187,003 research outputs found
LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA.
No full textThe DExD/H box RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene-5 (mda-5) sense viral RNA in the cytoplasm of infected cells and activate signal transduction pathways that trigger the production of type I interferons (IFNs). Laboratory of genetics and physiology 2 (LGP2) is thought to influence IFN production by regulating the activity of RIG-I and mda-5, although its mechanism of action is not known and its function is controversial. Here we show that expression of LGP2 potentiates IFN induction by polyinosinic-polycytidylic acid [poly(I:C)], commonly used as a synthetic mimic of viral dsRNA, and that this is particularly significant at limited levels of the inducer. The observed enhancement is mediated through co-operation with mda-5, which depends upon LGP2 for maximal activation in response to poly(I:C). This co-operation is dependent upon dsRNA binding by LGP2, and the presence of helicase domain IV, both of which are required for LGP2 to interact with mda-5. In contrast, although RIG-I can also be activated by poly(I:C), LGP2 does not have the ability to enhance IFN induction by RIG-I, and instead acts as an inhibitor of RIG-I-dependent poly(I:C) signaling. Thus the level of LGP2 expression is a critical factor in determining the cellular sensitivity to induction by dsRNA, and this may be important for rapid activation of the IFN response at early times post-infection when the levels of inducer are low
Extending the Model Driven Architecture with a preCIM level
No full textWhilst the successful alignment of business strategy and IT
development is an important topic, there are still few ways that this is possible.
The Model Driven Architecture (MDA) shows promise as an approach but is
focussed firmly in the IT domain at the level of the Platform Independent and
Platform Specific Models. The Computation Independent Model (CIM) is
targetted at business users, but this paper argues that the complexity of the CIM
level disenfranchises them. The concept of a preCIM
level could provide much
richness to the MDA process and give the domain user greater ownership of the
IT development that supports their processes
Embedding Requirements within the Model Driven Architecture
No full textThe Model Driven Architecture (MDA) brings benefits to software development, among them the potential for connecting software models with the business domain. This paper focuses on the upstream or Computation Independent Model (CIM) phase of the MDA. Our contention is that, whilst there are many models and notations available within the CIM Phase, those that are currently popular and supported by the Object Management Group (OMG), may not be the most useful notations for business analysts nor sufficient to fully support software requirements and specification.
Therefore, with specific emphasis on the value of the Business Process Modelling Notation (BPMN) for business analysts, this paper provides an example of a typical CIM approach before describing an approach which incorporates specific requirements techniques. A framework extension to the MDA is then introduced; which embeds requirements and specification within the CIM, thus further enhancing the utility of MDA by providing a more complete method for business analysis
Embedding requirements within the model driven architecture.
No full textThe Model Driven Architecture (MDA) is offered as one way forward in software systems modelling to connect software design with the business domain. The general focus of the MDA is the development of software systems by performing transformations between software design models, and the automatic generation of application code from those models. Software systems are provided by developers, whose
experience and models are not always in line with those of other stakeholders, which presents a challenge for the community. From reviewing the available literature, it is found that whilst many models and notations are available, those that are significantly supported by the MDA may not be best for use by non technical stakeholders. In addition, the MDA does not explicitly consider requirements and specification. This research begins by investigating the adequacy of the MDA requirements phase and examining the
feasibility of incorporating a requirements definition, specifically focusing upon model transformations. MDA
artefacts were found to serve better the software community and requirements were not appropriately integrated within the MDA, with significant extension upstream being required in order to sufficiently accommodate the business user in terms of a requirements definition. Therefore, an extension to the MDA framework is offered that directly addresses Requirements Engineering (RE), including the distinction of
analysis from design, highlighting the importance of specification. This extension is suggested to further the
utility of the MDA by making it accessible to a wider audience upstream, enabling specification to be a direct
output from business user involvement in the requirements phase of the MDA. To demonstrate applicability, this research illustrates the framework extension with the provision of a method and discusses the use of the
approach in both academic and commercial settings. The results suggest that such an extension is academically viable in facilitating the move from analysis into the design of software systems, accessible for business use and beneficial in industry by allowing for the involvement of the client in producing models sufficient enough for use in the development of software systems using MDA tools and techniques
A Model Driven Approach to Model Transformations
No full textThe OMG's Model Driven Architecture (MDA) initiative has been the focus of much attention in both academia and industry, due to its promise of more rapid and consistent software development through the increased use of models. In order for MDA to reach its full potential, the ability to manipulate and transform models { most obviously from the Platform Independent Model (PIM) to the Platform Specific Models (PSM) { is vital. Recognizing this need, the OMG issued a Request For Proposals (RFP) largely concerned with finding a suitable mechanism for trans-
forming models. This paper outlines the relevant background material, summarizes the approach taken by the QVT-Partners (to whom the authors belong), presents a non-trivial example using the QVT-Partners approach, and finally sketches out what the future holds for model transformations
spectrino Software: Spectra Visualization and Preparation for R
No full textspectrino is a spectra preparation software utility for the R language and environment for statistical computing. It is an operating-system specific tool, for use under Microsoft Windows, with specialized visualization, organization and preprocessing features for spectra. The software accepts spectral data from analytical instruments and then prepares a data structure to be introduced in R. spectrino has a rich set of features to create data structures and visually manipulate/compare spectra. The application is accessible by a library of functions from within R. These commands allow for the creation and manipulation of data structures in spectrino and the selective extraction of spectral data. Before exporting, the spectra are preprocessed according the requirements of consecutive discriminant analysis. This preprocessing is adjustable by a series of options.
GnRH receptor activation competes at a low level with growth signaling in stably transfected human breast cell lines
No full textBreakthrough Breast CancerBackground: Gonadotrophin releasing hormone (GnRH) analogs lower estrogen levels in pre-menopausal breast cancer patients. GnRH receptor (GnRH-R) activation also directly inhibits the growth of certain cells. The applicability of GnRH anti-proliferation to breast cancer was therefore analyzed. Methods: GnRH-R expression in 298 primary breast cancer samples was measured by quantitative immunofluorescence. Levels of functional GnRH-R in breast-derived cell lines were assessed using 125I-ligand binding and stimulation of 3H-inositol phosphate production. Elevated levels of GnRH-R were stably expressed in cells by transfection. Effects of receptor activation on in vitro cell growth were investigated in comparison with IGFI and EGF receptor inhibition, and correlated with intracellular signaling using western blotting. Results: GnRH-R immunoscoring was highest in hormone receptor (triple) negative and grade 3 breast tumors. However prior to transfection, functional endogenous GnRH-R were undetectable in four commonly studied breast cancer cell lines (MCF-7, ZR-75-1, T47D and MDA-MB-231). After transfection with GnRH-R, high levels of cell surface GnRH-R were detected in SVCT and MDA-MB-231 clones while low-moderate levels of GnRH-R occurred in MCF-7 clones and ZR-75-1 clones. MCF-7 sub-clones with high levels of GnRH-R were isolated following hygromycin phosphotransferase transfection. High level cell surface GnRH-R enabled induction of high levels of 3H-inositol phosphate and modest growth-inhibition in SVCT cells. In contrast, growth of MCF-7, ZR-75-1 or MDA-MB-231 clones was unaffected by GnRH-R activation. Cell growth was inhibited by IGF-I or EGF receptor inhibitors. IGF-I receptor inhibitor lowered levels of p-ERK1/2 in MCF-7 clones. Washout of IGF-I receptor inhibitor resulted in transient hyper-elevation of p-ERK1/2, but co-addition of GnRH-R agonist did not alter the dynamics of ERK1/2 rephosphorylation. Conclusions: Breast cancers exhibit a range of GnRH-R immunostaining, with higher levels of expression found in triple-negative and grade 3 cancers. However, functional cell surface receptors are rare in cultured cells. Intense GnRH-R signaling in transfected breast cancer cells did not markedly inhibit growth, in contrast to transfected HEK 293 cells indicating the importance of intracellular context. GnRH-R signaling could not counteract IGF-I receptortyrosine kinase addiction in MCF-7 cells. These results suggest that combinatorial strategies with growth factor inhibitors will be needed to enhance GnRH anti-proliferative effects in breast cancerPeer reviewe
Ontology transformation and reasoning for model-driven architecture
No full textModel-driven Architecture (MDA) is a software architecture
framework proposed by the Object Management Group OMG. MDA
emphasises the importance of modelling in the architectural design of service-based software systems. Ontologies can enhance the modelling aspects here. We present ontology-based transformation and reasoning techniques for a layered, MDA-based modelling approach. Different ontological
frameworks shall support domain modelling, architectural modelling and interoperability. Ontologies are beneficial due to their potential to formally define and automate transformations and to allow reasoning about models at all stages. Ontologies are suitable in particular for the Web Services platform due to their ubiquity within the Semantic Web and their application to support semantic Web services
A model driven approach to building implementable model transformations
No full textThe OMG's Model Driven Architecture (MDA) initiative has been the focus of much attention in both academia and industry, due to its promise of more rapid and consistent software development through the increased use of models. In order for MDA to reach its full potential, the ability to manipulate and transform models { most obviously from the Platform Independent Model (PIM) to the Platform
Specifc Models (PSM) { is vital. Recognizing this need, the OMG issued a Request For Proposals (RFP) largely concerned with finding a suitable mechanism for transforming models. This paper outlines the relevant background material, summarizes the approach taken by the QVT-Partners (to whom the authors belong), presents a non-trivial example using the QVT-Partners approach, and finally sketches out what the future holds for model transformations
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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