Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection

Effective therapies are urgently needed for the SARS-CoV-2/COVID-19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from large phage-displayed Fab, scFv, and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. A high-affinity Fab was selected from one of the libraries and converted to a full-size antibody, IgG1 ab1, which competed with human ACE2 for binding to RBD. It potently neutralized replication-competent SARS-CoV-2 but not SARS-CoV, as measured by two different tissue culture assays, as well as a replication-competent mouse ACE2-adapted SARS-CoV-2 in BALB/c mice and native virus in hACE2-expressing transgenic mice showing activity at the lowest tested dose of 2 mg/kg. IgG1 ab1 also exhibited high prophylactic and therapeutic efficacy in a hamster model of SARS-CoV-2 infection. The mechanism of neutralization is by competition with ACE2 but could involve antibody-dependent cellular cytotoxicity (ADCC) as IgG1 ab1 had ADCC activity in vitro. The ab1 sequence has a relatively low number of somatic mutations, indicating that ab1-like antibodies could be quickly elicited during natural SARS-CoV-2 infection or by RBD-based vaccines. IgG1 ab1 did not aggregate, did not exhibit other developability liabilities, and did not bind to any of the 5,300 human membrane-associated proteins tested. These results suggest that IgG1 ab1 has potential for therapy and prophylaxis of SARS-CoV-2 infections. The rapid identification (within 6 d of availability of antigen for panning) of potent mAbs shows the value of large antibody libraries for response to public health threats from emerging microbes

The RESET project: constructing a European tephra lattice for refined synchronisation of environmental and archaeological events during the last c. 100 ka

This paper introduces the aims and scope of the RESET project (. RESponse of humans to abrupt Environmental Transitions), a programme of research funded by the Natural Environment Research Council (UK) between 2008 and 2013; it also provides the context and rationale for papers included in a special volume of Quaternary Science Reviews that report some of the project's findings. RESET examined the chronological and correlation methods employed to establish causal links between the timing of abrupt environmental transitions (AETs) on the one hand, and of human dispersal and development on the other, with a focus on the Middle and Upper Palaeolithic periods. The period of interest is the Last Glacial cycle and the early Holocene (c. 100-8 ka), during which time a number of pronounced AETs occurred. A long-running topic of debate is the degree to which human history in Europe and the Mediterranean region during the Palaeolithic was shaped by these AETs, but this has proved difficult to assess because of poor dating control. In an attempt to move the science forward, RESET examined the potential that tephra isochrons, and in particular non-visible ash layers (cryptotephras), might offer for synchronising palaeo-records with a greater degree of finesse. New tephrostratigraphical data generated by the project augment previously-established tephra frameworks for the region, and underpin a more evolved tephra 'lattice' that links palaeo-records between Greenland, the European mainland, sub-marine sequences in the Mediterranean and North Africa. The paper also outlines the significance of other contributions to this special volume: collectively, these illustrate how the lattice was constructed, how it links with cognate tephra research in Europe and elsewhere, and how the evidence of tephra isochrons is beginning to challenge long-held views about the impacts of environmental change on humans during the Palaeolithic. © 2015 Elsevier Ltd.RESET was funded through Consortium Grants awarded by the Natural Environment Research Council, UK, to a collaborating team drawn from four institutions: Royal Holloway University of London (grant reference NE/E015905/1), the Natural History Museum, London (NE/E015913/1), Oxford University (NE/E015670/1) and the University of Southampton, including the National Oceanography Centre (NE/01531X/1). The authors also wish to record their deep gratitude to four members of the scientific community who formed a consultative advisory panel during the lifetime of the RESET project: Professor Barbara Wohlfarth (Stockholm University), Professor Jørgen Peder Steffensen (Niels Bohr Institute, Copenhagen), Dr. Martin Street (Romisch-Germanisches Zentralmuseum, Neuwied) and Professor Clive Oppenheimer (Cambridge University). They provided excellent advice at key stages of the work, which we greatly valued. We also thank Jenny Kynaston (Geography Department, Royal Holloway) for construction of several of the figures in this paper, and Debbie Barrett (Elsevier) and Colin Murray Wallace (Editor-in-Chief, QSR) for their considerable assistance in the production of this special volume.Peer Reviewe

Identification of two distinct fire regimes in Southern California: implications for economic impact and future change

The area burned by Southern California wildfires has increased in recent decades, with implications for human health, infrastructure, and ecosystem management. Meteorology and fuel structure are universally recognized controllers of wildfire, but their relative importance, and hence the efficacy of abatement and suppression efforts, remains controversial. Southern California's wildfires can be partitioned by meteorology: fires typically occur either during Santa Ana winds (SA fires) in October through April, or warm and dry periods in June through September (non-SA fires). Previous work has not quantitatively distinguished between these fire regimes when assessing economic impacts or climate change influence. Here we separate five decades of fire perimeters into those coinciding with and without SA winds. The two fire types contributed almost equally to burned area, yet SA fires were responsible for 80% of cumulative 1990-2009 economic losses ($3.1 Billion). The damage disparity was driven by fire characteristics: SA fires spread three times faster, occurred closer to urban areas, and burned into areas with greater housing values. Non-SA fires were comparatively more sensitive to age-dependent fuels, often occurred in higher elevation forests, lasted for extended periods, and accounted for 70% of total suppression costs. An improved distinction of fire type has implications for future projections and management. The area burned in non-SA fires is projected to increase 77% (±43%) by the mid-21st century with warmer and drier summers, and the SA area burned is projected to increase 64% (±76%), underscoring the need to evaluate the allocation and effectiveness of suppression investments

Size and Shape Constraints of (486958) Arrokoth from Stellar Occultations

International audienceWe present the results from four stellar occultations by (486958) Arrokoth, the flyby target of the New Horizons extended mission. Three of the four efforts led to positive detections of the body, and all constrained the presence of rings and other debris, finding none. Twenty-five mobile stations were deployed for 2017 June 3 and augmented by fixed telescopes. There were no positive detections from this effort. The event on 2017 July 10 was observed by the Stratospheric Observatory for Infrared Astronomy with one very short chord. Twenty-four deployed stations on 2017 July 17 resulted in five chords that clearly showed a complicated shape consistent with a contact binary with rough dimensions of 20 by 30 km for the overall outline. A visible albedo of 10% was derived from these data. Twenty-two systems were deployed for the fourth event on 2018 August 4 and resulted in two chords. The combination of the occultation data and the flyby results provides a significant refinement of the rotation period, now estimated to be 15.9380 ± 0.0005 hr. The occultation data also provided high-precision astrometric constraints on the position of the object that were crucial for supporting the navigation for the New Horizons flyby. This work demonstrates an effective method for obtaining detailed size and shape information and probing for rings and dust on distant Kuiper Belt objects as well as being an important source of positional data that can aid in spacecraft navigation that is particularly useful for small and distant bodies