Caught between a ROCK and a hard place: current challenges in structure-based drug design.

The discipline of structure-based drug design (SBDD) is several decades old and it is tempting to think that the proliferation of experimental structures for many drug targets might make computer-aided drug design (CADD) straightforward. However, this is far from true. In this review, we illustrate some of the challenges that CADD scientists face every day in their work, even now. We use Rho-associated protein kinase (ROCK), and public domain structures and data, as an example to illustrate some of the challenges we have experienced during our project targeting this protein. We hope that this will help to prevent unrealistic expectations of what CADD can accomplish and to educate non-CADD scientists regarding the challenges still facing their CADD colleagues.

Rock crack initiation triggered by energy digestion.

The critical value of rock failure is determined by irreversible deformation (inelastic deformation, damage, and other internal dissipation) processes and external conditions before rock failure. Nevertheless, a thorough explanation of the mechanism causing cracks in rock material has not yet been provided. The strain energy theory is applied in this work to assess the initiation of rock cracks and investigate the relationship between energy digestion and rock strength. Firstly, the uniaxial compression test was conducted on sandstone samples under quasi-static loading conditions and the results of energy evolution, non-linear cumulative digestion, and stored ultimate energy were obtained. Then, a novel algorithm for assessing the initiation of rock cracks has been put forth. The concept of energy digestion index (EDI), which is the ratio of digested energy over the external loading energy, has been developed to characterize the energy absorption capacity of rock material. The result shows a relationship between the maximum growth rate of energy digestion and the increasing rate of variable elasticity modulus and crack initiation. The mechanical characteristics and peak strength of the rock material are negatively correlated with the EDI. By monitoring the digested energy status, an evaluation of the residual strength is introduced based on the relationships, which will initiate further research into in-situ monitoring and failure prediction.

miRNA-mediated inhibition of an actomyosin network in hippocampal pyramidal neurons restricts sociability in adult male mice.

Social deficits are frequently observed in patients suffering from neurodevelopmental disorders, but the molecular mechanisms regulating sociability are still poorly understood. We recently reported that the loss of the microRNA (miRNA) cluster miR-379-410 leads to hypersocial behavior and anxiety in mice. Here, we show that ablating miR-379-410 in excitatory neurons of the postnatal mouse hippocampus recapitulates hypersociability, but not anxiety. At the cellular level, miR-379-410 loss in excitatory neurons leads to larger dendritic spines, increased excitatory synaptic transmission, and upregulation of an actomyosin gene network. Re-expression of three cluster miRNAs, as well as pharmacological inhibition of the actomyosin activator ROCK, is sufficient to reinstate normal sociability in miR-379-410 knockout mice. Several actomyosin genes and miR-379-410 family members are reciprocally dysregulated in isogenic human induced pluripotent stem cell (iPSC)-derived neurons harboring a deletion present in patients with Williams-Beuren syndrome, characterized by hypersocial behavior. Together, our results show an miRNA-actomyosin pathway involved in social behavior regulation.

A comprehensive DEMATEL-ISM model-based safety analysis of the Lianghekou earth-rock dam.

Earth-rock dam failures account for the largest proportion of all dam failure accidents. There are many factors inducing accidents in hydroelectric projects, and the relationships between them are intricate and complex. Therefore, it is crucial to explore the relationship between the influencing factors and identify the key factors leading to accidents. Through an analysis of the factors influencing earth rock dam failures, an index system for failure influence factors was constructed in this paper. Considering complexity and integration in influence factors analysis, a DEMATEL-ISM model (Decision Making Trial and Evaluation Laboratory; Interpretive Structural Model) analysis method was employed to examine the internal relationship among various factors based on the influence degree between them, and a MICMAC model (Matrix Impacts Cross-reference Multiplication Applied to a Classification methodology) was introduced to analyze the hierarchical relationship between various factors. The results showed that The results show that the seismic capacity and flood discharge capacity of the dam body are the key influencing factors of dam safety during the operation of the earth-rock dams. The comprehensive method employed in this paper overcame the complexity of evaluation results and was capable of more directly presenting relationships of factors. As suggested by these results, the analysis model employed in this paper has great significance for preparing a flexible-efficient management scheme for earth-rock dams.

Hydrogeochemical characteristics, driving factors, and health risk assessment of karst groundwater in Southwest Hubei Province, China.

In South China, karst groundwater is an important water resource for industrial, agricultural, and drinking purposes. However, karst aquifers are highly vulnerable to pollution, leading to deteriorating karst groundwater quality and posing potential health risks to local residents. In this study, 22 groundwater samples were collected from a karst aquifer in the southwestern part of Hubei Province. The hydrogeochemical characteristics and their controlling factors were examined, and the potential health risks associated with groundwater pollutant concentrations in karst groundwater were assessed. The results showed that the groundwater is slightly alkaline with low chemical oxygen demand values, indicating good water quality. The groundwater facies type was identified as HCO3-Ca at most sample spots, showing low total dissolved solids concentrations. Substantial spatial variations in Na+, CO3 2-, and NO2 - concentrations were found, whereas spatial variations in the K+, Ca2+, Cl-, HCO3 -, and F- concentrations were small. In addition, the dissolution of gypsum deposits and magnesium carbonate sedimentary rocks at sampling sites resulted in groundwater facies types of HCO3•SO4-Ca and HCO3-Ca•Mg, with low total dissolved solids concentrations. The karst groundwater chemistry in the study area was mainly controlled by water-rock interactions, as well as by the dissolution of gypsum deposits and magnesium carbonate sedimentary rocks at specific groundwater sampling sites. The groundwater Cl- concentrations were mainly affected by atmospheric precipitation. NO3 - was mainly derived from atmospheric precipitation, domestic sewage, septic tanks, and industrial activities, whereas SO4 2- was derived from atmospheric precipitation, sulfate rock dissolution, and sulfide mineral oxidation. These results highlight the absence of potential human health risks of NO3 - and F- to infants, children, and adults, as their concentrations are below the corresponding regional background values. In contrast, the potential health risks of Cl- cannot be ignored, particularly for infants. This study offers scientific guidelines for protecting and allocating local groundwater resources.

Sedimentological and petrophysical characterization of the Bokabil Formation in the Surma Basin for CO2 storage capacity estimation.

Large-scale geological sequestration of CO2 is one of the most effective strategies to limit global warming to below 2 °C, as recommended by the Intergovernmental Panel on Climate Change (IPCC). Therefore, identifying and characterizing high-quality storage units is crucial. The Surma Basin, with its four-way dip closed structures, high-quality reservoirs, and thick regional cap rocks, is an ideal location for CO2 storage. This study focuses on the Bokabil Formation, the most prominent reservoir unit in the Surma Basin. Detailed petrographic, petrophysical, XRD, and SEM analyses, along with mapping, have been conducted to evaluate the properties of the reservoir and cap rock within this formation. The Upper Bokabil Sandstone in the Surma Basin ranges from 270 to 350 m in thickness and consists of fine- to medium-grained subarkosic sandstones composed of 70-85% quartz and 5-12% feldspar, with good pore connectivity. Petrophysical analysis of data from four gas fields indicates that this unit has a total porosity of 21-27.4% and a low shale volume of 15-27%. Cross plots and outcrop observations suggest that most of the shales are laminated within the reservoir. The regional cap rock, known as the Upper Marine Shale (UMS), ranges in thickness from 40 to 190 m and contains 10-40 nm nano-type pores. A higher proportion of ductile materials with a significant percentage of quartz in the UMS indicates higher capillary entry pressures, enhancing its capacity to hold CO2. Using the CSLF method with a 6% cut-off of the available pore volume, it is estimated that 103 Mt, 110 Mt, 205 Mt, and 164 Mt of CO2 can be effectively stored in the Sylhet, Kailashtila, Habiganj, and Fenchuganj structures, respectively. Due to the shallow depth of the storage unit and the thick cap rock, the southern Surma Basin is the optimal location for CO2 injection.

Study on the size effect of rock burst tendency of red sandstone under uniaxial compression.

The study of rock burst tendency of rock masses with different sizes plays a key role in the prevention of rock burst. Through theoretical analysis, it is proposed that uniaxial compressive strength and deformation modulus ratio are the key mechanical parameters affecting rock burst occurrence. In order to find out the size effect of uniaxial compressive strength and deformation modulus ratio, theoretical analysis and uniaxial compression experiment are carried out on rock samples with different heights, different cross-sectional areas and different volumes. The results show that the smaller the uniaxial compressive strength is, the larger the deformation modulus ratio is, and the more likely rock burst are to occur. On the contrary, rock burst is still not easy to generate. The uniaxial compressive strength of rock samples with different heights, different cross-sectional areas and different volumes increases with the increase of rock sample size. The deformation modulus ratio of rock samples with different heights and different volumes shows an upward trend on the whole, while that of rock samples with different cross-sectional areas shows a downward trend on the whole. The fracture forms of rock are analyzed using the energy conversion law in the process of deformation and failure for three kinds of rock with different shapes and sizes.

Prediction of formation abrasiveness under the action of a PDC bit based on the fractal dimension of a rock surface.

During rock drilling, a drill bit will wear as it breaks the rock. However, there is no uniform grading standard for rock abrasiveness. To solve this problem, the wear mechanisms of a polycrystalline diamond compact (PDC) bit and the formation it is drilling into are analyzed in depth, and an abrasiveness evaluation method based on the fractal dimension of the rock surface topography is established. Initially, a three-dimensional digital model is generated from a scanning electron microscope image of the rock after drilling; next, an evaluation of the irregularities on the rock surface is performed using an adapted Weierstrass-Mandelbrot (W-M) function to ascertain the fractal dimensionality. Then, the microcontact characteristics of the contact surface between the formation and the PDC bit are analyzed, and the distribution of the microconvex contact points of the two-body friction pair in a region is obtained. Because the sliding friction between the drill bit and the rock produces a large amount of heat, according to the contact area formula of the friction surface and heat conduction theory, the temperature rise and overall temperature distribution of the formation and PDC bit under the condition of sliding friction are revealed, and the real contact area between the formation and the drill bit within a certain temperature range is obtained. Finally, the evaluation index of rock abrasiveness under sliding conditions is established by adopting the wear weight loss of the rock cutting tool per unit volume as the index of rock abrasiveness, and the model is verified by a microdrilling experiment. The research in this paper is highly important for improving the rock-breaking efficiency and bit service life during drilling.

Multi-method characterization of groundwater nitrate and sulfate contamination by karst mines in southwest China.

Groundwater contamination by nitrate and sulfate in mining areas is a significant challenge. Consequently, the inputs sources of these contaminants and their evolution have received considerable attention, with the knowledge gained critical for improved management of water quality. This study integrated data on multiple stable isotopes and water chemistry data and a Bayesian isotope mixing model to investigate the relative contributions of inputs sources of sulfate and nitrate sources to bodies of water in a karst mining area in southwest China. The outcomes indicated that hydrochemical component in the water bodies of the study area is mainly derived from the dissolution of silicate rocks, carbonate rocks and sulfate minerals as well as the oxidation of sulfides. The human and agricultural wastewater, soil nitrogen, and fertilizers were the predominant inputs sources of nitrate to the mine water environment; the predominant inputs sources of sulfide were mineral oxidation, evaporite dissolution, atmospheric deposition, and sewage. Groundwater is mainly recharged from atmospheric precipitation, and surface water is closely hydraulically connected to groundwater. Nitrogen and oxygen isotope composition and water chemistry indicative of nitrification dominate the nitrogen cycle in the study area. The oxidation of pyrite and bacterial sulfate reduction (SRB) had no significant impact on the stable isotopes of groundwater. The results of this study demonstrate the inputs of different sources to nitrate and sulfate in karst mines and associated transformation processes. The results of this study can assist in the conservation of groundwater quality in mining areas and can act as a reference for future related studies.

Chemical characterization of green liquor dregs from 16 Swedish pulp and paper mills between 2017 and 2019.

Green liquor dregs (GLD) is an alkaline by-product from the pulp and paper industry with a pH between 10 and 14. Today most of the produced GLD in Sweden is landfilled. As a fine-grained alkaline material, it might be possible to use it for acid-generating mining waste remediation. To increase the utilization, quality characteristics and environmental performance need to be determined. In this study samples were collected 5 times from 16 mills during a period of 2.5 years, and were characterized by analyzing dry matter content, loss on ignition (LOI) 550 °C and LOI 950 °C, elemental analysis, pH, electrical conductivity, and calorific value. The results were then evaluated using multivariate statistics (PCA) as well as being compared to other studies and Swedish till. The results show that even if GLD is heterogenous (both within a mill and between different mills) trends can be seen for samples from most mills. When samples do stand out, it is predominately related to the same four mills. Most of the studied parameters showed characteristics favorable for use as a remediant; however, TOC, sulfur, and some of the elements require further study. In general, this study concludes that GLD can be a viable option for the remediation of small orphaned sulfidic mining sites and thus worthy of further studies on the interaction between GLD and acidic mining waste.Overall, GLD can be a good alternative for cost-effective remediation of smaller orphaned mining sites. It is readily available in large quantities, has the qualities needed for remediation of many orphaned acidic mining sites, and can often be locally sourced near the mining site. The use of GLD for mining site remediation is likely also a more sustainable method compared to traditional remediation methods.

Diversity of fungi associated with petroglyph sites in the Negev Desert, Israel, and their potential role in bioweathering.

The petroglyphs of the Negev Desert, Israel, are famous and valuable archaeological remains. Previous studies have investigated the microbial communities associated with petroglyphs and their potential role in stone deterioration; nevertheless, the role of fungi remains unclear. In this study, the fungal communities present on the stone and, as a comparison, in the surrounding environment (soil and air) at Negev petroglyph sites were analyzed by means of culture-dependent and -independent (metagenomic) techniques. The metagenomic results showed a high fungal biodiversity in the soil, and both approaches highlighted the prevalence of species producing melanized, large, thick-walled spores (mainly Alternaria spp.). From the air sampling, mostly Cladosporium spp. were retrieved. On the other hand, on the rock, the results seem to indicate a low presence of fungi, but with a rock-specialized mycobiota consisting of extremotolerant microcolonial fungi (MCF) (e.g., Vermiconidia and Coniosporium) and lichens (Flavoplaca). In addition, low proportions of cosmopolitan fungi were detected on the stone, but the comparison of the data clearly indicates that they are transients from the surrounding environment. The ability of the isolated strains to dissolve CaCO3 and therefore be a potential threat to the petroglyphs (limestone substrate) was tested, but only one strain resulted in positive acid production under laboratory conditions. Nevertheless, both lichens and MCF detected in this study are well-known stone deteriogens, which may have a significant impact on the petroglyph's deterioration.

Effects of fasudil on glial cell activation induced by tooth movement.

BACKGROUND: Orthodontic pain affects the physical and mental health of patients. The spinal trigeminal subnucleus caudalis (SPVC) contributes to the transmission of pain information and serves as a relay station for integrating orofacial damage information. Recently, glial cells have been found to be crucial for both acute and maintenance phases of pain. It has also been demonstrated that rho kinase (ROCK) inhibitors can manage different pain models by inhibiting glial cell activation. Here, we hypothesized that orthodontic pain is related to glial cells in the SPVC, and Fasudil, a representative rho/rock kinase inhibitor, can relieve orthodontic pain by regulating the function of glial cells and the related inflammatory factors. In this study, we constructed a rat model of tooth movement pain and used immunofluorescence staining to evaluate the activation of microglia and astrocytes. Quantitative real-time PCR was used to detect the release of related cytokines and the expression of pain-related genes in the SPVC. Simultaneously, we investigated the effect of Fasudil on the aforementioned indicators. RESULTS: In the SPVC, the expression of c-Fos peaked on day 1 along with the expression of OX42 (related to microglial activation), CD16 (a pro-inflammatory factor), and CD206 (an anti-inflammatory factor) on day 3 after tooth movement, followed by a gradual decrease. GFAP-staining showed that the number of activated astrocytes was the highest on day 5 and that cell morphology became complex. After Fasudil treatment, the expression of these proteins showed a downward trend. The mRNA levels of pro-inflammatory factors (IL-1ß and TNF-α) peaked on day 3, and the mRNA expression of the anti-inflammatory factor TGF-ß was the lowest 3 days after tooth movement. Fasudil inhibited the mRNA expression of pain-related genes encoding CSF-1, t-PA, CTSS, and BDNF. CONCLUSION: This study shows that tooth movement can cause the activation of glial cells in SPVC, and ROCK inhibitor Fasudil can inhibit the activation of glial cells and reduce the expression of the related inflammatory factors. This study presents for the first time the potential application of Fasudil in othodontic pain.

Investigation of rock genesis and geodynamic significance based on Sr-Yb granite classification and geochemical characteristics: A case study from Guangxi, China.

The intrusive bodies in the study area are categorized into two intrusive units, γπK2 and ηoπK2, based on rock structure characteristics and intrusive contact relationships. The primary lithologies are granite porphyry and quartz monzonite porphyry. Through LA-ICP-MS zircon U-Pb dating, the weighted mean ages of zircon ^206Pb/^238U for these two units were determined to be 84.09 ± 0.86 Ma and 86.10 ± 0.76 Ma, respectively. According to geochemical characteristics and Sr-Yb granite classification, the quartz monzonite porphyry is classified as Zhejiang-Fujian type granite, and the granite porphyry as Nanling type granite. The study explores the geodynamic significance of granites in the area based on Sr-Yb granite classification, identifying the lower crust metamorphic facies as amphibolite facies. The source rocks are primarily basic granulites and felsic granulites, reflecting a thermally active lower crust with poorly developed fluids. Additionally, Sr-Yb granite classification aids in determining the crustal thickness of the lower crust, which is crucial for understanding continental geological evolution. This paper discusses the optimal locations and conditions for mineralizing fluid precipitation, noting that tungsten-tin mineralization is associated with Nanling type granites and that the mineralization process generally occurs later than the diagenetic process under conditions of low pressure and low oxygen fugacity. Tungsten-tin prospecting should focus on areas where the surrounding rock temperature ranges from 300 to 500 °C, with particular attention to the contact zones of sedimentary rocks or near structural fault zones.

Manipulating geological phosphorus resources for improved production and environmental outcomes during plant establishment.

Phosphorus (P) fertilisers are under scrutiny due to resource constraints and environmental impacts. Simple rock phosphate (RP) modifications with acids and co-applied with microbial inoculum could offer sustainable alternative P fertiliser products. We evaluated the effects of acid-treated rock phosphate (RP) in combination with fungal inoculum on plant establishment, environmental impacts (nutrient leaching) and soil quality in a 5-month pot trial. The treatments were evaluated in a clayey Vertisol and a silty Acrisol using cotton (Gossypium hirsutum) as a model plant. The RP treatments - apart from the unmodified and HCl products - were effective in promoting plant establishment with two of the microbial formulations superior to conventional P fertilisers by an average factor of 2 in both soil types (p < 0.05). All RP products restricted P leaching compared with conventional P fertilisers (p < 0.05), by an average factor of 5 for diammonium phosphate (DAP) in both soil types and 3 for the triple superphosphate TSP (only in Acrisol). Nitrate leaching from all treatments was high although much lower from the RP treatments compared with the conventional fertilisers towards the end of the establishment trial, by an average factor of 1.5 (p < 0.05). Ranking analysis revealed that some RP treatments showed evidence for improved ongoing soil quality, including decreased P leaching and soil acidification risks. Microbial analysis showed complex interactions between treatment and soil type. Nonetheless, inoculum persistence at the end of the plant establishment phase was observed for all pots analysed. Our results demonstrate that relatively simple modifications to RP could pave the way for developing sustainable P fertilisers.

Enhanced RHO-ROCK signaling is associated with CRELD2 production and fibroblast recruitment in cutaneous squamous cell carcinoma.

A key characteristic of cancer cells is their ability to induce changes in their microenvironment that render it permissive to tumor growth, invasion and metastasis. Indeed, these changes are required for tumor progression. Consequently, the tumor microenvironment is emerging as a key source of new targets against cancer, with novel therapies aimed at reversing tumor-promoting changes, reinstating a tumor-hostile microenvironment and suppressing disease progression. RHO-ROCK signaling, and consequent tension within the cellular actomyosin cytoskeleton, regulates a paracrine signaling cascade that establishes a tumor-promoting microenvironment. Here, we show that consistent with our observations in breast cancer, enhanced ROCK activity and consequent production of CRELD2 is associated with the recruitment and tumor-promoting polarization of cancer-associated fibroblasts in cutaneous squamous cell carcinoma. Our observations provide support for the notion that the role of RHO-ROCK signaling in establishing a tumor-promoting microenvironment may be conserved across patients and potentially also different cancer types.

Except for Robust Outliers, Rapamycin Increases Lesion Burden in a Murine Model of Cerebral Cavernous Malformations.

Cerebral cavernous malformation (CCM) is a hemorrhagic cerebrovascular disease where lesions develop in the setting of endothelial mutations of CCM genes, with many cases also harboring somatic PIK3CA gain of function (GOF) mutations. Rapamycin, an mTORC1 inhibitor, inhibited progression of murine CCM lesions driven by Ccm gene loss and Pik3ca GOF, but it remains unknown if rapamycin is beneficial in the absence of induction of Pik3ca GOF. We investigated the effect of rapamycin at three clinically relevant doses on lesion development in the Ccm3-/-PDGFb-icreERPositive murine model of familial CCM disease, without induction of Pik3ca GOF. Lesion burden, attrition, and acute and chronic hemorrhaging were compared between placebo and rapamycin-treated mice. Plasma miRNome was compared to identify potential biomarkers of rapamycin response. Outlier, exceptionally large CCM lesions (> 2 SD above the mean lesion burden) were exclusively observed in the placebo group. Rapamycin, across all dosages, may have prevented the emergence of large outlier lesions. Yet rapamycin also appeared to exacerbate mean lesion burden of surviving mice when outliers were excluded, increased attrition, and did not alter hemorrhage. miR-30c-2-3p, decreased in rapamycin-treated mouse plasma, has gene targets in PI3K/AKT and mTOR signaling. Progression of outlier lesions in a familial CCM model may have been halted by rapamycin treatment, at the potential expense of increased mean lesion burden and increased attrition. If confirmed, this can have implications for potential rapamycin treatment of familial CCM disease, where lesion development may not be driven by PIK3CA GOF. Further studies are necessary to determine specific pathways that mediate potential beneficial and detrimental effects of rapamycin treatment, and whether somatic PIK3CA mutations drive particularly aggressive lesions.

ROCK1 regulates glycolysis in pancreatic cancer via the c-MYC/PFKFB3 pathway.

BACKGROUND: Dysregulation of Rho-associated coiled coil-containing protein kinases (ROCKs) is involved in the metastasis and progression of various malignant tumors. However, how one of the isomers, ROCK1, regulates glycolysis in tumor cells is incompletely understood. Here, we attempted to elucidate how ROCK1 influences pancreatic cancer (PC) progression by regulating glycolytic activity. METHODS: The biological function of ROCK1 was analyzed in vitro by establishing a silenced cell model. Coimmunoprecipitation confirmed the direct binding between ROCK1 and c-MYC, and a luciferase reporter assay revealed the binding of c-MYC to the promoter of the PFKFB3 gene. These results were verified in animal experiments. RESULTS: ROCK1 was highly expressed in PC tissues and enriched in the cytoplasm, and its high expression was associated with a poor prognosis. Silencing ROCK1 inhibited the proliferation and migration of PC cells and promoted their apoptosis. Mechanistically, ROCK1 directly interacted with c-MYC, promoted its phosphorylation (Ser 62) and suppressed its degradation, thereby increasing the transcription of the key glycolysis regulatory factor PFKFB3, enhancing glycolytic activity and promoting PC growth. Silencing ROCK1 increased gemcitabine (GEM) sensitivity in vivo and in vitro. CONCLUSIONS: ROCK1 promotes glycolytic activity in PC cells and promotes PC tumor growth through the c-MYC/PFKFB3 signaling pathway. ROCK1 knockdown can inhibit PC tumor growth in vivo and increase the GEM sensitivity of PC tumors, providing a crucial clinical therapeutic strategy for PC.

Analysis of size effect and its influencing factors of brittle red sandstone with different heights.

We carried out uniaxial compression tests on brittle red sandstone with different heights. The test results show that the uniaxial compressive strength of rock sample increases first and then tends to be stable with the increase of the size, which is approximately stable between 75 and 81 MPa. Both elastic energy and dissipated energy increase with the increase of rock sample size. In order to further analyze the mechanism behind these phenomena, we combined advanced numerical simulation and theoretical analysis to explain these phenomena, and systematically analyzed the end face effect as one of the key factors affecting the uniaxial compression characteristics of brittle red sandstone for the first time. Small sized rock samples are very sensitive to end effect. The middle of the large sized rock samples is in a uniform compression state, and the effect of end effect is weakend. When there are rigid pads at both ends of the rock sample, there is an obvious elastic vertebral body during the loading process of the rock sample. The bearing capacity of rock samples with rigid pads is greater than that of rock samples without rigid pads, and the energy released during instantaneous failure of rock samples without rigid pads is greater than that of rock samples with rigid pads. The findings of this paper make a valuable contribution to establishing optimal study sample sizes and advancing the utilization of laboratory test mechanics parameters in engineering applications.

Experimental study of the effects of the void located at the pile tip on the load capacity of rock-socketed piles.

To address the design challenge of the rock-socketed piles posed by the void located below the pile tip, the physical laboratory model tests were designed and performed to simulate rock socketed piles using similar materials. The study investigates the behavior of the single pile under axial loading with the void located at varying distances from the pile tip. Through multi-level load tests, the variations of unit pile side friction, pile tip resistance, pile axial force and pile settlement are obtained for different positions of the void from the pile tip, as well as after grouting. Its comparison to the rock-socketed pile without void is performed as a reference to quantify the reduction in its bearing capacity. The results are presented in the form of graphs for different void positions and its grouting shows the influence on pile bearing capacity and emphasizes the importance of its detailed cautious investigation and introduction in the analysis. The 2D finite element modeling of the model pile-the void based on ABAQUS is performed to further investigate the influence of the void below pile tip on the bearing capacity of model pile, applying the Mohr Coulomb model as the constitutive model of rock mass behavior. The critical distance of the void below the pile tip is determined.

Tourism influences escape behavior of lizards in relationship with human clothing color.

Increased tourism pressure modifies animal behavior, including alterations in anti-predator responses and foraging activity. In areas with high tourist presence, animals may become accustomed to increased human activity and adjust the intensity of some defensive responses. An animal's anti-predation ability is usually estimated by measuring its Alert Initiation Distance (AID) and Flight Initiation Distance (FID). Both indexes are affected by multiple factors including the color of the observer's clothing. Animal behavior is also influenced by human presence, and individuals may become accustomed to increased human presence, e.g. in tourist areas. In this study, we analysed the escape behavior of the endemic Cyprus rock agama (Laudakia cypriaca) in relation to the observers clothing color. Our results showed that AIDs and FIDs of agamas in tourist areas were significantly shorter than those in non-tourist areas. Moreover, in non-tourist areas, AIDs and FIDs of agamas were significantly longer when the observer wore red clothes, compared to green and grey clothes. Our results may be helpful in planning research taking into account various colored clothing based on expected reptilian reactions. Furthermore, our results may determine the proximity at which humans interact with animals, considering clothing color, to prevent negative impacts especially on rare and protected lizard species.