Response mechanism

The main objective of air quality guidelines and standards is the protection of human health. Since fme particulates (PM,) are more likely to cause adverse health effects than coarse particulates, guidelines and standards referring to fine particulate concentrations are preferred to those referring to TSP, which includes coarse particulate concentrations. Scientific studies provide ample evidence of the relationship between exposure to short-term and long-term ambient particulate concentrations and human mortality and morbidity effects. However, the dose-response mechanism is not yet fully understood. Furthermore, according to the WHO, there is no safe threshold level below which health damage does not occur. 

There are numerous second messenger systems such as those utilizing cyclic AMP and cyclic GMP, calcium and calmodulin, phosphoinosiddes, and diacylglerol with accompanying modulatory mechanisms. Each receptor is coupled to these in a variety of ways in different cell types. Therefore, it can be seen that it is impractical to attempt to quantitatively define each stimulus-response mechanism for each receptor system. Fortunately, this is not an... 

The ability to reduce stimulus-response mechanisms to single mono tonic functions allows relative cellular response to yield receptor-specific drug parameters. 

The first idea to consider is the effect of receptor density on sensitivity of a functional system to agonists. Clearly, if quanta of stimulus are delivered to the stimulus-response mechanism of a cell per activated receptor the amount of the total stimulus will be directly proportional to the number of receptors activated. Figure 5.8 shows Gi-protein-mediated responses of melanophores transiently transfected with cDNA for human neuropeptide Y-l receptors. As can be seen from this figure, increasing receptor expression (transfection with increasing concentrations of receptor cDNA) causes an increased potency and maximal response to the neuropeptide Y agonist PYY. 

Previously, pharmacologists were constrained to the prewired sensitivity of isolated tissues for agonist study. As discussed in Chapter 2, different tissues possess different densities of receptor, different receptor co-proteins in the membranes, and different efficiencies of stimulus-response mechanisms. Judicious choice of tissue type could yield uniquely useful pharmacologic systems (i.e., sensitive screening tissues). However, before the availability of recombinant systems these choices were limited. With the ability to express different densities of human target proteins such as receptors has come a transformation in drug discovery. Recombinant cellular systems can now... 

By utilizing complete dose-response curves, the method devised by Barlow, Scott, and Stephenson [9] can be used to measure the affinity of a partial agonist. Using null procedures, the effects of stimulus-response mechanisms are neutralized and receptor-specific effects of agonists are isolated. This method, based on classical or operational receptor theory, depends on the concept of equiactive concentrations of drug. Under these circumstances, receptor stimuli can be equated since it is assumed that equal responses emanate from equal stimuli in any given system. An example of this procedure is given in Section 12.2.1. 

In terms of classical receptor theory—where response is a hyperbolic function of stimulus (Response = Stimulus/ (Stimulus 4- [3), [3 is a transducer function reflecting the efficiency of the stimulus-response mechanism of the system), and stimulus is given by Stimulus = [A] e/([A] + KA) (e is the efficacy of the agonist)— Response is given by... 

Stimulus-response coupling, 30—31 Stimulus-response mechanism biochemical nature of, 23-25 definition of, 9... 

The theory of the response mechanism has been thoroughly discussed (15). 

Describe the response mechanism of the fluoride ion-selective electrode. Explain clearly why the OH- is the major interfering ion in F ISE measurements. 

Cl. Dybing, E. et al.. Hazard characterization of chemicals in food and diet dose response, mechanisms and extrapolation issues. Food Chem. Toxicol, 40, 237, 2002. 

It is interesting to observe that response mechanisms to Fe deficiency have been studied almost exclusively using synthetic chelates such as EDTA and ED-... 

Liquid Membrane Ion-Selective Electrodes Response Mechanisms Studied by Optical Second Harmonic Generation and Photoswitchable lonophores as a Molecular Probe... 

Liquid membrane type ion-seleetive electrodes (ISEs) provide one of the most versatile sensing methods because it is possible to customize the sensory elements to suit the structure of the analyte. A wealth of different synthetic and natural ionophores has been developed, in the past 30 years, for use in liquid membrane type ISEs for various inorganic and organic ions [1], In extensive studies [2-4], the response mechanism of these ISEs has been interpreted in terms of thermodynamics and kinetics. However, there have been few achievements in the characterization of the processes occurring at the surface of ISEs at molecular level. 

The above SHG studies exhibited several most important facts in the response mechanisms occurring at the surfaces of ionophore incorporated liquid membrane ISEs. 

Although, as indicated by the above studies, the detector response mechanism is poorly understood, the working limits of commercially available detectors are fairly well characterized and the detector is not particularly difficult to use. The minimum detectable- quantity for nitrogen is about 10 g N/s and about 5 x... 

Jouvet, M. (1962). [Research on the neural structures and responsible mechanisms in different phases of physiological sleep.] Arch. Ital. Biol. 100, 125-206. 

Electric field sensitive dyes respond to changes in electrical membrane potential by a variety of different mechanisms with widely varying response times depending on their chemical structure and their interaction with the membrane. An understanding of the mechanisms of dye response and their response mechanisms is important for an appropriate choice of a probe for a particular application. The purpose of this chapter is, therefore, to provide an overview of the dyes presently available, how they respond to voltage changes, and give some examples of how they have been applied. Finally, because there is still scope for the development of new dyes with improved properties, some directions for future research will be discussed. 

The basis for the different response times of these probes is their response mechanism. In order to produce a change in fluorescence, a change in electric field must induce some movement either of the dye molecule as a whole or of its electrons. The degree of movement determines the speed of the fluorescence response. 

Using the principles of biological olfaction, electronic nose systems contain arrays of different types of cross-reactive vapor-sensitive sensors. While it is difficult to discriminate analytes entirely by their responses to a single type of sensor, using an array of sensors yields response patterns that can readily distinguish many different vapors. Ideally, the response mechanisms of the sensors are highly varied and encompass both physical and chemical phenomena1. 

Due to their response mechanism the polyion-selective electrodes are not sensitive to the small fragments of polyionic macromolecules. Thus, if an enzyme cleaves the polyionic molecule these sensors can be used for detection of enzyme activity. Polycation protamine is rich in arginine residues that make it a suitable substrate for protease-sensitive electrochemical assays. Real-time detection of trypsine activity was demonstrated with the protamine-selective electrode as a detector [38],... 

Unfortunately, in the presence of detectable polyions in the solution a strong potential drift is normally observed due to the instability of the ion concentration gradients. Moreover, the main disadvantage of polyion-selective potentiometric electrodes lies in the intrinsic irreversibility of the underlying response mechanism. The target polyions eventually displace the counter-ions in the membrane phase and consequently the sensor loses its response. 

Let us consider, for instance, the response mechanism of a polycation-selective galvanostatically controlled sensor. The polymeric membrane is in contact with a NaCl solution. The membrane of the sensor is formulated with a lipophilic salt, for instance, tetradodecylammonium dinonylnaphthalenesulfonate (TDDA-DNNS), which has a relatively high affinity to protamine. Even though protamine is presented in the sample, spontaneous extraction does not take place due to the high lipophilicity of TDDA-DNNS, thus the initial concentration of protamine or sodium cations in the membrane is close to zero. 

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