The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.
Massive multiple-input multiple-output (MIMO) wireless communications refers to the idea equipping cellular base stations (BSs) with a very large number of antennas, and has been shown to potentially allow for orders of magnitude improvement in spectral and energy efficiency using relatively simple (linear) processing. In this paper, we present a comprehensive overview of state-of-the-art research on the topic, which has recently attracted considerable attention. We begin with an information theoretic analysis to illustrate the conjectured advantages of massive MIMO, and then we address implementation issues related to channel estimation, detection and precoding schemes. We particularly focus on the potential impact of pilot contamination caused by the use of non-orthogonal pilot sequences by users in adjacent cells. We also analyze the energy efficiency achieved by massive MIMO systems, and demonstrate how the degrees of freedom provided by massive MIMO systems enable efficient single-carrier transmission. Finally, the challenges and opportunities associated with implementing massive MIMO in future wireless communications systems are discussed.
ForewordThe Pierre Auger Observatory has begun a major Upgrade of its already impressive capabilities, with an emphasis on improved mass composition determination using the surface detectors of the Observatory. Known as AugerPrime, the upgrade will include new 4 m 2 plastic scintillator detectors on top of all 1660 water-Cherenkov detectors, updated and more flexible surface detector electronics, a large array of buried muon detectors, and an extended duty cycle for operations of the fluorescence detectors.This Preliminary Design Report was produced by the Collaboration in April 2015 as an internal document and information for funding agencies. It outlines the scientific and technical case for AugerPrime 1 . We now release it to the public via the arXiv server. We invite you to review the large number of fundamental results already achieved by the Observatory and our plans for the future.The Pierre Auger Collaboration 1 As a result of continuing R&D, slight changes have been implemented in the baseline design since this Report was written. These changes will be documented in a forthcoming Technical Design Report. ix x Executive Summary Present Results from the Pierre Auger ObservatoryMeasurements of the Auger Observatory have dramatically advanced our understanding of ultra-high energy cosmic rays. The suppression of the flux around 5×10 19 eV is now confirmed without any doubt. Strong limits have been placed on the photon and neutrino components of the flux indicating that "top-down" source processes, such as the decay of superheavy particles, cannot account for a significant part of the observed particle flux. A largescale dipole anisotropy of ∼7% amplitude has been found for energies above 8×10 18 eV. In addition there is also an indication of the presence of a large scale anisotropy below the ankle. Particularly exciting is the observed behavior of the depth of shower maximum with energy, which changes in an unexpected, non-trivial way. Around 3×10 18 eV it shows a distinct change of slope with energy, and the shower-to-shower variance decreases. Interpreted with the leading LHC-tuned shower models, this implies a gradual shift to a heavier composition. A number of fundamentally different astrophysical model scenarios have been developed to describe this evolution. The high degree of isotropy observed in numerous tests of the small-scale angular distribution of UHECR above 4×10 19 eV is remarkable, challenging original expectations that assumed only a few cosmic ray sources with a light composition at the highest energies. Interestingly, the largest departures from isotropy are observed for cosmic rays with E > 5.8×10 19 eV in ∼20 • sky-windows. Due to a duty cycle of ∼15% of the fluorescence telescopes, the data on the depth of shower maximum extend only up to the flux suppression region, i.e. 4×10 19 eV. Obtaining more information on the composition of cosmic rays at higher energies will provide crucial means to discriminate between the model classes and to understand the origin of the observed flux suppre...
The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
Background 24The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public 25 health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to 26 correlate with recovery and protection of this disease. However, the characteristics of 27 these antibodies have not been well studied in association with the clinical 28 manifestations in patients. 30 Methods 31Plasma collected from 175 COVID-19 recovered patients with mild symptoms were 32 screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization 33 assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, 34 and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-35 specific NAbs and the spike-binding antibodies were monitored at the same time. 36 37 Findings 38 SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-39 2-specific NAbs were detected in patients from day 10-15 after the onset of the disease 40 and remained thereafter. The titers of NAb among these patients correlated with the 41 spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were 42 variable in different patients. Elderly and middle-age patients had significantly higher 43 plasma NAb titers (P<0.0001) and spike-binding antibodies (P=0.0003) than young 44 patients. Notably, among these patients, there were ten patients whose NAb titers were 45 under the detectable level of our assay (ID50: < 40); while in contrast, two patients, 46 showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb 47 titers were positive correlated with plasma CRP levels but negative correlated with the 48 lymphocyte counts of patients at the time of admission, indicating an association 49 between humoral response and cellular immune response.50 51 Interpretation 52The variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may 53 raise the concern about the role of NAbs on disease progression. The correlation of 54 NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the 55 interplay between virus and host immune response in coronavirus infections should be 56 further explored for the development of effective vaccine against SARS-CoV-2 virus. 57 Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for 58 prevention or treatment. Sciences 64 65 66 67 All rights reserved. No reuse allowed without permission.
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