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The bile canaliculus constitutes only about 13% of the contiguous surface membrane of the hepatocyte but must function in the ef cient transfer of chemical from the hepatocyte to the bile duct. Active transport proteins located on the canalicular membrane are responsible for the ef cient shuttling of chemicals across this membrane. These active transporters are members of a multi-gene superfamily of proteins known as the ATP-binding cassette transporters. Two subfamilies are currently recognized as having major roles in the hepatic elimination of xenobiotics, as well as endogenous materials. The P-glycoprotein (ABC B) subfamily is responsible for the elimination of a variety of structurally diverse compounds. P-glycoprotein substrates typically have one or more cyclic structures, a molecular weight of 400 or greater, moderate to low lipophilicity (log Kow < 2), and high hydrogen (donor)-bonding potential. Parent xenobiotics that meet these criteria and hydroxylated derivatives of more lipophilic compounds are typically transported by P-glycoproteins. The multidrug-resistance associated protein (ABC C) subfamily of proteins largely recognizes anionic chemicals. ABC C substrates are commonly conjugates of xenobiotics (i.e., glutathione, glucuronic acid, and sulfate conjugates). Thus conjugation

(a)

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will covalently bind lysine residues of any membrane protein, which may, in turn, effectively camou age all or part of the viral receptor.13 30 Direct immunocamou age of viruses was examined using SV40. The capsid of SV40 is primarily composed of viral protein 1 (VP1), which contains 25 lysine residues (Table 16.3). The entire capsid consists of 72 VP1 pentamers, thereby providing a suitable substrate for mPEG grafting.47 Viral lysates were combined with activated mPEG in PBS at a pH of 8.0 at room temperature for 30 minutes. In order to separate unmodi ed and mPEG-modi ed virus, an aqueous polymer twophase system of PEG and Dextran was used.48 PEG 8 kDa (43%, Sigma) was layered over 5% Dextran T500 (Pharmacia) in 150 mM NaCl and 10 mM sodium phosphate buffer, and the viral sample was added. The layers were mixed and allowed to separate for 1 hour at room temperature. In the two-phase system, unmodi ed virus had a greater af nity for the Dextran phase and the interface while modi ed virus separated to the PEG phase. Host cell modi cation was done by the direct overlay of activated BTCmPEG (5 or 20 kDa polymer at concentrations of 0 15 mM) in phosphate buffered saline (pH 7.8) at room temperature for

not only restricts passive diffusion of a lipophilic chemical but actually targets the xenobiotic for active transport across the canalicular membrane.

(b)

Fig. 14.11 TCP run. (a) Packet loss rate and (b) mean queue length as a function of a; (c) queueing delay-packet loss trade-off curve.

Protein Sequences of Virus Receptorsa A. MHC-1 (Cercopithecus aethiops) [Protein ID: AAL34325]

The lungs are highly specialized organs that function in the uptake and elimination of volatile materials (i.e., gasses). Accordingly, the lungs can serve as a primary site for the elimination of chemicals that have a high vapor pressure. The functional unit of the lung is the alveolus. These small, highly vascularized, membraneous sacs serve to exchange oxygen from the air to the blood (uptake), and conversely, exchange carbon dioxide from the blood to the air (elimination). This exchange occurs through passive diffusion. Chemicals that are suf ciently volatile also may diffuse across the alveolar membrane, resulting in removal of the chemical from the blood and elimination into the air.

with performance evaluation works [8, 15, 16] which show that queue length distribution decays more slowly for long-range dependent sources than for shortrange dependent sources. Figure 14.11(c) shows the queueing delay-packet loss trade-off curve for four levels of a. The individual performance points were obtained by varying buffer size while keeping bandwidth xed at the baseline value. The performance curves show that under highly self-similar traf c conditions, the negative effects of self-similarity are signi cantly ampli ed in the packet loss rate regime below 4%. A similar tradeoff relation exists for queueing delay and throughput. The effect of varying bandwidth to obtain the trade-off graphs and evaluation of the marginal bene t of network resources is shown in Figure 14.12. We observe that bandwidth affects a smooth, well-behaved performance curve with respect to self-similarity. It is, in part, due to this behavior that a ``small buffer capacity=large bandwidth'' resource provisioning policy is advocated. 14.4.7.2 Performance Evaluation Under Unreliable Communication Performance evaluations under unreliable, non- ow-controlled transport yield performance results that are signi cantly worse than their reliable, ow-controlled counterparts. In particular, the dependence of throughput-related measures such as effective throughput, packet loss, and packet retransmission is no longer gradual their shapes exhibit a superlinear dependence similar to the mean queue length relation in the reliable communication case. The superlinear dependence of queueing delay on the degree of self-similarity is further ampli ed, and so are trade-off relations between queueing delay and throughput. This is shown in Figure 14.13. 14.5 CONCLUSION

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