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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
Sun Mar 01 2015
Journal Name
Sust Journal Of Engineering And Computer Science (jecs)
Virtual failure influence of Roseires dam on Khartoum city using HEC-RAS Hydraulic simulation modeling
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Dam break is series phenomenon that can result in fatal consequences and loss of properties. Unfortunately, the observed consequences can only be available after the dam breaks. Therefore, it is important to anticipate what will happen prior to dam break to issue suitable warning and locate the possible risk areas. This study attempts to simulate the case of dam break in Blue Nile at Roseires dam and see its consequences downstream. Roseires dam lies at a distance of 630 km south of Khartoum, Sennar dam lies at about 260 km downstream of Roseires dam. In this study hydraulic model is developed based of Hydraulic Engineering Centre (HEC), River Analysis System (RAS), and HEC- RAS. The HEC-RAS based model is calibrated and validated usi

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Publication Date
Tue Nov 09 2021
Journal Name
Abu Dhabi International Petroleum Exhibition & Conference
Numerical Simulation of Gas Lift Optimization Using Artificial Intelligence for a Middle Eastern Oil Field
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Abstract<p>Artificial lift techniques are a highly effective solution to aid the deterioration of the production especially for mature oil fields, gas lift is one of the oldest and most applied artificial lift methods especially for large oil fields, the gas that is required for injection is quite scarce and expensive resource, optimally allocating the injection rate in each well is a high importance task and not easily applicable. Conventional methods faced some major problems in solving this problem in a network with large number of wells, multi-constrains, multi-objectives, and limited amount of gas. This paper focuses on utilizing the Genetic Algorithm (GA) as a gas lift optimization algorit</p> ... Show More
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Publication Date
Mon Oct 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
Fuzzy Multi-Objective Capacitated Transportation Problem with Mixed Constraints using different forms of membership functions
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In this research, the problem of multi- objective modal transport was formulated with mixed constraints to find the optimal solution. The foggy approach of the Multi-objective Transfer Model (MOTP) was applied. There are three objectives to reduce costs to the minimum cost of transportation, administrative cost and cost of the goods. The linear membership function, the Exponential membership function, and the Hyperbolic membership function. Where the proposed model was used in the General Company for the manufacture of grain to reduce the cost of transport to the minimum and to find the best plan to transfer the product according to the restrictions imposed on the model.

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Publication Date
Sat Jan 01 2022
Journal Name
International Journal Of Differential Equations
Dynamical Behaviours of Stage-Structured Fractional-Order Prey-Predator Model with Crowley-Martin Functional Response
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In this paper, the dynamic behaviour of the stage-structure prey-predator fractional-order derivative system is considered and discussed. In this model, the Crowley–Martin functional response describes the interaction between mature preys with a predator.  e existence, uniqueness, non-negativity, and the boundedness of solutions are proved. All possible equilibrium points of this system are investigated.  e su‰cient conditions of local stability of equilibrium points for the considered system are determined. Finally, numerical simulation results are carried out to con‹rm the theoretical results.

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Publication Date
Fri Mar 31 2017
Journal Name
Al-khwarizmi Engineering Journal
Active Vibration Suppression of Smart Cantilever Beam with Sliding Mode Observer Using Two Piezoelectric Patches
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This paper presents a vibration suppression control design of cantilever beam using two piezoelectric ‎patches. One patch was used as ‎an actuator element, while the other was used as a sensor. The controller design was designed via the balance realization reduction method to elect the reduced order model that is most controllable and observable. ‎the sliding mode observer was designed to estimate six states from the reduced order model but three states are only used in the control law. Estimating a number of states larger than that used is in order to increase the estimation accuracy. Moreover, the state ‎estimation error is proved bounded. An ‎optimal LQR controller is designed then using the ‎estimated states with the slid

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Publication Date
Fri Jul 01 2022
Journal Name
Journal Of Oral And Maxillofacial Surgery, Medicine, And Pathology
Rhinocerebral mucormycosis: An Iraqi experience of 16 consecutive cases followed up for up ten years
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Publication Date
Sun Sep 27 2020
Journal Name
Journal Of The College Of Education For Women
The Effect of Using Online Automated Feedback on Iraqi EFL Learners’ Writings at University Level
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Feedback on students’ assignments can be done in many different ways. Nowadays, the growing number of students at universities has increased the burden on the instructors to give feedback on students’ writings quickly and efficiently. As such, new methods of modern online automated feedback tools, such as Hemingway app and ecree,are used to assist and help instructors. Hence, this research is an explanatory study to examine the effect of using the online automated feedback on some Iraqi EFL learners’ writings at the university level. The study comprised 60 students enrolled in an English language course at the University of Anbar. They were divided randomly into two groups, experi

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
An approximate solution for solving linear system of integral equation with application on "Stiff" problems
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An approximate solution of the liner system of ntegral cquations fot both fredholm(SFIEs)and Volterra(SIES)types has been derived using taylor series expansion.The solusion is essentailly

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Publication Date
Mon Feb 04 2019
Journal Name
Journal Of The College Of Education For Women
Yacoub Ben Keles, the First of the Fatimid Ministers ( 368-380 A.H. / 978-990 A.D. )
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Minister Yacoub Ben Keles distinguished himself with leadership and administrative talents, as well as his abilities in the field of jurisprudence, which made him the top political, administrative and cultural scene of the Fatimid state and left its mark on it by influencing its fateful decisions.
He was the son of Kels of the Jews of Baghdad, where he learned writing and arithmetic, and moved with his father to Syria and then carried him to Egypt.
Egypt embraced the son of Kels, living in a transitional period from the Achaishid era to the Fatimid period. Both these two covenants reconciled this man to his career until he became minister in the Fatimids in 368 A.H. / 978 A.D.
His character was overshadowed by most of the state'

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Publication Date
Wed Nov 05 2014
Journal Name
International Journal Of Applied Mathematical Research
Approximate solution of a model describing biological species living together using a new iterative method
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