Boosting Heterosubtypic Neutralization Antibodies in Recipients of 2009 Pandemic H1N1 Influenza Vaccine

Our data demonstrated that the inoculation with vaccine derived from the 2009 pandemic influenza raised vigorous neutralization antibodies against both cognate H1N1 and heterotypic influenza viruses. This observation has important implication for vaccine development

Novel, Real-Time Cell Analysis for Measuring Viral Cytopathogenesis and the Efficacy of Neutralizing Antibodies to the 2009 Influenza A (H1N1) Virus

A novel electronic cell sensor array technology, the real-time cell analysis (RTCA) system, was developed to monitor cell events. Unlike the conventional methods labeling the target cells with fluorescence, luminescence, or light absorption, the RTCA system allows for label-free detection of cell processes directly without the incorporation of labels. Here, we used this new format to measure the cytopathic effect (CPE) of the 2009 influenza A (H1N1) virus and the efficacy of neutralizing antibodies in human sera to this virus. The real-time dynamic monitoring of CPE was performed on MDCK cell cultures infected with the H1N1 virus, ranging from 5.50×102 to 5.50×107 copies/mL. The resulting CPE kinetic curves were automatically recorded and were both time and viral load dependent. The CPE kinetics were also distinguishable between different H1N1 stains, as the onset of CPE induced by the A/Shanghai/37T/2009 H1N1 virus was earlier than that of the A/Shanghai/143T/2009 H1N1 virus. Furthermore, inhibition of H1N1 virus-induced CPE in the presence of human specific anti-sera was detected and quantified using the RTCA system. Antibody titers determined using this new neutralization test correlated well with those obtained independently via the standard hemagglutination inhibition test. Taken together, this new CPE assay format provided label-free and high-throughput measurement of viral growth and the effect of neutralizing antibodies, illustrating its potential in influenza vaccine studies

Fine-grained Generalization Analysis of Vector-Valued Learning

Many fundamental machine learning tasks can be formulated as a problem of learning with vector-valued functions, where we learn multiple scalar-valued functions together. Although there is some generalization analysis on different specific algorithms under the empirical risk minimization principle, a unifying analysis of vector-valued learning under a regularization framework is still lacking. In this paper, we initiate the generalization analysis of regularized vector-valued learning algorithms by presenting bounds with a mild dependency on the output dimension and a fast rate on the sample size. Our discussions relax the existing assumptions on the restrictive constraint of hypothesis spaces, smoothness of loss functions and low-noise condition. To understand the interaction between optimization and learning, we further use our results to derive the first generalization bounds for stochastic gradient descent with vector-valued functions. We apply our general results to multi-class classification and multi-label classification, which yield the first bounds with a logarithmic dependency on the output dimension for extreme multi-label classification with the Frobenius regularization. As a byproduct, we derive a Rademacher complexity bound for loss function classes defined in terms of a general strongly convex function

Evaluation of Interlaminar Stresses in Composite Laminates with a Bolt-Filled Hole Using a Linear Elastic Traction-Separation Description

Determination of the local interlaminar stress distribution in a laminate with a bolt-filled hole is helpful for optimal bolted joint design, due to the three-dimensional (3D) nature of the stress field near the bolt hole. A new interlaminar stress distribution phenomenon induced by the bolt-head and clamp-up load, which occurs in a filled-hole composite laminate, is investigated. In order to efficiently evaluate interlaminar stresses under the complex boundary condition, a calculation strategy that using zero-thickness cohesive interface element is presented and validated. The interface element is based on a linear elastic traction-separation description. It is found that the interlaminar stress concentrations occur at the hole edge, as well as the interior of the laminate near the periphery of the bolt head. In addition, the interlaminar stresses near the periphery of the bolt head increased with an increase in the clamp-up load, and the interlaminar normal and shear stresses are not at the same circular position. Therefore, the clamp-up load cannot improve the interlaminar stress distribution in the laminate near the periphery of the bolt head, although it can reduce the magnitude of the interlaminar shear stress at the hole edge. Thus, the interlaminar stress distribution phenomena may lead to delamination initiation in the laminate near the periphery of the bolt head, and should be considered in composite bolted joint design

Antimicrobial finishing of cotton fabric by atmospheric pressure plasma

In order to synthesize the antimicrobial cotton fabrics, two antimicrobial agents, 3-chloro-2-hydroxypropyltrimethyl ammonium chloride (TX-DF) and 3-(acrylamidopropyl) trimethylammonium chloride (APTAC), were grafted onto cotton fabrics by atmospheric pressure plasma treatment. Orthogonal array testing strategy (OATS) was applied to investigate the optimum treatment conditions of the atmospheric pressure plasma, including sputter-gas species, gas pressure, treatment power and time. The obtained cotton fabrics were characterized by fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and energy dispersive X-ray (EDS). And the results revealed the successful grafting of two antimicrobial agents on cotton fabrics. The antimicrobial efficiency of the plasma treated cotton fabric were studied and found that the TX-DF-treated cotton fabric inactivated 99.85% S. aureus and 99.07% E. coli O157:H7 in 30 min contact time. The cotton sample grafted with APTAC inactivated 74.6% S. aureus and 92.3% E. coli O 157:H7 in 30 min. The hand feeling of the plasma treated antimicrobial cotton fabrics ware measured by PhabrOmeter system, and the result showed that the plasma treatment has little effect on hand value. Thus, the antimicrobial property of cotton fabric finished with TX-DF by the argon/oxygen-plasma techniques achieved sound effects

Learning Term Embeddings for Lexical Taxonomies

Lexical taxonomies, a special kind of knowledge graph, are essential for natural language understanding. This paper studies the problem of lexical taxonomy embedding. Most existing graph embedding methods are difficult to apply to lexical taxonomies since 1) they ignore implicit but important information, namely, sibling relations, which are not explicitly mentioned in lexical taxonomies and 2) there are lots of polysemous terms in lexical taxonomies. In this paper, we propose a novel method for lexical taxonomy embedding. This method optimizes an objective function that models both hyponym-hypernym relations and sibling relations. A term-level attention mechanism and a random walk based metric are then proposed to assist the modeling of these two kinds of relations, respectively. Finally, a novel training method based on curriculum learning is proposed. We conduct extensive experiments on two tasks to show that our approach outperforms other embedding methods and we use the learned term embeddings to enhance the performance of the state-of-the-art models that are based on BERT and RoBERTa on text classification

Hemolysin function of Listeria is related to biofilm formation: transcriptomics analysis

Abstract Listeriolysin O (LLO) is the main virulence protein of Listeria monocytogenes (LM), that helps LM escape lysosomes. We previously found that the cellular immune response elicited by L.ivanovii (LI) is weaker than that elicited by LM. We speculated that this may be related to the function of ivanolysin O (ILO). Here, we constructed hemolysin gene deletion strain, LIΔilo, and a modified strain, LIΔilo::hly, in which ilo was replaced by hly. Prokaryotic transcriptome sequencing was performed on LI, LIΔilo, and LIΔilo::hly. Transcriptome differences between the three strains were compared, and genes and pathways with significant differences between the three strains were analyzed. Prokaryotic transcriptome sequencing results revealed the relationship of ilo to the ribosome, quorum sensing, and phosphotransferase system (PTS) pathways, etc. LIΔilo exhibited attenuated biofilm formation ability compared to LI. Biofilm formation was significantly recovered or even increased after replenishing hly. After knocking out ilo, the relative expression levels of some virulence genes, including sigB, prfA, actA, smcL, and virR, were up-regulated compared to LI. After replenishing hly, these genes were down-regulated compared to LIΔilo. The trend and degree of such variation were not completely consistent when cultured in media containing only monosaccharides or disaccharides. The results confirmed that hemolysin is related to some important biological properties of Listeria, including biofilm formation and virulence gene expression levels. This is the first comprehensive study on ILO function at the transcriptomic level and the first evidence of a relationship between Listeria hemolysin and biofilm formation

Constructing Spin-Adiabatic States for the Modeling of Spin-Crossing Reactions I. A Shared-Orbital Implementation

In the modeling of spin-crossing reactions, it has become popular to directly explore the spin-adiabatic surfaces. Specifically, through constructing spin-adiabatic states from a two-state Hamiltonian (with spin-orbit coupling matrix elements) at each geometry, one can readily employ advanced geometry optimization algorithms to acquire a “transition state" structure, where the spin crossing occurs. In this work, we report the implementation of a fully variational spin-adiabatic approach based on Kohn-Sham density functional theory spin states (sharing the same set of molecular orbitals) and the Breit-Pauli one-electron spin-orbit operator. For three model spin-crossing reactions [predissociation of N2O, singlet-triplet conversion in CH2, and CO association to Fe(CO)4], the spin-crossing points were easily obtained. Our results also indicated the Breit-Pauli one-electron spin-orbit coupling can vary significantly along the reaction pathway on the spin-adiabatic energy surface. On the other hand, due to the restriction that low-spin and high-spin states share the same set of molecular orbitals, the acquired spin-adiabatic energy surface shows a cusp (i.e. a first-order discontinuity) at the crossing point, which prevents the use of standard geometry optimization algorithms to pinpoint the crossing point. An extension with this restriction removed is being developed to achieve the smoothness of spin-adiabatic surfaces

Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution Rate

Palbociclib (PAL) is an effective anti-breast cancer drug, but its use has been partly restricted due to poor bioavailability (resulting from extremely low water solubility) and serious adverse reactions. In this study, two cocrystals of PAL with resorcinol (RES) or orcinol (ORC) were prepared by evaporation crystallization to enhance their solubility. The cocrystals were characterized by single crystal X-ray diffraction, Hirshfeld surface analysis, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared and scanning electron microscopy. The intrinsic dissolution rates of the PAL cocrystals were determined in three different dissolution media (pH 1.0, pH 4.5 and pH 6.8), and both cocrystals showed improved dissolution rates at pH 1.0 and pH 6.8 in comparison to the parent drug. In addition, the cocrystals increased the solubility of PAL at pH 6.8 by 2–3 times and showed good stabilities in both the accelerated stability testing and stress testing. The PAL-RES cocrystal also exhibited an improved relative bioavailability (1.24 times) than PAL in vivo pharmacokinetics in rats. Moreover, the in vitro cytotoxicity assay of PAL-RES showed an increased IC50 value for normal cells, suggesting a better biosafety profile than PAL. Co-crystallization may represent a promising strategy for improving the physicochemical properties of PAL with better pharmacokinetics