Quantitative innovations

Nanophotonic devices have several unique features, by which their predominance over conventional photonic devices has been established for application to next-generation information processing systems. One feature is undoubtedly their nanometer-scale dimensions beyond the diffraction limit, which is an example of a quantitative innovation of optical technology. However, it should be noted again that the true nature of nanophotonic devices involves their ability to realize qualitative innovations, originating from their unique features. These features are ... 

An important point is that these advances have been complemented by the concomitant development of innovative pulse-characterisation procedures such that all the features of femtosecond optical pulses - their energy, shape, duration and phase - can be subject to quantitative in situ scrutiny during the course of experiments. Taken together, these resources enable femtosecond lasers to be applied to a whole range of ultrafast processes, from the various stages of plasma formation and nuclear fusion, through molecular fragmentation and collision processes to the crucial, individual events of photosynthesis. 

The latest innovation is the introduction of ultra-thin silica layers. These layers are only 10 xm thick (compared to 200-250 pm in conventional plates) and are not based on granular adsorbents but consist of monolithic silica. Ultra-thin layer chromatography (UTLC) plates offer a unique combination of short migration distances, fast development times and extremely low solvent consumption. The absence of silica particles allows UTLC silica gel layers to be manufactured without any sort of binders, that are normally needed to stabilise silica particles at the glass support surface. UTLC plates will significantly reduce analysis time, solvent consumption and increase sensitivity in both qualitative and quantitative applications (Table 4.35). Miniaturised planar chromatography will rival other microanalytical techniques. 

The computer age has brought about considerable innovation in the operation of laboratory instrumentation. One consequence of this is the wider acceptance and utilization of the optical microscope as a quantitative analytical instrument. A brief literature survey illustrates the diversity of disciplines and optical methods associated with the development of computer interfaced optical microscopy. This is followed by a description of how our methods of fluorescence, interferometry and stereology, nsed for characterizing polymeric foams, have incorporated computers. 

Customer delight is a key requirement for consumer products. For example, the hand-feel of a fabric is an important measure of its quality. There exist many challenges to determine these quality factors in a more scientific way. However, even if only a semi-quantitative measurement can be devised, this can yield insights on how the underlying material or structural attributes control the quality factor. These insights can in turn be used to formulate innovative products. 

Another recent innovation is the QTrap mass spectrometer. The QTrap MS system combines the capabilities of a triple quadrupole mass spectrometer and a linear ion trap mass spectrometer into one MS system. Initially, the QTrap MS was used primarily as a tool for metabolite identification studies [34, 35, 38]. As reported by Li et al. [138], the QTrap MS can also be used as an excellent system for the quantitative analysis of discovery PK samples. The advantage of the QTrap MS system for quantitative analysis is that it can be used to look for plasma metabolites of the NCE and provide an easy way to monitor them while providing the quantitative data on the NCE. 

There is apparently still a complete lack of operationalisable, qualitative and/or initially quantitative indicators (e.g. in an ordinal scale) to determine the level of innovation. We made an attempt at defining these (cf Chapters 4.3 (Hypotheses) and 5.1.1), but did not have sufficient time to pursue this matter in more detail. 

Understandably, the impurity profiles of the same drug substance produced by different S3mthetic routes will differ qualitatively and quantitatively. This is commonly observed when a drug substance is provided by different suppliers. For example, the HPLC chromatograms from samples of fluoxetine hydrochloride obtained from four different suppliers show the differences in the impurities produced by the presumably different synthetic routes (Figure 1.1) [7]. Supplier A is the innovator company. Supplier B is in Italy, and Suppliers C and D are in India. 

The project portfolio enables an overview on the ongoing research activities. Numerous economic and technical parameters have been proposed to provide a meaningful picture. Examples are attractiveness, strategic fit, innovation, gross/net present value, expected profits, R D expenditures, development stage, probability of success, technology fit, and realization time. Most of these parameters cannot be determined quantitatively, at least during the early phases of a project. 

Statistical and computational methods have been used to quantify structure-activi relationships leading to quantitative structure-activity relationships (QSAR). The concqpt of QSAR can be dated back to the work of Crum, Brown and Fraser from 1868 to 1869, and Richardson, also in 1869. Many notable papers were published in the period leading up to the twentieth century by men such as Berthelot and Jungfleisch in 1872, Nemst in 1891, Ov ton in 1897 and Meyer in 1899 (7). Professor Corwin Hansch is now regarded by many as the father of QSAR, because of his work in the development of new and innovative techniques for QSAR. He and his co-woikers produced a paper that was to be known as the birtii of QSAR, and was oititled "Correlation of biological activity of phenoxyacetic acids with Hammett substituent constants and partition coefficients" (2). 

Particulate quantitative air sampling will be performed using device CI-500 innovation laser particle counter (serial no. mentioned on the monitoring format) according to SOP (provide number)... 

Systemic changes were investigated quantitatively via questions about environmental affairs groups in the firms. About 65X of interviewed firms had such groups. Although the primary purpose of environmental affairs units appears to be to aid the direct compliance effort, their new capabilities may have important long-term implications for the pattern of innovation in the primary lines of business. ... 

EPA is conducting an extensive study in order to more fully understand the impact of the premanufacturing review program on innovation in new chemicals. Although the lack of data in this area is discouraging, we are doing the best we can to quantitatively evaluate the effect on both the input (in terms of R D dollars) and the output (in terms of new chemical substances) of the innovative process. 

The preferred method for reduction and acetylation is that of Blakeney et al. (1983). Their innovation was to use DMSO as the solvent for sodium borohydride and to use 1-methylimidazole as the catalyst for the quantitative acetylation of alditols in the presence of borate. Methods commonly used to prepare alditol acetates prior to this had incorporated steps in which the borate was removed by repeated evaporations with methanol, which was slow and tedious. 

More innovative methods for examining relationships between individual LOE for the SQT include quantitative estimation of probability derived from odds ratio (Smith et al., 2002) and meta-analysis resulting in pooled, empirically derived P-values (Bailer et al., 2002). Comparison of odds ratio and meta-analysis with PCA for clustering sites into groups of similar impact (Reynoldson et al., 2002a) revealed similarities and differences. The differences between the three methods (PCA, odds ratio and meta-analysis) were ascribed to three factors, which almost certainly apply to all integrations the variables selected the manner in which information is combined within a LOE and, the statistical methodology employed. 

Rapid advances have been made in proteomic research, with growing success in protein quantitation utilizing MS technologies [74-76]. The quantitative tools from proteomics and other analytical innovations have great potential to be translated to macromolecule drug bioanalytical applications, and are discussed in the following sections. 

An impressive variety of LC/MS-based solutions, incorporating quantitative and qualitative process approaches, are now routinely applied to accelerate drug development. The results are significant and led to the successful development of innovative therapies and numerous novel drugs. The use of LC/MS with other technologies for sample preparation, analysis, and data management is now an inextricably linked element of drug development. 

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