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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
Thu Jan 01 2015
Journal Name
Journal Of The College Of Languages (jcl)
A Critical Discourse Analysis of the 2012 American Presidential Election Debates
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This study discusses the Critical Discourse Analysis of 2012 American Presidential Election Debate’. The researcher adopts a model proposed by Van Dijk’s (2006 d). Six ideological categories have been selected within the overall strategies of the ideological square are used. The categories are of three levels of discourse structure : (the meaning, the argumentation, and the rhetoric) .They have shown effective criteria for detecting the most disguised systems of racism and manipulation.

            Based on the analysis, it can be concluded that the elite discourses of candidates contribute to the reproduction of domination, Orientalism, and Islamophobia. This can be appl

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Publication Date
Sun Oct 29 2023
Journal Name
Iraqi National Journal Of Nursing Specialties
Impact of Chemotherapy upon Lifestyle for the Patient with BIadder Cancer
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Objectives: The study aimed to determine the effect of chemotherapy on the life style of patients who
receive chemotherapy.
Methodology: A descriptive study was conducted in Specialty Surgery Teaching Hospital, Al-yamok
Teaching Hospital, and Radiation and Nuclear Medicine Hospital in Baghdad for the period from May
2007 to October 2008. A purposive "non-probability" sample of (loo) patients with bladder cancer
who receive chemotherapy where concerned in this study.
A questionnaire fom was constnicted for the purpose of the study and it was comprised of
two parts. The questiormaire consists of (125) items. They include (1) demographic information (2)
assessment of lifestyle dimension. The content validity of the q

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Publication Date
Sat Jun 26 2021
Journal Name
Journal Of Engineering
Adsorption Desulfurization of Iraqi Light Naphtha Using Metals Modified Activated Carbon
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The study aims to evaluate the removal of sulfur content from Iraqi light naphtha produced in Al-Dora refinery by adsorption desulfurization DS technique using modified activated carbon MAC loaded with nickel Ni and copper Cu as single binary metals. The experiments were carried in a batch unit with various operating parameters;  MAC dosage, agitation speed, and a contact time of 300 min at constant initial sulfur concentration 155 ppm and temperature. The results showed higher DS% by AC/Ni-Cu (66.45)% at 500 rpm and 1 g dosage than DS (29.03)% by activated carbon AC, increasing MAC dosage, agitation speed, and contact time led to increasing DS% values.  The adsorption capacity of MAC results was recorded (16,

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Publication Date
Tue Jun 01 2021
Journal Name
Baghdad Science Journal
Three-Dimensional Nonlinear Integral Operator with the Modelling of Majorant Function
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In this paper, the process for finding an approximate solution of nonlinear three-dimensional (3D) Volterra type integral operator equation (N3D-VIOE) in R3 is introduced. The modelling of the majorant function (MF) with the modified Newton method (MNM) is employed to convert N3D-VIOE to the linear 3D Volterra type integral operator equation (L3D-VIOE). The method of trapezoidal rule (TR) and collocation points are utilized to determine the approximate solution of L3D-VIOE by dealing with the linear form of the algebraic system. The existence of the approximate solution and its uniqueness are proved, and illustrative examples are provided to show the accuracy and efficiency of the model.

Mathematical Subject Classificat

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Publication Date
Mon Jul 01 2019
Journal Name
Iop Conference Series: Materials Science And Engineering
On Estimation of the Stress – Strength Reliability Based on Lomax Distribution
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Abstract<p>The present paper concerns with the problem of estimating the reliability system in the stress – strength model under the consideration non identical and independent of stress and strength and follows Lomax Distribution. Various shrinkage estimation methods were employed in this context depend on Maximum likelihood, Moment Method and shrinkage weight factors based on Monte Carlo Simulation. Comparisons among the suggested estimation methods have been made using the mean absolute percentage error criteria depend on MATLAB program.</p>
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Publication Date
Wed Mar 23 2022
Journal Name
Modern Sport
Using Artificial intelligence to evaluate skill performance of some karate skills
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Human beings are starting to benefit from the technology revolution that witness in our time. Where most researchers are trying to apply modern sciences in different areas of life to catch up on the benefits of these technologies. The field of artificial intelligence is one of the sciences that simulate the human mind, and its applications have invaded human life. The sports field is one of the areas that artificial intelligence has been introduced. In this paper, artificial intelligence technology Fast-DTW (Fast-Dynamic Time Warping) algorithm was used to assess the skill performance of some karate skills. The results were shown that the percentage of improvement in the skill performance of Mai Geri is 100%.

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Publication Date
Sun Nov 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
Emissions Investigating of Carbon Dioxide Generated by the Iraqi Cement Industry
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Abstract<p>The most used material in the world after water is concrete, which depends mainly on its manufacture of cement leading to the emission of carbon dioxide (CO<sub>2</sub>), flying dust, and other greenhouse gasses (GHGs) resulting in pollution of the atmosphere. The emission of CO<sub>2</sub> from cement production is approximately 5% of the global anthropogenic CO<sub>2</sub>. This research focuses on investigating the amount of CO<sub>2</sub> emission from the Iraqi General Cement Company plants includes the cement factories of Kirkuk, Al-Qa’em, Fallujah, and Kubaisa, using the GHGs Protocol Measures Program (specifically cement based-method).</p> ... Show More
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Publication Date
Sat Apr 01 2023
Journal Name
Journal Of Engineering
Manufacture of Load Bearing Concrete Masonry Units Using Waste Demolishing Material
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The presence of construction wastes such as clay bricks, glass, wood, plastic, and others in large quantities causes serious environmental problems in the world. Where these wastes can be used to preserve the natural resources used in construction and reduce the impact of this problem on the environment, it also works to reduce the problem of high loads of concrete blocks. Clay bricks aggregate (AB) can be recycled as coarse aggregate and replaced with volumetric proportions of coarse aggregate by ( 5% and 10%), as well as the use of clay brick powder (PB) by replacing its weight of cement (5% and 10%) and reduced in the manufacture of concrete blocks (blocks). Four mixtures will be prepared and tested to learn how to re

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Publication Date
Thu Sep 01 2022
Journal Name
Journal Of Engineering
Properties of Roller-Compacted Concrete Pavement Containing Different Waste Material Fillers
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Waste materials might be utilized in various applications, such as sustainable roller compacted concrete pavements (RCCP), to lessen the negative environmental consequences of construction waste. The impacts of utilizing (brick, thermostone, granite, and ceramic) powders on the mechanical characteristics of RCCP are investigated in this study. To achieve this, the waste materials were crushed, grounded, and blended before being utilized as filler in the RCCP. After the mixes were prepared, compressive strength, splitting tensile strength, flexural strength, water absorption, density, and porosity were all determined. According to the research results, adding some of these powders, mainly brick and granite powder, enhances the mechanical

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Publication Date
Fri Nov 13 2020
Journal Name
Mechanics Of Advanced Materials And Structures
Enhancing the strength of reinforced concrete columns using steel embedded tubes
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This paper demonstrates an experimental and numerical study on the behavior of reinforced concrete (RC) columns with longitudinal steel embedded tubes positioned at the center of the column cross-section. A total of 12 pin-ended square sectional columns of 150 × 150 mm having a total height of 1400 mm were investigated. The considered variables were the steel tube diameters of 29, 58, and 76 mm and the load eccentricity (0, 50, and 150) mm. Accordingly, these columns were divided into three groups (four columns in each group) depending on the load eccentricity (e) to column depth (h) ratio (e/h = 0, 1/3, and 1). For each group, one column was solid (reference), and the other three columns contained steel tubes with hollow rat

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