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Large-scale rock formations, referred to as "rockmasses", consist of intact rock separated by pre-existing discontinuities (i.e., joints). The mechanical behavior of rockmasses is difficult to directly test in the laboratory due to the required specimen scale. Instead, Synthetic Rockmass Modeling (SRM) is often used to simulate field-scale rockmass behavior. SRM requires a calibrated discrete element model (DEM) of intact rock combined with a Discrete Fracture Network (DFN). While the SRM concept has been informally determined to provide reasonable results based on practitioner experience, detailed and peer-reviewed validation is lacking. The goal of this study was to evaluate the predictive capabilities of the SRM method. Previously available data on intact and rockmass analog laboratory specimens of Blanco Mera granite containing DFNs with two joint sets were used as a basis for the SRM created in this study. Specifically, the intact DEM was a Bonded Block Model (BBM), generated to match the grain structure and composition of Blanco Mera granite and the model's input parameters were calibrated so that the behavior of the BBM matched that of the intact laboratory specimens. The predictive capabilities of the model were evaluated by recreating the DFN from the jointed laboratory specimens within the intact BBM and comparing the behavior of the jointed models back to the jointed laboratory specimens, which has not been previously studied in the literature. The BBM was found capable of approximately predicting the behavior of rockmass analog specimens containing a pre-existing DFN without further calibration, which shows potential for the use of SRM in both industry and academia. Specifically, the BBM predicted the strength, dilatancy, and microfracturing behavior of the jointed laboratory specimens.

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Changes of failure mechanism with increasing confinement, from extensional to shear-dominated failure, are widely observed in the rupture of intact specimens at the laboratory scale and in rock masses. In an analysis published in 2018, both unconfined and triaxial compressive tests were conducted to investigate the strength characteristics of 84 specimens of a Utah coal, including the spalling limits, the ratio of apparent unconfined compressive strength to unconfined compressive strength (UCS), the damage characteristics, and the post-yield dilatancy. These mechanical characteristics were found to be strongly anisotropic as a function of the orientation of the cleats relative to the loading direction, defined as the included angle. A total of four different included angles were used in the work performed in 2018. The authors found that the degree of anisotropic strength differed according to the included angle. However, the transition from extensional to shear failure at the given confinements was not clearly identified. In this study, a total of 20 specimens were additionally prepared from the same coal sample used in the previous study and then tested under both unconfined and triaxial compressive conditions. Because the authors already knew the most contrasting cases of the included angles from the previous work using the four included angles, they chose only two of the included angles (0° and 30°) for this study. For the triaxial compressive tests, a greater confining stress than the mean UCS was applied to the specimens in an attempt to identify the brittle-ductile transition of the coal. The new results have been compiled with the previous results in order to re-evaluate the confinement-dependency of the coal behavior. Additionally, the different confining stresses are used as analogs for different width-to-height (W/H) conditions of pillar strength. Although the W/H ratios of the specimens were not directly considered during testing, the equivalent W/H ratios of a pillar as a function of the confining stresses were estimated using an existing empirical solution. According to this relationship, the W/H at which in situ pillar behavior would be expected to transition from brittle to ductile is identified.

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Characterizing a coal from an engineering perspective for design of mining excavations is critical in order to prevent fatalities, as underground coal mines are often developed in highly stressed ground conditions. Coal pillar bursts involve the sudden expulsion of coal and rock into the mine opening. These events occur when relatively high stresses in a coal pillar, left for support in underground workings, exceed the pillar's load capacity causing the pillar to rupture without warning. This process may be influenced by cleating, which is a type of joint system that can be found in coal rock masses. As such, it is important to consider the anisotropy of coal mechanical behavior. Additionally, if coal is expected to fail in a brittle manner, then behavior changes, such as the transition from extensional to shear failure, have to be considered and reflected in the adopted failure criteria. It must be anticipated that a different failure mechanism occurs as the confinement level increases and conditions for tensile failure are prevented or strongly diminished. The anisotropy and confinement dependency of coal behavior previously mentioned merit extensive investigation. In this study, a total of 84 samples obtained from a Utah coal mine were investigated by conducting both unconfined and triaxial compressive tests. The results showed that the confining pressure dictated not only the peak compressive strength but also the brittleness as a function of the major to the minor principal stress ratio. Additionally, an s-shaped brittle failure criterion was fitted to the results, showing the development of confinement-dependent strength. Moreover, these mechanical characteristics were found to be strongly anisotropic, which was associated with the orientation of the cleats relative to the loading direction.

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BACKGROUND: Validation of physiologic miRNA targets has been met with significant challenges. We employed HITS-CLIP to identify which miRNAs participate in liver regeneration, and to identify their target mRNAs. RESULTS: miRNA recruitment to the RISC is highly dynamic, changing more than five-fold for several miRNAs. miRNA recruitment to the RISC did not correlate with changes in overall miRNA expression for these dynamically recruited miRNAs, emphasizing the necessity to determine miRNA recruitment to the RISC in order to fully assess the impact of miRNA regulation. We incorporated RNA-seq quantification of total mRNA to identify expression-weighted Ago footprints, and developed a microRNA regulatory element (MRE) prediction algorithm that represents a greater than 20-fold refinement over computational methods alone. These high confidence MREs were used to generate candidate 'competing endogenous RNA' (ceRNA) networks. CONCLUSION: HITS-CLIP analysis provide novel insights into global miRNA:mRNA relationships in the regenerating liver.

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Isolation of hepatic progenitor cells is a promising approach for cell replacement therapy of chronic liver disease. The winged helix transcription factor Foxl1 is a marker for progenitor cells and their descendants in the mouse liver in vivo. Here, we purify progenitor cells from Foxl1-Cre; RosaYFP mice and evaluate their proliferative and differentiation potential in vitro. Treatment of Foxl1-Cre; RosaYFP mice with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet led to an increase of the percentage of YFP-labeled Foxl1(+) cells. Clonogenic assays demonstrated that up to 3.6% of Foxl1(+) cells had proliferative potential. Foxl1(+) cells differentiated into cholangiocytes and hepatocytes in vitro, depending on the culture condition employed. Microarray analyses indicated that Foxl1(+) cells express stem cell markers such as Prom1 as well as differentiation markers such as Ck19 and Hnf4a. Thus, the Foxl1-Cre; RosaYFP model allows for easy isolation of adult hepatic progenitor cells that can be expanded and differentiated in culture.

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