A novel series of multifunctional pyrazolo3,4-dpyrimidine-based glutamate analogs (6a-l and 7a,b) have been designed and synthesized as antifolate anticancer agents. Among the tested compounds, 6i ...exhibited the most potent anti-proliferative activity towards NSCLC, CNS, Ovarian, Prostate, Colon, Melanoma, Breast, and Renal cancers with good to weak cytostatic activity and non-lethal actions. 6i demonstrated higher selectivity for cancer than normal cells. 6i could significantly increase the accumulation of S-phase cells during the cell cycle distribution of cancer cells with high potency in the induction of apoptosis. The results unveiled that 6i probably acts through dual inhibition of DHFR and TS enzymes (IC
50
= 2.41 and 8.88 µM, correspondingly). Docking studies of 6i displayed that N1-p-bromophenyl and C3-Methyl groups participate in substantial hydrophobic interactions. The drug-likeness features inferred that 6i met the acceptance criteria of Pfizer. Taking together, 6i could be a promising prototype for further optimization as an effective anticancer drug.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This paper explores a solution to safeguard buried pipes located near constructions in the Al-Bisri region of Assiut Governorate by utilizing the concept of the characteristic damage state. This ...issue has escalated due to the increasing rate of construction activity near pipelines, resulting in a multitude of legal disputes. This study investigates the behavior of buried pipes when influenced by newly constructed buildings using the finite element method. The paper employs two-dimensional models of a 12-story reinforced concrete building with a raft foundation and a series of piles supporting the buried pipe. In this study, we used the PLAXIS software, a 2D plane strain program, to conduct numerical investigations. The soil was idealized using the Mohr–Coulomb model with a 15-node triangular element, while the piles and structures were idealized with a five-node isoperimetric beam element. The point of contact between the beam and the soil was represented by the interface element. Our research examined the distance between the pipe and the footing edge and the distance between the piles and the footing edge. The finite element model results provided nodal displacements and element straining actions for analysis. The results shed light on the behavior of the sheet pile wall and sewage pipe in various situations. The largest bending moment in the sewage pipe was seen in the absence of piling, in contrast, to pile support at Rx = 0.75. The bending moment in the pipe expanded and always occurred at the same location as Rx rose. The clay layer next to the pipe’s lateral deformation was significantly reduced after piling, with the greatest deformation occurring at Rx = 0.
Steel beams’ shear strength is one of the most important factors that influence how quickly webs buckle. Despite extensive studies having been performed over the previous three decades, the existing ...procedures did not achieve the necessary reliability to predict the ultimate shear resistance of plate girders. New techniques called Learner Techniques have started to be used over the last few years; these techniques were applied to calculate the steel beam shear strength. In this study, a Regression Learner Techniques model was built using data from 100 test results from previously published research. Based on the geometric and material properties of the web and flanges available in the published tests, a model was built using Artificial Neural Networks. Based on sensitivity analysis, a Cascade Forward Backpropagation Neural Networks (CFBNN) approach was utilized to anticipate the shear strength of steel beams. The proposed models outperformed current hybrid artificial intelligence models developed using the same collected datasets and demonstrated to accurately predict the ultimate shear strength. The performance of the models was evaluated using a range of statistical assessment methods, which led to a valuable conclusion. The CFBNN model achieved the highest root mean square (R2 = 0.95). The results corresponding to each test were verified by specimen shear strength values calculated by a theoretical approach. The resultant maximum shear force obtained by the proposed modified equation was compared with the experimental results and the shear force was estimated using two different approaches proposed by the European code. Finally, two approaches were used to verify the proposed model. The first approach was the data reported from an experimental shear test program conducted by the authors, and the second was the results of the shear values acquired experimentally by other researchers. Based on the test results of the previous studies and the current work, the suggested model gives an adequate degree of accuracy for estimating the shear strength of steel beams.
The most crucial event in a mining project is the selection of an appropriate mining method (MMS). Consequently, determining the optimal choice is critical because it impacts most of the other key ...decisions. This study provides a concise overview of the development of multiple selection methods using a cascade-forward backpropagation neural network (CFBPNN). Numerous methods of multicriteria decision-making (MCDM) are discussed and compared herein. The comparison includes several factors, such as applicability, subjectivity, qualitative and quantitative data, sensitivity, and validity. The application of artificial intelligence is presented and discussed using CFBPNN. The Chengchao iron mine was selected for this investigation to pick the optimum mining method. The results revealed that cut and fill stoping is the most appropriate mining method, followed by sublevel and shrinkage stoping methods. The least appropriate method is open-pit mining, followed by room and pillar and longwall mining methods.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This research investigates the influence of rock joint dip angle and spacing on the performance of arched roof tunnels. A sensitivity analysis was conducted using Rocscience RS2 software, enabling ...the evaluation of stress distribution and rock mass deformation. The analysis involved the identification of specific reference points on the tunnel’s back, walls, and floor to assess stress state, deformation, and the extent of plastic damage zones near the tunnel’s perimeter, in relation to the minimum embedment length of the primary rock support. The results revealed distinct stress patterns within the tunnel system. Tensile-induced stresses were minimal along the tunnel walls, while high compressive-induced stresses were observed around the tunnel’s back/roof and floor. Additionally, substantial rock deformation was observed at the tunnel’s periphery, as evidenced by measurements taken at the reference points. Notably, an increase in the dip angle of the joints resulted in reduced displacement, suggesting a potential strategy for mitigating deformation. Furthermore, the research highlighted the crucial role of joint spacing in ensuring tunnel stability. Decreasing joint spacing was found to impact tunnel stability significantly adversely, underscoring the importance of carefully considering joint spacing during the design and construction phases of arched roof tunnels. The analysis was validated by comparing the numerical modeling results with readings obtained from Multi-Points Borehole Extensometers (MPBXs) installed in the tunnel walls and roof. The comparison revealed variations of 16% at the tunnel’s right wall, 11% at the tunnel’s left wall, and 12% at the tunnel roof.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Slope instability of open-pit mines has adverse impacts on the overall mine profitability, safety and environment. The slope of an open-pit mine is crucially influenced by the slope geometry, quality ...of rock mass and presence of geological features and their properties. The objective of this study is to demonstrate a method to select the optimal overall slope angle of open-pit mines according to three design parameters, namely, safety (e.g., probability of instability), productivity (e.g., profit) and mining costs (e.g., cost of removal of overburden). Therefore, this study attempts a hybrid approach in which numerical modelling is integrated with probabilistic analysis to evaluate the stability of an open-pit mine at various overall slope angles. Two-dimensional elasto-plastic finite-element, RS2D, has been used to develop a series of models at different ultimate slope angles employing shear strength reduction technique (SSRT). Li’s point-estimate method of n3 has been invoked in deterministic analysis to tackle the inherent uncertainty associated with host rock mass properties. The results reveal that the mine profitability increases and the cost of overburden removal decreases as overall slope angle becomes steeper. However, the slope stability deteriorates. Therefore, it is highly advisable to combine these three design parameters (e.g., safety, productivity, and cost) together when selecting overall slope angle of open-pit mines.
Nonmedical use of modafinil (MOD) led to increased rates of overdose toxicity, road accidents, addiction, withdrawal, suicide, and mental illnesses. The current study aims to determine the probable ...MOD brain toxicity and elucidate the possible role of selenium (Se) in ameliorating the neurotoxicity in rat models. Fifty-four male Albino rats were randomly assigned into nine groups. The groups were G1 (control negative), G2 (Se0.1), G3 (Se0.2), G4 (MOD300), G5 (MOD600), G6 (Se0.1 + MOD300), G7 (Se0.2 + MOD300), G8 (Se0.1 + MOD600), and G9 (Se0.2 + MOD600). After finishing the experiment, blood and brain tissue were harvested for biochemical and histological investigation. Neurobehavior parameters were assessed. Tissue neurotransmitter levels and oxidative stress markers were assessed. Gene expression of PI3K/Akt/mTOR-GSK3B, orexin, and orexin receptor2 was measured by qRT-PCR. Histological and immunohistochemistry assessments, as well as molecular docking, were carried out. MOD-induced neurobehavioral toxicity exhibited by behavioral and cognitive function impairments, which are associated with decreased antioxidant activities, increased MDA levels, and decreases in neurotransmitter levels. Brain levels of mRNA expression of PI3K, Akt, and mTOR were decreased, while GS3K, orexin, and orexin receptors were significantly elevated. These disturbances were confirmed by histopathological brain changes with increased silver and Bax immunostaining and decreased crystal violet levels. MOD induced neurotoxic effects in a dose-dependent manner. Compared with the MOD groups, SE coadministration significantly attenuates MOD-induced toxic changes. Docking study shows the protective role of Se as an apoptosis inhibitor and inflammation inhibitor. In conclusion, Se could be used as a biologically effective antioxidant compound to protect from MOD neurobehavioral toxicity in Wistar rats by reversing behavioral alterations, inflammation, apoptosis, and oxidative injury.
Graphical Abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Feijoa sellowiana leaves and fruits have been investigated as a source of diverse bioactive metabolites. Extract and eight metabolites isolated from F. sellowiana leaves were evaluated for their ...enzymatic inhibitory activity against α-glucosidase, amylase, tyrosinase, acetylcholinestrerase and butyrylcholinesterase both in vitro and in silico. Feijoa leaves' extract showed strong antioxidant activity and variable levels of inhibitions against target enzymes with a strong anti-tyrosinase activity (115.85 mg Kojic acid equivalent/g). Additionally, α-tocopherol emerged as a potent inhibitor of AChE and BChE (5.40 & 10.38 mmol galantamine equivalent/g, respectively). Which was further investigated through molecular docking and found to develop key enzymatic interactions in AChE and BChE active sites. Also, primetin showed good anti BChE (11.70 mmol galantamine equivalent/g) and anti-tyrosinase inhibition (90.06 mmol Kojic acid equivalent/g) which was also investigated by molecular docking studies.
Highlights
Isolation of eight bioactive constituents from Feijoa sellowiana leaves.
In vitro assays using different enzymatic drug targets were investigated.
In silico study was performed to define compound interactions with target proteins.
Feijoa leaf is an excellent source of anti-AChE and antityrosinase bioactives.
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One of the crucial projects underway in Egypt is the lining of watercourses to withstand the outflow of water through their beds and flanks. Various materials have been used in this project, ...including limestone, sandstone, basalt, and dolomite, along with other building materials. This study focused on the evaluation of rock characteristics to determine their suitability for the construction of a canal lining. All rock characteristics should be classified in terms of technical and economic concerns related to mining rock specifications, such as mechanical and physical properties, and evaluated according to their weights and ratings. As a rule of decision making, management stakeholders select the rock types. The primary purpose of canal linings is to reduce water loss due to seepage. Methodologically, we adopted the technique for order of preference by similarity to ideal solution (TOPSIS), and derived an improved TOPSIS method based on experimental testing. This study attempted the first application of TOPSIS to canal linings and relevant construction materials. The analysis shows that limestone L1 is the best rock-building material for canal linings in Upper Egypt. Limestone L1 has the shortest geometric distance from the positive ideal solution and the longest geometric distance from the negative ideal solution. The results provide decision makers with strategic indicators to select among different rock types based on the total points assigned to all rock specifications.
At great depths, tunnel openings experience a tectonic stress field rather than overburden stress. This paper aims to examine the impact of different in situ stress ratios and multiple tunnel depths ...below the surface on the excavation induced-stresses and displacements around tunnel openings. Thus, a series of models has been built, using a two-dimensional elasto-plastic finite-elements code, RS2D, to conduct parametric stability analysis. The performance of tunnel opening is examined by evaluating the induced stress-deformation around the opening. The results indicate that ratio of wall convergence, roof sag and floor heave increase as in situ stress ratio and tunnel depth below surface increase. Additionally, the induced-stresses increase as depth and state of in situ stress increase. In addition, the extent of yielding zones into rock mass around tunnel roof and floor deteriorates as tunnel depth and in situ stress ratio increase. Moreover, the normal stress along rock joints is sharply dropped when joints pass in the vicinity of tunnel opening (e.g., centre of opening). As well, the direction of shear stress along joints is reversed. Consequently, inward shear displacement of rock, on the underside of the weakness plane, is produced as a result of slip occurrence.
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