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While there certainly can be gray areas when monitoring hardware (for example, it can be difficult to tell the difference between a down system and one that is running so slowly that it does not reply to queries), it is still easier to monitor hardware than applications There are several ways to monitor the health of an application The easiest, most general, and weakest monitoring method is to examine the system s process table The process table is a list of the programs that are running on a system at a particular point in time The process table offers information such as the amount of memory and CPU each process is consuming, when the process began running, and so forth (The precise set of information will vary from operating system to operating system, and often on the command-line arguments or other options that determine exactly how the command will run.

chain accesses to the application and calls to the core services in such a way as to generate the set of corresponding events in the infrastructure. Together, the executable program that comprises the user code, the API and the core will make up the adapter.

Figure 8.7. Ribosome display is used to display binding molecules; the noncovalent complex (ribosomes, protein, and mRNA) is stabilized by changing the medium composition and lowering the temperature (a). In mRNA peptide fusion, the link between genotype (mRNA) and phenotype (protein) is covalent (b).

) The process table does not provide any indication, however, that the process is running properly There is no way to tell from the process table if the application will respond to a query, or if it is hung or in some other way operating improperly All the process table will tell you is whether the process is running Since the process table is not reliable, there must be a better way to find out if an application is running properly There is, but it is much harder to implement You must query the application itself and see that you get an appropriate and timely response For some applications a query is easy For others it can be almost impossible Querying a database server is easy, for example; accepting queries is a fundamental part of what database servers do.

If you have an application that sends a basic SQL query to a database and watches for a response, you have a simple monitor for that database If the database doesn t respond to the test query, it won t respond to genuine user requests..

bacterial cell (2.6-mm diameter), and contain, on average, a single genetic variant. Advantages of this method when compared with cell expression methods include a higher number of useful compartments per milliliter of solution, and a fully controllable expression system.17 One disadvantage is the lack of a direct genotype phenotype linkage, which would be problematic if conditions favored coalescence of microcompartments. 8.5. IDENTIFICATION AND SELECTION OF SUCCESSFUL VARIANTS Screening is usually de ned as the identi cation of variants with the desired properties, whereas selection is the enrichment of desired variants in a new, smaller molecular library. Screening is limited in practice to 105 107 sequences, since it requires the assay of each variant, whereas selection (e.g., panning using immobilized ligands) may be used on much larger libraries for enrichment.

16

Screening commonly relies on the detection of an optical change, such as an absorbance or luminescence increase, via activation of a reporter gene, such as the b-galactosidase or luciferase gene. In eukaryotic cells, the so-called two hybrid 18 system has been described; it is used to screen and select for protein protein interactions. In the two-hybrid system, transcription of a reporter gene is activated through the interaction of two proteins, which reconstitute a transcription factor composed of DNA-binding and DNA-activation domains; commonly used reporters genes are LEU2 or HIS3 from yeast. When protein protein interaction occurs, transcription is activated, conferring to the cell the capacity to grow on minimal media (without leucine or histidine), allowing selection. Some highthroughput techniques are based on cell culture in low volume, high-density microtiter plates (6144 wells with volumes of 1 2 mL or less).19 Selection is based upon the functional properties of the evolved protein (phenotype). Binding to antigen immobilized in the wells of a microtiter plate or on the surfaces of magnetic beads are frequently used approaches. Flow cytometry sorting systems, some of which can sort up to 108 cells/h, represent a promising new class of selection technique.