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Angiotensin-converting enzyme 2 (ACE2) is protective in cardiovascular disease, lung injury and diabetes yet paradoxically underlies our susceptibility to SARs-CoV2 infection and the fatal heart and lung disease it can induce. Furthermore, diabetic patients have chronic, systemic inflammation and altered ACE2 expression resulting in increased risk of severe COVID-19 and the associated mortality. A drug that could increase ACE2 activity and inhibit cellular uptake of severe acute respiratory syndrome coronavirus 2 (SARs-CoV2), thus decrease infection, would be of high relevance to cardiovascular disease, diabetes and SARs-CoV2 infection. While the need for such a drug lead was highlighted over a decade ago receiving over 600 citations,1 to date, no such drugs are available.2 Here, we report the development of a novel ACE2 stimulator, designated ‘2A’(international PCT filed), which is a 10 amino acid peptide derived from a snake venom, and demonstrate its in vitro and in vivo efficacy against SARs-CoV2 infection and associated lung inflammation. Peptide 2A also provides remarkable protection against glycaemic dysregulation, weight loss and disease severity in a mouse model of type 1 diabetes. No untoward effects of 2A were observed in these pre-clinical models suggesting its strong clinical translation potential.

In light of climate change and growing numbers of people inhabiting riverine floodplains, worldwide demand for flood protection is increasing, typically through engineering approaches such as more and bigger levees. However, the well-documented “levee effect” of increased floodplain use following levee construction or enhancement often results in increased problems, especially when levees fail or are compromised by big flood events. Herein, we argue that there are also unintended socio-economic and ecological consequences of traditional engineering solutions that need to be better considered, communicated and weighed against alternative solutions. Socio-economic consequences include reduced aesthetic and recreational values as well as increased downstream flooding risk and reduced ecosystem services. Ecological consequences include hydraulic decoupling, loss of biodiversity and increased risk of contamination during flooding. In addition, beyond river losses of connectivity and natural riparian vegetation created by levees, changes in groundwater levels and increased greenhouse gas emissions are likely. Because flood protection requires huge financial investments and results in major and persistent changes to the landscape, more balanced decisions that involve all stakeholders and policy makers should be made in the future. This requires a transdisciplinary approach that considers alternative solutions such as green infrastructure and places emphasis on integrated flood management rather than on reliance on technical protection measures.

Supplementary information to: Non-natives: 141 scientists object Full list of co-signatories to a Correspondence published in Nature 475, 36 (2011); doi: 10.1038/475036a. Daniel Simberloff University of Tennessee, Knoxville, Tennessee, USA. dsimberloff@utk.edu Jake Alexander Institute of Integrative Biology, Zurich, Switzerland. Fred Allendorf University of Montana, Missoula, Montana, USA. James Aronson CEFE/CNRS, Montpellier, France. Pedro M. Antunes Algoma University, Sault Ste. Marie, Ontario, Canada. Sven Bacher University of Fribourg, Fribourg, Switzerland. Richard Bardgett Lancaster University, Lancaster, UK. Sandro Bertolino University of Turin, Grugliasco, Italy. Melanie Bishop Macquarie University, Sydney, Australia. Tim M. Blackburn Zoological Society of London, London, UK. April Blakeslee Smithsonian Environmental Research Center, Edgewater, Maryland, USA. Dana Blumenthal USDA Agricultural Research Service, Fort Collins, Colorado, USA. Alejandro Bortolus Centro Nacional Patagónico-CONICET, Puerto Madryn, Argentina. Ralf Buckley Griffith University, Southport, Queensland, Australia. Yvonne Buckley CSIRO Ecosystem Sciences and The University of Queensland, ARC Centre of Excellence in Environmental Decisions, St Lucia, Queensland, Australia. Jeb Byers The University of Georgia, Athens, Georgia, USA. Ragan M. Callaway University of Montana, Missoula, Montana, USA. Faith Campbell The Nature Conservancy, Arlington, Virginia, USA. Karl Campbell Island Conservation, Santa Cruz, California, USA. Marnie Campbell Central Queensland University, Queensland, Australia. James T. CarltonWilliams College — Mystic Seaport, Mystic, Connecticut, USA. Phillip Cassey University of Adelaide, Adelaide, South Australia, Australia. Jane Catford The University of Melbourne, Melbourne, Victoria, Australia. Laura Celesti-Grapow Sapienza University of Rome, Rome, Italy. John Chapman Hatfield Marine Science Center, Oregon State University, Newport, Oregon, USA. Paul Clark Natural History Museum, London, UK. Andre Clewell Tall Timbers Research Station, Tallahassee, Florida USA. João Canning Clode Smithsonian Environmental Research Center, Edgewater, Maryland USA Andrew Chang Smithsonian Environmental Research Center, Edgewater, Maryland, USA. Milan Chytrý Masaryk University, Brno, Czech Republic. Mick Clout University of Auckland, Auckland, New Zealand. Andrew Cohen Center for Research on Aquatic Bioinvasions, Richmond, California, USA. Phil Cowan Landcare Research, Palmerston North, New Zealand. Robert H. Cowie University of Hawaii, Honolulu, Hawaii, USA. Alycia W. Crall Colorado State University, Fort Collins, Colorado, USA. Jeff Crooks Tijuana River National Estuarine Research Reserve, Imperial Beach, California, USA. Marty Deveney South Australian Aquatic Sciences Centre,West Beach, Australia. Kingsley Dixon Kings Park and Botanic Garden,West Perth, Australia. Fred C. Dobbs Old Dominion University, Norfolk, Virginia, USA. David Cameron Duffy University of Hawaii Manoa, Honolulu, Hawaii, USA. Richard Duncan Lincoln University, Lincoln, New Zealand. Paul R. Ehrlich Stanford University, Stanford, California, USA. Lucius Eldredge Bishop Museum, Honolulu, Hawaii, USA. Neal Evenhuis Bishop Museum, Honolulu, Hawaii, USA. Kurt D. Fausch Colorado State University, Fort Collins, Colorado, USA. Heike Feldhaar University of Osnabrück, Osnabrück, Germany. Jennifer Firn Queensland University of Technology, Brisbane, Queensland, Australia. Amy Fowler Smithsonian Environmental Research Center, Edgewater, Maryland, USA. Bella Galil National Institute of Oceanography, Haifa, Israel. Emili Garcia-Berthou Universitat de Girona, Girona, Spain. Jonathan Geller Moss Landing Marine Laboratories, Moss Landing, California, USA. Piero Genovesi Italian National Institute for Environmental Protection and Research, Rome, Italy. Esther Gerber CABI Europe, Delemont, Switzerland. Francesca Gherardi Universita’ di Firenze, Firenze, Italy. Stephan Gollasch Hamburg, Germany. Doria Gordon University of Florida, Gainesville, Florida, USA. Jim Graham Colorado State University, Fort Collins, Colorado, USA. Paul Gribben University of Technology, Sydney, Australia. Blaine Griffen Smithsonian Environmental Research Center, Edgewater, Maryland, USA. Edwin D. Grosholz University of California, Davis, California, USA. Chad Hewitt Central Queensland University, Queensland, Australia. José L. Hierro CONICET-Universidad Nacional de La Pampa, La Pampa, Argentina. Philip Hulme Lincoln University, Lincoln, New Zealand. Pat Hutchings Australian Museum, Sydney, Australia. Vojtěch Jarošík Charles University, Prague, Czech Republic. Jonathan M. Jeschke Technische Universität München, Freising- Weihenstephan, Germany. Chris Johnson University of Tasmania, Hobart, Tasmania, Australia. Ladd Johnson Université Laval, Ville de Québec, Quebec, Canada. Emma L. Johnston University of New South Wales, Sydney, Australia. Carl G. Jones Durrell Wildlife Conservation Trust, Jersey, Channel Islands, UK. Reuben Keller University of Chicago, Chicago, Illinois, USA. Carolyn M. King University of Waikato, Hamilton, New Zealand. Bart G. J. Knols Academic Medical Center, Amsterdam, The Netherlands; K&S Consulting, Dodewaard, the Netherlands. Johannes Kollmann Technische Universität München, Freising, Germany. Thomas Kompas The Australian National University, Canberra, Australia. Peter M. Kotanen University of Toronto at Mississauga, Mississauga, Ontario, Canada. Ingo Kowarik Technische Universität Berlin, Berlin, Germany. Ingolf Kühn Helmholtz-Zentrum für Umweltforschung, Halle, Germany. Sabrina Kumschick Colorado State University, Fort Collins, Colorado, USA. Brian Leung McGill University, Montreal, Quebec, Canada. Andrew Liebhold USDA Forest Service, Morgantown, West Virginia, USA. Hugh MacIsaac University of Windsor, Windsor, Ontario, Canada. Richard Mack Washington State University, Pullman, Washington, USA. Deborah G. McCullough Michigan State University, East Lansing, Michigan, USA. Robbie McDonald The Food and Environmental Research Agency, Department for Environment, Food, and Rural Affairs, Stonehouse, UK. David M. Merritt United States Forest Service, Fort Collins, Colorado, USA. Laura Meyerson University of Rhode Island, Kingston, Rhode Island, USA. Dan Minchin Marine Organism Investigations, Killaloe, Ireland. Harold A. Mooney Stanford University, Stanford, California, USA. Jeffrey T. Morisette United States Geological Survey, Fort Collins Science Center, Fort Collins, Colorado, USA. Peter Moyle University of California, Davis, California, USA. Heinz Müller-Schärer Université de Fribourg/Pérolles, Fribourg, Switzerland. Brad R. Murray University of Technology Sydney, Sydney, Australia. Stefan Nehring Bundesamt für Naturschutz, Bonn, Germany. Wendy Nelson National Institute of Water and Atmospheric Research, Wellington, New Zealand. Wolfgang Nentwig University of Bern, Bern, Switzerland. Stephen J. Novak Boise State University, Boise, Idaho, USA. Anna Occhipinti Universita di Pavia, Pavia, Italy. Henn Ojaveer University of Tartu, Pärnu, Estonia. Bruce Osborne University College Dublin, Dublin, Ireland. Richard S. Ostfeld Cary Institute of Ecosystem Studies, Millbrook, New York, USA. John Parker Smithsonian Environmental Research Center, Edgewater, Maryland, USA. Judith Pederson Worcester, Massachusetts, USA. Jan Pergl Academy of Sciences of the Czech Republic, Pruhonice, Czech Republic. Megan L. Phillips University of Technology Sydney, Sydney, Australia. Petr Pyšek Academy of Sciences, Průhonice, Czech Republic. Marcel Rejmánek University of California, Davis, California, USA. Anthony Ricciardi McGill University, Montreal, Quebec, Canada. Carlo Ricotta University of Rome ‘La Sapienza’, Rome, Italy. David Richardson Stellenbosch University, Matieland, South Africa. Gil Rilov National Institute of Oceanography, Haifa, Israel. Euan Ritchie Deakin University, Burwood, Victoria, Australia. Peter A. Robertson Food and Environment Research Agency, York, UK. Joe Roman University of Vermont, Burlington, Vermont, USA. Gregory Ruiz Smithsonian Environmental Research Center, Edgewater, Maryland, USA. Hanno Schaefer Harvard University, Cambridge, Massachusetts, USA. Britta Schaffelke Australian Institute of Marine Science, Townsville, Australia. Kristina A. Schierenbeck California State University, Chico, California, USA. Don C. Schmitz Florida Fish and Wildlife Conservation Commission, Tallahassee, Florida, USA. Evangelina Schwindt Centro Nacional Patagónico-CONICET, Puerto Madryn, Argentina. Jim Seeb University of Washington, Seattle, Washington, USA. L. David Smith Smith College, Northampton, Massachusetts, USA. Gideon F. Smith University of Pretoria, Pretoria, South Africa. Thomas Stohlgren Colorado State University, Fort Collins, Colorado, USA. David L. Strayer Cary Institute of Ecosystem Studies, Millbrook, New York, USA. Donald Strong University of California, Davis, California,USA. William J. Sutherland University of Cambridge , Cambridge, UK. Thomas Therriault Pacific Biological Station, Nanaimo, British Columbia, Canada. Wilfried Thuiller Université Joseph Fourier, Grenoble, France. Mark Torchin Smithsonian Tropical Research Institute, Balboa, Panama. Wim van der Putten Netherlands Institute of Ecology, Wageningen, the Netherlands. Montserrat Vilà Estación Biológica de Doñana, Sevilla, Spain. Betsy Von Holle University of Central Florida, Orlando, Florida, USA. Inger Wallentinus University of Gothenburg, Goteborg, Sweden. David Wardle Swedish University of Agricultural Sciences, Umeå, Sweden. Mark Williamson University of York, York, UK. John Wilson Stellenbosch University, Matieland, South Africa. Marten Winter Helmholtz-Zentrum für Umweltforschung, Halle, Germany. Lorne M. Wolfe Georgia Southern University, Statesboro, Georgia, USA. Jeff Wright The University of Tasmania, Launceston, Australia. Marjorie Wonham Quest University, Squamish, British Columbia, Canada. Chela Zabin Smithsonian Environmental Research Center, Edgewater, Maryland, USA.

Detonation velocities were measured in mixtures of hydrogen and oxygen containing 25 to 75 mole % hydrogen at initial temperatures from 160° to 580°K. and initial pressures from 1/2 to 2 atm. The measurements were made in a number of tubes of different diameter to permit extrapolation to a tube of infinite diameter. Theoretical detonation characteristics were computed for the same range of conditions. The measured and computed velocities are in good agreement except in rich mixtures and at subatmospheric pressures. Schlieren photographs reveal that the detonation wave front is very thin for a stoichiometric mixture but degenerates to a complicated zone of interacting shock waves and turbulent combustion as the percentage of hydrogen is reduced. The detonation velocity is found to depend only slightly on initial temperature and pressure. The computed pressures behind the detonation and reflected waves are roughly proportional to initial pressure and to the reciprocal of the initial temperature.