In recent years, many studies have shown that it is meaningful to place rocks under stress paths corresponding to various loading and unloading conditions. However, the deformation evolution of rock ...under cyclic loading with consideration of the mechanical behavior and characteristics has rarely been studied under triaxial cyclic unloading and loading conditions. In practical engineering, particularly in underground or mining engineering, the stress increase in the rock mass in areas affected by mining is mainly caused by crack initiation and development when the rock is subjected to the effects of cyclic unloading and loading. In this study, variations in the stress–strain curves, irreversible strain, elastic modulus, and Poisson’s ratio are discussed and explained. The test results demonstrate that in comparison with a lower initial confining stress, increasing the initial confining pressure restrains the radial deformation of sandstone samples, and the degree of compaction of the sandstone samples rapidly increases in the failure stage. This results in the loss of the failure buffering process of the sandstone sample. Changes in the degree of compaction of the rock samples lead to obvious differences in the irreversible strain of the rock under different initial confining pressures and different limit unloading and loading cyclic confining stresses. The scanning electron microscopy and analysis results demonstrate that the macroscopic mechanical and microscopic physical properties of sandstone show different characteristics under different initial confining stresses.
A knowledge of permeability evolution with stress is important for the enhancement of coalbed methane production. In this study, a series of compaction-permeability tests with in-situ nuclear ...magnetic resonance (NMR) measurement were conducted by using a designed NMR testing system equipped with a loading device. Based on the NMR results, the permeability variation mechanism is investigated during the complete stress-strain process. The stress damage and its influence on permeability are analyzed. Experimental results illustrate that the permeability curve shows a slow decrease first, followed by a stable change, then a slow increase, and finally a sharp rise during the complete stress-strain process. Permeability evolution is closely related to coal pores. Adsorption pores have little contribution to the coal permeability while seepage pores contribute over 99% to the permeability. The permeability growth is found to lag behind the coal pores growth due to the poor connection of new pores. With the increase of damage, coal permeability increases nonlinearly. A power function can be used to describe the relationship for the tested samples.
Experimental research on the growth of internal flaws has rarely been reported due to the fact that it is difficult to cut internal flaws in specimens and cannot capture the initiation and ...propagation processes of internal flaws through direct observations. This paper proposed a method for creating internal flaws in specimens by utilizing the volatilization of camphor. A series of compression tests were performed on rock-like specimens including two embedded circular flaws, and CT techniques were used to investigate the internal damage behavior of flawed specimens. Experimental results illustrate that the strength and deformation properties of flawed specimens increase nonlinearly with the confining pressure as well as flaw inclination angle. Crack coalescence patterns and failure modes of flawed specimens depend on not only the confining pressure but also the flaw inclination angle. The crack coalescence pattern varies from wing crack coalescence to mixed tension-shear crack coalescence and then to the shear crack coalescence as the crack inclination angle increases. Confining pressure contributes to shear crack growth and has an inhibiting effect on the propagation of tension cracks. For specimens with the same flaw inclination angle, the failure mode changed from tension failure to mixed shear-tension failure or from mixed shear-tension failure to pure shear failure with the increase of confining pressure.
Lysosome‐related organelles (LROs) comprise a diverse group of cell type‐specific, membrane‐bound subcellular organelles that derive at least in part from the endolysosomal system but that have ...unique contents, morphologies and functions to support specific physiological roles. They include: melanosomes that provide pigment to our eyes and skin; alpha and dense granules in platelets, and lytic granules in cytotoxic T cells and natural killer cells, which release effectors to regulate hemostasis and immunity; and distinct classes of lamellar bodies in lung epithelial cells and keratinocytes that support lung plasticity and skin lubrication. The formation, maturation and/or secretion of subsets of LROs are dysfunctional or entirely absent in a number of hereditary syndromic disorders, including in particular the Hermansky‐Pudlak syndromes. This review provides a comprehensive overview of LROs in humans and model organisms and presents our current understanding of how the products of genes that are defective in heritable diseases impact their formation, motility and ultimate secretion.
Lysosome‐related organelles (LROs) are cell type‐specific subcellular structures that derive from both the secretory and endolysosomal pathways and that play key roles in numerous physiological systems, in most cases following stimulus‐dependent secretion of their contents. The biogenesis and/or secretion of LRO subsets are disrupted in hereditary syndromic disorders such as the Hermansky‐Pudlak syndromes and familial hemophagocytic lymphohistiocytosis. We comprehensively review LROs in humans and model organisms and the mechanisms by which products of disease genes regulate their formation, motility and ultimate secretion.
Background and Aims
To clarify high‐risk factors and develop a nomogram model to predict biochemical resolution or biochemical nonresolution (BNR) in patients with chronic DILI.
Approach and Results
...Retrospectively, 3655 of 5326 patients with chronic DILI were enrolled from nine participating hospitals, of whom 2866 underwent liver biopsy. All of these patients were followed up for over 1 year and their clinical characteristics were retrieved from electronic medical records. The endpoint was BNR, defined as alanine aminotransferase or aspartate aminotransferase >1.5× upper limit of normal or alkaline phosphatase >1.1× ULN, at 12 months from chronic DILI diagnosis. The noninvasive high‐risk factors for BNR identified by multivariable logistic regression were used to establish a nomogram, which was validated in an independent external cohort. Finally, 19.3% (707 of 3655) patients presented with BNR. Histologically, with the increase in liver inflammation grades and fibrosis stages, the proportion of BNR significantly increased. The risk of BNR was increased by 21.3‐fold in patients with significant inflammation compared to none or mild inflammation (p < 0.001). Biochemically, aspartate aminotransferase and total bilirubin, platelets, prothrombin time, sex, and age were associated with BNR and incorporated to construct a nomogram model (BNR‐6) with a concordance index of 0.824 (95% CI, 0.798–0.849), which was highly consistent with liver histology. These results were successfully validated both in the internal cohort and external cohort.
Conclusions
Significant liver inflammation is a robust predictor associated with biochemical nonresolution. The established BNR‐6 model provides an easy‐to‐use approach to assess the outcome of chronic DILI.
Rockbursts in deep tunnels subjected to high crustal stress were investigated using a general particle dynamics (GPD) code with the Holmquist–Johnson–Cook damage model (HJC). Under dynamic excavation ...disturbance, several numerical tests were carried out to investigate the dynamic failure patterns of surrounding rock masses with different preexisting cracks around deep tunnels. The numerical results showed that the GPD code can satisfactorily simulate the phenomenon of rockburst caused by crack evolution, including predicting the ejection velocity, rockburst location and ejected rock block volume. Moreover, the analysis of the circumferential stress in the surrounding rock of deep tunnels at the Jinping II Hydropower Station shows the efficiency of the GPD code. In addition, four typical rockburst, which occurred under different geological conditions at the Jinping II Hydropower Station, were analyzed by using the GPD code. The numerical simulations suggested that the GPD code can efficiently reproduce the 2D and 3D crack growth in the surrounding rock, which eventually leads to the occurrence of rockburst.
•Rockbursts in deep tunnels subjected to high crustal stress were investigated using a general particle dynamics code.•The numerical results showed that the GPD code can satisfactorily simulate the phenomenon of rockburst.•The GPD code can efficiently reproduce the 2D and 3D crack growth in the surrounding rock.
The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme ...inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown. COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors. We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood. In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs. This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.
Summary
Background
Treatment of chronic drug‐induced liver injury (DILI) or herb‐induced liver injury(HILI) is an important and unresolved challenge. There is no consensus regarding the indications ...for corticosteroids for chronic DILI/HILI.
Aims
To investigate the efficacy and safety of corticosteroid plus glycyrrhizin for patients with chronic DILI/HILI.
Methods
This was a randomised open‐label trial. Eligible patients with causality assessment using the updated RUCAM were randomly assigned (1:1) either to the steroid treatment group (48‐week stepwise dose reduction of methylprednisolone plus glycyrrhizin) or control group (glycyrrhizin alone). Liver biopsies were performed at baseline and at the end of the 48‐week treatment period. The primary outcome was the proportion of patients with sustained biochemical response (SBR). The secondary outcomes were improvement in liver histology, time to biochemical normalisation and safety.
Results
Of 80 participants, 70 (87.5%) completed the trial. The patients were predominantly female (77.5%), aged >40 years (77.5%) and had a hepatocellular injury pattern of DILI (71.2%). Compared to the control group, the treatment group showed a higher proportion of SBR (94.3% vs. 71.4%, p = 0.023), shorter biochemical normalisation time and histological improvements in both histological activity and fibrosis. The DILI and HILI subgroups, as well as the autoimmune hepatitis (AIH)‐like DILI and non‐AIH‐like subgroups, showed comparable responses. No severe adverse events were observed during the trial.
Conclusion
This study provides the first clinical evidence that corticosteroid plus glycyrrhizin therapy for chronic DILI with or without AIH‐like features can achieve both biochemical response and histological improvements with good safety. (ClinicalTrials.gov, NCT 02651350).
This paper aims to present a comprehensive survey on water quality soft-sensing of a wastewater treatment process (WWTP) based on artificial neural networks (ANNs). We mainly present problem ...formulation of water quality soft-sensing, common soft-sensing models, practical soft-sensing examples and discussion on the performance of soft-sensing models. In details, problem formulation includes characteristic analysis and modeling principle of water quality soft-sensing. The common soft-sensing models mainly include a back-propagation neural network, radial basis function neural network, fuzzy neural network (FNN), echo state network (ESN), growing deep belief network and deep belief network with event-triggered learning (DBN-EL). They are compared in terms of accuracy, efficiency and computational complexity with partial-least-square-regression DBN (PLSR-DBN), growing ESN, sparse deep belief FNN, self-organizing DBN, wavelet-ANN and self-organizing cascade neural network (SCNN). In addition, this paper generally discusses and explains what factors affect the accuracy of the ANNs-based soft-sensing models. Finally, this paper points out several challenges in soft-sensing models of WWTP, which may be helpful for researchers and practitioner to explore the future solutions for their particular applications.
In this study, multilevel and conventional unloading triaxial compression tests under different confining pressures are separately carried out to systematically reveal the deformation, energy ...evolution, and fracture characteristics of sandstone samples. Results show that under the multilevel unloading condition, the increase of the initial confining pressure has a more obvious inhibitory effect on the radial strain of sandstone, and the samples can fully exhibit elastic deformation and partial plastic deformation, showing obvious plastic characteristics. The radial energy growth factor is more sensitive than the axial energy growth factor during the process of confining pressure unloading, and the larger the initial confining pressure, the earlier the period-doubling bifurcation region and chaotic region are reached. To better understand the deformation and failure process of rock during engineering excavation, it is necessary to establish a constitutive relation describing the mechanical properties of rock. The three-step failure mode also proves that there are tensile and shear fractures in sandstone samples, in which the effects of tensile stress and shear stress are more or less interdependent in the failure process. It can be seen that multilevel unloading makes the energy conversion more adequate and reduces the sudden release of energy when the rock fails, reducing the possibility of rockburst and making the excavation unloading process safer. This will deepen the understanding of rock failure behavior and contribute to the better application of energy characteristics to relevant engineering practices.
PDF
