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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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
Thu Nov 29 2018
Journal Name
Iraqi Journal Of Science
Petrography and Provenance of the Sandstone of Injana and Mukdadiya Formations (Upper Miocene/Pliocene) at Duhok Governorate, Northern Iraq

A total of 23 samples are collected from Injana and Mukdadiya Formations representing: sandstone (14 samples from Injana Formation and 9 samples from Mukdadiya Formation). 19 sandstone samples are thin sectioned for petrographic study (10 thin sections from Injana and 9 thin sections from Mukdadiya) and 23 sandstone samples are selected for heavy minerals study (14 samples from Injana and 9 samples from Mukdadiya). The petrographic investigations revealed that the sandstone of Injana and Mukdadiya Formations are composed primarily of rock fragments (sedimentary, igneous and metamorphic), quartz (monocrystalline and polycrystalline) and feldspars (orthoclase, microcline and plagioclase). The matrix is subordinate and the cement is mostly

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Publication Date
Mon May 15 2023
Journal Name
Iraqi Journal Of Science
Combining Effect of Lower Rate of Trifluralin Herbicide and Sunflower residues on mycorrhizal association with cowpea and soil nitrification

Field and laboratory experiments were conducted during the course of study to
test if the sunflower residues along or with 50% full rate of trifluralin herbicide has
any impact on mycorrhizal association and soil nitrification which are important
processes for improving growth and productivity of crops. Results revealed that
incorporation of sunflower residues significantly increased spores number at 2, 4
and 6 weeks of residue decomposition compared to control treatment. However,
when the residues applied in combination with reduced rate of trifluralin herbicide,
sporulation was appreciably decreased by sunflower residues at 3 t ha-1 but it
remains almost the same at 6 t ha-1 rate of residues. Field soil amended

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Publication Date
Thu Dec 29 2016
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Isolation and Diagnosis of Aerobic Bacteria from Patients with Respiratory Tract Infection and Partial Characterization of Their Plasmid Profile

   In this study, the bacteria from sputum specimens of patients with respiratory tract infections were isolated in   IbnSina Teaching Hospital, Mosul city, Iraq.  The bacteria  were subjected to phenotypic and biochemical tests necessary for identification. Twenty five isolates of six different bacterial species were obtained, they are : Staphylococcus aureus, Streptococcus pneumonia, Moraxella cattarhalis, Escherichia coli, Klebsiella pnuemoniae and Pseudomona saeruginosa with ratios (64%, 12%, 8%, 8%, 4% and 4% ) respectively. The sensitivity and resistance of these isolates to 12 antibiotic were studied, where the Gentamycin appear to be more effective on most of the isolates while all the isolates showe

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Publication Date
Tue May 23 2023
Journal Name
Journal Of Engineering
Modeling and Simulation of Copper Removal from the Contaminated Soil by a Combination of Adsorption and Electro-kinetic Remediation

Electro-kinetic remediation technology is one of the developing technologies that offer great promise for the cleanup of soils contaminated with heavy metals. A numerical model was formulated to simulate copper (Cu) transport under an electric field using one-dimensional diffusion-advection equations describing the contaminant transport driven by chemical and electrical gradients in soil during the electro-kinetic remediation as a function of time and space. This model included complex physicochemical factors affecting the transport phenomena, such as soil pH value, aqueous phase reaction, adsorption, and precipitation. One-dimensional finitedifference computer program successfully predicted meaningful values for soil pH profiles and Cu

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Publication Date
Sun Apr 02 2017
Journal Name
Journal Of Educational And Psychological Researches
Self -affirmation and its relation of tendency toward perfection and the awareness of creativity among fine arts institutions students

The study aimed to identify self –affirmation degree, tendency degree toward perfection, awareness degree of creativity among fine arts institutions students, and the significant correlation between self -affirmation and its tendency toward perfection, and the awareness of creativity among fine arts institutions students. To achieve these objectives, the author had constructed two scales: one to measure self –affirmation among the sample based on “Lang& Jakobowski theory” (Lang& Jakobowski, 1973) that consisted of (54) item divided into two parts: qualitative and situational. The other scale is to measure the tendency toward perfection depend on (flett & Hewitt, 1991) that composed of (46) item divided into two sectio

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Publication Date
Sun Jan 30 2022
Journal Name
Iraqi Journal Of Science
Preparation and Characterization of New Mixed Ligand Complexes of (p-Methyl Anilino)-p-Chloro Phenyl Acetonitrile and Ethylene Diamine

New mixed ligand complexes of some metal ions Zn(II), Cd(II) and Hg(II) were prepared by reacting with mixture of two bidentate ligands [ HL = (P-methyl anilino) –P– chloro phenyl acetonitrile and en = ethylene diamine] in a molar ratio of 1:1:1[ M : HL : en] in ethanol . The ligand HL was previously prepared by Strecker’s procedure which includes the reaction of p- toluidine with P- chlorobenzaldehyde in the presence of KCN in acidic medium. The structures of new compounds were identified by elemental analyses, atomic absorption and thermal analyses TG/DTG in addition to FTIR and U.V-VIS. Spectra. The electrical conductivity measurements of metal complexes were also determined. From the obtained data the octahedral structure was s

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Publication Date
Sat Oct 01 2022
Journal Name
Digest Journal Of Nanomaterials And Biostructures
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Publication Date
Wed Jan 08 2020
Journal Name
Environment, Development And Sustainability
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Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
Synthesis and Characterization of Some New Monemer and Polymers Containing Hetero Cyclic Rings With Study of Their Physical Properties.

Number of new polyester and polyamide are prepared as derivatives from 5,5`-(1,4-phenylene)-bis-(1,3,4-thiadiazole-2-amine) [C1], three series of heterocyclic compounds were synthesized.The first series includes the Schiff base [C2] prepared from the reaction between compound [C1] with p-hydroxy benzaldehyde in presence of acetic acid and absolute ethanol , then these derivatives have reaction with maleic anhydride , phthalic anhydride and sodium azide, respectively to obtain the compounds [C3-5] contaning (oxazepine and tetrazole) rings.The third series of compounds [C1-5] has transformed to their polymers [C6-15] by reaction with adipoyl chloride and glutroyl chloride , respectively. The reaction was followed by T.L.C and ident

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Publication Date
Sat Jun 27 2020
Journal Name
Iraqi Journal Of Science
Influence of Laser Energy and Annealing on Structural and Optical Properties of CdS Films Prepared by Laser Induced Plasma

The current study was achieved on the effects of laser energy and annealing temperature on x-ray structural and optical properties, such as the UV-Visible spectra of cadmium sulfide (CdS). The films were prepared using pules laser deposition technique (PLD) under vacuum at a pressure of 2.5×10-2 mbar with different laser energies (500-800 mJ) and annealing at a temperature of 473K. X-ray diffraction patterns and intensity curves for the CdS showed that the formation of CdS multi-crystallization films at all laser energies. The optical properties of the films were studied and the variables affecting them were investigated in relation to laser energy and changes in temperature.

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