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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
Tue Jan 01 2019
Journal Name
Journal Of The College Of Languages (jcl)
Solzhenitsyn's Style of Artistic Research: Опыт стиля художественного исследования А.Солженицыным
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 Aleksandr Isayevich Solzhenitsyn was born in 1918 in Kislovodsk. His father was educated, and despite his peasantry origin, he got a university degree. Unfortunately, however, Solzhenitsyn could not recognize his father, for he died before his birth.

Solzhenitsyn was accused of being an opponent to the Soviet Union due to his activities of that time. He was exiled to a forced labour camp for eight years, on the surroundings of Moscow. He spent three years in Kazakhstan, and was sent to the life exile. He was set free in 1956. He worked as a teacher in in rural schools in Vladimir and then in Rezhran. 

His greatest works were in the reign of Kherchov, and in 1962 appeared his story under the title of "One day in

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Publication Date
Mon Apr 20 2026
Journal Name
Central European Journal Of International And Security Studies
The External Political Impacts of Rescheduling Iraq’s Debts Post-2003
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After 2003, Iraq underwent a profound political and economic transformation, accompanied by various challenges, including the burden of accumulated external debt. The post-regime government restructured Iraq’s debt within the framework of the ‘Paris Club’ and through bilateral negotiations with creditor countries. The debt rescheduling aimed to alleviate the financial burden and reintegrate Iraq into the global financial system, but this process was conditional upon implementing economic and political reforms. External political factors played a crucial role in debt rescheduling. Decisions regarding rescheduling were influenced by the political motives of major powers seeking to achieve strategic gains in Iraq. Additionally, t

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Publication Date
Sat Aug 01 2020
Journal Name
Key Engineering Materials
Quality Control of Production Lightweight Ferrocement Plate Using Sustainable Materials
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This research is concerned with a new type of ferrocement characterized by its lower density and enhanced thermal insulation. Lightweight ferrocement plates have many advantages, low weight, low cost, thermal insulation, environmental conservation. This work contain two group experimental : first different of layer ferrocement, second different of ratio aggregate to cement. The experiments were made to determined the optimum proportion of cement and lightweight aggregate (recycle thermestone ). A low W/C ratio of 0.4 was used with super plasticizer conforming to ASTM 494 Type G. The compressive strength of the mortar mixes is 20-25 MPa. The work also involved the determination of thermal properties .Thermal conductivity value of thi

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Publication Date
Sun Jan 02 2011
Journal Name
Education College Journal/al-mustansiriyah
Double Stage Shrinkage Estimators of Two Parameters Generalized Rayleigh Distribution
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Publication Date
Wed Sep 29 2021
Journal Name
Al-khwarizmi Engineering Journal
Simulation of a Self-Balancing Platform on the Mobile Car
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In the last years, the self-balancing platform has become one of the most common candidates to use in many applications such as flight, biomedical fields, industry. This paper introduced the simulated model of a proposed self-balancing platform that described the self–balancing attitude in (X-axis, Y-axis, or both axis) under the influence of road disturbance. To simulate the self-balanced platform's performance during the tilt, an integration between Solidworks, Simscape, and Simulink toolboxes in MATLAB was used. The platform's dynamic model was drawn in SolidWorks and exported as a STEP file used in the Simscape Multibody environment. The system is controlled using the proportional-integral-deriva

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Publication Date
Fri Mar 01 2019
Journal Name
Al-khwarizmi Engineering Journal
Improving Wear Properties of 392 Al Alloy Using Centrifugal Casting
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The microstructure and wear properties of 392 Al alloy with different Mg contents were studied using centrifugal casting. All melted alloys were heated to 800 ºC and poured into the preheated centrifugal casting mold (200-250 ºC) at different mould rotational speeds (1500, 1900 and 2300 r.p.m).  It is clear from the results obtained that wear rate was dependent on the Mg content, applied load and mould rotational speed. Furthermore, wear test showed that the minimum wear rate was found in the inner layer of produced rings at mould rotational speed of 1900 r.p.m and Mg content of 5%.

 

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Publication Date
Fri Nov 09 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Assessment of Patients' Satisfaction toward Nursing Care at Hemodialysis units
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Objectives: To assess patients' satisfaction to nursing care at hemodialysis units and determine the relationship
between patients' satisfaction and patients' demographic data.
Methodology: A descriptive study was carried out at hemodialysis units of Baghdad teaching hospitals from Feb.
4
th
, 2010 through Sep. 5
th, 2010. A purposive (non-probability) sample of (150) patients ta hemodialysis units ni
Baghdad teaching hospitals was selected. The data were collected through the use of constructing questionnaire
and by means of an interview technique with the patients; the questionnaire consists of two parts (1)
demographic data (2) patients' satisfaction to nursing care. The validity of the study questionnaire w

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Publication Date
Tue Jan 01 2019
Journal Name
Reviews In Medical Microbiology
Virulence factors genotyping of Klebsiella pneumoniae clinical isolates from Baghdad
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Seventy of Klebsiella pneumoniae isolates had been collected from some Hospitals in Baghdad city from October to December 2017. The 70 isolates were taken from diverse clinical specimens. All K. pneumoniae isolates were identified based on API 20 E and Vitek2 compact system. Antibiotics sensitivity test was carried out toward 10 antibiotics using discs diffusion method. The level of antibiotics resistance was 81.42% for Ceftriaxone, whereas the low level of antibiotics resistance was 37.14% for Piperacillin. K. pneumoniae isolates were typed genotypically by using two different methods of amplification, multiplex-PCR and enterobacterial repetitive intergenic consensus (ERIC)-PCR typing methods. Results showed that out of 70 isolates, there

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Publication Date
Tue Jun 04 2024
Journal Name
Computation
High-Performance Krawtchouk Polynomials of High Order Based on Multithreading
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Orthogonal polynomials and their moments serve as pivotal elements across various fields. Discrete Krawtchouk polynomials (DKraPs) are considered a versatile family of orthogonal polynomials and are widely used in different fields such as probability theory, signal processing, digital communications, and image processing. Various recurrence algorithms have been proposed so far to address the challenge of numerical instability for large values of orders and signal sizes. The computation of DKraP coefficients was typically computed using sequential algorithms, which are computationally extensive for large order values and polynomial sizes. To this end, this paper introduces a computationally efficient solution that utilizes the parall

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Publication Date
Mon Oct 02 2023
Journal Name
Journal Of Engineering
Numerical Assessment of Pipe Pile Axial Response under Seismic Excitation
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In engineering, the ground in seismically active places may be subjected to static and seismic stresses. To avoid bearing capacity collapse, increasing the system's dynamic rigidity, and/or reducing dynamic fluctuations, it may be required to employ deep foundations instead of shallow ones. The axial aptitude and pipe pile distribution of load under static conditions have been well reported, but more study is needed to understand the dynamic axial response. Therefore, this research discusses the outputs of the 3D finite element models on the soil-pile behavior under different acceleration intensities and soil states by using MIDAS GTS NX. The pipe pile was represented as a simple elastic, and a modified Mohr-Coulomb mode

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