I have invented "Internet Fish," a novel class of resource-discovery tools designed to help users extract useful information from the Internet. Internet Fish (IFish) are semi-autonomous, persistent information brokers; users deploy individual IFish to gather and refine information related to a particular topic. An IFish will initiate research, continue to discover new sources of information, and keep tabs on new developments in that topic. As part of the information-gathering process the user interacts with his IFish to find out what it has learned, answer questions it has posed, and make suggestions for guidance. Internet Fish differ from other Internet resource discovery systems in that they are persistent, personal and dynamic. As part of the information-gathering process IFish conduct extended, long-term conversations with users as they explore. They incorporate deep structural knowledge of the organization and services of the net, and are also capable of on-the-fly reconfiguration, modification and expansion. Human users may dynamically change the IFish in response to changes in the environment, or IFish may initiate such changes itself. IFish maintain internal state, including models of its own structure, behavior, information environment and its user; these models permit an IFish to perform meta-level reasoning about its own structure. To facilitate rapid assembly of particular IFish I have created the Internet Fish Construction Kit. This system provides enabling technology for the entire class of Internet Fish tools; it facilitates both creation of new IFish as well as additions of new capabilities to existing ones. The Construction Kit includes a collection of encapsulated heuristic knowledge modules that may be combined in mix-and-match fashion to create a particular IFish; interfaces to new services written with the Construction Kit may be immediately added to "live" IFish. Using the Construction Kit I have created a demonstration IFish specialized for finding World-Wide Web documents related to a given group of documents. This "Finder" IFish includes heuristics that describe how to interact with the Web in general, explain how to take advantage of various public indexes and classification schemes, and provide a method for discovering similarity relationships among documents.

In instances of mass fatality, such as plane crashes, natural disasters, or terrorist attacks, investigators may encounter hundreds or thousands of DNA specimens representing victims. For example, during the January 2010 Haiti earthquake, entire communities were destroyed, resulting in the loss of thousands of lives. With such a large number of victims the discovery of family pedigrees is possible, but often requires the manual application of analytical methods, which are tedious, time-consuming, and expensive. The method presented in this thesis allows for automated pedigree discovery by extending Link Discovery Tool (LDT), a graph visualization tool designed for discovering linkages in large criminal networks. The proposed algorithm takes advantage of spatial clustering of graphs of DNA specimens to discover pedigree structures in large collections of specimens, saving both time and money in the identification process.

We present WASP (World-friendly Active packets for ephemeral State Processing), a novel active networks architecture that enables ephemeral storage of information on routers in order to ease distributed application synchronisation and co-operation. We aimed at a design compatible with modern routers hardware and with network operators' goals. Our solution has to scale with the number of interfaces of the device and to support throughput of several Gbps. Throughout this thesis we searched for the best trade-off between features (platform exibility) and guarantees (platform safety), with as little performance sacri ce as possible. We picked the Ephemeral State Processing (ESP) router, developed by K. Calvert's team at University of Kentucky, as a starting point and extended it with our own virtual processor (VPU) to offer higher exibility to the network programmer. The VPU is a minimalist bytecode interpreter that manipulates the content of the "ephemeral state store" of the router according to a microprogram present in packets. It ultimately allows the microprogram to drop or forward the packet on any router, acting as remotely programmable filters around unmodified IP routing cores. We developed two implementations of WASP: a "reference" module for the Linux kernel, and, based on that prototype experience, a WASP filter application for the IXP2400 network processor that proves feasibility of our platform at higher speed. We extensively tested those two implementations against their ESP counterpart in order to estimate the overhead of our approach. High speed tests on the IXP were also performed to ensure WASP's robustness, and were actually rich in lessons for future development on programmable network devices. The nature of WASP makes it a platform of choice to detect properties of the network along a given path. Thanks to per-flow variables (even if ephemeral) and its ability to sustain custom processing at wire-speed, we can for instance implement lightweight measurement of QoS parameters or enforce application-specific congestion control. We have however opted -- in the context of this thesis -- for a focus on another use of the platform: using the ephemeral state to advertise and detect members of distributed applications (e.g. grid computing or peer-to-peer systems) in a purely decentralised way. To evaluate the benefits of this approach, we propose a model of a peer-to-peer community where peers try and join former neighbours, and we show through simulations how efficiency and quality of user experience evolve with the presence of more WASP routers in the network.

A drug discovery project typically starts with a pharmacological hypothesis: that the modulation of a specific molecular biological mechanism would be beneficial in the treatment of the targeted disease. In a small-molecule project, the next step is to identify hits, i.e. molecules that can effect this modulation. These hits are subsequently expanded into hit series, which are optimised with respect to pharmacodynamic and pharmacokinetic properties, through medicinal chemistry. Finally, a drug candidate is clinically developed into a new drug. This thesis concerns the use of structure-based virtual screening in the hit identification phase of drug discovery. Structure-based virtual screening involves using the known 3D structure of a target protein to predict binders, through the process of docking and scoring. Docking is the prediction of potential binding poses, and scoring is the prediction of the free energy of binding from those poses. Two new methodologies, based on post-processing of scoring results, were developed and evaluated using model systems. Both methods significantly increased the enrichment of true positives. Furthermore, correlation was observed between scores and simple molecular properties, and identified as a source of false positives in structure-based virtual screening. Two target proteins, Mycobacterium tuberculosis ribose-5-phosphate isomerase, a potential drug target in tuberculosis, and Plasmodium falciparum spermidine synthase, a potential drug target in malaria, were subjected to docking and virtual screening. Docking of substrates and products of ribose-5-phosphate isomerase led to hypotheses on the role of individual residues in the active site. Additionally, virtual screening was used to predict 48 potential inhibitors, but none was confirmed as an inhibitor or binder to the target enzyme. For spermidine synthase, structure-based virtual screening was used to predict 32 potential active-site binders. Seven of these were confirmed to bind in the active site.

This thesis analyzes major microarray repositories and presents a metadata framework both to address the current issues and to promote the main operations such as knowledge discovery, sharing, integration, and exchange. The proposed framework is demonstrated in a case study on real data and can be used for other high throughput repositories in biomedical domain. Not only the number of microarray experimentation increases, but also the size and complexity of the results rise in response to biomedical inquiries. And, experiment results are significant when examined in a batch and placed in a biological context. There have been standardization initiatives on content, object model, exchange format, and ontology. However, they have proprietary information space. There are backlogs and the data cannot be exchanged among the repositories. There is a need for a format and data management standard at present.iv v We introduced a metadata framework to include metadata card and semantic nets to make the experiment results visible, understandable and usable. They are encoded in standard syntax encoding schemes and represented in XML/RDF. They can be integrated with other metadata cards, semantic nets and can be queried. They can be exchanged and shared. We demonstrated the performance and potential benefits with a case study on a microarray repository. This study does not replace any product on repositories. A metadata framework is required to manage such huge data. We state that the backlogs can be reduced, complex knowledge discovery queries and exchange of information can become possible with this metadata framework.

The main purpose of this study is to analyse how the main themes of alienation and the search for identity is portrayed by Swedish author Inger Edelfeldt. I have applied the theories of Rita Felski concerning feminist novels of self-discovery, in which the development of the female identity is the main question. As Edelfeldt’s writing consists of literature for the young as well as adults, I have included material from both of these genres. I have also taken use of Ulla Lundqvists theories about Swedish juvenile books when examining aspects of the main character’s feelings of alienation and identity searching. The results of my analysis show that the reading of my material as feminist novels of self-discovery has revealed pervading charachteristics of alienation, love, friendship and psychological development. The genre-crossing tendency of Edelfeldt’s writing shows in that the theme of identity crisis and the search for identity is an important issue in all of her novels, despite the protagonist’s age. Finally, I show in my study, that by rejecting the heterosexual love-story narrative, Edelfeldts novels put the woman’s own psychological development in focus.

This paper seeks to fill a gap in the literature regarding the consequences of banning ‘naked’ Credit Default Swaps (CDS). In particular, I use the European Union’s Ban on ‘naked” Sovereign CDS as an event study to evaluate the impact that banning such derivative products has on the price discovery process in the credit markets. Using both Granger Causality tests and a Vector Error Correction Model, I find that before November 1, 2012, CDS are the clear price leader in the credit markets. However, since the official date the regulation was put into effect, CDS’ price leadership was eroded. Moreover, after the ban, CDS and Bond Yield Spreads are no longer cointegrated in the long run, suggesting that different pricing mechanisms now exist between the two securities

Intelligent Transportation Systems (ITS) are gaining momentum among researchers. ITS encompasses several technologies, including wireless communications, sensor networks, data and voice communication, real-time driving assistant systems, etc. These states of the art technologies are expected to pave the way for a plethora of vehicular network applications. In fact, recently we have witnessed a growing interest in Vehicular Networks from both the research community and industry. Several potential applications of Vehicular Networks are envisioned such as road safety and security, traffic monitoring and driving comfort, just to mention a few. It is critical that the existence of convenience or driving comfort services do not negatively affect the performance of safety services. In essence, the dissemination of safety services or the discovery of convenience applications requires the communication among service providers and service requesters through constrained bandwidth resources. Therefore, service discovery techniques for vehicular networks must efficiently use the available common resources. In this thesis, we focus on the design of bandwidth-efficient and scalable service discovery protocols for Vehicular Networks. Three types of service discovery architectures are introduced: infrastructure-less, infrastructure-based, and hybrid architectures. Our proposed algorithms are network layer based where service discovery messages are integrated into the routing messages for a lightweight discovery. Moreover, our protocols use the channel diversity for efficient service discovery. We describe our algorithms and discuss their implementation. Finally, we present the main results of the extensive set of simulation experiments that have been used in order to evaluate their performance.

This thesis is about protein profiling in blood-derived samples using suspension bead ar- rays built with protein affinity reagents, and the evaluation of binding characteristics and potential disease relation of such profiles. A central aim of the presented work was to discover and verify disease associated protein profiles in blood-derived samples such as serum or plasma. This was based on immobiliz- ing antigens or antibodies on color-coded beads for a multiplexed analysis. This concept generally allow for a dual multiplexing because hundreds of samples can be screened for hundreds of proteins in a miniaturized and parallelized fashion. At first, protein antigens were used to study humoral immune responses in cattle suffering from a mycoplasma infec- tion (Paper I). Here, the most immunogenic of the applied antigens were identified based on reactivity profiles from the infected cattle, and were combined into an antigen cocktail to serve as a diagnostic assay in a standard ELISA set-up. Next, antibodies and their em- ployment in assays with directly labeled human samples was initiated. This procedure was applied in a study of kidney disorders where screening of plasma resulted in the discovery of a biomarker candidate, fibulin-1 (Paper II). In parallel to the disease related applica- tions, systematic evaluations of the protein profiles were conducted. Protein profiles from 2,300 antibodies were classified on the bases of binding properties in relation to sample heating and stringent washing (Paper III). With a particular focus on heat dependent de- tectability, a method was developed to visualize those proteins that were captured to the beads in an immunoassay by using Western blotting (Paper IV). In conclusion, this thesis presents examples of the possibilities of comparative plasma profiling enabled by protein bead arrays. / <p>QC 20130208</p>

Proteins are essential building blocks in every living cell, and since the complete human genome was sequenced in 2004, researchers have attempted to map the human proteome, which is the functional representation of the genome. One such initiative is the Human Protein Atlas programme (HPA), which generates monospecific antibodies towards all human proteins and uses these for high-throughput tissue profiling on tissue microarrays (TMAs). The results are publically available at the website www.proteinatlas.org. In this thesis, TMAs were used for analysis of expression patterns in various research areas. Different search queries in the HPA were tested and evaluated, and a number of potential biomarkers were identified, e.g. proteins exclusively expressed in islets of Langerhans, but not in exocrine glandular cells or other abdominal organs close to pancreas. The identified candidates were further analyzed on TMAs with pancreatic tissues from normal and diabetic individuals, and colocalization studies with insulin and glucagon revealed that several of the investigated proteins (DGCR2, GBF1, GPR44 and SerpinB10) appeared to be beta cell specific. Moreover, a set of proteins differentially expressed in lung cancer stroma was further analyzed on a clinical lung cancer cohort in the TMA format, and one protein (CD99) was significantly associated with survival. In addition, TMAs with tissue samples from different species were generated, e.g. for mapping of influenza virus attachment in various human and avian tissues. The results showed that the gull influenza virus H16N3 attached to human respiratory tract and eye, suggesting possible transmission of the virus between gull and human. TMAs were also used for analysis of protein expression differences between humans and other primates, and two proteins (TCF3 and SATB2) proved to be significantly differentially expressed on the human lineage at both the protein level and the RNA level.   In conclusion, this thesis exemplifies the potential of the TMA technology, which can be used for analysis of expression patterns in a large variety of research fields, such as biomarker discovery, influenza virus research or further understanding of human evolution.