User Profile Management and Selection in Context-Aware Service Platforms for Networks Beyond 3G

In recent years, progress in the area of mobile telecommunications has changed our way of life, in the private as well as the business domain. Mobile and wireless networks have ever increasing bit rates, mobile network operators provide more and more services, and at the same time costs for the usage of mobile services and bit rates are decreasing. However, mobile services today still lack functions that seamlessly integrate into users’ everyday life. That is, service attributes such as context-awareness and personalisation are often either proprietary, limited or not available at all. In order to overcome this deficiency, telecommunications companies are heavily engaged in the research and development of service platforms for networks beyond 3G for the provisioning of innovative mobile services. These service platforms are to support such service attributes. Service platforms are to provide basic service-independent functions such as billing, identity management, context management, user profile management, etc. Instead of developing own solutions, developers of end-user services such as innovative messaging services or location-based services can utilise the platform-side functions for their own purposes. In doing so, the platform-side support for such functions takes away complexity, development time and development costs from service developers. Context-awareness and personalisation are two of the most important aspects of service platforms in telecommunications environments. The combination of context-awareness and personalisation features can also be described as situation-dependent personalisation of services. The support for this feature requires several processing steps. The focus of this doctoral thesis is on the processing step, in which the user’s current context is matched against situation-dependent user preferences to find the matching user preferences for the current user’s situation. However, to achieve this, a user profile management system and corresponding functionality is required. These parts are also covered by this thesis. Altogether, this thesis provides the following contributions: The first part of the contribution is mainly architecture-oriented. First and foremost, we provide a user profile management system that addresses the specific requirements of service platforms in telecommunications environments. In particular, the user profile management system has to deal with situation-specific user preferences and with user information for various services. In order to structure the user information, we also propose a user profile structure and the corresponding user profile ontology as part of an ontology infrastructure in a service platform. The second part of the contribution is the selection mechanism for finding matching situation-dependent user preferences for the personalisation of services. This functionality is provided as a sub-module of the user profile management system. Contrary to existing solutions, our selection mechanism is based on ontology reasoning. This mechanism is evaluated in terms of runtime performance and in terms of supported functionality compared to other approaches. The results of the evaluation show the benefits and the drawbacks of ontology modelling and ontology reasoning in practical applications.

Structural insights into the allosteric activation mechanism of cGMP-dependent protein kinase I

Cyclic GMP-dependent protein kinase (PKG) is a key transducer in the NO-cGMP signaling pathway. In this line, PKG has been considered an important drug target for treating hypertensive cardiovascular and pulmonary diseases. However, the investigation of PKG’s allosteric activation mechanism has been hampered by a lack of structural information. One of the fundamental questions on the cGMP-dependent activation of PKG is how the enzyme can distinguish cGMP over cAMP and selectively respond to cGMP. To ensure proper signaling, PKG must have developed unique features to ensure its activation upon the right activation signal. In this thesis, the cGMP-selective activation mechanism of PKG was studied through determining crystal structures of three truncated constructs of the regulatory domain [CNB-A (92-227), CNB-B (271-369), and CNB-A/B (92-351)] of PKG Iβ in the absence or presence of cyclic nucleotides. Herein, two individual CNB domain structures with biochemical data revealed that the C-terminal CNB domain (CNB-B) is responsible for cGMP selectivity, while the N-terminal CNB-domain (CNB-A) has a higher binding affinity for both cGMP and cAMP without showing any selectivity. Based on these crystal structures, mutagenesis studies were performed in which the critical residues for cyclic nucleotide selectivity and activation were identified. Furthermore, we discovered that the conformational changes of the C-terminal helix of the CNB-B that bridges between the regulatory and catalytic domains including the hydrophobic capping interaction are crucial for PKG activation. In addition, to observe the global conformation of the activated R-domain, I solved a co-crystal structure of the CNB-A/B with cGMP. Although a monomeric construct was crystallized, the structure displays a dimer. Strikingly, the CNB-A domain and its bound cGMP provide a key interface for this dimeric interaction. Using small angle X-ray scattering (SAXS), the existence of the cGMP-mediated dimeric interface within the CNB domains was confirmed. Furthermore, measuring cGMP-binding affinities (EC50) of the dimeric interface mutants as well as determining activation constants (Ka) revealed that the interface formation is important for PKG activation. To conclude, this thesis study provides a new mechanistic insight in PKG activation along with a newly found interface that can be targeted for designing PKG-specific activity modulators.