28 research outputs found

    The Three Dimensional Thirring Model for Small N_f

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    We formulate the three dimensional Thirring model on a spacetime lattice and study it for various even numbers of fermion flavors N_f by Monte Carlo simulation. We find clear evidence for spontaneous chiral symmetry breaking at strong coupling, contradicting the predictions of the 1/N_f expansion. The critical point appears to correspond to an ultra-violet fixed point of the renormalisation group; a fit to a RG-inspired equation of state in the vicinity of the fixed point yields distinct critical exponents for N_f=2 and N_f=4, while no fit is found for N_f=6, suggesting there is a critical number N_fc<6 beyond which no chiral symmetry breaking occurs. The spectrum of the N_f=2 theory is studied; the states examined vary sharply but continuously across the transition.Comment: 50 pages LaTeX, including 16 tables and 20 figures - uses style file ldd_art.sty (included

    Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens

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    SummaryBackgroundThe nasal vaccine candidate (NASVAC), comprising hepatitis B virus (HBV) surface (HBsAg) and core antigens (HBcAg), has been shown to be highly immunogenic in animal models.MethodsA phase I double-blinded, placebo-controlled randomized clinical trial was carried out in 19 healthy male adults with no serologic markers of immunity/infection to HBV. This study was aimed at exploring the safety and immunogenic profile of nasal co-administration of both HBV recombinant antigens. The trial was performed according to Good Clinical Practice guidelines. Participants ranged in age from 18 to 45 years and were randomly allocated to receive a mixture of 50μg HBsAg and 50μg HBcAg or 0.9% physiologic saline solution, as a placebo, via nasal spray in a five-dose schedule at 0, 7, 15, 30, and 60 days. A total volume of 0.5ml was administered in two dosages of 125μl per nostril. Adverse events were actively recorded 1h, 6h, 12h, 24h, 48h, 72h, 7 days and 30 days after each dose. Anti-HBs and anti-HBc titers were evaluated using corresponding ELISA kits at days 30 and 90.ResultsThe vaccine candidate was safe and well tolerated. Adverse reactions included sneezing (34.1%), rhinorrhea (12.2%), nasal stuffiness (9.8%), palate itching (9.8%), headache (9.8%), and general malaise (7.3%). These reactions were all self-limiting and mild in intensity. No severe or unexpected events were recorded during the trial. The vaccine elicited anti-HBc seroconversion in 100% of subjects as early as day 30 of the immunization schedule, while a seroprotective anti-HBs titer (≥10IU/l) was at a maximum at day 90 (75%). All subjects in the placebo group remained seronegative during the trial.ConclusionThe HBsAg–HBcAg vaccine candidate was safe, well tolerated and immunogenic in this phase I study in healthy adults. To our knowledge, this is the first demonstration of safety and immunogenicity for a nasal vaccine candidate comprising HBV antigens

    Autoantibodies against type I IFNs in patients with life-threatening COVID-19

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    Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

    Pervasive gaps in Amazonian ecological research

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    Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

    Genetic variation in pathogen-induced early hatching of toad embryos

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    Accelerated hatching is one of few defences available to embryos, and is effective against many egg-stage risks. We present the first analysis of genetic variation in hatching plasticity, examining premature hatching of American toad embryos in response to pathogenic water moulds. We reared eggs from half- and full-sib families in the presence and absence of water mould. Hatching age and hatchling size showed low cross-environment genetic correlations, suggesting that early-induced hatching can evolve largely independently of spontaneous hatching. We found less phenotypic and additive genetic variation for early-induced hatching than spontaneous hatching, and a stronger correlation between egg and induced hatchling sizes. Directional selection by the pathogen may have eroded variation in early-induced hatching, pushing it against the constraint of hatching gland development. Later hatching has a second, muscular component. This pattern of variation may characterize defences based on developmental transitions, although other inducible defences show more variation in induced phenotypes. © 2008 The Authors.Peer Reviewe
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