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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 Jan 01 2022
Journal Name
Structural Durability &amp; Health Monitoring
Seismic Analysis of Reinforced Concrete Silos under Far-Field and Near-Fault Earthquakes
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Publication Date
Sat Apr 13 2024
Journal Name
Journal Of Optics
Analysis of laser induced breakdown spectra for distinguish between healthy and carious teeth
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Dielectric barrier discharges (DBD) can be described as the presence of contact with the discharge of one or more insulating layers located between two cylindrical or flat electrodes connected to an AC/pulse dc power supply. In this work, the properties of the plasma generated by dielectric barrier discharge (DBD) system without and with a glass insulator were studied. The plasma was generated at a constant voltage of 4 kV and fixed distance between the electrodes of 5 mm, and with a variable flow rate of argon gas (0.5, 1, 1.5, 2 and 2.5) L/min. The emission spectra of the DBD plasmas at different flow rates of argon gas have been recorded. Boltzmann plot method was used to calculate the plasma electron temperature (Te), and Stark broadeni

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Publication Date
Tue Dec 22 2020
Journal Name
Clinical And Experimental Dental Research
Prevalence and factors influencing reporting of true periodontal chief complaints: A retrospective analysis
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Abstract<sec><title>Objectives

To investigate the prevalence of true periodontal chief complaints (CC) and the factors affecting their reporting by patients with periodontal diseases (PD).

Materials and Methods

This cross‐sectional study was based on retrospective analysis of available periodontal records. Different personal and demographic variables were obtained from these records including CC, age, gender, working status, past medical/dental history, smoking status and diagnosis. In addition, clinical parameters of plaque index, gingival index, probing pocket depth (PPD), and number of missing teeth. Periodontal CC were r

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Publication Date
Sun Oct 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
discriminate analysis and logistic regression existence of multicolleniarty problem(Empirical Study on Anemia)
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The method binery logistic regression and linear discrimint function of the most important statistical methods used in the classification and prediction when the data of the kind of binery (0,1) you can not use the normal regression therefore resort to binary logistic regression and linear discriminant function in the case of two group in the case of a Multicollinearity problem between the data (the data containing high correlation) It became not possible to use binary logistic regression and linear discriminant function, to solve this problem, we resort to Partial least square regression.

In this, search the comparison between binary lo

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Publication Date
Thu Mar 12 2020
Journal Name
Al-khwarizmi Engineering Journal
Inverse Kinematics Analysis and Simulation of a 5 DOF Robotic Arm using MATLAB
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Kinematics is the mechanics branch which dealswith the movement of the bodies without taking the force into account. In robots, the forward kinematics and inverse kinematics are important in determining the position and orientation of the end-effector to perform multi-tasks. This paper presented the inverse kinematics analysis for a 5 DOF robotic arm using the robotics toolbox of MATLAB and the Denavit-Hartenberg (D-H) parameters were used to represent the links and joints of the robotic arm. A geometric approach was used in the inverse kinematics solution to determine the joints angles of the robotic arm and the path of the robotic arm was divided into successive lines to accomplish the required tasks of the robotic arm.Therefore, this

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Publication Date
Sun Jun 07 2015
Journal Name
Baghdad Science Journal
Synthesis, Characterization, Thermal Analysis and Structural Studies of New Complexes with Tetradentate Ligand
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Some new complexes of 4-(5-(1,5-dimethyl-3-oxo-2-phenyl pyrazolidin-4- ylimino)-3,3-dimethyl cyclohexylideneamino) -1,5- dimethyl-2- phenyl -1H- pyrazol -3(2H) –one (L) with Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Pd(II), Re(V) and Pt(IV) were prepared. The ligand and its metal complexes were characterized by phisco- chemical spectroscopic techniques. The spectral data were suggested that the (L) as a neutral tetradentate ligand is coordinated with the metal ions through two nitrogen and two oxygen atoms. These studies revealed Octahedral geometries for all metal complexes, except square planar for Pd(II) complex. Moreover, the thermodynamic activation parameters, such as ?E*, ?H, ?S, ?G and K are calculated from the TGA curves using Coa

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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 studies. The reader's perception o

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Publication Date
Wed May 27 2020
Journal Name
Acta Biologica Szegediensis
Phytochemical analysis, cytotoxicity and antioxidant activity of cuckoo pint (Arum maculatum) leaf extract
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Arum maculatum is traditionally used for the control of many diseases and illnesses such as kidney pain, liver injury, hemorrhoids. However, the detailed biomedical knowledge about this species is still lacking. This study reports on the bioactive components and the possible mechanisms underlying the antioxidant, anti-inflammatory and cytotoxic activity of A. maculatum leaf extract. Gas chromatography-mass spectrometry (GC-MS) was used for phytochemical analysis. Assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ) (MTT) was used to determine the cytotoxicity in the murine cell line L20B upon exposure to different extract concentrations for 24 h. Enzyme-linked immunosorbent assay (ELISA) was used to detect pro-in

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Publication Date
Fri Apr 01 2022
Journal Name
Baghdad Science Journal
Collection, Storage and Protein Extraction Method of Gingival Crevicular Fluid for Proteomic Analysis
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Gingival crevicular fluid (GCF) may reflect the events associated with orthodontic tooth movement. Attempts have been conducted to identify biomarkers reflecting optimum orthodontic force, unwanted sequallea (i.e. root resorption) and accelerated tooth movement. The aim of the present study is to find out a standardized GCF collection, storage and total protein extraction method from apparently healthy gingival sites with orthodontics that is compatible with further high-throughput proteomics. Eighteen patients who required extractions of both maxillary first premolars were recruited in this study. These teeth were randomly assigned to either heavy (225g) or light force (25g), and their site specific GCF was collected at baseline and aft

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Publication Date
Mon Jan 01 2024
Journal Name
Aip Conference Proceedings
Modeling and analysis of thermal contrast based on LST algorithm for Baghdad city
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