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Luminous and high-frequency peaked blazars: the origin of the gamma-ray emission from PKS 1424+240
(2017)
Context. The current generation of ground-based Cherenkov telescopes, together with the LAT instrument on-board the Fermi satellite, have greatly increased our knowledge of gamma-ray blazars. Among them, the high-frequency-peaked BL Lacertae object (HBL) PKS 1424+240 (z similar or equal to 0.6) is the farthest persistent emitter of very-high-energy (VHE; E >= 100 GeV) gamma-ray photons. Current emission models can satisfactorily reproduce typical blazar emission assuming that the dominant emission process is synchrotron-self-Compton (SSC) in HBLs; and external-inverse-Compton (EIC) in low-frequency-peaked BL Lacertae objects and flat-spectrum-radio-quasars. Alternatively, hadronic models are also able to correctly reproduce the gamma-ray emission from blazars, although they are in general disfavored for bright quasars and rapid flares. Aims. The blazar PKS 1424+240 is a rare example of a luminous HBL, and we aim to determine which is the emission process most likely responsible for its gamma-ray emission. This will impact more generally our comprehension of blazar emission models, and how they are related to the luminosity of the source and the peak frequency of the spectral energy distribution. Methods. We have investigated different blazar emission models applied to the spectral energy distribution of PKS 1424+240. Among leptonic models, we study a one-zone SSC model (including a systematic study of the parameter space), a two-zone SSC model, and an EIC model. We then investigated a blazar hadronic model, and finally a scenario in which the gamma-ray emission is associated with cascades in the line-of-sight produced by cosmic rays from the source. Results. After a systematic study of the parameter space of the one-zone SSC model, we conclude that this scenario is not compatible with gamma-ray observations of PKS 1424+240. A two-zone SSC scenario can alleviate this issue, as well as an EIC solution. For the latter, the external photon field is assumed to be the infra-red radiation from the dusty torus, otherwise the VHE gamma-ray emission would have been significantly absorbed. Alternatively, hadronic models can satisfactorily reproduce the gamma-ray emission from PKS 1424+240, both as in-source emission and as cascade emission.
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.