The State of the Art in Language Workbenches. Conclusions from the Language Workbench Challenge

Language workbenches are tools that provide high-level mechanisms for the implementation of (domain-specific) languages. Language workbenches are an active area of research that also receives many contributions from industry. To compare and discuss existing language workbenches, the annual Language Workbench Challenge was launched in 2011. Each year, participants are challenged to realize a given domain-specific language with their workbenches as a basis for discussion and comparison. In this paper, we describe the state of the art of language workbenches as observed in the previous editions of the Language Workbench Challenge. In particular, we capture the design space of language workbenches in a feature model and show where in this design space the participants of the 2013 Language Workbench Challenge reside. We compare these workbenches based on a DSL for questionnaires that was realized in all workbenches

OFraMP: a fragment-based tool to facilitate the parametrization of large molecules

An Online tool for Fragment-based Molecule Parametrization (OFraMP) is described. OFraMP is a web application for assigning atomic interaction parameters to large molecules by matching sub-fragments within the target molecule to equivalent sub-fragments within the Automated Topology Builder (ATB, atb.uq.edu.au) database. OFraMP identifies and compares alternative molecular fragments from the ATB database, which contains over 890,000 pre-parameterized molecules, using a novel hierarchical matching procedure. Atoms are considered within the context of an extended local environment (buffer region) with the degree of similarity between an atom in the target molecule and that in the proposed match controlled by varying the size of the buffer region. Adjacent matching atoms are combined into progressively larger matched sub-structures. The user then selects the most appropriate match. OFraMP also allows users to manually alter interaction parameters and automates the submission of missing substructures to the ATB in order to generate parameters for atoms in environments not represented in the existing database. The utility of OFraMP is illustrated using the anti-cancer agent paclitaxel and a dendrimer used in organic semiconductor devices. Graphical abstract: OFraMP applied to paclitaxel (ATB ID 35922).[Figure not available: see fulltext.

Engineered Bivalent Ligands to Bias ErbB Receptor-mediated Signaling and Phenotypes

The ErbB receptor family is dysregulated in many cancers, and its therapeutic manipulation by targeted antibodies and kinase inhibitors has resulted in effective chemotherapies. However, many malignancies remain refractory to current interventions. We describe a new approach that directs ErbB receptor interactions, resulting in biased signaling and phenotypes. Due to known receptor-ligand affinities and the necessity of ErbB receptors to dimerize to signal, bivalent ligands, formed by the synthetic linkage of two neuregulin-1β (NRG) moieties, two epidermal growth factor (EGF) moieties, or an EGF and a NRG moiety, can potentially drive homotypic receptor interactions and diminish formation of HER2-containing heterodimers, which are implicated in many malignancies and are a prevalent outcome of stimulation by native, monovalent EGF, or NRG. We demonstrate the therapeutic potential of this approach by showing that bivalent NRG (NN) can bias signaling in HER3-expressing cancer cells, resulting in some cases in decreased migration, inhibited proliferation, and increased apoptosis, whereas native NRG stimulation increased the malignant potential of the same cells. Hence, this new approach may have therapeutic relevance in ovarian, breast, lung, and other cancers in which HER3 has been implicated

Molecular mechanisms that underlie the receptor specificity of ErbB ligands

Contains fulltext : 74880.pdf (publisher's version ) (Open Access)RU Radboud Universiteit Nijmegen, 12 januari 2010243 p

Interaction Design for Fragment-Based Molecule Parameterisation

Computational chemists frequently use molecular simulations in computer-aided drug design. As input, these simulations require molecules that have been parameterised with atom charges. Typically, these charges are obtained from complex quantum-mechanical calculations, which are only feasible for small molecules. We propose a new approach for molecule parameterisation, which uses matching fragments from a repository of molecules that have already been parameterised. This approach has been implemented in a system called OFraMP, for which two dierent interaction designs have been compared in a user study. We found that a reactive interaction design without automation yields better results than one that proactively makes suggestions to the user. This version is also preferred by the experiment participants. With a few improvements to the fragment matching algorithm, OFraMP should become a system that produces high-quality results in a shorter time than the current quantum-mechanical calculation systems

Quantification of ErbB3 receptor density on human breast cancer cells, using a stable radio-labeled mutant of NRG1beta

Item does not contain fulltext5 p

Interactive visualization and task management on the 48-core Intel SCC

International audienceIn this paper we propose and describe how we have built a tool that enables a user to interactively monitor and manage a many-core system like the 48-core experimental Single-chip Cloud Computer (SCC), which was created by Intel Labs targeting the many-core research community. We provide the user with a visual representation of the current state of the system on multiple levels of detail, such as chip, core and task. We allow the user to create, start, pause and migrate tasks across different cores. We also allow the user to easily adjust the voltage and frequency of the chip. However this tool can run on any PC with a screen and input devices, we have optimized the interface to run on a multi-touch device for the best ease of use

Interactive visualization and task management on the 48-core Intel SCC

In this paper we propose and describe how we have built a tool that enables a user to interactively monitor and manage a many-core system like the 48-core experimental Singlechip Cloud Computer (SCC), which was created by Intel Labs targeting the many-core research community. We provide the user with a visual representation of the current state of the system on multiple levels of detail, such as chip, core and task. We allow the user to create, start, pause and migrate tasks across different cores. We also allow the user to easily adjust the voltage and frequency of the chip. However this tool can run on any PC with a screen and input devices, we have optimized the interface to run on a multi-touch device for the best ease of use