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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
Fri Jan 07 2022
Journal Name
Materials
Impact Behavior of Composite Reinforced Concrete Beams with Pultruded I-GFRP Beam
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The present study experimentally and numerically investigated the impact behavior of composite reinforced concrete (RC) beams with the pultruded I-GFRP and I-steel beams. Eight specimens of two groups were cast in different configurations. The first group consisted of four specimens and was tested under static load to provide reference results for the second group. The four specimens in the second group were tested first under impact loading and then static loading to determine the residual static strengths of the impacted specimens. The test variables considered the type of encased I-section (steel and GFRP), presence of shear connectors, and drop height during impact tests. A mass of 42.5 kg was dropped on the top surface at the m

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Publication Date
Wed May 01 2019
Journal Name
Iop Conference Series: Materials Science And Engineering
The impact of UAV flight planning parameters on topographic mapping quality control
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Abstract<p>There is a growing need for up-to-date data for rapid decision making in the modern digital age. Recently, the need for high-resolution topographic maps is highly demanding by most mapping clients. With the maturing automatic structure from mobile and multi-view stereoscopy software, small organizations and individuals now have the ability to make their own surveys based on mobile mapping devices. This study looks at how feasible using low-cost Unmanned Aerial Vehicle (UAV) as a mobile mapping device for photogrammetric topographical surveys. It is showing the impact of different UAV flight settings and parameters on the accuracy of mapping products. An automatic scenario for photogra</p> ... Show More
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Publication Date
Mon May 09 2022
Journal Name
Proceedings Of The Institution Of Mechanical Engineers, Part C: Journal Of Mechanical Engineering Science
Finite element analysis of class II mandibular unilateral distal extension partial dentures
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The current paper aims to investigate the stress distribution developed in Kennedy Class II mandibular distal extension removable partial dentures due to applying a unilateral load condition in both vertical and lateral oblique directions. 3D models of mandible bone and RPD framework were first built based on actual patient data and later exported to ANSYS software to implement the numerical analysis. For realistic analysis, the model considered the frictional contact between the RPD retainers with the teeth and mucosa with the resin denture base by applying the feature of small sliding. To ensure maximum longevity and suitability of restoration, two different metallic RPDs constructed from commercially pure titanium (CP Ti) and cob

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Publication Date
Sun Mar 31 2024
Journal Name
The Iraqi Geological Journal
Exploring the Impact of Petrophysical Uncertainties on Recoverable Reserves: A Case Study
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Reliable estimation of critical parameters such as hydrocarbon pore volume, water saturation, and recovery factor are essential for accurate reserve assessment. The inherent uncertainties associated with these parameters encompass a reasonable range of estimated recoverable volumes for single accumulations or projects. Incorporating this uncertainty range allows for a comprehensive understanding of potential outcomes and associated risks. In this study, we focus on the oil field located in the northern part of Iraq and employ a Monte Carlo based petrophysical uncertainty modeling approach. This method systematically considers various sources of error and utilizes effective interpretation techniques. Leveraging the current state of a

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Publication Date
Sat Feb 28 2026
Journal Name
Himalayan Journal Of Education
Pragmatic formatting of poetic discourse according to Al-A’sha: An analytical study.
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This practical research aims to study playfulness in Al- A'sha's poetry by analyzing the context and rhetorical interaction between the poetic text and the various sources and quotations it contains. The study relies on a theoretical framework derived from the sciences of playfulness to highlight how linguistic, social, and cultural context influences the construction of poetic meanings, and how rhetorical interaction plays a pivotal role in poetry's communication with the recipient and other texts. Through analyzing selected examples of Al-A'sha's poetry, it becomes clear that the poet was not merely a transmitter of words, but rather an active participant in a network of discursive exchanges with his cultural and literary heritage, borro

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Publication Date
Mon Sep 04 2017
Journal Name
Journal Of The College Of Education For Women
Adolf Hitler, existence and his political victim until junuary, 1933 Dr.Suaad Rood Sheer Mohammed (PhD) Dr. Qassim Abdul Amir Waseem
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This study aims to track and analysis Hitler's personality by explaining the impact of the social environment in shaping his behavior and addressing the defeat of Germany in the World War 1 and its impact on building his political personality and included his political activism and his policy to get rid of the terms of the Versailles Military Treaty in the light of his plans in his book ( Kifahi) The nature of the study had to be divided into an introduction and two topics followed by the conclusion of the most important results, in addition to a list of references and a summary in English and from God the Good luck.

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Publication Date
Fri Nov 11 2022
Journal Name
Surgical Neurology International
Brown-Sequard syndrome associated with a spinal cord injury caused by a retained screwdriver: A case report and literature review
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Background:

Nonmissile penetrating spine injury (NMPSI) represents a small percent of spinal cord injuries (SCIs), estimated at 0.8% in Western countries. Regarding the causes, an NMPSI injury caused by a screwdriver is rare. This study reports a case of a retained double-headed screwdriver in a 37-year-old man who sustained a stab injury to the back of the neck, leaving the patient with a C4 Brown-Sequard syndrome (BSS). We discuss the intricacies of the surgical management of such cases with a literature review.

Methods:

PubMed database was searched by the following combined formula of medical subjects headings,

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Publication Date
Thu Nov 12 2020
Journal Name
Journal Of Petroleum Research And Studies
Production Optimization for Natural Flow and ESP Well A Case Study on Well NS-5 Mishrif Formation-Nasriya Oil Field
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As the reservoir conditions are in continuous changing during its life, well production rateand its performance will change and it needs to re-model according to the current situationsand to keep the production rate as high as possible.Well productivity is affected by changing in reservoir pressure, water cut, tubing size andwellhead pressure. For electrical submersible pump (ESP), it will also affected by numberof stages and operating frequency.In general, the production rate increases when reservoir pressure increases and/or water cutdecreases. Also the flow rate increase when tubing size increases and/or wellhead pressuredecreases. For ESP well, production rate increases when number of stages is increasedand/or pump frequency is

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Publication Date
Fri Jun 30 2023
Journal Name
Mathematical Modelling Of Engineering Problems
Enhanced Prosthesis Control Through Improved Shoulder Girdle Motion Recognition Using Time-Dependent Power Spectrum Descriptors and Long Short-Term Memory
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Surface electromyography (sEMG) and accelerometer (Acc) signals play crucial roles in controlling prosthetic and upper limb orthotic devices, as well as in assessing electrical muscle activity for various biomedical engineering and rehabilitation applications. In this study, an advanced discrimination system is proposed for the identification of seven distinct shoulder girdle motions, aimed at improving prosthesis control. Feature extraction from Time-Dependent Power Spectrum Descriptors (TDPSD) is employed to enhance motion recognition. Subsequently, the Spectral Regression (SR) method is utilized to reduce the dimensionality of the extracted features. A comparative analysis is conducted between the Linear Discriminant Analysis (LDA) class

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Publication Date
Sat Sep 01 2018
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Director's leadership features and Impact on productive efficiency Study at Iraqi general insurance company: Study at Iraqi general insurance company
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أدى التغير السريع في البيئة الخارجية للمنظمة إلى  ظهور حالة من التنافس الشديد مما زاد تخوف الشركات من فقدان الحصة السوقية والخسارة . مما حدا بالمنظمات إلى الاهتمام بوجود مدير يحمل صفات وخصائص قيادية لما فيه من ميزات في تنظيم الإنتاج  ومقابلة الطلب وتقليل التكاليف وتطوير الأداء للحصول على ميزة تنافسية تحافظ او تزيد من حصتها السوقية وإرباحها .

تسعى الدراسة الى تحديد عدد من الاهداف كان اهمها معرفة الع

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