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Point cloud modeling of rock slopes using LIDAR and Structure-from-Motion digital stereophotogrammetry provides,at a minimum, thousands of facets and facet normals that can be used to identify the densities of orientations of rock massdiscontinuities, the geometries of potentially removable blocks, and the character of the excavation face. As part of the EngineeringGeology graduate curriculum at the Civil and Environmental Engineering program at the University of California, Berkeley we teachgraduate students an integrated methodology for [a] gathering point cloud information be laser or camera; [b] computing facets andfacet normals form point clouds for stereonet presentation and geometric analysis of block dimension; [c] extract rock massdiscontinuities from stereonet data to analyze key blocks, assess discontinuous deformation analysis (DDA) behavior, and modelrock slope stability. These new methods require a suite of different software tools discussed in the paper to move through the workflowprocess. Computational rock mechanics provides data sets that are orders of magnitude richer in detail and result in betterunderstanding of rock slope and tunnel key block behavior. Full application of computational rock mechanics methods should reducethe cost of bolting by identifying critical support orientations and design loads.

Left ventricular noncompaction cardiomyopathy is associated with heart failure, arrhythmia, and sudden cardiac death. The developmental mechanism underpinning noncompaction in the adult heart is still not fully understood, with lack of trabeculae compaction, hypertrabeculation, and loss of proliferation cited as possible causes. To study this, we utilised a mouse model of aberrant Rho kinase (ROCK) signalling in cardiomyocytes, which led to a noncompaction phenotype during embryogenesis, and monitored how this progressed after birth and into adulthood. The cause of the early noncompaction at E15.5 was attributed to a decrease in proliferation in the developing ventricular wall. By E18.5, the phenotype became patchy, with regions of noncompaction interspersed with thick compacted areas of ventricular wall. To study how this altered myoarchitecture of the heart influenced impulse propagation in the developing and adult heart, we used histology with immunohistochemistry for gap junction protein expression, optical mapping, and electrocardiography. At the prenatal stages, a clear reduction in left ventricular wall thickness, accompanied by abnormal conduction of the ectopically paced beat in that area, was observed in mutant hearts. This correlated with increased expression of connexin-40 and connexin-43 in noncompacted trabeculae. In postnatal stages, left ventricular noncompaction was resolved, but the right ventricular wall remained structurally abnormal through to adulthood with cardiomyocyte hypertrophy and retention of myocardial crypts. Thus, this is a novel model of self-correcting embryonic hypertrabeculation cardiomyopathy, but it highlights that remodelling potential differs between the left and right ventricles. We conclude that disruption of ROCK signalling induces both morphological and electrophysiological changes that evolve over time, highlighting the link between myocyte proliferation and noncompaction phenotypes and electrophysiological differentiation. [ABSTRACT FROM AUTHOR]

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]

In 1972 a group of Mormon missionaries in Spain formed a band known as Los Salt Lake City. Playing primarily folk and rock music, they toured the country, gave radio and press interviews, and released two albums and an EP. Their experience is recounted and assessed in relation to the musical context of Spain at the time, including the social, religious, and political implications of the musical context. [ABSTRACT FROM AUTHOR]

Since the classical element model cannot describe the nonlinear characteristics of rock during the entire compressive creep process, nonlinear elements and creep damage are generally introduced in the model to resolve this issue. However, several previous studies have reckoned that creep damage in rock only occurs in the accelerated creep stage and is only described by the Weibull distribution. Nevertheless, the creep damage mechanism of rocks is still not clearly understood. In this study, a reasonable representation of the damage variables of solid materials is presented. Specifically, based on the Gurson damage model, the damage state functions reflecting the constant creep stage and accelerated creep stage of rock are established. Further, the one-dimensional and three-dimensional creep damage constitutive equations of rock are derived by modifying the Nishihara model. Finally, the creep-acoustic emission tests of phyllite under different confining pressures are conducted to examine the creep damage characteristics of phyllite. And the proposed constitutive model is verified by analyzing the results of creep tests performed on saturated phyllite. Overall, this study reveals the relationship between the creep characteristics of rocks and the corresponding damage evolution pattern, which bridges the gap between the traditional theory and the quantitative analysis of rock creep and its damage pattern. [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]

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that leads to respiratory decline caused by scarring and thickening of lung tissues. Multiple pathways contribute to the fibrotic process in this disease, such as inflammation, epithelial-to-mesenchymal transition, and oxidative stress. The Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway is a key regulator of profibrotic signaling, as it affects the organization of actin-myosin and the remodeling of the extracellular matrix. ROCK1/2, a downstream effector of RhoA, is overexpressed in patients with IPF and is a promising target for IPF therapy. However, because of the hypotensive side effects of ROCK1/2 inhibitors, selective ROCK2 compounds are being explored. In this study, we report the discovery of GNS-3595, a potent and selective ROCK2 inhibitor that has ∼80-fold selectivity over ROCK1 at physiological concentrations of ATP. GNS-3595 effectively inhibited ROCK2-mediated phosphorylation of myosin light chain and reduced the expression of fibrosis-related proteins (e.g., collagen, fibronectin, and α-smooth muscle actin) in various in vitro cellular models. GNS-3595 also prevented transforming growth factor β–induced fibroblast-to-myofibroblast transition. In addition, in a bleomycin-induced mouse model of pulmonary fibrosis, therapeutic exposure to GNS-3595, suppressed lung fibrosis, stabilized body weight loss, and prevented fibrosis-induced lung weight gain. Transcriptome and protein expression analysis from lung tissues showed that GNS-3595 can revert the fibrosis-related gene expression induced by bleomycin. These results indicate that GNS-3595 is a highly potent, selective, and orally active ROCK2 inhibitor with promising therapeutic efficacy against pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

AbstractThe ‘New Rock’ bands active in Japan since the late 1960s preferred setting rock music to lyrics in English. Thus, when new band Happy End began attempting to sing rock in Japanese, a backlash from English-language rockers led by The Flower Travelin’ Band emerged in response. An unusually heated controversy between these two lyrical approaches marked publications in the emerging Japanese rock press in the early 70s. Building upon previous scholarship which connects this so-called ‘Japanese rock debate’ to narratives of post-colonialism, I argue for interpreting the rock debate foremost as a product of a particular time when rock was seen as a medium that connected a community of youth to a global counterculture. By investigating the actual contours of the discourse in the Japanese rock press, I demonstrate that the issue of language and linguistics was less pressing to New Rockers than more existential issues of identity, ideology, and generational politics. Further, I posit that Happy End was able to succeed with Japanese lyrics not only because of their inventive linguistic adaptations, but because the force of opposition to Japanese lyrics naturally declined as the counterculture ideals of the early 1970s began to fade. [ABSTRACT FROM AUTHOR]

This article proposes an intercultural analysis of gesture and timbre in Fujikura Dai's neo for solo shamisen (2014). I analyze neo through the concept of te, a term used by shamisen players to refer to 1) recurring melodic patterns; and 2) their characteristic fingerings, hand positions, and performance techniques. My analysis of neo highlights how a performer's use of te can shape the form of a piece. Through aural and visual analysis of performances by shamisen player Honjoh Hidejirō, I demonstrate how the form of neo unfolds through changes in te. Weaving together the embodied knowledge of shamisen players, Japanese and U.S./Canadian theories of fretboard topography, and performance analysis, my consideration of te serves as an intercultural mode of analysis that reflects Fujikura's and Honjoh's backgrounds in Western art music, shamisen performance, and rock. [ABSTRACT FROM AUTHOR]

The connection between the Late Bronze Age (LBA) Aegean costumes and social, cultural and political changes is a rather unexplored topic. Probably the only exception are kilts, the connection of which to such changes on Crete during the 15th century BCE remains a commonly discussed topic in studies focusing on the LBA Aegean iconography and other data sets. However, many questions remain open and the topic is far from exhausted. In this paper I build on the work of various scholars who have studied LBA Aegean kilts in the context of social, political and cultural changes. I diachronically study the changes in the representations of kilts since the beginning of the LBA in the Aegean until the end of the Palatial period on the Greek Mainland (ca. 1700/1600–1200 BCE). Moreover, I examine the spatial distribution of specific kilt types in different periods. In cases of several different kilt types appearing in contemporary contexts in the same region, I explore whether similar costumes might have had different social connotations within the same communities. Moreover, I examine the influence of elite power structures and socio-political changes on the perception of kilts. However, I do not observe kilts as passive reflections of specific social, cultural and political contexts, but rather as material forms actively used in the creation of social realities. [ABSTRACT FROM AUTHOR]

In this study, FDEM (ECZM), which is the combined finite-discrete element method (FDEM) based on an extrinsic cohesive zone model (ECZM), was improved by incorporating a novel algorithm that makes it easier to insert the cohesive elements than the conventional adaptive remeshing and a scheme to avoid the generation of dormant cohesive element, which is generated as a result of inserting a single cohesive element within the FDEM mesh. The improved FDEM (ECZM) was implemented in a self-developed 2-dimensional code, and it was first validated against a numerical experiment assuming a virtual rock. Subsequently, the proposed FDEM was applied to model the uniaxial compression and the Brazilian tests of siliceous mudstones under quasi-static loading. The results of the proposed FDEM simulations reasonably captured the trends of fracturing and stress-strain curves observed in the experiments well. The proposed scheme can also be extended to parallel computation based on general-purpose-graphic-processing-unit (GPGPU) and 3-dimensional FDEM (ECZM) with minimal efforts. [ABSTRACT FROM AUTHOR]

A complete inventory of 16 mineral type localities and 1 rock type locality in Romania, as well as their assessed geoheritage characteristics and values are presented for the first time. Thirty-nine mineral species, one chemical element and one common rock type were discovered, described and named in Romania. Most of these are closely linked to traditional mining areas: the Baia Mare region, the Apuseni Mts. and the Banat region. Three mineral type localities are outstandingly rich: Săcărâmb/Nagyág in the southern Apuseni Mts. (8 new minerals), Baia Sprie/Felsőbánya in the Baia Mare region (6 new minerals), and Băița Bihor/Rézbánya in the Northern Apuseni Mts. (6 new minerals). The scientific, educational and touristic value and significance of the type localities regarded as „geosites” and „geodiversity sites” are discussed. Based on the quantitative assessment of the scientific, educational and touristic values, the type localities were hierarchically classified, Baia Sprie, Săcărâmb and Măgura Uroiului being the highest ranked. From the geoconservation perspective, site protection and valuation strategies at local and/or regional scales are envisaged. [ABSTRACT FROM AUTHOR]

Historicamente a arte esteve em vários momentos atrelada aos movimentos que se mostravam de resistência a algum tipo de opressão imposta. Dentre as mais diversas manifestações artísticas, certamente a música é a que consegue alcançar mais pessoas, principalmente após o advento dos meios de comunicação de massa. A partir dessas questões iniciais pretende-se investigar as relações que a música-gênero Rock, sobretudo a de autoria feminina, estabelece com a arte-educação desenvolvida em ambientes escolares e em coletivos culturais, tornando-se uma atividade criadora onde educadores e educandos trocam experiências, conseguem transmitir sua realidade social, seus anseios, sonhos e buscam resistir a tantas formas de coerção por parte da sociedade atual. Assim, o presente texto expõe os passos iniciais da pesquisa a ser desenvolvida no biênio 2023-2024 no curso de Mestrado em Educação e Cultura (PPGEDUC/ UFPA Cametá/Pará). Dessa forma, o texto traz os referenciais teóricos e autores/as estudados, bem como as colaborações destes na construção, desconstrução e reconstrução de conceitos, práticas e saberes da arte rock.

In this study, an innovative breakthrough pressure detection system for shale oil is introduced. Experiments were conducted on source rocks from three main rock types in the upper member of the Lower Ganchaigou Formation in the Western Qaidam depression, in Qinghai, China. The results show that the differences between the breakthrough pressures of laminated calcareous mudstone (LCM), siltstone (SS), and massive mixed mudstone (MMM) in the formation are of several orders of magnitude. In particular, the shale oil breakthrough pressure of laminated calcareous mudstone is more than five times greater in the vertical bedding direction than in the horizontal bedding direction. As black medium shale oil turns into yellow light shale oil, the breakthrough pressures in the same lithology and direction are reduced by two-thirds. In laminated mudstone the horizontal breakthrough pressure is lower than the vertical, while in massive mixed mudstone the vertical breakthrough pressure is lower. A composite migration model for shale oil in hybrid strata—horizontal migration along bedding and vertical migration through micro-fractures—is proposed. The results are of great significance for understanding the accumulation of shale oil and for identifying exploration targets. [ABSTRACT FROM AUTHOR]

Abstract To gain insights into the spatial distribution of non-penetrating cracks during the rock fracture process, a comprehensive uniaxial compression test is conducted on cubic gypsum specimens (100 mm × 100 mm × 100 mm) containing two non-penetrating cracks. The two pre-formed cracks are rectangular, with dimensions of 25 mm length, 2 mm width, and depths of 80 mm and 35 mm on adjacent sides of the specimen. The depth of the 80 mm crack can be adjusted from 0° to 150° in increments of 30°, while the other is fixed at a 45° angle. The results show that the spatial distribution of non-penetrating cracks can significantly influence the strength of the specimen. Initially, the strength of the specimen exhibits an upward trend and subsequently declines as the pre-crack inclination angle of the main rupture plane increases, ultimately reaching its pinnacle at 90°. The total percentage of tensile cracks in specimens with different inclinations are found to be 57%, 57%, 63%, 77%, 68%, and 61%, respectively. This change aligns seamlessly with the fluctuation in specimen strength as influenced by the angle of inclination. Non-penetrating cracks can also induce spalling on the specimen surface and give rise to anti-wing cracks, thereby exacerbating the spalling on the specimen surface. The inclinations of non-penetrating cracks can inevitably exert a certain influence on the propagation of neighboring non-penetrating cracks. Additionally, the macro-scale shear fracture of the specimen often occurs on the side of the non-penetrating crack that is deeper. The curved tensile fracture surface formed by the extension of the non-penetrating crack bears resemblance to the non-penetrating region in its ability to somewhat restrain the propagation of new cracks. Even under uniaxial compression, the spalling surface of the specimen containing spatial non-penetrating cracks frequently exhibits fracture characteristics belonging to I-III mode fracture, while its interior may display characteristics belonging to I-II-III mode fracture. These findings hold significant implications for comprehending and elucidating the genuine fracture process and three-dimensional fracture theory of rocks.

Purpose. The main purpose of the study is to systematize and analyse in-depth current trends in the field of landslide prevention and development in different countries of the world, especially in Ukraine, as well as to consider and highlight the main factors that cause landslides, and to study in detail the methods of their prediction and minimization of relevant risks. Methodology. Landslides are a serious geological hazard. Currently, there is a tendency to increase the frequency of landslides due to anthropogenic impact worldwide. The natural processes of the geological environment, together with the development of mineral deposits, massive and large-scale land development, lead to the intensification of landslide processes. The cause of landslide formation is an imbalance between the shear force of gravity and the retaining forces. Findings. The number of landslides in recent years has been analysed and their distribution on different continents has been considered in detail. The causes of landslides in Ukraine and other countries of the world are identified and systematized. The urgency of the problem of landslide phenomena in Ukraine is considered, and the need for progressive study of landslide formation processes in order to prevent them is emphasized. The importance of continuous monitoring of slope stability is emphasized to reduce risks and improve safety. Originality. A comprehensive study of current trends in the occurrence and development of landslides in different countries of the world and Ukraine in particular was carried out, taking into account the latest advances in the field of geology, geomechanics and construction. Based on the analysis, conclusions were drawn about the need for progressive study of landslide processes in order to prevent them. Practical value. The results of the review of landslide prevention trends can be effectively used to improve natural risk management strategies, as well as to develop new and improve existing engineering measures aimed at preventing landslides. This, in turn, will help to improve the safety of both the population and critical infrastructure.

In order to improve the Hoek-Brown strength criterion not considering the influence of intermediate principal stress on rock strength, the evolutions of rock strength were investigated according to the results of the rock true triaxial compression test. The intermediate principal stress coefficient was introduced to quantify the effect on rock strength. Considering the relationships between the parameter of the Hoek-Brown strength criterion and the rock stress levels, the modified Hoek-Brown strength criterion for the true triaxial stress was then established with the Lagrange interpolation method. The spatial envelope characteristics of the modified strength criterion were analyzed. The best-fitting errors of seven rocks with true triaxial test results were finally compared with the three other three-dimensional strength criteria to verify the rationality of the modified strength criterion. The research results indicate that the rock strength increases gradually with the increase of minimum principal stress, and increases first and then decreases with the increase of intermediate principal stress, which presents a significant interval effect. The modified strength criterion not only has the advantage of the Hoek-Brown strength criterion in the nonlinear characteristics of the meridian plane but also describes the basic characteristics of rock strength in stress space. The spatial envelope surfaces for the modified strength criteria with the linear and quadratic interpolation are the non-equilateral hexagonal pyramidal surfaces and conical surfaces, which can meet the requirement of continuous smoothness in the tension-compression meridian plane interval. The modified strength criterion can better predict the true triaxial strength of rocks and reasonably reflect the influence of intermediate principal stress on the rock strength. The modified strength criterion with the quadratic interpolation improves the prediction accuracy of rock strength by about 1.2 to 2.0 times compared to the criterion with linear interpolation. The modified strength criterion has good agreement with the true triaxial test results of different hard and brittle rocks compared with other true triaxial strength criteria, which shows the applicability and reliability of the modified strength criterion.

Earthquakes are natural events and it is quite easy and beneficial to convert them to wealth (national asset) rather than catastrophe. The earthquakes exert their catastrophe on the buildings/structures founded in soil grounds. There is not even a single case study of an earthquake that caused a catastrophe where structures/buildings are founded on/in a rocky ground that is not proper for agriculture. However, almost all inland earthquakes, particularly strike-slip and normal fault zones ultimately create larger and thicker soil mantle, which is heated by (a) kinetic energy created by particle movements and (b) higher geothermal gradient peculiar to active fault zones. So, people should use fertile soil plains for agriculture and surrounding rocky lands for settlement in accordance with the recommendations of Mother Nature and State Laws and in accordance with the maxim "Love the nature, never challenge it”.

The Ras homology (Rho) family of GTPases serves various functions, including promotion of cell migration, adhesion, and transcription, through activation of effector molecule targets. One such pair of effectors, the Rho‐associated coiled‐coil kinases (ROCK1 and ROCK2), induce reorganization of actin cytoskeleton and focal adhesion through substrate phosphorylation. Studies on ROCK knockout mice have confirmed that ROCK proteins are essential for embryonic development, but their physiological functions in adult mice remain unknown. In this study, we aimed to examine the roles of ROCK1 and ROCK2 proteins in normal adult mice. Tamoxifen (TAM)‐inducible ROCK1 and ROCK2 single and double knockout mice (ROCK1flox/flox and/or ROCK2flox/flox;Ubc‐CreERT2) were generated and administered a 5‐day course of TAM. No deaths occurred in either of the single knockout strains, whereas all of the ROCK1/ROCK2 double conditional knockout mice (DcKO) had died by Day 11 following the TAM course. DcKO mice exhibited increased lung tissue vascular permeability, thickening of alveolar walls, and a decrease in percutaneous oxygen saturation compared with noninducible ROCK1/ROCK2 double‐floxed control mice. On Day 3 post‐TAM, there was a decrease in phalloidin staining in the lungs in DcKO mice. On Day 5 post‐TAM, immunohistochemical analysis also revealed reduced staining for vascular endothelial (VE)‐cadherin, β‐catenin, and p120‐catenin at cell–cell contact sites in vascular endothelial cells in DcKO mice. Additionally, VE‐cadherin/β‐catenin complexes were decreased in DcKO mice, indicating that ROCK proteins play a crucial role in maintaining lung function by regulating cell–cell adhesion.

The operation of oil production wells is accompanied by the invasion of well killing fluids into a near wellbore zone while well intervention which deteriorates rock permeability and decreases well oil rate. In order to restore the permeability of the rock in the near wellbore zone of the formation, it is proposed in this work to use ultrasonic alternating loading during well inflow stimulation. To study the effect of alternating loading on the permeability of rocks, a laboratory set-up is developed and filtration experiments are carried out. The rock studied was sandstone of medium permeability. The experimental studies included four stages: filtration of the killing fluid (calcium chloride solution) in the forward direction (simulating well killing); keeping the sample in conditions of pumped kill fluid; filtration of kerosene in the opposite direction (simulating an inflow stimulation) until the maximum possible restoration of permeability; filtration of kerosene in the reverse direction under ultrasonic alternating loading conditions for additional permeability restoration. It was revealed, that under conditions of ultrasonic alternating loading, the pore space of the rock, previously blocked by particles of the killing fluid, is unblocked and the permeability of the samples is restored. An analysis was made of the mechanism of blocking the pore space with the killing fluid and restoring the permeability of the rock.

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]

This study proposes a fractal damage calculation method that understands the blasting damage laws at the macroscopic, mesoscopic, and microscopic scales of rock. The findings indicated that the binary graph derived from the Moments algorithm can represent minute cracks and exhibit less noise within the image. This makes the algorithm suitable for identifying and extracting macroscopic damage. A three-dimensional (3D) reconstruction technique offers visualization of the macroscopic rock damage following an explosion. The extent of this damage is quantitatively assessed using the box dimension. In addition, a multifractal method is introduced to comprehensively evaluate the macroscopic and mesoscopic damage to rock post-blasting. The multifractal dimension calculations analysis reveals that the mesoscopic damage to rock following blasting is a significant factor in the overall blasting damage. The box dimension presents a straightforward, macroscopic evaluation method for assessing 3D macroscopic fractures. On the other hand, the multifractal dimension can more accurately evaluate the macroscopic cracks and mesoscopic damage resulting from blasting. Both methods emphasize different aspects and are equally effective for assessing blasting damage. Highlights: This study proposes a fractal damage calculation method that understands the blasting damage laws at the macroscopic, mesoscopic, and microscopic scales of rock. The box dimension is a straightforward macroscopic evaluation method for assessing 3D macroscopic fractures. The multifractal dimension more accurately evaluates the macroscopic cracks and mesoscopic damage from blasting. After ordinary charge initiations, blasting damage exhibited a bimodal distribution along the borehole's axis, peaking in the charging section. [ABSTRACT FROM AUTHOR]

Creep tests under constant stress are among the most important tests for investigating the time-dependent behavior of rock. In previous studies, creep tests were conducted under various loading and environmental conditions; however, it was very difficult to demonstrate accelerating creep at failure at stresses less than 50% of strength in conventional creep tests. In this study, a new test method is proposed that combines an alternating loading-rate test and a creep test in the post-failure region. The accelerating creep as well as the loading-rate dependence of strength were successfully obtained simultaneously from a single specimen. This test method was applied to three rock types under dry and wet conditions. The results of Sanjome andesite under both dry and wet conditions, Kimachi sandstone under dry conditions, and Tage tuff under dry conditions showed a similar relationship between creep strain, creep strain rate, and residual time (i.e., creep lifetime minus elapsed time), from high to low creep stress levels, and a close relationship between accelerating creep and the loading-rate dependence of strength. Further, the mechanism responsible for the time dependence was found not to change significantly from high to low stress levels. In contrast, different results were obtained when high and low creep stress levels were compared in Kimachi sandstone and Tage tuff under wet conditions. The larger increase in creep strain with increasing creep strain rate at lower creep stress levels was related to the shape of the stress–strain curve in the post-failure region. Highlights: A new test method was proposed that combined an alternating loading-rate test and a creep test in the post-failure region. Accelerating creep at failure was discussed in detail based on the test results from high to low creep stress levels. Test results showed a close relationship between accelerating creep and the loading-rate dependence of strength. [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]

Background: Rho kinase (ROCK) pathway plays a critical role in post‐COVID‐19 pulmonary fibrosis (PCPF) and its intervention with angiotensin‐converting enzyme 2 (ACE2) and vascular endothelial growth factor (VEGF) will be a potential therapeutic target. Objectives: The present study was conducted to investigate the efficacy of zoledronate (ZA) on carbon tetrachloride (CCl4) induced pulmonary fibrosis (PF) in rats through targeting ACE2, ROCK, and VEGF signaling pathways. Methods: Fifty male Wistar rats were divided into five groups: control, vehicle‐treated, PF, PF‐ZA 50, and PF‐ZA 100 groups. ZA was given in two different doses 100 and 50 μg/kg/week intraperitoneally. After anesthesia, mean arterial blood pressure (MBP) was measured. After scarification, lung coefficient was calculated. Lung levels of ACE 2, interleukin‐1β (IL‐1β), transforming growth factor‐β (TGF‐β), VEGF, glutathione (GSH), and superoxide dismutase (SOD) were measured. Expression of ROCK, phosphorylated myosin phosphatase target subunit 1 (P‐MYPT1), and matrix metalloproteinase (MMP‐1), along with histopathological changes and immune‐histochemical staining for lung α‐smooth muscle actin (α‐SMA), tumor necrosis factor‐alpha (TNFα), and caspase‐3, were evaluated. Results: ZA significantly prevented the decrease in MBP. ZA significantly increased ACE2, GSH, and SOD and significantly decreased IL‐1β, TGF‐β, and VEGF in lung in comparison to PF group. ZA prevented the histopathological changes induced by CCl4. ZA inhibited lung expression of ROCK, P‐MYPT1, MMP‐1, α‐SMA, TNFα, and caspase‐3 with significant differences favoring the high dose intervention. Conclusion: ZA in a dose‐dependent manner prevented the pathological effect of CCl4 in the lung by targeting mevalonate pathway. It could be promising therapy against PCPF. [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]

The introduction of thousands of wind turbines along the North American Atlantic continental shelf over the next decade will constitute the largest regional change in marine substrates since the retreat of the Laurentide Ice Sheet over 14,000 years ago. Here, two large data sets, SMAST drop camera survey (242,949 samples, 2003 to 2019) and the US Geological Survey databases (27,784 samples, 1966 to 2011), are combined to derive sea floor surficial substrate probability maps for the Northeastern US continental shelf from Virginia Beach to the Gulf of Maine to 300 m depth (218,571 km2). Geostatistical models were used to estimate the probability of five geologic and one biogenic substrate types being present at a 250 m resolution, and the proportional contribution of each substrate type to the seabed composition at a 500 m resolution. By providing the first synoptic maps depicting the probability of a particular substrate or combination of substrates occurring at any location on the Northeastern US continental shelf, including planned wind energy sites, we aim to (1) provide insights regarding how substrates in the areas selected for wind energy development compare with other locations, (2) motivate the development of a priori expectations for ecosystem changes to inform monitoring and research efforts going forward, and (3) to provide a baseline characterization of the Northeastern US continental shelf surficial substrates to support robust examination of the future changes observed in areas impacted by wind energy installations. [ABSTRACT FROM AUTHOR]

More than 650 reversible and irreversible post-translational modifications (PTMs) of proteins have been listed so far. Canonical PTMs of proteins consist of the covalent addition of functional or chemical groups on target backbone aminoacids or the cleavage of the protein itself, giving rise to modified proteins with specific properties in terms of stability, solubility, cell distribution, activity, or interactions with other biomolecules. PTMs of protein contribute to cell homeostatic processes, enabling basal cell functions, allowing the cell to respond and adapt to variations of its environment, and globally maintaining the constancy of the milieu interieur (the body's inner environment) to sustain human health. Abnormal protein PTMs are, however, associated with several disease states, such as cancers, metabolic disorders, or neurodegenerative diseases. Abnormal PTMs alter the functional properties of the protein or even cause a loss of protein function. One example of dramatic PTMs concerns the cellular prion protein (PrPC), a GPI-anchored signaling molecule at the plasma membrane, whose irreversible post-translational conformational conversion (PTCC) into pathogenic prions (PrPSc) provokes neurodegeneration. PrPC PTCC into PrPSc is an additional type of PTM that affects the tridimensional structure and physiological function of PrPC and generates a protein conformer with neurotoxic properties. PrPC PTCC into PrPSc in neurons is the first step of a deleterious sequence of events at the root of a group of neurodegenerative disorders affecting both humans (Creutzfeldt-Jakob diseases for the most representative diseases) and animals (scrapie in sheep, bovine spongiform encephalopathy in cow, and chronic wasting disease in elk and deer). There are currently no therapies to block PrPC PTCC into PrPSc and stop neurodegeneration in prion diseases. Here, we review known PrPC PTMs that influence PrPC conversion into PrPSc. We summarized how PrPC PTCC into PrPSc impacts the PrPC interactome at the plasma membrane and the downstream intracellular controlled protein effectors, whose abnormal activation or trafficking caused by altered PTMs promotes neurodegeneration. We discussed these effectors as candidate drug targets for prion diseases and possibly other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

In engineering construction, rocks broken by mining and tunnel excavation are often used as concrete aggregates, and rock fragmentation influences the elastic modulus of concrete. To improve the efficiency of rock breaking and the application effects of rock aggregates, this work proposed a method for evaluating rock breakability and the impact of the produced aggregate on the elastic modulus of concrete. The breakability of rock and its impact on concrete performance were studied based on fractal theory. A physical parameter characterization method was proposed to quickly compare the difficulty of rock fragmentation, characterizing the breakability of rocks and the processability of aggregates. The relationship between the relative specific surface area of aggregates and their main physical properties was established. The influence of rock breakability on the elastic modulus of concrete was analyzed through laboratory tests of uniaxial compression on concrete. Results demonstrate that the content of firm components in the rock mineral composition is significant, and the particle content of the main mineral components is positively correlated with the relative specific surface area of the fragmented aggregates. The relative specific surface area of the aggregates is negatively correlated with the fineness modulus and apparent density of the aggregates and positively correlated with the stone powder content and crushing index. The relative specific surface area of the aggregates shows a linear decreasing relationship with the water-to-binder ratio and elastic modulus. For C30 (C40) concrete, the water-to-binder ratio increased by 19.4% (21.4%), and the static compressive elastic modulus increased by 22.5% (25.0%). This study provides a particular guiding significance for the rapid and effective breaking of rock bodies and the resource utilization of aggregates. [ABSTRACT FROM AUTHOR]

Purpose. Development of effective composite plugging systems for reliable fastening of oil and gas wells in difficult mining-geological conditions of deposits of Ukraine. Methods. The proposed research is based on an analytical and industrial study of the problems of the well construction and fastening in the conditions of chemogenic deposit occurrence when applying the analysis of geophysical research materials. The research of tamponage solutions and buffer liquids was carried out using standard devices and methods that meet the set of requirements for testing cements and technological systems for well construction. Processing of research results was carried out in MATHSAD and EXCEL. Composite cement CEM V according to the European standard EN 197-1, tamponage cement 1-G, krents - high-basic C2F CaSO4 and low-basic 3(CF) CaSO4 calcium sulfoferites were used for the research. Findings. It was established that the basic plugging material, as well as technological solutions for fastening wells in difficult mining-geological conditions, do not ensure compliance of the well as an engineering structure with operational reliability indicators. As a result, violations in the fastening system are quite often recorded, which require significant time and financial costs for their elimination, and sometimes lead to well liquidation. In order to increase the reliability of fastening wells, it is necessary to use multi-component tamponade systems modified by krents. Calcium sulfoferrite admixtures have been proved to accelerate the kinetics of early strength and contribute to the formation of cement stone with improved characteristics. The need to use effective buffer systems to improve the quality of fastening is substantiated. Originality. On the basis of assessment, systematization and detailed study of geophysical material and features of well fastening under the conditions of exposure to chemogenic sediments, the necessity of using composite plugging material was established. The conducted studies have proved that to ensure reliable fastening of wells in difficult mining-geological conditions, it is necessary to use multicomponent composite plugging material modified by calcium sulfoferites with accelerated kinetics of early strength, which form cement stone with a densely packed structure. Practical implications. Based on the industrial material evaluation and detailed laboratory studies, technological solutions have been developed to increase the reliability of well fastening due to the introduction of multi-component composite plugging material modified by krents and buffer liquids. [ABSTRACT FROM AUTHOR]

Purpose. Development of highly effective composite diamond-containing materials based on WC‒Co matrices with CrB2 additives with improved mechanical and performance properties for creating matrices of rock-cutting tools for drilling oil and gas wells. Methodology. The assigned tasks were solved using a comprehensive research method, which includes a review and synthesis of literary sources; conducting analytical studies of existing composite diamond-containing materials; scanning electron microscopy (SEM) methods; X-ray phase analysis methods; calculation of experimental data by the Rietveld method, developed for the characterization of crystalline materials by powder X-ray diffraction; the Williamson-Hall technique. Findings. It has been established that the structure of the initial 94 %WC–6 %Co composite consists of WC phases with crystal lattice parameters a = 0.2906, c = 0.2837 nm and graphite with lattice parameters a = 0.2461, c = 0.6708 nm. The addition of chromium diboride to the composition of the 94 %WC–6 %Co sample leads to the decomposition of the CrB2 phase and the formation of the final phase composition: WC + B2CoW2 + Cgraphite + solid solution of tungsten and carbon in cobalt. Originality. It was shown for the first time that if the WC–6Co system is characterized by insignificant solubility of the components in each other, then in the WC–Co–CrB2 system there is a significant mutual dissolution of the components, which leads to a decrease in their sizes during the sintering process. When the threshold concentration (~4 %) of chromium diboride in the charge is reached, phases of the hexagonal WC group and new phases of the orthorhombic group B2CoW2 and amorphous carbon inclusions begin to form in the structure of the composite. Practical value. A highly effective composite diamond-containing material based on WC‒Co matrices with CrB2 additives with increased mechanical (hardness, crack resistance, compressive and bending strength) and operational (wear resistance, productivity) properties has been developed to create a highly effective rock-cutting tool for drilling oil and gas wells. [ABSTRACT FROM AUTHOR]

The Niger Delta, a cornerstone of Nigeria's oil and gas sector, plays a significant role in the Nation's energy landscape. This research concentrates on enhancing reservoir characterization, specifically emphasizing advancing rock facies classification. Employing advanced machine-learning methodologies and a dataset from 12 wells containing crucial well log parameters, such as Gamma Ray, Resistivity Micro-Spherical, Volume of Shale, Resistivity Deep, Resistivity Medium, Density, and Porosity, we conducted a rigorous evaluation of various classification models. The Random Forest algorithm emerged as the optimal choice, achieving an impressive F1 score of 0.93 and an accuracy of 0.93 on the cross-validation set. A meticulous analysis of identified facies classes, including Shale, Lower Shoreface, Middle Shoreface, Upper Shoreface, Transition Shoreface, Over Bank, and Channel, through confusion matrices, offered profound insights into the Model's efficiency. Feature importance analysis underscored the critical role of variables such as volume of shale, gamma ray, porosity, and bulk density in driving accurate predictions. This research significantly advances subsurface exploration in the Niger Delta, highlighting the effectiveness of machine learning for geologic characterization within the region's intricate geological landscape. [ABSTRACT FROM AUTHOR]

AbstractFor rock structures exposed in the natural condition, water-induced weakening (including water softening and chemical weathering) is thought to be the main reason for its’ stiffness and strength degradation, thus it is of great significance to study the mechanical properties of rocks under the influence of water. In this study, a hexagonal close-packed particle assembly (2D) composed of bonded circular particles with same diameter is considered to approximate a typical soft rock, where the composite contact model for rock materials considering the water-induced wakening is adopted to define the microscopic mechanical reactions between particles. Based on homogenisation theory and lattice model, the stress-strain relationship and strength criteria for rock considering water-induced weakening, as well as the quantitative correlation between macroscopic elastic and strength parameters with microscopic parameters are obtained. The effects of water softening and chemical weathering respectively characterised by saturation and mass loss ratio on macroscopic mechanical behaviours of rock are analysed in detail. The long-term ageing effects of water-induced weakening are also analysed. All results are in good agreement with the laboratory test results, verifying the applicability of the theoretical solution for analysing the effect of water-induced weakening on mechanical behaviours of rock. [ABSTRACT FROM AUTHOR]

Earthquakes are natural events and it is quite easy and beneficial to convert them to wealth (national asset) rather than catastrophe. The earthquakes exert their catastrophe on the buildings/structures founded in soil grounds. There is not even a single case study of an earthquake that caused a catastrophe where structures/buildings are founded on/in a rocky ground that is not proper for agriculture. However, almost all inland earthquakes, particularly strike-slip and normal fault zones ultimately create larger and thicker soil mantle, which is heated by (a) kinetic energy created by particle movements and (b) higher geothermal gradient peculiar to active fault zones. So, people should use fertile soil plains for agriculture and surrounding rocky lands for settlement in accordance with the recommendations of Mother Nature and State Laws and in accordance with the maxim "Love the nature, never challenge it”. [ABSTRACT FROM AUTHOR]

A thorough understanding of the evolution of strain and damage accumulation is a prerequisite for effective control of the surrounding rock to ensure good stability and better maintenance of underground structures. In this work, we have proposed a new way of adjusting the fractional order to obtain a new variable fractional order rheological model to describe the evolution of mechanical properties and to model the stress-strain response of the rock during plastic flow. It is proved that the function law of our variable order fractional model is defined by five parameters a , b , m , n , α 0. An analysis of the different parameters of the fractional model confirms that the mechanical behavior of the rock hardens and softens faster when the confining pressure is high. Moreover, the definition of our fractional model by a continuous function of the plastic strain allows us to explore in more detail the hardening/softening duality of the mechanical behavior of the rock. This fractional model not only allows us to model the stress-strain relationship of the rock more accurately and with a relatively short calculation time, it also allows us to model the stress-strain relationship of the rock more accurately and with a relatively short calculation time, but also to accurately capture the contraction-dilation volume transition of quasi-fragile rocks. We believe that the results of this work will help in the decision making process for the construction of underground structures. • A new fractional model is established by a continuous function of plastic strain. • Its continuous form is necessary to evaluate the influence of confining pressure. • The new model more accurately describes the stress-strain relationship of the rock. • This model also reflects the rock's compression-dilation volume transition. [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]

The classical Mohr–Coulomb criterion has an extremely wide range of applications in the field of engineering geology, while it cannot accurately characterize rock failure under high confining stresses. Therefore, a nonlinear modification is implemented based on the Mohr–Coulomb criterion for achieving wider usage in all stress environments. The cohesion and internal friction angle are firstly calculated by regression based on the triaxial experiments of diorite and other typical rocks in different confining stress ranges, and the variation modes of cohesion and internal friction angle are then formalized and integrated into the classical Mohr–Coulomb criterion. Using the experimental results of 435 triaxial compression tests in existing publications, the predictions of the modified criterion are compared with those of the previous nonlinear criteria, which show that the predicted values of the modified criterion are in good agreement with the measured strength. Compared with the previous nonlinear criteria, the modified criterion has a wider application range and always maintains a higher accuracy. Highlights: A modified nonlinear Mohr–Coulomb criterion is proposedThe accuracy of the proposed criterion is verified by 435 triaxial tests.The proposed criterion shows a higher accuracy than previous nonlinear criteria [ABSTRACT FROM AUTHOR]

The Ras homology (Rho) family of GTPases serves various functions, including promotion of cell migration, adhesion, and transcription, through activation of effector molecule targets. One such pair of effectors, the Rho‐associated coiled‐coil kinases (ROCK1 and ROCK2), induce reorganization of actin cytoskeleton and focal adhesion through substrate phosphorylation. Studies on ROCK knockout mice have confirmed that ROCK proteins are essential for embryonic development, but their physiological functions in adult mice remain unknown. In this study, we aimed to examine the roles of ROCK1 and ROCK2 proteins in normal adult mice. Tamoxifen (TAM)‐inducible ROCK1 and ROCK2 single and double knockout mice (ROCK1flox/flox and/or ROCK2flox/flox;Ubc‐CreERT2) were generated and administered a 5‐day course of TAM. No deaths occurred in either of the single knockout strains, whereas all of the ROCK1/ROCK2 double conditional knockout mice (DcKO) had died by Day 11 following the TAM course. DcKO mice exhibited increased lung tissue vascular permeability, thickening of alveolar walls, and a decrease in percutaneous oxygen saturation compared with noninducible ROCK1/ROCK2 double‐floxed control mice. On Day 3 post‐TAM, there was a decrease in phalloidin staining in the lungs in DcKO mice. On Day 5 post‐TAM, immunohistochemical analysis also revealed reduced staining for vascular endothelial (VE)‐cadherin, β‐catenin, and p120‐catenin at cell–cell contact sites in vascular endothelial cells in DcKO mice. Additionally, VE‐cadherin/β‐catenin complexes were decreased in DcKO mice, indicating that ROCK proteins play a crucial role in maintaining lung function by regulating cell–cell adhesion. [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]

Rho kinase (ROCK) inhibitors (RKIs) have been available commercially as topical ocular hypotensive agents for approximately a decade. RKIs have promise as their presumed mechanism of action is increased trabecular meshwork (TM) outflow, the presumed primary site of pathology in open-angle glaucoma. We reviewed recent literature on netarsudil, ripasudil, H-1337, and VVN539 as monotherapy and in combination with other topical ocular hypotensive agents. With a unique primary mechanism of increase in trabecular outflow, these agents target the glaucomatous pathology in aqueous humor dynamics. The ocular hypotensive efficacy of netarsudil, once-daily (q.d.), is in the range of non-cardioselective beta-adrenoceptor antagonists. Ripasudil, given twice-daily (b.i.d.), is somewhat less effective. H-1337 and VVN539, at an early development stage, both seem to have efficacy in the range of netarsudil. Conjunctival hyperemia is an adverse event common to all RKIs tested to date. The greater adoption of RKIs in therapy may be limited by financial considerations, at least in the U.S. We searched PubMed for the keywords netarsudil (AR13324), ripasudil (K-115), H-1337, and VVN539 as of November 2023. We found 349 citations which we reviewed for consideration in this review. Herein we summarize primary research reports, excluding news stories or meeting abstracts. We also searched to find new trials of interest. [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]

Small GTPases are monomeric (approximately 21 kDa) proteins that regulate a number of biological processes, such as vesicle transport, cell division cycle, cell migration, invasion, adhesion, proliferation, and DNA repair. They are also involved in carcinogenesis and neurodegenerative diseases. Some of these proteins, such as the Rho family proteins, are essential regulators of actin cytoskeleton, controlling cell adhesion and motility. This review examines both normal and pathological processes in human cells that are regulated by small GTPases of the Rho family. Particular attention is paid to small GTPase inhibitors and their use in the treatment of various diseases. [ABSTRACT FROM AUTHOR]

Background: Rho-kinase (ROCK) regulates actomyosin contraction, coronary vasospasm, and cytoskeleton dynamics. ROCK and of NADPH oxidase (NOX) play an essential role in cardiovascular disease and proteoglycan synthesis, which promotes atherosclerosis by trapping low density lipoprotein. ROCK is activated by endothelin-1 (ET1) and transactivates the transforming growth factor beta receptor (TGFβR1), intensifying Smad signaling and proteoglycan production. This study aimed to identify the role of myosin light chain phosphatase (MLCP) as a downstream target of ROCK in TβR1 transactivation. Methods: Vascular smooth muscle cells were treated with ET1 and inhibitors of ROCK and MLCP were added. The phosphorylation levels of Smad2C, myosin light chain (MLC), and MLCP were monitored by western blot, and the mRNA expression of chondroitin 4-O-sulfotransferase 1 (C4ST1) was assessed by quantitative real-time PCR. Results: We examined ROCK's role in ET1-induced TGFβR1 activation. ROCK phosphorylated MLCP at the MYPT1 T853 residue, blocked by the ROCK inhibitor Y27632. ROCK also increased MLC phosphorylation and actomyosin contraction in response to ET1, enhanced by the phosphatase inhibitor Calyculin A. Calyculin A also increased C4ST1 expression, GAG-chain synthesizing enzymes. Conclusions: This work suggests that ROCK is involved in ET1-mediated TβR1 activation through increased MLCP phosphorylation, which leads to Smad2C phosphorylation and stimulates C4ST1 expression. [ABSTRACT FROM AUTHOR]

This paper demonstrates the importance of a proper contact algorithm selection when a constitutive model is correlated and validated, especially in the case of brittle materials. A parametric study is carried out to study the influence of contact parameters on the outcomes of the numerical simulations of a dynamic compression test. The split Hopkinson pressure bar (SHPB) model is developed, and sandstone rock is considered as a representative material having considerably different properties compared to SHPB bars. The finite element method (FEM) and smoothed particle hydrodynamics (SPH) were used to simulate specimen behaviour using a LS-Dyna solver. Two contact types based on the penalty method are analysed: nodes to surface (FEM and SPH) and surface to surface (FEM only). Furthermore, three approaches of contact stiffness calculation are used for each contact type. The waveform data and failure patterns are then compared among all simulated cases and the corresponding experimental outcomes. It is found that the soft constraint stiffness (SOFT = 1) provides the best outcomes, especially in the case of one-way contact, and is nearly insensitive to stiffness scaling parameters. By contrast, standard (SOFT = 0) and segment-based (SOFT =2) approaches require a substantial effort in adjusting the stiffness scaling parameters to obtain satisfactory results. This paper provides valuable guidance for correlating and validating parameters of constitutive models for rock and other brittle materials in the SHPB test. [ABSTRACT FROM AUTHOR]

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