Online Review Censorship

Ample anecdotal evidence in the media notes that many businesses seek to ‘silence’ negative reviews, e.g., via legal threat. Despite attention toward this issue, we are aware of no systematic analyses addressing it. We address that gap here, leveraging review data from TripAdvisor.com. First, we estimate that ~1% of truthful reviews are deleted within six months of posting and that negative reviews are significantly more likely to be deleted, consistent with a mechanism of censorship. The effect is substantial; we estimate that a 1-star decrease in rating valence is associated with an approximate 25% (0.25pp) increase in the probability of deletion. Second, we examine how freedom of expression (FoE) in a country associates with characteristics of (uncensored) online reviews. We find that FoE associates with larger review volumes, lower review valence, and faster review posting. We discuss implications for online ratings platforms, consumers, and research opportunities

Auxin-induced WUS expression is essential for embryonic stem cell renewal during somatic embryogenesis in Arabidopsis

Somatic embryogenesis requires auxin and establishment of the shoot apical meristem (SAM). WUSCHEL (WUS) is critical for stem cell fate determination in the SAM of higher plants. However, regulation of WUS expression by auxin during somatic embryogenesis is poorly understood. Here, we show that expression of several regulatory genes important in zygotic embryogenesis were up-regulated during somatic embryogenesis of Arabidopsis. Interestingly, WUS expression was induced within the embryonic callus at a time when somatic embryos could not be identified morphologically or molecularly. CorrectWUS expression, regulated by a defined critical level of exogenous auxin, is essential for somatic embryo induction. Furthermore, it was found that auxin gradients were established in specific regions that could then give rise to somatic embryos. The establishment of auxin gradients was correlated with the induced WUS expression. Moreover, the auxin gradients appear to activate PIN1 polar localization within the embryonic callus. Polarized PIN1 is probably responsible for the observed polar auxin transport and auxin accumulation in the SAM and somatic embryo. Suppression of WUS and PIN1 indicated that both genes are necessary for embryo induction through their regulation of downstream gene expression. Our results reveal that establishment of auxin gradients and PIN1-mediated polar auxin transport are essential for WUS induction and somatic embryogenesis. This study sheds new light on how auxin regulates stem cell formation during somatic embryogenesis

Primary care practitioners’ diagnostic action when the patient may have cancer : an exploratory vignette study in 20 European countries

Availability of data To avoid the risk of identification of individual participants, the datasets generated and analysed during the current study are not publicly available. However, they are available (with any possible identifying information redacted) from the corresponding author on reasonable request. Funding This study received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. ALN’s time is supported by the National Institute for Health Research (NIHR) Imperial Patient Safety Translation Research Centre, with her infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). Acknowledgements We would like to thank all the PCPs who piloted the questionnaire and those who completed the survey. We would also like to thank the European GP Research Network for its support. We are grateful to Prof. Barbara Silverman and Prof. Lital Keinan for the data on cancer survival rates in Israel, and to Dr Yochai Schonmann for his work on those data. Two of the vignettes were used by kind permission of the ICBP; we also thank Dr Peter Murchie and Dr Rhona Auckland, who generously provided the other two vignettes. Prof. Antonius Schneider kindly organised the Technical University of Munich’s data collection.Peer reviewedPublisher PD

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Short Day Transcriptomic Programming During Induction of Dormancy in Grapevine

Bud dormancy in grapevine is an adaptive strategy for the survival of drought, high and low temperatures and freeze dehydration stress that limit the range of cultivar adaptation. Therefore, development of a comprehensive understanding of the biological mechanisms involved in bud dormancy is needed to promote advances in selection and breeding, and to develop improved cultural practices for existing grape cultivars. The seasonally indeterminate grapevine, which continuously develops compound axillary buds during the growing season, provides an excellent system for dissecting dormancy, because the grapevine does not transition through terminal bud development prior to dormancy. This study used gene expression patterns and targeted metabolite analysis of two grapevine genotypes that are short photoperiod responsive (Vitis riparia) and non-responsive (V. hybrid, Seyval) for dormancy development to determine differences between bud maturation and dormancy commitment. Grapevine gene expression and metabolites were monitored at seven time points under long (LD, 15 h) and short (SD, 13 h) day treatments. The use of age-matched buds and a small (2 h) photoperiod difference minimized developmental differences and allowed us to separate general photoperiod from dormancy specific gene responses. Gene expression profiles indicated three distinct phases (perception, induction and dormancy) in SD-induced dormancy development in V. riparia. Different genes from the NAC DOMAIN CONTAINING PROTEIN 19 and WRKY families of transcription factors were differentially expressed in each phase of dormancy. Metabolite and transcriptome analyses indicated ABA, trehalose, raffinose and resveratrol compounds have a potential role in dormancy commitment. Finally, a comparison between V. riparia compound axillary bud dormancy and dormancy responses in other species emphasized the relationship between dormancy and the expression of RESVERATROL SYNTHASE and genes associated with C3HC4-TYPE RING FINGER and NAC DOMAIN CONTAINING PROTEIN 19 transcription factors

P. falciparum and P. vivax Epitope-Focused VLPs Elicit Sterile Immunity to Blood Stage Infections

In order to design P. falciparum preerythrocytic vaccine candidates, a library of circumsporozoite (CS) T and B cell epitopes displayed on the woodchuck hepatitis virus core antigen (WHcAg) VLP platform was produced. To test the protective efficacy of the WHcAg-CS VLPs, hybrid CS P. berghei/P. falciparum (Pb/Pf) sporozoites were used to challenge immunized mice. VLPs carrying 1 or 2 different CS repeat B cell epitopes and 3 VLPs carrying different CS non-repeat B cell epitopes elicited high levels of anti-insert antibodies (Abs). Whereas, VLPs carrying CS repeat B cell epitopes conferred 98% protection of the liver against a 10,000 Pb/Pf sporozoite challenge, VLPs carrying the CS non-repeat B cell eptiopes were minimally-to-non-protective. One-to-three CS-specific CD4/CD8 T cell sites were also fused to VLPs, which primed CS-specific as well as WHcAg-specific T cells. However, a VLP carrying only the 3 T cell domains failed to protect against a sporozoite challenge, indicating a requirement for anti-CS repeat Abs. A VLP carrying 2 CS repeat B cell epitopes and 3 CS T cell sites in alum adjuvant elicited high titer anti-CS Abs (endpoint dilution titer \u3e1x106) and provided 80–100% protection against blood stage malaria. Using a similar strategy, VLPs were constructed carrying P. vivax CS repeat B cell epitopes (WHc-Pv-78), which elicited high levels of anti-CS Abs and conferred 99% protection of the liver against a 10,000 Pb/Pv sporozoite challenge and elicited sterile immunity to blood stage infection. These results indicate that immunization with epitope-focused VLPs carrying selected B and T cell epitopes from the P.falciparum and P. vivax CS proteins can elicit sterile immunity against blood stage malaria. Hybrid WHcAg-CS VLPs could provide the basis for a bivalent P. falciparum/P. vivax malaria vaccine

A trematode parasite derived growth factor binds and exerts influences on host immune functions via host cytokine receptor complexes

The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allow- ing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF) superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL)-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory recep- tor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is depen- dent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs) in their evasion of antibody- dependent cell cytotoxicity (ADCC) by reducing the NO response of macrophages—again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for damp- ened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow for a reduced effector response targetingjuvenile parasites which we demonstrate extends to an abrogation of the ADCC response. Thus suggesting that FhTLM is a stage specific evasion molecule that utilises host cytokine receptors. These findings are the first to clearly demonstrate the interaction of a helminth cytokine with a host receptor complex resulting in immune modifications that facilitate the non-protective chronic immune response which is characteristic of F. hepatica infection