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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
Harold pinter and Iraq: An analysis of war(2003)
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Publication Date
Sat Dec 01 2018
Journal Name
Al-khwarizmi Engineering Journal
Dynamic Analysis of Thin Composite Cylindrical and Spherical Shells
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In this work, an investigation for the dynamic analysis of thin composite cylindrical and spherical shells is presented. The analytical solution is based upon the higher order shear deformation theory of elastic shells from which the developed equations are derived to deal with orthotropic layers. This will cover the determination of the fundamental natural frequencies and mode shapes for simply supported composites cylindrical and spherical shells.

      The analytical results obtained by using the derived equations were confirmed by the finite element technique using the well known Ansys package. The results have shown a good agreement with a maximum percentage of discrepancy, which gives a confidence o

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Publication Date
Fri Jul 21 2023
Journal Name
Journal Of Engineering
EXPERIMENTAL AND NUMERICAL STRESS ANALYSIS OF INVOLUTE SPLINED SHAFT
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In this study, the induced splined shaft teeth contact and bending stresses have been investigated numerically using finite element method(Ansys package version 11.0) with changing the most effecting design parameter,(pressure angle, teeth number, fillet radius and normal module), for internal and external splined shaft. Experimental work has been achieved using two dimensional photoelastic techniques to get the contact and bending stresses; the used material is Bakelite sheet type “PSM-4”.
The results of numerical stress analysis indicate that, the increasing of the pressure angle and fillet radius decrease the bending stress and increase the contact stress for both internal and external spline shaft teeth while the increasing of

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Publication Date
Wed Aug 28 2024
Journal Name
Mathematical Modelling Of Engineering Problems
Structural and Stress Analysis of NACA0012 Wing Using SolidWorks
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Publication Date
Sun Jul 09 2023
Journal Name
Journal Of Engineering
Buckling Analysis of Stiffened and Unstiffened Laminated Composite Plates
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The present study focused mainly on the analysis of stiffened and unstiffened composite laminated plates subjected to buckling load. Analytical, numerical and experimental analysis for different cases has been considered. The experimental investigation is to manufacture the laminates and to find mechanical properties of glass-polyester such as longitudinal, transverse young modulus, shear modulus. The compressive test was carried to find the critical buckling load of plate. The design parameters of the laminates such as aspect ratio, thickness ratio, boundary conditions and number of stiffeners were investigated using high order shear deformation theory (HOST) and Finite element coded by ANSYS .The main conclusion was the buckling load c

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Publication Date
Thu Jan 01 2009
Journal Name
Bayt Alhekma
COMPARATIVE ANALYSIS OF RUSSIAN AND ARABIC PHRASEOLOGICAL UNITS (TURNS)
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Abstract The study aimed at reviewing translation theories proposed to address problems in translation studies. To the end, translation theories and their applications were reviewed in different studies with a focus on issues such as critical discourse analysis, cultural specific items and collocation translation.

Publication Date
Wed May 29 2019
Journal Name
Journal Of Legal Sciences
The extent of responsibility - the seller of Alcohol or the provider – the civil towards the drug addicts and their victims "A comparative study"
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There are many harmful acts that occur from drunkards in this case, especially those resulting from car accidents. The world is witnessing dozens or even hundreds of car accidents due to alcohol consumption. These accidents often result in serious injuries that could lead to the death of the drunk driver and those in the car As well as other persons present in the other vehicles with which the incident occurred or pedestrians on the street, as well as damage to private or public property, and if the order of return of the affected persons on the pretext of civil liability (tort) is made as a direct cause of the harmful act, Is entitled Do they like this refer to the liquor seller or their provider as the culprit? Or are they not related to

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Publication Date
Fri Apr 01 2022
Journal Name
Desalination And Water Treatment
MgCl2 and MgSO4 as draw agents in forward osmosis process for East Baghdad oilfield produced water treatment
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This study investigated a novel application of forward osmosis using different types of draw solutions for oilfield produced water treatment from the East Baghdad oilfield affiliated to the Midland Oil Company (Iraq). Magnesium chloride (MgCl2) and magnesium sulfate (MgSO4) were used as draw solutions in forward osmosis process to evaluate their effectiveness. Experiments were conducted in a laboratory scale forward osmosis system with cellulose triacetate hollow fiber membrane. In this work, sodium chloride solution was used as a feed solution with a concentration of 76 g/L (same concentration as the East Baghdad oilfield produced water) and the applied external pressure on the feed solution side was 2 bar. The impact of draw solution (DS)

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Publication Date
Thu Dec 10 2009
Journal Name
Iraqi Journal Of Laser
Immuno-hematological and biochemical changes in diabetic retinopathy patient`s blood after treatment by Nd-YAG laser
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Diabetic retinopathy is one of most important complications of diabetes mellitus that can be treated by Nd:YAG laser. Laser is used in ophthalmic practice for photocoagulation and photodisruption. The purpose of this study is to evaluate changes in immunological ,hematological and biochemical values after treatment of diabetic retinopathy by laser. Blood samples from 10 patients suffering from diabetic retinopathy were taken before and after laser treatment to coagulate retina to prevent leakage and hemorraghe to avoid deterioration of vision.In group one (4 patients = 40%), blood tests were done one day after treatment. In group two (6 patients =60%) tests were done 7 days after treatment with laser. The study showed no clear changes in

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Publication Date
Thu Jan 31 2019
Journal Name
Journal Of Engineering
Heat Transfer Analysis of Conventional Round Tube and Microchannel Condensers in Automotive Air Conditioning System
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In this paper, an experimental analysis of conventional air-cooled and microchannel condensers in automotive vapor compression refrigeration cycle concerning heat transfer coefficient and energy using R134a as a refrigerant was presented. The performance of two condensers and cycles tested regarding ambient temperature which it was varied from 40oC to 65oC, while the indoor temperature and load have been set to be 23oC and 2200 W respectively. Results showed that the microchannel condenser has 224 % and 77 % higher refrigerant side and air side heat transfer coefficient respectively than the coefficients of the conventional condenser. Thus, the COP, in case of using the microchannel

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