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The second step is a site-speci c transportation of the drug, meaning that the drug-loaded BCP micelle should be selectively captured by the target (pathological sites) The third step is that once arrived on the target the BCP micelle opens the door to allow the drug to be released While the stable encapsulation of drug is crucial for giving the nanocarrier the time required to ferry the drug to the target, it could also render the drug release on the target more dif cult at a later time For each of the three steps, there has been much research effort aimed at developing effective strategies For the stable encapsulation, the crosslinking of BCP micelles is useful to provide the structural integrity and to slow down the leakage of the drug through crosslinked polymer chains (Thurmond et al, 1996).



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The server application provides remote objects with operations that neither have a return value nor report exceptions. E E E In many situations a client application needs to invoke an operation on a remote object merely to notify the remote object of an event. The client does not expect a return value. Reliability of the invocation is not critical, as the invocation is used merely as a notification. Consider a simple logging service implemented as a remote object. Clients use it to record log messages. Recording of log messages must not influence the execution of the client. For example, an invocation of the logging service must not block. Loss of individual log messages is acceptable. Such a scenario is quite typical for distributed implementations of patterns such as Model-View-Controller [BMR+96] or Observer [GHJV95], especially if the view or observer is notified constantly and old data is stale data. Therefore: Provide FIRE AND FORGET operations. When invoked, the REQUESTOR sends the invocation across the network, returning control to the calling client immediately. The client does not receive any acknowledgement from the invocation of the operation either for success or failure.





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Sample output: The soft labels appear. Press Enter and they reappear with color applied. If the slk_touch() was not issued in line 24, then the new color attributes would not have been seen. (Comment out that line, and recompile to see.)

slk_refresh(), touchwin()

For the sitespeci c transportation, the functionalization of the micelle shell with a targeting ligand that can be recognized by a receptor highly exposed by the target remains the most appealing approach (Nasongkla et al, 2006) Finally, to release the drug quickly or in a controlled fashion after the micelle arrives on the target, the micelle should be structurally disrupted To this regard, a large number of BCP micelles have been designed to be able to react to an external stimulus, most of which are sensitive to pH change (Bellomo et al, 2004; Bae et al, 2003; Gillies and Frechet, 2003) This exploits the fact that tumor tissues are known to be slightly acidic (pH B68) and the endosomal and lysosomal compartments of cells have even lower pH (pH B5 6) with respect to the physiological pH 74 (Haag, 2004; Gillies and Frechet, 2003).

standend()

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When the client invokes a FIRE AND FORGET operation, the REQUESTOR marshals the parameters and sends them to the server.

If BCP micelles contain acid-labile bonds in their structures, inside the cells, the acidic pH can break those chemical bonds and the structural disruption of the micelle can lead to the release of the loaded drug (Gillies and Frechet, 2003) Thermosensitive BCP micelles have also been much studied (Qin et al, 2006; Schilli et al, 2004; Chung et al, 2000) Like pH, change in temperature is also an event that polymer micelles can encounter in the body If the BCP contains, for example, a poly(N-isopropylacrylamide) (PNIPAAm)based hydrophilic block whose lower critical solution temperature (LCST) can be adjusted to be above 371C through copolymerization with a hydrophilic comonomer (Taillefer et al, 2000), its micelle can be stable at ToLCST, but disrupted by the phase separation at TWLCST.

int standend(void); int wstandend(WINDOW *win);

The function has no arguments. Refer to the w entry later in this appendix for information on the win argument.

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