Approaching parameter estimation from the discrete-time domain is the dominating paradigm in system identification. Identification of continuous-time models on the other hand is motivated by the fact that modelling of physical systems often take place in continuous-time. For many practical applications there is also a genuine interest in the parameters connected to these physical models. The most important element of time- and frequency-domain identification from sampled data is the discrete-time system, which is connected to the parameters of the underlying continuous-time system. For input-output models, it governs the frequency response from the sampled input to the sampled output. In case of time series, it models the spectrum of the sampled output. As the rate of sampling increase, the relationship between the discrete- and continuous-time parameters can become more or less ill-conditioned. Mainly, because the gathering of the poles of the discrete-time system around the value 1 in the complex plane will produce numerical difficulties while mapping back to the continuous-time parameters. We will therefore investigate robust alternatives to using the exact discrete-time system, which are based on more direct use of the continuous-time system. Another, maybe more important, reason for studying such approximations is that they will provide insight into how one can deal with non-uniformly sampled data. An equally important issue in system identification is the effect of model choice. The user might not know a lot about the system to begin with. Often, the model will only capture a particular aspect of the data which the user is interested in. Deviations can, for instance, be due to mis-readings while taking measurements or un-modelled dynamics in the case of dynamical systems. They can also be caused by misunderstandings about the continuous-time signal that underlies sampled data. From a user perspective, it is important to be able to control how and to what extent these un-modelled aspects influence the quality of the intended model. The classical way of reducing the effect of modelling errors in statistics, signal processing and identification in the time-domain is to introduce a robust norm into the criterion function of the method. The thesis contains results which quantify the effect of broad-band disturbances on the quality of frequency-domain parameter estimates. It also contains methods to reduce the effect of narrow-band disturbances or frequency domain outliers on frequency-domain parameter estimates by means of methods from robust statistics.

Protein-protein interactions are of vital importance to the cell as they mediate the assembly of protein complexes that carry out diverse biological functions. Many proteins involved in cellular signaling are built by the combinatorial use of peptide recognition modules (PRMs), which are small protein domains that bind to their cognate ligands by recognizing short linear peptide motifs. Thousands of PRMs are found in nature, requiring improved methods to better elucidate their molecular determinants of binding and to allow accurate mapping of their interaction networks. In this thesis, I describe the development and application of phage-displayed peptide libraries to map the binding specificities of two common PRMs. First, I generated specificity profiles for 82 C. elegans and human PDZ domains that could be organized into a specificity map. The map revealed that PDZ domains have far greater substrate sequence specificity than previously believed, providing significant insights into the relationships between PDZ structure and specificity, and allowing specificity prediction for uncharacterized domains. My results were used to predict both endogenous and pathogenic PDZ interactions. This analysis revealed that viruses have evolved ligands that specifically mimic PDZ domains to subvert host cell immunity. Second, I analyzed the binding specificity for the SH3 domain family in S. cerevisae. I found that, like PDZ domains, SH3 domains have binding specificities that are more detailed than the conventional classification system. The phage-derived specificity profiles were combined with data from oriented peptide and yeast two-hybrid screening to generate a highly accurate SH3 domain interaction network. Given the prominent role of SH3 domains in endocytosis, the SH3 domain interaction data was used to predict the dynamic localization of several uncharacterized endocytosis proteins, which was subsequently confirmed by cell-based assays. The application of the techniques described here to other PRM families will significantly improve protein interaction maps for signaling pathways, which will illuminate our understanding of the cell circuitry, allow the use of PRMs as general affinity reagent and detection tools, and guide the development of small molecule inhibitors that mimic their peptide ligands for therapeutic intervention.

Protein-protein interactions are of vital importance to the cell as they mediate the assembly of protein complexes that carry out diverse biological functions. Many proteins involved in cellular signaling are built by the combinatorial use of peptide recognition modules (PRMs), which are small protein domains that bind to their cognate ligands by recognizing short linear peptide motifs. Thousands of PRMs are found in nature, requiring improved methods to better elucidate their molecular determinants of binding and to allow accurate mapping of their interaction networks. In this thesis, I describe the development and application of phage-displayed peptide libraries to map the binding specificities of two common PRMs. First, I generated specificity profiles for 82 C. elegans and human PDZ domains that could be organized into a specificity map. The map revealed that PDZ domains have far greater substrate sequence specificity than previously believed, providing significant insights into the relationships between PDZ structure and specificity, and allowing specificity prediction for uncharacterized domains. My results were used to predict both endogenous and pathogenic PDZ interactions. This analysis revealed that viruses have evolved ligands that specifically mimic PDZ domains to subvert host cell immunity. Second, I analyzed the binding specificity for the SH3 domain family in S. cerevisae. I found that, like PDZ domains, SH3 domains have binding specificities that are more detailed than the conventional classification system. The phage-derived specificity profiles were combined with data from oriented peptide and yeast two-hybrid screening to generate a highly accurate SH3 domain interaction network. Given the prominent role of SH3 domains in endocytosis, the SH3 domain interaction data was used to predict the dynamic localization of several uncharacterized endocytosis proteins, which was subsequently confirmed by cell-based assays. The application of the techniques described here to other PRM families will significantly improve protein interaction maps for signaling pathways, which will illuminate our understanding of the cell circuitry, allow the use of PRMs as general affinity reagent and detection tools, and guide the development of small molecule inhibitors that mimic their peptide ligands for therapeutic intervention.

Univ., Diss.--Bern, 1999.

Univ., Diss.--Frankfurt am Main, 2002. / Literaturverz. S. XV - XIX.

Univ., Diss., 2009--Mainz. / Includes bibliographical references.

Cette thèse traite du rôle de la chaperonne d'histone ASF1 dans la déposition des histones au cours de la réplication. / That thesis is about the role of ASF1 in histone deposition during replication.

Protection of domain names The aim of this work is to place domain names in the legal system, to try their legal classification, explore ways they can be compromised, and to analyze the possibilities of their protection. Particular attention is paid to the international management of domain names and legal grounds of the issue. Given that the topic of protection of domain names is relatively little explored, particular primary sources of relevant information will be subject to review, ie international standards and laws, as well as technical articles and case law. Resources will be handled mainly by descriptive and analytical research method, sometimes complemented by a historical method. The first part defines the basic concepts largely of a technical nature relating to the internet and domain names whose knowledge is essential to understand the issue and its legal assessment. The second part defines the term and the concept of domains and domain names and their permissible forms, and also presents a typology of Top Level Domains. The third part deals with international and national management of domains and domain names. It presents the most important authorities in the field of domain names, key institutions and organizations, the circumstances of their foundation, and international and national...

Many companies and organisations today suffer from Denial-of-Service (DoS) attacks, which can have direct and indirect economical consequences. This thesis tackles this problem with a novel approach by utilising domain specific behaviour and knowledge. The goal is to distinguish malicious attacks from legitimate usage and to alter overall system behaviour at the event of a DoS attack. Distributed DoS attacks (DDoS) are examined as well as a category suggested in this thesis, namely Domain DoS attacks. A simple e-commerce system is developed based on the principles of Domain-Driven Design in order to test the given approach. Five examples of DoS attacks are presented and tested towards the system. The results indicate that utilising domain behaviour is a suitable approach in order to mitigate DoS attacks, but it requires deep integration with the application itself. / Många företag och organisationer lider idag av Denial-of-Service-attacker (DoS-attacker), som kan få direkta och indirekta ekonomiska konsekvenser. Denna avhandling ser nytänkande på detta problem genom att dra nytta av domänspecifikt beteende och kunskap. Målet är att skilja skadliga attacker från legitimt användande och att ändra systemets beteende i händelse av en DoS-attack. Distribuerade DoS-attacker (DDoS) undersöks så väl som en kategori föreslagen i denna avhandling, kallad Domän DoS-attacker. Ett enkelt e-handelssystem utvecklas baserat på principer från domändriven design i syfte att testa den givna tesen. Fem exempel av DoS-attacker är presenterade och testade gentemot systemet. Resultaten indikerar att utnyttjandet av domänbeteende är ett lämpligt tillvägagångssätt för att avvärja DoS-attacker, men att det kräver djup integration med applikationen.

The Src homology 3 domain (SH3) and cysteine rich domain (C1) 3 (Stac3) gene is a novel gene copiously expressed in skeletal muscle. The objective of this research was to determine the role of Stac3 in development, specifically in skeletal muscle. We achieved this objective by evaluating the phenotypic effects of Stac3 gene inactivation on development in mice. At birth homozygous Stac3 null (Stac3-/-) mice died perinatally and remained in fetal position with limp limbs, but possessed otherwise normal organs based on gross and histological evaluations. The primary phenotypes displayed at term in Stac3-/- mice were reduced late gestational body weights, increased prevalence of myotubes with centrally located nuclei and severe deformities throughout all skeletal muscles. At embryonic day 18.5 (E18.5) Stac3-/- mice displayed a 12.7% reduction (P < 0.001) in weight compared to wild type (Stac3+/+) or heterozygous (Stac3+/-) littermates while at E15.5 body weights and morphology were similar. At birth (P0) and at E17.5, Stac3-/- mice had 59% and 24% (P < 0.001) more myotubes with centrally located nuclei, respectively, than Stac3+/- or Stac3+/+ littermates. Stac3-/- mice also displayed increased myotube and myofiber cross sectional area at P0 (P < 0.001) and E17.5 (P < 0.05) with disorganized fiber bundling. Overall, these data show Stac3 is necessary for development of viable offspring and suggest Stac3 plays a critical role in fetal development where its primary phenotype is exhibited in skeletal muscle. / Master of Science