Domain of response

While it is the Study Director who is ultimately responsible for the quality of the study as a whole, he/she cannot be held responsible for the quality of each and every data point and each and every single record. This is clearly the domain of responsibility of the study personnel, who are are responsible for recording raw data promptly and accurately and in compliance with these Principles of Good Laboratory Practice, and are responsible for the equality of their data . Certainly, these raw data will be scrutinised by the Study Director, who will use them for the preparation of the final study report certainly these raw data will be checked by Quality Assurance for their compliance with the provisions of the GLP Principles. However, data quality cannot be obtained retrospectively by control measures ( quality cannot be controlled into the data ), data have to be recorded in such a way that quality is an intrinsic characteristic of these records. Thus, this responsibility of study personnel for the quality of their data cannot be emphasised strongly enough. 

Ductility is the ability of a structure, its components, or the materials used therein, to maintain resistance in the inelastic domain of response. It includes the ability to sustain large deformations and the capacity to absorb energy by hysteretic behavior. Displacement ductility is defined as the ultimate strain of the material divided by its yield strain. For an anchor in tension, it may be taken as the elongation of the anchor at maximum tension load divided by the elongation at yield. 

No polymer is ever 100% crystalline at best, patches of crystallinity are present in an otherwise amorphous matrix. In some ways, the presence of these domains of crystallinity is equivalent to cross-links, since different chains loop in and out of the same crystal. Although there are similarities in the mechanical behavior of chemically cross-linked and partially crystalline polymers, a significant difference is that the former are irreversibly bonded while the latter are reversible through changes of temperature. Materials in which chemical cross-linking is responsible for the mechanical properties are called thermosetting those in which this kind of physical cross-linking operates, thermoplastic. 

In spite of the absence of the C-terminal domains, the DNA-binding domains of lambda repressor form dimers in the crystals, as a result of interactions between the C-terminal helix number 5 of the two subunits that are somewhat analogous to the interactions of the C-terminal p strand 3 in the Cro protein (Figure 8.7). The two helices pack against each other in the normal way with an inclination of 20° between the helical axes. The structure of the C-terminal domain, which is responsible for the main subunit interactions in the intact repressor, remains unknown. 

Figure 8.7 The N-terminal domains of lambda repressor form dimers, in spite of the absence of the C-terminal domains that are mainly responsible for dimer formation in the intact repressor. The dimers are formed by interactions between a helix 5 from each subunit. The different subunits are colored green and brown, except the helix-turn-hellx motif, which is colored blue and red as in Figure 8.4. (Adapted from C. Pabo and M. Lewis, Nature 298 443-447, 1982.)...

TBP mutants lacking the N-terminal region are fully functional in promoter binding and stimulation of basal transcription and therefore these two functions must be provided by the C-terminal domain. Furthermore, the C-terminal domain of yeast TBP contains all the functions essential for normal yeast cell growth and for responses to specific transcriptional activators with a net negative charge. This C-terminal domain contains two homologous... 

In summary, a DNA-supported asymmetric interface located within the DNA-binding domains of these nuclear receptors provides the molecular basis for receptor heterodimers to distinguish between closely related response elements. RXR can provide a repertoire of different dimerization surfaces, each one unique for a specific partner, allowing dimers to form that are adapted to the length of the spacer region in their corresponding response elements. 

An additional pathway leading to very efficient EFN-(3 responses involves one of the Toll-like-recqDtors (TLR), TLR3 which also senses dsRNA and is mainly expressed in dendritic cells (DC) and macrophages. Signal transduction then proceeds via the adaptor molecule TICAM/TRIF associated with the TER.-domain of... 

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