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ionization camera over a metallic plate. When a high-energy beam impacts the sample (Fig. 15.2), a fraction of its energy is transferred, mainly to the solvent molecules; in this way excessive analyte fragmentation is avoided. Some analyte and matrix molecules are desorbed to the gas phase, and if they are not already charged, they can be charged in the gas phase by reaction with the surrounding gas-phase ions. Charged molecules are propelled electrostatically to the mass analyzer and, eventually, reach the detector. Fast atom bombardment was the rst soft ionization method, and was introduced in 1981. One year later, molecules as large as human insulin were analyzed, and became the benchmark for resolution and sensitivity.5

If the required savings was $1 million, then: CD = 1,105,160 / 8,943.5 = $123.57 per minute or $7,414.28 per hour

This requires the definition of technical architectures and communication modes, but also involves supervising exchanges: what data in what transmission delay, what restart parameters in case of incidents, what solutions for maintaining the continuity of activities Enterprises assemble applications developed by their own IT with commercial software packages, on varied hardware, and use high-performance networks for communication, which in turn necessitates acquiring tools to supervise services This is not an easy message to convey to General Management, and an economic approach is expected to justify such investments: increased control in exchange for fewer incidents To succeed here, a certain maturity in tracking quality and measuring the financial and client consequences of incidents is required Finally time.

Table 3.4 Cost of Downtime and Return on Investments REQUIRED SAVINGS $0 $100,000 $250,000 $500,000 $1,000,000 $2,000,000 $5,000,000 COST OF DOWNTIME PER MINUTE (C D ) $11.76 $22.94 $39.71 $67.66 $123.57 $235.38 $570.82 RETURN ON INVESTMENT N/A 95.1% 237.7% 475.8% 950.9% 1,901.9% 4,754.7% DAYS TO PAYBACK ON A FIVE-YEAR INVESTMENT N/A 1,919 days (Just over five years) 768 days (A little over two years) 384 days 192 days 96 days 38 days

Figure 15.2. FAB ionization source. Total volume of sample and matrix is typically at the microliter (mL) level.

Determine your required savings and solve for the required cost of downtime to see if it s reasonable for your environment. However, if you are seriously considering implementing measures to increase your availability, it s a good bet that your cost of downtime exceeds $11.76 per minute ($705 per hour) by quite a bit.

Taken to its logical limit, the definition of high availability cited in the preceding text implies that every system can potentially have a different threshold of availability before it achieves high availability. This is absolutely correct. Computer systems vary widely in their tolerance of downtime. Some systems cannot handle even the briefest interruption in service without catastrophic results, whereas others can handle brief interruptions, but not extended ones, and others can even handle extended outages while still delivering on their required returns on investment. Consider the following examples:

15212 Electrospray Ionization Electrospray is an especially soft ionization method, capable of generating molecular ions (without fragmentation) from biological macromolecules present in aqueous solution For this reason, it has received increased attention in terms of its applicability to protein and DNA analysis Figure 153 shows a diagram of this ionization source The hollow stainless steel needle is maintained at a few kilovolts (kV) relative to the chamber walls and the cylindrical cathode surrounding it The liquid sample enters at a rate of 1 20 mL/ min through the needle, but lower ow rates (10 100 nL/min) are becoming more common in modern instrumentation The electric eld at the needle tip disperses the liquid by Coulombic forces into a ne spray of charged droplets These droplets migrate in the eld toward the glass capillary inlet.

Computers whose failures cause a loss of human life, such as hospital life support systems or avionics systems, generally have the highest requirements for availability. Slightly less critical computers can be found running e-commerce web

A ow of drying gas (typically N2 at 100 mL/s) evaporates the solvent from the droplets, so that their diameter decreases, and the surface charge density on each droplet increases When this surface charge density reaches the Rayleigh limit, the Coulombic repulsion is approximately equal to the surface tension, and the droplet explodes into smaller droplets This process continues until the eld due to the surface charge density is strong enough to ionize the macromolecules, which are then propelled through the skimmer and into the magnetic sector Most biological macromolecules that are ionized in this manner are multiply charged 15213 Matrix-Assisted Laser Desorption/Ionization In this ionization method, the analyte is combined with a matrix compound, in a molar ratio of $1:1000, and evaporated onto a metallic plate The matrix compound is chosen to absorb strongly at the laser wavelength used.

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