Recent advancements in cell culture engineering have allowed drug manufacturers to achieve higher productivity by driving higher product titers through cell line engineering and high‐cell densities. However, these advancements have shifted the burden to clarification and downstream processing where the difficulties now revolve around removing higher levels of process‐ and product‐related impurities. As a result, a lot of research efforts have turned to developing new approaches and technologies or process optimization to still deliver high quality biological products while controlling cost of goods. Here, we explored the impact of a novel single use technology employing chromatographic principle‐based clarification for a process‐intensified cell line technology. In this study, a 16% economic benefit ($/g) was observed using a single‐use chromatographic clarification compared to traditional single‐use clarification technology by improving the overall product cost through decreased operational complexity, higher loading capacity, increased product recovery, and higher impurity clearance. In the end, the described novel chromatographic approach significantly simplified and enhanced the cell culture fluid harvest unit operation by combining the reduction of insoluble and key soluble contaminants of the harvest fluid into a single stage.
There are generally said to be three components of the structural unit of enamel: the interprismatic substance, a continuous phase which in cross-section looks like a net; a separate phase, the rods, which have rather complex cross-sections; and a third phase, the sheath, which more or less completely covers each prism and is accordingly seen in cross-sections as a more or less complete ring around each rod. The sheath, after the early stages of histogenesis, is space rather than membrane and becomes smaller and smaller as the calcification of the erupted tooth reaches completion. 1-3 Statements of the changes in these three elements as the enamel becomes carious have been conflicting. In the recent literature numerous investigators have suggested that the interprismatic substance was preferentially removed by the acid of caries, leaving the rod material undissolved until later.4 6 These reports are at variance, however, with older investigations7' 8 which suggest that the sheath or the rod itself is attacked first.In the study described here it is shown that the sheath is the first component of the enamel to become involved in the carious process and the cross-striations and the bodies of the prisms next and that this order of attack has great significance for the nature of the carious process.
MATERIALS AND METHODSThirteen permanent teeth with early white-spot caries and one unerupted third molar were examined. Longitudinal sections 200 pt thick were cut in series from each tooth, so that two or more sections of each lesion were obtained. There were no lesions in the unerupted tooth, and only one section near the center was chosen for study. Each longitudinal section was marked by means of small holes drilled in the dentin and by a thin metal-foil strip glued near the lesion. Photographs were made in polarized light after the lesions were marked. After this a transverse cut was made through the longitudinal section in the region of the lesion, and another photograph was taken. In this way a tracing of the second photograph could be superimposed on the first, properly oriented by means of the markers, and a line drawn showing the precise level at which the transverse section was cut from the longitudinal section (see Figs. 1 and 2). Furthermore, since a portion of the metal-foil marker appeared on the transverse section, the distance from it of any field studied under the microscope could be ascertained, and this field located on the photograph of the longitudinal section.The transverse sections were prepared by gluing the 200-p longitudinal sections to a
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