A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice.

BACKGROUND: The spread of SARS-CoV-2 has caused a worldwide pandemic that has affected almost every aspect of human life. The development of an effective COVID-19 vaccine could limit the morbidity and mortality caused by infection and may enable the relaxation of social-distancing measures. Age is one of the most significant risk factors for poor health outcomes after SARS-CoV-2 infection; therefore, it is desirable that any new vaccine candidates elicit a robust immune response in older adults. METHODS: Here, we use in-depth immunophenotyping to characterize the innate and adaptive immune response induced upon intramuscular administration of the adenoviral vectored ChAdOx1 nCoV-19 (AZD-1222) COVID-19 vaccine candidate in mice. FINDINGS: A single vaccination generates spike-specific Th1 cells, Th1-like Foxp3+ regulatory T cells, polyfunctional spike-specific CD8+ T cells. and granzyme-B-producing CD8 effectors. Spike-specific IgG and IgM are generated from both the early extrafollicular antibody response and the T follicular helper cell-supported germinal center reaction, which is associated with the production of virus-neutralizing antibodies. A single dose of this vaccine generated a similar type of immune response in aged mice but of a reduced magnitude than in younger mice. We report that a second dose enhances the immune response to this vaccine in aged mice. CONCLUSIONS: This study shows that ChAdOx1 nCoV-19 induces both cellular and humoral immunity in adult and aged mice and suggests a prime-boost strategy is a rational approach to enhance immunogenicity in older persons. FUNDING: This study was supported by BBSRC, Lister institute of Preventative Medicine, EPSRC VaxHub, and Innovate UK

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201

Host Cell Transcriptome Profile during Wild-Type and Attenuated Dengue Virus Infection

10.1371/journal.pntd.0002107PLoS Neglected Tropical Diseases73

Adherence measurements and corrosion resistance in primer/hot-dip galvanized steel systems

This paper focuses on the adherence during ageing of a primer (made of polyester resins crosslinked with melamine) applied onto hot-dip galvanized (HDG) steel for coil coating application and its influence on corrosion protection. A chromium-free surface treatment, composed of fluorotitanic acid, phosphoric acid, manganese phosphate, and vinylphenol was applied on the HDG steel to obtain high corrosion resistance and high adherence of a polyester and melamine primer. The influence of the manganese phosphate on the corrosion and adherence was investigated. To measure the adherence between the metal and the primer, a three-point flexure test was set up. The adherence was then linked with corrosion resistance during ageing, using electrochemical impedance spectroscopy

Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders

Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways

Bounds on the density of sources of ultra-high energy cosmic rays from the Pierre Auger Observatory

We derive lower bounds on the density of sources of ultra-high energy cosmic rays from the lack of significant clustering in the arrival directions of the highest energy events detected at the Pierre Auger Observatory. The density of uniformly distributed sources of equal intrinsic intensity was found to be larger than similar to (0.06 – 5) x 10(-4) Mpc(-3) at 95% CL, depending on the magnitude of the magnetic defections. Similar bounds, in the range (0.2 – 7) x 10(-4) Mpc(-3), were obtained for sources following the local matter distribution.We are very grateful to the following agencies and organizations for financial support,: Comision Nacional de Energia Atomica, Fundacion Antorchas, Gobierno De La, Provincia de Ailendoza. Municipalidad de Malargile. INDM floldings and Valle Las Lenas, in gratitude for their continuing cooperation over land access. Argentina; the Australian Research Council; Conselho Nacional de Desenvolvimento Cientifico e 'Tecnologico (CNPq), Financiadora de Estudos e Projetos (FINEP), Fundacdo de Amparo a Pesquisa do Est ado de Rio de Janeiro (FAP HRJ), Fundacdo de Amparo Pesquisa do Estado de Sdo Paulo (FAPESP), Ministerio de Ciencia e Tecnologia (IVICT), Brazil; AVCR AVOZ10100502 and AVOZ10100522, GAAV KJB100100904, AISMT-CR LA08016, LG11044, 1VIEB111003, MSAI0021620859, LA08015, TACR TA01010517 and GA U.K. 119810, Czech Republic; Centre de Calcul I-N2P3/CNRS, Centre National de la -Recherche Scientifique ((1 NRS), Conseil Regional Ile-de-France, f)epartement, Physique Nuclealre et Corpusculaire (I N( Departement Sciences de l'Univers (SDU-INSU/CNRS), France; Bundesministerium fur Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DITG), Finanzministerium Baden-Wurttemberg, flelmholtz-Gemeinschaft Deutscher Forschungszentren Ministerium fur Wissenschaft und Forschung, Nordrhein-Westfalen, Ministerimn fur Wissenschaft, Forschung und Kunst, Baden-WUrttemberg, Germany; Istituto Nazion ale di Fisica Nucleare (INFN), Ministero dell'Istruzione, delhLniversita e della Ricerca (MIUR), Italy: Consejo Nacional de Ciencia y Tecnologia (CONACYT), Mexico; Ministerie van Onden s Cultuur on NVetenschap Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO), Stichting voor Rmdamenteel Onderzoek der Materie (FOM), Netherlands; Ministry of Science and Higher Education, Grant Nos. N N202 200239 and N N202 207238, Poland; Portuguese national funds and FEDER funds within COMPETE - Programa Operacional Factores de Competitividade through Fundacao para a Ciencia e a Tecnologia, Portugal; Romanian Authority for Scientific Research ANCS, CNDI-UEFISETD1 partnership projects nr.20/2012 and nr.194/2012, project nr.1 /ASPERA2/20I2 ERA-NET and PN-IIRU-PD-2011-3-0145-17, Romania; Ministry for Higher Education, Science, and 'Technology, Slovenian Research Agency, Slovenia; Comunidad de Madrid, FEDER funds, Ministerio de Ciencia e Innovacion and Consolider-Ingenio 2010 (( PAN), X unta de Galicia Spain; Science and Technology Facilities Council, United kingdom; Department of Luergy, Contract Nos. DE-ACO2-07(11-111359, DE-FR02-04E1(41300, DE-FG02-99E1(41107, National Science Foundation, Grant No. 0450696, The Grainger Foundation U.S.A.; NAFOSTED, Vietnam; Marie Curie-IRSES/HPLANET, European Particle Physics Latin American Network, European Union 7th Frarneworlc Program. Grant No. IIRSES-2009-GA-246806; and UNESCO.Peer reviewe

Identifying clouds over the Pierre Auger Observatory using infrared satellite data

We describe a new method of identifying night-time clouds over the Pierre Auger Observatory using infrared data from the Imager instruments on the GOES-12 and GOES-13 satellites. We compare cloud. identifications resulting from our method to those obtained by the Central Laser Facility of the Auger Observatory. Using our new method we can now develop cloud probability maps for the 3000 km(2) of the Pierre Auger Observatory twice per hour with a spatial resolution of similar to 2.4 km by similar to 5.5 km. Our method could also be applied to monitor cloud cover for other ground-based observatories and for space-based observatories. (C) 2013 Elsevier B.V. All rights reserved.The successful installation, commissioning, and operation of the Pierre Auger Observatory would not have been possible without the strong commitment and effort from the technical and adminis- trative staff in Malargüe. We are very grateful to the following agencies and organiza- tions for financial support: Comisión Nacional de Energía Atómica, Fundación Antorchas, Gobierno De La Provincia de Mendoza, Municipalidad de Malargüe, NDM Holdings and Valle Las Leñas, in gratitude for their continuing cooperation over land access, Argentina; the Australian Research Council; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Projetos (FINEP), Fundação de Amparo à Pesquisa do Estado de Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Ministério de Ciência e Tecnolo- gia (MCT), Brazil; AVCR AV0Z10100502 and AV0Z10100522, GAAV KJB100100904, MSMT-CR LA08016, LG11044, MEB111003, MSM0021620859, LA08015, TACR TA01010517 and GA UK 119810, Czech Republic; Centre de Calcul IN2P3/CNRS, Centre Na- tional de la Recherche Scientifique (CNRS), Conseil Régional Ile-de- France, Département Physique Nucléaire et Corpusculaire (PNC- IN2P3/CNRS), Département Sciences de l’Univers (SDU-INSU/ CNRS), France; Bundesministerium für Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), Finanzministeri- um Baden-Württemberg, Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF), Ministerium für Wissenschaft und Forschung, Nordrhein-Westfalen, Ministerium für Wissenschaft, Forschung und Kunst, Baden-Württemberg, Germany; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR), Italy; Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico; Ministerie van Ond- erwijs, Cultuur en Wetenschap, Nederlandse Organisatie voor Wet- enschappelijk Onderzoek (NWO), Stichting voor Fundamenteel Onderzoek der Materie (FOM), Netherlands; Ministry of Science and Higher Education, Grant Nos. N N202 200239 and N N202 207238, Poland; Portuguese national funds and FEDER funds with- in COMPETE - Programa Operacional Factores de Competitividade through Fundação para a Ciência e a Tecnologia, Portugal; Roma- nian Authority for Scientific Research ANCS, CNDI-UEFISCDI part- nership projects nr.20/2012 and nr.194/2012, project nr.1/ ASPERA2/2012 ERA-NET and PN-II-RU-PD-2011-3-0145-17, Roma- nia; Ministry for Higher Education, Science, and Technology, Slove- nian Research Agency, Slovenia; Comunidad de Madrid, FEDER funds, Ministerio de Ciencia e Innovación and Consolider-Ingenio 2010 (CPAN), Xunta de Galicia, Spain; The Leverhulme Foundation, Science and Technology Facilities Council, United Kingdom; Department of Energy, Contract Nos. DE-AC02-07CH11359, DE- FR02-04ER41300, DE-FG02-99ER41107, National Science Founda- tion, Grant No. 0450696, The Grainger Foundation USA; NAFO- STED, Vietnam; Marie Curie-IRSES/EPLANET, European Particle Physics Latin American Network, European Union 7th Framework Program, Grant No. PIRSES-2009-GA-246806; and UNESCO. We would like to thank the former Michigan Tech students: Nathan Kelley-Hoskins, Kyle Luck and Arin Nelson for their impor- tant contribution to the development of this paper. We would like to thank NOAA for the GOES satellite data that we freely down- loaded from their website. Also, we would like to mention in these acknowledgments Dr. Steve Ackerman and Dr. Tony Schreiner for very valuable conversationsPeer reviewe

Depth Of Maximum Of Air-shower Profiles At The Pierre Auger Observatory. I. Measurements At Energies Above 1017.8ev

901

Constraints on the origin of cosmic rays above 101810^{18} eV from large scale anisotropy searches in data of the Pierre Auger Observatory

A thorough search for large scale anisotropies in the distribution of arrival directions of cosmic rays detected above $10^{18}$ eV at the Pierre Auger Observatory is reported. For the first time, these large scale anisotropy searches are performed as a function of both the right ascension and the declination and expressed in terms of dipole and quadrupole moments. Within the systematic uncertainties, no significant deviation from isotropy is revealed. Upper limits on dipole and quadrupole amplitudes are derived under the hypothesis that any cosmic ray anisotropy is dominated by such moments in this energy range. These upper limits provide constraints on the production of cosmic rays above $10^{18}$ eV, since they allow us to challenge an origin from stationary galactic sources densely distributed in the galactic disk and emitting predominantly light particles in all directions.Peer Reviewe

Arecibo PALFA survey and Einstein@Home: Binary pulsar discovery by volunteer computing

We report the discovery of the 20.7ms binary pulsar J1952+2630, made using the distributed computing project Einstein@Home in Pulsar ALFA survey observations with the Arecibo telescope. Follow-up observations with the Arecibo telescope confirm the binary nature of the system. We obtain a circular orbital solution with an orbital period of 9.4hr, a projected orbital radius of 2.8lt-s, and a mass function of f = 0.15 M ⊙ by analysis of spin period measurements. No evidence of orbital eccentricity is apparent; we set a 2σ upper limit e ≲ 1.7 × 10 -3 . The orbital parameters suggest a massive white dwarf companion with a minimum mass of 0.95 M ⊙ , assuming a pulsar mass of 1.4 M ⊙ . Most likely, this pulsar belongs to the rare class of intermediate-mass binary pulsars. Future timing observations will aim to determine the parameters of this system further, measure relativistic effects, and elucidate the nature of the companion star. © 2011. The American Astronomical Society. All rights reserved