Scope of the thesis

Further characterisation of structural requirements for ligands at the dopamine D2 and D3 receptor studies with thienylethylamine as a possible pharmacophore  

This chapter describes the synthesis and in vitro pharmacology of a novel series of dopamine receptor ligands, in which the classical phenylethylamine pharmacophore is replaced by a thienylethylamine moiety. In general, the novel compounds showed moderate affinity for the dopamine D2 and D3 receptors. The results showed that a thienylethylamine moiety can act as a dopamine pharmacophore on these receptors. When the thienylethylamine moiety is fixed in a rigid system the affinity for the dopamine receptor is increased, however, in the tricyclic hexahydrothianaphthoxazine structure, the affinity for the dopamine receptors is diminished. 

This chapter is based on Rodenhuis, N. Vermeulen, E.S. Wikstrom, H.V. Pugsley, T.A. Wise, L.D. Dijkstra, D. (2000) Further characterization of structural requirements for ligands at the dopamine D2 and D3 receptor studies with thienylethylamines as a possible pharmacophore. J. Med. Chem. submitted. 

Dopamine, and most of the known dopamine receptor agonists, binds with higher affinity to the dopamine D3 than to the dopamine D2 receptor. Due to the close homology between the dopamine D2 and D3 receptors, especially in the transmembrane domains (-80%), it is difficult to predict dopamine D2 versus dopamine D3 receptor selectivity based on receptor models. Malmberg et al.115 suggested that the observed dopamine D3 receptor selectivity may not be due to a single specific interaction but rather to a small difference in conformation between the dopamine D3 and D2 receptors. 

Chart 2.1 Chemical structures of /ram-9-hydroxy-N- -propyl-2,3,4a,5,6, l()b-hcxahydro-4//-naphth[ 1.26] [ 1,4]oxazinc (PHNO, 27a), /ram-9-hydroxy-4-(2-phcnylcthyl)- 

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For purposes of limiting the scope of the thesis, the reactor will use a directly coupled closed Brayton cycle for power conversion and will use highly enriched Uranium Nitride fuel. The sections of the thesis will be ... 

The scope of the thesis is to study and develop small-scale processes for ionic liquid-based extractions that can intensify the liquid-liquid separations of the spent nuclear fuel reprocessing cycle. In addition, modeUing methodologies are proposed to evaluate the applicability of the small-scale extractors in reprocessing large volumes of nuclear waste in industrial scale. 

In the scope of the thesis, a steady-state model of polymer electrolyte membrane fuel cell was made by Matlab. The model was based on simplified chemical and electrical equations. The most important performance related parameters, namely operation temperature and pressure, were parametrically investigated. Output voltage, electrical output power, heat generation, material inputs and outputs, and efficiencies according to first and second law of thermodynamics were plotted by the change of temperature and pressure against current density. 

To define a system, a clear system border has to be present between system and environment. However, this system border depends on the scope of the researcher, in t Veld (Veld in t, 1999). A system s view of an organization is shown in Figure 16. This system s view of an organization will be used in the remainder of this thesis. 

Rogers thesis [2] includes an enormous scope with many objectives. It consists of more than 600 pages with all the details. Long lists of measuring data, with a font size that is hardly readable, are provided in the main part of the thesis. Consequently, the details sometimes conceal the overall objectives and the main result. However, it is an impressive piece of work. 

In previous chapters, detailed theoretical principles of CT processes in general and photoinduced CT processes in particular have been provided. The next step is the practical application of these principles to systems which will be discussed within the scope of this thesis, namely organic -conjugated donor-acceptor supramo-lecular assemblies. Furthermore, we will draw our attention to CT processes, which are triggered by photochemical stimuli. They provide the theoretical background, which is required to understand the charge-transport properties of wire-type molecular bridges. 

Energy transfer reactions in systems containing the herein investigated molecular wire structures have already been investigated in Erlangen. Two well-characterized examples, which were investigated within the scope of this thesis will be presented in more detail. This lines out the characteristic features of photoinduced energy transfer reactions. 

Field flow fraction (FFF) is an elution technique suitable for molecules with a molecular weight > 1000 and large molecules are beyond the scope of this thesis. However, reports on investigated substances with FFF are widespread and cover applications such as the separation and characterization of proteins [31] and enzymes [32], the separation of human and animal cells [33] and the molecular weight and particle size distribution of polymers [34, 35], FFF is a relatively new approach in biotechnology therefore practical experiences are not yet abundant. 

To start with, the present chapter will address some fundamental concepts of liquid crystals to enable a thorough comprehension of the aims and scope of this thesis. The properties of and the discovery of the thermotropic SmC phase will be dealt with in more detail, as they are essential for understanding the significance of the thesis presented. Finally, examples of lyotropic analogs of the achiral smectic C (SmC) phase, which were known up to now, will be discussed in this introductory chapter. 

A good introduction to the theory of Extended Absorption X-ray Fine Structure (EXAFS) is given by Als-Nielsen and McMorrow [2], while a more detailed consideration of EXAFS and its application to amorphous materials is given by Filipponi [20, 21]. While a full discussion is beyond the scope of this thesis, a brief mention should be made of the salient points relevant to glassy samples. 

Before kinetic information can be extracted from this number MWD, two criteria must be met (i) the MWD must be of the correct shape and (ii) it must also be scaled correctly, according to equation 4.3. The former criterion, however, could be systematically violated in several ways. This can be the result of inaccurate SEC calibration, inaccurate Mark-Houwink coefficients, non-linear baseline drift, the occurrence of column broadening during a SEC analysis and the non-linear optical properties of a series of oligomers. It goes beyond the scope of this thesis to discuss all these effects. Here, the discussion will be limited to only two of these effects column broadening and non-linear optical properties of oligomers. 

Despite the mentioned successes, there are still plenty of challenges to face. Upon others, open questions are the electronic structure, reactivity and behavior towards more complex molecules/reactions and under realistic conditions. Within the scope of this thesis, using (exclusively) Pt clusters, under well defined (UHV) and applied (ambient) reaction conditions (see Fig. 1.1) different issues are tackled. 

The particular approaches, concepts and collaborations chosen in this work to fulfill the scope of this thesis are stated in the following and summarized in a sketch in Fig.1.1. 

Possible routes to the formation of ethylidyne are shown in Fig. 2.1b, despite experimental [34-36, 49, 53, 54, 56-58] and theoretical [44, 51, 59, 60] efforts, the elementary steps involved in the transformation from ethene to ethylidyne are still debated. Further, the influence of co-adsorbates (i.e. oxygen, CO) on the reactivity (as a function of coverage) have been studied [39, 53, 57, 61, 62], however are not within scope of this thesis and are not discussed. 

Redfield theory [18-20] is a microscopic semi-classical theory of spin relaxation in which the spin system is treated quantum mechanically whilst the coupling of the spins with the lattice is treated classically. In this classical approximation, the spin states are in equilibrium and a correction factor is needed to ensure the spin ensemble relaxes to the correct limits. This problem can be overcome by treating the lattice quantum mechanically, however, the details and nature of the computational details are beyond the scope of this thesis. In this section a brief introduction to Redfield theory for spin relaxation is provided, a more detailed analysis of the theory can be found elsewhere [21]. 

To put the various contributions to the modeling of codeposition of particles into perspective, not only must the relevant electrochemical literature be reviewed, but also that in the field of filtration. Theories on the mechanisms of capture and encapsulation of particles during metal deposition have only begun to appear in the last two decades. The scope of this section will be to summarize the models published since 1970, and give the basis for their explanation. (A review of the older work can be found in the Ph.D. thesis of C. Buelens [58].) Let us see review the models in chronological order. 

Chapter 1 provided a general research area, where the problem of measuring safety pro-actively was identified in literature and in practice. This was done by sketching a recent accident and discussing how safety was measured in the past and currently. Moreover, it highlighted that the pro-active measurement of safety is still a problem in the chemical process industry. The development of substantially more understanding of how to pro-actively indicate accidents in the chemical process industry, was finally derived as the scope of this study and will be discussed in the remaining Chapters of this thesis. 

Finally in Chapter 8, all conclusions made during the research will be discussed in respect to the overall scope and research questions posed in this thesis. From this discussion general conclusions about the research performed in this thesis will be made. The research objective and research questions will be listed to check if the objective is achieved and if the questions can be answered completely and correctly. Finally, any additional questions arising from this research will suggest the scope of future research. 

Rather than evaluate risks and the corresponding perceptions that establish risk levels, the thesis proposes to examine the extent of regulatory action necessary to ensure the correct management of a hazardous material and the likelihood that there is the need to take such a regulatory response. Extent of regulatory action therefore describes the scope and degree of risk communication, control and enforcement that regulators could need to take to respond to risk and social perceptions of risk. 

The development in the field of cation-exchange and anion-exchange resins have been discussed mainly on the basis of the monomers used for the synthesis of polymer matrices. Many of the chemical systems studied do not appear to be of commercial significance at first sight. Nevertheless, enough scope exists in designing novel syn-thesis/modification based on such systems so as to render them more useful and economically viable. 

An expert system shell developed in the MYCIN project is EMYCIN, which was used to develop other expert systems. One of these systems is PUEE, designed for the domain of heart disorders. Another outcome was the ventilator manager (VM) program developed as a collaborative research project between Stanford University and Pacific Medical Center in San Francisco within the scope of a Ph.D. thesis by Lawrence M. Fagan [6]. VM was designed to interpret on-line quantitative data in the intensive care unit. The system measures the patient s heart rate, blood pressure, and the status of operation of a mechanical ventilator that assists the patient s breathing. Based on this information, the system controls the ventilator and makes necessary adjustments. 

This section covers several topics the history of the important components for the reactor, how these components work, and why these components were chosen. The primary motivation was to design a functional reactor not to explore all the myriad of possibilities that exist. This meant that not all the alternatives for any given component would be examined, just ones that appeared to fulfill the desired goals. As a result several simplifications were implemented for this thesis to reduce the scope. 

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