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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 Dec 29 2021
Journal Name
Al-khwarizmi Engineering Journal
Analysis and Evaluation of a Quasi-Passive Lower Limb Exoskeleton for Gait Rehabilitation
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Lower extremity exoskeletons can assist with performing particular functions such as gait assistance, and physical therapy support for subjects who have lost the ability to walk. This paper presents the analysis and evaluation of lightweight and adjustable two degrees of freedom, quasi-passive lower limb device to improve gait rehabilitation. The exoskeleton consists of a high torque DC motor mounted on a metal plate above the hip joint, and a link that transmits assistance torque from the motor to the thigh. The knee joint is passively actuated by spring installed parallel with the joint. The action of the passive component (spring) is combined with mechanical output of the motor to provide a good control on the designed exoskeleton whi

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Publication Date
Mon Jan 01 2024
Journal Name
Computer Modeling In Engineering &amp; Sciences
A Review and Bibliometric Analysis of the Current Studies for the 6G Networks
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Publication Date
Wed Jul 31 2024
Journal Name
Cureus
Neuro-Ophthalmic Manifestations of Carotid Cavernous Fistulas: A Systematic Review and Meta-Analysis
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Publication Date
Mon Oct 17 2022
Journal Name
Sustainability
Analysis and Residual Behavior of Encased Pultruded GFRP I-Beam under Fire Loading
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In this paper, fire resistance and residual capacity tests were carried out on encased pultruded glass fiber-reinforced polymer (GFRP) I-beams with high-strength concrete beams. The specimens were loaded concurrently under 25% of the ultimate load and fire exposure (an increase in temperature of 700 °C) for 70 min. Subsequently, the fire-damaged specimens were allowed to cool and then were loaded statically until failure to explore the residual behaviors. The effects of using shear connectors and web stiffeners on the residual behavior were investigated. Finite Element (FE) analysis was developed to simulate the encased pultruded GFRP I-beams under the effect of fire loading. The thermal analyses were performed using the general-pu

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Publication Date
Sat Jun 06 2020
Journal Name
Journal Of The College Of Education For Women
Schema Theory and Text- worlds: A Cognitive Stylistic Analysis of Selected Literary Texts
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Cognitive stylistics also well-known as cognitive poetics is a cognitive approach to language. This study aims at examining literary language by showing how Schema Theory and Text World Theory can be useful in the interpretation of literary texts. Further, the study attempts to uncover how readers can connect between the text world and the real world. Putting it differently, the study aims at showing how the interaction between ‘discourse world’ and ‘text world’. How readers can bring their own experience as well as their background knowledge to interact with the text and make interpretive connections.       

Schema and text world theories are useful tools in cognitive stylistic stud

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Publication Date
Wed Apr 01 2015
Journal Name
Journal Of Educational And Psychological Researches
Analysis of Palestinian Ministry of Education Test Results in Mathfor Eighth Graders basic Public Schools in Tulkarm
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هدفت هذه الدراسة إلى تحليل نتائج الاختبار الوطني الموحد الذي تطبقه وزارة التربية والتعليم الفلسطينية في مادة الرياضيات لطلبة الصف الثامن الأساسي في المدارس الحكومية في محافظة طولكرم، وذلك لمعرفة مستوى الطلبة على هذا الاختبار في ضوء متغيرات الجنس والمنطقة التعليمية ونوع المدرسة، ومعرفة علاقة التحصيل على هذا الاختبار بتحصيل الطلبة المدرسي والمعدل العام. ولتحقيق ذلك تم تحليل درجات (3218) طالباً وطالبة؛ وهم ي

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Publication Date
Sun Dec 04 2011
Journal Name
Baghdad Science Journal
Effect of Magnetic Treatment of water for irrigation and seed Qualities of the Plant vegetative growth corundum oriandrum sativum of
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Cultured fruits of theCorundum Coriandrum sativum were sown On 11/11 / 2008 in basins containing 15 kg of soil (Silty Loam) .Fruits were divided into two parts the first was soaked in normanl water and the second was magnetized for a period of 24 hours Irrigation was up to (75% of capacity field.Two types of water (normal water and magnetized water)with three repetitions were used the access to magnetic water was supplied from a special electric device. Recorded measurements were plant height the number of stems / plant, weight of plant, number of flowers, 1000 seed weight) during the cultivation period, which ended on 11/5/2009. Results indicated the absence of any effect of magnetic water on plant growth of Fenugreek while seeds tre

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Publication Date
Tue Jan 01 2019
Journal Name
Spe Europec Featured At 81st Eage Conference And Exhibition
Development of Artificial Neural Networks and Multiple Regression Analysis for Estimating of Formation Permeability
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Publication Date
Thu May 18 2023
Journal Name
Journal Of Engineering
Design and Analysis of Electro-Hydraulic Servo System for Speed Control of Hydraulic Motor
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In this study, the electro-hydraulic servo system for speed control of fixed displacement hydraulic motor using proportional valve and (PID) controller is investigated theoretically ,experimentally and simulation . The theoretical part includes the derivation of the nonlinear mathematical model equation of (valve – motor ) combination system and the derivation of the transfer function for the complete hydraulic system , the stability test of the system during the operation through the transfer function using MATLAB package
V7.1 have been done. An experimental part includes design and built hydraulic test rig and simple PID controller .The best PID gains have been calculated experimentally and simulation, speed control performance te

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Publication Date
Sun Sep 11 2022
Journal Name
Mathematics
Modeling and Analysis of the Influence of Fear on a Harvested Food Web System
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The food web is a crucial conceptual tool for understanding the dynamics of energy transfer in an ecosystem, as well as the feeding relationships among species within a community. It also reveals species interactions and community structure. As a result, an ecological food web system with two predators competing for prey while experiencing fear was developed and studied. The properties of the solution of the system were determined, and all potential equilibrium points were identified. The dynamic behavior in their immediate surroundings was examined both locally and globally. The system’s persistence demands were calculated, and all conceivable forms of local bifurcations were investigated. With the aid of MATLAB, a numerical simu

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