423 research outputs found

    Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

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    Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

    A search for point sources of EeV photons

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    Measurements of air showers made using the hybrid technique developed with the fluorescence and surface detectors of the Pierre Auger Observatory allow a sensitive search for point sources of EeV photons anywhere in the exposed sky. A multivariate analysis reduces the background of hadronic cosmic rays. The search is sensitive to a declination band from -85{\deg} to +20{\deg}, in an energy range from 10^17.3 eV to 10^18.5 eV. No photon point source has been detected. An upper limit on the photon flux has been derived for every direction. The mean value of the energy flux limit that results from this, assuming a photon spectral index of -2, is 0.06 eV cm^-2 s^-1, and no celestial direction exceeds 0.25 eV cm^-2 s^-1. These upper limits constrain scenarios in which EeV cosmic ray protons are emitted by non-transient sources in the Galaxy.Comment: 28 pages, 10 figures, accepted for publication in The Astrophysical Journa

    Azimuthal asymmetry in the risetime of the surface detector signals of the Pierre Auger Observatory

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    The azimuthal asymmetry in the risetime of signals in Auger surface detector stations is a source of information on shower development. The azimuthal asymmetry is due to a combination of the longitudinal evolution of the shower and geometrical effects related to the angles of incidence of the particles into the detectors. The magnitude of the effect depends upon the zenith angle and state of development of the shower and thus provides a novel observable, (secθ)max(\sec \theta)_\mathrm{max}, sensitive to the mass composition of cosmic rays above 3×10183 \times 10^{18} eV. By comparing measurements with predictions from shower simulations, we find for both of our adopted models of hadronic physics (QGSJETII-04 and EPOS-LHC) an indication that the mean cosmic-ray mass increases slowly with energy, as has been inferred from other studies. However, the mass estimates are dependent on the shower model and on the range of distance from the shower core selected. Thus the method has uncovered further deficiencies in our understanding of shower modelling that must be resolved before the mass composition can be inferred from (secθ)max(\sec \theta)_\mathrm{max}.Comment: Replaced with published version. Added journal reference and DO

    Reconstruction of inclined air showers detected with the Pierre Auger Observatory

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    We describe the method devised to reconstruct inclined cosmic-ray air showers with zenith angles greater than 6060^\circ detected with the surface array of the Pierre Auger Observatory. The measured signals at the ground level are fitted to muon density distributions predicted with atmospheric cascade models to obtain the relative shower size as an overall normalization parameter. The method is evaluated using simulated showers to test its performance. The energy of the cosmic rays is calibrated using a sub-sample of events reconstructed with both the fluorescence and surface array techniques. The reconstruction method described here provides the basis of complementary analyses including an independent measurement of the energy spectrum of ultra-high energy cosmic rays using very inclined events collected by the Pierre Auger Observatory.Comment: 27 pages, 19 figures, accepted for publication in Journal of Cosmology and Astroparticle Physics (JCAP

    The Pierre Auger Observatory: Contributions to the 34th International Cosmic Ray Conference (ICRC 2015)

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    Contributions of the Pierre Auger Collaboration to the 34th International Cosmic Ray Conference, 30 July - 6 August 2015, The Hague, The NetherlandsComment: 24 proceedings, the 34th International Cosmic Ray Conference, 30 July - 6 August 2015, The Hague, The Netherlands; will appear in PoS(ICRC2015

    Grain yield and its components study and their association with normalized difference vegetation index (NDVI) under terminal water deficit and well-irrigated conditions in wheat (Triticum durum Desf. and Triticum aestivum L.)

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    Six genotype of Triticum aestivum L. in 1991 and one genotype of Triticum durum Desf. and three of T. aestivum L. in 1992 were studied under different water regimes: full irrigation (R1), mild water stress (R3) and severe water stress (R2) at Magneraud (France). Traits evaluated were grain yield and its components, stress susceptibility index (SSI) and normalized difference vegetation index (NDVI). The analysis of variance revealed significant differences between regimes and among the cultivars for all traits except between regimes for thousand grains weight in 1991. The regime × variety interaction was significant for grain yield, thousand grains weight and NDVI in 1992 and for grain yield in 1991. For all traits, durum wheat (T. durum Desf.) has higher reduction in the two water stress than the common wheat (T. aestivum L.). Correlations studies revealed that grain yield, grains number/m², thousand grains weight and NDVI were associated with each other except for correlations between thousand grains weight on one hand and grain yield (1992) and grains number/m² (1991) on the other hand. 51.55, 27.88, 4.12% (1991) and 75, 43 and 20.2% (1992) of grain yield, grains/m² and thousand grains weight variability, respectively were explained by means NDVI variability. The grain yield and grains number/m² could be predicted using a single regression with NDVI.Keywords: Grain yield, grain yield components, NDVI, durum wheat and bread wheat

    Evaluation of fungicides for the management of pearl millet [ Pennisetum glaucum (L.)] blast caused by Magnaporthe grisea

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    Blast disease caused by Magnaporthe grisea has emerged as a serious threat to pearl millet cultivation in India. Most of the hybrids being grown in India are susceptible to blast as not much efforts have been made to breed for blast resistance in pearl millet. In the absence of host plant resistance, the disease can be effectively managed with chemical fungicides. Therefore, nine fungicides, chlorothalonil, tricyclazole, hexaconazole, kasugamycin, benomyl, carbendazim, tebuconazole + trifloxystrobin, propiconazole and metalaxyl + mancozeb were tested for their efficacy to manage blast disease on a blast susceptible pearl millet line ICMB 95444. Different combinations of seed treatment and foliar sprays were tested: seed treatment alone, seed treatment + one spray, seed treatment + two sprays, seed treatment + three sprays. None of the fungicides was found effective when used as seed treatment. Results of this study clearly demonstrated that the disease can be effectively managed with three sprays of tebuconazole + trifloxystrobin (Nativo) or propiconazole (Tilt)

    Balancing repair and tolerance of DNA damage caused by alkylating agents

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    Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity
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