Ribosome display of mammalian receptor domains

Many mammalian receptor domains, among them a large number of potential therapeutic target proteins, are highly aggregation-prone upon heterologous expression in bacteria. This severely limits functional studies of such receptor domains and also their engineering towards improved properties. One of these proteins is the Nogoreceptor, which plays a central role in mediating the inhibition of axon growth and functional recovery after injury of the adult mammalian central nervous system. We show here that the ligand binding domain of the Nogoreceptor folds to an active conformation in ternary ribosomal complexes, as formed in ribosome display. In these complexes the receptor is still connected, via a C-terminal tether, to the peptidyl tRNA in the ribosome and the mRNA also stays connected. The ribosome prevents aggregation of the protein, which aggregates as soon as the release from the ribosome is triggered. In contrast, no active receptor was observed in phage display, where aggregation appears to prevent incorporation of the protein into the phage coat. This strategy sets the stage for rapidly studying defined mutations of such aggregation-prone receptors in vitro and to improve their properties by in vitro evolution using the ribosome display technology.     

Mapping feature models onto domain models: ensuring consistency of configured domain models

We present an approach to model-driven software product line engineering which is based on feature models and domain models. A feature model describes both common and varying properties of the instances of a software product line. The domain model is composed of a structural model (package and class diagrams) and a behavioral model (story diagrams). Features are mapped onto the domain model by annotating elements of the domain model with features. An element of a domain model is specific to the features included in its feature annotation. An instance of the product line is defined by a set of selected features (a feature configuration). A configuration of the domain model is built by excluding all elements whose feature set is not included in the feature configuration. To ensure consistency of the configured domain model, we define constraints on the annotations of inter-dependent domain model elements. These constraints guarantee that a model element may be selected only when the model elements are also included on which it depends. Violations of dependency constraints may be removed automatically with the help of an error repair tool which propagates features to dependent model elements.     

Guanine and plasmid DNA binding of mono- and trinuclear fac-[Re(CO)3]+ complexes with amino acid ligands

We have synthesized and fully characterized four new complexes comprising the fac-[Re(CO)3]+ moiety and the ligands NH3, L-proline (Pro), or N,N-dimethylglycine (dmGly). The reaction of [Re(H2O)3(CO)3]+ with the two amino acids gives trinuclear complexes of general formula [Re(L)(CO)3]3 (where L = amino acid). We have studied the in vitro behavior of these compounds with guanine and DNA in order to understand whether the cytotoxicity exhibited by certain rhenium complexes based on the fac-[Re(CO)3]+ core is due to the formation of nucleobase complexes and inter- or intrastrand links between DNA bases. We have performed model studies with guanine and studied the structural effects induced by different rhenium(I) tricarbonyl complexes on PhiX174 plasmid DNA by electrophoretic methods. Our results show that rhenium complexes with two available coordination sites interact with plasmid DNA to form a stable adduct that is likely to involve two bases.     

Polymerization Catalysis in Liquid Propylene: High Activities and Molecular Weights in Propylene/CO Copolymerization Reactions

Summary: The dicationic [(dppp)Pd(NCCH₃)₂](BF₄)₂ catalyst (dppp = 1,3‐bis(diphenylphosphino)propane) was applied in a liquid monomer, two phase process for the CO/propene copolymerization reaction. For the first time it was possible to synthesize propene/CO copolymers with an activity up to 7 500 g/(mol · h) and molecular weights of 500 000 g/mol. Activities up to 40 000 g/(mol · h) could be obtained with the use of the unsymmetric catalyst [(CF₃‐dppp)Pd(NCCH₃)](BF₄)₂ (CF₃‐dppp = 1‐diphenylphosphino‐3‐bis[3,5‐di(trifluormethyl)phenyl]phosphinopropane) in homogeneous liquid propene solution.

Granules found after copolymerization.     

Towards language-to-language transformation

This paper proposes a simplicity-oriented approach and framework for language-to-language transformation of, in particular, graphical languages. Key to simplicity is the decomposition of the transformation specification into sub-rule systems that separately specify purpose-specific aspects. We illustrate this approach by employing a variation of Plotkin’s Structural Operational Semantics (SOS) for pattern-based transformations of typed graphs in order to address the aspect ‘computation’ in a graph rewriting fashion. Key to our approach are two generalizations of Plotkin’s structural rules: the use of graph patterns as the matching concept in the rules, and the introduction of node and edge types. Types do not only allow one to easily distinguish between different kinds of dependencies, like control, data, and priority, but may also be used to define a hierarchical layering structure. The resulting Type-based Structural Operational Semantics (TSOS) supports a well-structured and intuitive specification and realization of semantically involved language-to-language transformations adequate for the generation of purpose-specific views or input formats for certain tools, like, e.g., model checkers. A comparison with the general-purpose transformation frameworks ATL and Groove, illustrates along the educational setting of our graphical WebStory language that TSOS provides quite a flexible format for the definition of a family of purpose-specific transformation languages that are easy to use and come with clear guarantees.

     

Real-Time Global Illumination for VR Applications

Real-time global illumination in VR systems enhances scene realism by incorporating soft shadows, reflections of objects in the scene, and color bleeding. The Virtual Light Field (VLF) method enables real-time global illumination rendering in VR. The VLF has been integrated with the Extreme VR system for real-time GPU-based rendering in a Cave Automatic Virtual Environment.     

An algebra of hybrid systems

Hybrid systems are heterogeneous systems characterised by the interaction of discrete and continuous dynamics. We present a trajectory-based algebraic model for describing hybrid systems; the trajectories used are closely related to streams. The algebra is based on left quantales and left semirings and provides a new application for these algebraic structures. We show that hybrid automata, which are probably the standard tool for describing hybrid systems, can conveniently be embedded into our algebra. Moreover we point out some important advantages of the algebraic approach. In particular, we show how to handle Zeno effects, which are excluded by most other authors. The development of the theory is illustrated by a running example and a larger case study.     

Tool-supported enhancement of diagnosis in model-driven verification

We show on a case study from an autonomous aerospace context how to apply a game-based model-checking approach as a powerful technique for the verification, diagnosis, and adaptation of system behaviors based on temporal properties. This work is part of our contribution within the SHADOWS project, where we provide a number of enabling technologies for model-driven self-healing. We propose here to use GEAR, a game-based model checker, as a user-friendly tool that can offer automatic proofs of critical properties of such systems. Although it is a model checker for the full modal μ-calculus, it also supports derived, more user-oriented logics. With GEAR, designers and engineers can interactively investigate automatically generated winning strategies for the games, by this way exploring the connection between the property, the system, and the proof. This work has been partially supported by the European Union Specific Targeted Research Project SHADOWS (IST-2006-35157), exploring a Self-Healing Approach to Designing cOmplex softWare Systems. The project’s web page is at . This article is an extended version of Renner et al. [18] presented at ISoLA 2007, Poitiers, December 2007.