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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
Sat Jul 01 2023
Journal Name
Industrial Laboratory. Materials Diagnostics
OPTIMIZATION OF PLASMA-ASSISTED DESORPTION/IONIZATIONMASS SPECTROMETRY FOR ANALYSIS OF IBUPROFEN
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In medical practice, nonsteroidal anti-inflammatory drugs (NSAIDs) are often used to treat osteoarthritis and rheumatoid arthritis. Ibuprofen is a well-known NSAID, analgesic, and antipyretic medication. This chemical is an active ingredient of several oral medications that are offered in tablet, gel pellet, and syrup forms and has higher efficacy, tolerance, and side effect rates than other compounds, including pyrazolone derivatives. We present a unique plasma-assisted desorption/ionization mass spectrometry (PADI-MS) approach for improving pharmaceutically important solids using an ibuprofen tablet as a model solid sample. The goal of the study is to create an innovative mass spectrometric method that could be used for quick and accur

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Publication Date
Mon Aug 01 2011
Journal Name
Journal Of Engineering
RELIABILITY ANALYSIS OF THE SEISMIC STABILITY OF EMBANKMENTS REINFORCED WITH STONE COLUMNS
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Geotechnical engineers have always been concerned with the stabilization of slopes. For this purpose,
various methods such as retaining walls, piles, and geosynthetics may be used to increase the safety factor of slopes prone to failure. The application of stone columns may also be another potential alternative for slope stabilization. Such columns have normally been used for cohesive soil improvement. Most slope analysis and design is based on deterministic approach i.e a set of single valued design parameter are adopted and a set of single valued factor of safety (FOS) is determined. Usually the FOS is selected in view of the understanding and knowledge of the material parameters, the problem geometry, the method of analysis and the

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Publication Date
Sat Jan 02 2021
Journal Name
Journal Of The College Of Languages (jcl)
Pragmatic Analysis of the Translation of English Culture-Specific Proverbs into Arabic
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Translating culture-specific proverbs (CSPs) is a challenging task since they often occur in a peculiar context. Further, CSPs are intended to imply meanings that extend far beyond the literal meaning of such a kind of proverbs. As far as English and Arabic are concerned, translators often encounter problems in translating CSPs due to cultural differences between the source language(SL) and the target language (TL) as well as what seems to be the lack of equivalence for some CSPs.

In view of this, the present study aims at investigating the translation of CSPs in three English-Arabic dictionaries of proverbs, namely Dictionary of Common English Proverbs Translated and Explained (2004), One thousand and One English Pr

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Publication Date
Wed Aug 31 2022
Journal Name
Sciencerise: Pharmaceutical Science
The morphological analysis of crystalline methadone: a novel combination of microscopy techniques
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The aim: to evaluate combined microscopy techniques for determining the morphological and optical properties of methadone hydrochloride (MDN) crystals. Materials and methods: MDN crystal formation was optimized using a closed container method and crystals were characterized using polarized light microscope (PLM), scanning electron microscopy (SEM) and confocal microscopy (CM). SEM and CM were used to determine MDN crystal thickness and study its relationship with crystal retardation colours using the Michel-Levy Birefringence approach. Results: Dimensions (mean±SD) of diamond shaped MDN crystals were confirmed using SEM and CM. Crystals were 46.4±15.2 Vs 32.0±8.3 µm long, 28.03±8.2 Vs 20.85±5.5 µm wide, and 6.62±

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Publication Date
Wed Aug 11 2021
Journal Name
Journal Of The College Of Languages
Pragmatic Analysis of the Translation of English Culture -specific Proverbs into Arabic
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Publication Date
Fri Jun 16 2023
Journal Name
Acta Scientiarum Polonorum Administratio Locorum
An analysis of Baghdad’s masterplans based on the development of green areas
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Motives: Baghdad is the capital city and an important political, administrative, social, cultural and economic centre of Iraq. Baghdad’s growth and development has been significantly influenced by efforts to accommodate various needs of its steadily growing population. Uncontrolled population and urban growth have exerted negative effects in numerous dimensions, including environmental sustainability because urban expansion occurred in green spaces within the city and the surrounding areas.Aim: The aim of this study was to examine the planning solutions in Baghdad’s green areas in the past and at present, and to identify the key changes in the city’s green areas, including changes in the ratio of green urban spaces to the tota

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Publication Date
Mon Oct 02 2023
Journal Name
Journal Of Engineering
Numerical Analysis of the Stability of Bridge Foundation Pile under Earthquakes Effect
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This study was chosen because of the entry of our regions into the seismic zone recently, where Diyala governorate was hit by the Halabja earthquake in 2017 by 7.3Mw. Therefore, the impact of earthquakes will be studied on the AL-Mafraq bridge foundations piles located in Iraq- east of Baghdad in Diyala Governorate and the extent of its resistance to the Halabjah, EL-Centro, and Kobe earthquakes with acceleration 0.1g, 0.34g, and 0.58g respectively. After modeling and performing the analysis by using Midas Gts-Nx software, the settlement (mm) results at nine nodes (four nodes for the pile cap and five nodes for the piles) were obtained for each of Halabjah, EL-Centro, and Kobe earthquakes to know the resistance of the br

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Publication Date
Sun Jun 18 2023
Journal Name
International Journal Of Development In Social Sciences And Humanities
A CRITICAL DISCOURSE ANALYSIS OF SELECTED POLITICAL SPEECH ON ONLINE EDUCATION
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PDBN Rashid, International Journal of Development in Social Sciences and Humanities, 2023

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Publication Date
Mon Dec 03 2018
Journal Name
Journal Of Engineering
Comparative Analysis of Various Multicarrier Modulation Techniques for Different Multilevel Converters
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The applications of Multilevel Converter (MLC) are increased because of the huge demand for clean power; especially these types of converters are compatible with the renewable energy sources. In addition, these new types of converters have the capability of high voltage and high power operation. A Nine-level converter in three modes of implementation; Diode Clamped-MLC (DC-MLC), Capacitor Clamped-MLC (CC-MLC), and the Modular Structured-MLC (MS-MLC) are analyzed and simulated in this paper. Various types of Multicarrier Modulation Techniques (MMTs) (Level shifted (LS), and Phase shifted (PS)) are used for operating the proposed Nine level - MLCs. Matlab/Simulink environment is used for the simulation, extracting, and ana

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Publication Date
Mon Oct 09 2023
Journal Name
2023 Ieee 34th International Symposium On Software Reliability Engineering Workshops (issrew)
Semantics-Based, Automated Preparation of Exploratory Data Analysis for Complex Systems
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