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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 Jun 01 2020
Journal Name
Journal Of Engineering
Reliability Analysis of Multibit Error Correcting Coding and Comparison to Hamming Product Code for On-Chip Interconnect
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Error control schemes became a necessity in network-on-chip (NoC) to improve reliability as the on-chip interconnect errors increase with the continuous shrinking of geometry. Accordingly, many researchers are trying to present multi-bit error correction coding schemes that perform a high error correction capability with the simplest design possible to minimize area and power consumption. A recent work, Multi-bit Error Correcting Coding with Reduced Link Bandwidth (MECCRLB), showed a huge reduction in area and power consumption compared to a well-known scheme, namely, Hamming product code (HPC) with Type-II HARQ. Moreover, the authors showed that the proposed scheme can correct 11 random errors which is considered a high

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Publication Date
Mon Jan 01 2024
Journal Name
Aip Conference Proceedings
Lab on-a-chip-based, an integrated microfluidic device lo-cost, rapid, and sensitive analysis of Augmentin
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Microfluidic devices provide distinct benefits for developing effective drug assays and screening. The microfluidic platforms may provide a faster and less expensive alternative. Fluids are contained in devices with considerable micrometer-scale dimensions. Owing to this tight restriction, drug assay quantities are minute (milliliters to femtoliters). In this research, a microfluidic chip consisting of micro-channels carved on substrate materials built using an Acrylic (Polymethyl Methacrylate, PMMA) chip was designed using a Carbon Dioxide (CO2) laser machine. The CO2 parameters influence the chip’s width, depth, and roughness. To have a regular channel surface, and low roughness, the laser power (60 W), with scanning speed (250 m/s)

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Publication Date
Sat Oct 01 2022
Journal Name
Advances In Structural Engineering
Experimental and FE analysis of composite RC beams with encased pultruded GFRP I-beam under static loads
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Publication Date
Wed May 10 2023
Journal Name
Journal Of Planner And Development
Analysis and evaluation of related factors affecting community Participation as a policy to upgrade residential slums area
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have suffered from deteriorating residential neighborhoods, poor economic, social and urban living conditions of the population and deteriorating the infrastructural and superior services. These problems were the secretions of these cities' rapid urbanization. Based on the principles of sustainable urban planning and in order to achieve adequate opportunities for the lives of the population and provide them with sustainable livelihoods, policies have emerged to upgrade along the lines of community participation and programmes to reform and develop those neighbourhoods, raise their efficiency and make them livable. Thus, the problem of research was identified "The absence of a comprehensive cognitive perception of the most prominent facto

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Publication Date
Wed Jan 17 2018
Journal Name
Journal Of Engineering And Applied Sciences
PREPARATION, CHARACTERIZATION AND THERMAL ANALYSIS OF POLYMERIC BLEND NANOCOMPOSITES BASED ON PVA-PVPPEGDOPED WITH ZINC OXIDE NANOPARTICLES
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Publication Date
Fri Nov 01 2019
Journal Name
Journal Of Physics: Conference Series
Data Processing, Storage, and Analysis: Applying Computational Procedures to the Case of a Falling Weight Deflectomer (FWD)
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In the field of civil engineering, the adoption and use of Falling Weight Deflectometers (FWDs) is seen as a response to the ever changing and technology-driven world. Specifically, FWDs refer to devices that aid in evaluating the physical properties of a pavement. This paper has assessed the concepts of data processing, storage, and analysis via FWDs. The device has been found to play an important role in enabling the operators and field practitioners to understand vertical deflection responses upon subjecting pavements to impulse loads. In turn, the resultant data and its analysis outcomes lead to the backcalculation of the state of stiffness, with initial analyses of the deflection bowl occurring in conjunction with the measured or assum

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Publication Date
Wed Nov 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
Applied Study on Analysis of Fixed, Random and Mixed Panel Data Models Measured at specific time intervals
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This research sought to present a concept of cross-sectional data models,  A crucial double data to take the impact of the change in time and obtained from the measured phenomenon of repeated observations in different time periods, Where the models of the panel  data were defined by different types of fixed , random and mixed, and Comparing them by studying and analyzing the mathematical relationship between the influence of time with a set of basic variables Which are the main axes on which the research is based and is represented by the monthly revenue of the working individual and the profits it generates, which represents the variable response And its relationship to a set of explanatory variables represented by the

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Publication Date
Sat Oct 01 2022
Journal Name
Advances In Structural Engineering
Experimental and FE analysis of composite RC beams with encased pultruded GFRP I-beam under static loads
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Encasing glass fiber reinforced polymer (GFRP) beam with reinforced concrete (RC) improves stability, prevents buckling of the web, and enhances the fire resistance efficiency. This paper provides experimental and numerical investigations on the flexural performance of RC specimens composite with encased pultruded GFRP I-sections. The effect of using shear studs to improve the composite interaction between the GFRP beam and concrete was explored. Three specimens were tested under three-point loading. The deformations, strains in the GFRP beams, and slippages between the GFRP beams and concrete were recorded. The embedded GFRP beam enhanced the peak loads by 65% and 51% for the composite specimens with and without shear connectors,

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Synthesis, structural study, antimicrobial activity and theoretical treatment of Cr(III), Ni(II), Pt(IV) and Zn(II) complexes with 2-hydroxy-4-Nitro phenyl piperonalidene
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The complexes of the 2-hydroxy-4-Nitro phenyl piperonalidene with metal ions Cr(III), Ni(II), Pt(IV) and Zn(II) were prepared in ethanolic solution. These complexes were characterized by spectroscopic methods, conductivity, metal analyses and magnetic moment measurements. The nature of the complexes formed in ethanolic solution was study following the molar ratio method. From the spectral studies, monomer structures proposed for the nickel (II) and Zinc (II) complexes while dimeric structures for the chromium (III) and platinum (IV) were proposed. Octahedral geometry was suggested for all prepared complexes except zinc (II) has tetrahedral geometry, Structural geometries of these compounds were also suggested in gas phase by using

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Publication Date
Tue May 01 2018
Journal Name
The Journal Of Immunology
Resveratrol treatment alters lung microbiome in the murine ovalbumin-induced asthma model by increasing mucus-degrading <i>Akkermansia muciniphila</i>.
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Abstract<p>Asthma is a chronic inflammatory disease that involves the narrowing of the lung airways and excessive mucus production. Resveratrol (RES), a polyphenolic stilbene, is known to control asthmatic attacks via different molecular mechanisms. However, no studies have examined the effect of resveratrol on the microbiome in the ovalbumin (OVA)-induced asthma mouse model. In this study, we induced asthma in BALB/c mice by injecting OVA followed by 7 days treatment with RES. Plethysmography showed that the expiratory resistance in the lung tissue was significantly reduced in the RES treated group, while mean volume, peak expiratory flow, and frequency of respiration was increased. Histopathol</p> ... Show More
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