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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
Wed Jul 01 2015
Journal Name
Journal Of Engineering
Pharmaceutical Wastewater Treatment Associated with Renewable Energy Generation in Microbial Fuel Cell Based on Mobilized Electroactive Biofilm on Zeolite Bearer
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In this study, a novel application of lab-scale dual chambered air-cathode microbial fuel cell (MFC) has been developed for simultaneous bio-treatment of real pharmaceutical wastewater and renewable electricity generation. The microbial fuel cell (MFC) was provided with zeolite-packed anodic compartment and a cation exchange membrane (CEM) to separate the anode and cathode. The performance of the proposed MFC was evaluated in terms of COD removal and power generation based on the activity of the bacterial consortium in the biofilm mobilized on zeolite bearer. The MFC was fueled with real pharmaceutical wastewater having an initial COD concentration equal to 800 mg/L and inoculated with anaerobic aged sludge. Results demo

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Publication Date
Mon Apr 02 2018
Journal Name
Banha University
A Pragma-Semantic Analysis of Deontic and Epistemic Modality of legal Language in Selected Texts تحليل دلالي –تداولي لموقفية الالزام والمعرفية في اللغة القانونية لنصوص مختارة
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Publication Date
Wed Oct 22 2025
Journal Name
Journal Of Physical Education
An Analysis of some motor variables of butterfly stroke and their relationship to success in the 50-meter butterfly race for national team swimmers (candidate category)
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Publication Date
Fri Jul 01 2016
Journal Name
Al–bahith Al–a'alami
A Semiotic Approach to the Analysis of the News Story
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This study attempts to provide an approach analysis for the news, depending on the bases and principles which conceptuality semiotic researchers of this field first of them «A. J. Gremas» for the theory of «narrative discourse analysis», to more clarify we tried to apply it on a published press- news, to concludes the most important steps and methods that are necessary to follows gain more understanding of the press- news.

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Publication Date
Wed Oct 01 2014
Journal Name
Journal Of Economics And Administrative Sciences
Organizational Structure Analysis Via the dimension of the Organic synthesis
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The study focused on the identification of the natural relation between the organizational components, and the most important is the organizational structure, which not hid its effect on each function and operation of the organizational structure through commanding the individual craters and its forms according to the requirement of these function, also it has relation with an organic synthesis that between the dimensions of the organic synthesis and the practice side in the commission of Integrity.

The problem of the research pensioned in some questions about hypothesis and theoretical parts, in which they go a mention about the hypothesis questions is to use all the knowledge's in this atmosphere and th

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Publication Date
Sat Apr 09 2016
Journal Name
Photonic Sensors
Parametric Analysis of NO2 Gas Sensor Based on Carbon Nanotubes
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Publication Date
Sat Dec 01 2012
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
MICROFACIES ANALYSIS OF SHIRANISH FORMATION AT HIJRAN SECTION- NE IRAQ
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Shiranish Formation (Late Campanian- Maastrichtian) that cropping out north east Iraq, is studied by microfacies analysis of 52 thin section collected from Hijran Section, about 10 km west Shaqlawa Town, Governorate of Erbil. According to petrography, mineralogy and organic contents, rocks are subdivided to crystalline carbonate and microfacies units (biowackstone, packstone, and mudstone facies). Biowackstone facies have high ratio of the rock components, while the other facies have low ratio. Microfacies analysis led to relatively quiet deep marine environment.

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Publication Date
Mon Jan 01 2024
Journal Name
Aip Conference Proceedings
Comparative analysis of deep learning techniques for lung cancer identification
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One of the diseases on a global scale that causes the main reasons of death is lung cancer. It is considered one of the most lethal diseases in life. Early detection and diagnosis are essential for lung cancer and will provide effective therapy and achieve better outcomes for patients; in recent years, algorithms of Deep Learning have demonstrated crucial promise for their use in medical imaging analysis, especially in lung cancer identification. This paper includes a comparison between a number of different Deep Learning techniques-based models using Computed Tomograph image datasets with traditional Convolution Neural Networks and SequeezeNet models using X-ray data for the automated diagnosis of lung cancer. Although the simple details p

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Publication Date
Sun Mar 01 2020
Journal Name
Journal Of Engineering
Thermal Performance Analysis of Compact Heat Exchangers for Thermoelectric Generators
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The efficiency of internal combustion engines (ICE) is usually about thirty percent of the total energy of the fuel. The residual energy is lost in the exhaust gas, the lubrication, and the cooling water in the radiators. Recently much of the researcher’s efforts have focused on taking advantage of wasted energy of the exhaust gas. Using a thermoelectric generator (TEG) is one of the promising ways. However, TEG depends entirely on the temperature difference, which may be offered by the exhaust muffler. An experimental test has been conducted to study the thermal performance of a different muffler internal design. The researchers resort to the use of lost energy in an ICE using TEG, which is one of the ways to take adv

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Publication Date
Fri Mar 30 2018
Journal Name
International Journal Of Multimedia And Image Processing
The Design of a Multimedia-Forensic Analysis Tool (M-FAT)
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Digital forensics has become a fundamental requirement for law enforcement due to the growing volume of cyber and computer-assisted crime. Whilst existing commercial tools have traditionally focused upon string-based analyses (e.g., regular expressions, keywords), less effort has been placed towards the development of multimedia-based analyses. Within the research community, more focus has been attributed to the analysis of multimedia content; they tend to focus upon highly specialised specific scenarios such as tattoo identification, number plate recognition, suspect face recognition and manual annotation of images. Given the ever-increasing volume of multimedia content, it is essential that a holistic Multimedia-Forensic Analysis Tool (M-

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