28 research outputs found

    Employing an orthotopic model to study the role of epithelial-mesenchymal transition in bladder cancer metastasis.

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    Epithelial-to-mesenchymal transition (EMT) has been implicated in the progression of bladder cancer. To study its contribution to bladder cancer metastasis, we established new xenograft models derived from human bladder cancer cell lines utilizing an orthotopic "recycling" technique that allowed us to isolate and examine the primary tumor and its corresponding circulating tumor cells (CTC's) and metastatic lesions. Using whole genome mRNA expression profiling, we found that a reversible epithelial-to-mesenchymal transition (EMT) characterized by TGFβ pathway activation and SNAIL expression was associated with the accumulation of CTCs. Finally, we observed that conditional silencing of SNAIL completely blocked CTC production and regional/distant metastasis. Using this unique bladder cancer xenograft model, we conclude that metastasis is dependent on a reversible EMT mediated by SNAIL

    A holistic multi-methodology for sustainable renovation

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    A review of the barriers for building renovation has revealed a lack of methodologies, which can promote sustainability objectives and assist various stakeholders during the design stage of building renovation/retrofitting projects. The purpose of this paper is to develop a Holistic Multi-methodology for Sustainable Renovation, which aims to deal with complexity of renovation projects. It provides a framework through which to involve the different stakeholders in the design process to improve group learning and group decision-making, and hence make the building renovation design process more robust and efficient. Therefore, the paper discusses the essence of multifaceted barriers in building renovation regarding cultural changes and technological/physical changes. The outcome is a proposal for a multi-methodology framework, which is developed by introducing, evaluating and mixing methods from Soft Systems Methodologies (SSM) with Multiple Criteria Decision Making (MCDM). The potential of applying the proposed methodology in renovation projects is demonstrated through a case study

    Editorial: The role of information systems methodology in software engineering

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    Paving the path to a geoscience gateway

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    Geoscience is one of the most prominent research areas today, involved in modelling and analysing the evolvement of Earth systems for the betterment of mankind. Geoscientists engaged in geoscience research and experiments often use sophisticated software tools such as Geographic Information Systems (GIS). Nevertheless, as computational geoscience is an emerging field, effective management and utilization of available geoscience data remains a major challenge

    Coinage Metal Pyrazolates [(3,5-(CF<sub>3</sub>)<sub>2</sub>Pz)M]<sub>3</sub> (M = Au, Ag, Cu) as Buckycatchers

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    The synthesis and characterization of supramolecular assemblies {C<sub>60</sub><b>[M<sub>3</sub>]<sub>4</sub></b>}<sub>∞</sub> consisting of C<sub>60</sub> and coinage metal pyrazolates <b>[M<sub>3</sub>]</b> (i.e., [(3,5-(CF<sub>3</sub>)<sub>2</sub>Pz)­M]<sub>3</sub>, where Pz = pyrazolate and M = Au, Ag, and Cu) are reported. {C<sub>60</sub><b>[Cu<sub>3</sub>]<sub>4</sub></b>}<sub>∞</sub>, {C<sub>60</sub><b>[Ag<sub>3</sub>]<sub>4</sub></b>}<sub>∞</sub> and {C<sub>60</sub><b>[Au<sub>3</sub>]<sub>4</sub></b>}<sub>∞</sub> form isomorphous crystals. The <b>[M<sub>3</sub>]</b> moieties adopt a concave conformation to complement the convex C<sub>60</sub> surface. They exist as dimers of trimers (i.e., hexanuclear <b>[M<sub>3</sub>]<sub>2</sub></b> units) that are held together by three close M···M metallophilic interactions at 3.1580(17), 3.2046(7), and 3.2631(7) Å for copper, silver, and gold systems, respectively. The <b>[M<sub>3</sub>]<sub>2</sub></b> moieties surround each C<sub>60</sub> in a tetrahedral fashion, while each <b>[M<sub>3</sub>]<sub>2</sub></b> is sandwiched by two C<sub>60</sub> molecules to form a supramolecular 3D assembly

    Development of a model to predict prostate cancer at the apex (PCAP model) in patients undergoing robot-assisted radical prostatectomy

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    Purpose: To develop a model based on preoperative variables to predict apical prostate cancer. Methods: We performed a retrospective analysis of 459 patients who underwent a robotic assisted radical prostatectomy (RALP) between January 2016 and September 2017. All patients had a preoperative biopsy and mpMRI of the prostate. Significant apical pathology (SAP) was defined as those patients who had a dominant nodule at the apex with a Gleason score &gt; 6 and/or ECE at the apex. Binary logistic regression analyses were adopted to predict SAP. Variables included in the model were PSA, apical lesions prostate imaging reporting and data system (PI-RADS) score and apical biopsy Gleason score. The area under the curve (AUC) of the model was computed. Results: A total of 121 (43.2%) patients had SAP. On univariable analysis, all apex-specific variables investigated emerged as predictors of SAP (all p &lt; 0.05). On multivariable analysis PSA and apical PI-RADS score &gt; 3 (all p &lt; 0.05) emerged as significant predictors of SAP. The AUC of the model was 0.722. Conclusion: Patients with PI-RADS 3, 4 or 5 lesions at the apex were three times as more likely to have true SAP compared to those who have PI-RADS &lt; 3 or negative mpMRI prior to undergoing RALP

    Action in context and context in action: Modelling complexity in multimedia systems development

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    Whereas multimedia systems development (MSD) is inherently complex, and increasingly so, little is known about how multimedia designers manage or cope with this complexity. In particular, little is known about complexity beyond technical and process levels, and how such complexity impacts design activity. In this paper we construct a model of MSD based on the formulation of the broader concept of context complexity. This concept, which subsumes but also transcends technical and process complexity, is used to explain design strategies and their consequences. We identify four design contexts that explain, and are also explained by, complexity. These contexts map out the 'landscape for action' over which design activity takes place. They shape the design environment and the responses taken to it. We use a grounded theory approach to study what designers actually do (as opposed to theorising what they should do). We argue that a better understanding of context determined and context determining strategies better informs interventions aimed at improving MSD design practice. Our main conclusion is that interventions should be directed to those situations where there is a mismatch between the level of complexity in the design context and the level of complexity in the design strategy taken in response to that context. We call these situations 'breakdown' contexts and examine their causes and consequences in greater detail. Our claimed contribution is to broaden the concept of design breakdowns through a specific understanding of the role and impact of (context) complexity in MSD
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