Influence of time-dependence on failure of echelon rock joints through a novel DEM model

This is an Accepted Manuscript of an article published by Taylor & Francis Group in [European Journal of Environmental and Civil Engineering] on [September 2015], available online at: http://www.tandfonline.com/10.1080/19648189.2015.1064624This article investigates the time-dependent influence on the shear failure behaviour of parallel rock joints in the echelon arrangement due to chemical weathering, which can be treated as a generalised time-dependency of the rock material. A time-dependent parameter alpha, identifying the accumulated relative mass removal of bonding material, has been implemented into a novel distinct element method bond contact model. This model is based on a series of mechanical test on bonded aluminium rods with different bond geometries. The numerical direct shear test results of echelon rock joints characterised by different values of alpha show that increasing time-dependent parameter alpha can lead to a lower crack initiation and peak stresses. This is accompanied by a growing ratio of the microscopic compressive-shear-torsional (CST) bond failure number of bond failures to the total number of failures, except for the case without weathering influence. High values of alpha render the material bridge a weaker part to be cut through, generating a large number of CST bond breakages along the central shear axis.Peer ReviewedPostprint (author's final draft

Multivariate Time Series Density Clustering Algorithm Using Shapelet Space

Multivariate time series clustering has become an important research topic in the task of time series analysis. Compared with univariate time series, the research of multivariate time series is more complex and difficult. Although many clustering algorithms for multivariate time series have been proposed, these algorithms still have difficulties in solving the accuracy and interpretation at the same time. Firstly, most of the current work does not consider the length redundancy and variable correlation of multivariable time series, resulting in large errors in the final similarity matrix. Secondly, the data are commonly used in the clustering process with the division paradigm, when the numerical space presents a complex distribution, this idea does not perform well, and it does not have the explanatory power of each variable and space. To address the above problems, this paper proposes a multivariate time series adaptive weight density clustering algorithm using Shapelet (high information-rich continuous subsequence) space (MDCS). This algorithm firstly performs a Shapelet search for each variable, and obtains its own Shapelet space through an adaptive strategy. Then, it weights the numerical distribution generated by each variable to obtain a similarity matrix that is more consistent with the characteristics of data distribution. Finally, the data are finally allocated using the shared nearest neighbor density peak clustering algorithm with improved density calculation and secondary allocation. Experimental results on several real datasets demonstrate that MDCS has better clustering results compared with current state-of-the-art clustering algorithms, with an average increase of 0.344 and 0.09 in the normalized mutual information and Rand index, balancing performance and interpretability

c-FLIP Degradation Mediates Sensitization of Pancreatic Cancer Cells to TRAIL-Induced Apoptosis by the Histone Deacetylase Inhibitor LBH589

Great efforts have been made to develop novel and efficacious therapeutics against pancreatic cancer to improve the treatment outcomes. Tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) is such a therapeutic cytokine with selective killing effect toward malignant cells. However, some human pancreatic cancers are intrinsically resistant to TRAIL-mediated apoptosis or therapy. In this study, we have shown that the histone deacetylase inhibitor LBH589 can synergize with TRAIL to augment apoptosis even in TRAIL-resistant cells. LBH589 decreased c-FLIP levels in every tested cell line and survivin levels in some of the tested cell lines. Enforced expression of ectopic c-FLIP, but not survivin, abolished the cooperative induction of apoptosis by the combination of LBH589 and TRAIL, indicating that c-FLIP downregulation plays a critical role in LBH589 sensitization of pancreatic cancer cells to TRAIL. Moreover, LBH589 decreased c-FLIP stability and the presence of the proteasome inhibitor MG132 prevented c-FLIP from reduction by LBH589. Correspondingly, we detected increased levels of ubiqutinated c-FLIP in LBH589-treated cells. These data thus indicate that LBH589 promotes ubiqutin/proteasome-mediated degradation of c-FLIP, leading to downregulation of c-FLIP. Collectively, LBH589 induces c-FLIP degradation and accordingly sensitizes pancreatic cancer cells to TRAIL-induced apoptosis, highlighting a novel therapeutic regimen against pancreatic cancer

A tryst of ‘blood pressure control- sex- comorbidities’:the odyssey of basic public health services in Yunnan in quest for truth

Background: The Basic Public Health Service (BPHS), a recently announced free healthcare program, aims to combat the most prevalent Noncommunicable Disease-“Hypertension” (HTN)-and its risk factors on a nationwide scale. In China, there is a rife that HTN less impacts women during their lifetime. We, therefore, aimed to evaluate the sex disparity in hypertension patients with comorbidities among south-west Chinese and the contribution of BPHS to address that concern. Methods: We have opted for a multistage stratified random sampling method to enroll hypertensive patients of 35 years and older, divided them into BPHS and non-BPHS groups. We assessed the sex disparity in HTN patients with four major comorbidities- Dyslipidemia, Diabetes Mellitus (DM), Cardiovascular Disease (CVD), and Chronic Kidney Disease (CKD), and descriptive data were compiled. Odds ratios from logistic regression models estimated the effectiveness of BPHS in the management of HTN with comorbidities. Results: Among 1521 hypertensive patients,1011(66.5%) were managed in the BPHS group. The proportion of patients who had at least one comorbidity was 70.7% (95% confidence interval [CI]: 66.3-76.8%), patients aged 65 years and older were more likely to have coexisting comorbidities. Participants who received the BPHS showed significant blood pressure (BP) control with two comorbidities (odds ratio [OR] = 2.414, 95% CI: 1.276–4.570), three or more (OR = 5.500, 95%CI: 1.174–25.756). Patients with dyslipidemia and DM also benefited from BPHS in controlling BP (OR = 2.169, 95% CI: 1.430–3.289) and (OR = 2.785, 95%CI: 1.242–6.246), respectively. In certain high-income urban survey centers, there was sex differences in the HTN management provided by BPHS, with men having better BP control rates than women. Conclusions: Perhaps this is the first study in China to succinctly show the effectiveness and sex disparity regarding “management of hypertensive comorbidities”. This supports that the BPHS program plays a pivotal role in controlling BP, therefore should recommend the national healthcare system to give women a foremost priority in BPHS, especially to those from low-socioeconomic and low-scientific literacy regions.</p

Insights into APC/C: from cellular function to diseases and therapeutics

Anaphase-promoting complex/cyclosome (APC/C) is a multifunctional ubiquitin-protein ligase that targets different substrates for ubiquitylation and therefore regulates a variety of cellular processes such as cell division, differentiation, genome stability, energy metabolism, cell death, autophagy as well as carcinogenesis. Activity of APC/C is principally governed by two WD-40 domain proteins, Cdc20 and Cdh1, in and beyond cell cycle. In the past decade, the results based on numerous biochemical, 3D structural, mouse genetic and small molecule inhibitor studies have largely attracted our attention into the emerging role of APC/C and its regulation in biological function, human diseases and potential therapeutics. This review will aim to summarize some recently reported insights into APC/C in regulating cellular function, connection of its dysfunction with human diseases and its implication of therapeutics

An investigation on loose cemented granular materials via DEM analyses

This paper presents the results of a numerical study carried out by 2D discrete element method analyses on the mechanical behavior and strain localization of loose cemented granular materials. Bonds between particles were modeled in order to replicate the mechanical behavior observed in a series of laboratory tests performed on pairs of glued aluminum rods which can fail either in tension or shear (Jiang et al. in Mech Mater 55:1–15, 2012). This bond model was implemented in a DEM code and a series of biaxial compression tests employing lateral flexible boundaries were performed. The influence of bond strength and confinement levels on the mechanical behavior and on the onset of shear bands and their propagation within the specimens were investigated. Comparisons were also drawn with other bond models from the literature. A new dimensionless parameter incorporating the effects of both bond strength and confining pressure, called BS, was defined. The simulations show that shear strength and also dilation increase with the level of bond strength. It was found out that for increasing bond strength, shear bands become thinner and oriented along directions with a higher angle over the horizontal. It also emerged that the onset of localization coincided with the occurrence of bond breakages concentrated in some zones of the specimens. The occurrence of strain localization was associated with a concentration of bonds failing in tension