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necessarily provide results that are more meaningful in a biological context (167, 168, 172) Nonspeci c interactions caused by crowding are unavoidable in vivo, as the crowding itself is an intrinsic property of most or all physiological uid media Therefore, many important aspects of macromolecular behavior in such media cannot be understood without taking the nonspeci c interactions into account The main effect of macromolecular crowding on biochemical equilibria is to favor the association of macromolecules Crowding usually favors aggregation, particularly for slow-folding chains This effect is greater for small polypeptides, since larger proteins have slower diffusion and, therefore, reduced encounter rate (172) The effect of macromolecular crowding on protein behavior can be modeled by using high concentrations of macromolecules that mimic those found in living cells and do not directly interact with the macromolecules being investigated, except via steric repulsion (172).

If these or other big events appear on your horizon, visit a tax professional sooner rather than later You d hate to nd out after the fact that the tax collector wants more than you bargained for

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Commonly used synthetic crowding agents include dextrans, Ficolls [synthetic polymers of sucrose, poly(sucroseco-epichlorhydrin)], PEG, and polyvinyl alcohol Unfortunately, utilization of any of these crowding agents in ESI MS studies at relevant concentrations (>1%) seems to be problematic due to the protein ion signal suppression (as discussed earlier in this section) Another serious problem is caused by the intrinsic heterogeneity of synthetic polymers giving rise to a wide distribution of ion peaks in the ESI mass spectra (see 9 for a detailed discussion of the ESI MS of synthetic polymers), which would almost certainly interfere with the protein ion signal This problem can be eliminated by using inert ubiquitous proteins (such as lysozyme, serum albumin, or hemoglobin) as crowding agents Once again, nano-ESI may become an indispensable tool in such studies due to its increased tolerance to high concentrations of proteins in solution (165) 1143.

it s time to see a tax pro Many people out there call themselves tax experts Some are really just tax preparers If in doubt, your best bet is to visit a tax professional who has completed the Canadian Institute of Chartered Accountants In-depth Tax Course This is a three-year comprehensive course that only those specializing in tax full-time are permitted to take Most students of the course are chartered accountants, but you ll also nd a handful of lawyers and certi ed general or certi ed management accountants as well

Complexity of Macromolecular Interactions in vivo Another important aspect of macromolecular behavior in vivo is the extreme complexity of the interactions due to the very high number of participants in such interactions Throughout most of this book, our attention has been focused on studies that use the reductionist approach to the problem Each biological process is considered as a set of well-de ned steps, or interactions in which the number of players is reduced to a minimum The advantages of this approach are obvious, since it allows a huge many-body problem to be substituted with the analysis of properties of individual key biomolecules and their interactions with a limited number of key partners The implicit assumption here is that if the function and properties of each individual component of a system are characterized, then the functioning of the entire system can be understood by a simple superposition.

TO MAKE A LONG STORY SHORT:

Think of taxes any time big events happen in life Visit a tax professional before the events take place, if possible

As pointed out by Westerhoff and co-workers, this principle is true in theory but in practice is often false because of a widespread nonlinearity in biological.

If one thing can be said about Canadian taxpayers, it s that we re a passive bunch By this I mean that many Canadians are content to accept any assessment issued by CRA, under the assumption that CRA must be right I

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admit, when the government receives your tax return, takes a look at it, and then issues you an assessment notice making changes to the return you ve led, it s easy to assume that you or your tax preparer probably made a mistake when filling out the forms Bad assumption The folks at CRA are prone to making mistakes as often as anyone else

Open Horizon, Inc. Product type: Product name: Web site: E-mail: Address: Phone: Fax: Middleware, secure connectivity Ambrosia, Connection http://www.openhorizon.com info@openhorizon.com 601 Gateway Boulevard, Suite 800 South San Francisco, CA 94080 415-869-2200 415-869-2201

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