Flexible technique

NMR is a remarkably flexible technique that can be effectively used to address many analytical issues in the development of biopharmaceutical products. Although it is already more than 50 years old, NMR is still underutilized in the biopharmaceutical industry for solving process-related analytical problems. In this chapter, we have described many simple and useful NMR applications for biopharmaceutical process development and validation. In particular, quantitative NMR analysis is perhaps the most important application. It is suitable for quantitating small organic molecules with a detection limit of 1 to 10 p.g/ml. In general, only simple one-dimensional NMR experiments are required for quantitative analysis. The other important application of NMR in biopharmaceutical development is the structural characterization of molecules that are product related (e.g., carbohydrates and peptide fragments) or process related (e.g., impurities and buffer components). However, structural studies typically require sophisticated multidimensional NMR experiments. 

Raman spectra encode information about a sample s molecular stracture and chemical enviroiunent. Fortunately, that information is readily accessible since Raman speetroscopy is an extremely flexible technique, both in what it can measure and how the measurements ean be made. 

SIMCA is a very flexible technique since it allows variation in a large number of parameters such as scaling or weighting of the original variables, number of components, expanded or contracted score range, and confidence level applied. 

Systematic optimization of the Universal-IPCR protocol revealed the full potential of the flexible technique. The research group of Watanabe and coworkers, introduced in Section 3.1 with the detection of TNF -a [34, 39, 80], has excelled in adaptation of this protocol to various antigens. 

Sedimentation FFF, applied in the above manner, yields highly detailed size distribution curves. It is convenient and accurate. Importantly, sedimentation FFF is a highly flexible technique. It can be adapted to nearly all particle types in virtually any suspending medium. It yields particle density as well as size and size distribution. Our recent work has shown that it can be used to probe both size and density distributions in complex colloids, defined as systems having colloidal particles of variable chemical composition. Complex colloids are important in many biological and environmental studies. 

Many different types of QSAR models and chemical descriptors for a wide range of endpoints are developed and published over the years. This makes QSAR a very flexible technique to be adapted for many different situations and a quite powerful technique that can provide a wealth of information. This has also a great potential for new QSAR models with every new experimental data. 

A Flexible Technique for Process System Safety and Reliability Analysis... 

This process applies not only to the production of acetone, but more generally to the conversion of aliphatic secondary alcohols to the corresponding ketones. It constitutes a highly flexible technique, making it possible to treat isopropanol and 2-butanol in the same plant, in successive runs. 

Depending on the experimental design, the number of Abs involved in the immunocomplex formation reaction is varying. A t-Ag, like a bacteria toxin, can be directly immobilized on a reaction substrate and can be quantified with a labeled detection antibody (d-Ab) in a direct immunoassay, involving a single t5q)e of Ab. This technique is however limited, since t-Ags for direct surface immobilization have to be available. A more flexible technique, called sandwich immunoassay, consists to flank the t-Ag to be detected between a capture antibody (c-Ab) linked to a reaction substrate and a labeled d-Ab (see Fig. 3b). In this technique, the t-Ag is specific for both c-Ab and d-Ab. Also an enzyme can be used to label the d-Ab, and, in... 

In Japan and Europe there is increasing demand for light distillates for producing petrochemicals and increasing governmental pressure to lower the sulfur content of residuals. The H-Oil process represents a flexible technique to (1) lower the sulfur content of residuals, and (2) maximize the yield of light distillates from low value residuals, or (3) simultaneously and economically satisfy both these objectives. 

An interesting data structure, called flexibility tree, can be employed in the search for the docked complex structure and it allows to combine several flexibility techniques [95]. The data structure hierarchically encodes the flexibility of a protein in variables that allow several protein parts to experience different kinds of moves. Flexibility of domains may be described via normal mode or hinge motions, and side chains are allowed to explore rotameric states. Flexibility trees for protein and ligand are implemented in Flip Dock that provides a genetic algorithm to optimize the variables to gain an induced fit complex ]96]. 

Nuclear magnetic resonance is a flexible technique with many applications [1, 2]. For substances dissolved in solution, NMR observation of H, N, and... 

The engineer designing and building equipment to restore contaminated solvent to a reusable condition has the full range of imit operations at his disposal. However, it is most likely that he will choose distillation, which exploits differences in volatility, as the most effective and flexible technique for his purposes. 

Production of preformed nanoparticles in the gas phase Several methods have been found to produce gas-phase nanoparticles. However, they all involve the production of a supersaturated metal vapor that condenses into particles. This method is the most flexible technique for the synthesis of metal nanoparticles and it is the way to produce tightly mass-selected nanoparticles of virtually any material or alloy in environments ranging from free particles... 

The study of epitaxial interfaces between crystals of different nature is an example of this flexible technique. The interface is modeled by creating two slabs and letting them interact to form a sort of supra-slab model (i.e., a wafer), as shown schematically in Figure 43. Care must be paid to the lattice mismatch because the 2-D unit cells, with different size, must match at the interface. 

Model checking can be seen as a more flexible technique as it allows the veri-flcation of temporal properties, whereas FSM equivalence checking is restricted to showing that two sequential circuits behave identically. It is well suited for modeling and verifying fully-synchronous systems which usually require the verification of general safety and liveness properties of type it always holds that.. sometimes it will happen that... . Transition systems are represented by temporal structures. A prominent and widely used implementation of symbolic CTL model checking is the SMV system (K.L. McMillan 1993). 

While the above characteristics and advantages have been discussed specifically in reference to thermal FFF, much the same can be said in regard to the other FFF subtechniques, including sedimentation FFF, electrical FFF, and flow FFF. All of these are flexible techniques subject to ready optimization. Their application to polymers will be described after establishing the necessary theoretical framework for FFF. 

SPE dominates in extraction of pesticides from water samples and it represents presumably the most flexible technique for clean-up of food extracts. SPME and SBSE use a fused-silica fiber or a stir bar, respectively, coated by a sorptive material (usually polydimethylsiloxane, PDMS, or its modifications) for partition (i.e., not complete isolation) of analytes. These techniques are convenient and fast however, their application in quantitative MMRMs for analysis of pesticides in complex food samples is rather limited. The main disadvantages relate to strong matrix effects (matrix-dependent partition of analytes and deterioration of the coating by irreversible adsorbed matrix components), insufficiently wide polarity range to extract diverse pesticide residues, and variability of method sensitivity for different analytes depending on their partition coefficients. 

SPOT-synthesis is a facile and very flexible technique for the simultaneous parallel solid phase chemical synthesis. Series of compounds or compound... 

Neutron scattering is a very flexible technique, which allows to probe structures with sizes from the near atomic to the near micrometre scale. This made SANS a method of choice when the hierarchical structure of complex materials must be elucidated, especially in conjunction with other techniques such as WAXD, SAXS or light scattering. ... 

The construction and organization of surface structures on a nanoscale level is fundamental for the growth of surface with novel and valuable properties. Using self-assembly of macromolecules to form surface nanopatterns is rising as a promising and flexible technique [4-11]. One of the main advantages of this process is that large surface areas can be customized promptly and at relatively low cost. 

Molecular combing is a flexible technique, in that many different substrates have been used, including gold, silicon, silica, - ... 

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