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adefovir17 may hasten its use by the viral enzyme This group, as well as changes in the rest of the molecule, bring the process to a halt once incorporated, killing the infected cell The early promise of modi ed nucleosides as compounds to treat HIV infection did not halt the search for candidates from other chemical classes Problems inherent in the nucleoside included the relatively high cost of starting materials, some drugrelated side effects, as well as the observation that prolonged use led to the development of drug-resistant strains By the middle 1980s, laboratories in both the National Cancer Institute18 and pharmaceutical companies had in place high-capacity, semiautomated screens for identifying compounds that protected cells in tissue culture from the effects of HIV A number of compounds were uncovered by these tests that bore no structural relation to the nucleoside (Fig 7).

The sustainable differentiators that register well above the experience baseline are people driven. These are employees who care to do their best, be it in innovating the products or services or delivering outstanding customer service. Companies that seek lasting, sustainable, differentiating attributes must reexamine their employees experiences to determine how to build humandriven attributes into their value proposition consistently. This goes beyond the tired old story of the one employee who dared to break the rules. This is about building an entire operation of rule breakers. It requires a different culture and conditions for such behavior to be nourished and cultivated.

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In spite of their chemically very different structures, nevirapine,19 delaviridine,20 and efavirenz21 all act by a very similar mechanism Each of these molecules binds directly to a site on the reverse transcriptase enzyme given the name non nucleoside reverse transcriptase inhibitor (NNRTI) binding pocket It has been shown that the binding interaction of the drugs with this site leads to distortions of the three-dimensional shape of the enzyme; this change in con guration impedes enzyme function22 The relatively low toxicity of the compounds comes from the fact that they have no af nity for corresponding enzymes involves in DNA replication of normal cells Although effective in vitro, the NNRTIs elicited the evolution of resistant strains even more quickly than the nucleoside transcriptase inhibitors They are, as a consequence, almost always administered as part of a multidrug cocktail.

The protein coat that covers the virion DNA or RNA strand plays a very important role in the agents propagation It is that coat that rst provides protection for the genome from environmental damage in its time between hosts Some plant virions for example remain infective for years The protein coat also provides the structures and biochemical mechanisms required for cell entry Many viruses such as HIV have special recognition sites on the protein coat for surface features on the host immune cell white cells that are their target Synthesis of the protein coat is thus an essential.

margins (relative to the industry), and good capital ef ciency.15 (An example of capital ef ciency is an airline carrier getting the most from its eet.) While most everyone understands the rst two in uences, the last one is less well understood. Here is an alternative variation of the economic pro t formula that does not change the calculated answer from the prior equations, but it forces you to think more deeply about the equation s elements: Economic Pro t (EP) = [(Pro t*/average invested capital) WACC] average invested capital = [ROAIC WACC] average invested capital where WACC = the lenders and equity owners weighted average cost of capital ROAIC = return on average investment in capital, calculated as follows: ROAIC = Pro t Margin [Pro t */Revenue] Velocity [Revenue/average invested capital] = Pro t*/average invested capital A review of the equations forces a company to evaluate its ability to generate more revenues from its invested capital (velocity) in conjunction with its pro t margins, to assess its broader ROAIC percentage s annual performance which in turn can affect its economic value or economic pro t.

This last term is the nth-order spur with amplitude given in the spur-level table. The terms not shown are at lower frequencies. This frequency j also occurs in other terms in Eq. (4.1) but with amplitudes raised to higher powers. As a result, at suf ciently low signal levels the term shown in Eq. (11) dominates. For n odd, we can see from Table P.1 that the strongest IMs have i = (n 1)/2. These are also the most troublesome producing frequencies near 1 (t) and 2 (t). We can expand the corresponding term in Eq. (7), by applying the process that we used to obtain Eq. (11) to each of its two cosines, to give vn,(n 1)/2 ( (t)) = An c[n, (n 1)/2] cos(n 1)/2 1 (t) cos(n+1)/2 2 (t) = + An c[n, (n 1)/2] (12)

If the IF is to be detected, that is, if its power is to be measured or if modulation is to be extracted from it, all spurious signals should be below some threshold.

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