The function and maintenance of muscle stem cells (Mu
SC
s) are tightly regulated by signals originating from their niche environment. Skeletal myofibers are a principle component of the Mu
SC
niche and are in direct contact with the muscle stem cells. Here, we show that Myf6 establishes a ligand/receptor interaction between muscle stem cells and their associated muscle fibers. Our data show that Myf6 transcriptionally regulates a broad spectrum of myokines and muscle‐secreted proteins in skeletal myofibers, including
EGF
.
EGFR
signaling blocks p38
MAP
kinase‐induced differentiation of muscle stem cells. Homozygous deletion of Myf6 causes a significant reduction in the ability of muscle to produce
EGF
, leading to a deregulation in
EGFR
signaling. Consequently, although Myf6‐knockout mice are born with a normal muscle stem cell compartment, they undergo a progressive reduction in their stem cell pool during postnatal life due to spontaneous exit from quiescence. Taken together, our data uncover a novel role for Myf6 in promoting the expression of key myokines, such as
EGF
, in the muscle fiber which prevents muscle stem cell exhaustion by blocking their premature differentiation.
Muscle-specific transcription factor MyoD orchestrates the myogenic gene expression program by binding to short DNA motifs called E-boxes within myogenic cis-regulatory elements (CREs). Genome-wide analyses of MyoD cistrome by chromatin immnunoprecipitation sequencing shows that MyoD-bound CREs contain multiple E-boxes of various sequences. However, how E-box numbers, sequences and their spatial arrangement within CREs collectively regulate the binding affinity and transcriptional activity of MyoD remain largely unknown. Here, by an integrative analysis of MyoD cistrome combined with genome-wide analysis of key regulatory histones and gene expression data we show that the affinity landscape of MyoD is driven by multiple E-boxes, and that the overall binding affinity—and associated nucleosome positioning and epigenetic features of the CREs—crucially depend on the variant sequences and positioning of the E-boxes within the CREs. By comparative genomic analysis of single nucleotide polymorphism (SNPs) across publicly available data from 17 strains of laboratory mice, we show that variant sequences within the MyoD-bound motifs, but not their genome-wide counterparts, are under selection. At last, we show that the quantitative regulatory effect of MyoD binding on the nearby genes can, in part, be predicted by the motif composition of the CREs to which it binds. Taken together, our data suggest that motif numbers, sequences and their spatial arrangement within the myogenic CREs are important determinants of the cis-regulatory code of myogenic CREs.
In this paper, a fuzzy disturbance observer and a high-gain disturbance observer based on a variable structure controller are applied to deal with imprecise multi-shaft with web materials linkage systems taking into account the variation of the moment of inertia. Specifically, a high-gain disturbance observer and an adaptive fuzzy algorithm are separately applied to estimate system uncertainties and external disturbances. The high-gain disturbance observer is designed with auxiliary variables to avoid the amplification of the measurement disturbance, and the fuzzy disturbance observer has the advantage that it does not depend on model information. The convergence properties of the tracking error are analytically proven using Lyapunov’s theory. The obtained numerical results demonstrate the validity and the adaptive performance of the proposed control law in case the system is exposed to uncertainties and disturbances. Important remarks on the design process and performance benchmarks of the two observers are also demonstrated.
When controlling a Dual-Active-Bridge (DAB) DC/DC converter, the high frequency terminal current is usually measured for use in the current feedback controller. In order to measure that current, a wide bandwidth sensor accompanied with high-speed amplifiers are required. Furthermore, a high Analog-to-Digital sampling rate is also necessary for sampling and processing the measured data. To avoid those expensive requirements, this paper proposes an alternative control method for the DAB converter. In the proposed method, the terminal current is estimated by a reduced-order proportional integral observer. A technique is also proposed to reduce the phase drift effect when the voltages at two terminals are not matched. Afterwards, a combined current feedforward-voltage feedback control system is developed to enhance the system dynamics and to regulate the output voltage. This control system needs only the information of the terminal voltages and no current sensor is required. Experimental results show that the observer can estimate the terminal current very quickly with the accuracy of more than 98%. In addition, the output voltage is well regulated with a fluctuation of less than ±2.6% and a settling time of less than 6.5 ms in the presence of a 30% load change.
In this paper, design and optimization method of a three-phase dual-active-bridge DC/DC converter is discussed. Three single phase transformers connected in star-star configuration were designed with large leakage inductance aiming to eliminate the need for external inductors. Switching frequency, peak flux density, number of turns, number of layers, etc., were optimized using non-linear programming technique for minimizing the overall converter loss. Experimental results on a 10 kW prototype show that the optimized converter can operate efficiently an efficacy of up to 98.65% and a low-temperature rise of less than 70 degrees Celsius on both transformers and semiconductor devices.
This paper proposes a new modulation strategy for a dual-active-bridge converter. The target of the new strategy is to suppress the circulating current in the converter by minimizing the load angle. The soft-switching operational area is expanded by employing frequency variation together with phase shift modulation. Unlike published modulation methods based on frequency variation, the strategy proposed in this paper can operate under the light or heavy power transmission regardless of the frequency limitation as well as the voltage ratio. As confirmed by experiments, the new strategy can boost the overall efficiency by up to 7% compared to the conventional single-phase-shift method.
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