Unique reporter-based sensor platforms to monitor signalling in cells

Introduction: In recent years much progress has been made in the development of tools for systems biology to study the levels of mRNA and protein, and their interactions within cells. However, few multiplexed methodologies are available to study cell signalling directly at the transcription factor level. <p/>Methods: Here we describe a sensitive, plasmid-based RNA reporter methodology to study transcription factor activation in mammalian cells, and apply this technology to profiling 60 transcription factors in parallel. The methodology uses two robust and easily accessible detection platforms; quantitative real-time PCR for quantitative analysis and DNA microarrays for parallel, higher throughput analysis. <p/>Findings: We test the specificity of the detection platforms with ten inducers and independently validate the transcription factor activation. <p/>Conclusions: We report a methodology for the multiplexed study of transcription factor activation in mammalian cells that is direct and not theoretically limited by the number of available reporters

Strike, occupy, transform! Students, subjectivity and struggle

This article uses student activism to explore the way in which activists are challenging the student as consumer model through a series of experiments that blend pedagogy and protest. Specifically, I suggest that Higher Education is increasingly becoming an arena of the postpolitical, and I argue that one of the ways this student-consumer subjectivity is being (re)produced is through a series of ‘depoliticisation machines’ operating within the university. This article goes on to claim that in order to counter this, some of those resisting the neoliberalisation of higher education have been creating political-pedagogical experiments that act as ‘repoliticisation machines’, and that these experiments countered student-consumer subjectification through the creation of new radical forms of subjectivity. This paper provides an example of this activity through the work of a group called the Really Open University and its experiments at blending, protest, pedagogy and propaganda

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe

Nucleases as a barrier to gene silencing in the cotton boll weevil, Anthonomus grandis.

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A cartography of the possible: reflections on militant ethnography in and against the edu-factory

This paper examines militant research through the lens of several challenges the author faced when experimenting with it as part of their PhD research. It engages with ongoing debates about the role and complexity of militant methodologies within-against-beyond the university. Specifically it suggests that the political economy of the academy is a challenge to militant research through the growing influence of the law of value within increasingly marketised academic contexts. This paper argues that the academic-recuperation-machine has the potential to assimilate what it terms the ‘minor knowledge’ created through militant research within its circuits of institutionalisation and commodification, becoming just another output or tool in the toolbox. Relatedly it suggests these challenges do not simply require a reflection on positionality vis-à-vis academia/activism, but a collective struggle around academic labour in-against-beyond the university and how militant researcher might remain ‘in but not of’ the neoliberal university

Persistent left superior vena cava: Review of the literature, clinical implications, and relevance of alterations in thoracic central venous anatomy as pertaining to the general principles of central venous access device placement and venography in cancer patients

Persistent left superior vena cava (PLSVC) represents the most common congenital venous anomaly of the thoracic systemic venous return, occurring in 0.3% to 0.5% of individuals in the general population, and in up to 12% of individuals with other documented congential heart abnormalities. In this regard, there is very little in the literature that specifically addresses the potential importance of the incidental finding of PLSVC to surgeons, interventional radiologists, and other physicians actively involved in central venous access device placement in cancer patients. In the current review, we have attempted to comprehensively evaluate the available literature regarding PLSVC. Additionally, we have discussed the clinical implications and relevance of such congenital aberrancies, as well as of treatment-induced or disease-induced alterations in the anatomy of the thoracic central venous system, as they pertain to the general principles of successful placement of central venous access devices in cancer patients. Specifically regarding PLSVC, it is critical to recognize its presence during attempted central venous access device placement and to fully characterize the pattern of cardiac venous return (i.e., to the right atrium or to the left atrium) in any patient suspected of PLSVC prior to initiation of use of their central venous access device

SOME INNOVATIVE STATISTICAL TOOLS FOR SUSTAINABILITY OF THE RESEARCH PRODUCTION PROCESS

New control charts and their assessments determining the normality of the quality criterion are carried out in the article. Using these charts, the degree of stability of the production process is studied using one example. In practice, the stability of the process under study is important. It depends on ordinary (random) and special (nonrandom) reasons. These reasons strongly affect the distribution of the process under study. Distributions may vary in position, spread, and shape. They can be checked using asymmetry and excess coefficients. If only the usual causes of variations occur, then the results of the process form a distribution that is stable over time and predictable. If there are special reasons for the variations, then the result of the process is not stable in time. If it is established that the process is stable and able to meet the requirements at the moment, additional studies should be performed. Moreover, if a sufficient amount of data is collected, then they are built on a control map, and if no specific reasons are found, then long-term reproducibility factors can be calculated. The article contains new control charts and their assessments determining the stability of the process under study. Using these cards on one example, the degree of stability of the production process is investigated