Fluorinated aromatic polyimide (FAPI) films with rigid polymer backbones have been prepared by chemical imidization approach. The polyimide films exhibited excellent mechanical properties including ...elastic modulus of up to 8.4 GPa and tensile strength of up to 326.7 MPa, and outstanding thermal stability including glass transition temperature (
) of 346.3-351.6 °C and thermal decomposition temperature in air (
) of 544.1-612.3 °C, as well as high colorless transmittance of >81.2% at 500 nm. Moreover, the polyimide films showed stable dielectric constant and low dielectric loss at 10-60 GHz, attributed to the close packing of rigid polymer backbones that limited the deflection of the dipole in the electric field. Molecular dynamics simulation was also established to describe the relationship of molecular structure and dielectric loss.
Antibody cocktails represent a promising approach to prevent SARS-CoV-2 escape. The determinants for selecting antibody combinations and the mechanism that antibody cocktails prevent viral escape ...remain unclear. We compared the critical residues in the receptor-binding domain (RBD) used by multiple neutralizing antibodies and cocktails and identified a combination of two antibodies CoV2-06 and CoV2-14 for preventing viral escape. The two antibodies simultaneously bind to non-overlapping epitopes and independently compete for receptor binding. SARS-CoV-2 rapidly escapes from individual antibodies by generating resistant mutations in vitro, but it doesn't escape from the cocktail due to stronger mutational constraints on RBD-ACE2 interaction and RBD protein folding requirements. We also identified a conserved neutralizing epitope shared between SARS-CoV-2 and SARS-CoV for antibody CoV2-12. Treatments with CoV2-06 and CoV2-14 individually and in combination confer protection in mice. These findings provide insights for rational selection and mechanistic understanding of antibody cocktails as candidates for treating COVID-19.
In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
, a pandemic. With ...rapidly accumulating numbers of cases and deaths reported globally
, a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18-55 years of age), who were randomized to receive 2 doses-separated by 21 days-of 10 μg, 30 μg or 100 μg of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 μg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9-4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate.
The B.1.1.7 variant (also known as Alpha) of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the UK in the summer of 2020. The prevalence of this variant increased rapidly owing to an ...increase in infection and/or transmission efficiency
. The Alpha variant contains 19 nonsynonymous mutations across its viral genome, including 8 substitutions or deletions in the spike protein that interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that of the 8 individual spike protein substitutions, only N501Y resulted in consistent fitness gains for replication in the upper airway in a hamster model as well as in primary human airway epithelial cells. The N501Y substitution recapitulated the enhanced viral transmission phenotype of the eight mutations in the Alpha spike protein, suggesting that it is a major determinant of the increased transmission of the Alpha variant. Mechanistically, the N501Y substitution increased the affinity of the viral spike protein for cellular receptors. As suggested by its convergent evolution in Brazil, South Africa and elsewhere
, our results indicate that N501Y substitution is an adaptive spike mutation of major concern.
Limiting the rate and extent of starch digestion is a major target for increasing the nutritional value of cereal-based foods. One mechanism that could be exploited is the ability of intact cell ...walls to protect intracellular starches from enzyme hydrolysis, but the extent to which this mechanism is valid for cereal endosperm cells is not well understood. This study aimed to isolate individual intact cellular structures from cereals, viz. wheat and sorghum, in order to elucidate the effect of intactness of cell walls on enzymic hydrolysis of entrapped starch. Intact cells were isolated from dry milled flour obtained using three grinding rolls coupled with a wet sieving technique using selected sieves having varying apertures. The intact cellular structure in wheat and sorghum hindered the hydrolysis of entrapped starch as observed from the lower extent of digestion (9 and 7%) compared to deliberately broken cells (19 and 17% under the same conditions). The extent of digestion was markedly increased once the intact cells were cooked (33 and 26% for wheat and sorghum cooked cells), but this was less than half the digestion extent of non-encapsulated cooked starches (77 and 62% respectively). Microscopic observations coupled with fluorescence labelling of enzyme, cell walls and starch suggest a) wheat and sorghum cell walls are effective barriers for access of amylase; and b) both an extensive protein matrix (particularly in sorghum) and non-catalytic binding of amylase on cell wall surfaces can limit the amylolysis of starch within intact cells. Furthermore, the presence of incompletely gelatinised starch inside cooked intact cells, suggests limited swelling of granules trapped inside the cells. This study shows how preservation of cellular matrices in cereal-based foods could be beneficial for increasing the amount of enzyme resistant starch in cereals with added nutritional benefits.
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•Intact cell rich fractions were isolated using dry milling-wet sieving techniques.•An individual cell wall provided barrier to ingress of amylolytic enzymes inside cells.•Non-catalytic binding of enzymes on cell walls impeded starch digestion in vitro.•Hydrocolloids (starch, protein) interaction in sorghum further attenuated amylolysis.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuing to evolve around the world, generating new variants that are of concern on the basis of their potential for altered ...transmissibility, pathogenicity, and coverage by vaccines and therapeutic agents
. Here we show that serum samples taken from twenty human volunteers, two or four weeks after their second dose of the BNT162b2 vaccine, neutralize engineered SARS-CoV-2 with a USA-WA1/2020 genetic background (a virus strain isolated in January 2020) and spike glycoproteins from the recently identified B.1.617.1, B.1.617.2, B.1.618 (all of which were first identified in India) or B.1.525 (first identified in Nigeria) lineages. Geometric mean plaque reduction neutralization titres against the variant viruses-particularly the B.1.617.1 variant-seemed to be lower than the titre against the USA-WA1/2020 virus, but all sera tested neutralized the variant viruses at titres of at least 1:40. The susceptibility of the variant strains to neutralization elicited by the BNT162b2 vaccine supports mass immunization as a central strategy to end the coronavirus disease 2019 (COVID-19) pandemic globally.
In this paper, we proposed a new robust twin support vector machine (called R-TWSVM) via second order cone programming formulations for classification, which can deal with data with measurement noise ...efficiently. Preliminary experiments confirm the robustness of the proposed method and its superiority to the traditional robust SVM in both computation time and classification accuracy. Remarkably, since there are only inner products about inputs in our dual problems, this makes us apply kernel trick directly for nonlinear cases. Simultaneously we does not need to solve the extra inverse of matrices, which is totally different with existing TWSVMs. In addition, we also show that the TWSVMs are the special case of our robust model and simultaneously give a new dual form of TWSVM by degenerating R-TWSVM, which successfully overcomes the existing shortcomings of TWSVM.
► A new robust twin support vector machine was proposed. ► The method is based on second order cone programming. ► The method can solve data with measurement noise and has good properties.
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