We report on the design, synthesis, and structure activity relationship studies of novel Org 27569 analogues as potential allosteric modulators of the CB1 receptors. We also investigated by computer modelling the possible location of the allosteric site on CB1 and the binding confirmation of the allosteric ligands. Docking of the synthesised molecules is also performed and the results are compared to the results of the biological bioassays. The synthesis of non-fused indole analogues of Org 27569 is described. These analogues were systematically varied to study the importance of key functional groups for CB1 allosteric activity. It was found that the two NH groups of the indole derivatives are required for activity. Activity is also significantly improved for analogues possessing a hydroxymethyl group or a hydrophobic chain at position 3 of the indole moiety. SAR analysis also shows that the presence of a dialkylamino group at the <i>para-</i>position on the aromatic side chain further improves the activity. Conformationally restricted analogues (fused indoles) of Org 27569 were prepared to determine the possible binding conformation of Org 27569.<i> </i>An analogue having the two NH groups directed in the same direction exhibited a moderate ability to enhance CP55,940 affinity and gave significant decrease in [³⁵S]GTPγS binding at 1μM, indicating the possible binding conformation for the Organon derivatives. Molecular modelling studies allowed locating a possible binding pocket for the CB1 allosteric ligands. The study described here should help the design of ligands of the CB1 allosteric site that possess higher biological activities and specificities. The results should pave the way for the discovery of the anti-obesity drugs of the future.

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Since to trace and examine all of the insurance companies that were involved in scandal and fraud would be far too extensive a task for this study, seven companies have been chosen for examination because they best illustrate the consequences of weak insurance regulation in Texas. In studying each company major emphasis has been given to the factors which contributed directly to the eventual receivership of the company.

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This thesis aims to establish computer methods for the transient stability analysis of electric power systems which operate isolated from the large interconnected system. A typical isolated system is characterized by a compact network in which the size of the load is relatively large when compared to the total, installed generation capacity. The stability problems are thus more severe for this system than for the grid-type system. This results in the need for more accurate representations for the system components in the computer studies. This work considers particularly the prime mover and the induction motor modelling. The accurate modelling for turbo-charged diesel engines and single shaft gas turbines is considered first due to the significative presence of these types of prime movers in the isolated systems. The quasi-steady approach is adopted in the development of these models. The induction motor modelling is then dealt with and an accurate model which accounts for the deep-bar effects and includes the stator transients is presented. In addition, this work also investigates the possibility of substituting all these detailed models by simple, reduced models in the computer simulations since the latter pose less problem in assembling the necessary data than the former ones. Furthermore, some theoretical aspects for the representation of synchronous machines, automatic voltage regulators and transformers are included in the thesis. Some insight on the numerical integration method used in the stability program - the Trapezoidal implicit - is also given in the text with the advantages and disadvantages being stated. Several studies are shown in the thesis which aim firstly to compare the various models for prime mover and induction motor representations and secondly to test the complete simulation package when dealing with stability analyses of typical isolated systems.

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This thesis resolves around problems arising for the existing legal framework from the use of novel software-­‐based policing tools during criminal investigations. The increasing dependence on information and communication technologies and the Internet means that more aspects of people’s lives move online, and crime follows them. This has triggered the development of innovative, autonomous investigative technologies that are increasingly replacing human officers for the policing of the online sphere. While only recently discussions of the legal status of embodied and unembodied robotical devices have gained more widespread attention, discussions of the legal status of autonomous agent technology are not new. They have focussed however in the past on applications in the private domain, enabling contract formation online. No systematic study has so far been carried out that looks at the use of autonomous agent technology when deployed by state actors, to fulfil core state functions. This thesis starts with the hypothesis that the use of automated, intelligent devices to replicate core police functions in the online world will increase in the future. Looking at first emerging technologies, but with an eye towards future deployment of much more capable software tools that fulfil policing functions on the Internet, this thesis looks at the challenges this poses for regulators and software developers. Based on extensive qualitative research interviews with stakeholders from two different jurisdictions (Germany & UK) this thesis finds that these novel policing technologies challenge existing legal frameworks, which are still premised on the parameters of the offline world. It therefore develops an alternative governance model for these policing tools, which enables their law-­‐compliant use and prevents rights violations of suspects. In doing so it draws upon both worlds, the technical and the legal, while also incorporating the empirical research results from the interviews with experts. The first part of this thesis analyses the technical foundations of these software-­‐based policing tools. Here, one of the key findings is that the current governance system focuses on ex-­‐ante authorisation of very specific, individual software tools without developing a systematic classification. This contradicts the principle of sustainable law making. To overcome this piecemeal approach, as a first contribution to existing research this work defines a new class of investigative technologies – mobile, intelligent and autonomous (MIA) policing tools ‐ based on the findings of the technical analysis. Identifying such a natural class of present and future technologies that pose the same type of legal issues should facilitate the sustainable governance of these new policing tools. The second part of this thesis analyses two specific legal issues: cross-­jurisdictional investigations and the evidentiary value of the seized data. These issues were identified as most pressing by the experts interviewed for this work. This analysis reveals that investigative activities of MIA tools are potentially in conflict with international law principles and criminal procedure law. In order to gain legitimacy, these new policing tools need to operate within the parameters of the existing legal framework. This thesis argues that given the unique technical capabilities of MIA tools, the primary approach to achieving this is to assign legal responsibility to these tools. The third part of this thesis develops a novel governance approach to ensure that MIA tools operate within the parameters of the legal framework, and therefore obtain legitimacy and relevance, also with regard to the investigative results. This approach builds on existing research identifying code as a regulatory modality and contributes to the field of legal theory. It constitutes a solution for the governance problems of MIA tools, however, it requires currently lacking collaboration among stakeholders and cross-­disciplinary research.

Parent education programs were introduced nearly 30 years ago with a primary focus on teaching parents strategies to identify and reduce incidences of noncompliance in their children, and have been the single most successful treatment approach for reducing problem behavior. However, few parent education programs address emotion regulation and its role in children's development despite the fact that research has consistently demonstrated that children who are unable to successfully regulate emotions are more likely to develop behavioral problems. Specifically, most programs fail to address the concepts of effortful control and negative affectivity, two important components of child temperament, and their effects on children's behavior. Research has suggested that children who are emotionally regulated develop greater social competence, resulting in better, more positive, relationships. Thus, parents who teach their children to express and regulate their emotions in socially appropriate ways promote the development of prosocial behaviors in their children. In response, the goal of this study was to examine whether adding an emotion component aimed at teaching parents successful strategies for socializing children's emotions would affect overall parenting and children's emotion regulation above and beyond a traditional behavioral model. Twenty-five parents participated in a three-week parent education program. Parents learned strategies for managing their children's misbehavior. Moreover, parents learned about temperament, how these dispositional traits affect children's behavior, and successful strategies for aiding children in emotion management. At each session, parents completed measures designed to assess their children's temperament and behavior. Additionally, parents completed measures regarding their parenting practices and styles as well as feelings of parental efficacy. Repeated measures ANOVAs were run to determine whether changes in children's temperament or parenting emerged over time. Hierarchical multiple regressions were also computed to determine the effects of parents' practices, styles and efficacy on change in children's levels of effortful control and negative affectivity. Results suggest that parents' choice of disciplinary strategies affects children's ability to regulate their emotions, and that participation in the emotion module positively affected overall parenting and children's emotion regulation.

The current investigation examines the relationship between parenting, emotion regulation, and symptoms of psychopathology in maltreating and non-maltreating parent-child dyads. The participants in this study were 114 children (67 maltreated and 57 non-maltreated) from ages 1 to 4. Child affect and effortful control along with parent affect were observed during a parentchild interaction procedure. Symptoms of psychopathology were measured using the Child Behavior Checklist. The maltreated children in this study exhibited more irritability/anger, affect lability, and internalizing symptomatology, along with less positive affect than their non-maltreated peers. These data also suggest that parental affect is related to internalizing symptomatology; but this relationship is stronger for the maltreated group. Contrary to expectations emotion regulation did not fully mediate the relationship between parenting and psychopathology. Clusters of maladaptive affect, "angry" and "labile", emerged in the maltreated group along with a more "resilient" group characterized by positive affect, positive parental affect, and lower levels of psychopathology.