4,001 research outputs found
Multigrid algorithms for hp-version interior penalty discontinuous Galerkin methods on polygonal and polyhedral meshes
In this paper we analyze the convergence properties of two-level and W-cycle multigrid solvers for the numerical solution of the linear system of equations arising from hp-version symmetric interior penalty discontinuous Galerkin discretizations of second-order elliptic partial differential equations on polygonal/polyhedral meshes. We prove that the two-level method converges uniformly with respect to the granularity of the grid and the polynomial approximation degree p, provided that the number of smoothing steps, which depends on p, is chosen sufficiently large. An analogous result is obtained for the W-cycle multigrid algorithm, which is proved to be uniformly convergent with respect to the mesh size, the polynomial approximation degree, and the number of levels, provided the latter remains bounded and the number of smoothing steps is chosen sufficiently large. Numerical experiments are presented which underpin the theoretical predictions; moreover, the proposed multilevel solvers are shown to be convergent in practice, even when some of the theoretical assumptions are not fully satisfied
Climate Variability and Ross River Virus Transmission in Townsville Region, Australia 1985 to 1996
Background How climate variability affects the transmission of infectious diseases at a regional level remains unclear. In this paper, we assessed the impact of climate variation on the Ross River virus (RRv) transmission in the Townsville region, Queensland, north-east Australia. Methods Population-based information was obtained on monthly variations in RRv cases, climatic factors, sea level, and population growth between 1985 and 1996. Cross-correlations were computed for a series of associations between climate variables (rainfall, maximum temperature, minimum temperature, relative humidity and high tide) and the monthly incidence of RRv disease over a range of time lags. The impact of climate variability on RRv transmission was assessed using the seasonal auto-regressive integrated moving average (SARIMA) model. Results There were significant correlations of the monthly incidence of RRv to rainfall, maximum temperature, minimum temperature and relative humidity, all at a lag of 2 months, and high tide in the current month. The results of SARIMA models show that monthly average rainfall (β=0.0012, p=0.04) and high tide (β=0.0262, p=0.01) were significantly associated with RRv transmission, although temperature and relative humidity did not seem to have played an important role in the Townsville region. Conclusions Rainfall, and high tide were likely to be key determinants of RRv transmission in the Townsville region
Higgs friends and counterfeits at hadron colliders
We consider the possibility of "Higgs counterfeits" - scalars that can be
produced with cross sections comparable to the SM Higgs, and which decay with
identical relative observable branching ratios, but which are nonetheless not
responsible for electroweak symmetry breaking. We also consider a related
scenario involving "Higgs friends," fields similarly produced through gg fusion
processes, which would be discovered through diboson channels WW, ZZ, gamma
gamma, or even gamma Z, potentially with larger cross sections times branching
ratios than for the Higgs. The discovery of either a Higgs friend or a Higgs
counterfeit, rather than directly pointing towards the origin of the weak
scale, would indicate the presence of new colored fields necessary for the
sizable production cross section (and possibly new colorless but electroweakly
charged states as well, in the case of the diboson decays of a Higgs friend).
These particles could easily be confused for an ordinary Higgs, perhaps with an
additional generation to explain the different cross section, and we emphasize
the importance of vector boson fusion as a channel to distinguish a Higgs
counterfeit from a true Higgs. Such fields would naturally be expected in
scenarios with "effective Z's," where heavy states charged under the SM produce
effective charges for SM fields under a new gauge force. We discuss the
prospects for discovery of Higgs counterfeits, Higgs friends, and associated
charged fields at the LHC.Comment: 27 pages, 5 figures. References added and typos fixe
Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice
The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic
Latent cluster analysis of ALS phenotypes identifies prognostically differing groups
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes.
METHODS
Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method.
RESULTS
The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001).
CONCLUSION
The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research
Polymer formulated self-amplifying RNA vaccine is partially protective against influenza virus infection in ferrets
COVID-19 has demonstrated the power of RNA vaccines as part of a pandemic response toolkit. Another virus with pandemic potential is influenza. Further development of RNA vaccines in advance of a future influenza pandemic will save time and lives. As RNA vaccines require formulation to enter cells and induce antigen expression, the aim of this study was to investigate the impact of a recently developed bioreducible cationic polymer, pABOL for the delivery of a self-amplifying RNA (saRNA) vaccine for seasonal influenza virus in mice and ferrets. Mice and ferrets were immunized with pABOL formulated saRNA vaccines expressing either haemagglutinin (HA) from H1N1 or H3N2 influenza virus in a prime boost regime. Antibody responses, both binding and functional were measured in serum after immunization. Animals were then challenged with a matched influenza virus either directly by intranasal inoculation or in a contact transmission model. While highly immunogenic in mice, pABOL-formulated saRNA led to variable responses in ferrets. Animals that responded to the vaccine with higher levels of influenza virus-specific neutralizing antibodies were more protected against influenza virus infection. pABOL-formulated saRNA is immunogenic in ferrets, but further optimization of RNA vaccine formulation and constructs is required to increase the quality and quantity of the antibody response to the vaccine
Supermassive black holes do not correlate with galaxy disks or pseudobulges
The masses of supermassive black holes are known to correlate with the
properties of the bulge components of their host galaxies. In contrast, they
appear not to correlate with galaxy disks. Disk-grown pseudobulges are
intermediate in properties between bulges and disks. It has been unclear
whether they do or do not correlate with black holes in the same way that
bulges do, because too few pseudobulges were classified to provide a clear
result. At stake are conclusions about which parts of galaxies coevolve with
black holes, possibly by being regulated by energy feedback from black holes.
Here we report pseudobulge classifications for galaxies with dynamically
detected black holes and combine them with recent measurements of velocity
dispersions in the biggest bulgeless galaxies. These data confirm that black
holes do not correlate with disks and show that they correlate little or not at
all with pseudobulges. We suggest that there are two different modes of black
hole feeding. Black holes in bulges grow rapidly to high masses when mergers
drive gas infall that feeds quasar-like events. In contrast, small black holes
in bulgeless galaxies and galaxies with pseudobulges grow as low-level
Seyferts. Growth of the former is driven by global processes, so the biggest
black holes coevolve with bulges, but growth of the latter is driven locally
and stochastically, and they do not coevolve with disks and pseudobulges.Comment: 6 pages, 3 Postscript figures, 1 table; to appear in Nature (20
January 2011
On the compatibility of benevolence and self-interest:philanthropy and entrepreneurial orientation
This article explores the philanthropy of owner–managers of small- and medium-sized enterprises (SMEs) investigating whether and why more entrepreneurially oriented SMEs are also more likely to engage in philanthropic activities. We find support for a positive link between entrepreneurial orientation (EO) and philanthropy in a representative sample of 270 Lithuanian SMEs controlling for alternative explanations. We highlight that philanthropy is relatively common among SME owner–managers and thus complement existing research which views philanthropy as sequentially following wealth generation. In line with our theorizing, further qualitative findings point to drivers of philanthropy beyond those considered in the dominant strategic-instrumental perspective. Building on social-psychological theories of motivation, we argue and confirm that philanthropy can also be an expression of owner–managers’ altruistic values; these values can be compatible and even mutually reinforcing with entrepreneurship. Our study is set in a transition economy, Lithuania, facilitating the analysis of heterogeneity in attitudes toward philanthropy
Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice
Several vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies
Differential spatial repositioning of activated genes in Biomphalaria glabrata snails infected with Schistosoma mansoni
Copyright @ 2014 Arican-Goktas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships.NIH and Sandler Borroughs Wellcome Travel Fellowshi
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