Indirect approach

A challenging task in material science as well as in pharmaceutical research is to custom tailor a compound s properties. George S. Hammond stated that the most fundamental and lasting objective of synthesis is not production of new compounds, but production of properties (Norris Award Lecture, 1968). The molecular structure of an organic or inorganic compound determines its properties. Nevertheless, methods for the direct prediction of a compound s properties based on its molecular structure are usually not available (Figure 8-1). Therefore, the establishment of Quantitative Structure-Property Relationships (QSPRs) and Quantitative Structure-Activity Relationships (QSARs) uses an indirect approach in order to tackle this problem. In the first step, numerical descriptors encoding information about the molecular structure are calculated for a set of compounds. Secondly, statistical and artificial neural network models are used to predict the property or activity of interest based on these descriptors or a suitable subset. 

An alternative approach is the use of pH-sensitive fluorophores (Lichtenberg and Barenholz, lOSS). These probes are located at the lipid-water interface and their fluorescence behavior reflects the local surface pH, which is a function of the surface potential at the interface. This indirect approach allows the use of vesicles independent of their particle size. Recently, techniques to measure the C potential of Liposome dispersions on the basis of dynamic light scattering became commercially available (Muller et al., 1986). 

Belpassi, L., Tarantelli, F., Sgamellotti, A., Gdtz, A.W. and Visscher, L. (2007) An indirect approach to the determination of the nuclear quadrupole moment by four-component relativistic DFT in molecular calculations. Chemical Physics Letters, 442, 233-237. 

Today, the first question can sometimes be studied directly using techniques that are described in later chapters, but this was not an option for the early pharmacologists. Also, the only responses that could then be measured (e.g., the contraction of an intact piece of smooth muscle or a change in the rate of the heart beat) were indirect, in the sense that many cellular events lay between the initial step (activation of the receptors) and the observed response. For these reasons, the early workers had no choice but to devise ingenious indirect approaches, several of which are still important. These are based on modeling (i.e., making particular assumptions about) the two... 

The revealed preference method is an indirect approach that is used in order to monetize use values. This method observes the real choice between money and the environmental goods. Methods often include observations of consumers or producers behaviour or actions, such as the hedonic price method and the production function method. The hedonic price method determines values from actual market transactions. These transactions are used to see how the price of a market commodity varies when a related environmental good changes, such as the effects of noise or air pollution on house prices. The production function method is used to estimate the value of the environmental effects on production. This method is suitable when consumption or production of a private good is affected by the environmental good. An example is the valuation of ground-level ozone levels by valuing the impact on the production of wheat or timber, which has market prices. The problem with the revealed preference method is that it does not contain all the individuals values that affect the WTP. 

Pork is the product of a very complex process. All the various characteristics of pork quality cannot be assessed directly in each carcass because these measurements and assessments would be too expensive. Therefore, previous scientific quality assessment of meat is primarily an indirect approach based on a few easily detectable quantitative traits and on the prescription of minimal standards in relation to the product in terms of size or composition and in relation to the production process. The prescriptions and the exclusion criteria vary between countries or between labelling programmes. The most encompassing prescriptions are enshrined in the EC regulation on organic livestock production (EEC No. 2092/91). Owing to this approach, extreme deviations in quality traits and deleterious effects are prevented. However, there is still space left within these framework conditions for huge variability in pork quality. 

Figure 22.21 Antibodies may be conjugated to liposomes using an indirect approach incorporating a (strept)avidin-biotin system. Biotinylated liposomes may be complexed with biotinylated antibodies using (strept)avidin as a bridging molecule or may be complexed with an antibody-(strept)avidin conjugate.

Here we will describe the methods that are used to derive critical limits for soil, based on direct ecotoxicological effects on microorganisms and plants. The indirect approaches (food web models) to derive critical limits for soil based on critical limits for terrestrial fauna such as MPC values for target organisms will be also considered. 

An understanding of crystallization is important for the systematic development of crystal engineering, but it is not a simple phenomenon and many would agree that it is still far too difficult to study in a rigorous way, either experimentally or theoretically. However, indirect approaches to the study of crystallization are evolving. Three possible types of crystals that may be pertinent to this endeavor are (1) polymorphs - these represent cases of alternative crystallization, (2) pseudosymmetric structures with multiple molecules in the asymmetric unit - these could represent cases of incomplete crystallization, and (3) solvated crystals or pseudopolymorphs -these may represent cases of interrupted crystallization. These three scenarios are now sketched very briefly and the treatment given is necessarily selective. 

Most techniques for process data reconciliation start with the assumption that the measurement errors are random variables obeying a known statistical distribution, and that the covariance matrix of measurement errors is given. In Chapter 10 direct and indirect approaches for estimating the variances of measurement errors are discussed, as well as a robust strategy for dealing with the presence of outliers in the data set. 

As discussed before, in a strict sense, there is always some degree of dependence between the sample data. An alternative approach is to make use of the covariance matrix of the constraint residuals to eliminate the dependence between sample data (or the influence of unsteady-state behavior of the process during sampling periods). This is the basis of the so-called indirect approach. 

In the estimation of fr from the conventional indirect approach, using the Keller et al. (1992) method, ( c) is given by... 

A comparison with the target covariance shows that the conventional indirect approach gives a very good estimation of the covariance in this case ... 

Without outliers. The estimation of P both from the conventional indirect approach PC and from the robust approach 4/r gave similar results when compared with the target covariance matrix (P ... 

In former times, eradication took the form of destroying the flies savanna or woodland habitats, or slaughtering wild host animals. These indirect approaches were environmentally ruinous, and they gave way eventually to insecticides, sprayed either from the air or directly on the ground. In more recent years, attention has... 

A. Principles of Chiral Separation in LC Direct and Indirect Approaches... 

---