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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
Mon Mar 18 2019
Journal Name
Civil Engineering Journal
Circularization Technique for Strengthening of Plain Concrete Short Square Columns Subjected to a Uniaxial Compression Compressive Pressure
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This paper presents an experimental study for strengthening existing columns against axial compressive loads. The objective of this work is to study the behavior of concrete square columns strengthening with circulation technique. In Iraq, there are significantly more reinforced rectangular and square columns than reinforced circular columns in reinforced concrete buildings. Moreover, early research studies indicated that strengthening of rectangular or square columns using wraps of CFRP (Carbon Fiber Reinforced Polymer) provided rather little enhancement to their load-carrying capacity. In this paper, shape modification technique was performed to modify the shape (cross section) of the columns from square columns into circular colu

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Publication Date
Sat Jun 01 2013
Journal Name
Journal Of Economics And Administrative Sciences
Comparison Ridge regression method with some classical methods to estimate the parameters of Lomax distribution by simulation
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Abstract

In this research provide theoretical aspects of one of the most important statistical distributions which it is Lomax, which has many applications in several areas, set of estimation methods was used(MLE,LSE,GWPM) and compare with (RRE) estimation method ,in order to find out best estimation method set of simulation experiment (36) with many replications  in order  to get mean square error and used it to make compare , simulation experiment  contrast with (estimation method, sample size ,value of location and shape parameter) results show that estimation method effected by simulation experiment factors and ability of using other estimation methods such as(Shrinkage, jackknif

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Publication Date
Mon Sep 01 2014
Journal Name
Al-khwarizmi Engineering Journal
Comparison of Fatigue Life Behavior between Two Different Composite Materials Subjected to Shot Peening at Different Times
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This paper investigated the fatigue life behavior of two composite materials subjected to different times of shot peening (2, 4 and 6 min).The first material prepared from unsaturated polyester with E-glass reinforcement by 33% volume fraction. While, the second one was prepared from unsaturated polyester with aluminum powder by2.5% volume fraction. The experimental results showed that the improvement in endurance limit was obtained (for the first material) at 2, 4 and 6 min shot peening times where the percentage of maximum improvement was 25% at shot peening time of 6 min. While, the endurance limit of the second material decreased at shot peening times of 2, 4 and 6 min where the percentage of maximum reduction was 29 % at shot peenin

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Publication Date
Sun Jun 01 2014
Journal Name
Journal Of Economics And Administrative Sciences
Estimate the Best production function of the General Company for Iraqi Cement for the period (1996-2010)
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     The General Company for Iraqi Cement is regarded as one of the companies that contribute to support the Iraqi economy. It contributes to provide the material of cement which fulfils the consumer and investment need in the markets in competitive prices and not to resort to the importing of the cement from abroad. That would save a great share of the purchase parity of the poor sectors of society. The estimation  of production function will contribute to putting the company.

The application functions of  the standard production of  benefit critical to clarify the actual relationship between production & its components, & allow to clarify the i

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Publication Date
Sat Jan 20 2024
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
First Record of Phoretic Mite from Red Palm Weevil Rhynchophorus ferrugiuneus (Olivier,1790) from Basrah, Southern Iraq
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The red palm weevil Rhynchophorus ferrugineus (Olivier, 1790), which belongs to the family Curculionidae, order Coleoptera, is one of the most important palm pests, which leads to heavy losses in date palms. In the last few years, it has been recorded in Iraq, from Safwan city south of Iraq, where it was detected on date palm trees (Phoenix dactylifera L, Arecales: Arecaceae). In the current study, specimens of adult weevils were collected from infested date palms (Phoenix dactylifera), that showed signs of infection in Safwan district, south of Basra province. The results of the investigation showed the presence of phoretic mites associated with the red palm weevil Rhynchophorus ferrugineus (Olivier,

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Publication Date
Wed Feb 20 2019
Journal Name
Iraqi Journal Of Physics
The measurements of neutron Fermi Age for selected Nuclear Reactor shielding materials using the Indium foil technique
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The Neutron Fermi Age, t, and the neutron slowing down density,   q (r, t) , have been measured for some materials such as Graphite and Iron by using gamma spectrometry system UCS-30 with NaI (Tl) detector. This technique was applied for Graphite and Iron materials by using Indium foils covered by Cadmium and the measurements done at the Indium resonance of 1.46 eV. These materials are exposed to a plane 241Am/Be neutron source with recent activity 38 mCi. The measurements of the Fermi Age were found to be t = 297 ± 21 cm2 for Graphite, t = 400 ± 28 cm2 for Iron. Neutron slowing down density was also calculated depending on the recent experimental t value and distance.

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Publication Date
Thu Sep 01 2011
Journal Name
Journal Of Economics And Administrative Sciences
Comparison of BASE methods with other methods for estimating the measurement parameter for WEBB distribution using simulations
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  Weibull distribution is considered as one of the most widely  distribution applied in real life, Its similar to normal distribution in the way of applications, it's also considered as one of the distributions that can applied in many fields such as industrial engineering to represent replaced and manufacturing time ,weather forecasting, and other scientific uses in reliability studies and survival function in medical and communication engineering fields.

   In this paper, The scale parameter has been estimated for weibull distribution using Bayesian method based on Jeffery prior information as a first method , then enhanced by improving Jeffery prior information and then used as a se

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Publication Date
Sun Nov 26 2017
Journal Name
Journal Of Engineering
Numerical Study of Heat Transfer Enhancement for a Flat Plate Solar Collector by Adding Metal Foam Blocks
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Numerical study has been conducted to investigate the thermal performance enhancement of flat plate solar water collector by integrating the solar collector with metal foam blocks.The flow is assumed to be steady, incompressible and two dimensional in an inclined channel. The channel is provided with eight foam blocks manufactured form copper. The Brinkman-Forchheimer extended Darcy model is utilized to simulate the flow in the porous medium and the Navier-Stokes equation in the fluid region. The energy equation is used with local thermal equilibrium (LTE) assumption to simulate the thermofield inside the porous medium. The current investigation covers a range of solar radiation intensity at 09:00 AM, 12:00 PM, and 04:00

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Publication Date
Tue Dec 31 2013
Journal Name
Al-khwarizmi Engineering Journal
Design of an Adaptive PID Neural Controller for Continuous Stirred Tank Reactor based on Particle Swarm Optimization
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 A particle swarm optimization algorithm and neural network like self-tuning PID controller for CSTR system is presented. The scheme of the discrete-time PID control structure is based on neural network and tuned the parameters of the PID controller by using a particle swarm optimization PSO technique as a simple and fast training algorithm. The proposed method has advantage that it is not necessary to use a combined structure of identification and decision because it used PSO. Simulation results show the effectiveness of the proposed adaptive PID neural control algorithm in terms of minimum tracking error and smoothness control signal obtained for non-linear dynamical CSTR system.

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Cytotoxic Assay of Nigella sativa Leaf Callus Extract (Thymol) on Hep-2 Cell Line Using ELISA Assay
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Extract from cell culture of medicinal plant like Nigella sativa have been assessed for its cytotoxic properties. Thymol is likely responsible for the theraputic effects of  Nigella sativa leaf callus extract. In this short study the inhibitory effect of Nigella sativa leaf callus extract (Thymol) has been studied on Human Lorgnx Epidrmoid Carcinoma (Hep-2) cell line during different exposure period of time (24, 48 and 72 hrs.) using different concentration of the extract (1000, 500, 400, 300, 200 and 100 µg/ml). The optical density of the Hep-2 cells has been readed on 492 nm wave length. Thymol –induced cytotoxicity was (500 µg/ml) which inhibit cell growing compared to the control and this

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