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Heat penetration depends on the solid-liquid ratio and the food distribution inside the can. In canned sausage distributed along the vertical axis, a convection-conduction mechanism takes place; if the solid material is loosely packed, the heating rate will be faster. In general, 30% of the can volume should be lled with a liquid, such as brine, to provide a high heat-transference rate. The brine is always added after the solids; in the case of pastes, the lling operations are generally carried out with automatic lling equipments; care must be taken not to incorporate bubbles. The headspace must be 0.5% of total can volume; ef ciency during the exhausting phase depends on the headspace.

Cell-cell and cell-extracellular matrix interactions are critical for proper cellular processes in numerous organ systems Speci cally, such interactions have been demonstrated to be key determinants of hepatocyte function For example, it has been well documented that isolated hepatocytes cultured in monolayer culture display a rapid loss of phenotype [Bissell et al, 1973; Dunn et al, 1989; Leffert and Paul, 1972; Reid et al, 1980; Selden et al, 1999], preventing the effectiveness of these cells in long-term applications Cell-cell interactions, both homotypic (hepatocyte-hepatocyte) and heterotypic (hepatocyte-nonparenchymal), have been demonstrated to exhibit positive effects on hepatocyte function In particular, hepatocyte viability and a variety of liver functions have been shown to be stabilized for weeks in vitro on cocultivation with liver-derived cell types as well as some non-liver-derived populations [Bhatia et al, 1999].

However, despite the signi cant amount of data existing on potential mediators of cell communication in cocultures, the mechanisms by which coculture of hepatocytes with other cells induces and stabilizes liver-speci c function and viability remain primarily unde ned Current experiments in our laboratory are examining these processes To study the role of cell-cell interactions in hepatocellular function, we previously developed and characterized a exible method of micropatterning cocultures of hepatocytes and an embryonic broblast cell line (3T3-J2) on solid substrates (US Patent No 6,133,030) [Bhatia et al, 1997] In this approach, photolithographic techniques were used to pattern collagen I on glass substrates, which served as an adhesive substrate for primary rat hepatocytes After hepatocyte attachment and spreading, 3T3-J2 broblasts were plated, by serum-mediated adhesion, in the remaining intermixed regions.

The versatility of this technique allowed the design of culture con gurations that included variations in homotypic hepatocyte interactions, broblast cell number, as well as heterotypic interactions Cocultures were conducted in which the heterotypic interface could be varied over three orders of magnitude, with the ratio of cell populations remaining constant (See Fig 153) [Bhatia et al, 1999] Total cell numbers were held constant by holding.

Continuation of converse: Give reasons for the labeled inequalities:

102 103 Dp (nm)

= D(P1 ||P2 ).

where bT ( ) = E T and bT ( ) is the derivative of bT ( ) with respect to . The proof of this is left as a problem at the end of the chapter. Example 11.10.2 Let X1 , X2 , . . . , Xn be i.i.d. N( , 2 ), 2 known. 1 Here J ( ) = n/ 2 . Let T (X1 , X2 , . . . , Xn ) = X n = n Xi . Then E (Xn )2 = 2 /n = 1/J ( ). Thus, Xn is the minimum variance unbiased estimator of , since it achieves the Cram r Rao lower bound. e The Cram r Rao inequality gives us a lower bound on the variance e for all unbiased estimators. When this bound is achieved, we call the estimator ef cient. De nition An unbiased estimator T is said to be ef cient if it meets 1 the Cram r Rao bound with equality [i.e., if var(T ) = J ( ) ]. e

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