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Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors
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Introduction:

Allosteric inhibition of EGFR tyrosine kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies.

Methods:

A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy.

Results:

Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity.

Conclusion:

Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

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Publication Date
Fri Nov 01 2019
Journal Name
Journal Of Engineering
Assessment the Engineering Characteristics of the Smear Zone around PVDs Using Laboratory Tests
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Smear zone is usually formed around the prefabricated vertical drains (PVD’s) due to mandrel driving. The geotechnical properties of the soil in this zone exhibit significant changes that affect the performance of the PVD’s. The most relevant property in this respect is the coefficient of permeability. So far, no serious attention is paid to investigate the effects of shearing under large shear strains on the geotechnical properties of the soft soil in Fao region. In this study, an extensive laboratory testing program was conducted to assess the characteristics of the smear zone with an emphasis on the permeability coefficient of Fao soft soil. The results show that the permeability of the smear zone is about 70% of

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Publication Date
Sun Jun 23 2019
Journal Name
Journal Of The College Of Basic Education
Numerical Solution of Non-linear Delay Differential Equations Using Semi Analytic Iterative Method
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Publication Date
Thu Oct 01 2020
Journal Name
Alexandria Engineering Journal
The operational matrix of Legendre polynomials for solving nonlinear thin film flow problems
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Publication Date
Tue Jan 08 2019
Journal Name
Lubricants
Influence of Sample Mixing Techniques on Engine Oil Contamination Analysis by Infrared Spectroscopy
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For the most reliable and reproducible results for calibration or general testing purposes of two immiscible liquids, such as water in engine oil, good emulsification is vital. This study explores the impact of emulsion quality on the Fourier transform infrared (FT-IR) spectroscopy calibration standards for measuring water contamination in used or in-service engine oil, in an attempt to strengthen the specific guidelines of ASTM International standards for sample preparation. By using different emulsification techniques and readily available laboratory equipment, this work is an attempt to establish the ideal sample preparation technique for reliability, repeatability, and reproducibility for FT-IR analysis while still considering t

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Publication Date
Fri Sep 03 2021
Journal Name
Buildings
Structural Efficiency of Hollow Reinforced Concrete Beams Subjected to Partial Uniformly Distributed Loading
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Reinforced concrete (RC) beams containing a longitudinal cavity have become an innovative development and advantage for economic purposes of light-weight members without largely affecting their resistance against the applied loads. This type of openings can also be used for maintenance purposes and usage space of communication lines, pipelines, etc. RC beams are primarily loaded in the plane of the members, which are two-dimensional in a plane stress state and the dominant structural behaviours include bending, shear, or combination of both. In the present study, six numerical models of RC beams with and without openings were simulated by using commercial finite element software ANSYS to evaluate the structural behaviours of those b

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Publication Date
Sun Mar 01 2026
Journal Name
Journal Of Engineering
Heat Dissipation Performance of High-Power CPUs using Finned Copper Foam Heat Sinks
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Thermal management has become a major issue in the latest high performance computing machines because high CPU temperatures result in inefficient performance and decreased hardware life span. In this work, the cooling performance of a finned metal foam heat sink (FMFHS) was examined. The pore density values of tested copper metal foam (CMF) samples with different values of PPI 5, 10 and 20, with a constant porosity of 90%. For reference, these samples were measured by a conventional Aluminum plate-fin heat sink (CHS). The work was performed under experimental conditions in which air directed over the heat sink surface at air velocities (2.5, 3.0 and 3.5 m/s). The environmental temperature was fixed at 27 °C. Findings

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Publication Date
Tue Sep 01 2015
Journal Name
2015 Ieee International Circuits And Systems Symposium (icsys)
Investigating the impact of on-chip interconnection noise on Dynamic Thermal Management efficiency
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Dynamic Thermal Management (DTM) emerged as a solution to address the reliability challenges with thermal hotspots and unbalanced temperatures. DTM efficiency is highly affected by the accuracy of the temperature information presented to the DTM manager. This work aims to investigate the effect of inaccuracy caused by the deep sub-micron (DSM) noise during the transmission of temperature information to the manager on DTM efficiency. A simulation framework has been developed and results show up to 38% DTM performance degradation and 18% unattended cycles in emergency temperature under DSM noise. The finding highlights the importance of further research in providing reliable on-chip data transmission in DTM application.

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Publication Date
Tue Feb 01 2022
Journal Name
Civil Engineering Journal
Calibration of a New Concrete Damage Plasticity Theoretical Model Based on Experimental Parameters
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The introduction of concrete damage plasticity material models has significantly improved the accuracy with which the concrete structural elements can be predicted in terms of their structural response. Research into this method's accuracy in analyzing complex concrete forms has been limited. A damage model combined with a plasticity model, based on continuum damage mechanics, is recommended for effectively predicting and simulating concrete behaviour. The damage parameters, such as compressive and tensile damages, can be defined to simulate concrete behavior in a damaged-plasticity model accurately. This research aims to propose an analytical model for assessing concrete compressive damage based on stiffness deterioration. The prop

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Publication Date
Tue Nov 07 2017
Journal Name
Spe Symposium: Production Enhancement And Cost Optimisation
Wettability Alteration of Carbonate Rocks via Nanoparticle-Anionic Surfactant Flooding at Reservoirs Conditions
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Nanofluids, liquid suspensions of nanoparticles (NPs) dispersed in deionized (DI) water, brine, or surfactant micelles, have become a promising solution for many industrial applications including enhanced oil recovery (EOR) and carbon geostorage. At ambient conditions, nanoparticles can effectively alter the wettability of the strongly oil-wet rocks to water-wet. However, the reservoir conditions present the greatest challenge for the success of this application at the field scale. In this work, the performance of anionic surfactant-silica nanoparticle formulation on wettability alteration of oil-wet carbonate surface at reservoir conditions was investigated. A high-pressure temperature vessel was used to apply nano-modification of oil-wet

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Publication Date
Tue Jun 01 2021
Journal Name
Iop Conference Series: Earth And Environmental Science
Adsorption of heavy metal ions using activated carbon derived from Eichhornia (water hyacinth)
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Abstract<p>Removal of heavy metal ions such as, cadmium ion (Cd <sup>2+</sup>) and lead ion (Pb <sup>2+</sup>) from aqueous solution onto Eichhornia (water hyacinth) activated carbon (EAC) by physiochemical activation with potassium hydroxide (KOH) and carbon dioxide (CO<sub>2</sub>) as the activating agents were investigated. The Eichhornia activated carbon was characterized by Brunauer Emmett Teller (BET), Fourier Transform Infrared spectroscopy (FTIR), and Scanning Electron Microscopy (SEM) techniques. Whereas, the effect of adsorbent dosage, contact time of pH, and metal ion concentration on the adsorption process have been investigated using the batch process t</p> ... Show More
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