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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 Jan 29 2024
Journal Name
Polymer Bulletin
An experimental study to investigate the effect of aluminum nanorod-reinforced epoxy matrix nanocomposites
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Publication Date
Sat Sep 30 2023
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Performance of Electro-Fenton Process for Phenol Degradation Using Nickel Foam as a Cathode
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Toxic substances have been released into water supplies in recent decades because of fast industrialization and population growth. Fenton electrochemical process has been addressed to treat wastewater which is very popular because of its high efficiency and straightforward design. One of the advanced oxidation processes (AOPs) is electro-Fenton (EF) process, and electrode material significantly affects its performance. Nickel foam was chosen as the source of electro-generated hydrogen peroxide (H2O2) due to its good characteristics. In the present study, the main goals were to explore the effects of operation parameters (FeSO4 concentration, current density, and electrolysis time) on the catalytic performance that was optimized by r

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Publication Date
Thu Dec 09 2021
Journal Name
Journal Of Polymer Research
A new generation of cable grade poly(vinyl chloride) containing heavy metal free modifier
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Abstract<p>Many additives are used to improve the performance of cables in terms of increasing their flame retardancy, thermal stability, thermal conductivity, and other characteristics. Unfortunately, most of these additives contain heavy metals. Therefore, the main objective of this study is to introduce a material representing a new generation of environmentally friendly heavy metal-free stabilizers for cable grade poly(vinyl chloride) that can compete with traditional materials in terms of performance and distinctive properties. This unique additive is Oxydtron, a synthetic silicate or simply nanocement. The tests performed are rheological properties represented by a capillary rheometry analysis, limiting o</p> ... Show More
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Publication Date
Fri Sep 02 2022
Journal Name
Military Medical Science Letters
SOLID LIPID NANOPARTICLES AS A PROMISING APPROACH FOR DELIVERY OF ANTICANCER AGENTS: REVIEW ARTICLE
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Publication Date
Sun Jan 01 2023
Journal Name
Lecture Notes On Data Engineering And Communications Technologies
Deep Learning-Based Approach for Classifying the Severity of Metal Corrosion Using Sem Images
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Publication Date
Sun Apr 06 2008
Journal Name
Diyala Journal For Pure Science
Preliminary Test Bayesian –Shrunken Estimators for the Mean of Normal Distribution with Known Variance
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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
The reasons for the failure of Bishara CO2 compressor belonging to Southern Fertilizer Company
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In this research study failed Annunciation No. 10 for the fourth phase of the pressure of carbon dioxide of the company for Southern Fertilizers and repeated the failures more than once for the same gospel was a detailed study of the gospel included a series tests for properties Mechanical and Structural addition to the tests microscopic and scanning electron microscope shows m This study parameters and a failure Elal well as the existence of an old internal cracks in the metal of the Annunciation

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Publication Date
Wed Jan 01 2025
Journal Name
Journal Of Applied Spectroscopy
Evaluation of Stability Constant for Vitamin B1 Depending on Stoichiometric Curves by Visible Spectroscopy
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The measurement of vitamin B1 in pure and pharmaceutical formulations was proposed by using a straightforward and sensitive spectrophotometric approach. Sulfacetamide (SFA) is diazotized, then coupled with vitamin B1 in alkaline media to produce a colored azo dye complex with a stability constant of 5.597 × 105 L/mol. The product is stable, with a maximum absorption wavelength of 489.5 nm, molar absorptivity of 10108 L/mol∙cm, Sandell's sensitivity of 0.0334 μg/cm2, detection limit of 0.0135 μg/mL, and Beer's law being observed over the concentration range of 0.2–20.0 μg/mL. The stability constant and stoichiometry of the produced azo dye were calculated using the continuous variation (Job's) and mole ratio methods. The suggested ap

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Publication Date
Wed Feb 01 2023
Journal Name
Baghdad Science Journal
Study the Nuclear Structure of Some Even-Even Ca Isotopes Using the Microscopic Theory
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The root-mean square-radius of proton, neutron, matter and charge radii, energy level, inelastic longitudinal form factors, reduced transition probability from the ground state to first-excited 2+ state of even-even isotopes, quadrupole moments, quadrupole deformation parameter, and the occupation numbers for some calcium isotopes for A=42,44,46,48,50 are computed using fp-model space and FPBM interaction. 40Ca nucleus is regarded as the inert core for all isotopes under this model space with valence nucleons are moving throughout the fp-shell model space involving 1f7/2, 2p3/2, 1f5/2, and 2p1/2 orbits. Model space is used to present calculations using FPBM intera

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Publication Date
Sun Sep 22 2019
Journal Name
Baghdad Science Journal
Thermal Conductivity Performance of Silica Aerogel after Exposition on Different Heating under Ambient Pressure
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         The varied thermal conductivity (insulation) of silica aerogel with heating for different pH has been investigated, it has been depended on ambient pressure drying method in the preparing silica aerogel samples, also six different pH of samples (1, 2, 3, 7, 8 and 9) were treated under five degree of heating with (50,100,150,200 and 250) ᴼC. This technique is important to test the carry-outs hydrophobic silica to temperature without high-quality material changes in the basic characteristics. The hot-wire technique is used in this work to examine the thermal conductivity, Fourier Transform Infrared Spectroscopy (FTIR) depended to characterize the bonds and their artificial by heating. Resu

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