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

Association between Protective and Deleterious HLA Alleles with Multiple Sclerosis in Central East Sardinia

The human leukocyte antigen (HLA) complex on chromosome 6p21 has been unambiguously associated with multiple sclerosis (MS). The complex features of the HLA region, especially its high genic content, extreme polymorphism, and extensive linkage disequilibrium, has prevented to resolve the nature of HLA association in MS. We performed a family based association study on the isolated population of the Nuoro province (Sardinia) to clarify the role of HLA genes in MS. The main stage of our study involved an analysis of the ancestral haplotypes A2Cw7B58DR2DQ1 and A30Cw5B18DR3DQ2. On the basis of a multiplicative model, the effect of the first haplotype is protective with an odds ratio (OR) = 0.27 (95% confidence interval CI 0.13–0.57), while that of the second is deleterious, OR 1.78 (95% CI 1.26–2.50). We found both class I (A, Cw, B) and class II (DR, DQ) loci to have an effect on MS susceptibility, but we saw that they act independently from each other. We also performed an exploratory analysis on a set of 796 SNPs in the same HLA region. Our study supports the claim that Class I and Class II loci act independently on MS susceptibility and this has a biological explanation. Also, the analysis of SNPs suggests that there are other HLA genes involved in MS, but replication is needed. This opens up new perspective on the study of MS

Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry

Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug is available to directly treat the disease and prevent virus spreading. In a search for a drug against COVID-19, we have performed a massive X-ray crystallographic screen of repurposing drug libraries containing 5953 individual compounds against the SARS-CoV-2 main protease (Mpro), which is a potent drug target as it is essential for the virus replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds binding to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and five non-peptidic compounds showed antiviral activity at non-toxic concentrations. Interestingly, two compounds bind outside the active site to the native dimer interface in close proximity to the S1 binding pocket. Another compound binds in a cleft between the catalytic and dimerization domain of Mpro. Neither binding site is related to the enzymatic active site and both represent attractive targets for drug development against SARS-CoV-2. This X-ray screening approach thus has the potential to help deliver an approved drug on an accelerated time-scale for this and future pandemics

Constraints on dark matter to dark radiation conversion in the late universe with DES-Y1 and external data

84siWe study a class of decaying dark matter models as a possible resolution to the observed discrepancies between early- and late-time probes of the universe. This class of models, dubbed DDM, characterizes the evolution of comoving dark matter density with two extra parameters. We investigate how DDM affects key cosmological observables such as the CMB temperature and matter power spectra. Combining 3x2pt data from Year 1 of the Dark Energy Survey,Planck-2018 CMB temperature and polarization data, Supernova (SN) Type Ia data from Pantheon, and BAO data from BOSS DR12, MGS and 6dFGS, we place new constraints on the amount of dark matter that has decayed and the rate with which it converts to dark radiation. The fraction of the decayed dark matter in units of the current amount of dark matter, $zeta$, is constrained at 68% confidence level to be <0.32 for DES-Y1 3x2pt data, <0.030 for CMB+SN+BAO data, and <0.037 for the combined dataset. The probability that the DES and CMB+SN+BAO datasets are concordant increases from 4% for the $Lambda$CDM model to 8% (less tension) for DDM. Moreover, tension in $S_8=sigma_8sqrt{Omega_m/0.3}$ between DES-Y1 3x2pt and CMB+SN+BAO is reduced from 2.3$sigma$ to 1.9$sigma$. We find no reduction in the Hubble tension when the combined data is compared to distance-ladder measurements in the DDM model. The maximum-posterior goodness-of-fit statistics of DDM and $Lambda$CDM are comparable, indicating no preference for the DDM cosmology over $Lambda$CDM....partially_openopenChen, Angela; Huterer, Dragan; Lee, Sujeong; Ferté, Agnès; Weaverdyck, Noah; Alonso Alves, Otavio; Leonard, C. Danielle; MacCrann, Niall; Raveri, Marco; Porredon, Anna; Di Valentino, Eleonora; Muir, Jessica; Lemos, Pablo; Liddle, Andrew; Blazek, Jonathan; Campos, Andresa; Cawthon, Ross; Choi, Ami; Dodelson, Scott; Elvin-Poole, Jack; Gruen, Daniel; Ross, Ashley; Secco, Lucas F.; Sevilla, Ignacio; Sheldon, Erin; Troxel, Michael A.; Zuntz, Joe; Abbott, Tim; Aguena, Michel; Allam, Sahar; Annis, James; Avila, Santiago; Bertin, Emmanuel; Bhargava, Sunayana; Bridle, Sarah; Brooks, David; Carnero Rosell, Aurelio; Carrasco Kind, Matias; Carretero, Jorge; Costanzi, Matteo; Crocce, Martin; da Costa, Luiz; Elidaiana da Silva Pereira, Maria; Davis, Tamara; Doel, Peter; Eifler, Tim; Ferrero, Ismael; Fosalba, Pablo; Frieman, Josh; Garcia-Bellido, Juan; Gaztanaga, Enrique; Gerdes, David; Gruendl, Robert; Gschwend, Julia; Gutierrez, Gaston; Hinton, Samuel; Hollowood, Devon L.; Honscheid, Klaus; Hoyle, Ben; James, David; Jarvis, Mike; Kuehn, Kyler; Lahav, Ofer; Maia, Marcio; Marshall, Jennifer; Menanteau, Felipe; Miquel, Ramon; Morgan, Robert; Palmese, Antonella; Paz-Chinchon, Francisco; Plazas Malagón, Andrés; Roodman, Aaron; Sanchez, Eusebio; Scarpine, Vic; Schubnell, Michael; Serrano, Santiago; Smith, Mathew; Suchyta, Eric; Tarle, Gregory; Thomas, Daniel; To, Chun-Hao; Varga, Tamas Norbert; Weller, Jochen; Wilkinson, ReeseChen, Angela; Huterer, Dragan; Lee, Sujeong; Ferté, Agnès; Weaverdyck, Noah; Alonso Alves, Otavio; Leonard, C. Danielle; Maccrann, Niall; Raveri, Marco; Porredon, Anna; Di Valentino, Eleonora; Muir, Jessica; Lemos, Pablo; Liddle, Andrew; Blazek, Jonathan; Campos, Andresa; Cawthon, Ross; Choi, Ami; Dodelson, Scott; Elvin-Poole, Jack; Gruen, Daniel; Ross, Ashley; Secco, Lucas F.; Sevilla, Ignacio; Sheldon, Erin; Troxel, Michael A.; Zuntz, Joe; Abbott, Tim; Aguena, Michel; Allam, Sahar; Annis, James; Avila, Santiago; Bertin, Emmanuel; Bhargava, Sunayana; Bridle, Sarah; Brooks, David; Carnero Rosell, Aurelio; Carrasco Kind, Matias; Carretero, Jorge; Costanzi, Matteo; Crocce, Martin; da Costa, Luiz; Elidaiana da Silva Pereira, Maria; Davis, Tamara; Doel, Peter; Eifler, Tim; Ferrero, Ismael; Fosalba, Pablo; Frieman, Josh; Garcia-Bellido, Juan; Gaztanaga, Enrique; Gerdes, David; Gruendl, Robert; Gschwend, Julia; Gutierrez, Gaston; Hinton, Samuel; Hollowood, Devon L.; Honscheid, Klaus; Hoyle, Ben; James, David; Jarvis, Mike; Kuehn, Kyler; Lahav, Ofer; Maia, Marcio; Marshall, Jennifer; Menanteau, Felipe; Miquel, Ramon; Morgan, Robert; Palmese, Antonella; Paz-Chinchon, Francisco; Plazas Malagón, Andrés; Roodman, Aaron; Sanchez, Eusebio; Scarpine, Vic; Schubnell, Michael; Serrano, Santiago; Smith, Mathew; Suchyta, Eric; Tarle, Gregory; Thomas, Daniel; Chun-Hao, To; Varga, Tamas Norbert; Weller, Jochen; Wilkinson, Rees