Towards a competitive and sustainable OA market in Europe - A study of the open access market and policy environment

Deliverable 5.3 of OpenAIRE WP5: FP7 Post Grant Gold Open Access Pilot. This deliverable consists of a study and an annex - and it will be supplemented by a roadmap in May 2017. This study considers the economic factors contributing to the current state of the open-access publishing market, and evaluates the potential for European policymakers to enhance market competition and sustainability in parallel to increasing access. It was commissioned within the scope of the OpenAIRE FP7 Post-Grant Open Access Pilot, and it will be accompanied by a Roadmap document developed with inputs from an expert workshop to be held in The Hague on 20 April 2017. In accordance with the project brief, the study aims to: Explore the current status of the OA publishing market Analyse existing OA publishing business models Evaluate how different national and international policies are complementing each other as a means to achieve a transition to OA Evaluate the impact of the Framework Programme 7 Post-grant OA pilot and its implications for future similar initiatives and the transition to OA. Provide a roadmap leading to a sustainable and competitive market The transition to open access concerns all kinds of academic research outputs, including monographs, journal articles, and data. This study focuses on open access to peer-reviewed research articles, which constitute the bulk of the market and the primary mechanism through which research is disseminated across disciplinary communities and beyond. This report is supplemented by an Annex containing a mid-term evaluation of the FP7 Post-Grant Open Access Pilot.This report will be accompanied by a Roadmap document developed with inputs from an expert workshop to be held in The Hague on 20 April 201

Repetitive Sampling and Control Threshold Improve 16S rRNA Gene Sequencing Results From Produced Waters Associated With Hydraulically Fractured Shale

Sequencing microbial DNA from deep subsurface environments is complicated by a number of issues ranging from contamination to non-reproducible results. Many samples obtained from these environments – which are of great interest due to the potential to stimulate microbial methane generation – contain low biomass. Therefore, samples from these environments are difficult to study as sequencing results can be easily impacted by contamination. In this case, the low amount of sample biomass may be effectively swamped by the contaminating DNA and generate misleading results. Additionally, performing field work in these environments can be difficult, as researchers generally have limited access to and time on site. Therefore, optimizing a sampling plan to produce the best results while collecting the greatest number of samples over a short period of time is ideal. This study aimed to recommend an adequate sampling plan for field researchers obtaining microbial biomass for 16S rRNA gene sequencing, applicable specifically to low biomass oil and gas-producing environments. Forty-nine different samples were collected by filtering specific volumes of produced water from a hydraulically fractured well producing from the Niobrara Shale. Water was collected in two different sampling events 24 h apart. Four to five samples were collected from 11 specific volumes. These samples along with eight different blanks were submitted for analysis. DNA was extracted from each sample, and quantitative polymerase chain reaction (qPCR) and 16S rRNA Illumina MiSeq gene sequencing were performed to determine relative concentrations of biomass and microbial community composition, respectively. The qPCR results varied across sampled volumes, while no discernible trend correlated contamination to volume of water filtered. This suggests that collecting a larger volume of sample may not result in larger biomass concentrations or better representation of a sampled environment. Researchers could prioritize collecting many low volume samples over few high-volume samples. Our results suggest that there also may be variability in the concentration of microbial communities present in produced waters over short (i.e., hours) time scales, which warrants further investigation. Submission of multiple blanks is also vital to determining how contamination or low biomass effects may influence a sample set collected from an unknown environment

Analysing the performance of low-cost air quality sensors, their drivers, relative benefits and calibration in cities—a case study in Sheffield

Traditional real-time air quality monitoring instruments are expensive to install and maintain; therefore, such existing air quality monitoring networks are sparsely deployed and lack the measurement density to develop high-resolution spatiotemporal air pollutant maps. More recently, low-cost sensors have been used to collect high-resolution spatial and temporal air pollution data in real-time. In this paper, for the first time, Envirowatch E-MOTEs are employed for air quality monitoring as a case study in Sheffield. Ten E-MOTEs were deployed for a year (October 2016 to September 2017) monitoring several air pollutants (NO, NO2, CO) and meteorological parameters. Their performance was compared to each other and to a reference instrument installed nearby. E-MOTEs were able to successfully capture the temporal variability such as diurnal, weekly and annual cycles in air pollutant concentrations and demonstrated significant similarity with reference instruments. NO2 concentrations showed very strong positive correlation between various sensors. Mostly, correlation coefficients (r values) were greater than 0.92. CO from different sensors also had r values mostly greater than 0.92; however, NO showed r value less than 0.5. Furthermore, several multiple linear regression models (MLRM) and generalised additive models (GAM) were developed to calibrate the E-MOTE data and reproduce NO and NO2 concentrations measured by the reference instruments. GAMs demonstrated significantly better performance than linear models by capturing the non-linear association between the response and explanatory variables. The best GAM developed for reproducing NO2 concentrations returned values of 0.95, 3.91, 0.81, 0.005 and 0.61 for factor of two (FAC2), root mean square error (RMSE), coefficient of determination (R2), normalised mean biased (NMB) and coefficient of efficiency (COE), respectively. The low-cost sensors offer a more affordable alternative for providing real-time high-resolution spatiotemporal air quality and meteorological parameter data with acceptable performance

Hypoxia regulates FGFR3 expression via HIF-1α and miR-100 and contributes to cell survival in non-muscle invasive bladder cancer

Background: Non-muscle invasive (NMI) bladder cancer is characterised by increased expression and activating mutations of FGFR3. We have previously investigated the role of microRNAs in bladder cancer and have shown that FGFR3 is a target of miR-100. In this study, we investigated the effects of hypoxia on miR-100 and FGFR3 expression, and the link between miR-100 and FGFR3 in hypoxia. Methods: Bladder cancer cell lines were exposed to normoxic or hypoxic conditions and examined for the expression of FGFR3 by quantitative PCR (qPCR) and western blotting, and miR-100 by qPCR. The effect of FGFR3 and miR-100 on cell viability in twodimensional (2-D) and three-dimensional (3-D) was examined by transfecting siRNA or mimic-100, respectively. Results: In NMI bladder cancer cell lines, FGFR3 expression was induced by hypoxia in a transcriptional and HIF-1a-dependent manner. Increased FGFR3 was also in part dependent on miR-100 levels, which decreased in hypoxia. Knockdown of FGFR3 led to a decrease in phosphorylation of the downstream kinases mitogen-activated protein kinase (MAPK) and protein kinase B (PKB), which was more pronounced under hypoxic conditions. Furthermore, transfection of mimic-100 also decreased phosphorylation of MAPK and PKB. Finally, knocking down FGFR3 profoundly decreased 2-D and 3-D cell growth, whereas introduction of mimic-100 decreased 3-D growth of cells. Conclusion: Hypoxia, in part via suppression of miR-100, induces FGFR3 expression in bladder cancer, both of which have an important role in maintaining cell viability under conditions of stress

p21-activated kinase 1: PAK'ed with potential

The p21-activated kinases (PAKs) are central players in growth factor signaling networks and morphogenetic processes that control proliferation, cell polarity, invasion and actin cytoskeleton organization. This raises the possibility that interfering with PAK activity may produce significant anti-tumor activity. In this perspective, we summarize recent data concerning the contribution of the PAK family member, PAK1, in growth factor signaling and tumorigenesis. We further discuss mechanisms by which inhibition of PAK1 can arrest tumor growth and promote cell apoptosis, and the types of cancers in which PAK1 inhibition may hold promise

Expression of delta-like ligand 4 (Dll4) and markers of hypoxia in colon cancer

BACKGROUND: Delta-like ligand 4 (Dll4) is a Notch ligand that is upregulated by hypoxia and vascular endothelial growth factor-A (VEGF-A) and is reported to have a role in tumor angiogenesis. Evidence from xenograft studies suggests that inhibiting Dll4-Notch signalling may overcome resistance to anti-VEGF therapy. The aim of this study was to characterise the expression of Dll4 in colon cancer and to assess whether it is associated with markers of hypoxia and prognosis. METHOD: In all, 177 colon cancers were represented in tissue microarrays. Immunohistochemistry was performed using validated antibodies against Dll4, VEGF, hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, prolyl hydroxylase (PHD)1, PHD2, PHD3 and carbonic anhydrase 9 (CA9). RESULTS: The expression of Dll4 was observed preferentially in the endothelium of 71% (125 out of 175) of colon cancers, but not in the endothelium adjacent to normal mucosa (none out of 107, P<0.0001). The expression of VEGF was significantly associated with HIF-2alpha (P<0.0001) and Dll4 (P=0.010). Only HIF-2alpha had a significant multivariate prognostic effect (hazard ratio 1.61, 95% confidence interval 1.01-2.57). Delta-like ligand 4 was also expressed by neoplastic cells, particularly neoplastic goblet cells. CONCLUSION: Endothelial expression of Dll4 is not a prognostic factor, but is significantly associated with VEGF. Assessing endothelial Dll4 expression may be critical in predicting response to anti-VEGF therapies

Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages

Phenotypic differences between individuals and species are controlled in part through differences in expression of a relatively conserved set of genes. Genes expressed in the immune system are subject to especially powerful selection. We have investigated the evolution of both gene expression and candidate enhancers in human and mouse macrophages exposed to glucocorticoid (GC), a regulator of innate immunity and an important therapeutic agent. Our analyses revealed a very limited overlap in the repertoire of genes responsive to GC in human and mouse macrophages. Peaks of inducible binding of the GC receptor (GR) detected by chromatin immunoprecipitation-Seq correlated with induction, but not repression, of target genes in both species, occurred at distal regulatory sites not promoters, and were strongly enriched for the consensus GR-binding motif. Turnover of GR binding between mice and humans was associated with gain and loss of the motif. There was no detectable signal of positive selection at speciesspecific GR binding sites, but clear evidence of purifying selection at the small number of conserved sites.We conclude that enhancer divergence underlies the difference in transcriptional activation after GC treatment between mouse and human macrophages. Only the shared inducible loci show evidence of selection, and therefore these loci may be important for the subset of responses to GC that is shared between species