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ISRM Suggested Method: Determining Deformation and Failure Characteristics of Rocks Subjected to True Triaxial Compression
The purpose of this ISRM Suggested Method is to introduce a guideline on determining deformation and failure characteristics of rocks subjected to true triaxial compression on different stress path. The true triaxial testing apparatus was reviewed by means of the function and engineering application. Some key techniques, such as stress and strain measurements, and reduction of end effect between specimen and metal platens, preventing metal platens interference, were stated and suggested in detail. Methodology of specimen processing, specimen shape, and testing procedure are characterized. There is an explanation of the experimental data processing on stress–strain curves, strength, and fracture mode.
Journal Article
Latent Dirichlet allocation (LDA) and topic modeling: models, applications, a survey
Topic modeling is one of the most powerful techniques in text mining for data mining, latent data discovery, and finding relationships among data and text documents. Researchers have published many articles in the field of topic modeling and applied in various fields such as software engineering, political science, medical and linguistic science, etc. There are various methods for topic modelling; Latent Dirichlet Allocation (LDA) is one of the most popular in this field. Researchers have proposed various models based on the LDA in topic modeling. According to previous work, this paper will be very useful and valuable for introducing LDA approaches in topic modeling. In this paper, we investigated highly scholarly articles (between 2003 to 2016) related to topic modeling based on LDA to discover the research development, current trends and intellectual structure of topic modeling. In addition, we summarize challenges and introduce famous tools and datasets in topic modeling based on LDA.
Journal Article
NAFLD and Diabetes: Two Sides of the Same Coin? Rationale for Gene-Based Personalized NAFLD Treatment
The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly and at the forefront of worldwide concern. Characterized by excessive fat accumulation in the liver, NAFLD regularly coexists with metabolic disorders, including type 2 diabetes, obesity, and cardiovascular disease. It has been well established that the presence of NAFLD increases the incidence of type 2 diabetes, while diabetes aggravates NAFLD to more severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, recent progress on the genotype/phenotype relationships in NAFLD patients indicates the development of NAFLD with a relative conservation of glucose metabolism in individuals with specific gene variants, such as the patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 protein (TM6SF2) variants. This review will focus on the clinical and pathophysiological connections between NAFLD and type 2 diabetes and will also discuss a disproportionate progression of NAFLD and diabetes, and the different responses to lifestyle and drug intervention in NAFLD patients with specific gene variants that may give insight into personalized treatment for NAFLD.
Journal Article
The role of the LncRNA-FA2H-2-MLKL pathway in atherosclerosis by regulation of autophagy flux and inflammation through mTOR-dependent signaling
Atherosclerosis is a progressive, chronic inflammation in arterial walls. Long noncoding RNAs (lncRNAs) participate in inflammation, but the exact mechanism in atherosclerosis is unclear. Our microarray analyses revealed that the levels of lncRNA-FA2H-2 were significantly decreased by oxidized low-density lipoprotein (OX-LDL). Bioinformatics analyses indicated that mixed lineage kinase domain-like protein (MLKL) might be regulated by lncRNA-FA2H-2. In vitro experiments showed that lncRNA-FA2H-2 interacted with the promoter of the MLKL gene, downregulated MLKL expression, and the binding sites between −750 and 471 were necessary for lncRNA-FA2H-2 responsiveness to MLKL. Silencing lncRNA-FA2H-2 and overexpression of MLKL could activate inflammation and inhibited autophagy flux. Both lncRNA-FA2H-2 knockdown and overexpression of MLKL could significantly aggravate inflammatory responses induced by OX-LDL. We found that the 3-methyladenine (3-MA) and Atg7-shRNA enhanced inflammatory responses induced by knockdown of lncRNA-FA2H-2 and overexpression of MLKL. We demonstrated that the effects of MLKL on autophagy might be associated with a mechanistic target of rapamycin (mTOR)-dependent signaling pathways. In vivo experiments with apoE knockout mice fed a western diet demonstrated that LncRNA-FA2H-2 knockdown decreased microtubule-associated expression of microtubule-associated protein 1 light chain 3 II and lysosome-associated membrane protein 1, but increased expression of sequestosome 1 (p62), MLKL, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and interleukin-6 in atherosclerotic lesions. Our findings indicated that the lncRNA-FA2H-2-MLKL pathway is essential for regulation of autophagy and inflammation, and suggested that lncRNA-FA2H-2 and MLKL could act as potential therapeutic targets to ameliorate atherosclerosis-related diseases.
Journal Article
Experimental Study of Failure Differences in Hard Rock Under True Triaxial Compression
In view of a previous study of the intermediate principal stress effect at a limited σ2 range, a series of true triaxial tests, covering a full range of intermediate principal stresses that vary from the generalized triaxial compression stress state (σ2 = σ3) to the generalized triaxial tensile stress state (σ1 = σ2), was carried out on sandstone and granite samples. The experimental results revealed that the deformation, failure strength and failure mode have a significant dependence on the stress state. As an effect of the intermediate principal stress on crack evolution, the deformation difference known as stress-induced deformation anisotropy occurred and should be considered when developing the mechanical model. Moreover, a post-peak deformation with a step-shaped stress drop is observed and illustrates that there will be a multi-stage bearing capacity after the rock failure. The peak strength is non-symmetrical with the increasing σ2 and is closely related to the Lode angle. Based on the final fracture surface and SEM analysis under true triaxial compression, three failure modes and failure zones, including tension failure, shear failure and mixed failure, are delineated and discussed. Combining the failure mode and the strength under true triaxial compression, it is found that the strength variation exhibited a close relationship to the failure mechanism.
Journal Article
Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease
A randomized, parallel controlled, open-label clinical trial was conducted to evaluate the effect of a botanic compound berberine (BBR) on NAFLD.
A randomized, parallel controlled, open-label clinical trial was conducted in three medical centers (NIH Registration number: NCT00633282). A total of 184 eligible patients with NAFLD were enrolled and randomly received (i) lifestyle intervention (LSI), (ii) LSI plus pioglitazone (PGZ) 15mg qd, and (iii) LSI plus BBR 0.5g tid, respectively, for 16 weeks. Hepatic fat content (HFC), serum glucose and lipid profiles, liver enzymes and serum and urine BBR concentrations were assessed before and after treatment. We also analyzed hepatic BBR content and expression of genes related to glucose and lipid metabolism in an animal model of NAFLD treated with BBR.
As compared with LSI, BBR treatment plus LSI resulted in a significant reduction of HFC (52.7% vs 36.4%, p = 0.008), paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles (all p<0.05). BBR was more effective than PGZ 15mg qd in reducing body weight and improving lipid profile. BBR-related adverse events were mild and mainly occurred in digestive system. Serum and urine BBR concentrations were 6.99ng/ml and 79.2ng/ml, respectively, in the BBR-treated subjects. Animal experiments showed that BBR located favorably in the liver and altered hepatic metabolism-related gene expression.
BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism.
ClinicalTrials.gov NCT00633282.
Journal Article
Influences of Schistosity Structure and Differential Stress on Failure and Strength Behaviors of an Anisotropic Foliated Rock Under True Triaxial Compression
Foliated rocks are often encountered in underground engineering, and the spatial orientation relationship between its foliation and in situ stress controls the stability of the surrounding rock. This is closely related to the anisotropy of the mechanical properties of foliated rocks. The anisotropic mechanical properties of thin foliated rock under the influences of foliation and stress can be obtained by laboratory testing; however, there have been few experimental studies on foliated rocks under true triaxial compression at present. Foliated rocks are in a three-dimensional unequal stress state in deep excavation engineering; thus, to evaluate the stability of surrounding rock and scientifically guide the support design, a systematic true triaxial test considering the loading orientations (β, ω) of schistosity for a foliated gneiss was conducted. The results show that the strength and failure of the gneiss are greatly affected by inherent structure and stress conditions. More specifically, the larger the ω and σ2, the greater is the strength, and the failure mode tends to be controlled by the differential stress. Finally, a new empirical true triaxial anisotropic failure criterion was proposed according to the variations of strength with loading angle and stress conditions. This criterion can reflect the tendency and sensitivity of the change in the strength to σ2 at different ω and β, and can satisfy the need to model degradation from the true triaxial stress state to the conventional triaxial stress state. This criterion provides a new approach to characterize the strength of anisotropic rocks and improve the design of engineering works in practice.HighlightsThe strength and failure of the foliated gneiss are affected by the loading angle of schistosity structure and differential stress.When the differential stress is larger, the larger the angles ω and β, the more does the failure mode tend to be controlled by stress induction.The strength of the foliated gneiss has a strengthening effect on ω, and the larger the β, the weaker is the strengthening effect of ω.A new empirical true triaxial anisotropic failure criterion is proposed according to the variations of strength with ω, β, and stress conditions.
Journal Article
C/EBPβ enhances platinum resistance of ovarian cancer cells by reprogramming H3K79 methylation
Chemoresistance is a major unmet clinical obstacle in ovarian cancer treatment. Epigenetics plays a pivotal role in regulating the malignant phenotype, and has the potential in developing therapeutically valuable targets that improve the dismal outcome of this disease. Here we show that a series of transcription factors, including C/EBPβ, GCM1, and GATA1, could act as potential modulators of histone methylation in tumor cells. Of note, C/EBPβ, an independent prognostic factor for patients with ovarian cancer, mediates an important mechanism through which epigenetic enzyme modifies groups of functionally related genes in a context-dependent manner. By recruiting the methyltransferase DOT1L, C/EBPβ can maintain an open chromatin state by H3K79 methylation of multiple drug-resistance genes, thereby augmenting the chemoresistance of tumor cells. Therefore, we propose a new path against cancer epigenetics in which identifying and targeting the key regulators of epigenetics such as C/EBPβ may provide more precise therapeutic options in ovarian cancer.
In ovarian cancer, the mechanism of chemoresistance is a key question. Here, the authors demonstrate that C/EBPβ and DOT1L together increase methylation of H3K79, which upregulates expression of oncogenic genes and drives poor platinum response and poor survival in ovarian cancer.
Journal Article
Clinical characteristics of coronavirus disease 2019 (COVID-19) in patients out of Wuhan from China: a case control study
Background
A large-scale global outbreak of coronavirus disease-19 (COVID-19) out of Wuhan, from China, occurred in January 2020. To examine the clinical characteristics of COVID-19 in infected patients out of Wuhan, from China.
Methods
Thirteen patients were confirmed to be infected with novel coronavirus-2019 (2019-nCoV) between January 27 and February 8, 2020, in Baoji city, Shannxi, northwestern China. Epidemiological and clinical information, and computed to morphology imaging data from all COVID-19 patients were collected; cases were divided into two groups according to the severity of infection (mild or severe).
Results
Nine (9/13) COVID-19 patients exhibited mild disease severity, and defined as second-generation human-to-human transmission cases. Most patients (11/13) had a history of travel to or from Wuhan. There were no differences in sex and age between the mild and severe cases (all
P
> 0.05). A moderate degree of fever (11/13), cough (13/13), and fatigue (8/13) were common symptoms; however, there was no statistical difference between mild and severe cases in this regard (all
P
> 0.05). Oxyhemoglobin saturation and oxygenation index decreased, and C-reactive protein (CRP) and serum amyloid A (SAA) levels were elevated in all patients with COVID-19 infection, with statistically significant differences between those with severe disease and mild infection (all
P
< 0.05). Twelve of 13 COVID-19 patients exhibited changes in chest CT imaging features, and time course changes were different between mild and severe cases (all
P
< 0.05).
Conclusion
Most cases of COVID-19 infection were second-generation human-to-human transmissions from Wuhan and were mild in severity. The clinical characteristics of COVID-19 varied. Oxyhemoglobin saturation, oxygenation index, CRP and SAA levels, and CT features were reliable parameters to evaluate the severity of COVID-19 infection. However, a few patients with mild COVID-19 disease lacked typical characteristics such as fever and changes in CT imaging features.
Journal Article