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Uniaxial compressive strength (UCS) of rocks is one of the main parameters required in the design of geotechnical projects such as tunnels, dams, or rock slopes. According to the literature, there are a large number of predictive regression equations to evaluate the UCS from the point load index (PLI) and Brazilian tensile strength (BTS). However, the equations developed in previous studies have different accuracies in UCS prediction. A more accurate prediction of the UCS will result in a more appropriate design of the geotechnical project, and thus ensure its success during operation. In the present paper, a comparative study was conducted between the accuracy of PLI and BTS in predicting the UCS of the limestone and sandstone. Moreover, the role of porosity (n) on the accuracy of predicting the UCS from PLI and BTS was investigated. Some statistical indices were used to investigating the accuracy of predictive regression equations of UCS. The results revealed that the UCS of rocks can be predicted with a higher accuracy using BTS compared with PLI. Also, the findings showed that the n had a significant role in increasing the accuracy of PLI- and BTS-based regression equations of the UCS predictive. The predictive equations established in the present study can be used in practical applications for indirect evaluation of limestone and sandstone UCS in the site of a geotechnical project. [ABSTRACT FROM AUTHOR]

Underground engineering frequently encounters the challenges of high temperatures and high confining pressures. The combined effects of temperature and confining pressure can significantly alter the mechanical properties of rock. Evaluating the impact of these factors on rock is a crucial aspect of engineering. This study investigates the mechanical properties of rocks under various temperature and stress conditions, focusing on the deformation and failure characteristics of four typical rock types: granite, red sandstone, gray sandstone, and shale under temperature-confining pressure coupling. The results indicate that high temperatures cause internal structural damage and crack propagation in rocks, leading to a reduction in compressive strength and elastic modulus. Conversely, high confining pressures can inhibit crack propagation and enhance rock deformation capacity. Additionally, significant differences were observed in the mechanical responses of different rocks; red sandstone and shale predominantly exhibited shear failure under the coupled effects of temperature and confining pressure, whereas granite and gray sandstone exhibited bulging failure. Based on the experimental results, an elastic modulus fitting model considering the temperature-confining pressure coupling effect was proposed, and the parameters of the Drucker–Prager criterion were modified. A constitutive model was constructed to accurately reflect the stress–strain state of rocks under the coupled effects of temperature and confining pressure. The constitutive model results show good agreement with the experimental findings. [ABSTRACT FROM AUTHOR]

Inflammation is implicated in the etiology of obesity-related diseases. Thromboxane-prostanoid receptor (TPR) is known to play a role in mediating an inflammatory response in a variety of cells. Gut-derived lipopolysaccharide (LPS), a TLR4 agonist, is elevated in obesity. Moreover, free fatty acids (FFAs) are important mediators of obesity-related inflammation. However, the role and mechanisms by which TPR regulates the inflammatory response in human immune cells remain unclear. We sought to determine the link between TPR and obesity and the role/mechanisms by which TPR alters LPS- or stearic acid (SA)-induced inflammatory responses in PBMCs. Cells were pre-treated with agents blocking TPR signaling, followed by treatment with LPS or stearic acid (SA). Our findings showed that TPR mRNA levels are higher in PBMCs from individuals with obesity. Blockade of TPR as well as ROCK, which acts downstream of TPR, attenuated LPS- and/or SA-induced pro-inflammatory responses. On the other hand, TPR activation using its agonist enhanced the pro-inflammatory effects of LPS and/or SA. Of note, the TPR agonist by itself elicits an inflammatory response, which was attenuated by blocking TPR or ROCK. Our data suggest that TPR plays a key role in promoting an inflammatory response in human PBMCs, and this effect is mediated via TLR4 and/or ROCK signaling. [ABSTRACT FROM AUTHOR]

Fatigue damage can occur in surface rock engineering due to various factors, including earthquakes, blasting, and impacts. The underlying cause for the variations in physical and mechanical properties of the rock resulting from impact loading is the alteration in the internal pore structure. To investigate the evolution characteristics of the pore structure under impact fatigue damage, red sandstone subjected to cyclic impact compression by split Hopkinson pressure bar (SHPB) was analyzed using nuclear magnetic resonance (NMR) technology. The parameters describing the evolution of pore structure were obtained and quantified using fractal methods. The development of the pore structure in rocks subjected to cyclic impact was quantitatively analyzed, and two fractal evolution models based on pore size and pore connectivity were constructed. The results indicate that with an increasing number of impact loading cycles, the porosity of the red sandstone gradually increases, the T2 cutoff (T2c) value decreases, the most probable gray value of magnetic resonance imaging (MRI) increases, the pores' connectivity is enhanced, and the fractal dimension decreases gradually. Moreover, the pore distribution space tends to transition from three-dimensional to two-dimensional, suggesting the expansion of dominant pores into clusters, forming microfractures or even macroscopic fissures. The findings provide valuable insights into the impact fatigue characteristics of rocks from a microscopic perspective and contribute to the evaluation of time-varying stability and the assessment of progressive damage in rock engineering. [ABSTRACT FROM AUTHOR]

Under compressive loading, rocks emit electromagnetic waves, and monitoring electromagnetic signals has become a key means of predicting dynamic rock disasters. To understand how dynamic potential is generated in rocks under compressive loading, the relationship between the compressive loading (P) and the stimulated potential (E) is seen as a circuit system (H(t)). A circuit analysis model has been established to study how rock particles restructure under compressive loading. Experimental tests were conducted to measure the input excitation (E) and output response (Uσ(t)) or (Iσ(t)) of the rock specimens, with four types of rocks being tested. The experiments revealed that voltage, current, frequency, and impedance changed during the particle reorganization process under compressive loading, showing that the electromagnetic radiation of the rock specimens mainly came from the current generated by the internal particle reorganization. The intensity of electromagnetic radiation was found to depend on the load size and dynamic impedance (Zσ), with the dynamic impedance (Zσ) consisting of the microelement total resistance (Rσ), capacitance (Cσ), and inductance (Lσ). The variation of dynamic impedance (Zσ) is related to the rock type. The research findings have contributed to elucidating the mechanism of electromagnetic radiation generated by rocks under load. [ABSTRACT FROM AUTHOR]

Glaucoma is a chronic neurodegenerative disease that poses a significant threat of irreversible blindness worldwide. Current treatments for glaucoma focus on reducing intraocular pressure (IOP), which is the only modifiable risk factor. Traditional anti-glaucomatous agents, including carbonic anhydrase inhibitors, beta-blockers, alpha-2 agonists, and prostaglandin analogs, work by either improving uveoscleral outflow or reducing aqueous humor production. Rho kinase (ROCK) inhibitors represent a novel class of anti-glaucomatous drugs that have emerged from bench to bedside in the past decade, offering multifunctional characteristics. Unlike conventional medications, ROCK inhibitors directly target the trabecular meshwork outflow pathway. This review aims to discuss the mechanism of ROCK inhibitors in reducing IOP, providing neuroprotection, and preventing fibrosis. We also highlight recent studies and clinical trials evaluating the efficacy and safety of ROCK inhibitors, compare them with other clinical anti-glaucomatous medications, and outline future prospects for ROCK inhibitors in glaucoma treatment. [ABSTRACT FROM AUTHOR]

Lung epithelial development relies on the proper balance of cell proliferation and differentiation to maintain homeostasis. When this balance is disturbed, it can lead to diseases like cancer, where cells undergo hyperproliferation and then can undergo migration and metastasis. Lung cancer is one of the deadliest cancers, and even though there are a variety of therapeutic approaches, there are cases where treatment remains elusive. The rho-associated protein kinase (ROCK) has been thought to be an ideal molecular target due to its role in activating oncogenic signaling pathways. However, in a variety of cases, inhibition of ROCK has been shown to have the opposite outcome. Here, we show that ROCK inhibition with y-27632 causes abnormal epithelial tissue development in Xenopus laevis embryonic skin, which is an ideal model for studying lung cancer development. We found that treatment with y-27632 caused an increase in proliferation and the formation of ciliated epithelial outgrowths along the tail edge. Our results suggest that, in certain cases, ROCK inhibition can disturb tissue homeostasis. We anticipate that these findings could provide insight into possible mechanisms to overcome instances when ROCK inhibition results in heightened proliferation. Also, these findings are significant because y-27632 is a common pharmacological inhibitor used to study ROCK signaling, so it is important to know that in certain in vivo developmental models and conditions, this treatment can enhance proliferation rather than lead to cell cycle suppression. [ABSTRACT FROM AUTHOR]

Freeze–thaw effect is one of the most important environmental conditions that rocks may be subjected to. Through laboratory model tests, the damage characteristics of rocks under the FTC were studied. Based on assuming that the strength of rocks subject to the FTC follows the Weibull distribution, the cumulative damage variable of the number of FTCs was introduced. A cumulative damage constitutive model of shear strength attenuation of rock that meets the Mohr–Coulomb criterion is established. The rationality and applicability of the proposed damage constitutive model are verified by comparing the results of rock shear strength parameters under cyclic freeze–thaw loads. [ABSTRACT FROM AUTHOR]

The shear performance of the binary interface formed by mortar and rock cementation is a key factor influencing the stability and safety of basic engineering projects related to livelihood and economy since concrete has become one of the most widely used materials in engineering. Therefore, it is an urgent practical problem to further explore and clarify the shear failure mechanism of the mortar–rock binary interface. In response to the current research objective focused on fully bonded interfaces, this paper constructed binary interface models with different bonded conditions to perform direct shear experiments using numerical simulation methods, and the effect of bonded conditions on the shear behavior of the mortar–rock binary interface was analyzed. The results indicate that the bonded conditions have a significant influence on the shear mechanical behavior of the mortar–rock binary interface, which is mainly reflected in the stress-displacement curve characteristics, the shear strength, the fracture development and the stress distribution state. The research findings are of great theoretical significance for the further study of shear mechanics at the mortar–rock binary interface and of great practical significance for safe construction, resource conservation and disaster warning. [ABSTRACT FROM AUTHOR]

To investigate the dynamic response of fractured rock under cyclic loading and unloading, a WHY-300/10 microcomputer-controlled electro-hydraulic servo universal testing machine was used to conduct uniaxial cyclic loading and unloading tests. Simultaneously, acoustic emission (AE) and a CCD high-speed camera were employed to monitor the fracturing characteristics of sandstone. The mechanical properties, energy evolution, AE characteristics, and deformation of 45° sandstone were analyzed. The results indicate that as the load cycle level increases, both the elastic modulus and deformation modulus exhibit a "parabolic" increase, with a rapid rise initially and a slower rate of increase later. The damping ratio generally shows a decreasing trend but tends to rise near the peak load. The total energy, elastic energy, dissipated energy, damping energy, and damage energy all follow exponential function increases with the load level. The b-value fluctuates significantly during the stable crack propagation phase, unstable crack propagation phase, and peak phase. When the FR (Felicity ratio > 1), the rock is relatively stable; when the FR (Felicity ratio < 1), the rock gradually extends towards an unstable state. The Felicity ratio can be used as a predictive tool for the precursors of rock failure. Shear fractures dominate during the compaction and peak phases, while tensile fractures dominate during the crack propagation phase, ultimately leading to a failure characterized by tensile fracture. High-speed camera observations revealed that deformation first occurs at the tips of the prefabricated cracks and gradually spreads and deflects toward the ends of the sandstone. This study provides theoretical support for exploring the mechanical behavior and mechanisms of fractured rock under cyclic loading and unloading, and it has significant practical implications. [ABSTRACT FROM AUTHOR]

Most recent tunnel designs rely on more thorough analyses of the intricate rock interactions. The three principal techniques for excavating rock tunneling are drill-and-blast for complete or partial cross-sections, TBM only for circular cross-sections with full faces, and road header for small portions. Tunnel-boring machines (TBM) are being utilized to excavate an increasing number of tunnels. Newer studies have demonstrated that subterranean structures such as tunnels produce a variety of consequences during and after ground shaking, challenging the long-held belief that they are among the most earthquake-resistant structures. Consequently, engineering assessment has become crucial for these unique structures from both the geotechnical and structural engineering standpoints. The designer should evaluate the underground structure's safety to ensure it can sustain various applied loads, considering both seismic loads and temporary and permanent static loads. This paper investigates how adding elastic, soft material between a circular tunnel and the surrounding rock affects seismic response. To conduct the study, Midas/GTS-NX was used to model the TBM tunnel and the nearby rock using the finite element (F.E.) method to simulate the soil–tunnel interactions. A time–history analysis of the El Centro (1940) earthquake was used to calculated the stresses accumulated in the tunnels during seismic episodes. Peak ground accelerations of 0.10–0.30 g, relative to the tunnel axis, were used for excitation. The analysis utilized a time step of 0.02 s, and the duration of the seismic event was set at 10 s. Numerical models were developed to represent tunnels passing through rock, with the traditional grout pea gravel vs. isolation layer. A parametric study determined how isolation material characteristics like shear modulus, Poisson's ratio, and unit weight affect tunnel-induced stresses. In the meantime, this paper details the effects of various seismic isolation materials, such as geofoam, foam concrete, and silicon-based isolation material, to improve protection against seismic shaking. The analysis's findings are discussed, and how seismic isolation affects these important structures' performance and safety requirements is explained. [ABSTRACT FROM AUTHOR]

Currently, drilling of directional oil and gas wells under complex technical-technological and mining-geological conditions requires the use of drill pipes made of various materials. In turn, to choose rational modes of strengthening drill pipes and drill string layouts, information on the contact forces and friction forces of the drill string pipes on boreholes is necessary. Drill pipe curved sections friction with boreholes and drill bit resistance moment changes are the main causes of uneven rotation of a drill string during rotary or combined drilling methods and the occurrence of parametric oscillations. To reduce the cost of mechanical energy for well wiring, it is necessary to take into account the "drill string–borehole rocks" force interaction to estimate the magnitude of the frictional forces and their influence on the technological parameters of the drilling process. To solve this problem, mathematical models of "conventionally vertical and inclined drill string sections–borehole" were built. Based on the industrial data, an analysis of the force interaction of a deformed drill string composed of pipes made of different materials (aluminum, titanium, steel) was carried out. Analytical dependences were obtained for determining the contact forces and friction of the pipes on boreholes. A numerical study of the change of these power factors depending on the depth of the well under conditions of intensive vibration loading was carried out. The amplitude values of these forces, the frequency of their change for good sections, as well as the places for the most rational installation of drill pipes in the layout of the drill string were estimated. It was established that the intensity of contact and friction forces for steel drill pipes is greater than for titanium or aluminum ones. It is shown that the greater impact of a solid steel string on contact forces and frictional forces compared to a layout with sections of titanium or aluminum pipes in the range of vibration frequencies of 8–22 Hz corresponds to a bit rotation frequency of 70–80 rpm. The practical application of the obtained research results will contribute to the improvement of technical and economic indicators of the well drilling process. [ABSTRACT FROM AUTHOR]

Rho-kinase (ROCK) inhibitors represent a new category of anti-glaucoma medications. Among them, Fasudil hydrochloride, a selective ROCK inhibitor, has demonstrated promising outcomes in glaucoma treatment. It works by inhibiting the ROCK pathway, which plays a crucial role in regulating the trabecular meshwork and canal of Schlemm's aqueous humor outflow. This study aims to investigate the ocular absorption pathway of Fasudil hydrochloride and, subsequently, develop a nanoparticle-based delivery system for enhanced corneal absorption. Employing the ionic gelation method and statistical experimental design, the factors influencing chitosan nanoparticle (Cs NP) characteristics and performance were explored. Fasudil in vitro release and ex vivo permeation studies were performed, and Cs NP ocular tolerability and cytotoxicity on human lens epithelial cells were evaluated. Permeation studies on excised bovine eyes revealed significantly higher Fasudil permeation through the sclera compared to the cornea (370.0 μg/cm2 vs. 96.8 μg/cm2, respectively). The nanoparticle size (144.0 ± 15.6 nm to 835.9 ± 23.4 nm) and entrapment efficiency range achieved (17.2% to 41.4%) were predominantly influenced by chitosan quantity. Cs NPs showed a substantial improvement in the permeation of Fasudil via the cornea, along with slower release compared to the Fasudil aqueous solution. The results from the Hen's Egg Test Chorioallantoic Membrane (HET-CAM) and Bovine Corneal Opacity and Permeability (BCOP) tests indicated good conjunctival and corneal biocompatibility of the formulated chitosan nanoparticles, respectively. Lens epithelial cells displayed excellent tolerance to low concentrations of these nanoparticles (>94% cell viability). To the best of our knowledge, this is the first report on the ocular absorption pathway of topically applied Fasudil hydrochloride where the cornea has been identified as a potential barrier that could be overcome using Cs NPs. [ABSTRACT FROM AUTHOR]

GPR55 is involved in many physiological and pathological processes. In cancer, GPR55 has been described to show accelerating and decelerating effects in tumor progression resulting from distinct intracellular signaling pathways. GPR55 becomes activated by LPI and various plant-derived, endogenous, and synthetic cannabinoids. Cannabinoids such as THC exerted antitumor effects by inhibiting tumor cell proliferation or inducing apoptosis. Besides its effects through CB1 and CB2 receptors, THC modulates cellular responses among others via GPR55. Previously, we reported a reduction in Ki67-immunoreactive nuclei of human glioblastoma cells after GPR55 activation in general by THC and in particular by LPI. In the present study, we investigated intracellular mechanisms leading to an altered number of Ki67+ nuclei after stimulation of GPR55 by LPI and THC. Pharmacological analyses revealed a strongly involved PLC-IP3 signaling and cell-type-specific differences in Gα-, Gβγ-, RhoA-ROCK, and calcineurin signaling. Furthermore, immunochemical visualization of the calcineurin-dependent transcription factor NFAT revealed an unchanged subcellular localization after THC or LPI treatment. The data underline the cell-type-specific diversity of GPR55-associated signaling pathways in coupling to intracellular G proteins. Furthermore, this diversity might determine the outcome and the individual responsiveness of tumor cells to GPR55 stimulation by cannabin oids. [ABSTRACT FROM AUTHOR]

The mechanical properties of fractured rock have always been a focal point in the rock mechanics field. Based on previous research, this paper proposes improvements to the SPH method and applies it to the study of crack propagation in fractured rocks. By conducting uniaxial compression tests and simulating crack propagation on various specimens with different crack shapes, the characteristics of crack propagation were obtained. The comparison between the simulated results in this study and existing experimental and numerical simulation results confirms the validity of the SPH method employed in this paper. The present study utilizes the proposed methodology to analyze the influence of the crack angle, width, and orientation on crack propagation. The SPH method employed in this study effectively demonstrates the expansion process of fractured rock under uniaxial compression, providing valuable insights for the engineering applications of SPH. [ABSTRACT FROM AUTHOR]

The peak dilation angle is an important mechanical feature of rock discontinuities, which is significant in assessing the mechanical behaviour of rock masses. Previous studies have shown that the efficiency and accuracy of traditional experimental methods and analytical models in determining the shear dilation angle are not completely satisfactory. Machine learning methods are popular due to their efficient prediction of outcomes for multiple influencing factors. In this paper, a novel hybrid machine learning model is proposed for predicting the peak dilation angle. The model incorporates support vector regression (SVR) techniques as the primary prediction tools, augmented with the grid search optimization algorithm to enhance prediction performance and optimize hyperparameters. The proposed model was employed on eighty-nine datasets with six input variables encompassing morphology and mechanical property parameters. Comparative analysis is conducted between the proposed model, the original SVR model, and existing analytical models. The results show that the proposed model surpasses both the original SVR model and analytical models, with a coefficient of determination (R2) of 0.917 and a mean absolute percentage error (MAPE) of 4.5%. Additionally, the study also reveals that normal stress is the most influential mechanical property parameter affecting the peak dilation angle. Consequently, the proposed model was shown to be effective in predicting the peak dilation angle of rock discontinuities. [ABSTRACT FROM AUTHOR]

With the development of data collection and storage capabilities in recent decades, abundant data have been accumulated in geotechnical engineering fields, providing opportunities for the usage of machine learning approaches. Thus, a rising number of scholars are adopting machine learning techniques to settle geotechnical issues. In this paper, the application of three popular machine learning algorithms, support vector machine (SVM), artificial neural network (ANN), and decision tree (DT), as well as other representative algorithms in geotechnical engineering, is reviewed. Meanwhile, the applicability of diverse machine learning algorithms in settling specific geotechnical engineering issues is compared. The main findings are as follows: ANN, SVM, and DT have been widely adopted to solve a variety of geotechnical engineering issues, such as the classification of soil and rock types, predicting the properties of geotechnical materials, etc. Based on the collected relevant research, the performance of random forest (RF) in sorting soil types and assessing landslide susceptibility is satisfying; SVM has high precision in classifying rock types and forecasting rock deformation; and backpropagation ANNs and Hopfield ANNs are recommended to forecast rock compressive strength and soil settlement, respectively. [ABSTRACT FROM AUTHOR]

The Rho associated coiled-coil containing protein kinase (ROCK1 and ROCK2) and myotonic dystrophy-related Cdc-42 binding kinases (MRCKα and MRCKβ) are critical regulators of cell proliferation and cell plasticity, a process intimately involved in cancer cell migration and invasion. Previously, we reported the discovery of a novel small molecule (DJ4) selective multi-kinase inhibitor of ROCK1/2 and MRCKα/β. Herein, we further characterized the anti-proliferative and apoptotic effects of DJ4 in non-small cell lung cancer and triple-negative breast cancer cells. To further optimize the ROCK/MRCK inhibitory potency of DJ4, we generated a library of 27 analogs. Among the various structural modifications, we identified four additional active analogs with enhanced ROCK/MRCK inhibitory potency. The anti-proliferative and cell cycle inhibitory effects of the active analogs were examined in non-small cell lung cancer, breast cancer, and melanoma cell lines. The anti-proliferative effectiveness of DJ4 and the active analogs was further demonstrated against a wide array of cancer cell types using the NCI-60 human cancer cell line panel. Lastly, these new analogs were tested for anti-migratory effects in highly invasive MDA-MB-231 breast cancer cells. Together, our results demonstrate that selective inhibitors of ROCK1/2 (DJE4, DJ-Allyl) inhibited cell proliferation and induced cell cycle arrest at G2/M but were less effective in cell death induction compared with dual ROCK1/2 and MRCKα/β (DJ4 and DJ110). [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis is a life-threatening disease that has been attributed to several causes. Specifically, vascular injury is thought to be involved in the pathogenesis of fibrosis. The effects of the antifibrotic drug pirfenidone on angiogenesis have not been fully elucidated. This study aimed to investigate the effects of pirfenidone in human lung fibroblast–endothelial cell co-culture network formation and to analyze the underlying molecular mechanisms. Human lung fibroblasts were co-cultured with human umbilical vein endothelial cells to establish a co-culture network cell sheet. The influence of pirfenidone was evaluated for protective effect on the endothelial network in cell sheets stimulated with transforming growth factor β (TGF-β). Results indicated that TGF-β disrupted the network formation. Pirfenidone and Y27632 (Rho-associated coiled-coil containing protein kinase [Rho-kinase or ROCK] inhibitor) protected against the TGF-β–induced endothelial network disruption. TGF-β activated Rho-kinase signaling in cells composing the co-culture cell sheet, whereas pirfenidone and Y27632 inhibited these effects. In conclusion, TGF-β–induced Rho-kinase activation and disrupted endothelial network formation. Pirfenidone suppressed TGF-β–induced Rho-kinase activity in cell sheets, thereby enabling vascular endothelial cells networks to be preserved in the cell sheets. These findings suggest that pirfenidone has potential vascular network–preserving effect via inhibiting Rho-kinase activity in vascular injury, which is a precursor to pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

The dominant technology in hard rock mining is drilling and blasting; therefore, the importance of fragment size estimation is an essential problem in the mining industry. By using a theoretical foundation that explains rock-fracturing mechanisms by blasting, a 3D fragmentation model with general applicability was developed. The main capabilities of the model are the ability to consider different and complex blasting patterns, both with parallel and non-parallel boreholes, and different explosive and rock properties. The geological input of the model is defined by generating the primary blocks within rock mass using discrete fracture networks. The model handles different, complex geological setups and blasting scenarios that include bench, ring, and tunneling blasting. Also, it considers borehole deviation, misfires, and the influence of previous blasts. Full-scale ring blasts were carried out to validate the model against real-world data, and the results showed a high level of agreement between model predictions and in situ data. In situ data were collected using image processing methodology and WipFrag v4 software. X50 and X80 size values showed a maximum error in prediction of around 15%, while R2 values between fragmentation curves were approximately 90% without a detailed model calibration to the obtained data. [ABSTRACT FROM AUTHOR]

To investigate the effects of long-term freeze–thaw cycles on the physical and mechanical properties as well as the attenuation trend of rocks, this study conducted saturated freeze–thaw tests on coarse sandstone and fine sandstone samples collected from the slopes of Muli Coal Mine in Qinghai Province. The samples underwent different numbers of freeze–thaw cycles, and their porosity, longitudinal wave velocity, and uniaxial compression strength were studied. The variations in the physical and mechanical properties of the two types of sandstone with respect to the number of freeze–thaw cycles were analyzed. Take uniaxial compressive strength (UCS) as the integrity index, and decay laws of rock integrity were analyzed based on the decay equation suggested in previous studies. We found that the decay index λ, which is commonly assumed to be constant, varies with the number of freeze–thaw cycles. Furthermore, the λ values varied between different rock types. For fine sandstone, the λ decreases with an increase in the number of freeze–thaw cycles, ranging from 0.00385 to 0.005. However, for coarse sandstone, the λ initially decreases and then increases with an increase in the number of freeze–thaw cycles. The range of λ for coarse sandstone is between 0.00376 and 0.00481. Finally, we established a relationship between the decay index, porosity, and longitudinal wave velocity in the fine sandstones. This relationship provides a more straightforward way to evaluate the integrity of fine sandstones subjected to different numbers of freeze–thaw cycles. [ABSTRACT FROM AUTHOR]

In order to study the dynamic stress distribution and the fracture area of rock around the tunnel under different orientations of blasting disturbance, AUTODYN finite difference method software was used to conduct numerical simulation research. Gauge monitoring points were set around the numerical model of the tunnel to conduct real-time monitoring of the stress distribution, displacement and fracture area of the tunnel. Based on the analysis of the stress wave propagation law, the following conclusions are obtained: (1) under the condition of the same blasting loads, the stress and displacement of the tunnel is relatively small when the blasting disturbance source is located above the roof, i.e., the stress state of the tunnel is relatively stable and the fracture area around the tunnel is minimal; (2) from the uniaxial stress around the tunnel and the tunnel peripheral displacement, it can be seen that the displacement caused by horizontal direction stress of the tunnel is the largest, and the deformation is mainly concentrated above the floor and at the shoulder, while the vertical wall part has almost no deformation; (3) for brittle materials such as rock, the arch-shaped stress-bearing surface is more likely to disperse stress, while the straight wall and flat floor of the tunnel cannot well disperse stress, resulting in uneven stress on the stress-bearing surface, uncoordinated deformation and ultimately, failure. [ABSTRACT FROM AUTHOR]

In order to enhance the ability to represent rock feature information and finally improve the rock identification performance of convolution neural networks (CNN), a new pooling mode was proposed in this paper. According to whether the pooling object was the last convolution layer, it divided pooling layers into the sampling pooling layer and the classification pooling layer. The adaptive pooling method was used in the sampling pooling layer. The pooling kernels adaptively adjusted were designed for each feature map. The second-order pooling method was used by the classification pooling layer. The second-order feature information based on outer products was extracted from the feature pair. The changing process of the two methods in forward and back propagation was deduced. Then, they were embedded into CNN to build a rock thin section image identification model (ASOPCNN). The experiment was conducted on the image set containing 5998 rock thin section images of six rock types. The CNN models using max pooling, average pooling and stochastic pooling were set for comparison. In the results, the ASOPCNN has the highest identification accuracy of 89.08% on the test set. Its indexes are superior to the other three models in precision, recall, F1 score and AUC values. The results reveal that the adaptive and second-order pooling methods are more suitable for CNN model, and CNN based on them could be a reliable model for rock identification. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformations (CCM) are developmental venous dysplasias which present as abnormally dilated blood vessels occurring mainly in the brain. Alterations in vascular biology originate from somatic mutations in genes regulating angiogenesis and endothelial-to-mesenchymal transition. Vascular lesions may occur at any time and develop silently, remaining asymptomatic for years. However, symptomatic disease is often debilitating, and patients are prone to develop drug-resistant epilepsy and hemorrhages. There is no cure, and surgical treatment is recommended only for superficial lesions on cortical areas. The study of lesion biology led to the identification of different pathways related to disease onset and progression, of which RhoA/Rho-associated protein kinase (ROCK) shows activation in different subsets of patients. This work will explore the current knowledge about the involvement of ROCK in the many aspects of CCM disease, including isoform-specific actions, and delineate the recent development of ROCK inhibitors for CNS-targeted diseases. [ABSTRACT FROM AUTHOR]

Y-27632 inhibits Rho-associated coiled-coil-containing protein kinase (ROCK) signaling, which is involved in various embryonic developmental processes, including angiogenesis, by controlling actin cytoskeleton assembly and cell contractility. Administration of Y-27632 impairs cytoskeletal arrangements in post-gastrulation chick embryos, leading to ventral body wall defects (VBWDs). Impaired angiogenesis has been hypothesized to contribute to VBWDs. ROCK is essential in transmitting signals downstream of vascular endothelial growth factor (VEGF). VEGF-mediated angiogenesis induces gene expressions and alterations of the actin cytoskeleton upon binding to VEGF receptors (VEGFRs). The aim of this study was to investigate effects of Y-27632 on angiogenesis in post-gastrulation chick embryos during early embryogenesis. After 60 h incubation, embryos in shell-less culture were treated with Y-27632 or vehicle for controls. Y-27632-treated embryos showed reduced extra-embryonic blood vessel formation with impaired circulation of the yolk sac, confirmed by fractal analysis. Western blot confirmed impaired ROCK downstream signaling by decreased expression of phosphorylated myosin light chain. Interestingly, RT-PCR demonstrated increased gene expression of VEGF and VEGFR-2 1 h post-treatment. Protein levels of VEGF were higher in Y-27632-treated embryos at 8 h following treatment, whereas no difference was seen in membranes. We hypothesize that administration of Y-27632 impairs vessel formation during angiogenesis, which may contribute to failure of VWB closure, causing VBWDs. [ABSTRACT FROM AUTHOR]

Under conditions of low or medium stress, rocks that are in the compression state exhibit perceivable nonlinear elastic characteristics. After a comprehensive review of the existing nonlinear elastic models of rocks and joints, we proposed a new unified nonlinear elastic model. This new model contains two parameters with clear definitions, namely, the initial elastic modulus Eni and the modulus change rate m. This model covers a variety of existing models, including the simple exponential model, BB model and two-part Hooke's model, etc. Based on the RMT experimental system, a large number of uniaxial compression tests for dolomite, granite, limestone and sandstone were performed, and their nonlinear deformation stress‒strain curves were obtained and fit with the unified nonlinear elastic model. The results show that the rocks have obvious nonlinear elastic characteristics in their initial compression stage, and that the unified nonlinear elastic model is able to describe these phenomena rather well. In addition, an empirical formula for predicting the uniaxial compressive strength of the rock was constructed, corresponding to the unified nonlinear elastic model. [ABSTRACT FROM AUTHOR]

This paper presents a machine learning-based approach to estimating the compressive strength and elastic modulus of rocks. A hybrid model, GWO-ELM, was built based on an extreme learning machine network optimized by the grey wolf algorithm. The proposed model was carried out on 101 experimental datasets, and four commonly used models were used as benchmarks to evaluate the accuracy of the proposed model. The results showed that the proposed hybrid model can accurately achieve the prediction of elastic modulus and compressive strength with high correlation coefficients and small prediction errors. The prediction performance of the hybrid model is significantly better than the other four original models, and it is an alternative model for predicting the compressive strength and elastic modulus of rocks, which is recommended as an auxiliary tool for real-time prediction of rock mechanical properties. [ABSTRACT FROM AUTHOR]

The dynamic fracture process of rock materials is of importance for several industrial applications, such as drilling for geothermal installation. Numerical simulation can aid in increasing the understanding about rock fracture; however, it requires precise knowledge about the dynamical mechanical properties alongside information about the initiation and propagation of cracks in the material. This work covers the detailed dynamic mechanical characterisation of two rock materials—Kuru grey granite and Kuru black diorite—using a Split-Hopkinson Pressure Bar complemented with high-speed imaging. The rock materials were characterised using the Brazilian disc and uniaxial compression tests. From the high-speed images, the instant of fracture initiation was estimated for both tests, and a Digital Image Correlation analysis was conducted for the Brazilian disc test. The nearly constant tensile strain in the centre was obtained by selecting a rectangular sensing region, sufficiently large to avoid complicated local strain distributions appearing between grains and at voids. With a significantly high camera frame rate of 671,000 fps, the indirect tensile strain and strain rates on the surface of the disc could be evaluated. Furthermore, the overloading effect in the Brazilian disc test is evaluated using a novel methodology consisting of high-speed images and Digital Image Correlation analysis. From this, the overloading effects were found to be 30 and 23%. The high-speed images of the compression tests indicated fracture initiation at 93 to 95% of the peak dynamic strength for granite and diorite, respectively. However, fracture initiation most likely occurred before this in a non-observed part of the sample. It is concluded that the indirect tensile strain obtained by selecting a proper size of the sensing region combined with the high temporal resolution result in a reliable estimate of crack formation and subsequent propagation. [ABSTRACT FROM AUTHOR]

Rock is used as a foundation and building material in many engineering projects and it is important to determine/predict its engineering properties before project construction. Petrographic and textural characteristics are useful parameters for predicting engineering properties of rocks in such applications. In this research, fifteen rock samples were taken and their engineering characteristics, namely dry and saturated unit weights, porosity, water absorption, slake durability index (SDI), Schmidt rebound hardness (SRH), ultrasonic P-wave velocity (UPV), and uniaxial compressive strength (UCS), were measured in the laboratory. Petrographic and textural characteristics of the rocks, determined from thin section and X-ray diffraction investigations, led to the evaluation of the texture coefficient (TC). Based on simple regression analysis (SRA), the TC values have direct relationships with density, SDI, SRH, UPV, and UCS, and inverse relationships with porosity and water absorption. Experimental models were developed using multiple regression analysis (MRA) and artificial neural network (ANN) to predict Id2, SRH, UPV, and UCS of the tested rocks from the values of TC. Some statistical parameters including Pearson regression coefficient (R), coefficient values account for (VAF), root mean square error (RMSE), mean absolute percentage error (MAPE), and performance index (PI) were calculated to assess the performances of the MRA and ANN models. The correlations between experimental and calculated values of Id2, SRH, UPV, and UCS indicated that predicted values of the ANN models are more valid than the MRA. Additionally, the residual error of the ANN models varies less than the MRA. Finally, it has been concluded that the SRA, MRA, and ANN methods can successfully predict the rock engineering properties from the TC. [ABSTRACT FROM AUTHOR]

The flat-joint model, which constructs round particles as polygons, can suppress rotation after breakage between particles and simulate more larger compression and tension ratios than the linear parallel-bond model. The flat-joint contact model was chosen for this study to calibrate the rock for 3D experiments. In the unit experiments, the triaxial unit was loaded with flexible boundaries, and the influence of each microscopic parameter on the significance magnitude of the macroscopic parameters (modulus of elasticity E, Poisson's ratio ν, uniaxial compressive strength UCS, crack initiation strength σci, internal friction angle φ and uniaxial tensile strength TS) was analysed by ANOVA (Analysis of Variance) in an orthogonal experimental design. Among them, Eƒ, kƒ has a significant effect on E; Cƒ and kƒ have a significant effect on ν; Cƒ, σƒ and kƒ have a significant effect on UCS; Cƒ; σƒ and Eƒ have a significant effect on TS; Rsd has a significant effect on σci; and φf, Eƒ, kƒ, μƒ, and σƒ have a significant effect on φ. Regressions were then carried out to establish the equations for calculating the macroscopic parameters of the rock material so that the three-dimensional microscopic parameters of the PFC can be quantitatively analysed and calculated. The correctness of the establishment of the macroscopic equations was verified by comparing the numerical and damage patterns of uniaxial compression, Brazilian splitting, and triaxial experiments with those of numerical simulation units in the chamber. [ABSTRACT FROM AUTHOR]

Abrasive waterjet (AWJ) has been widely used for the cutting of hard materials such as rocks. The AWJ cutting of rocks has been well documented in the relevant literature. In these studies, one-pass cutting is employed as the cutting mode. There is no study focusing on the two-pass AWJ cutting of rocks. Therefore, this study aims to fill this gap. Therefore, in the current study, the physicomechanical properties of the rock subjected to cutting are first determined. Following, the workpieces are cut with both one-pass and two-pass cutting modes. In the tests, cutting time is kept constant to compare the performances of cutting modes in terms of the smooth cutting depth and surface roughness. Kerf profiles of the cutting modes are also compared. In the study, significant relationships were not determined between the cutting parameters (abrasive flow rate and standoff distance) and performance outputs for the cutting modes. This may be attributed to the cutting parameters studied in a narrow range. The results indicate that two-pass cutting with higher speeds provides higher smooth depths than one-pass cutting at lower speeds. Two-pass cutting increases smooth depth up to 47%. Results show that surface quality could be improved by two-pass cutting, expanding the smooth zone and reducing the sizes of the striations. The results also show that two-pass cutting improves surface roughness by up to 25%. It is revealed that kerf wall inclination is reduced by two-pass cutting in the upper and lower parts of the kerf. A widened portion caused by the first pass is observed in the final kerf. It can be noted that two-pass cutting cannot provide any improvement in the top kerf width. [ABSTRACT FROM AUTHOR]

Liver sinusoidal endothelial cells (LSECs) facilitate the efficient transport of macromolecules and solutes between the blood and hepatocytes. The efficiency of this transport is realized via transcellular nanopores, called fenestrations. The mean fenestration size is 140 ± 20 nm, with the range from 50 nm to 350 nm being mostly below the limits of diffraction of visible light. The cellular mechanisms controlling fenestrations are still poorly understood. In this study, we tested a hypothesis that both Rho kinase (ROCK) and myosin light chain (MLC) kinase (MLCK)-dependent phosphorylation of MLC regulates fenestrations. We verified the hypothesis using a combination of several molecular inhibitors and by applying two high-resolution microscopy modalities: structured illumination microscopy (SIM) and scanning electron microscopy (SEM). We demonstrated precise, dose-dependent, and reversible regulation of the mean fenestration diameter within a wide range from 120 nm to 220 nm and the fine-tuning of the porosity in a range from ~0% up to 12% using the ROCK pathway. Moreover, our findings indicate that MLCK is involved in the formation of new fenestrations—after inhibiting MLCK, closed fenestrations cannot be reopened with other agents. We, therefore, conclude that the Rho-ROCK pathway is responsible for the control of the fenestration diameter, while the inhibition of MLCK prevents the formation of new fenestrations. [ABSTRACT FROM AUTHOR]

Prime materials involved in a problem such as underground structures are concrete, reinforcement steel, and geo-material surrounding the tunnel. Among these three materials, concrete and steel are manufactured materials and their properties can be controlled up to a certain extent. However, geo-material is a naturally occurring material whose constitutive properties vary from region to region, making it highly unpredictable. Findings from one study cannot be applied to other geotechnical problems directly, especially in the case of tunnels subjected to surface explosions. The blast wave generated has to travel through the geo-material before it interacts with the tunnel. As the shock wave propagates radially, its characteristics are likely to be altered by the geo-material. Limited study has been carried out considering this problem. In the present study, the effect of various types of geo-material on the blast response of tunnels subjected to surface explosions is investigated. Finite element analysis has been carried out using LS-DYNA®, wherein the problem has been modeled using the multi-material arbitrary Lagrangian–Eulerian (MM-ALE) method. Materials with fluid behavior such as air, explosives, and soil are modeled using ALE formulation. Other materials including tunnel lining, reinforcement steel, and rock are modeled using Lagrangian formulation. Blast loading is simulated using the Jones–Wilkins–Lee (JWL) equation of state. Geo-materials considered for the comparative study are sandy loam, saturated clayey soil, sandstone, and granite. Vertical displacement measured at the crown of the tunnel is used to determine the response of the tunnel. Sandy loam soil, being a highly compressible soil, exhibits non-linear and fluid-like behavior under high-strain loading such as explosions. Tunnels undergo extreme deformation in the case of sandy loam soil and clayey soil compared to rock cases. Further, the effect of saturation in sandy loam on tunnel stability is studied. It is observed that with the increase in saturation of soil, more blast energy is transmitted to the structure, which results in higher deformation. Lastly, the effect of the weathering of rock on the tunnel's response is investigated in the case of sandstone and granite. It was observed that weathering in rock led to more displacement of tunnel crown when compared to intact rock. [ABSTRACT FROM AUTHOR]

Circular/spherical rigid particle models that were initially applied to rock fracture studies were not able to match the ratio of the compressive strength to tensile strength that occurs in rock. In addition, the predicted macroscopic friction angle was much lower than the known hard rock experimental values. Several enhancements have been proposed to address these issues, namely the use of a clumped particle logic or the adoption of polygonal/polyhedral grain structures, either rigid or flexible. In this work, a flexible 2D DEM based particle model (PM) that allows deformable particles to interact in a simplified way is presented. The proposed flexible PM model keeps the contact interaction simplicity and the reduced computational costs characteristic of circular rigid particle models. The PM model is tested using biaxial tests and Brazilian tests. A discussion regarding the influence of the grain deformability on the macroscopic elastic and strength response is presented. It is shown that, when compared with a rigid model, the proposed flexible PM model predicts more reasonable indirect tensile strength to direct tensile strength ratio and requires a smaller value of contact fracture energy to give a good agreement with known experimental data. It is also shown that the proposed flexible PM model can predict a behaviour similar to that obtained using a flexible PM model through inner particle discretization that is more computationally demanding. [ABSTRACT FROM AUTHOR]

As one typical heterogeneous material, the heterogeneity of rock micro parameters has an important effect on its macro mechanical behavior. The study of the heterogeneity of micro parameters is more important to reveal the root cause of deformation and failure. However, as a typical heterogeneous material, the current testing and inversion method is not suitable for micro parameters measurement for the rock. Aiming at obtaining the distribution of micro Young's modulus and micro Poisson's ratio of the rock, based on the digital image correlation method (DIC) and finite element method (FEM), this paper proposed a parameter field inversion method, namely the DF-PF inversion method. Its inversion accuracy is verified using numerical simulation and laboratory uniaxial compression test. Considering the influences of heterogeneity, stress state and dimension difference, the average inversion error of Young's modulus field and Poisson's ratio field are below 10%, and the proportion of elements with an error of less than 15% accounts for more than 86% in the whole specimen model. Compared with the conventional measuring method, the error of macro Young's modulus and macro Poisson's ratio calculated by the DF-PF inversion method is less than 2.8% and 9.07%, respectively. Based on the statistical analysis of Young's modulus field and Poisson's ratio field, the parameter homogeneity and quantitative function relation between the micro parameter and the principal strain can also be obtained in laboratory tests. The DF-PF inversion method provides a new effective method of testing Young's modulus field and Poisson's ratio field of the rocks under complex stress states. [ABSTRACT FROM AUTHOR]

The additive effects of an α2-adrenergic agonist, brimonidine (BRI), on the pan-ROCK inhibitor (ROCK-i), ripasudil (Rip), and the ROCK2-I, KD025, on adipogenic differentiation (DIF+) were examined using two- or three-dimension (2D or 3D) cultures of 3T3-L1 cells. The following analyses were carried out: (1) lipid staining (2D and 3D), (2) real-time measurements of cellular metabolism (2D), (3) mRNA expression of DIF+ related genes and extracellular matrix molecules (ECMs) including collagen (Col)-1, -4, and -6, and fibronectin (Fn), and (4) the sizes and physical properties of the 3D spheroids. The findings indicate that DIF+ induced (1) a substantial enhancement in lipid staining and enhanced expression of the Pparγ and Fabp4 genes, (2) significantly larger and softer 3D spheroids, and (3) down-regulation of Col1 and Fn and up-regulation of Col4 and Col6 genes. Treatment with Rip alone caused a significant enhancement in adipogenesis of both the 2D and 3D cultured 3T3-L1 cells and in the physical properties of the 3D spheroids; these effects were substantially inhibited by BRI, and the effects induced by BRI or KD025 were not insignificant. These collective findings indicate that the addition of BRI inhibited the Rip-induced enhancement of DIF+ in 3T3-L1 cells, presumably by modulating ROCK1 signaling. [ABSTRACT FROM AUTHOR]

Experimental studies were carried out to analyze the impact of optimizers and learning rate on the performance of deep learning-based algorithms for rock thin-section image classification. A total of 2634 rock thin-section images including three rock types—metamorphic, sedimentary, and volcanic rocks—were acquired from an online open-source science data bank. Four CNNs using three different optimizer algorithms (Adam, SGD, RMSprop) under two learning-rate decay schedules (lambda and cosine decay modes) were trained and validated. Then, a systematic comparison was conducted based on the performance of the trained model. Precision, f1-scores, and confusion matrix were adopted as the evaluation indicators. Trials revealed that deep learning-based approaches for rock thin-section image classification were highly effective and stable. Meanwhile, the experimental results showed that the cosine learning-rate decay mode was the better option for learning-rate adjustment during the training process. In addition, the performance of the four neural networks was confirmed and ranked as VGG16, GoogLeNet, MobileNetV2, and ShuffleNetV2. In the last step, the influence of optimization algorithms was evaluated based on VGG16 and GoogLeNet, and the results demonstrated that the capabilities of the model using Adam and RMSprop optimizers were more robust than that of SGD. The experimental study in this paper provides important practical value for training a high-precision rock thin-section image classification model, which can also be transferred to other similar image classification tasks. [ABSTRACT FROM AUTHOR]

The prediction of rate-dependent compressive strength of rocks in dynamic compression experiments is still a notable challenge. Four machine learning models were introduced and employed on a dataset of 164 experiments to achieve an accurate prediction of the rate-dependent compressive strength of rocks. Then, the relative importance of the seven input features was analyzed. The results showed that compared with the extreme learning machine (ELM), random forest (RF), and the original support vector regression (SVR) models, the correlation coefficient R2 of prediction results with the hybrid model that combines the particle swarm optimization (PSO) algorithm and SVR was highest in both the training set and the test set, both exceeding 0.98. The PSO-SVR model obtained a higher prediction accuracy and a smaller prediction error than the other three models in terms of evaluation metrics, which showed the possibility of the model as a rate-dependent compressive strength prediction tool. Additionally, besides the static compressive strength, the stress rate is the most important influence factor on the rate-dependent compressive strength of the rock among the listed input parameters. Moreover, the strain rate has a positive effect on the rock strength. [ABSTRACT FROM AUTHOR]

A visible and near-infrared imaging spectrometer (VNIS) loaded by the Chang'e-4 rover is the primary method for detecting the mineral composition of the lunar surface in the landing region. However, different data processing methods yield inconsistent mineral modes in measured lunar soil and rocks. To better constrain the mineral modes of the soil and rocks measured by Chang'e-4 VNIS, a noritic-gabbroic rock with a mineral composition similar to that of the lunar highland rocks is measured by scanning electron microscopy (SEM), the spare flight model of Chang'e-4 VNIS and TerraSpec-4 of ASD. Backscattered electron and energy dispersive spectrometry show that olivine, pyroxene, and plagioclase modal mineral abundances are 12.9, 35.0, and 52.2%, respectively. The estimated results of the spectrum by the Hapke radiative transfer model are 7.5, 39.3, and 53.2% for olivine, pyroxene, and plagioclase, respectively, which is consistent with to those of SEM mapping within error. In contrast, the estimated results of the modified Gaussian model are 29 and 71% for olivine and pyroxene, respectively, indicating the absence of plagioclase. Based on our implemented Hapke model, we decode the data of the two rocks detected by the rover on the 3rd and 26th lunar days of mission operations. The obtained results suggest that both rocks are norite or gabbro with noticeable differences. The first rock, with more olivine and pyroxene, may have been excavated from the Finsen crater. The second rock, with more plagioclase, may have been ejected from the southwestern edge of the Von Kármán crater, indicating the initial lunar crust. [ABSTRACT FROM AUTHOR]

Fractures commonly exist in rock masses; the coalescence of fractures provides fluid flow pathways in a fractured rock mass and greatly increases the flow capacity of fractured rock. This work aims to study the characteristics of nonlinear flow in fractures. A series of tests were conducted and indicated that the Forchheimer law performed well when describing the nonlinear relationship between hydraulic gradient and flow. The test results also indicate that higher water pressure may induce stronger nonlinearity. Additionally, the linear and nonlinear coefficients of the Forchheimer law increase with a decrease in the particle size of the filling material in fractures. On the basis of the laboratory results, the classical Forchheimer law was modified by considering the influence of stress on the variation of fracture aperture. A hydro-mechanical coupling model for fractured rock masses was built and programmed with a subroutine through ABAQUS. Furthermore, a random discrete fracture network was generated and simulated to prove that a high flow velocity will result in a nonlinear flow, not only in a single fracture, but also in a fracture network. The numerical results from fractured rock masses show that a ratio of the flow to the hydraulc gradient will change the flow from linear to weak nonlinearity and, finally, to strong nonlinearity with an increase in the hydraulic gradient. It also shows that the linear and nonlinear coefficients increase with an increase in the confining pressure and that they decrease with an increase in the aperture. Due to the complexity of fracture channels, a nonlinear flow is likely to occur in a fractured rock mass. Finally, the developed model was applied to simulate the flow behavior of underground engineering; the results show that the smaller the hydraulic aperture is, the higher the water pressure is required to be in order to change the flow regime from linear to nonlinear. [ABSTRACT FROM AUTHOR]

Discontinuities are natural structures that exist in rocks and can affect the stability of rock structures. In this article, the influence of notch presence on the strength and failure evolution around a hole in compressed rock specimens is investigated numerically. Firstly, the uniaxial compressive test on a rock specimen with a circular hole is modeled, and the failure evolution in the specimen is simulated. In a separate model, notches are created at the surface of the hole. Results show that, when the notches are created in the model, a failure zone around the hole is transferred to a distance away from the surface of the hole. In addition, a parametric study is carried out to investigate the influence of the notch length and the confining pressure on the fracturing behavior of the specimen. Numerical results presented in this article indicate that the presence of notches at the surface of the hole and their dimensions can affect the fracturing mechanism of the specimen. In some cases, the failure at the boundary of the hole is prevented when the notches of certain dimensions are added to the hole. The insights gained from this numerical study may be helpful to control the failure around underground excavations. [ABSTRACT FROM AUTHOR]

Featured Application: Quick and non-destructive applications of Infrared Thermography on rocks. Infrared thermography is a growing technology in the engineering geological field both for the remote survey of rock masses and as a laboratory tool for the non-destructive characterization of intact rock. In this latter case, its utility can be found either from a qualitative point of view, highlighting thermal contrasts on the rock surface, or from a quantitative point of view, involving the study of the surface temperature variations. Since the surface temperature of an object is proportional to its emissivity, the knowledge of this last value is crucial for the correct calibration of the instrument and for the achievement of reliable thermal outcomes. Although rock emissivity can be measured according to specific procedures, there is not always the time or possibility to carry out such measurements. Therefore, referring to reliable literature values is useful. In this frame, this paper aims at providing reference emissivity values belonging to 15 rock types among sedimentary, igneous and metamorphic categories, which underwent laboratory emissivity estimation by employing a high-sensitivity thermal camera. The results show that rocks can be defined as "emitters", with emissivity generally ranging from 0.89 to 0.99. Such variability arises from both their intrinsic properties, such as the presence of pores and the different thermal behavior of minerals, and the surface conditions, such as polishing treatments for ornamental stones. The resulting emissivity values are reported and commented on herein for each different studied lithology, thus providing not only a reference dataset for practical use, but also laying the foundation for further scientific studies, also aimed at widening the rock aspects to investigate through IRT. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformation (CCM) is a disease characterized by mulberry shaped clusters of dilated microvessels, primarily in the central nervous system. Such lesions can cause seizures, headaches, and stroke from brain bleeding. Loss-of-function germline and somatic mutations of a group of genes, called CCM genes, have been attributed to disease pathogenesis. In this review, we discuss the impact of CCM gene encoded proteins on cellular signaling, barrier function of endothelium and epithelium, and their contribution to CCM and potentially other diseases. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. TBIs, which range in severity from mild to severe, occur when a traumatic event, such as a fall, a traffic accident, or a blow, causes the brain to move rapidly within the skull, resulting in damage. Long-term consequences of TBI can include motor and cognitive deficits and emotional disturbances that result in a reduced quality of life and work productivity. Recovery from TBI can be challenging due to a lack of effective treatment options for repairing TBI-induced neural damage and alleviating functional impairments. Central nervous system (CNS) injury and disease are known to induce the activation of the small GTPase RhoA and its downstream effector Rho kinase (ROCK). Activation of this signaling pathway promotes cell death and the retraction and loss of neural processes and synapses, which mediate information flow and storage in the brain. Thus, inhibiting RhoA-ROCK signaling has emerged as a promising approach for treating CNS disorders. In this review, we discuss targeting the RhoA-ROCK pathway as a therapeutic strategy for treating TBI and summarize the recent advances in the development of RhoA-ROCK inhibitors. [ABSTRACT FROM AUTHOR]

Fracture toughness is used to characterize rock resistance to fracturing and it is important in theoretical research and engineering applications. Mode-I fracture toughness can be predicted on the basis of an empirical relationship between fracture toughness (KIC) and tensile strength (σt). In underground engineering, rocks are often subjected to different temperatures. Therefore, this paper explores the effect of temperature on the relationship between mode-I fracture toughness and tensile strength. The results show that the change trends in the KIC and σt values of rocks at temperatures from 20 °C to 600 °C are broadly consistent with each other. For rocks heat-treated to the same temperature, the KIC of the rock increases with an increase in σt. This positive correlation between KIC and σt is different in rocks heat-treated to different temperatures. Critical crack propagation radius (rIC) is an important factor in the relationship between KIC and σt and is related to the type of rock and the conditions under which it is tested. For the same rock, rIC is quite different after it has been exposed to different temperatures. The positive correlation between KIC and σt results from a similarity in the fracture morphology and properties of failure when rock is destroyed in fracture and tensile tests. [ABSTRACT FROM AUTHOR]

This Special Issue covers the broad topic of structural integrity of non-metallic materials, and it is concerned with the modelling, assessment and reliability of structural elements of any scale. In particular, the articles being contained in this issue concentrate on the mechanics of fracture and fatigue in relation to applications to a variety of non-metallic materials, including concrete and cementitious composites, rocks, glass, ceramics, bituminous mixtures, composites, polymers, rubber and soft matters, bones and biological materials, advanced and multifunctional materials. [ABSTRACT FROM AUTHOR]

The Johnson–Holmquist-II(JH-2) model is introduced as the constitutive model for rock materials in tunnel smooth blasting. However, complicated and/or high-cost experiments need to be carried out to obtain the parameters of the JH-2 constitutive model. This study chooses Barre granite as an example to propose a quick and convenient determination method for the parameters of the JH-2 model using a series of computational and extrapolated methods. The validity of the parameters is verified via comparing the results of 3D numerical simulations with laboratory blast-loading experiments. Subsequently, the verified parameter determination method, together with the JH-2 damage constitutive model, is applied in the numerical simulation of smooth blasting in Zigaojian tunnel, Hangzhou–Huangshan high-speed railway. The overbreak/underbreak induced by rock blasting and joints/discontinuities is well estimated through comparing the damage contours resulting from the numerical study with the tunnel profiles measured from the tunnel site. The peak particle velocities (PPVs) of the near field are extracted to estimate the damage scope and damage degree for the surrounding rock mass of the tunnel on the basis of PPV damage criteria. This method can be used in the excavation of rock tunnels subjected to large strains, high strain rates, and high pressures, thereby reducing safety risk and economic losses. [ABSTRACT FROM AUTHOR]

In the present publication, the performance of an implicit gradient-enhanced damage-plasticity model is evaluated with special focus on the prediction of complex failure modes such as shear failure. Hence, it complements studies on predominant mode I failure frequently found in the literature. To this end, an implicit gradient-enhanced damage-plasticity rock model is presented and validated by means of 2D and 3D finite element simulations of both laboratory tests on intact rock specimens as well as a large-scale structural benchmark related to failure of rock mass. Thereby, a wide range of loading conditions comprising unconfined and/or confined, tensile and/or compressive stress states is considered. The capability of the gradient-enhanced rock model for representing the mechanical response objectively with respect to the finite element discretization and realistically compared to measurement data is assessed. It is shown that complex failure modes and the respective load–displacement curves are predicted in a mesh-insensitive manner. [ABSTRACT FROM AUTHOR]

Uranium isotopes have been used as mechanistic or time scale tracers of natural processes. This paper describes the occurrence and redistribution of U in the Vendian aquifer of a paleo-valley in NW Russia. Forty-four rock samples were collected from nine boreholes with depths up to 160 m, and 25 groundwater samples were collected from 23 boreholes with depths up to 300 m. The U, Fe concentration, and 234U/238U activity ratio were determined in the samples. Estimations were made of the 14C and 234U-238U residence time of groundwater in the aquifer. It has been established that the processes of chemical weathering of Vendian deposits led to the formation of a strong oxidation zone, developed above 250 m.b.s.l. The inverse correlation between the concentrations of uranium and iron is a result of removal of U from paleo-valley slopes in oxidizing conditions, accumulation of U at the bottom of the paleo-valley in reducing conditions, and accumulation of Fe on the slopes and removal from the bottom of the paleo-valley. Almost all U on the slopes has been replaced by a newly formed hydrogenic U with a higher 234U/238U activity ratio. After, dissolution and desorption of hydrogenic U occurred from the slopes during periods with no glaciations and marine transgressions. Elevated concentrations of U are preserved in reduced lenses at the paleo-valley bottom. In these areas, the most dangerous aspect is the flow of groundwater from the underlying horizons, since during the operation of water supply wells it can lead to the creation of local zones of oxidizing conditions in the perforated screens zone and the transition of uranium into solution. For groundwater under oxidizing conditions, an increase in the concentration of uranium is characteristic of an increase in the residence time (age) of water in the aquifer. Also, the 234U/238U activity ratio increases with increasing radioactivity of groundwater. Therefore, the most rational approach is to use groundwater for drinking water supply from the slopes of the Northern Dvina basin. [ABSTRACT FROM AUTHOR]