Disagreeable reflections

For all of the most disagreeable reflections in the. 1st file, Fo is much greater thanFc. 

A closer look into the. 1st file can help all the most disagreeable reflections are observed much stronger than calculated (F F ) and for all of them I = 3n ... 

Most Disagreeable Reflections ( if suppressed or used for Rfree)... 

There are also many high residual electron density peaks with values of more than 1 e /A. Omission of the most disagreeable reflections with AF /s.u. > 6 (files nonml-03. ) lowers the / -values and also the residual density, but the result is not yet satisfactory. Disorder or solvent molecules are not detectable. 

Most Disagreeable Reflections found in the file nonml-02.1st and saving it as nonml-03.ins. 

However, the number of unique reflections is artificially high 3435, compared to 2302 reflections for the detwinned file. In the list of most disagreeable reflections in the file nonm2-02.1st, most of them still have > Fc. 

As previously discussed, compound form differs markedly between early discovery and the late discovery/development interface. The early discovery compound is poorly characterized as to its crystalline form - it may be nonsolid, amorphous, or possibly crystalline but uncharacterized as to polymorphic form. The late discovery/development interface compound is crystalline as defined by phase-contract microscopy or powder X-ray diffraction, and its polymorphic and salt form is frequently characterized. This difference has profound implications for the design of a discovery solubility assay. The key question is this Is it better to design an early discovery solubility assay as a separate type of experiment, or is it better to try to automate a traditional thermodynamic solubility assay to handle the very large number of compounds likely to be encountered in early discovery Another way to state this question is this Does it make sense to run a thermodynamic solubility assay on poorly crystalline early discovery compounds This is the type of question about which reasonable people could disagree. However, this author does have a distinct opinion. It is much better to set up a distinctively different solubility assay in early discovery and to maintain a clear distinction between the assay type appropriate in early discovery and the assay type appropriate at the late discovery/ development interface. Two issues are relevant to this opinion One relates to the need for a solubility assay to reflect/predict early discovery stage oral absorption and the other relates to people/chemistry issues. 

While we realize that some others will disagree, we suggest that it cannot be automatically assumed that the somatic signs cannot reflect a centrally-mediated emotional or motivational state. For this reason, we refer to them not as somatic signs, but as somatically expressed behaviors. ... 

For imidazoll,2-a]pyridine, two sets of data are shown (from different authors) and the values disagree both in magnitude and positional order (the same is true of the it densities) this reflects the lack of reliability of current MO methods. For pyrrolopyridines (azaindoles) (8.89), the 3-position is predicted to be the most reactive site in each case (83T2851). 

The trends seen for AA, AT and TA steps are also shared for the whole group of sequences included in the RR, RY and YR populations, respectively. With this in mind, one would predict that AT, GC and E4 are good promoter sequences, because they are formed by an alternation of RY steps that produce the appropriate roll profile, and YR steps, which are the most flexible and thereby easier to unstack and bend. Note that the roll profiles are asymmetric, and they show a greater tendency to bend towards the major groove than towards the minor groove. This would be reflected in the anisotropic bendability which was invoked by Kahn and coworkers to explain cyclization efficiency of DNA minicircles [97]. Where we disagree is in the direction of the anisotropy. They propose that MLP is bent towards the minor groove, and that this equilibrium conformation acts as an inhibitor of the formation of unproductive complexes. 

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