BackgroundDNA methylation is an epigenetic modification that plays an important role during mammalian development. Around birth in humans, the main site of red blood cell production moves from the fetal liver to the bone marrow. DNA methylation changes at the β-globin locus and a switch from fetal to adult hemoglobin production characterize this transition. Understanding this globin switch may improve the treatment of patients with sickle cell disease and β-thalassemia, two of the most common Mendelian diseases in the world. The goal of our study was to describe and compare the genome-wide patterns of DNA methylation in fetal and adult human erythroblasts.MethodsWe used the Illumina HumanMethylation 450 k BeadChip to measure DNA methylation at 402,819 CpGs in ex vivo-differentiated erythroblasts from 12 fetal liver and 12 bone marrow CD34+ donors.ResultsWe identified 5,937 differentially methylated CpGs that overlap with erythroid enhancers and binding sites for erythropoiesis-related transcription factors. Combining this information with genome-wide association study results, we show that erythroid enhancers define particularly promising genomic regions to identify new genetic variants associated with fetal hemoglobin (HbF) levels in humans. Many differentially methylated CpGs are located near genes with unanticipated roles in red blood cell differentiation and proliferation. For some of these new candidate genes, we confirm the correlation between DNA methylation and gene expression levels in red blood cell progenitors. We also provide evidence that DNA methylation and genetic variation at the β-globin locus independently control globin gene expression in adult erythroblasts.ConclusionsOur DNA methylome maps confirm the widespread dynamic changes in DNA methylation that occur during human erythropoiesis. These changes tend to happen near erythroid enhancers, further highlighting their importance in erythroid regulation and HbF production. Finally, DNA methylation may act independently of the transcription factor BCL11A to repress fetal hemoglobin production. This provides cues on strategies to more efficiently re-activate HbF production in sickle cell disease and β-thalassemia patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-014-0122-2) contains supplementary material, which is available to authorized users.
The current paper aims at presenting and examining an implementation on a digital signal processor (DSP) of the conventional space vector pulse width modulation (CSVPWM) so as to control the dual three phase permanent magnet synchronous motors (DTP-PMSM) drives applied on electric ship propulsion. It is also an attempt to accomplish a developed control of this technique based on vector space decomposition (VSD) strategy. By this strategy, the analysis and the control of the machine are achieved in three two-dimensional orthogonal subspaces. Among the 12 voltage vectors having maximum, the conventional technique namely the adjacent two-vectors (12SA2V) is chosen. Thereby, the test platform allows the implementation of the chosen vectors which are modeled on MATLAB/Simulink using block diagrams and the automatically generated code which is targeted in the DSP card processor. Simulation and experimental results have exposed the efficiency of the proposed test bench of 5 KW prototype machine by using a low-cost TMS32F28379D.
<p><span lang="EN-US">A Field Oriented Control (FOC) strategy based on a 24-Sector Vector Space Decomposition (24SVSD) technique used to control a Dual Three-Phase Permanent Magnet Synchronous Motor (DTP-PMSM) applied on electric ship propulsion prototype is presented in this paper. This machine is supplied by Dual Three-Phase Voltage Source Inverter (DTP-VSI). This study carried out on these multiphase machines has revealed that the large zero sequence harmonic current components on (z<sub>1</sub>, z<sub>2</sub>) subspace, constitutes major drawbacks; despite their advantages. The machine’s dynamic model is accomplished in three two-dimensional and orthogonal subspaces. In order to reduce more extra stator harmonic currents that produces losses, the current work is also concering of to consider the three different approaches for the sake of boosting the machine’s efficiency. Thus, the principle selection of the reference voltage vector and the time calculation method are presented in details. The proposed strategy effectiveness is validated by simulation results.</span></p>
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