Needle search

With these massive amounts of data produced in HTS for combinatorial libraries, tools become necessary to make it possible to navigate through these data and to extract the necessary information, to search - as is said quite often -for a needle in a haystack. 

For those readers who are not yet familiar with mass spectrometry, the introduction provides an explanation of the basics of mass spectrometry and its instrumentation as well as practical aspects and applications in bioanalysis. Next, a block of three chapters shows different affinity selection procedures suitable to identify hits from combinatorial compound libraries. This subject, being metaphorically speaking a search for a needle in a haystack, is of outstanding relevance for big pharma . The techniques described here offer real high throughput capabilities and are implemented already in the routine industrial screening... 

Taxol—One of the most effective modern cancer drugs, came out of a massive government search for new cancer medicines from plants. Taxol is used to treat cancer of the ovary, breast, and certain forms of lung cancer. Taxol comes from the bark and needles of a yew tree. 

The search for small isolated sites of erosion or corrosion can sometimes become like looking for the needle in the haystack. An isolated thin area can be easily missed or skipped over depending on the density of the examination pattern. 

A recent successful application of these methods was the work at Roche on DNA gyrase [146]. The LUDI maps for this site are shown in Fig. 4.6. Pharmacophores derived from these maps were used to search the corporate database using LUDI and Catalyst. Structures were deliberately chosen to be of low molecular weight and were screened at high concentration, so-called needle screening. The subsequent actives were then further developed via structure-based design techniques and medicinal chemistry to give several different series of active compounds. 

Patency of airway, blood pressure, temperature, pupillary retlex and blood glucose concentration need to be monitored repeatedly and a search should be made for evidence of trauma or needle-marks at the time of admission. A careful history and physical examination will give the correct diagnosis in over 90% of cases. Other biochemical tests can help in diagnosis or for the continued monitoring of comatose patients. 

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