Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells

Calretinin (CALB2) is a diagnostic marker for epithelioid mesothelioma. It is also a prognostic marker since patients with tumors expressing high calretinin levels have better overall survival. Silencing of calretinin decreases viability of epithelioid mesothelioma cells. Our aim was to elucidate mechanisms regulating calretinin expression in mesothelioma. Analysis of calretinin transcript and protein suggested a control at the mRNA level. Treatment with 5-aza-2′-deoxycytidine and analysis of TCGA data indicated that promoter methylation is not likely to be involved. Therefore, we investigated CALB2 promoter by analyzing ~1kb of genomic sequence surrounding the transcription start site (TSS) + 1 using promoter reporter assay. Deletion analysis of CALB2 proximal promoter showed that sequence spanning the –161/+80bp region sustained transcriptional activity. Site-directed analysis identified important cis- regulatory elements within this –161/+80bp CALB2 promoter. EMSA and ChIP assays confirmed binding of NRF-1 and E2F2 to the CALB2 promoter and siRNA knockdown of NRF-1 led to decreased expression of calretinin. Cell synchronization experiment showed that calretinin expression was cell cycle regulated with a peak of expression at G1/S phase. This study provides the first insight in the regulation of CALB2 expression in mesothelioma cells

DADA: data assimilation for the detection and attribution of weather and climate-related events

A new nudging method for data assimilation, delay‐coordinate nudging, is presented. Delay‐coordinate nudging makes explicit use of present and past observations in the formulation of the forcing driving the model evolution at each time step. Numerical experiments with a low‐order chaotic system show that the new method systematically outperforms standard nudging in different model and observational scenarios, also when using an unoptimized formulation of the delay‐nudging coefficients. A connection between the optimal delay and the dominant Lyapunov exponent of the dynamics is found based on heuristic arguments and is confirmed by the numerical results, providing a guideline for the practical implementation of the algorithm. Delay‐coordinate nudging preserves the easiness of implementation, the intuitive functioning and the reduced computational cost of the standard nudging, making it a potential alternative especially in the field of seasonal‐to‐decadal predictions with large Earth system models that limit the use of more sophisticated data assimilation procedures

The Stakeholder Challenge: Dealing with Challenging Situations Involving Stakeholders

Project managers are an occupational group who is exposed to high levels of stress caused by various aspects such as resources and communication or working relationships. One particularly challenging area is the interaction with stakeholders, who are often perceived to “be difficult”. With this study, we investigate how project managers cope with challenging situations involving stakeholders in projects. We do this through a qualitative study involving interviews and focus groups to explore the lived experiences of the project managers in specific situations. Our findings suggest that a project manager perspective on stakeholder management is particularly valuable to account for contextual factors such as sources of challenging situations. We propose a project coping model which transfers Lazarus and Folkman’s stress and coping model into the project context and adds the layer of project coping to emphasise the project managers’ perception of accountability and commitment to the project

Reconciling views of project success : a multiple stakeholder model

This paper presents a new model encompassing all the important critical attributes to measure project success across different stakeholder groups. The study investigates the possibility that project failure is a result of the interpretations of the criteria and factors used for success by multiple stakeholder groups. Unique projects must have their outcome parameters monitored and controlled to minimize the chances of failure and the likely major financial and managerial ramifications for the organization. Early testing of the model supports its use to increase the shared, multiple stakeholder perception of project success leading to more informed decision making and motivation of employees

Failure, success, and maturity in projects

The information technology industry has experienced a tremendous growth over the last 30 years but still beleaguered by failed projects. Failure cases are typically dominated by large and complex projects. Moreover, the percentage of projects being developed above their limits of time, budgeted cost and quality is still high. However, in defining project success, are these the only parameters that make the difference? According to the PMI Project Management Body of Knowledge, Project Management is about delivering a product or service on time, within the allocated budget and according to customer defined quality and specification, by a motivated project team. Indeed, success as well as failure, appears to be linked to a wide range of factors