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Differentiated osteoclasts have a short life span. We tested various cytokines and growth factors for the effects on the survival of purified mature osteoclasts. In the absence of any added factors, osteoclasts exhibited the survival rate of less than 25% after a 24-h incubation. Among the tested factors, tumor necrosis factor-␣ (TNF-␣) was found to increase the survival rate to ϳ80%. The TNF-␣-enhanced survival of osteoclasts appeared to be associated with reduction in apoptosis and suppression of caspase activation. The antiapoptotic signaling pathways involved in the TNF-␣-induced osteoclast survival were investigated. TNF-␣ treatment increased the phosphorylation of Akt in osteoclasts, which was suppressed by a phosphatidylinositol 3-kinase inhibitor LY294002 and an Src family kinase-selective inhibitor PP1. These inhibitors also attenuated the TNF-␣ stimulation of osteoclast survival. In addition an increase in the phosphorylation of ERK was observed upon TNF-␣ stimulation. PD98059, a specific inhibitor of the ERKactivating kinase MEK-1, abolished the TNF-␣-induced ERK phosphorylation and osteoclast survival, and in these responses the involvement of Grb2 and ceramide was observed. These results suggest that TNF-␣ promotes the survival of osteoclasts by engaging the phosphatidylinositol 3-kinase Akt and MEK/ERK signaling pathways.Osteoclasts are multinucleated cells responsible for bone resorption, which occurs throughout the life as well as during bone development. These cells are continuously formed from the monocyte/macrophage lineage of hematopoietic cells to replace dying cells. The formation and activation of osteoclasts are regulated by numerous cytokines, hormones, and growth factors. Recently, a tumor necrosis factor (TNF) 1 family molecule, receptor activator of nuclear factor B ligand (RANKL; also called TRANCE, ODF, and OPGL), was found to play essential roles for osteoclast differentiation and activation (1-4). Subsequently, many osteotrophic factors were shown to induce the expression of RANKL on supporting osteoblastic/ stromal cells explaining the necessity of cell-to-cell contact between the supporting cells and osteoclast progenitor cells for differentiation of the latter (1, 5). Binding of RANKL to its receptor RANK, a TNF receptor (TNFR) family protein present on osteoclast lineage and dendritic cells, induces a strong activation of NF-B and c-Jun N-terminal kinase through the membrane-proximal adaptor molecules TNFR-associated factors (TRAFs) (3, 4, 6 -10). The crucial roles of RANK and RANKL were clearly shown in knock-out mice that displayed osteopetrosis that results from the lack of osteoclast formation (11, 12). Once terminally differentiated, osteoclasts have a short life span and undergo apoptotic cell death. Survival of osteoclasts appears to be dependent on osteotrophic factors presented by osteoblast/stromal cells, and in the absence of the supporting cells, osteoclasts readily undergo apoptosis (13). Some studies have also reported that the survival of osteoclasts is regulate...

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In mineral exploration, resource assessment, or natural hazard assessment, many layers of geoscience maps such as Iithology, structure, geophysics, geochemistry, hydrology, slope stability, mineral deposits, and preprocessed remotely sensed data can be used as evidence to delineate potential areas for further investigation. Today's PC-based data base management systems, statistical packages, spreadsheets, image processing systems, and geographical information systems provide almost unlimited capabilities of manipulating data. Generally such manipulations make a strategic separation of spatial and nonspatial attributes, which are conveniently linked in relational data bases. The first step in integration procedures usually consists of studying the individual characteristics of map features and interrelationships, and then representing them in numerical form (statistics) for finding the areas of high potential (or impact).Data representation Is a transformation of our experience of the real world into a computational domain. As such, it must comply with models and rules to provide us with useful Information. Quantitative representation of spatially distributed map patterns or phenomena plays a pivotal role in integration because it also determines the types of combination rules applied to them. Three representation methods--probabUity measures, DempsterShafer belief functions, and membership functions in fuzzy sets--and their corresponding estimation procedures are presented here with analyses of the implications and of the assumptions that are required in each approach to thematic mapping. Difficulties associated with the construction of probability measures, belief functions, and membership functions are also discussed; alternative procedures to overcome these difficulties are proposed. These proposed techniques are illustrated by using a simple, artificially constructed data set.