The particle mechanics method is used to simulate the process of thermally induced micro- and macrocracks in granite, to elucidate the mechanisms responsible for temperature-dependent mechanical ...properties. The numerical results are quantified and compared with existing results from other experimental data in the literature. The results indicate that heating generally reduces the compressive and tensile strengths of granites, first because of increasing thermal stresses, and second because of the generation of tensile microcracks. Rock mechanical properties are reduced in specimens subjected to heating–cooling cycles, solely because of the increase in density of thermally induced tensile microcracks. The presence of a thermal gradient induces the formation of macrocracks, which propagate from relatively cool to relatively warm areas. It is also observed that the boundary condition of the specimen can also affect the development of microcracks.
A clear understanding of the convective heat transfer characteristics in the three-dimensional (3D) rough rock fracture is important for evaluating heat recovery in fractured reservoirs. A granite ...sample containing a Brazilian-induced artificial fracture, which was tested at increasing normal compressive stresses, was adopted to build 3D numerical models for rough rock fractures. At each stress level, flow-through simulation tests with different injection velocities were performed to examine the effect of fracture geometrical alterations induced by changing stresses on the heat transfer processes within hot fractured rock samples. Meanwhile, a hypothetical rough fracture and a parallel plate fracture, with an equivalent mechanical aperture to the artificial fracture, were constructed for the same heat transfer simulations as references. The results show that the flow and heat transfer behaviors in three types of fractures are significantly different, and the difference becomes more obvious as the normal stress and flow velocity increase. The alterations in asperity contacts and void spaces due to stress changes increase the heterogeneities of the distributions of streamlines and water temperatures in the artificial fracture. The tortuosity induced by the global fluctuation of the surface roughness in the hypothetical fracture cannot describe the flow and heat transport in the artificial fracture. The heat transfer coefficient in three types of fractures decreases non-linearly as the hydraulic aperture increases. Under the same hydraulic aperture, the heat transfer coefficient is larger in the hypothetical fracture than in the other two fractures. The channeling flow within the artificial fracture under high normal stresses weakens the heat transfer, resulting in the smallest heat transfer coefficient compared to the other two fractures. An empirical model was developed to describe the relationship between the normalized heat transfer coefficient and the hydraulic aperture, and this model was validated well using the published heated flow-through experimental results.
•Heat transfer in 3D parallel plate fracture, hypothetical fracture and Brazilian-induced artificial fracture were compared.•An empirical model of the heat transfer coefficient in the 3D rough rock fracture with heterogeneous apertures was proposed.•The empirical model was validated using the heated flow-through experimental results.
•Unloading-induced instability of critically stressed fractures is studied using displacement-driven and unloading-driven shear tests.•Stress state significantly influences fracture activation, but ...the effects of unloading rate and fluid condition are relatively minor.•Maximum seismic moment due to unloading-induced fracture instability is predicted and verified based on the experimental data.
Hundreds of anthropogenic earthquakes have recently occurred worldwide due to underground space creation and energy extraction. The mechanism behind the human-induced geohazards is most likely associated with the reduction of normal stress on pre-existing fractures and faults. This study reports a series of laboratory experiments to investigate the mechanism of unloading-induced fracture activation, and proposes a simple approach to predict the maximum seismic moment for a critically stressed fracture. The unloading-driven shear test results exhibit that the unloading process induces the stress states of the sawcut and natural fractures to approach the Mohr-Coulomb failure envelope, and the normal stress unloading rate influences the peak slip rate. The fracture instability is dependent on the relationship between the stiffness of the system and the slip weakening rate of the fracture, and the shear dilation mainly occurs after the fracture activation. The test results also show that the critical shear stress of the sawcut fracture during the unloading-driven shear test is approximately equal to the residual shear strength after the displacement-driven fracture slip. This relationship inspires us to develop a new approach to estimate the maximum seismic moment. Our data demonstrate that the maximum seismic moments for both the fractures obtained from the unloading-driven shear tests are all below the upper limit lines, indicating that the proposed approach is reasonable. The uncertainty analysis shows that the accurate estimation of fault size can improve the maximum seismic moment prediction.
The evolution of gouge materials in rock fractures or faults undergoing shear can change fracture properties in terms of shear strength and dilation, fluid transmissivity and retardation for ...contaminants. In order to conceptually understand gouge mechanical behaviors including movement, microcracking, abrasion and redistribution, particle mechanics models were used to simulate single- and multi-gouge particles in a rough fracture segment undergoing shear. The results show that gouge particles behave in two different ways under low and high normal stresses, respectively. Under low normal stress, gouge particles mainly roll with the moving fracture walls, with little surface damage and small dilation during the shear process. Under high normal stress, gouge particles can be crushed into a few major pieces and a large number of minor comminuted particles, accompanied by more severe damage (abrasion and microcracking) in fracture walls and continuous fracture closure. The modeling results were also compared with published experiments and used to explain the observed macroscopic behaviors of rock fracture undergoing shear. The effects of microparameters used in the particle mechanics models on the simulation of gouge behaviors were also investigated through sensitivity analysis.
Rock fractures are major conduits for fluid flow in fractured rocks, and the convective heat transfer between rock fracture surfaces and circulating fluid is a critical issue in heat recovery in ...fractured rocks. It has been demonstrated that fracture surface roughness has a significant influence on the mechanical, hydraulic, thermal and transport behavior of single fractures. This study aimed to assess the effects of local surface roughness of fractures on fluid flow and heat transfer processes at the macroscopic scale of fracture networks. Two distributions of Joint Roughness Coefficient (JRC) were determined based on the JRC data in Oskarshamn/Forsmark, Sweden and Bakhtiary, Iran. Two empirical models relating hydraulic apertures to mechanical apertures were considered. A total of ninety-one realizations that considered different JRC distributions and empirical models of mechanical-hydraulic apertures were studied. The results show that fracture surface roughness can affect the fluid flow and heat transfer processes in fracture networks to various extents, mainly depending on the empirical models of mechanical-hydraulic apertures. In other words, the role of fracture surface roughness in macroscopic fluid flow and heat transfer in fractured rocks is critical, when using a model of mechanical-hydraulic apertures that predicts significant reduced hydraulic apertures. Discrete fracture networks models with the normal distribution of JRC are less permeable than those with the lognormal distribution of JRC, using the fitting parameters of in-situ JRC data.
•JRC distributions in fracture networks were determined based on the in-situ data.•Fracture roughness can affect the macroscopic fluid flow and heat transfer processes.•A proper e/E model is critical in modeling fluid flow and heat transfer in DFN models.
Programmed death protein 1 (PD-1) interaction with PD-L1 deliver immunosuppressive environment for tumor growth, and its blockade with directed monoclonal antibodies (anti-PD-1/anti-PD-L1) has shown ...remarkable clinical outcome. Lately, their soluble counterparts, sPD-1 and sPD-L1, have been detected in plasma, and elevated levels have been associated with advanced disease, clinical stages, and worst prognosis for cancer patients. Elevated plasma levels of sPD-L1 have been correlated with worst prognosis in several studies and has displayed a persistent outlook. On the other hand, sPD-1 levels have been inconsistent in their predictive and prognostic ability. Pretherapeutic higher sPD-1 plasma levels have shown to predict advanced disease state and to a lesser extent worst prognosis. Any increase in sPD-1 plasma level post therapeutically have been correlated with improved survival for various cancers.
and
studies have shown sPD-1 ability to bind PD-L1 and PD-L2 and block PD-1/PD-L1 interaction. Local delivery of sPD-1 in cancer tumor microenvironment through local gene therapy have demonstrated an increase in tumor specific CD8+ T cell immunity and tumor growth reduction. It had also exhibited enhancement of T cell immunity induced by vaccination and other gene therapeutic agents. Furthermore, it may also lessen the inhibitory effect of circulating sPD-L1 and enhance the effects of mAb-based immunotherapy. In this review, we highlight various aspects of sPD-1 role in cancer prediction, prognosis, and anti-cancer immunity, as well as, its therapeutic value for local gene therapy or systemic immunotherapy in blocking the PD-1 and PD-L1 checkpoint interactions.
Highly mineralized and acid/alkaline groundwater is critical to the short- or long-term stability of fractured rock masses in geological engineering. Understanding the impact of water-rock ...interactions on mechanical properties of fractured rock masses is important but challenging. This study investigated the physicochemical interactions between chemical solutions and granite fractures which can directly control the mechanical behaviors of fractured rock masses. Direct shear tests were performed on artificial granite fracture samples immersed in chemical solutions with different pHs for 30 and 150 days. The results show that the solution of pH = 2 has the most significant influence on fracture shear properties, followed by the solutions of pH = 12 and pH = 7. The deionized water has the minimal influence on fracture shear properties. The shear properties of fractures immersed in acid and alkaline solutions are sensitive to immersion time, whereas the shear properties of fractures immersed in neutral solutions are not significantly affected by immersion time. The weakening mechanisms of the water-rock chemical interaction are different in different chemical solutions. Dissolution mainly works in acid solutions, whereas the competing minerals dissolution and precipitation/crystallization occur in alkaline solutions. This is why alkaline solutions have less significant influence on fracture shear properties than acid solutions.
•Shear behaviors of granite fractures immersed in different pH solutions are studied.•The mechanisms responsible for fracture weakening induced by physicochemical water-rock interactions are discussed.•A coefficient to evaluate the effect of physicochemical water-rock interactions on fracture peak strength is proposed.
Radiotherapy is the mainstay of brain metastasis (BM) management. Radiation necrosis (RN) is a serious complication of radiotherapy. Bevacizumab (BV), an anti-vascular endothelial growth factor ...monoclonal antibody, has been increasingly used for RN treatment. We systematically reviewed the medical literature for studies reporting the efficacy and safety of bevacizumab for treatment of RN in BM patients.
PubMed, Medline, EMBASE, and Cochrane library were searched with various search keywords such as "bevacizumab" OR "anti-VEGF monoclonal antibody" AND "radiation necrosis" OR "radiation-induced brain necrosis" OR "RN" OR "RBN" AND "Brain metastases" OR "BM" until 1st Aug 2020. Studies reporting the efficacy and safety of BV treatment for BM patients with RN were retrieved. Study selection and data extraction were carried out by independent investigators. Open Meta Analyst software was used as a random effects model for meta-analysis to obtain mean reduction rates.
Two prospective, seven retrospective, and three case report studies involving 89 patients with RN treated with BV were included in this systematic review and meta-analysis. In total, 83 (93%) patients had a recorded radiographic response to BV therapy, and six (6.7%) had experienced progressive disease. Seven studies (n = 73) reported mean volume reductions on gadolinium-enhanced T1 (mean: 47.03%, +/- 24.4) and T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI images (mean: 61.9%, +/- 23.3). Pooling together the T1 and T2 MRI reduction rates by random effects model revealed a mean of 48.58 (95% CI: 38.32-58.85) for T1 reduction rate and 62.017 (95% CI: 52.235-71.799) for T2W imaging studies. Eighty-five patients presented with neurological symptoms. After BV treatment, nine (10%) had stable symptoms, 39 (48%) had improved, and 34 (40%) patients had complete resolution of their symptoms. Individual patient data was available for 54 patients. Dexamethasone discontinuation or reduction in dosage was observed in 30 (97%) of 31 patients who had recorded dosage before and after BV treatment. Side effects were mild.
Bevacizumab presents a promising treatment strategy for patients with RN and brain metastatic disease. Radiographic response and clinical improvement was observed without any serious adverse events. Further class I evidence would be required to establish a bevacizumab recommendation in this group of patients.
The effect of water on the shear behavior of joints in rock is critical for determining the stability of jointed rocks subjected to changes in water levels. In this study, a series of direct shear ...tests on joints in dry and wet sandstone samples were conducted under constant normal loads to investigate the influence of wetting on joint shear behavior. The results show that the peak shear strength of sandstone joints can be lowered by about 20%–24% owing to wetting, but the saturation-induced reduction of joint shear strength is probably not sensitive to the duration of immersion. The deformation behavior of sandstone joints can also be affected by wetting in that peak shear displacement can increase, joint shear stiffness may be reduced, and shear-induced normal displacement may switch from dilation to contraction. A simplified hypothetical example of a steep rock slope was used to demonstrate the role of wetting in lowering the factor of safety. This example indicated that only considering the purely mechanical effect of pore pressure, but neglecting the wetting-induced weakening of rock joints may overestimate the slope stability and be highly risky for practical rock engineering.
•A series of direct shear tests on wetting-treated joint specimens was conducted.•Peak shear strength of sandstone joints was lowered by about 20–24% due to wetting.•The behavior of wet sandstone joints was not sensitive to the length of immersion.
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