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The initial rate of reaction is therefore directly proportional to initial substrate concentration at low [S], and can be used to quantitate substrate. This is shown in the initial linear region of the plot of reaction rate against substrate concentration in Figure 2.5, where the slope in this region is equal to Vmax =Km . The second simpli cation of Eq. 2.17 occurs at high substrate concentration. If the substrate concentration greatly exceeds Km , then S = Km S % 1 and n % Vmax . Under these conditions, n Vmax k2 E 0 2:19

When an application runs too slowly, that may still be an availability issue, since the user cannot get his job done in a timely manner We also take a business-oriented approach, never losing sight of the fact that every bit of protection whether mirrored disks, backup systems, or extra manpower for system design costs real money We have tried to balance costs and benefits, or at least help you to balance costs and benefits After all, no two sites or systems are the same What may be important to you may not matter a bit to the guy down the hall One of the hardest jobs facing designers of highly available systems is scoping out the costs of a particular level of protection, which are frequently higher than the people running the business would like.

In an era where computer hardware prices shrink logarithmically, it s hard to explain to management that you can t get fault-tolerant system operation at desktop PC prices Our goal is to help define the metrics, the rules, and the guidelines for making and justifying these cost/benefit tradeoffs Availability is commonly measured in nines 9999 percent uptime is four nines Our goal is to help you increase the number of nines you can achieve within your engineering constraints, and the number you can afford within your budget and cost constraints At the same time, we ll question the industry s dependence on nines as the only gauge of availability We ll frequently refer to cost/benefit or cost/complexity trade-offs.

The initial reaction rate is now independent of [S], as shown in the plateau region of Figure 1.5. The rate now depends linearly on enzyme concentration, and a plot of initial rate against total enzyme concentration will have a slope of k2 . Thus, at high substrate concentrations, initial reaction rates can be used to determine enzyme concentrations. In practice, Eq. 2.18 may be used if S < 0:1Km , while Eq. 2.19 is useful if S > 10 Km . Remember that the steady-state assumption underlying these expressions is only valid if S ) E 0 , and that, in practice, substrate concentrations in excess of 103 E 0 are used. 2.5.2. Experimental Determination of Michaelis Menten Parameters Equations 2.18 and 2.19 show that the two regions of analytical utility in the rate versus substrate concentration pro le of an enzyme occur at S < 0:1 Km (for substrate quantitation) and S > 10 Km (for enzyme quantitation). In developing a new assay, or in adapting an established assay to new conditions, it is thus important to establish the Km value of the enzyme. It is of practical importance to also establish

Such decisions abound in technology-driven companies: Buy or build Faster time to market or more features Quick and dirty or morally correct but slower Our job is to provide some guidelines for making these decisions We ll try to avoid taking editorial stances, because there are very few absolutes in engineering design..

9

Figure 2.7. Eadie Hofstee plot for n measurements with varying [S].

network, using a name service such as DHCP, NIS, or DNS. Networked filesystems like NFS and Windows SMB services, along with naming, directory, and security services, add to complexity of network operation. A failure in any of these services, caused by any of the failures previously noted or by a failure in the system software providing the service, usually results in a network outage. Latency. Excessive load, broadcast, Address Resolution Protocol (ARP) storms, or a denial-of-service attack render a network nearly useless as the useful throughput drops precipitously. While not a network failure per se, latency creates the illusion of an outage to the nodes connected to it, and it furthers our premise that performance is an aspect of availability. The next sections explore the physical and logical failures in more detail, providing first-level detection mechanisms. Using this basis, we describe several approaches to building reliable networks tolerant of these failure modes.