Neuregulins with an Ig-like domain are essential for mouse myocardial and neuronal development.

Neuregulins are ligands for the erbB family of receptor tyrosine kinases and mediate growth and differentiation of neural crest, muscle, breast cancer, and Schwann cells. Neuregulins contain an epidermal growth factor-like domain located C-terminally to either an Ig-like domain or a cysteine-rich domain specific to the sensory and motor neuron-derived isoform. Here it is shown that elimination of the Ig-like domain-containing neuregulins by homologous recombination results in embryonic lethality associated with a deficiency of ventricular myocardial trabeculation and impairment of cranial ganglion development. The erbB receptors are expressed in myocardial cells and presumably mediate the neuregulin signal originating from endocardial cells. The trigeminal ganglion is reduced in size and lacks projections toward the brain stem and mandible. We conclude that IgL-domain-containing neuregulins play a major role in cardiac and neuronal development.

Phage display selection of ligand residues important for Src homology 3 domain binding specificity.

The Src homology 3 (SH3) domain is a 50-aa modular unit present in many cellular proteins involved in intracellular signal transduction. It functions to direct protein-protein interactions through the recognition of proline-rich motifs on associated proteins. SH3 domains are important regulatory elements that have been demonstrated to specify distinct regulatory pathways important for cell growth, migration, differentiation, and responses to the external milieu. By the use of synthetic peptides, ligands have been shown to consist of a minimum core sequence and to bind to SH3 domains in one of two pseudosymmetrical orientations, class I and class II. The class I sites have the consensus sequence ZP(L/P)PP psi P whereas the class II consensus is PP psi PPZ (where psi is a hydrophobic residue and Z is a SH3 domain-specific residue). We previously showed by M13 phage display that the Src, Fyn, Lyn, and phosphatidylinositol 3-kinase (PI3K) SH3 domains preferred the same class I-type core binding sequence, RPLPP psi P. These results failed to explain the specificity for cellular proteins displayed by SH3 domains in cells. In the current study, class I and class II core ligand sequences were displayed on the surface of bacteriophage M13 with five random residues placed either N- or C-terminal of core ligand residues. These libraries were screened for binding to the Src, Fyn, Lyn, Yes, and PI3K SH3 domains. By this approach, additional ligand residue preferences were identified that can increase the affinity of SH3 peptide ligands at least 20-fold compared with core peptides. The amino acids selected in the flanking sequences were similar for Src, Fyn, and Yes SH3 domains; however, Lyn and PI3K SH3 domains showed distinct binding specificities. These results indicate that residues that flank the core binding sequences shared by many SH3 domains are important determinants of SH3 binding affinity and selectivity.

A protein-binding domain, EH, identified in the receptor tyrosine kinase substrate Eps15 and conserved in evolution.

In this report we structurally and functionally define a binding domain that is involved in protein association and that we have designated EH (for Eps15 homology domain). This domain was identified in the tyrosine kinase substrate Eps15 on the basis of regional conservation with several heterogeneous proteins of yeast and nematode. The EH domain spans about 70 amino acids and shows approximately 60% overall amino acid conservation. We demonstrated the ability of the EH domain to specifically bind cytosolic proteins in normal and malignant cells of mesenchymal, epithelial, and hematopoietic origin. These observations prompted our search for additional EH-containing proteins in mammalian cells. Using an EH domain-specific probe derived from the eps15 cDNA, we cloned and characterized a cDNA encoding an EH-containing protein with overall similarity to Eps15; we designated this protein Eps15r (for Eps15-related). Structural comparison of Eps15 and Eps15r defines a family of signal transducers possessing extensive networking abilities including EH-mediated binding and association with Src homology 3-containing proteins.

Domain Globalization: Using Languages to Support Technical and Social Coordination

When a project is realized in a globalized environment, multiple stakeholders from different organizations work on the same system. Depending on the stakeholders and their organizations, various (possibly overlapping) concerns are raised in the development of the system. In this context a Domain Specific Language (DSL) supports the work of a group of stakeholders who are responsible for addressing a specific set of concerns. This chapter identifies the open challenges arising from the coordination of globalized domain-specific languages. We identify two types of coordination: technical coordination and social coordination. After presenting an overview of the current state of the art, we discuss first the open challenges arising from the composition of multiple DSLs, and then the open challenges associated to the collaboration in a globalized environment.

Independent component analysis for domain independent watermarking

A new principled domain independent watermarking framework is presented. The new approach is based on embedding the message in statistically independent sources of the covertext to mimimise covertext distortion, maximise the information embedding rate and improve the method's robustness against various attacks. Experiments comparing the performance of the new approach, on several standard attacks show the current proposed approach to be competitive with other state of the art domain-specific methods.

ArchWiSeN: uma estratégia baseada em modelos para desenvolvimento de aplicações para redes de sensores e atuadores sem fio

Wireless Sensor and Actuator Networks (WSAN) are a key component in Ubiquitous Computing Systems and have many applications in different knowledge domains. Programming for such networks is very hard and requires developers to know the available sensor platforms specificities, increasing the learning curve for developing WSAN applications. In this work, an MDA (Model-Driven Architecture) approach for WSAN applications development called ArchWiSeN is proposed. The goal of such approach is to facilitate the development task by providing: (i) A WSAN domain-specific language, (ii) a methodology for WSAN application development; and (iii) an MDA infrastructure composed of several software artifacts (PIM, PSMs and transformations). ArchWiSeN allows the direct contribution of domain experts in the WSAN application development without the need of specialized knowledge on WSAN platforms and, at the same time, allows network experts to manage the application requirements without the need for specific knowledge of the application domain. Furthermore, this approach also aims to enable developers to express and validate functional and non-functional requirements of the application, incorporate services offered by WSAN middleware platforms and promote reuse of the developed software artifacts. In this sense, this Thesis proposes an approach that includes all WSAN development stages for current and emerging scenarios through the proposed MDA infrastructure. An evaluation of the proposal was performed by: (i) a proof of concept encompassing three different scenarios performed with the usage of the MDA infrastructure to describe the WSAN development process using the application engineering process, (ii) a controlled experiment to assess the use of the proposed approach compared to traditional method of WSAN application development, (iii) the analysis of ArchWiSeN support of middleware services to ensure that WSAN applications using such services can achieve their requirements ; and (iv) systematic analysis of ArchWiSeN in terms of desired characteristics for MDA tool when compared with other existing MDA tools for WSAN.

Two case studies on generating administrative process applications with AdminDSL

Some organizations end up reimplementing the same class of business process over and over: an "administrative process", which consists of managing a form through several states and involving various roles in the organization. This results in wasted time that could be dedicated to better understanding the process or dealing with the fine details that are specific to the process. Existing virtual office solutions require specific training and infrastructure andmay result in vendor lock-in. In this paper, we propose using a high-level domain-specific language (AdminDSL) to describe the administrative process and a separate code generator targeting a standard web framework. We have implemented the approach using Xtext, EGL and the Django web framework, and we illustrate it through two case studies: a synthetic examination process which illustrates the architecture of the generated code, and a real-world workplace survey process that identified several future avenues for improvement.

Toward Self-Organising Service Communities

This paper discusses a framework in which catalog service communities are built, linked for interaction, and constantly monitored and adapted over time. A catalog service community (represented as a peer node in a peer-to-peer network) in our system can be viewed as domain specific data integration mediators representing the domain knowledge and the registry information. The query routing among communities is performed to identify a set of data sources that are relevant to answering a given query. The system monitors the interactions between the communities to discover patterns that may lead to restructuring of the network (e.g., irrelevant peers removed, new relationships created, etc.).

Enhancing the Expressiveness of the Bunge-Wand-Weber Ontology

In practical terms, conceptual modeling is at the core of systems analysis and design. The plurality of modeling methods available has however been regarded as detrimental, and as a strong indication that a common view or theoretical grounding of modeling is wanting. This theoretical foundation must universally address all potential matters to be represented in a model, which consequently suggested ontology as the point of departure for theory development. The Bunge–Wand–Weber (BWW) ontology has become a widely accepted modeling theory. Its application has simultaneously led to the recognition that, although suitable as a meta-model, the BWW ontology needs to be enhanced regarding its expressiveness in empirical domains. In this paper, a first step in this direction has been made by revisiting BUNGE’s ontology, and by proposing the integration of a “hierarchy of systems” in the BWW ontology for accommodating domain specific conceptualizations.

Automated code checking

Most buildings constructed in Australia must comply with the Building Code of Australia (BCA). Checking for compliance against the BCA is a major task for both designers and building surveyors. This project carries out a prototype research using the EDM Model Checker and the SMC Model Checker for automated design checking against the Building Codes of Australia for use in professional practice. In this project, we develop a means of encoding design requirements and domain specific knowledge for building codes and investigate the flexibility of building models to contain design information. After assessing two implementations of EDM and SMC that check compliance against deemed-to-satisfy provision of building codes relevant to access by people with disabilities, an approach to automated code checking using a shared object-oriented database is established. This project can be applied in other potential areas – including checking a building design for non-compliance of many types of design requirements. Recommendations for future development and use in other potential areas in construction industries are discussed

Automated code checking

Most buildings constructed in Australia must comply with the Building Code of Australia (BCA). Checking for compliance against the BCA is a major task for both designers and building surveyors. This project carries out a prototype research using the EDM Model Checker and the SMC Model Checker for automated design checking against the Building Codes of Australia for use in professional practice. In this project, we develop a means of encoding design requirements and domain specific knowledge for building codes and investigate the flexibility of building models to contain design information. After assessing two implementations of EDM and SMC that check compliance against deemed-to-satisfy provision of building codes relevant to access by people with disabilities, an approach to automated code checking using a shared object-oriented database is established. This project can be applied in other potential areas – including checking a building design for non-compliance of many types of design requirements. Recommendations for future development and use in other potential areas in construction industries are discussed.

A genetic algorithm for the multi-source and multi-sink minimum vertex cut problem and its applications

We present a new penalty-based genetic algorithm for the multi-source and multi-sink minimum vertex cut problem, and illustrate the algorithm’s usefulness with two real-world applications. It is proved in this paper that the genetic algorithm always produces a feasible solution by exploiting some domain-specific knowledge. The genetic algorithm has been implemented on the example applications and evaluated to show how well it scales as the problem size increases.

Fabrication of osteochondral scaffolds with stereolithography

The osteochondral defect is a classical model for a multiple-tissue problem[1]. Tissue engineering of either bone or cartilage imposes different demands on a scaffold concerning porosity, pore size and interconnectivity. Furthermore, local release of tissue-specific growth factors necessitates a tailored architecture. For the fabrication of an osteochondral scaffold with region specific architecture, an advanced technique is required. Stereolithography is a rapid prototyping technique that allows for the creation of such 3D polymer objects with well-defined architecture. Its working principle is the partial irradiation of a resin, causing a liquid-solid transition. By irradiating this resin by a computer-driven light source, a solid 3D object is constructed layer by layer. To make biodegradable polymers applicable in stereolithography, low-molecular weight polymers have to be functionalised with double bonds to enable photo-initiated crosslinking.

Financial planning and well-being

The aim of this paper is to provide a review of the theoretical and research literature on the ways in which financial planning can enhance well-being. In reviewing the literature, the paper develops a conceptual framework for thinking about the extended value of financial planning, beyond financial outcomes, by examining the process of planning in the financial domain and its relationship to life satisfaction, living an intentional life, attainment of life goals, and the development of a sense of mastery. An essential element of psychological well-being is engagement in life tasks and roles. Planning can be considered a life management strategy that enables individuals to control and structure their lives. Having meaningful goals and the plans to achieve those goals enable individuals to experience higher levels of life engagement and well-being (MacLeod et al., 2008). Recent research on well-being suggests that domain-specific behaviours contribute to domain-specific satisfactions, which in turn contribute to an individual’s overall satisfaction with life (Easterlin, 2003; 2006). Thus changes in domain satisfaction, such as financial satisfaction, are likely to effect changes in life satisfaction.

Adult learning in a workplace context

In light of the changing nature of contemporary workplaces, this chapter attempts to identify employer expectations and the associated skills required to workers to function effectively in such workplaces. Workers are required to participate in informed discussion about their specific jobs and to contribute to the overall development of organisations. This requires deep understanding of domain-specific knowledge, which at times can be very complex. Workers are also required to take responsibility for their actions and are expected to be flexible so that they can be deployed to other related jobs depending on demand. Finally, workers are expected to be pro-active, be able to anticipate situations and continuously update their knowledge to address new situations. This chapter discusses the nature of knowledge and skills that will facilitate the above qualities.