The present study was carried out to characterize the fetuin-mineral complex (FMC), a high molecular mass complex of calcium phosphate mineral and the proteins fetuin and matrix Gla protein (MGP) that was initially discovered in serum of rats treated with etidronate and appears to play a critical role in inhibiting calcification in vivo. Fetuin purified from the FMC contains 3.3 mol of protein-bound phosphate. There is 1.3 mg of FMC/ml of serum 6 h after etidronate injection, and the FMC is 46% fetuin and 53% mineral by mass. Formation of the FMC in the first 6 h after etidronate injection does not increase serum fetuin despite the fact that 50% of serum fetuin is associated with the FMC, and clearance of the FMC in the 9 -24-h interval lowers total serum fetuin by 50%. These observations suggest that the fetuin component of the FMC is derived from fetuin initially in serum and that clearance of the FMC removes the associated fetuin from circulation. One additional protein was consistently present in all preparations of the FMC, spp24 (secreted phosphoprotein 24). This 24-kDa protein is similar in domain structure to fetuin and, like fetuin and MGP, contains several residues of phosphoserine and accumulates in bone. Exogenous spp24 associated strongly with the FMC when added to serum containing it. These observations suggest that spp24 may, like fetuin and MGP, play a role in inhibiting calcification.The present experiments are a continuation of our investigations into the mechanisms by which proteins interact specifically with mineral in vivo to prevent the calcification of arteries and other soft tissues. In a previous study (1), we described the discovery of a complex of calcium, phosphate, fetuin, 1 and matrix Gla protein in the serum of rats treated with the bone active bisphosphonate etidronate and showed that the appearance of this complex in serum correlates with the inhibition of bone mineralization by etidronate. The fetuin-mineral complex reaches maximal levels 6 -9 h after etidronate injection and causes a 4-fold increase in total serum calcium without causing any increase in ionic calcium levels.The proteins associated with the fetuin-mineral complex, fetuin and matrix Gla protein (MGP), have both been shown to function as potent inhibitors of calcification in vitro. Fetuin is a 59-kDa protein that consists of two N-terminal cystatin domains and a smaller C-terminal domain. Fetuin is synthesized by the liver and secreted into blood, where it is found at a concentration of ϳ1 mg/ml in the rat (2). Previous studies have demonstrated that fetuin is the major calcification inhibitor found in serum (3, 4). Fetuin is also one of the most abundant noncollagenous proteins found in mammalian bone (5-10), with a concentration of ϳ1 mg of fetuin/g of bone in rat (9). MGP is a small, 10-kDa vitamin K-dependent protein (11) that is secreted by a wide variety of cell types, including vascular smooth muscle cells, and is found in bone at a concentration of 0.2 mg/g in the rat (12). Genetic and biochemical studies ...

The present studies were carried out to evaluate the possible association between the presence of the fetuinmineral complex in serum and vitamin D-induced artery calcification. The first experiment shows that there is a fetuin-mineral complex in the blood of rats in which extensive calcification of the artery media has been induced by treatment with vitamin D for 96 h, and that there is no detectable fetuin-mineral complex in the blood of rats in which artery calcification has been inhibited by concurrent treatment with ibandronate or osteoprotegerin. The second experiment shows that the timing of vitamin D-induced artery calcification correlates with the timing of the maximal increase in serum fetuin-mineral complex levels. Whereas both results indicate that serum levels of the fetuin-mineral complex are indeed associated with vitamin D-induced artery calcification, the biochemical basis for this association is presently unclear. One possibility is that high levels of the fetuin-mineral complex cause defects in the ability of fetuin to prevent the growth of the mineral component, which then seeds artery calcification. Another possibility is that the fetuin-mineral complex is the downstream product of a pathway that begins with the true causative agent, and that the serum level of the fetuinmineral complex is a marker for the activity of this agent in blood. An unexpected finding of the present studies is that vitamin D-induced artery calcification is also correlated with a 65 to 75% reduction in serum fetuin, a reduction that appears to be caused by the clearance of the fetuin-mineral complex from serum.We recently proposed the hypothesis that artery calcification is linked to bone resorption to explain the association between increased bone resorption and increased artery calcification that has been seen in the vitamin D-treated rat (1), in the osteoprotegerin-deficient mouse (2), and in patients with postmenopausal osteoporosis (see Ref. 3 for references). One prediction of the hypothesis that artery calcification is linked to bone resorption is that inhibitors of bone resorption should inhibit artery calcification (3). In previous studies we tested this prediction using three different types of bone resorption inhibitors, each with an entirely different mode of action on the osteoclast: the amino bisphosphonates alendronate and ibandronate (3), the cytokine osteoprotegerin (4), and the V-H ϩ -ATPase inhibitor SB 242784 (5). Each bone resorption inhibitor potently inhibited artery calcification.Our working hypothesis is that a causative agent for artery calcification arises in bone, travels in blood, and then induces calcification in the artery wall. A necessary condition for this blood-born theory of artery calcification is that bone resorption inhibitors affect blood chemistry in a way that is plausibly associated with their ability to prevent artery calcification. In previous studies we have shown that this putative change in blood chemistry cannot simply be changes in serum calcium and phosphate, because ...

This paper presents a fault detection method for short circuits based on the correlation coefficient of voltage curves. The proposed method utilizes the direct voltage measurements from the battery cells, and does not require any additional hardware or effort in modeling during fault detection. Moreover, the inherent mathematical properties of the correlation coefficient ensure the robustness of this method as the battery pack ages or is imbalanced in real applications. In order to apply this method online, the recursive moving window correlation coefficient calculation is adopted to maintain the detection sensitivity to faults during operation. An additive square wave is designed to prevent false positive detections when the batteries are at rest. The fault isolation can be achieved by identifying the overlapped cell in the correlation coefficients with fault flags. Simulation and experimental results validated the feasibility and demonstrated the advantages of this method.

Freely moving rats exhibit complex motor and cardiovascular responses to tactile stimulation (12.5 psi air puff, 100-ms duration). In naive Wistar-Kyoto rats, the behavioral response is characterized by a short-latency (25 +/- 1 ms) jumping event, the magnitude of which habituates to repeated stimuli. In a paradigm of consecutive tactile stimuli, each delivered at 30-s intervals, the arterial pressure (AP) response is consistent in profile (36.4 +/- 1.7 mmHg, initial stimulus) and habituates rapidly (15.4 +/- 2.2 mmHg, at 20th stimulus). Rates of habituation of the jumping behavior and AP increase are similar and significantly correlated (P less than 0.01), suggesting partial common mediation. Heart rate changes are bimodal and highly dependent on stimulus number. Initial stimuli elicit bradycardia (-42 +/- 7 beats/min), habituating to extinction by stimulus 10. A temporally delayed tachycardia becomes evident by trial 5 (19 +/- 5 beats/min) and persists unchanged throughout the remainder of the 30-stimulus session. Delayed tachycardia may represent activation of secondary autonomic mechanisms. The nature of cardiovascular responses elicited by the tactile stimulus suggests a somatomotor reflex mediated through the ventrolateral medulla. Adrenal enucleation exaggerated the magnitude of transient bradycardia and abolished extinction of bradycardia with repeated stimuli. Adrenal medullary secretion has only minor importance in direct mediation of the response, but this study suggests that adrenal function plays an important role in tonically setting the level of cardiac responsiveness to parasympathetic vs. sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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