Invasion and MMP expression profile in desmoid tumours

Desmoid tumours are locally invasive soft tissue tumours in which beta-catenin mediated TCF-dependent transcription is activated. The role of soluble factors secreted by the myofibroblastic desmoid tumour, which could stimulate tumour invasiveness, was investigated. Using collagen gel invasion assays, the presence of factors stimulating invasion in desmoid conditioned media (CM) could be established. Since matrix metalloproteinases (MMPs) have been implicated in the process of tumoral invasion, the expression levels of the MMP family members were evaluated. Quantitative reverse transcription-PCR was used to determine the expression levels of MMP1, MMP2, MMP3, MMP7, MMP11, MMP12, MMP13, MMP14 and the inhibitors TIMP1, TIMP2 and TIMP3. Besides overexpression of MMP7, a known TCF-dependent target gene, a striking upregulation of the expression levels of MMP1, MMP3, MMP11, MMP12 and MMP13 in desmoid tumours, compared to unaffected fibroblasts from the same patients, was found. Treating the CM of desmoids with a synthetic and a physiologic MMP inhibitor reduced the invasion-stimulating capacity of the desmoid CM by approximately 50%. These results suggest the involvement of soluble factors, released by the desmoid cells, in stimulating invasion and implicate the MMPs as facilitators of invasion

Analytic frameworks for assessing dialogic argumentation in online learning environments

Over the last decade, researchers have developed sophisticated online learning environments to support students engaging in argumentation. This review first considers the range of functionalities incorporated within these online environments. The review then presents five categories of analytic frameworks focusing on (1) formal argumentation structure, (2) normative quality, (3) nature and function of contributions within the dialog, (4) epistemic nature of reasoning, and (5) patterns and trajectories of participant interaction. Example analytic frameworks from each category are presented in detail rich enough to illustrate their nature and structure. This rich detail is intended to facilitate researchers’ identification of possible frameworks to draw upon in developing or adopting analytic methods for their own work. Each framework is applied to a shared segment of student dialog to facilitate this illustration and comparison process. Synthetic discussions of each category consider the frameworks in light of the underlying theoretical perspectives on argumentation, pedagogical goals, and online environmental structures. Ultimately the review underscores the diversity of perspectives represented in this research, the importance of clearly specifying theoretical and environmental commitments throughout the process of developing or adopting an analytic framework, and the role of analytic frameworks in the future development of online learning environments for argumentation

Development and uptake of an online systematic review platform: the early years of the CAMARADES Systematic Review Facility (SyRF)

Preclinical research is a vital step in the drug discovery pipeline and more generally in helping to better understand human disease aetiology and its management. Systematic reviews (SRs) can be powerful in summarising and appraising this evidence concerning a specific research question, to highlight areas of improvements, areas for further research and areas where evidence may be sufficient to take forward to other research domains, for instance clinical trial. Guidance and tools for preclinical research synthesis remain limited despite their clear utility. We aimed to create an online end-to-end platform primarily for conducting SRs of preclinical studies, that was flexible enough to support a wide variety of experimental designs, was adaptable to different research questions, would allow users to adopt emerging automated tools and support them during their review process using best practice. In this article, we introduce the Systematic Review Facility (https://syrf.org.uk), which was launched in 2016 and designed to support primarily preclinical SRs from small independent projects to large, crowdsourced projects. We discuss the architecture of the app and its features, including the opportunity to collaborate easily, to efficiently manage projects, to screen and annotate studies for important features (metadata), to extract outcome data into a secure database, and tailor these steps to each project. We introduce how we are working to leverage the use of automation tools and allow the integration of these services to accelerate and automate steps in the systematic review workflow

NLL soft and Coulomb resummation for squark and gluino production at the LHC

We present predictions of the total cross sections for pair production of squarks and gluinos at the LHC, including the stop-antistop production process. Our calculation supplements full fixed-order NLO predictions with resummation of threshold logarithms and Coulomb singularities at next-to-leading logarithmic (NLL) accuracy, including bound-state effects. The numerical effect of higher-order Coulomb terms can be as big or larger than that of soft-gluon corrections. For a selection of benchmark points accessible with data from the 2010-2012 LHC runs, resummation leads to an enhancement of the total inclusive squark and gluino production cross section in the 15-30 % range. For individual production processes of gluinos, the corrections can be much larger. The theoretical uncertainty in the prediction of the hard-scattering cross sections is typically reduced to the 10 % level.Comment: 45 pages, 16 Figures, LaTex. v2: published version. Grids with numerical results for the NLL cross sections for squark and gluino production at the 7/8 TeV LHC are included in the submission and are also available at http://omnibus.uni-freiburg.de/~cs1010/susy.htm

S-COL: A Copernican turn for the development of flexibly reusable collaboration scripts

Collaboration scripts are usually implemented as parts of a particular collaborative-learning platform. Therefore, scripts of demonstrated effectiveness are hardly used with learning platforms at other sites, and replication studies are rare. The approach of a platform-independent description language for scripts that allows for easy implementation of the same script on different platforms has not succeeded yet in making the transfer of scripts feasible. We present an alternative solution that treats the problem as a special case of providing support on top of diverse Web pages: In this case, the challenge is to trigger support based on the recognition of a Web page as belonging to a specific type of functionally equivalent pages such as the search query form or the results page of a search engine. The solution suggested has been implemented by means of a tool called S-COL (Scripting for Collaborative Online Learning) and allows for the sustainable development of scripts and scaffolds that can be used with a broad variety of content and platforms. The tool’s functions are described. In order to demonstrate the feasibility and ease of script reuse with S-COL, we describe the flexible re-implementation of a collaboration script for argumentation in S-COL and its adaptation to different learning platforms. To demonstrate that a collaboration script implemented in S-COL can actually foster learning, an empirical study about the effects of a specific script for collaborative online search on learning activities is presented. The further potentials and the limitations of the S-COL approach are discussed

Analyzing collaborative learning processes automatically

In this article we describe the emerging area of text classification research focused on the problem of collaborative learning process analysis both from a broad perspective and more specifically in terms of a publicly available tool set called TagHelper tools. Analyzing the variety of pedagogically valuable facets of learners’ interactions is a time consuming and effortful process. Improving automated analyses of such highly valued processes of collaborative learning by adapting and applying recent text classification technologies would make it a less arduous task to obtain insights from corpus data. This endeavor also holds the potential for enabling substantially improved on-line instruction both by providing teachers and facilitators with reports about the groups they are moderating and by triggering context sensitive collaborative learning support on an as-needed basis. In this article, we report on an interdisciplinary research project, which has been investigating the effectiveness of applying text classification technology to a large CSCL corpus that has been analyzed by human coders using a theory-based multidimensional coding scheme. We report promising results and include an in-depth discussion of important issues such as reliability, validity, and efficiency that should be considered when deciding on the appropriateness of adopting a new technology such as TagHelper tools. One major technical contribution of this work is a demonstration that an important piece of the work towards making text classification technology effective for this purpose is designing and building linguistic pattern detectors, otherwise known as features, that can be extracted reliably from texts and that have high predictive power for the categories of discourse actions that the CSCL community is interested in

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Sigma-phase in Fe-Cr and Fe-V alloy systems and its physical properties

A review is presented on physical properties of the sigma-phase in Fe-Cr and Fe-V alloy systems as revealed both with experimental -- mostly with the Mossbauer spectroscopy -- and theoretical methods. In particular, the following questions relevant to the issue have been addressed: identification of sigma and determination of its structural properties, kinetics of alpha-to-sigma and sigma-to-alpha phase transformations, Debye temperature and Fe-partial phonon density of states, Curie temperature and magnetization, hyperfine fields, isomer shifts and electric field gradients.Comment: 26 pages, 23 figures and 83 reference

The moderating role of transformational leadership on HR practices in M&A integration

Scant research exists examining the effect of HRM practices on employee behavior in M&A integration and the role that leaders play within this. This paper develops a conceptual framework that focuses on the moderating role of transformational leadership on the achievement of human integration and organizational identification in M&A integration. We argue that communication, employee involvement, teamwork, and training and development have a positive effect on employee behavior and their identification with the newly formed organization. Moreover, we argue that transformational leadership behaviors will moderate the implementation of HRM practices in M&As, leading to positive employee behavior and employee identification in the new organization. We suggest that further research is necessary to test propositions of the present study in order to achieve finer-grained understanding of the role of transformational leadership on the achievement of human integration and organizational identification in M&A integration