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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
Sun Feb 01 2015
Journal Name
Journal Of Engineering
Vibration Analysis of a Composite Plate with Delamination
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The use of composite materials has vastly increased in recent years. Great interest is therefore developed in the damage detection of composites using non- destructive test methods. Several approaches have been applied to obtain information about the existence and location of the faults. This paper used the vibration response of a composite plate to detect and localize delamination defect based on the modal analysis. Experiments are conducted to validate the developed model. A two-dimensional finite element model for multi-layered composites with internal delamination is established. FEM program are built for plates under different boundary conditions. Natural frequencies and modal displacements of the intact and damaged

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Publication Date
Thu Jun 30 2022
Journal Name
Journal Of Economics And Administrative Sciences
Analysis of Models (NAGARCH & APGARCH) by Using Simulations
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Simulation experiments are a means of solving in many fields, and it is the process of designing a model of the real system in order to follow it and identify its behavior through certain models and formulas written according to a repeating software style with a number of iterations. The aim of this study is to build a model  that deals with the behavior suffering from the state of (heteroskedasticity) by studying the models (APGARCH & NAGARCH) using (Gaussian) and (Non-Gaussian) distributions for different sample sizes (500,1000,1500,2000) through the stage of time series analysis (identification , estimation, diagnostic checking and prediction). The data was generated using the estimations of the parameters resulting f

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Publication Date
Sat Sep 01 2018
Journal Name
Alustath Journal For Human And Social Sciences
Critical Discourse Analysis of Donald Trump's Inaugural Speech
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       Political speeches are represented in different shapes as political forum, events or as inaugural speech. This research critically analyzes the inaugural Speech of the President Donald Trump which was delivered on 20th ,January, 2017 from the site<www.cnn.com> retrieved on 10th ,May,2017. The objectives of the study are: First: classifying and discussing well known micro structures (linguistic feature) of the speech, and second: classifying the macro structures i.e. the delivered political inaugural speech  in which he includes social structures. To reach to the objectives of the study, the researcher will adopt Norman Fairclough’s three dimensional Analytical Model(

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Publication Date
Tue Aug 01 2023
Journal Name
Journal Of Engineering
Geomechanics Analysis of Well Drilling Instability: A Review
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Wellbore instability is a significant problem faced during drilling operations and causes loss of circulation, caving, stuck pipe, and well kick or blowout. These problems take extra time to treat and increase the Nonproductive Time (NPT). This paper aims to review the factors that influence the stability of wellbores and know the methods that have been reached to reduce them. Based on a current survey, the factors that affect the stability of the wellbore are far-field stress, rock mechanical properties, natural fractures, pore pressure, wellbore trajectory, drilling fluid chemicals, mobile formations, naturally over-pressured shale collapse, mud weight, temperature, and time. Also, the most suitable ways to reduce well

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Publication Date
Sun Jan 01 2012
Journal Name
The Journal Of Arts Faculty Of Baghdad University
Genre Analysis of Iraqi EFL Graduates’ Dissertation Acknowledgements
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Publication Date
Fri Jan 01 2021
Journal Name
Int. J. Nonlinear Anal. Appl.
Analysis of a harvested discrete-time biological models
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This work aims to analyze a three-dimensional discrete-time biological system, a prey-predator model with a constant harvesting amount. The stage structure lies in the predator species. This analysis is done by finding all possible equilibria and investigating their stability. In order to get an optimal harvesting strategy, we suppose that harvesting is to be a non-constant rate. Finally, numerical simulations are given to confirm the outcome of mathematical analysis.

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Publication Date
Wed Dec 29 2021
Journal Name
Al-khwarizmi Engineering Journal
Analysis of Magnetorheological Normally Close Directional Control Valve
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This valve is intended for use in valves for steering movement, using the qualities of the Magneto-rheological (MR) fluid to regulate the fluid, direct contact without the utilization of moving parts like a spool, a connection between electric flux, and fluid power was made, The simulation was done to employ the" finite element method of magnetism (FEMM)" to arrive at the best design. This software is used for magnetic resonance valve finite element analysis. The valve's best performance was obtained by using a closed directional control valve in the normal state normally closed (NC) MR valve, with simulation results revealing the optimum magnetic flux density in the absence of a current and the shedding condition, as well as the optimum pr

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Publication Date
Tue Dec 09 2014
Journal Name
Journal Of The College Of Education For Women
A Stylistic Analysis of Bisson’s Bears Discover Fire
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This paper aims at analyzing Terry Bisson’s short story Bears Discover Fire stylistically by following both Gerard Genette’s theory of narratology (1980) and Short and Leech (1981) strategy for analyzing fictional works. Also trying to examine to what extent these models are applicable in analyzing the selected story. Stylistic analysis procedures help the readers/researchers to identify specific linguistic features in order to support literary interpretation and appreciation of literary texts. Style in fiction concentrates not on what is written, but on how a text is written. Each writer has his own style and techniques which distinguish him from other writers

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Publication Date
Sat Feb 02 2019
Journal Name
Journal Of The College Of Education For Women
Linguistic Analysis as Mean of Soliciting Patients concerns
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Publication Date
Sun Aug 01 2021
Journal Name
International Journal Of Agricultural And Statistical Sciences
STATISTICAL ANALYSIS OF PATIENTS INFECTED WITHCORONAVIRUS USING MANOVA
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Statistics has an important role in studying the characteristics of diverse societies. By using statistical methods, the researcher can make appropriate decisions to reject or accept statistical hypotheses. In this paper, the statistical analysis of the data of variables related to patients infected with the Coronavirus was conducted through the method of multivariate analysis of variance (MANOVA) and the statement of the effect of these variables.