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Introduction: Genome integrity is maintained by a number of pathways which recognize and repair both exogenous and endogenous DNA damage. Deficiency in these pathways results in mutations that accelerate tumorigenesis. A subgroup of cancers such as those with mutations in the BRCA/ Fanconi anemia (FA) pathway have been reported to benefit from DNA damaging chemotherapy. Previously, we identified a molecular subgroup in breast cancer characterised by upregulation of immune genes. This group referred to as the DNA damage repair deficient (DDRD) group also showed enhanced response to DNA damaging chemotherapy. Here, we identify the same subgroup in prostate cancer and investigate the mutations associated with the subgroup in prostate cancer. Experimental procedures: Unsupervised hierarchical clustering in primary prostate cancer identified a subset of patients which demonstrated activation of immune signalling genes and enrichment for BRCA mutations, representing the DDRD group. Using data from The Cancer Genome Atlas (TCGA), we show that mutation of the MED12 gene is associated with the DDRD group. In order to study the role of MED12 in prostate cancer, isogenic cell lines with knockdown of MED12 were generated using RNAi technology. We evaluated the expression of immune genes in these cell lines using RT-qPCR. Immunofluorescence, DNA-RNA immunoprecipitation and western blot analyses were also used in the characterization of these cell lines. Results: Our data reveals that the loss of MED12 leads to a significant upregulation of the immune genes associated with DNA repair deficiency; CXCL10, CCL5, MX1 and the immune check-pointing gene PD-L1 (p<0.05). Accumulation of γH2AX foci was identified in cells depleted in MED12 (p<0.001). A significant increase in DNA-RNA hybrids (Rloops) was also observed in MED12- deficient cells (p<0.0001) indicating an endogenous source of genomic instability. Furthermore, we show the presence of cytosolic nucleic acid which triggers immune response via the STING/TBK1/IRF3 pathway which is characteristic of the DDRD-like phenotype in MED12-deficient cells.Conclusion: Mutations in the MED12 gene have previously been reported in 5 % of prostate cancer. Our findings demonstrate that the loss of MED12 in prostate cancer results in a DDRD-like phenotype. Upon further characterization, MED12 may be used as a predictor of response to stratify patients for chemotherapy or immune checkpoint targeted therapy in prostate cancer Citation Format: Folake A. Orafidiya, Catherine Davidson, Richard D. Wilkinson, Steve M. Walker, Laura A. Knight, Paul D. Harkin, Nuala McCabe, Richard D. Kennedy. Loss of MED12 predicts for a DNA damage repair deficiency phenotype and activates immune signalling via the STING pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 578.

The dictionary definition refers to surpassing, outwitting or the act of 'reaching out'. The Funding Councils see it as "widening access and improving participation in higher education…… to equip people to operate productively within the global knowledge economy. It also offers social benefits, including better health, lower crime and a more tolerant and inclusive society".Here in the Physical Sciences, whilst reaching out to widen access is an important part of our agenda, we see Outreach activities as primarily being targeted at improving the recruitment and retention of students. Many Physical Science departments are struggling to attract sufficient numbers of students and virtually all of us are also unhappy that the more able students are not choosing science for their higher and further education. This has led to the complete closure of a number of departments; a merger with cognate disciplines for some, or relegation to a 'service teaching' role for others. Since 1996, 28 universities have stopped offering chemistry degrees and almost a third of university physics departments have closed in the same period. Despite this dramatic fall in capacity, there is still a shortfall that is a major cause of concern for all but a handful of institutions.There is a great deal of confusion within Universities as to how and why this situation has arisen and in this article I will attempt to collect and summarise items that have a direct bearing on these issues.The first part will include the results of surveys into student preferences, public attitudes to science and scientists and lecturers' own opinions on the subject. The second part will summarise the recommendations from a number of sources who have given much thought to alleviating the situation and the final section will look at a selected number of institutions that are actively generating materials and methods that could be more widely adopted in order to improve the current climate.

There is a substantial minority of students who do not have the necessary physics background to tackle parts of most first year physical chemistry courses and for whom some kind of remedial action is required.Software tools have been developed to address the problem with priority beingassigned to topics most frequently occurring in the curricula. After discussion with colleagues, the topic of ‘Particles and Waves in Chemistry’ was selected. The tools consist of simulations (and high quality diagrams with relevant animations) designed to accompany tutorials or workshops. They are not ‘stand-alone’ programs and assume that the teacher has covered the basic groundwork. In this way, the material does not impose any learning style and should be treated as a simple resource similar to an illustration or photograph. Substantial numbers of numerical problems (in practice, an infinite number) are included for use as reinforcement learning tools – a technique that has been shown to be extremely effective in tackling specific numerical shortcomings.Given that the overwhelming majority of the targeted students have chosen to avoid physics, great care has been taken to ensure that the context enclosing the materials is identifiable as chemistry only.