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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
Tue Oct 15 2024
Journal Name
Civileng
Structural Performance of a Hollow-Core Square Concrete Column Longitudinally Reinforced with GFRP Bars under Concentric Load
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Concrete columns with hollow-core sections find widespread application owing to their excellent structural efficiency and efficient material utilization. However, corrosion poses a challenge in concrete buildings with steel reinforcement. This paper explores the possibility of using glass fiber-reinforced polymer (GFRP) reinforcement as a non-corrosive and economically viable substitute for steel reinforcement in short square hollow concrete columns. Twelve hollow short columns were meticulously prepared in the laboratory experiments and subjected to pure axial compressive loads until failure. All columns featured a hollow square section with exterior dimensions of (180 × 180) mm and 900 mm height. The columns were categorized into

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Publication Date
Tue Sep 11 2018
Journal Name
Iraqi Journal Of Physics
Contrast enhancement of infrared images using Adaptive Histogram Equalization (AHE) with Contrast Limited Adaptive Histogram Equalization (CLAHE)
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The objective of this paper is to improve the general quality of infrared images by proposes an algorithm relying upon strategy for infrared images (IR) enhancement. This algorithm was based on two methods: adaptive histogram equalization (AHE) and Contrast Limited Adaptive Histogram Equalization (CLAHE). The contribution of this paper is on how well contrast enhancement improvement procedures proposed for infrared images, and to propose a strategy that may be most appropriate for consolidation into commercial infrared imaging applications.
The database for this paper consists of night vision infrared images were taken by Zenmuse camera (FLIR Systems, Inc) attached on MATRIC100 drone in Karbala city. The experimental tests showed sign

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Publication Date
Wed Jan 10 2024
Journal Name
Journal Of Optics
Pulsed laser deposition of Pd/WO3 nanoparticles on Si nanostructure for highly sensitive room-temperature gas sensors
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Publication Date
Fri Apr 01 2022
Journal Name
Baghdad Science Journal
The Cut-off Values of Triglycerides - Glucose Index for Metabolic Syndrome Associated with Type 2 Diabetes Mellitus
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       The co-occurrence of metabolic syndrome with type 2 diabetes mellitus (T2DM) will potentiate the morbidity and mortality that may be associated with each case. Fasting triglycerides-glucose index (TyG index) has been recommended as a useful marker to predict metabolic syndrome. Our study aimed to introduce gender-specific cut-off values of triglycerides- glucose index   for diagnosing metabolic syndrome associated with type 2 diabetes mellitus. The data were collected from Baghdad hospitals between May - December 2019. The number of eligible participants was 424. National cholesterol education program, Adult Treatment Panel III criteria were used to define metabolic syndrome. Measurement of fasting blood glucose, lipid pro

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Publication Date
Sun Jan 01 2012
Journal Name
Advances In Materials Physics And Chemistry
The Effect of Zn Concentration on the Optical Properties of Cd<sub>10–x</sub>Zn<sub>x</sub>S Films for Solar Cells Applications
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Publication Date
Thu Sep 01 2022
Journal Name
Iaes International Journal Of Robotics And Automation
Implementation of a complex fractional order proportional-integral-derivative controller for a first order plus dead time system
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This paper presents the implementation of a complex fractional order proportional integral derivative (CPID) and a real fractional order PID (RPID) controllers. The analysis and design of both controllers were carried out in a previous work done by the author, where the design specifications were classified into easy (case 1) and hard (case 2) design specifications. The main contribution of this paper is combining CRONE approximation and linear phase CRONE approximation to implement the CPID controller. The designed controllers-RPID and CPID-are implemented to control flowing water with low pressure circuit, which is a first order plus dead time system. Simulation results demonstrate that while the implemented RPID controller fails to stabi

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Publication Date
Mon Jun 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
The possibility of Using the Low-Cost External Antenna with Smartphone for Accurate Surveying Applications by RTX Technology
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Abstract<p>Real Time Extended (RTX) technology works to take advantage of real-time data comes from the global network of tracking stations together with inventor locating and compression algorithms to calculate and relaying the orbit of satellite, satellite atomic clock, and any other systems corrections to the receivers, which lead to real-time correction with high accuracy. These corrections will be transferred to the receiver antenna by satellite (where coverage is available) and by IP (Internet Protocol) for the rest of world to provide the accurate location on the screen of smartphone or tablet by using specific software. The purpose of this study was to assess the accuracy of Global Navig</p> ... Show More
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Publication Date
Fri Jan 01 2021
Journal Name
Italian Journal Of Pure And Applied Mathematics
A note on (m, n)-full stability Banach algebra modules relative to an ideal H of Am×n
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In this paper the concept of (m, n)- fully stable Banach Algebra-module relative to ideal (F − (m, n) − S − B − A-module relative to ideal) is introducing, we study some properties of F − (m, n) − S − B − A-module relative to ideal and another characterization is given

Publication Date
Mon Feb 01 2021
Journal Name
Engenharia Agrícola
HYPERSPECTRAL SPECTROSCOPY TO DETECT DIFFERENT RESPONSES OF TWO SOYBEAN (GLYCINE MAX) CULTIVARS TO CHARCOAL ROT (MACROPHOMINA PHASEOLINA) TOXIN
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Publication Date
Wed Nov 14 2018
Journal Name
Fiber And Integrated Optics
Design Investigation of 2 × 2 Mach–Zehnder Optical Switch Based on a Metal–Polymer–Silicon Hybrid Plasmonic Waveguide
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In this paper, a miniaturized 2 × 2 electro-optic plasmonic Mach– Zehnder switch (MZS) based on metal–polymer–silicon hybrid waveguide is presented. Adiabatic tapers are designed to couple the light between the plasmonic phase shifter, implemented in each of the MZS arms, and the 3-dB input/output directional couplers. For 6 µm-long hybrid plasmonic waveguide supported by JRD1 polymer (r33= 390 pm/V), a π-phase shift voltage of 2 V is obtained. The switch is designed for 1550 nm operation wavelength using COMSOL software and characterizes by 2.3 dB insertion loss, 9.9 fJ/bit power consumption, and 640 GHz operation bandwidth

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