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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
Sat Apr 03 2021
Journal Name
Lubricants
UV-Visible Spectrophotometer for Distinguishing Oxidation Time of Engine Oil
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Samples of gasoline engine oil (SAE 5W20) that had been exposed to various oxidation times were inspected with a UV-Visible (UV-Vis) spectrophotometer to select the best wavelengths and wavelength ranges for distinguishing oxidation times. Engine oil samples were subjected to different thermal oxidation periods of 0, 24, 48, 72, 96, 120, and 144 hours, resulting in a range of total base number (TBN) levels. Each wavelength (190.5 – 849.5 nm) and selected wavelength ranges were evaluated to determine the wavelength or wavelength ranges that could best distinguish among all oxidation times. The best wavelengths and wavelength ranges were analyzed with linear regression to determine the best wavelength or range to predict oxidation t

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Publication Date
Thu Sep 13 2018
Journal Name
Baghdad Science Journal
Laser Improves Biogas Production by Anaerobic Digestion of Cow Dung
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This study investigates the digestion of cow dung (CD) for biogas production at laboratory scales. The study was carried out through anaerobic fermentation using cow dung as substrate. The digester was operated at ambient temperatures of 39.5 °C for a period of 10 days. The effect of iron powder in controlling the production of hydrogen sulfide (H2S) has been tested. The optimum concentration of iron powder was 4g/L with the highest biogas production. A Q – swatch Nd:YAG laser has been used to mix and homogenize the components of one of the six digesters and accelerate digestion. At the end of digestion, all digestions effluent was subjected to 5 laser pulses with 250mJ/pules to dispose waste biomass.

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Publication Date
Tue Jun 01 2021
Journal Name
2021 Ieee/cvf Conference On Computer Vision And Pattern Recognition Workshops (cvprw)
Alps: Adaptive Quantization of Deep Neural Networks with GeneraLized PositS
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Publication Date
Thu Mar 01 2007
Journal Name
Al-khwarizmi Engineering Journal
The Inverse Solution Of Dexterous Robot By Using Neural Networks
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The inverse kinematics of redundant manipulators has infinite solutions by using conventional methods, so that, this work presents applicability of intelligent tool (artificial neural network ANN) for finding one desired solution from these solutions. The inverse analysis and trajectory planning of a three link redundant planar robot have been studied in this work using a proposed dual neural networks model (DNNM), which shows a predictable time decreasing in the training session. The effect of the number of the training sets on the DNNM output and the number of NN layers have been studied. Several trajectories have been implemented using point to point trajectory planning algorithm with DNNM and the result shows good accuracy of the end

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Publication Date
Sun Mar 01 2009
Journal Name
Al-khwarizmi Engineering Journal
Multidimensional Systolic Arrays of LMS Algorithm Adaptive (FIR) Digital Filters
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A multidimensional systolic arrays realization of LMS algorithm by a method of mapping regular algorithm onto processor array, are designed. They are based on appropriately selected 1-D systolic array filter that depends on the inner product sum systolic implementation. Various arrays may be derived that exhibit a regular arrangement of the cells (processors) and local interconnection pattern, which are important for VLSI implementation. It reduces latency time and increases the throughput rate in comparison to classical 1-D systolic arrays. The 3-D multilayered array consists of 2-D layers, which are connected with each other only by edges. Such arrays for LMS-based adaptive (FIR) filter may be opposed the fundamental requirements of fa

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Publication Date
Mon Dec 30 2019
Journal Name
Journal Of Nano- And Electronic Physics
Photodetector Properties of Polyaniline/CuO Nanostructures Synthesized by Hydrothermal Technique
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In this work, pure and copper mixed oxide PAni nanofiber thin films are successfully synthesized on silicon substrates by hydrothermal method and spin coating technique at room temperature with thickness of about 325 nm. The structural, surface morphological, optical and photoconductivity properties have been investigated. The XRD results showed that PAni films have crystalline nature, CuO and PAni/CuO nanostructure composites are monoclinic polycrystalline structure. The FESEM images of PAni clearly indicate that it has nanofiber-like structure, whereas the CuO film has spongelike shape. The surface morphology analysis of PAni/CuO composite shows that nanofiber caped with inorganic material which is CuO is a core-shell structure. Op

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Publication Date
Sun Jan 01 2017
Journal Name
Ieee Access
On Computational Aspects of Tchebichef Polynomials for Higher Polynomial Order
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Publication Date
Sun Jun 01 2025
Journal Name
Journal Of Discrete Mathematical Sciences And Cryptography
Some results on the non-zero divisor graphs of Zn
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In this work, we study several features of the non-zero divisor graphs (ℵZD- graph) for the ring Zn of integer modulo n. For instance, the clique number, radius, girth, domination number, and the local clustering coefficient are determined. Furthermore, we present an algorithm that calculates the clique number and draws the non-zero divisor for the ring Zn.

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Publication Date
Sun Sep 30 2018
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Potato Starch for Enhancing the Properties of the Drilling Fluids
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Different additives are used in drilling fluids when the demanded properties cannot be gotten with clays. Drilling muds needs several additives and materials to give good characteristics. There are local alternatives more suitable for enhancing the rheology and filtration of drilling fluids. An experimental work had been conducted to assess the suitability of using potato starch to enhance rheological properties and filtration in drilling mud. This study investigated the potato starch as a viscosifier and fluid losses agent in drilling fluid. Results from this study proved that rheological properties of potato starch mud increased when pH of drilling fluid is increased.  Potato starch could be used to enhance gel strength at low pH

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Publication Date
Fri Mar 01 2019
Journal Name
Al-khwarizmi Engineering Journal
Improving Wear Properties of 392 Al Alloy Using Centrifugal Casting
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The microstructure and wear properties of 392 Al alloy with different Mg contents were studied using centrifugal casting. All melted alloys were heated to 800 ºC and poured into the preheated centrifugal casting mold (200-250 ºC) at different mould rotational speeds (1500, 1900 and 2300 r.p.m).  It is clear from the results obtained that wear rate was dependent on the Mg content, applied load and mould rotational speed. Furthermore, wear test showed that the minimum wear rate was found in the inner layer of produced rings at mould rotational speed of 1900 r.p.m and Mg content of 5%.

 

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