Mechanism based approach

Section 4.1 briefly describes some of the commonly employed experimental tools and procedures. Chaudhury et al., Israelachvili et al. and Tirrell et al. employed contact mechanics based approach to estimate surface energies of different self-assembled monolayers and polymers. In these studies, the results of these measurements were compared to the results of contact angle measurements. These measurements are reviewed in Section 4.2. The JKR type measurements are discussed in Section 4.2.1, and the measurements done using the surface forces apparatus (SFA) are reviewed in Section 4.2.2. 

Density functional theory (DFT),32 also a semi-empirical method, is capable of handling medium-sized systems of biological interest, and it is not limited to the second row of the periodic table. DFT has been used in the study of some small protein and peptide surfaces. Nevertheless, it is still limited by computer speed and memory. DFT offers a quantum mechanically based approach from a fundamentally different perspective, using electron density with an accuracy equivalent to post Hartree-Fock theory. The ideas have been around for many years,33 34 but only in the last ten years have numerous studies been published. DFT, compared to ab initio... 

Structural and Toxic Mechanism-Based Approaches to Designing Safer Chemicals... 

Several known mechanism-based approaches, such as dissolution-controlled, diffusion and/or erosion-controlled, combination of dissolution and diffusion-controlled, and osmotically-controlled... 

R. Talreja, A damage mechanics based approach to durability assessment of composite materials, Composites and Finely Graded Materials, in ASME, Materials Division, vol. 80 ed. by T. Srinivasan et al. pp. 151-156 (1997)... 

Finally, the diversity of extrapolation techniques relates to the diversity of technical solutions that have been defined in the face of the various extrapolation problems. Methods may range from simple to complex, or from empirical-statistical methods that describe sets of observations (but do not aim to explain them) to mechanism-based approaches (in which a hypothesized mechanism was guiding in the derivation of the extrapolation method). In addition, they may range from those routinely accepted in formal risk assessment frameworks to unique problem-specific approaches, and from laboratory-based extrapolations consisting of 1 or various kinds of modeling to physical experiments that are set up to mimic the situation of concern (with the aim to reduce the need for extrapolation modeling). 

Tier-4 highly specific approaches, for example, methods using mechanism-based approaches, plus physical models (models that mimic the situation of concern experimentally, such as microcosms or mesocosms)... 

In the mechanism-based approach, a model is validated by its ability to reproduce observed temporal behaviors, i.e. wave forms, phase relationships, parameter dependences, and stability properties under many different conditions. For oscillatory phenomena, prediction of amplitudes and frequencies (using independently determined parameters) play a significant role. Further validation of the model is based on its ability to predict the outcome of new experiments, performed under conditions not previously examined. Among the advantages of this approach are that the model can be gradually expanded without changing already consolidated parts and that the model, in principle at least, allows translation by replacement of, e.g. parameters from animal studies by parameters relevant to man. 

This mechanism-based approach for eliciting catalytic antibodies has demonstrated promising opportunities for biocatalyst generation, and for the first time, it shows the possibility of being competitive with natural enzymes. The application of this second-generation catalytic antibody in the synthesis of several natural products gives credence to their potential applicability and demonstrates their scope. 

Physiologically based phannacokinetic/pharmacodynamic (PBPK/PD) modeling has proven useful in many areas of toxicology and therapeutics. This quantitative, mechanism-based approach has allowed limited experimental in vivo and in vitro data to be quantitatively integrated with physiological data so as to facilitate predictions of the behavior of organisms under different exposure conditions. Specifically, it has been used for ... 

We started the national cooperative drug discovery groups in natural products and we now have groups in chemistry and mechanism-based approaches where we partnered with individuals utilizing some of their specific talents to solve multidisciplinary problems. The government funds the project at a similar level. We have about 8 million to 10 million allocated to this area. 

Nagai J. [Molecular mechanisms underlying renal accumulation of aminoglycoside antibiotics and mechanism-based approach for developing nonnephrotoxic aminoglycoside therapy]. Yakugaku Zasshi 126 327-335,2006. 

Mechanism-based approach for the evaluation of drug-drug interaction potential... 

Hausheer FH, Kochat H, Parker AR, et al. New approaches to drug discovery and development a mechanism-based approach to pharmaceutical research and its application... 

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