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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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Abstract<sec> <title>Background

Chronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy.

Methods

Epigenome-wide analysis of DNA methylation was performed for 20 patients at two timepoints during treatment. The prognostic significance of differentially methylated regions (DMRs) was assessed in independent cohorts of 139 and 163 patients. Their functional role in drug sensitivity was assessed in vitro.

Results

We identified 490 DMRs following exposure to therapy, of which 31 were CLL-specific and independent of changes occurring in normal B-cell development. Seventeen DMR-associated genes were identified as differentially expressed following treatment in an independent cohort. Methylation of the HOXA4, MAFB and SLCO3A1 DMRs was associated with post-treatment patient survival, with HOXA4 displaying the strongest association. Re-expression of HOXA4 in cell lines and primary CLL cells significantly increased apoptosis in response to treatment with fludarabine, ibrutinib and idelalisib.

Conclusion

Our study demonstrates enrichment for multiple CLL-specific epigenetic traits in response to chemotherapy that predict patient outcomes, and particularly implicate epigenetic silencing of HOXA4 in reducing the sensitivity of CLL cells to therapy.

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Publication Date
Mon Feb 01 2021
Journal Name
Engenharia Agrícola
HYPERSPECTRAL SPECTROSCOPY TO DETECT DIFFERENT RESPONSES OF TWO SOYBEAN (GLYCINE MAX) CULTIVARS TO CHARCOAL ROT (MACROPHOMINA PHASEOLINA) TOXIN
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Publication Date
Tue Dec 11 2018
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Contribution of Some Managerial Accounting Techniques to Achieve Market Share Requirements / Applied researchin the Al-Muthanna Cement Company
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The research aims to achieve market share requirements and reach the targeted competitive price through the application of management accounting techniques represented by continuous improvement technique and target costing under an Activity Based Cost (ABC) system and Activity Based Management (ABM), In Muthanna Cement Company to reach the rationalization of the cost of the product and maintain the required quality and improve the profitability of the company.

The problem of research has emerged in the inability of local firms to enter into effective competition with other companies operating in the same economic sector, Because of the high cost of its products, Which led to the sale of the product at prices below its cost, and t

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Publication Date
Thu Jun 01 2023
Journal Name
International Journal Of Artificial Intelligence (ij-ai)
Evaluation of massive multiple-input multiple-output communication performance under a proposed improved minimum mean squared error precoding
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<span lang="EN-US">The fundamental of a downlink massive multiple-input multiple-output (MIMO) energy- issue efficiency strategy is known as minimum mean squared error (MMSE) implementation degrades the performance of a downlink massive MIMO energy-efficiency scheme, so some improvements are adding for this precoding scheme to improve its workthat is called our proposal solution as a proposed improved MMSE precoder (PIMP). The energy efficiency (EE) study has also taken into mind drastically lowering radiated power while maintaining high throughput and minimizing interference issues. We further find the tradeoff between spectral efficiency (SE) and EE although they coincide at the beginning but later their interests become con

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Publication Date
Wed Jan 01 2020
Journal Name
Journal Of Biotech Research
Bacteriocin Production by Staphylococcus Epidermidis the Normal Flora of Outer Ear: A Potential Probiotic Against Outer Ear Infections
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Publication Date
Sun Jun 07 2009
Journal Name
Baghdad Science Journal
The adsorption-desorption process as a method for separation of nitrogen-carbon dioxide gas mixture using activated carbon
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Gas adsorption phenomenon on solid surface has been used as a mean in separation and purification of gas mixture depending on the difference in tendencies of each component in the gas mixture to be adsorbed on the solid surface according to its behaviour. This work concerns to study the possibilities to separate the gas mixture using adsorption-desorption phenomenon on activated carbon. The experimental results exhibit good separation factor at temperature of -40 .

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Publication Date
Tue Apr 30 2024
Journal Name
Iraqi Journal Of Science
The Influence of Biologically Synthesized Copper Nanoparticles on the Biofilm Produced by Staphylococcus haemolyticus 1solated from Seminal Fluid
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     Staphylococcus haemolyticus is one of the most frequently isolated coagulase-negative staphylococci. The ability to form biofilm is considered as one of the most important virulence factors of coagulase negative staphylococci. There is only limited knowledge of the nature of S. haemolyticus biofilms. This study was aimed at evaluating the ability of S. haemolyticus strains to produce biofilm in the presence of copper oxide nanoparticles (CuONPs). The biological synthesis of nanoparticles is an environmentally friendly approach for large-scale production of nanoparticles. Copper oxide nanoparticles were produced in the current study from the S. haemolyticus viable cell filtrate. UV-visible (UV-Vis) spectroscopy, X-ray diffra

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Publication Date
Mon May 27 2019
Journal Name
Al-khwarizmi Engineering Journal
Investigation the Influence of SPIF Parameters on Residual Stresses for Angular Surfaces Based on Iso-Planar Tool Path
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Incremental Sheet Metal Forming (ISMF) is a modern sheet metal forming technology which offers the possibility of manufacturing 3D complex parts of thin sheet metals using the CNC milling machine. The surface quality is a very important aspect in any manufacturing process. Therefore, this study focuses on the resultant residual stresses by forming parameters, namely; (tool shape, step over, feed rate, and slope angle) using Taguchi method for the products formed by single point incremental forming process (SPIF). For evaluating the surface quality, practical experiments to produce pyramid like shape have been implemented on aluminum sheets (AA1050) for thickness (0.9) mm. Three types of tool shape used in this work, the spherical tool ga

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Publication Date
Fri Mar 01 2019
Journal Name
Al-khwarizmi Engineering Journal
Design of PV Solar Energy Generator using MPPT Technique to Control Single Input/Multiple Outputs (DC-DC) Converter
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The paper presents the design of a system consisting of a solar panel with Single Input/Multiple Outputs (DC-DC) Buck Converter by using Simulink dialogue box tools in MATLAB software package for simulation the system. Maximum Power Point Tracking (MPPT) technique depending on Perturb and Observe (P&O) algorithm is used to control the output power of the converter and increase the efficiency of the system. The characteristics of the MSX-60 PV module is chosen in design of the system, whereas the electrical characteristics (P-V, I-V and P-I curves) for the module are achieved, that is affected by the solar radiation and temperature variations. The proposed design module has been found to be stable for any change in atmospheric tempera

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Publication Date
Thu Sep 01 2022
Journal Name
Iaes International Journal Of Robotics And Automation
Implementation of a complex fractional order proportional-integral-derivative controller for a first order plus dead time system
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This paper presents the implementation of a complex fractional order proportional integral derivative (CPID) and a real fractional order PID (RPID) controllers. The analysis and design of both controllers were carried out in a previous work done by the author, where the design specifications were classified into easy (case 1) and hard (case 2) design specifications. The main contribution of this paper is combining CRONE approximation and linear phase CRONE approximation to implement the CPID controller. The designed controllers-RPID and CPID-are implemented to control flowing water with low pressure circuit, which is a first order plus dead time system. Simulation results demonstrate that while the implemented RPID controller fails to stabi

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Publication Date
Sat Feb 01 2014
Journal Name
Journal Of Economics And Administrative Sciences
Assessing the efficiency Economic performance of the diyala General company for electrical industries for the Period (2000-2010)
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     Facing industrial companies many pressures and challenges due to rapid changes in the business environment of contemporary, which requires them to do their performance look more inclusive rather than limiting performance evaluation on the financial perspective in spite of its importance, prompting companies to rethink their reality competitive through the adoption of methodologies and new philosophies to manage competitiveness of total quality management, and re-engineering of production processes, and knowledge management,... etc., as This study framework cognitive and practical "to evaluate the performance of a company Diyala General Electric Industries and how to rehabilitate

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