The capacity of mesenchymal stem cells (MSCs) to differentiate into functional osteoblasts is tightly controlled by transcription factors that trigger osteoblast commitment and differentiation. The ...role of Twist1, a basic helix‐loop‐helix (bHLH) transcription factor, in osteogenic differentiation of MSCs remains unclear. Here we investigated the role of Twist1 in the osteogenic differentiation program of murine C3H10T1/2 mesenchymal cells. We showed that molecular silencing of Twist1 using short hairpin RNA (shRNA) expression moderately increased C3H10T1/2 cell proliferation and had no effect on cell survival. In contrast, Twist1 silencing enhanced osteoblast gene expression and matrix mineralization in vitro. Biochemical analyses revealed that Twist1 silencing increased the expression of FGFR2 protein level, which was reduced by a mutant Runx2. Consistent with this finding, Twist1 silencing increased ERK1/2 and PI3K signaling. Moreover, molecular or pharmacological inhibition of FGFR2 or of ERK1/2 and PI3K signaling partly abolished the increased osteoblast gene expression induced by Twist1 silencing in C3H10T1/2 cells. These results reveal that Twist1 silencing upregulates osteoblast differentiation of murine mesenchymal cells in part via activation of FGFR2 expression and downstream signaling pathways, which provides novel insights into the molecular signals by which this transcription factor regulates the osteogenic differentiation program in MSCs. J. Cell. Biochem. 110: 1147–1154, 2010. Published 2010 Wiley‐Liss, Inc.
Genetic mutations of Twist, a basic helix-loop-helix transcription factor, induce premature fusion of cranial sutures in Saethre-Chotzen syndrome (SCS). We report here a previously undescribed ...mechanism involved in the altered osteoblastogenesis in SCS. Cranial osteoblasts from an SCS patient with a Twist mutation causing basic helix-loop-helix deletion exhibited decreased expression of E3 ubiquitin ligase Cbl compared with wild-type osteoblasts. This was associated with decreased ubiquitin-mediated degradation of phosphatidyl inositol 3 kinase (PI3K) and increased PI3K expression and PI3K/Akt signaling. Increased PI3K immunoreactivity was also found in osteoblasts in histological sections of affected cranial sutures from SCS patients. Transfection with Twist or Cbl abolished the increased PI3K/Akt signaling in Twist mutant osteoblasts. Forced overexpression of Cbl did not correct the altered expression of osteoblast differentiation markers in Twist mutant cells. In contrast, pharmacological inhibition of PI3K/Akt, but not ERK signaling, corrected the increased cell growth in Twist mutant osteoblasts. The results show that Twist haploinsufficiency results in decreased Cbl-mediated PI3K degradation in osteoblasts, causing PI3K accumulation and activation of PI3K/Akt-dependent osteoblast growth. This provides genetic and biochemical evidence for a role for Cbl-mediated PI3K signaling in the altered osteoblast phenotype induced by Twist haploinsufficiency in SCS.
A new thermal model, which allows temperature distribution determination inside a supercapacitor cell, is developed. The model is tested for a supercapacitor based on the activated carbon and organic ...electrolyte technology. In hybrid vehicle applications, supercapacitors are used as energy-storage devices, offering the possibility of providing the peak-power requirement. They are charged and discharged at a high current rate. The problem with this operating mode is the large amount of heat produced in the device which can lead to its destruction. An accurate thermal modeling of the internal temperature is required to design a cooling system for supercapacitor module, meeting the safety and reliability of the power systems. The purpose of this paper is to study the supercapacitor temperature distribution in steady and transient states. A thermal model is developed; it is based on the finite-differential method which allows for the supercapacitor thermal resistance determination. The originality of this paper is in the fact that a thermocouple (type K) was placed inside the supercapacitor from Maxwell Technologies. A test bench is realized. The cases of supercapacitor thermal distribution using natural and forced convection are studied. Simulations and experimental results are reported to validate the proposed model. The results obtained with this model may be used to determine the cooling system required for actual supercapacitor applications.
This paper presents a multiphysical battery pack model, along with a procedure to identify its parameters and its application to state-of-charge (SOC) determination using an extended Kalman filter ...(EKF). The model enables the reproduction of the electric and thermal behaviors of batteries with high accuracy. A methodology is proposed to identify the parameters of the model and optimize them. The model is experimentally validated with measurements run on high-energy-density ThunderSky cells. A comparison of measurements and model results shows that the electrical model error is below 1.6% and that the error of the thermal model is below 2.5%. The model is used as an EKF basis to reliably estimate the battery SOC. The results are also experimentally verified through measurements showing that the proposed model performs better than other simpler models and determination methods.
Our aim is to introduce the concept of double-measure ergodic and double-measure pseudo-almost periodic functions in Stepanov’s sense. In addition, we present numerous interesting results, such as ...the composition theorems and completeness properties, for these two spaces of considered functions. We also establish the existence and uniqueness for double-measure pseudo-almost periodic mild solutions in Stepanov’s sense for some evolution equations.
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