Bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) can differentiate into osteoblasts (OBs), adipocytes, or chondrocytes. As BMSCs undergo OB differentiation, they up-regulate mitochondrial oxidative phosphorylation (OxPhos). Here, we investigated the mechanism(s) connecting mitochondrial OxPhos to OB differentiation. First, we found that treating BMSC-like C3H10T1/2 cells with an OxPhos inhibitor reduces their osteogenic potential. Interestingly, ATP levels were not reduced, as glycolysis compensated for the decreased OxPhos. Thus, mitochondria support OB differentiation not only by supplying ATP, but also by other mechanisms. To uncover these mechanisms, we stimulated OxPhos in C3H10T1/2 cells by replacing media glucose with galactose and observed that this substitution increases both OxPhos and osteogenesis even in the absence of osteoinducers. β-Catenin, an important signaling pathway in osteogenesis, was found to be responsive to OxPhos stimulation. β-Catenin activity is maintained by acetylation, and mitochondria generate the acetyl donor acetyl-CoA, which upon entering the Krebs cycle is converted to citrate capable of exiting mitochondria. Cytosolic citrate is converted back to acetyl-CoA by ATP citrate lyase (ACLY). We found that inhibiting ACLY with SB204990 (SB) reverses the galactose-induced β-catenin activity and OB differentiation. This suggested that acetylation is involved in β-catenin activation after forced OxPhos stimulation, and using immunoprecipitation, we indeed detected SB-sensitive β-catenin acetylation. Both β-catenin acetylation and activity increased during osteoinduction coincident with OxPhos activation. These findings suggest that active mitochondria support OB differentiation by promoting β-catenin acetylation and thus activity.
This paper discusses the potential application of Interacting Multiple Model (1MM) filtering to the multi-radar Air Defense System application. This application includes a wide variety of potential target and radar characteristics. The paper begins with a discussion of the three 1MM filter models that have been chosen and the choice of Markov transition matrix under the condition of variable update rate filtering. A comparison is given of the track prediction performance of the 1MM method with that of a single model filtering system that uses maneuver detection for gain and covariance adjustment. Results show the 1MM approach to be uniformly better than a conventional filter that has been designed for the Air Defense System application. However, the relative improvement of the 1MM approach is a strong function of the quality of the radar measurement data. Since data association is a key tracking issue, 1MM filtering will be adapted for use as part of a Multiple Hypothesis Tracking (MHT) System. For this purpose, 1MM gating and tmck scoring expressions are discussed and the methods validated through simulation.
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