Experimental Researches on Long-Term Strength of Granite Gneiss

It is important to confirm the long-term strength of rock materials for the purpose of evaluating the long-term stability of rock engineering. In this study, a series of triaxial creep tests were conducted on granite gneiss under different pore pressures. Based on the test data, we proposed two new quantitative methods, tangent method and intersection method, to confirm the long-term strength of rock. Meanwhile, the isochronous stress-strain curve method was adopted to make sure of the accuracy and operability of the two new methods. It is concluded that the new methods are suitable for the study of the long-term strength of rock. The effect of pore pressure on the long-term strength of rock in triaxial creep tests is also discussed

Stability and Failure Mechanism Analyses of the Zhenggang Landslide in Southwestern China

The Zhenggang landslide is an ancient complex landslide located at southeastern Tibetan Plateau, China. Due to intensive rainfalls in 2008 and heavy snowfalls in 2009, the Zhenggang landslide exhibited a high probability of reactivation once again. In this study, geological structure, matter features, and macrodeformations of the Zhenggang landslide (including Zone I and Zone II) were investigated for uncovering its formation mechanism and evolution tendency first, and then the stability and failure mechanism analyses of the Zhenggang landslide were conducted in detail by a combined limit equilibrium and finite element analysis method. Results of geological investigations indicate that the Zhenggang landslide has undergone sliding several times and is in a metastable state now. The distribution of the activity of the landslide is a retrogressive landslide in Zone I but an advancing landslide in Zone II. Such conclusions are further proved by the numerical stability and failure analyses

Estimation of Elasticity of Porous Rock Based on Mineral Composition and Microstructure

Estimation of elastic parameters of porous rock like the compressibility of sandstone is scientifically important and yet an open issue. This study illustrates the estimation of the elastic compressibility of sandstone (ECS) based on the assumption that the ECS is determined closely by the mineral composition and microstructures. In this study, 37 samples are collected to evaluate the estimations of the ECS obtained by different methods. The regression analysis is first implemented using the 37 samples. The results show that ECS exhibits linear relations with the rock minerals, pores, and applied compressive stress. Then the support vector machine (SVM) optimized by the particle swarm optimization algorithm (PSO) is examined to generate estimations of the ECS based on the mineral composition and microstructures. The SVM is trained with 30 samples to search for optimal parameters using the PSO, and thus the estimation model is established. Afterwards, this model is validated to give predictions of the left 7 samples. By comparison with the regression methods, the proposed strategy, that is, the PSO optimized SVM, performs much better on the training samples and shows a good capability in generating estimations of the ECS of the 7 testing samples based on the mineral composition and microstructures

Study on Spectrum Estimation in Biophoton Emission Signal Analysis of Wheat Varieties

The photon emission signal in visible range (380 nm–630 nm) was measured from various wheat kernels by means of a low noise photomultiplier system. To study the features of the photon emission signal, the spectrum estimation method of the photon emission signal is described for the first time. The biophoton emission signal, belonging to four varieties of wheat, is analyzed in time domain and frequency domain. It shows that the intensity of the biophoton emission signal for four varieties of wheat kernels is relatively weak and has dramatic changes over time. Mean and mean square value are obviously different in four varieties; the range was, respectively, 3.7837 and 74.8819. The difference of variance is not significant. The range is 1.1764. The results of power spectrum estimation deduced that the biophoton emission signal is a low frequency signal, and its power spectrum is mostly distributed in the frequency less than 0.1 Hz. Then three parameters, which are spectral edge frequency, spectral gravity frequency, and power spectral entropy, are adopted to explain the features of the kernels’ spontaneous biophoton emission signal. It shows that the parameters of the spontaneous biophoton emission signal for different varieties of wheat are similar

Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors

Development of heat shock protein 90 (Hsp90) C‐terminal inhibitors has emerged as an exciting strategy for the treatment of cancer. Previous efforts have focused on modifications to the natural products novobiocin and coumermycin. Moreover, variations in both the sugar and amide moieties have been extensively studied, whereas replacements for the coumarin core have received less attention. Herein, 24 cores were synthesized with varying distances and angles between the sugar and amide moieties. Compounds that exhibited good anti‐proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity, were those that placed the sugar and amide moieties between 7.7 and 12.1 Å apart along with angles of 180°.Angle of attack: The distance and angle between the N‐methylpiperidine and the biaryl side chain was analyzed in an effort to develop more potent Hsp90 C‐terminal inhibitors. Compounds that exhibited good anti‐proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity were those that placed the sugar and amide moieties between 7.7 and 12.1 Å apart along with angles of 180°.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136281/1/chem201504955_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136281/2/chem201504955.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136281/3/chem201504955-sup-0001-misc_information.pd

Synthesis and Biological Evaluation of Coumarin Replacements of Novobiocin as Hsp90 Inhibitors

Since Hsp90 modulates all six hallmarks of cancer simultaneously, it has become an attractive target for the development of cancer chemotherapeutics. In an effort to develop more efficacious compounds for Hsp90 inhibition, novobiocin analogues were prepared by replacing the central coumarin core with naphthalene, quinolinone, and quinoline surrogates. These modifications allowed for modification of the 2-position, which was previously unexplored. Biological evaluation of these compounds suggests a hydrophobic pocket about the 2-position of novobiocin. Anti-proliferative activities of these analogues against multiple cancer cell lines identified 2-alkoxyquinoline derivatives to exhibit improved activity

Structure-guided design of an Hsp90â N-terminal isoform-selective inhibitor

The 90 kDa heat shock protein (Hsp90) is a molecular chaperone responsible for folding proteins that are directly associated with cancer progression. Consequently, inhibition of the Hsp90 protein folding machinery results in a combinatorial attack on numerous oncogenic pathways. Seventeen small-molecule inhibitors of Hsp90 have entered clinical trials, all of which bind the Hsp90 N-terminus and exhibit pan-inhibitory activity against all four Hsp90 isoforms. pan-Inhibition of Hsp90 appears to be detrimental as toxicities have been reported alongside induction of the pro-survival heat shock response. The development of Hsp90 isoform-selective inhibitors represents an alternative approach towards the treatment of cancer that may limit some of the detriments. Described herein is a structure-based approach to design isoform-selective inhibitors of Hsp90β, which induces the degradation of select Hsp90 clients without concomitant induction of Hsp90 levels. Together, these initial studies support the development of Hsp90β-selective inhibitors as a method to overcome the detriments associated with pan-inhibition

Level of physical activity among middle-aged and older Chinese people: evidence from the China health and retirement longitudinal study

Background: With data from different regions accumulated, physical inactivity (PI) was found to be pandemic worldwide. Using China Health and Retirement Longitudinal Study (CHARLS), a nationwide longitudinal survey data, we aimed to delineate the prevalence, incidence and risk factors of physical inactivity (PI) among Chinese people aged 45 years and older. Methods: The CHARLS covered nearly all provinces, autonomous regions, municipalities of mainland China. With data from CHARLS, three cross-sectional analyses and a cohort analysis were conducted. In cross-sectional studies, we used surveys at 2011, 2013 and 2015 to examine the prevalence and its trend of PI. Multivariate generalized linear model was conducted in survey at 2011 to examine the risk factors for prevalent PI. Multiple imputation of missing values was used and results before and after imputation were compared. In cohort analysis, we identified people free of PI at 2011 and followed them up until 2015 to estimate the incidence of PI. Generalized estimating equation was used to examine the risk factors associated with incidence PI. In all analyses, PI was defined as insufficient physical activity according to the International Physical Activity Questionnaire (IPAQ) criterion. Results: 6650, 5946 and 9389 participants were eligible for cross-sectional analyses, and 4525 participants were included for cohort analysis. The weighted prevalence of PI was 22.25% (95% CI: 20.63–23.95%) in 2011, 20.64% (95% CI: 19.22–22.14%) in 2013 and 19.31% (95% CI: 18.28–20.38%) in 2015. In multivariate analysis, PI was associated with older age, higher education, overweight, obesity and difficulties in daily living, and was negatively associated with working and higher level of expenditure. No material change was detected in results after multiple imputation. In cohort analysis, older age, abundant public facilities, difficulties in daily living were identified as risk factors of incidence PI, while urban areas, college and above education, and working were protective factors. Conclusions: PI is pandemic in 45 years and older people in China. People with older age, difficulties in daily living and people who are not working are at higher risk. More efforts should be paid in estimating and promoting leisure-time physical activities

Gut-joint axis in knee synovitis: gut fungal dysbiosis and altered fungi–bacteria correlation network identified in a community-based study

Objectives: Knee synovitis is a highly prevalent and potentially curable condition for knee pain; however, its pathogenesis remains unclear. We sought to assess the associations of the gut fungal microbiota and the fungi–bacteria correlation network with knee synovitis. Methods: Participants were derived from a community-based cross-sectional study. We performed an ultrasound examination of both knees. A knee was defined as having synovitis if its synovium was ≥4 mm and/or Power Doppler (PD) signal was within the knee synovium area (PD synovitis). We collected faecal specimens from each participant and assessed gut fungal and bacterial microbiota using internal transcribed spacer 2 and shotgun metagenomic sequencing. We examined the relation of α-diversity, β-diversity, the relative abundance of taxa and the interkingdom correlations to knee synovitis. Results: Among 977 participants (mean age: 63.2 years; women: 58.8%), 191 (19.5%) had knee synovitis. β-diversity of the gut fungal microbiota, but not α-diversity, was significantly associated with prevalent knee synovitis. The fungal genus Schizophyllum was inversely correlated with the prevalence and activity (ie, control, synovitis without PD signal and PD synovitis) of knee synovitis. Compared with those without synovitis, the fungi–bacteria correlation network in patients with knee synovitis was smaller (nodes: 93 vs 153; edges: 107 vs 244), and the average number of neighbours was fewer (2.3 vs 3.2). Conclusion: Alterations of gut fungal microbiota and the fungi–bacteria correlation network are associated with knee synovitis. These novel findings may help understand the mechanisms of the gut-joint axis in knee synovitis and suggest potential targets for future treatment