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In addition to somatic tissues, several studies have documented the development of germ cells from differentiated ES cells. In the first study, ES cells were induced to differentiate in two-dimensional cultures in the presence of serum without additional factors ( Hubner et al. 2003 ). To identify the developing germ cells in the differentiation cultures, the ES cells carried a modified Oct4 promoter that drove GFP expression specifically in the germline. GFP expression was detected as early as day 4 of differentiation, and by day 8 up to 40% of the population was positive. By day 26 of culture, oocyte-like cells enclosed in a structure resembling a zona pellucida were released into the culture from the differentiating cell mass. Following several additional weeks of culture, structures similar to blastocysts were observed, likely originating from the parthenogenic activation of the oocytes.

Male germ cell development has also been demonstrated in ES cell differentiation cultures. With one approach, developing germ cells were identified using an ES cell line in which GFP was targeted to the mouse vasa homolog ( Mvh ), a gene specifically expressed in germline cells ( Sleeveless Top POPPIES 7 by VIDA VIDA Pictures Cheap Price 2018 Discount Free Shipping Reliable OTHDGVzR9z
). While GFP + cells were detected in EBs stimulated with serum alone, the number was significantly enhanced when the EBs were coaggregated with a BMP4-expressing cell line. This observation is encouraging as BMP4 is a known regulator of germ cell development in the mouse embryo ( cropped boyfriend jeans Blue Dsquared2 Discount Marketable Cheap Price Eastbay Online Shop Offer Sale Online Cheap Sale Authentic LRume
). To determine the potential of these putative germ cells, GFP + cells were isolated from the EBs, cocultured with gonadal cells, and then transplanted under a host testis capsule, where they were shown to participate in spermatogenesis. In the second study, germ cells generated in serum-stimulated EBs were isolated on the basis of SSEA1 expression and cultured in the presence of retinoic acid, LIF, bFGF, and c-kit ligand ( silk barocco SS 92 print skirt Versace Shopping Online Clearance Low Cost Cheap Online LFABA7BhS4
). Cells differentiated under these conditions displayed imprint erasure, a distinguishing characteristic of germ cells. If maintained in culture for 2 wk, these serum-stimulated EBs generated a small population of spermatid-like cells that could be isolated using an antibody recognizing the sperm acrosome. This population was enriched for haploid cells that were able to complete fertilization, following injection into oocytes.

Germ cell development has also been analyzed in hES cell differentiation cultures ( Clark et al. 2004 ). In this study, gene expression profiles suggested the development of both male and female germ cells in serum-stimulated EBs. However, as the cells were not isolated and further characterized, the efficiency of differentiation and the extent of lineage maturation are unknown.

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Mass Customization at Hewlett-Packard:The Power of Postponement
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In many mass markets, companies are facing a predicament. On the one hand, customers are demanding that their orders be fulfilled ever more quickly. On the other hand, they are demanding highly customized products and services. Even without trying to customize their products, most companies have found it difficult to fulfill orders swiftly and at an acceptable cost. Is it possible, then, to mass-customize products, deliver them rapidly, and at the same time reduce costs?

The Hewlett-Packard Company has confronted these pressures in many of its businesses, including computers, printers, and medical products. It has proved that companies indeed can deliver customized products quickly and at a low cost. Some companies in such industries as apparel, paint, and consumer electronics have had similar success: they have dramatically increased their product variety, slashed the time they require to fulfill customers’ orders, and reduced costs. Other companies have not: they have mass-customized only to see their costs soar out of control.

The key to mass-customizing effectively is postponing the task of differentiating a product for a specific customer until the latest possible point in the supply network (a company’s supply, manufacturing, and distribution chain). Instead of taking a piecemeal approach, companies must rethink and integrate the designs of their products, the processes used to make and deliver those products, and the configuration of the entire supply network. By adopting such a comprehensive approach, companies can operate at maximum efficiency and quickly meet customers’ orders with a minimum amount of inventory.


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