Hierarchical models for service-oriented systems

We present our approach to the denotation and representation of hierarchical graphs: a suitable algebra of hierarchical graphs and two domains of interpretations. Each domain of interpretation focuses on a particular perspective of the graph hierarchy: the top view (nested boxes) is based on a notion of embedded graphs while the side view (tree hierarchy) is based on gs-graphs. Our algebra can be understood as a high-level language for describing such graphical models, which are well suited for defining graphical representations of service-oriented systems where nesting (e.g. sessions, transactions, locations) and linking (e.g. shared channels, resources, names) are key aspects

An Algebra of Hierarchical Graphs

We define an algebraic theory of hierarchical graphs, whose axioms characterise graph isomorphism: two terms are equated exactly when they represent the same graph. Our algebra can be understood as a high-level language for describing graphs with a node-sharing, embedding structure, and it is then well suited for defining graphical representations of software models where nesting and linking are key aspects

Undersøgelser over Frøsamlers Værdi til Indsamling af Korn og Ukrudtsfrø i Kornmarker.

Undersøgelser over Frøsamlers Værdi til Indsamling af Korn ogUkrudtsfrø i Kornmarker

On the expressiveness of forwarding in higher-order communication

Abstract. In higher-order process calculi the values exchanged in communications may contain processes. There are only two capabilities for received processes: execution and forwarding. Here we propose a limited form of forwarding: output actions can only communicate the parallel composition of statically known closed processes and processes received through previously executed input actions. We study the expressiveness of a higher-order process calculus featuring this style of communication. Our main result shows that in this calculus termination is decidable while convergence is undecidable.

New in vitro interaction-parasite reduction ratio assay for early derisk in clinical development of antimalarial combinations

The development and spread of drug-resistant phenotypes substantially threaten malaria control efforts. Combination therapies have the potential to minimize the risk of resistance development but require intensive preclinical studies to determine optimal combination and dosing regimens. To support the selection of new combinations, we developed a novel in vitro-in silico combination approach to help identify the pharmacodynamic interactions of the two antimalarial drugs in a combination which can be plugged into a pharmacokinetic/pharmacodynamic model built with human monotherapy parasitological data to predict the parasitological endpoints of the combination. This makes it possible to optimally select drug combinations and doses for the clinical development of antimalarials. With this assay, we successfully predicted the endpoints of two phase 2 clinical trials in patients with the artefenomel-piperaquine and artefenomel-ferroquine drug combinations. In addition, the predictive performance of our novel in vitro model was equivalent to that of the humanized mouse model outcome. Last, our more informative in vitro combination assay provided additional insights into the pharmacodynamic drug interactions compared to the in vivo systems, e.g., a concentration-dependent change in the maximum killing effect (Emax) and the concentration producing 50% of the killing maximum effect (EC50) of piperaquine or artefenomel or a directional reduction of the EC50 of ferroquine by artefenomel and a directional reduction of Emax of ferroquine by artefenomel. Overall, this novel in vitro-in silico-based technology will significantly improve and streamline the economic development of new drug combinations for malaria and potentially also in other therapeutic areas

Dynamics of a Staphylococcus aureus infective endocarditis simulation model

Infective endocarditis (IE) is a serious infection of the inner surface of heart, resulting from minor lesions in the endocardium. The damage induces a healing reaction, which leads to recruitment of fibrin and immune cells. This sterile healing vegetation can be colonized during temporary bacteremia, inducing IE. We have previously established a novel in vitro IE model using a simulated IE vegetation (IEV) model produced from whole venous blood, on which we achieved stable bacterial colonization after 24h. The bacteria were organized in biofilm aggregates and displayed increased tolerance towards antibiotics. In this current study, we aimed at further characterizing the time course of biofilm formation and the impact on antibiotic tolerance development. We found that a S. aureus reference strain, as well as three clinical IE isolates formed biofilms on the IEV after 6h. When treatment was initiated immediately after infection, the antibiotic effect was significantly higher than when treatment was started after the biofilm was allowed to mature. We could follow the biofilm development microscopically by visualizing growing bacterial aggregates on the IEV. The findings indicate that mature, antibiotic-tolerant biofilms can be formed in our model already after 6h, accelerating the screening for optimal treatment strategies for IE