A Hybrid Radial Basis Function-Pseudospectral Method for Thermal Convection in a 3-D Spherical Shell

A novel hybrid spectral method that combines radial basis function (RBF) and Chebyshev pseudospectral methods in a “2 + 1” approach is presented for numerically simulating thermal convection in a 3‐D spherical shell. This is the first study to apply RBFs to a full 3‐D physical model in spherical geometry. In addition to being spectrally accurate, RBFs are not defined in terms of any surface‐based coordinate system such as spherical coordinates. As a result, when used in the lateral directions, as in this study, they completely circumvent the pole issue with the further advantage that nodes can be “scattered” over the surface of a sphere. In the radial direction, Chebyshev polynomials are used, which are also spectrally accurate and provide the necessary clustering near the boundaries to resolve boundary layers. Applications of this new hybrid methodology are given to the problem of convection in the Earth’s mantle, which is modeled by a Boussinesq fluid at infinite Prandtl number. To see whether this numerical technique warrants further investigation, the study limits itself to an isoviscous mantle. Benchmark comparisons are presented with other currently used mantle convection codes for Rayleigh number (Ra) 7 × 103 and 105. Results from a Ra = 106 simulation are also given. The algorithmic simplicity of the code (mostly due to RBFs) allows it to be written in less than 400 lines of MATLAB and run on a single workstation. We find that our method is very competitive with those currently used in the literature

Interpolating fields of carbon monoxide data using a hybrid statistical-physical model

Atmospheric Carbon Monoxide (CO) provides a window on the chemistry of the atmosphere since it is one of few chemical constituents that can be remotely sensed, and it can be used to determine budgets of other greenhouse gases such as ozone and OH radicals. Remote sensing platforms in geostationary Earth orbit will soon provide regional observations of CO at several vertical layers with high spatial and temporal resolution. However, cloudy locations cannot be observed and estimates of the complete CO concentration fields have to be estimated based on the cloud-free observations. The current state-of-the-art solution of this interpolation problem is to combine cloud-free observations with prior information, computed by a deterministic physical model, which might introduce uncertainties that do not derive from data. While sharing features with the physical model, this paper suggests a Bayesian hierarchical model to estimate the complete CO concentration fields. The paper also provides a direct comparison to state-of-the-art methods. To our knowledge, such a model and comparison have not been considered before.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS168 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Development of influenza H7N9 virus like particle (VLP) vaccine: Homologous A/Anhui/1/2013 (H7N9) protection and heterologous A/chicken/Jalisco/CPA1/2012 (H7N3) cross-protection in vaccinated mice challenged with H7N9 virus

AbstractThe recent emergence of severe human illness caused by avian-origin influenza A(H7N9) viruses in China has precipitated a global effort to rapidly develop and test vaccine candidates. To date, non-A(H7N9) H7 subtype influenza vaccine candidates have been poorly immunogenic and difficulties in production of A(H7N9) virus seed strains have been encountered. A candidate recombinant A(H7N9) vaccine consisting of full length, unmodified hemagglutinin (HA) and neuraminidase (NA) from the A/Anhui/1/2013 and the matrix 1 (M1) protein from the A/Indonesia/05/2005 (H5N1) were cloned into a baculovirus vector. Baculovirus infected Spodoptera frugiperda (Sf9) insect cells secreted virus like particles (VLP) composed of HA, NA, and M1 that resemble mature influenza virions. Genetic construction of vaccine from acquisition of an H7N9 genomic sequence to production of A(H7N9) VLP occurred in 26 days. The immunogenicity and efficacy of A/Anhui/1/2013 (H7N9) VLP vaccine administered on days 0 and 14 were evaluated in a lethal wild-type challenge Balb/c mouse model. Control groups included a non-homologous H7 vaccine (A/chicken/Jalisco/CPA1/2012 (H7N3)-VLP), and A/Indonesia/05/2005 (H5N1)-VLP, or placebo. All vaccines were administered with or without ISCOMATRIX. A(H7N9) VLP elicited hemagglutination-inhibition (HAI) antibody titers of ≥1:64 against the homologous virus, cross-reactive HAI against the heterologous A(H7N3), and 3- to 4-fold higher HAI responses in corresponding ISCOMATRIX subgroups. Similarly, all doses of H7N9 VLP elicited anti-neuraminidase (NA) antibody, with 3- to 4-fold higher responses measured in the corresponding ISCOMATRIX subgroups. The non-homologous H7 vaccine induced both H7N3 and H7N9 HAI but no N9 anti-NA antibodies. A lethal murine wild-type A/Anhui/1/2013 (H7N9) challenge demonstrated 100% survival of all animals receiving A(H7N9) and A(H7N3) vaccine, versus 0% survival in A(H5N1) vaccine and placebo groups. Together, the data demonstrate that recombinant H7N9 vaccine can be rapidly developed that was immunogenic and efficacious supporting testing in man as a pandemic influenza H7N9 vaccine candidate

Respiratory syncytial virus fusion glycoprotein expressed in insect cells form protein nanoparticles that induce protective immunity in cotton rats.

Respiratory Syncytial Virus (RSV) is an important viral agent causing severe respiratory tract disease in infants and children as well as in the elderly and immunocompromised individuals. The lack of a safe and effective RSV vaccine represents a major unmet medical need. RSV fusion (F) surface glycoprotein was modified and cloned into a baculovirus vector for efficient expression in Sf9 insect cells. Recombinant RSV F was glycosylated and cleaved into covalently linked F2 and F1 polypeptides that formed homotrimers. RSV F extracted and purified from insect cell membranes assembled into 40 nm protein nanoparticles composed of multiple RSV F oligomers arranged in the form of rosettes. The immunogenicity and protective efficacy of purified RSV F nanoparticles was compared to live and formalin inactivated RSV in cotton rats. Immunized animals induced neutralizing serum antibodies, inhibited virus replication in the lungs, and had no signs of disease enhancement in the respiratory track of challenged animals. RSV F nanoparticles also induced IgG competitive for binding of palivizumab neutralizing monoclonal antibody to RSV F antigenic site II. Antibodies to this epitope are known to protect against RSV when passively administered in high risk infants. Together these data provide a rational for continued development a recombinant RSV F nanoparticle vaccine candidate

Design of thioether cyclic peptide scaffolds with passive permeability and oral exposure

Advances in the design of permeable peptides and in the synthesis of large arrays of macrocyclic peptides with diverse amino acids have evolved on parallel, but independent tracks. Less precedence combines their respective attributes, in turn limiting potential to identify permeable peptide ligands for key protein targets. Herein, we present one strategy for focusing the powerful ligand-finding capability of DNA- or RNA-templated peptide synthesis within permeability-biased property space. Despite higher than standard molecular weights (from 774 to 1076 g·mol-1), the 6-, 7-, and 8-mer cyclic peptides of the present contribution are partially N-methylated to achieve low energy conformations with low desolvation penalties. The N-methylation patterns were selected using in silico methods, then experimentally validat-ed with high passive permeability and oral exposure. Further, the present work shows that chemical structures that overlap the synthetic capabilities of DNA- or RNA-templated peptide syntheses in water, can be both permeable and orally exposed. We envision that, by retaining the backbone N-methylation pattern and consequent bias toward per-meability, one can generate large peptide arrays with sufficient side chain diversity to identify permeability-biased lig-ands to a variety of protein targets