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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
Thu Oct 01 2009
Journal Name
Iraqi Journal Of Physics
Calculation of the Longitudinal Electron Scattering Form Factors for the 2s-1d Shell Nuclei
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Inelastic longitudinal electron scattering form factors have been calculated for isoscaler transition
T = 0 of the (0+ ®2+ ) and (0+ ®4+ ) transitions for the 20Ne ,24Mg and 28Si nuclei. Model
space wave function defined by the orbits 1d5 2 ,2s1 2 and 1d3 2 can not give reasonable result for
the form factor. The core-polarization effects are evaluated by adopting the shape of the Tassie-
Model, together with the calculated ground Charge Density Distribution CDD for the low mass 2s-1d
shell nuclei using the occupation number of the states where the sub-shell 2s is included with an
occupation number of protons (a ) .

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Publication Date
Sun Mar 01 2009
Journal Name
Journal Of Economics And Administrative Sciences
Methods of forecasting demandOn the blood substanceApplied study at the National Blood Transfusion Center
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The current research deals with short term forecasting of demand on Blood material, and its' problem represented by increasing of forecast' errors in The National Center for Blood Transfusion because using inappropriate method of forecasting by Centers' management, represented with Naive Model. The importance of research represented by the great affect for forecasts accuracy on operational performance for health care organizations, and necessity of providing blood material with desired quantity and in suitable time. The literatures deal with subject of short term forecasting of demand with using the time series models in order to getting of accuracy results, because depending these models on data of last demand, that is being sta

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Publication Date
Sat Oct 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
Bayesian Estimator for the Scale Parameter of the Normal Distribution Under Different Prior Distributions
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In this study, we used Bayesian method to estimate scale parameter for the normal distribution. By considering three different prior distributions such as the square root inverted gamma (SRIG) distribution and the non-informative prior distribution and the natural conjugate family of priors. The Bayesian estimation based on squared error loss function, and compared it with the classical estimation methods to estimate the scale parameter for the normal distribution, such as the maximum likelihood estimation and th

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Publication Date
Thu Oct 01 2020
Journal Name
Test Engineering & Management
Strengthening of non-liner finite element RCMD Beam with Large Square Opening Using CFRP
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Publication Date
Sat Sep 30 2023
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Desulphurization of Simulated Oil Using SAPO-11 with CNT's as Adsorbent: A Kinetic Study
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In this study, sulfur was removed from imitation oil using oxidative desulfurization process. Silicoaluminophosphate (SAPO-11) was prepared using the hydrothermal method with a concentration of carbon nanotubes (CNT) of 0% and 7.5% at 190 °C crystallization temperature. The final molar composition of the as-prepared SAPO-11 was Al2O3: 0.93P2O5: 0.414SiO2. 4% MO/SAPO-11 was prepared using impregnation methods. The produced SAPO-11 was described using X-ray diffraction (XRD) and Brunauer-Emmet-Teller (N2 adsorption–desorption isotherms). It was found that the addition of CNT increased the crystallinity of SAPO-11. The results showed that the surface area of SAPO-11 cont

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Publication Date
Wed Dec 01 2021
Journal Name
Iraqi Journal Of Physics
Optical, Structural, Morphological Properties of Chromium (III) Oxide Nanostructure Synthesized Using Spray Pyrolysis Technique
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Nanostructure of chromium oxide (Cr2O3-NPs) with rhombohedral structure were successfully prepared by spray pyrolysis technique using Aqueous solution of Chromium (III) chloride CrCl3 as solution. The films were deposited on glass substrates heated to 450°C using X-ray diffraction (XRD) shows the nature of polycrystalline samples. The calculated lattice constant value for the grown Cr2O3 nanostructures is a = b = 4.959 Å & c = 13.594 Å and the average crystallize size (46.3-55.6) nm calculated from diffraction peaks, Spectral analysis revealed FTIR peak characteristic vibrations of Cr-O Extended and Two sharp peaks present at 630 and 578 cm-1 attributed to Cr-O “stretching

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Publication Date
Thu Jan 13 2022
Journal Name
Medical &amp; Biological Engineering &amp; Computing
An integrated entropy-spatial framework for automatic gender recognition enhancement of emotion-based EEGs
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Publication Date
Thu Sep 30 2004
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Simulation the Radiation Zone of Al-Mussaib Power Plant by using Monte Carlo Method
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Publication Date
Wed Jun 30 2021
Journal Name
International Journal Of Intelligent Engineering And Systems
Promising Gains of 5G Networks with Enhancing Energy Efficiency Using Improved Linear Precoding Schemes
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Publication Date
Fri Dec 01 2023
Journal Name
Political Sciences Journal
Exploring the Effects of European Union Conditionality Language on European Mediterranean Human Rights Dialogue
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Since more than a decade, human rights dialogue in the European Mediterranean Region has been marked by a number of tensions. Although a number of factors contribute to such disputes, the effect of human rights conditionality, which ties EU economic cooperation progression with partner countries human rights advancement, on the dialogue has not been studied. Understanding the aspects, impacts, and effects of conditionality on Euro-Med relations is crucial for furthering dialogue. Yet this variable has been almost entirely neglected in academic and policy research. The research concludes several direct and indirect impacts of conditionality on human rights dialogue using a mixed methodology approach. Direct effects are reflected in the wi

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