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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 Jul 21 2023
Journal Name
Journal Of Engineering
ADJUSTING OFF – CENTERING PROCESS FOR A BLOW MOLDED PLASTIC PRODUCT BY USE OF WINQSB SOFTWARE
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In most manufacturing processes, and in spite of statistical control, several process capability indices refer to non conformance of the true mean (µc ) from the target mean ( µT ), and the variation is also high. In this paper, data have been analyzed and studied for a blow molded plastic product (Zahi Bottle) (ZB). WinQSB software was used to facilitate the statistical process control, and process capability analysis and some of capability indices. The relationship between different process capability indices and the true mean of the process were represented, and then with the standard deviation (σ ), of achievement of process capability value that can reduce the standard deviation value and improve production out of theoretical con

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Publication Date
Fri Sep 30 2011
Journal Name
Al-khwarizmi Engineering Journal
Steady State Performance Investigation of a Three Phase Induction Motor Running Off Unbalanced Supply Voltages
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The objective of this work is to investigate the performance of a conventional three phase induction motor supplied by unbalanced voltages. An effort to study the motor steady state performance under this disturbance is introduced. Using per phase equivalent circuit analysis with the concept of symmetrical components approach, the steady state performance is theoretically calculated. Also, a model for the induction motor with the MATLAB/Simulink SPS tools has been implemented and steady state results were obtained. Both results are compared and show good correlation as well. The simulation model is introduced to support and enhance electrical engineers with a complete understanding for the steady state performance of a fully loaded induc

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Publication Date
Fri Jun 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
An update on Nanoparticle Formulation Design of Piperine to Improve its Oral bioavailability: A Review
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Piperine, a crystalline alkaloid compound isolated from Piper nigrum, piper longum, and other types of piper, has had many fabulous pharmacological advantages for preventing and treating some specific diseases, such as analgesic, anti-inflammatory, hepatoprotective, antimetastatic, antithyroid, immunomodulatory, antitumor, rheumatoid arthritis, osteoarthritis, Alzheimer's, and improving the bioavailability of other drugs. However, its potential for clinical use through oral usage is hindered by water solubility and poor bioavailability. The low level of oral bioavailability is caused by low solubility in water and is photosensitive, susceptible to isomerization by UV light, which causes piperine concentration to decrease. Many different

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Publication Date
Fri Jan 01 2021
Journal Name
Desalination And Water Treatment
Electrosorption of cadmium ions from the aqueous solution by a MnO2/carbon fiber composite electrode
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The nanostructured MnO2 /carbon fiber (CF) composite electrode was prepared using the anodic electrodeposition process. The crystal structure and morphology of MnO2 particles were determined with X-ray diffraction and field-emission scanning electron microscopy. The electrosorptive properties of the prepared electrode were investigated in the removal of cadmium ions from aqueous solution, and the effect of pH, cell voltage, and ionic strength was optimized and modeled using the response surface methodology combined with Box–Behnken design. The results confirm that the optimum conditions to remove Cd(II) ions were: pH of 6.03, a voltage of 2.77 V, and NaCl concentration of 3 g/L. The experimental results showed a good fit for the Freundli

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Publication Date
Sat Jan 01 2022
Journal Name
Indonesian Journal Of Electrical Engineering And Computer Science
Construct an efficient distributed denial of service attack detection system based on data mining techniques
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<span>Distributed denial-of-service (DDoS) attack is bluster to network security that purpose at exhausted the networks with malicious traffic. Although several techniques have been designed for DDoS attack detection, intrusion detection system (IDS) It has a great role in protecting the network system and has the ability to collect and analyze data from various network sources to discover any unauthorized access. The goal of IDS is to detect malicious traffic and defend the system against any fraudulent activity or illegal traffic. Therefore, IDS monitors outgoing and incoming network traffic. This paper contains a based intrusion detection system for DDoS attack, and has the ability to detect the attack intelligently, dynami

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Publication Date
Thu Mar 23 2023
Journal Name
Arab Gulf Journal Of Scientific Research
Influence pH on virulence genes of <i>Pseudomonas aeruginosa</i>analyzed by RT-PCR method
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Purpose

The purpose of this study was to determine the influence of environmental pH on production of biofilms and virulence genes expression in Pseudomonas aeruginosa.

Design/methodology/approach

Among 303 clinical and environmental samples 109 (61 + 48) isolates were identified as clinical and environmental P. aeruginosa isolates, respectively. Clinical samples were obtained from patients in the Al-Yarmouk hospital in Baghdad city, Iraq. Waste water from Al-Yarmouk hospital was used from site before treatment unit to collect environmental samples. The ability of prod

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Publication Date
Wed Jul 01 2020
Journal Name
Journal Of Engineering
Using Adaptive Neuro Fuzzy Inference System to Predict Rate of Penetration from Dynamic Elastic Properties
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Rate of penetration plays a vital role in field development process because the drilling operation is expensive and include the cost of equipment and materials used during the penetration of rock and efforts of the crew in order to complete the well without major problems. It’s important to finish the well as soon as possible to reduce the expenditures. So, knowing the rate of penetration in the area that is going to be drilled will help in speculation of the cost and that will lead to optimize drilling outgoings. In this research, an intelligent model was built using artificial intelligence to achieve this goal.  The model was built using adaptive neuro fuzzy inference system to predict the rate of penetration in

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Publication Date
Fri Mar 31 2017
Journal Name
Al-khwarizmi Engineering Journal
Active Vibration Suppression of Smart Cantilever Beam with Sliding Mode Observer Using Two Piezoelectric Patches
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This paper presents a vibration suppression control design of cantilever beam using two piezoelectric ‎patches. One patch was used as ‎an actuator element, while the other was used as a sensor. The controller design was designed via the balance realization reduction method to elect the reduced order model that is most controllable and observable. ‎the sliding mode observer was designed to estimate six states from the reduced order model but three states are only used in the control law. Estimating a number of states larger than that used is in order to increase the estimation accuracy. Moreover, the state ‎estimation error is proved bounded. An ‎optimal LQR controller is designed then using the ‎estimated states with the slid

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Publication Date
Tue Mar 01 2022
Journal Name
Iop Conference Series: Earth And Environmental Science
Effluent Quality Assessment Monitoring of Al-Rustamiya Sewage Treatment Plant Using Geographical Information System (GIS)
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Abstract<p>Water quality assessment offers a scientific basis for water resource development and management. This research aims to assessment of Al-Rustamiya sewage treatment plant depending on annually changes and produces maps that declare changes on parameter during a period (2015-2018). Based on prior Government Department Baghdad Environment data which annually feature changes for samples from Northern Rustamiya have been estimated as a working model. Drawn a map of the Diyala River shows annual changes in the characteristics of the Diyala River, based on northern and southern Rustamiya effluent samples, and Diyala River samples. The characteristics that research focused on were biochemical</p> ... Show More
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Publication Date
Wed Jan 01 2020
Journal Name
Periodicals Of Engineering And Natural Sciences
Forecasting the exchange rate of the Iraqi dinar against the US dollar using Markov chains
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