Scaling Milton Keynes power requirements for electrical transportation

Milton Keynes is home to the UK’s first installation of a wirelessly charged passenger bus route. This Inductive Power Transfer (IPT) system enables a fleet of 8 electric buses to service a demanding 15-mile urban route. Opportunistic wireless charging of the batteries during the layover time at the routes allows reducing the size of the batteries, consequently improving cost and performance characteristics of the bus. This paper aims to analyze the effects of electric buses on the electricity distribution grid. In particular, the paper analyses scalability of the IPT solution to all urban routes in Milton Keynes and compares peak power requirements generated at different points in the network with typical industrial and commercial (I&C) loads

Pushing the limits of surface-enhanced raman spectroscopy (SERS) with deep learning : identification of multiple species with closely related molecular structures

Raman spectroscopy is a non-destructive and label-free molecular identification technique capable of producing highly specific spectra with various bands correlated to molecular structure. Moreover, the enhanced detection sensitivity offered by Surface-Enhanced Raman spectroscopy (SERS) allows analyzing mixtures of related chemical species in a relatively short measurement time. Combining SERS with deep learning algorithms allows in some cases to increase detection and classification capabilities even further. The present study evaluates the potential of applying deep learning algorithms to SERS spectroscopy to differentiate and classify different species of bile acids, a large family of molecules with low Raman cross sections and molecular structures that often differ by a single hydroxyl group. Moreover, the study of these molecules is of interest for the medical community since they have distinct pathological roles and are currently viewed as potential markers of gut microbiome imbalances. A Convolutional Neural Network (CNN) model was developed and used to classify SERS spectra from five bile acid species. The model succeeded in identifying the five analytes despite very similar molecular structures and was found to be reliable even at low analyte concentrations

Effectiveness of serious games and impact of design elements on engagement and educational outcomes in healthcare professionals and students : a systematic review and meta-analysis protocol

Introduction Serious games (SGs) are interactive and entertaining digital software with an educational purpose. They engage the learner by proposing challenges and through various design elements (DEs; eg, points, difficulty adaptation, story). Recent reviews suggest the effectiveness of SGs in healthcare professionals’ and students’ education is mixed. This could be explained by the variability in their DEs, which has been shown to be highly variable across studies. The aim of this systematic review is to identify, appraise and synthesise the best available evidence regarding the effectiveness of SGs and the impact of DEs on engagement and educational outcomes of healthcare professionals and students. Methods and analysis A systematic search of the literature will be conducted using a combination of medical subject headings terms and keywords in Cumulative Index of Nursing and Allied Health, Embase, Education Resources Information Center, PsycInFO, PubMed and Web of Science. Studies assessing SGs on engagement and educational outcomes will be included. Two independent reviewers will conduct the screening as well as the data extraction process. The risk of bias of included studies will also be assessed by two reviewers using the Effective Practice and Organisation of Care criteria. Data regarding DEs in SGs will first be synthesised qualitatively. A meta-analysis will then be performed, if the data allow it. Finally, the quality of the evidence regarding the effectiveness of SGs on each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Ethics and dissemination As this systematic review only uses already collected data, no Institutional Review Board approval is required. Its results will be submitted in a peerreviewed journal by the end of 2018

Hunters and Their Perceptions of Public Access: A View from Afield

Declining hunter participation threatens cultural traditions and public support for conservation, warranting examination of the forces behind the downward trajectory. Access to lands for hunting, an often-cited reason for non participation, may play a critical role in the retention and recruitment of hunters. Meeting the access needs of a diverse hunting constituency requires understanding how hunters use and perceive access opportunities, particularly public-access sites. Given that perceptions of access are entirely place based and degrade with time, traditional postseason survey methods may fail to adequately quantify the value of public access to the hunting constituency. To overcome the potential limitations of postseason surveys, we conducted on-site assessments of hunter perceptions of habitat quality, game abundance, ease of access, and crowding as well as whether the experience met the hunters’ expectations and their likelihood to return to hunt. Over 3 y, we interviewed 3,248 parties of which 71.5% were hunting. Most parties (65.9%) reported having no private access within the region of Nebraska where they were interviewed. Parties (67.6%) were largely limited to two or fewer hunters, most of whom were adult males (84.3%) who were, on average, 41.2 y old. The perception of public-access sites was generally positive, but 43.1% of parties indicated that game abundance was below average despite 59.2% of parties seeing game and 37.3% harvesting at least one animal. Similar to other explorations of hunter satisfaction, we found game abundance, and in particular harvest success, had the most consistent relationship with hunter perception of public access. By surveying multiple types of hunters across sites that encompass a range of social and ecological conditions, we gained a broader understanding of how hunters perceive public access in real time, which will help to inform future management decisions to foster and improve public-access programs

Insights for the melt migration, the volcanic activity and the ultrafast lithosphere delamination related to the Yellowstone plume (Western USA)

The Yellowstone–East Snake River Plain hotspot track has been intensely studied since several decades and is widely considered to result from the interaction of a mantle plume with the North American plate. An integrated conclusive geodynamic interpretation of this extensive data set is however presently still lacking, and our knowledge of the dynamical processes beneath Yellowstone is patchy. It has been argued that the Yellowstone plume has delaminated the lower part of the thick Wyoming cratonic lithosphere. We derive an original dynamic model to quantify delamination processes related to mantle plume–lithosphere interactions. We show that fast (∼300 ka) lithospheric delamination is consistent with the observed timing of formation of successive volcanic centres along the Yellowstone hotspot track and requires (i) a tensile stress regime within the whole lithosphere exceeding its failure threshold, (ii) a purely plastic rheology in the lithosphere when stresses reach this yield limit, (iii) a dense lower part of the 200 km thick Wyoming lithosphere and (iv) a decoupling melt horizon inside the median part of the lithosphere. We demonstrate that all these conditions are verified and that ∼150 km large and ∼100 km thick lithospheric blocks delaminate within 300 ka when the Yellowstone plume ponded below the 200 km thick Wyoming cratonic lithosphere. Furthermore, we take advantage of the available extensive regional geophysical and geological observation data sets to design a numerical 3-D upper-mantle convective model. We propose a map of the ascending convective sheets contouring the Yellowstone plume. The model further evidences the development of a counter-flow within the lower part of the lithosphere centred just above the Yellowstone mantle plume axis. This counter-flow controls the local lithospheric stress field, and as a result the trajectories of feeder dykes linking the partial melting source within the core of the mantle plume with the crust by crosscutting the lithospheric mantle. This counter-flow further explains the 50 km NE shift observed between the mantle plume axis and the present-day Yellowstone Caldera as well as the peculiar shaped crustal magma chambers

HDAC Inhibition with Valproate Improves Direct Cytotoxicity of Monocytes against Mesothelioma Tumor Cells

peer reviewedThe composition of the tumor microenvironment (TME) mediates the outcome of chemo- and immunotherapies in malignant pleural mesothelioma (MPM). Tumor-associated macrophages (TAMs) and monocyte myeloid-derived immunosuppressive cells (M-MDSCs) constitute a major fraction of the TME. As central cells of the innate immune system, monocytes exert well-characterized functions of phagocytosis, cytokine production, and antibody-dependent cell-mediated cytotoxicity (ADCC). The objective of this study was to evaluate the ability of monocytes to exert a direct cytotoxicity by cell-to-cell contact with MPM cells. The experimental model is based on cocultures between human blood-derived monocytes sorted by negative selection and mesothelioma cell lines. Data show (i) that blood-derived human monocytes induce tumor cell death by direct cell-to-cell contact, (ii) that VPA is a pharmacological enhancer of this cytotoxic activity, (iii) that VPA increases monocyte migration and their aggregation with MPM cells, and (iv) that the molecular mechanisms behind VPA modulation of monocytes involve a downregulation of the membrane receptors associated with the M2 phenotype, i.e., CD163, CD206, and CD209. These conclusions, thus, broaden our understanding about the molecular mechanisms involved in immunosurveillance of the tumor microenvironment and open new prospects for further improvement of still unsatisfactory MPM therapies

Contribution of lysine deacetylases to the therapy of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare cancer arising from mesothelial cells from the pleura. The first line chemotherapy of the epithelioid subtype of MPM is based on a combined regimen of cisplatin and an antifolate (pemetrexed). Recently, immunotherapy with two checkpoint inhibitors (PD-1, nivolumab and CTLA-4, ipilimumab) showed promising results for the sarcomatoid subtype. Despite this major breakthrough, the median overall survival of patients only reached 18.1 months, compared to 14 months in standard chemotherapy. With an objective response rate of 40%, only a subset of patients benefits from immunotherapy. Therefore, options for second line treatment are still mandatory. We previously proposed a therapy based on the combination of a topoisomerase inhibitor (doxorubicin) and a lysine deacetylase inhibitor (valproate, VPA) (Scherpereel et al, European Respiratory Journal 37:129-135). We identified one of the key determinants that modulates the chemoresistance (Staumont et al, Cancers 12:1484). In this study, we aimed to further investigate the mechanisms involved by analyzing the effect of VPA on the tumor microenvironment and more particularly on the interactions between monocytes and tumor cells. We showed that VPA affects the viability of doxorubicin-treated mesothelioma cells and promotes their apoptosis. The use of caspase and calpeptin inhibitors demonstrated that apoptosis occurs through a caspase-dependent mechanism involving both intrinsic and extrinsic pathway. Western blot analysis revealed that the combination of VPA and doxorubicin increases the expression of clived-Bid, Bax and cytochrome c while decreasing the expression of Bcl-2 and Bcl-XL. Transcriptomic analysis unveiled that epithelioid mesothelioma cells express more p21, Fas, Bbc3 and TP53INP1 upon treatment compared to the sarcomatoid subtype. To investigate the role of the microenvironment, we designed two models to study the influence of tumor-associated monocytes. Mesothelioma cells were co-cultured with THP-1 monocytes differentiated in presence of PMA. Flow cytometry, confocal microscopy and live imaging demonstrated that THP-1-derived monocytes are able to interact and kill tumor cells. Furthermore, VPA promotes the interaction between monocytes and tumor cells and fosters the cytotoxic activity of monocytes. In contrast to PMA, VPA does not affect the motility of THP-1 monocytes. These observations were validated and extended to primary monocytes isolated from peripheral blood. Increased cytotoxicity of primary monocytes is correlated with a reduced frequency of CD16+ cells. In this model, VPA augments the average speed of primary monocytes. Finally, RNA sequencing highlighted the key mechanisms involved in monocyte antitumor activity. In conclusion, we demonstrate that VPA directly affects the survival of tumor cells and indirectly modulates the cytotoxic activity of monocytes in the microenvironment

Plant-dominated assemblage and invertebrates from the lower Cenomanian of Jaunay-Clan, western France

International audienceTwo fossil localities are reported on the "LGV SEA" railroad from the Lower Cenomanianof Jaunay-Clan (JC), near Poitiers, western France. The laminated mudstones yielded plantfossils including ferns (Cladophlebis, Osmundophyllum, Ruffordia goeppertii, Sphenopteris),conifers (Brachyphyllum, Dammarophyllum, Pagiophyllum), and terrestrial and aquaticfreshwater angiosperms (Eucalyptolaurus depreii, Ploufolia). They are associated with acoleopteran insect that shows systematic affinities to the modern subfamily Chrysomeli-nae (Chrysomelidae). This assemblage suggests connections with arborescent vegetationgrowing in calm freshwater environment. Brackish to marine invertebrates also occurand include a dakoticancroid crab (Brachyura, Podotremata, Dakoticancroidea) and a fewbivalves (Brachidontes). They suggest brackish episodes during pond sedimentation in acoastal environment. Lastly, vertebrates are represented by an isolated feather