Weights for relative motives; relation with mixed complexes of sheaves

The main goal of this paper is to define the so-called Chow weight structure for the category of Beilinson motives over any 'reasonable' base scheme $S$ (this is the version of Voevodsky's motives over $S$ defined by Cisinski and Deglise). We also study the functoriality properties of the Chow weight structure (they are very similar to the well-known functoriality of weights for mixed complexes of sheaves). As shown in a preceding paper, the Chow weight structure automatically yields an exact conservative weight complex functor (with values in $K^b(Chow(S))$). Here $Chow(S)$ is the heart of the Chow weight structure; it is 'generated' by motives of regular schemes that are projective over $S$. Besides, Grothendiek's group of $S$-motives is isomorphic to $K_0(Chow(S))$; we also define a certain 'motivic Euler characteristic' for $S$-schemes. We obtain (Chow)-weight spectral sequences and filtrations for any cohomology of motives; we discuss their relation to Beilinson's 'integral part' of motivic cohomology and to weights of mixed complexes of sheaves. For the study of the latter we introduce a new formalism of relative weight structures.Comment: a few minor corrections mad

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

Differential graded motives: weight complex, weight filtrations and spectral sequences for realizations; Voevodsky vs. Hanamura

We describe the Voevodsky's category $DM^{eff}_{gm}$ of motives in terms of Suslin complexes of smooth projective varieties. This shows that Voeovodsky's $DM_{gm}$ is anti-equivalent to Hanamura's one. We give a description of any triangulated subcategory of $DM^{eff}_{gm}$ (including the category of effective mixed Tate motives). We descibe 'truncation' functors $t_N$ for $N>0$. $t=t_0$ generalizes the weight complex of Soule and Gillet; its target is $K^b(Chow_{eff})$; it calculates $K_0(DM^{eff}_{gm})$, and checks whether a motive is a mixed Tate one. $t_N$ give a weight filtration and a 'motivic descent spectral sequence' for a large class of realizations, including the 'standard' ones and motivic cohomology. This gives a new filtration for the motivic cohomology of a motif. For 'standard realizations' for $l,s\ge 0$ we have a nice description of $W_{l+s}H^i/W_{l-1}H^i(X)$ in terms of $t_s(X)$. We define the 'length of a motif' that (modulo standard conjectures) coincides with the 'total' length of the weight filtration of singular cohomology. Over a finite field $t_0Q$ is (modulo Beilinson-Parshin conjecture) an equivalence.Comment: Several linguistic corrections made; section 2.3 was corrected als

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

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