The search trend reached its peak in February and May 2022, the valley in January 2022, and the search volume in other time periods tended to be stable. Conclusion: Baidu Index can understand the public's interest in inclusive education. The study shows that the rising search trend of inclusive education is closely related to the implementation of the Action Plan. The search volume of the "Law on the Protection of Persons with Disabilities " and "Regulation on the Education of Persons with Disabilities" is basically the same as that of "inclusive education", but the average search volume daily of "inclusive education" is slightly higher than that of "Regulation on the Education of Persons with Disabilities"

    Neddylation inhibitor MLN4924 suppresses cilia formation by modulating AKT1

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    Abstract The primary cilium is a microtubule-based sensory organelle. The molecular mechanism that regulates ciliary dynamics remains elusive. Here, we report an unexpected finding that MLN4924, a small molecule inhibitor of NEDD8-activating enzyme (NAE), blocks primary ciliary formation by inhibiting synthesis/assembly and promoting disassembly. This is mainly mediated by MLN4924-induced phosphorylation of AKT1 at Ser473 under serum-starved, ciliary-promoting conditions. Indeed, pharmaceutical inhibition (by MK2206) or genetic depletion (via siRNA) of AKT1 rescues MLN4924 effect, indicating its causal role. Interestingly, pAKT1-Ser473 activity regulates both ciliary synthesis/assembly and disassembly in a MLN4924 dependent manner, whereas pAKT-Thr308 determines the ciliary length in MLN4924-independent but VHL-dependent manner. Finally, MLN4924 inhibits mouse hair regrowth, a process requires ciliogenesis. Collectively, our study demonstrates an unexpected role of a neddylation inhibitor in regulation of ciliogenesis via AKT1, and provides a proof-of-concept for potential utility of MLN4924 in the treatment of human diseases associated with abnormal ciliogenesis.https://deepblue.lib.umich.edu/bitstream/2027.42/148214/1/13238_2019_Article_614.pd

    Autonomic Innervation and Segmental Muscular Disconnections at the Human Pulmonary Vein-Atrial Junction Implications for Catheter Ablation of Atrial-Pulmonary Vein Junction

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    ObjectivesThis study sought to examine the muscle connections and autonomic nerve distributions at the human pulmonary vein (PV)-left atrium (LA) junction.BackgroundOne approach to catheter ablation of atrial fibrillation (AF) is to isolate PV muscle sleeves from the LA. Elimination of vagal response further improves success rates.MethodsWe performed immunohistochemical staining on 192 circumferential venoatrial segments (32 veins) harvested from 8 autopsied human hearts using antibodies to tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT).ResultsMuscular discontinuities of widths 0.1 to 5.5 mm (1.1 Ā± 1.0 mm) and abrupt 90Ā° changes in fiber orientation were found in 70 of 192 (36%) and 36 of 192 (19%) of PV-LA junctions, respectively. Although these anisotropic features were more common in the anterosuperior junction (p < 0.01), they were also present around the entire PV-LA junction. Autonomic nerve density was highest in the anterosuperior segments of both superior veins (p < 0.05 versus posteroinferior) and inferior segments of both inferior veins (p < 0.05 vs. superior), highest in the LA within 5 mm of the PV-LA junction (p < 0.01), and higher in the epicardium than endocardium (p < 0.01). Adrenergic and cholinergic nerves were highly co-located at tissue and cellular levels. A significant proportion (30%) of ganglion cells expressed dual adrenocholinergic phenotypes.ConclusionsMuscular discontinuities and abrupt fiber orientation changes are present in >50% of PV-LA segments, creating significant substrates for re-entry. Adrenergic and cholinergic nerves have highest densities within 5 mm of the PV-LA junction, but are highly co-located, indicating that it is impossible to selectively target either vagal or sympathetic nerves during ablation procedures

    Job satisfaction and its related factors among emergency department physicians in China

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    BackgroundJob satisfaction is recognized as an important factor affecting the performance and quality of medical services of emergency department physicians. However, little is known about the status of job satisfaction among emergency department physicians in China. This study aimed to explore the current level of job satisfaction and its associated factors among emergency department physicians in China.MethodsA nationwide cross-sectional survey was conducted in China from July to August 2018. A total of 10,457 emergency department physicians completed the questionnaire. The structured online questionnaire collected information on socio-demographic characteristics, work-related factors, work-family conflict, and job satisfaction. Student's t-test or ANOVA were used to compare the job satisfaction scores in different characters. The generalized linear model was used to investigate the related factors of job satisfaction among emergency department physicians.ResultsThe respondents' job satisfaction average score was 12.2 Ā± 3.6, of which 42.01% were satisfied of which the job. The results showed that emergency department physicians over 41 years old, with a higher income and working in central and western regions were positively associated with job satisfaction. In contrast, bachelor degree and above, fixed posts, long years of service, a high frequency of night shift, perceived shortage of physicians, perceived medical errors, and higher work-family conflict scores were negatively correlated with job satisfaction among emergency department physicians.ConclusionJob satisfaction of emergency department physicians in China is low. It is suggested that hospital administrators could improve the job satisfaction of emergency department physicians by establishing an acceptable shift system, ensuring adequate emergency department staffing, increasing their income appropriately and alleviating work-family conflict

    Effect of Berberine on PPAR Ī±

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    Rhizoma coptidis, the root of Coptis chinensis Franch, has been used in China as a folk medicine in the treatment of diabetes for thousands of years. Berberine, one of the active ingredients of Rhizoma coptidis, has been reported to improve symptoms of diabetes and to treat experimental cardiac hypertrophy, respectively. The objective of this study was to evaluate the potential effect of berberine on cardiomyocyte hypertrophy in diabetes and its possible influence on peroxisome proliferator-activated receptor-Ī± (PPARĪ±)/nitric oxide (NO) signaling pathway. The cardiomyocyte hypertrophy induced by high glucose (25.5ā€‰mmol/L) and insulin (0.1ā€‰Ī¼mol/L) (HGI) was characterized in rat primary cardiomyocyte by measuring the cell surface area, protein content, and atrial natriuretic factor mRNA expression level. Protein and mRNA expression were measured by western blot and real-time RT-PCR, respectively. The enzymatic activity of NO synthase (NOS) was measured using a spectrophotometric assay, and NO concentration was measured using the Griess assay. HGI significantly induced cardiomyocyte hypertrophy and decreased the expression of PPARĪ± and endothelial NOS at the mRNA and protein levels, which occurred in parallel with declining NOS activity and NO concentration. The effect of HGI was inhibited by berberine (0.1 to 100ā€‰Ī¼mol/L), fenofibrate (0.3ā€‰Ī¼mol/L), or L-arginine (100ā€‰Ī¼mol/L). MK886 (0.3ā€‰Ī¼mol/L), a selective PPARĪ± antagonist, could abolish the effects of berberine and fenofibrate. NG-nitro-L-arginine-methyl ester (100ā€‰Ī¼mol/L), a NOS inhibitor, could block the effects of L-arginine, but only partially blocked the effects of berberine. These results suggest that berberine can blunt HGI-induced cardiomyocyte hypertrophy in vitro, through the activation of the PPARĪ±/NO signaling pathway

    Unveiling the spatial-temporal variation of urban land use efficiency of Yangtze River Economic Belt in China under carbon emission constraints

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    Under the constraint of carbon emission, measuring and analyzing the spatial-temporal evolution characteristics of urban land use efficiency in the Yangtze River Economic Belt is the inherent requirement of its ecological protection and sustainable development. In this paper, we calculated the urban land use efficiency of 107 cities in the Yangtze River Economic Belt from 2006 to 2020 by using the SBM-Undesirable model with unexpected output, and analyzed its temporal evolution trend and spatial correlation relationship by using kernel density and spatial autocorrelation method. The results showed that: except in 2020, the urban land use efficiency was generally low due to the COVID-19 epidemic, and the urban land use efficiency in other years was mostly concentrated in the middle levels, and showed a trend of slow fluctuation and rise year by year. The difference of urban land use efficiency level between regions increased, and the dispersion degree in upstream, midstream and downstream increased with each passing year. Urban land use efficiency spatial imbalance was significant, and the urban land use efficiency level of large and medium-sized cities was generally lower than that of cities with low economic development level. The spatial correlation was weak, and the global spatial autocorrelation was basically insignificant, while the local spatial agglomeration areas were mainly distributed in the upstream and downstream regions, with a small distribution range and weak spatial interaction. The distribution areas of the standard deviation ellipse were gradually flattened, and the center of gravity as a whole shift significantly to the southwest. The research results are helpful to understand the development history and future trend of urban land use efficiency in various regions, and propose that cities should consider the impact of public crisis events in advance, reasonably control the scale of land expansion, and lead coordinated development and other reasonable suggestions when formulating land use policies
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