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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 04 2019
Journal Name
Journal Of The College Of Education For Women
Some Methodological Notes on Ibn Al-Jezri Book: Ghayat Al-Nihaya (The Aim of the End): Some Methodological Notes on Ibn Al-Jezri Book: Ghayat Al-Nihaya (The Aim of the End)
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Abstract
Dame Ngaio Edith Marsh (1899-1982), a writer of detective fiction, was born
at Christchurch, New Zealand. Her hero, Chief Detective Inspector Roderick Alleyn,
appears in her first novel, A Man Lay Dead (1934), and in subsequent novels
including Death and the Dancing Footman (1942). She wrote twenty detective novels.
The Dancing Footman, Thomas, listening to a playful song from the smokingroom's
radio where William lay dead after being killed by his brother, Nicholas,
provides the most suspected guest at Highfold with badly needed alibi. The murderer,
Nicholas, plans an almost perfect crime, but the dance of this footman spoils his
scheme. When Alleyn and his group of policemen stage a show in which the

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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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Publication Date
Thu Jan 04 2024
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Achieving customer satisfaction by booking electronic flight tickets via the Internet of Things technology
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Abstract:

                The aim of this research is to highlight the importance of achieving customer satisfaction by using information technology and Internet networks in the process of purchasing flight tickets, and switching from the traditional method of purchasing and payment operations to the electronic method, to reduce the financial and non-financial risks associated with the traditional purchasing process, as well as saving time, effort and costs for the customer. The researcher used the deductive approach in linking the variables (achieving customer satisfaction and Internet of Things technology for booking electronic tickets)

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Publication Date
Tue Sep 04 2007
Journal Name
Nahrainuniversity
MASS TRANSFER OF NAPHTHALENE FROM AN IMMERSED SURFACE TO A SAND-AIR FLUIDIZED BED
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Fluidization process is widely used by a great assortment of industries worldwide and represents a trillion dollar industry [6]. They are currently used in separation, classification, drying and mixing of particles, chemical reactions and regeneration processes; one of these processes is the mass transfer from an immersed surface to a gas fluidized bed

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Publication Date
Fri Jun 29 2018
Journal Name
Journal Of Engineering
The Effect of Circular Perforation on a V-Corrugated Fin Performance under Natural Convection
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An experimental investigation has been made to study the influence of using v-corrugated aluminum fin on heat transfer coefficient and heat dissipation in a heat sink. The geometry of fin is changed to investigate their performance. 27 circular perforations with 1 cm diameter were made. The holes designed into two ways, inline arrangement and staggered in the corrugated edges arrangement. The experiments were done in enclosure space under natural convection. Three different voltages supplied to the heat sink to study their effects on the fins performance. All the studied cases are compared with v-corrugated smooth solid fin. Each experiment was repeated two times to reduce the error and the data recorded after reaching t

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Publication Date
Wed Jan 01 2025
Journal Name
Iraqi National Journal Of Earth Science (injes)
The Effect of Satellite Image Fusion on the Classification Process by Using Multiple Sensors
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