Impact of mesh resolution for MISMIP and MISMIP3d experiments using Elmer/Ice

International audienceThe dynamical contribution of marine ice sheets to sea level rise is largely controlled by grounding line (GL) dynamics. Two marine ice sheet model intercomparison exercises , namely MISMIP and MISMIP3d, have been proposed to the community to test and compare the ability of models to capture the GL dynamics. Both exercises are known to present a discontinuity of the friction at the GL, which is believed to increase the model sensitivity to mesh resolution. Here, using Elmer/Ice, the only Stokes model which completed both intercomparisons, the sensitivity to the mesh resolution is studied from an extended MISMIP experiment in which the friction continuously decreases over a transition distance and equals zero at the GL. Using this MISMIP-like setup, it is shown that the sensitivity to the mesh resolution is not improved for a vanishing friction at the GL. For the original MISMIP experiment, i.e. for a discontinuous friction at the GL, we further show that the results are moreover very sensitive to the way the friction is interpolated in the close vicinity of the GL. In the light of these new insights, and thanks to increased computing resources, new results for the MISMIP3d experiments obtained for higher resolutions than previously published are made available for future comparisons as the Supplement

Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein

The IGROVCDDP cisplatin-resistant ovarian cancer cell line is also resistant to paclitaxel and models the resistance phenotype of relapsed ovarian cancer patients after first-line platinum/taxane chemotherapy. A TaqMan low-density array (TLDA) was used to characterise the expression of 380 genes associated with chemotherapy resistance in IGROVCDDP cells. Paclitaxel resistance in IGROVCDDP is mediated by gene and protein overexpression of P-glycoprotein and the protein is functionally active. Cisplatin resistance was not reversed by elacridar, confirming that cisplatin is not a P-glycoprotein substrate. Cisplatin resistance in IGROVCDDP is multifactorial and is mediated in part by the glutathione pathway and decreased accumulation of drug. Total cellular glutathione was not increased. However, the enzyme activity of GSR and GGT1 were up-regulated. The cellular localisation of copper transporter CTR1 changed from membrane associated in IGROV-1 to cytoplasmic in IGROVCDDP. This may mediate the previously reported accumulation defect. There was decreased expression of the sodium potassium pump (ATP1A), MRP1 and FBP which all have been previously associated with platinum accumulation defects in platinum-resistant cell lines. Cellular localisation of MRP1 was also altered in IGROVCDDP shifting basolaterally, compared to IGROV-1. BRCA1 was also up-regulated at the gene and protein level. The overexpression of P-glycoprotein in a resistant model developed with cisplatin is unusual. This demonstrates that P-glycoprotein can be up-regulated as a generalised stress response rather than as a specific response to a substrate. Mechanisms characterised in IGROVCDDP cells may be applicable to relapsed ovarian cancer patients treated with frontline platinum/taxane chemotherapy

Development and application of a data-driven reaction classification model : comparison of an electronic lab notebook and the medicinal chemistry literature

Reaction classification has often been considered an important task for many different applications, and has traditionally been accomplished using hand-coded rule-based approaches. However, the availability of large collections of reactions enables data-driven approaches to be developed. We present the development and validation of a 336-class machine learning-based classification model integrated within a Conformal Prediction (CP) framework in order to associate reaction class predictions with confidence estimations. We also propose a data-driven approach for 'dynamic' reaction fingerprinting to maximise the effectiveness of reaction encoding, as well as developing a novel reaction classification system that organises labels in four hierarchical levels (SHREC: Sheffield Hierarchical REaction Classification). We show that the performance of the CP augmented model can be improved by defining confidence thresholds to detect predictions that are less likely to be false. For example, the external validation of the model reports 95% of predictions as correct by filtering out less than 15% of the uncertain classifications. The application of the model is demonstrated by classifying two reaction datasets: one extracted from an industrial ELN and the other from the medicinal chemistry literature. We show how confidence estimations and class compositions across different levels of information can be used to gain immediate insights on the nature of reaction collections and hidden relationship between reaction classes

Proteomic and functional analyses of the virion transmembrane proteome of cyprinid herpesvirus 3

Virion transmembrane proteins (VTPs) mediate key functions in the herpesvirus infectious cycle. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses. The present study was devoted to CyHV-3 VTPs. Using mass spectrometry approaches, we identified 16 VTPs of the CyHV-3 FL strain. Mutagenesis experiments demonstrated that eight of these proteins are essential for viral growth in vitro (ORF32, ORF59, ORF81, ORF83, ORF99, ORF106, ORF115, and ORF131), and eight are non-essential (ORF25, ORF64, ORF65, ORF108, ORF132, ORF136, ORF148, and ORF149). Among the non-essential proteins, deletion of ORF25, ORF132, ORF136, ORF148, or ORF149 affects viral replication in vitro, and deletion of ORF25, ORF64, ORF108, ORF132, or ORF149 impacts plaque size. Lack of ORF148 or ORF25 causes attenuation in vivo to a minor or major extent, respectively. The safety and efficacy of a virus lacking ORF25 were compared to those of a previously described vaccine candidate deleted for ORF56 and ORF57 (Δ56-57). Using quantitative PCR, we demonstrated that the ORF25 deleted virus infects fish through skin infection and then spreads to internal organs as reported previously for the wild-type parental virus and the Δ56-57 virus. However, compared to the parental wild-type virus, the replication of the ORF25 deleted virus was reduced in intensity and duration to levels similar to those observed for the Δ56-57 virus. Vaccination of fish with a virus lacking ORF25 was safe but had low efficacy at the doses tested. This characterization of the virion transmembrane proteome of CyHV-3 provides a firm basis for further research on alloherpesvirus VTPs. IMPORTANCE Virion transmembrane proteins play key roles in the biology of herpesviruses. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses and the causative agent of major economic losses in common and koi carp worldwide. In this study of the virion transmembrane proteome of CyHV-3, the major findings were: (i) the FL strain encodes 16 virion transmembrane proteins; (ii) eight of these proteins are essential for viral growth in vitro; (iii) seven of the non-essential proteins affect viral growth in vitro, and two affect virulence in vivo; and (iv) a mutant lacking ORF25 is highly attenuated but induces moderate immune protection. This study represents a major breakthrough in understanding the biology of CyHV-3 and will contribute to the development of prophylactic methods. It also provides a firm basis for the further research on alloherpesvirus virion transmembrane proteins

Towards the solution of the CP/CAC_{P}/C_{A} anomaly in shell-model calculations of muon capture

Recently many authors have performed shell-model calculations of nuclear matrix elements determining the rates of the ordinary muon capture in light nuclei. These calculations have employed well-tested effective interactions in large scale shell-model studies. For one of the nuclei of interest, namely $^{28}$Si, there exists recent experimental data which can be used to deduce the value of the ratio $C_{P}/C_{A}$ by using the calculated matrix elements. Surprisingly enough, all the abovementioned shell-model results suggest a very small value ($\simeq 0$) for $C_{P}/C_{A}$, quite far from the PCAC prediction and recent data on muon capture in hydrogen. We show that this rather disturbing anomaly is solved by employing effective transition operators. This finding is also very important in studies of the scalar coupling of the weak charged current of leptons and hadrons.Comment: Revtex, 6 pages, 2 figs include

The whole and its parts : why and how to disentangle plant communities and synusiae in vegetation classification

Most plant communities consist of different structural and ecological subsets, ranging from cryptogams to different tree layers. The completeness and approach with which these subsets are sampled have implications for vegetation classification. Non‐vascular plants are often omitted or sometimes treated separately, referring to their assemblages as “synusiae” (e.g. epiphytes on bark, saxicolous species on rocks). The distinction of complete plant communities (phytocoenoses or holocoenoses) from their parts (synusiae or merocoenoses) is crucial to avoid logical problems and inconsistencies of the resulting classification systems. We here describe theoretical differences between the phytocoenosis as a whole and its parts, and outline consequences of this distinction for practise and terminology in vegetation classification. To implement a clearer separation, we call for modifications of the International Code of Phytosociological Nomenclature and the EuroVegChecklist. We believe that these steps will make vegetation classification systems better applicable and raise the recognition of the importance of non‐vascular plants in the vegetation as well as their interplay with vascular plants

The evolutionary status of the semiregular variable QYSge

Repeated spectroscopic observations made with the 6m telescope of yielded new data on the radial-velocity variability of the anomalous yellow supergiant QYSge. The strongest and most peculiar feature in its spectrum is the complex profile of NaI D lines, which contains a narrow and a very wide emission components. The wide emission component can be seen to extend from -170 to +120 km/s, and at its central part it is cut by an absorption feature, which, in turn, is split into two subcomponents by a narrow (16km/s at r=2.5) emission peak. An analysis of all the Vr values leads us to adopt for the star a systemic velocity of Vr=-21.1 km/s, which corresponds to the position of the narrow emission component of NaI. The locations of emission-line features of NaI D lines are invariable, which point to their formation in regions that are external to the supergiant's photosphere. Differential line shifts of about 10km/s are revealed. The absorption lines in the spectrum of QYSge have a substantial width of FWHM~45 km/s. The method of model atmospheres is used to determine the following parameters: Teff=6250K, lg g=2.0, and microturbulence Vt=4.5km/s. The metallicity of the star is found to be somewhat higher than the solar one with an average overabundance of iron-peak elements of [Met/H]=+0.20. The star is found to be slightly overabundant in carbon and nitrogen, [C/Fe]=+0.25, [N/Fe]=+0.27. The alpha-process elements Mg, Si, and Ca are slightly overabundant [alpha/H]=+0.12. The strong sodium excess, [Na/Fe]=+0.75, is likely to be due to the dredge-up of the matter processed in the NeNa cycle. Heavy elements of the s-process are underabundant relative to the Sun. On the whole, the observed properties of QYSge do not give grounds for including this star into the group of RCrB or RVTau-type type objects.Comment: 29 pages, 8 figures, 4 tables; accepted by Astrophys. Bulleti

GALEX J201337.6+092801: The lowest gravity subdwarf B pulsator

We present the recent discovery of a new subdwarf B variable (sdBV), with an exceptionally low surface gravity. Our spectroscopy of J20136+0928 places it at Teff = 32100 +/- 500, log(g) = 5.15 +/- 0.10, and log(He/H) = -2.8 +/- 0.1. With a magnitude of B = 12.0, it is the second brightest V361 Hya star ever found. Photometry from three different observatories reveals a temporal spectrum with eleven clearly detected periods in the range 376 to 566 s, and at least five more close to our detection limit. These periods are unusually long for the V361 Hya class of short-period sdBV pulsators, but not unreasonable for p- and g-modes close to the radial fundamental, given its low surface gravity. Of the ~50 short period sdB pulsators known to date, only a single one has been found to have comparable spectroscopic parameters to J20136+0928. This is the enigmatic high-amplitude pulsator V338 Ser, and we conclude that J20136+0928 is the second example of this rare subclass of sdB pulsators located well above the canonical extreme horizontal branch in the HR diagram.Comment: 5 pages, accepted for publication in ApJ Letter

Methicillin resistance is not a predictor of severity in community-acquired Staphylococcus aureus necrotizing pneumonia—results of a prospective observational study

AbstractStaphylococcal necrotizing pneumonia (NP) is a severe disease associated with Panton–Valentine leucocidin (PVL). NP was initially described for methicillin-susceptible Staphylococcus aureus (MSSA) infection, but cases associated with methicillin-resistant S. aureus (MRSA) infection have increased concomitantly with the incidence of community-acquired MRSA worldwide. The role of methicillin resistance in the severity of NP remains controversial. The characteristics and outcomes of 133 patients with PVL-positive S. aureus community-acquired pneumonia (CAP) were compared according to methicillin resistance. Data from patients hospitalized for PVL-positive S. aureus CAP in France from 1986 to 2010 were reported to the National Reference Centre for Staphylococci and were included in the study. The primary end point was mortality. Multivariate logistic modelling and the Cox regression were used for subsequent analyses. We analysed 29 cases of PVL-MRSA and 104 cases of PVL-MSSA pneumonia. Airway haemorrhages were more frequently associated with PVL-MSSA pneumonia. However, no differences in the initial severity or the management were found between these two types of pneumonia. The rate of lethality was 39% regardless of methicillin resistance. By Cox regression analysis, methicillin resistance was not found to be a significant independent predictor of mortality at 7 or 30 days (p 0.65 and p 0.71, respectively). Our study demonstrates that methicillin resistance is not associated with the severity of staphylococcal necrotizing pneumonia

Evidence of temperature-dependent effects on the estrogenic response of fish: implications with regard to climate change

The official published version can be obtained from the link below - Copyright @ 2008 Elsevier BV.Chemical risk assessment is fraught with difficulty due to the problem of accounting for the effects of mixtures. In addition to the uncertainty arising from chemical-to-chemical interactions, it is possible that environmental variables, such as temperature, influence the biological response to chemical challenge, acting as confounding factors in the analysis of mixture effects. Here, we investigate the effects of temperature on the response of fish to a defined mixture of estrogenic chemicals. It was anticipated that the response to the mixture may be exacerbated at higher temperatures, due to an increase in the rate of physiological processing. This is a pertinent issue in view of global climate change. Fathead minnows (Pimephales promelas) were exposed to the mixture in parallel exposure studies, which were carried out at different temperatures (20 and 30 degrees C). The estrogenic response was characterised using an established assay, involving the analysis of the egg yolk protein, vitellogenin (VTG). Patterns of VTG gene expression were also analysed using real-time QPCR. The results revealed that there was no effect of temperature on the magnitude of the VTG response after 2 weeks of chemical exposure. However, the analysis of mixture effects at two additional time points (24 h and 7 days) revealed that the response was induced more rapidly at the higher temperature. This trend was apparent from the analysis of effects both at the molecular and biochemical level. Whilst this indicates that climatic effects on water temperature are not a significant issue with regard to the long-term risk assessment of estrogenic chemicals, the relevance of short-term effects is, as yet, unclear. Furthermore, analysis of the patterns of VTG gene expression versus protein induction gives an insight into the physiological mechanisms responsible for temperature-dependent effects on the reproductive phenology of species such as roach. Hence, the data contribute to our understanding of the implications of global climate change for wild fish populations.This work was funded by a grant from the Natural Environment Research Council NE/D00389X/1). Additional support was provided by a small research grant from the Fisheries Society of the British Isles