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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
Wed Mar 24 2021
Journal Name
Ieee Access
Smart IoT Network Based Convolutional Recurrent Neural Network With Element-Wise Prediction System
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An Intelligent Internet of Things network based on an Artificial Intelligent System, can substantially control and reduce the congestion effects in the network. In this paper, an artificial intelligent system is proposed for eliminating the congestion effects in traffic load in an Intelligent Internet of Things network based on a deep learning Convolutional Recurrent Neural Network with a modified Element-wise Attention Gate. The invisible layer of the modified Element-wise Attention Gate structure has self-feedback to increase its long short-term memory. The artificial intelligent system is implemented for next step ahead traffic estimation and clustering the network. In the proposed architecture, each sensing node is adaptive and able to

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Publication Date
Sun Apr 30 2023
Journal Name
Iraqi Geological Journal
Evaluating Machine Learning Techniques for Carbonate Formation Permeability Prediction Using Well Log Data
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Machine learning has a significant advantage for many difficulties in the oil and gas industry, especially when it comes to resolving complex challenges in reservoir characterization. Permeability is one of the most difficult petrophysical parameters to predict using conventional logging techniques. Clarifications of the work flow methodology are presented alongside comprehensive models in this study. The purpose of this study is to provide a more robust technique for predicting permeability; previous studies on the Bazirgan field have attempted to do so, but their estimates have been vague, and the methods they give are obsolete and do not make any concessions to the real or rigid in order to solve the permeability computation. To

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Publication Date
Mon Dec 25 2017
Journal Name
Al-khwarizmi Engineering Journal
A new Cumulative Damage Model for Fatigue Life Prediction under Shot Peening Treatment
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 Abstract

In this paper, fatigue damage accumulation were studied using many methods i.e.Corton-Dalon (CD),Corton-Dalon-Marsh(CDM), new non-linear model and experimental method. The prediction of fatigue lifetimes based on the two classical methods, Corton-Dalon (CD)andCorton-Dalon-Marsh (CDM), are uneconomic and non-conservative respectively. However satisfactory predictions were obtained by applying the proposed non-linear model (present model) for medium carbon steel compared with experimental work. Many shortcomings of the two classical methods are related to their inability to take into account the surface treatment effect as shot peening. It is clear that the new model shows that a much better and cons

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Publication Date
Sat Apr 01 2023
Journal Name
Chemical Methodologies
A Novel Design for Gas Sensor of Zinc Oxide Nanostructure Prepared by Hydrothermal Annealing Technique
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Publication Date
Sat Apr 01 2023
Journal Name
Baghdad Science Journal
Characterization of a novel pathway for xanthene degradation by the engineered strain Sphingobium yanoikuyae B1DR
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Polyaromatic hydrocarbons (PAHs) are a group of aromatic compounds that contain at least two rings. These compounds are found naturally in petroleum products and are considered the most prevalent pollutants in the environment. The lack of microorganism capable of degrading some PAHs led to their accumulation in the environment which usually causes major health problems as many of these compounds are known carcinogens. Xanthene is one of the small PAHs which has three rings. Many xanthene derivatives are useful dyes that are used for dyeing wood and cosmetic articles. However, several studies have illustrated that these compounds have toxic and carcinogenic effects. The first step of the bacterial degradation of xanthene is conducted by d

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Publication Date
Mon Jun 28 2021
Journal Name
Journal Of The College Of Education For Women
The Developmental Role of Social Work in Reducing Social Extremism:A Field Study in Baghdad University-College of Mass Communication as a Model: محمد حميد علوان
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This study deals with the role that social work profession plays in all its fields to reduce social extremismat home, or school or within society. The study aims to: examine the historical roots of social work in the Iraqi society, investigate the objectives of the developmental role of social work, review the theories of social extremism, its characteristics, and causes, and to analyze the developmental role of social work to limit social extremism. To meet the objectives of the study, a descriptive analytical approach has been adopted. It involves using the social sampling survey method, i.e., a questionnaire tool in the University of Baghdad community-College of Media. The sample was randomly selected to include (100) students from th

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Publication Date
Tue Jun 11 2019
Journal Name
Al-kindy College Medical Journal
Evaluation of Application of Nutritional Status Assessment for Children Under 5 years by Using IMCI Program in a Sample of Primary Health Care Centers in Baghdad City
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Background: World Health Organization (WHO) and United Nation International Children Fund (UNICEF) developed a strategy known as Integrated Management of Childhood Illness (IMCI); which aims to reduce less than five years children morbidity and mortality in developing countries.

Objective: To assess the completion of the IMCI format status in primary health care centers, Baghdad.

Methods:  A cross sectional study with analytic element was conducted during the period from 15th  of January till 15th  May 2016 in selected Primary health centers in Baghdad, Iraq. The sample consists of form of child files less than 2 months and form from 2

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Publication Date
Wed Dec 01 2010
Journal Name
Journal Of Economics And Administrative Sciences
Openness Management by Figures as a Model of Integrity and Transparency
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Competitive advantage is a substantial  strategic objective for organizations. It requires high levels in the quality of products and services provided to customers, continuous improvement of costing , care for creativity and innovative employees, and speed unique to the marketing and financial engineering, and business re-engineering processes. The situation in this area, requires actors to attract and develop human resources, including help in proper implementation of the strategic tasks that targeted by those institutions. According to the opinions and viewpoints of management scholars, the competitive advantage resource is the most important issue for organizations in the third millennium, which can be a

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Publication Date
Fri Jan 17 2020
Journal Name
Cihan University-erbil Scientific Journal
Characterization of Lactobacillus Isolates from Human Mouth and Feces as Probiotics
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Probiotics are live microbes that give many health benefits to human beings and animals, the most studied and commonly used probiotics are Gram-positive bacteria; lactobacilli and bifidobacteria. At nowadays, Lactobacillus spp. constitute more than two-thirds of the total numbers of probiotic species. The present study aimed to characterize Lactobacillus that locally isolated from human mouth and feces as probiotics. A total of three Lactobacillus isolates; Lactobacillus fermentum Lb2, Lactobacillus rhamnosus Lb9, and Lactobacillus paracasei Lb10 were investigated in respect to acid and bile salts tolerance, antibiotics susceptibility, and cell surface hydrophobicity in vitro using bacterial adhesion to hydrocarbons method. In compa

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Publication Date
Mon Jan 01 2018
Journal Name
Journal Of Cosmetics, Dermatological Sciences And Applications
Cutaneous Leishmaniasis as Imitator of Skin Diseases and a Diagnostic Challenge
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