Optimization protocols

Presented in Table 1 is a list of the parameters in Eqs. (2) and (3) and the type of target data used for their optimization. The infonnation in Table 1 is separated into categories associated with those parameters. It should be noted that separation into the different categories represents a simplification in practice there is extensive correlation between the different parameters, as discussed above for example, changes in bond parameters that affect the geometry may also have an influence on AGsoivation for a given model compound. These correlations require that parameter optimization protocols include iterative approaches, as will be discussed below. 

R Abagyan, P Argos. Optimal protocol and trajectory visualization for conformational searches of peptides and proteins. I Mol Biol 225 519-532, 1992. 

MicrocrystalUne zeolites such as beta zeolite suffer from calcination. The crystallinity is decreased and the framework can be notably dealuminated by the steam generated [175]. Potential Br0nsted catalytic sites are lost and heteroatoms migrate to extra-framework positions, leading to a decrease in catalytic performance. Nanocrystals and ultrafine zeolite particles display aggregation issues, difficulties in regeneration, and low thermal and hydrothermal stabilities. Therefore, calcination is sometimes not the optimal protocol to activate such systems. Application of zeolites for coatings, patterned thin-films, and membranes usually is associated with defects and cracks upon template removal. 

With modern multislice scanners and optimized protocols," CTA images can provide excellent visualization of the primary intracranial arteries (i.e., the proximal anterior, middle, and posterior cerebral arteries), their smaller secondary... 

For the installation of the pyrrolidinylethanol moiety 10 on the aryl group, we first tested Buchwald s Cu-catalyzed conditions with 10, aryl iodide 12, Cs2C03, Cul and 1,10-phenanthroline at 110°C in toluene to prepare the penultimate 49 [14a], The reaction was very slow, giving only 5-10% conversion even after 2 days. The reaction was faster at higher temperatures but two impurities 50 and 51 were observed (Scheme 5.14). To find the optimal conditions, xylene and diglyme were tested as solvents, lithium, potassium and cesium carbonates were screened as bases and 2,2 -bipyridy], TMEDA and l-(2-dimethylaminoethyl)-4-methylpiperazine were examined as ligands. The optimized protocol was identified as 10mol% of... 

Castrillo, J. L. Hayes, A. Mohammed, S. Gaskell, S. J. Oliver, S. G. An optimized protocol for metabolome analysis in yeast using direct infusion electrospray mass spectrometry. Phytochemistry 2003, 62, 929-937. 

Gill et al.21 Archival FFPE spinal cord tissue both paraformaldehyde-fixed frozen rat spinal cord tissue and paraffin-embedded same tissue To establish an optimal protocol for detection of low-abundance protein (NeuN) in human spinal cord FFPE tissue sections, testing three AR solutions of pH 6, alkaline, and acidic buffer, with three heating conditions 95,100, and 105°C Heating FFPE tissue sections in an alkaline buffer yields most effective AR-IHC staining results. 

Shi SR, Cote RJ, Yang C, et al. Development of an optimal protocol for antigen retrieval a test battery approach exemplified with reference to the staining of retinoblastoma protein (pRB) in formalin-fixed paraffin sections. J. Pathol. 1996 179 347-352. 

In order to develop a more efficient, and practical protocol of DNA extraction based on heating procedure, we performed a serial study to test various chemicals in a combination with heating, in order to identify an optimal protocol. As a result, we developed a simple protocol of boiling FFPE tissue sections in a solution of sodium hydroxide (NaOH) or potassium hydroxide... 

First, a limited study was performed using breast cancer tissue to establish an optimal protocol of DNA extraction for a-CGH analysis that would allow comparison of a-CGH results after boiling in different solutions three pH values of 7, 9, and 12 of Britton and Robinson buffer solution, and a 0.1 M sodium hydroxide solution. DNA samples extracted from frozen and from FFPE tissue sections by a nonheating protocol were employed, and the results were compared a protocol of boiling samples in 0.1 M sodium hydroxide gave optimal results. 

Figure 5.1 Diagrammatic explanation of standardization of IHC via AR and test battery to achieve a maximal retrieval level by an optimal protocol of AR. The intensity of IHC (axis y) is inversely correlated with the time of formalin fixation (axis x) as indicated by a reduced slope. Three arrows indicate a potential maximal retrieval level that may equalize the intensity of IHC to a comparable result for routinely processed, paraffin-embedded tissues with various time of fixation. Reproduced with permission from Shi et alHistotechnol. 1999 22 177-192.

Based on the similarity of formalin-induced chemical modification between nucleic acids and proteins, the efficiency of heating protocols for DNA/RNA extraction has been demonstrated (see Chapter 3 for detail). Basic AR principle including heating condition and pH value of AR solution as well as certain chemicals may play roles to establish optimal protocols. 

Consequently, which strategy is utilized in reaction optimization experiments is highly dependent on the type of instrument used. Whilst multimode reactors employ powerful magnetrons with up to 1500 W microwave output power, monomode reactors apply a maximum of only 300 W. This is due to the high density microwave field in a single-mode set-up and the smaller sample volumes that need to be heated. In principle, it is possible to translate optimized protocols from monomode to multimode instruments and to increase the scale by a factor of 100 without a loss of efficiency (see Section 4.5). 

Wadhwani P, Afonin S, Ieromino M, Buerck J, Ulrich AS (2006) Optimized protocol for synthesis of cyclic gramicidin S starting amino acid is key to high yield. J Org Chem 71 55-61... 

The optimized protocol has also been applied to a wide range of open-chain and cyclic dienes (for selected examples, see Table 11.11) [113], The latter generally give higher yields than non-terminal alkenes and cycloalkenes, except for strained ones such as JV-benzyl-pyrroline, cyclopentene, and norbornene (Table 11.10, entries 20—22). 

A published synthetic scheme (36) of a four component Ugi reaction (Fig. 6) has been used as an example to demonstrate the use of the SA optimization protocol for the simultaneous optimization of multiple properties. Because two of the four components are fixed in the scheme, only two diversity sites remain for optimization. These two sites come from primary amines (R1NH2) and aldehydes (R2CHO), respectively. We have collected from the ACD (Available Chemical Directory) structures of primary amines and aldehydes available from ALDRICH and LANCASTER. Compounds with reactive or unstable structural patterns are removed. As a result, 779 primary amines and 246 aldehydes are considered. 

Following their optimized protocol, the Rueping group prepared various... 

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