1,024 research outputs found

    Superhero comics and the digital communications circuit: a case study of <i>Strong Female Protagonist</i>

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    This article examines the ongoing superhero webcomic Strong Female Protagonist (2012-present), by Brannon Lee Mulligan and Molly Ostertag and employs it as a case study to analyse the new communications circuit created by the digital production and delivery of comics. It adopts a perspective drawn from Book History to frame the communication model of print comics and to evaluate how webcomics such as Strong Female Protagonist redefine the role of readers, authors and publishers

    The Role of Regulated mRNA Stability in Establishing Bicoid Morphogen Gradient in Drosophila Embryonic Development

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    The Bicoid morphogen is amongst the earliest triggers of differential spatial pattern of gene expression and subsequent cell fate determination in the embryonic development of Drosophila. This maternally deposited morphogen is thought to diffuse in the embryo, establishing a concentration gradient which is sensed by downstream genes. In most model based analyses of this process, the translation of the bicoid mRNA is thought to take place at a fixed rate from the anterior pole of the embryo and a supply of the resulting protein at a constant rate is assumed. Is this process of morphogen generation a passive one as assumed in the modelling literature so far, or would available data support an alternate hypothesis that the stability of the mRNA is regulated by active processes? We introduce a model in which the stability of the maternal mRNA is regulated by being held constant for a length of time, followed by rapid degradation. With this more realistic model of the source, we have analysed three computational models of spatial morphogen propagation along the anterior-posterior axis: (a) passive diffusion modelled as a deterministic differential equation, (b) diffusion enhanced by a cytoplasmic flow term; and (c) diffusion modelled by stochastic simulation of the corresponding chemical reactions. Parameter estimation on these models by matching to publicly available data on spatio-temporal Bicoid profiles suggests strong support for regulated stability over either a constant supply rate or one where the maternal mRNA is permitted to degrade in a passive manner

    Biological predictive factors in rectal cancer treated with preoperative radiotherapy or radiochemotherapy

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    We analysed the expression of microsatellite instability, p53, p21, vascular endothelial growth factor and thymidylate synthase (TS) in pretreatment biopsy specimens from 57 locally advanced rectal cancers. The aim of the study was to correlate the expression of these markers with pathological response. Nineteen patients were treated with preoperative concomitant radiotherapy (RT) and fluorouracil/oxaliplatin-based chemotherapy (RCT), while 38 had RT alone. Pathological complete remission (pCR) and microfoci residual tumour (micR) occurred more frequently in patients treated with RCT (P=0.002) and in N0 tumours (P=0.004). Among patients treated with RCT, high TS levels were associated with a higher response rate (pCR+micR; P=0.015). No such correlation was found in the RT group. The other molecular factors were of no predictive value. Multivariate analysis confirmed a significant interaction between nodal status and the probability of achieving a pathological response (P=0.023) and between TS expression and treatment, indicating that a high TS level is predictive of a higher pathological response in the RCT subset (P=0.007). This study shows that lymph node status is the most important predictive factor of tumour response to preoperative treatment. Thymidylate synthase expression assessed immunohistochemically from pretreatment tumour biopsies may be a useful predictive marker of rectal tumour response to preoperative RCT

    Characterization of an Ionization Readout Tile for nEXO

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    A new design for the anode of a time projection chamber, consisting of a charge-detecting "tile", is investigated for use in large scale liquid xenon detectors. The tile is produced by depositing 60 orthogonal metal charge-collecting strips, 3~mm wide, on a 10~\si{\cm} ×\times 10~\si{\cm} fused-silica wafer. These charge tiles may be employed by large detectors, such as the proposed tonne-scale nEXO experiment to search for neutrinoless double-beta decay. Modular by design, an array of tiles can cover a sizable area. The width of each strip is small compared to the size of the tile, so a Frisch grid is not required. A grid-less, tiled anode design is beneficial for an experiment such as nEXO, where a wire tensioning support structure and Frisch grid might contribute radioactive backgrounds and would have to be designed to accommodate cycling to cryogenic temperatures. The segmented anode also reduces some degeneracies in signal reconstruction that arise in large-area crossed-wire time projection chambers. A prototype tile was tested in a cell containing liquid xenon. Very good agreement is achieved between the measured ionization spectrum of a 207^{207}Bi source and simulations that include the microphysics of recombination in xenon and a detailed modeling of the electrostatic field of the detector. An energy resolution σ/E\sigma/E=5.5\% is observed at 570~\si{keV}, comparable to the best intrinsic ionization-only resolution reported in literature for liquid xenon at 936~V/\si{cm}.Comment: 18 pages, 13 figures, as publishe

    The potential of unmanned aerial systems for sea turtle research and conservation: A review and future directions

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    This is the final version. Available on open access from Inter Research via the DOI in this recordThe use of satellite systems and manned aircraft surveys for remote data collection has been shown to be transformative for sea turtle conservation and research by enabling the collection of data on turtles and their habitats over larger areas than can be achieved by surveys on foot or by boat. Unmanned aerial vehicles (UAVs) or drones are increasingly being adopted to gather data, at previously unprecedented spatial and temporal resolutions in diverse geographic locations. This easily accessible, low-cost tool is improving existing research methods and enabling novel approaches in marine turtle ecology and conservation. Here we review the diverse ways in which incorporating inexpensive UAVs may reduce costs and field time while improving safety and data quality and quantity over existing methods for studies on turtle nesting, at-sea distribution and behaviour surveys, as well as expanding into new avenues such as surveillance against illegal take. Furthermore, we highlight the impact that high-quality aerial imagery captured by UAVs can have for public outreach and engagement. This technology does not come without challenges. We discuss the potential constraints of these systems within the ethical and legal frameworks which researchers must operate and the difficulties that can result with regard to storage and analysis of large amounts of imagery. We then suggest areas where technological development could further expand the utility of UAVs as data-gathering tools; for example, functioning as downloading nodes for data collected by sensors placed on turtles. Development of methods for the use of UAVs in sea turtle research will serve as case studies for use with other marine and terrestrial taxa

    Clusters of galaxies : observational properties of the diffuse radio emission

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    Clusters of galaxies, as the largest virialized systems in the Universe, are ideal laboratories to study the formation and evolution of cosmic structures...(abridged)... Most of the detailed knowledge of galaxy clusters has been obtained in recent years from the study of ICM through X-ray Astronomy. At the same time, radio observations have proved that the ICM is mixed with non-thermal components, i.e. highly relativistic particles and large-scale magnetic fields, detected through their synchrotron emission. The knowledge of the properties of these non-thermal ICM components has increased significantly, owing to sensitive radio images and to the development of theoretical models. Diffuse synchrotron radio emission in the central and peripheral cluster regions has been found in many clusters. Moreover large-scale magnetic fields appear to be present in all galaxy clusters, as derived from Rotation Measure (RM) studies. Non-thermal components are linked to the cluster X-ray properties, and to the cluster evolutionary stage, and are crucial for a comprehensive physical description of the intracluster medium. They play an important role in the cluster formation and evolution. We review here the observational properties of diffuse non-thermal sources detected in galaxy clusters: halos, relics and mini-halos. We discuss their classification and properties. We report published results up to date and obtain and discuss statistical properties. We present the properties of large-scale magnetic fields in clusters and in even larger structures: filaments connecting galaxy clusters. We summarize the current models of the origin of these cluster components, and outline the improvements that are expected in this area from future developments thanks to the new generation of radio telescopes.Comment: Accepted for the publication in The Astronomy and Astrophysics Review. 58 pages, 26 figure

    Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor

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    derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2

    Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers.

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    Cells in simple epithelia orient their mitotic spindles in the plane of the epithelium so that both daughter cells are born within the epithelial sheet. This is assumed to be important to maintain epithelial integrity and prevent hyperplasia, because misaligned divisions give rise to cells outside the epithelium. Here we test this assumption in three types of Drosophila epithelium; the cuboidal follicle epithelium, the columnar early embryonic ectoderm, and the pseudostratified neuroepithelium. Ectopic expression of Inscuteable in these tissues reorients mitotic spindles, resulting in one daughter cell being born outside the epithelial layer. Live imaging reveals that these misplaced cells reintegrate into the tissue. Reducing the levels of the lateral homophilic adhesion molecules Neuroglian or Fasciclin 2 disrupts reintegration, giving rise to extra-epithelial cells, whereas disruption of adherens junctions has no effect. Thus, the reinsertion of misplaced cells seems to be driven by lateral adhesion, which pulls cells born outside the epithelial layer back into it. Our findings reveal a robust mechanism that protects epithelia against the consequences of misoriented divisions.The authors are grateful to R. Nieuwburg, the St Johnston group, and other Gurdon Institute members for suggestions. We thank the Bloomington Stock Center, J. Knoblich, and the TRiP at Harvard Medical School (NIH/NIGMS R01-GM084947) for fly stocks. We thank N. Lowe for technical assistance. This work was supported by a Wellcome Trust Principal Fellowship to D.St.J. (080007), and by core support from the Wellcome Trust (092096) and Cancer Research UK (A14492). D.T.B. was supported by a Marie Curie Fellowship and the Wellcome Trust. H.E.L. was supported by a Herchel Smith Studentship.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ncb324

    Role of Scrib and Dlg in anterior-posterior patterning of the follicular epithelium during Drosophila oogenesis

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    <p>Abstract</p> <p>Background</p> <p>Proper patterning of the follicle cell epithelium over the egg chamber is essential for the <it>Drosophila </it>egg development. Differentiation of the epithelium into several distinct cell types along the anterior-posterior axis requires coordinated activities of multiple signaling pathways. Previously, we reported that <it>lethal(2)giant larvae </it>(<it>lgl</it>), a <it>Drosophila </it>tumor suppressor gene, is required in the follicle cells for the posterior follicle cell (PFC) fate induction at mid-oogenesis. Here we explore the role of another two tumor suppressor genes, <it>scribble </it>(<it>scrib</it>) and <it>discs large </it>(<it>dlg</it>), in the epithelial patterning.</p> <p>Results</p> <p>We found that removal of <it>scrib </it>or <it>dlg </it>function from the follicle cells at posterior terminal of the egg chamber causes a complete loss of the PFC fate. Aberrant specification and differentiation of the PFCs in the mosaic clones can be ascribed to defects in coordinated activation of the EGFR, JAK and Notch signaling pathways in the multilayered cells. Meanwhile, the clonal analysis revealed that loss-of-function mutations in <it>scrib/dlg </it>at the anterior domains result in a partially penetrant phenotype of defective induction of the stretched and centripetal cell fate, whereas specification of the border cell fate can still occur in the most anterior region of the mutant clones. Further, we showed that <it>scrib </it>genetically interacts with <it>dlg </it>in regulating posterior patterning of the epithelium.</p> <p>Conclusion</p> <p>In this study we provide evidence that <it>scrib </it>and <it>dlg </it>function differentially in anterior and posterior patterning of the follicular epithelium at oogenesis. Further genetic analysis indicates that <it>scrib </it>and <it>dlg </it>act in a common pathway to regulate PFC fate induction. This study may open another window for elucidating role of <it>scrib/dlg </it>in controlling epithelial polarity and cell proliferation during development.</p
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