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The article focuses on improving emotion generation in dialogue systems by considering personality traits, aiming to enhance user engagement and service quality. It mentions through the proposed task of Personality-affected Emotion Generation and the development of the Personality EmotionLines Dataset (PELD), the study addresses challenges in integrating personality and emotional factors while modeling personality as a transition weight, resulting in improved emotion generation performance.

Novel physical phenomena arising from the complex interplay between the spin, charge, orbital, and lattice orders can emerge in perovskite-type oxide heterostructures. Here, we investigate the lattice and electronic structures on the interface of the YBa2Cu3O7/LaAlO3 heterostructure prepared by pulsed laser deposition with the combination of spherical aberration-corrected scanning transmission electron microscopy and density functional theory. Both reconstructed and normal interfaces are observed at sub-angstrom resolution, and these superconducting planes closest to the corresponding interface known as CuO2(a) and CuO2(c) planes, respectively. Due to the lattice reconstruction and charge density redistribution, CuO2(a) plane moves closer to the reconstructed interface with bond length of in-plane Cu and apical oxygen reduced. Consequently, the d3z2−r2 orbital loss electrons further results in two orbitals (dx2−y2 and d3z2−r2) crossing the Fermi level, showing two-band superconductivity behavior at the reconstructed interface. However, the CuO2(c) plane remains unaffected due to the protection of the charge reservoir layer at the normal interface and exhibits electronic structures similar to bulk cuprate superconductors, where only dx2−y2 orbitals contribute to the states at the Fermi level. These results suggest that the interfacial reconstruction might be a possible pathway to manipulate the electronic structures of the superconducting oxide heterostructures. [ABSTRACT FROM AUTHOR]

Recently, the search of superconducting materials with topological states has attracted extensive interest due to their exotic properties. By using first-principles calculations, we predict that RuC monolayer is a two-dimensional topological insulator (TI) and shows a TI–superconductor transition under electron doping, leading to a superconducting transition temperature Tc of 1.4 K. Further analysis reveals that the emergence of superconductivity in RuC depends critically on the existence of flatband optical phonons as well as the appearance of multiple electron-pockets and phonon mode softening induced by doping. Moreover, we find that Li-intercalated RuC (LiRuC) is a thermal dynamically stable, superconducting material with a high Tc of 9.8 K, benefitting from the strong electron–phonon coupling. Many other superconductors with flat phonon bands are also predicted via elemental substitution in LiRuC. Our results will broaden the research interest in exploring more superconductors and modulating their physical properties through flat phonon bands. [ABSTRACT FROM AUTHOR]

In this paper, we consider an eigenvalue problem defined on a two-patch domain. Our first aim is to show that the two-patch eigenvalue problem is equivalent to the eigenvalue problem of a measure differential equation defined on an one-patch domain. Our second aim is to study the existence of principal eigenvalue of the measure differential equation, and we will prove the principal eigenvalue is continuously depending on the weight measure in the weak⁎ topology of the measure space. Our third aim is to solve a minimization problem on principal eigenvalues. Some main results of this paper have interesting relations with population dynamics. We will interpret these results in terms of survival chances and optimal distribution of resources. [ABSTRACT FROM AUTHOR]

In this paper, we consider eigenvalue problems of a second-order measure differential equation. We first study some general theories regarding the completely continuity of eigenvalues, the variational characterizations of eigenvalues, and the oscillating properties of eigenfunctions. Then, we solve the following minimization problem: when the m -th Neumann eigenvalue is given, to find explicitly what measures will have the minimal total variation. As applications of this minimization problem, we will solve some extremal problems of eigenvalues and construct some optimal classes of non-degenerate measures for the second-order measure differential equations. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) causes the infectious disease COVID-19 (coronavirus disease 2019), which was first reported in Wuhan, China, in December 2019. Despite extensive efforts to control the disease, COVID-19 has now spread to more than 100 countries and caused a global pandemic. SARS-CoV-2 is thought to have originated in bats; however, the intermediate animal sources of the virus are unknown. In this study, we investigated the susceptibility of ferrets and animals in close contact with humans to SARS-CoV-2. We found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but ferrets and cats are permissive to infection. Additionally, cats are susceptible to airborne transmission. Our study provides insights into the animal models for SARS-CoV-2 and animal management for COVID-19 control. [ABSTRACT FROM AUTHOR]

In this paper, we consider the Dirichlet eigenvalue problems of second-order measure differential equations with a general distribution of potentials. The following optimization problem will be solved: when the m-th eigenvalue is known, we will find explicitly what distribution of potentials will have the minimal total variation. The main tool used herein is some deep continuity results on eigenvalues. [ABSTRACT FROM AUTHOR]

The methods of the quantitative assay of the antiviral activity of interferons (IFNs) (type I, II or III) are very important during carrying out of the research of them, since they were found. Here a recombinant vesicular stomatitis virus expressing green fluorescent protein (GFP) (VSV/GFP) and MDBK cells were used to develop an antiviral assay (AVA) for IFNs. This method was carried out on a 96-well cell culture plate, and the half reduction of virus replication was quantified by assaying GFP. To quantify GFP, cell lysis buffer was directly added to the wells infected with VSV/GFP to lyse cells, the VSV/GFP was then inactivated, and relative fluorescence unit (RFU) of GFP was measured and used to calculate the antiviral activity. This method needed only one step instead of three steps in the staining method with naphthol blue black, medium with phenol red can be used, and it had good reproducibility. The GFP-containing samples could be stored at 4 °C in a wet box for at least 1 week without affecting the assay results. In addition, the results obtained with this method were similar to those obtained with the staining method. In conclusion, a safe, rapid, convenient and low-cost AVA of IFN based on recombinant VSV/GFP was established. [ABSTRACT FROM AUTHOR]

Elderly humans over 65 years old are at great risk to pathogenesis by influenza virus infection. However, although influenza vaccines provide effective protection in healthy young adults, protection of elderly adults is substantially lower even with a good match between the vaccine and the circulating influenza virus. To gain insight of the underlying mechanism for the reduced immunogenicity of influenza vaccines in the aged population, we investigated immunogenicity of influenza virus-like particle vaccines in aged mice, which represent a useful model for studying aging associated impairment in immune responses. Specifically, we investigated the effect of inhibiting regulatory T cells in aged mice on induction of protective immune responses by influenza vaccines. Our results showed that injecting anti-CD25 antibodies could down-regulate CD25 on the surface of regulatory T cells and significantly increase the levels of antibody responses induced by VLP immunization in aged mice. Further, the profiles of antibody responses were also changed towards Th1 type by regulatory T cell blockage in aged mice. Moreover, aged mice that were treated by anti-CD25 antibodies prior to vaccination were more effectively protected against lethal influenza virus challenge. [ABSTRACT FROM AUTHOR]

Pre-trained language models (PLMs) have achieved noticeable success on a variety of natural language processing tasks, such as sequence labeling. In particular, the existing sequence labeling methods fine-tune PLMs on large-scale labeled data, which can avoid training the sequence labeling models from scratch. The fine-tuning process still requires large amounts of labeled training data so as to be effective. However, obtaining rich annotated data for sequence labeling is a time-consuming and expensive process, creating a substantial barrier for directly applying the PLMs trained on general-purpose large-scale text data to sequence labeling. In this paper, we investigate sequence labeling tasks from a novel perspective and propose a general framework that uses labeled clue sentences to mitigate the problem of insufficient annotation data for sequence labeling. Specifically, we first retrieve the labeled clue sentences for each original sentence in the training set based on the semantic (or syntactic) relevance. Here, the number of annotated clue sentences determines the expansion degree of the training set. Then, we modify the transformer's self-attention mechanism to not only exploit the contextual information of the original sentence but also leverage the contextual and label information of the labeled clue sentences. In addition, we devise a mask label strategy to further avoid over-fitting by randomly masking out the labels of certain tokens in the clue sentence and then predicting these mask labels based on the context of the tokens corresponding to the mask labels. We verify the effectiveness and generalizability of the proposed framework on three sequence labeling tasks, including Chinese Named Entity Recognition, English Named Entity Recognition, and Aspect Term Extraction. Extensive experimental results show that our method can yield state-of-the-art or competitive results on the three tasks. • A general framework uses labeled clues to mitigate labeled data shortages. • Two retrieved ways of labeled clue sentences are designed. • Mask label strategy is devised to avoid over-fitting. • Transformer's self-attention is modified to exploit original and clue sentences. • We verify effectiveness of the proposed framework on three sequence labeling tasks. [ABSTRACT FROM AUTHOR]

We established two Madin-Darby canine kidney (MDCK) cell lines stably expressing human airway transmembrane protease: transmembrane protease, serine 2 (TMPRSS2) and mosaic serine protease large form (MSPL) which support multicycle growth of two H5 highly pathogenic avian influenza viruses (HPAIV) recombinant vaccines (Re-5 and Re-6) and an H9 avian influenza virus (AIV) recombinant vaccine (Re-9) in the absence of trypsin. Data showed that the cell lines stably expressed TMPRSS2 and MSPL after 20 serial passages. Both MDCK-TMPRSS2 and MDCK-MSPL could proteolytically cleave the HA of Re-5, Re-6, and Re-9 and supported high-titer growth of the vaccine without exogenous trypsin. Re-5, Re-6, and Re-9 efficiently infected and replicated within MDCK-TMPRSS2 and MDCK-MSPL cells and viral titer were comparable to the virus grown in MDCK cells with TPCK-trypsin. Thus, our results indicate a potential application for these cell lines in cell-based influenza vaccine production and may serve as a useful tool for HA proteolytic cleavage-related studies. [ABSTRACT FROM AUTHOR]

Abstract: Nipah virus (NiV), a member of the Paramyxoviridae family, causes deadly encephalitis in humans and huge economic losses to the pig industry. Here, we generated recombinant avirulent Newcastle disease virus (NDV) LaSota strains expressing the NiV G and F proteins respectively (designated as rLa-NiVG and rLa-NiVF), and evaluated their immunogenicity in mice and pigs. Both rLa-NiVG and rLa-NiVF displayed growth properties similar to those of LaSota virus in chicken eggs. Co-infection of rLa-NiVG and rLa-NiVF caused marked syncytia formation, while intracerebral co-inoculation of these viruses in mice showed they were safe in at least one mammalian species. Animal immunization studies showed rLa-NiVG and rLa-NiVF induced NiV neutralizing antibody responses in mice and pigs, and F protein-specific CD8+ T cell responses in mice. Most importantly, rLa-NiVG and rLa-NiVF administered alone or together, induced a long-lasting neutralizing antibody response in pigs. Recombinant rLa-NiVG/F thus appear to be promising NiV vaccine candidates for pigs and potentially humans. [Copyright &y& Elsevier]

Outbreaks of coronaviruses (CoVs), especially severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have posed serious threats to humans and animals, which urgently calls for effective broad‐spectrum antivirals. RNA‐dependent RNA polymerase (RdRp) plays an essential role in viral RNA synthesis and is an ideal pan‐coronaviral therapeutic target. Herein, based on cryo‐electron microscopy and biochemical approaches, gossypol (GOS) is identified from 881 natural products to directly block SARS‐CoV‐2 RdRp, thus inhibiting SARS‐CoV‐2 replication in both cellular and mouse infection models. GOS also acts as a potent inhibitor against the SARS‐CoV‐2 variant of concern (VOC) and exerts same inhibitory effects toward mutated RdRps of VOCs as the RdRp of the original SARS‐CoV‐2. Moreover, that the RdRp inhibitor GOS has broad‐spectrum anti‐coronavirus activity against alphacoronaviruses (porcine epidemic diarrhea virus and swine acute diarrhea syndrome coronavirus), betacoronaviruses (SARS‐CoV‐2), gammacoronaviruses (avian infectious bronchitis virus), and deltacoronaviruses (porcine deltacoronavirus) is showed. The findings demonstrate that GOS may serve as a promising lead compound for combating the ongoing COVID‐19 pandemic and other coronavirus outbreaks. [ABSTRACT FROM AUTHOR]

Abstract: Vaccination is a key strategy for preventing influenza virus infections. Here, we generated a reassortant virus (SC/AAca) containing the hemagglutinin and neuraminidase genes from a 2009 pandemic influenza virus A/Sichuan/1/2009 (H1N1) (SC/09) and six internal genes from the cold-adapted virus A/Ann Arbor/6/60 (H2N2) (AAca). The SC/AAca reassortant induced a sound humoral immune response and complete protection against homologous SC/09 virus challenge in mice after intranasal administration of an at least 106 50% egg infectious dose (EID50) of SC/AAca. SC/AAca inoculation also induced significant CD4+ and CD8+ T cell responses and provided solid protection against heterologous H1N1 and H5N1 virus challenge. Our results suggest that this 2009 H1N1 live vaccine will provide protection against both 2009 pandemic and seasonal H1N1 virus infection and might reduce the severity of H5N1 virus infection in humans. The induction of cross-reactive virus-specific T cell responses may be an effective approach to develop universal influenza vaccines. [Copyright &y& Elsevier]

Abstract: Influenza virus-like particles (VLPs) were produced in Sf9 insect cells by co-expressing the matrix protein M1 and the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) using the recombinant baculovirus expression system. The VLPs were morphologically similar to influenza virions. Both HA and NA proteins were incorporated into VLPs and these proteins retained their functional activities. Further, influenza VLPs but not inactivated influenza viruses (IIV) stimulated secretion of inflammatory cytokines from mouse bone marrow-derived dendritic cells (BMDC). Immunogenicity of influenza VLPs and their protective efficacies against lethal influenza virus challenge were evaluated in young and aged mice. Immunization with influenza VLPs induced strong antibody responses against HA that inhibited hemagglutination by influenza virus, similar to IIV vaccines. Compared to young mice, antibody responses in aged mice immunized with a low dose of either influenza VLPs or IIV vaccines exhibited markedly reduced avidity for HA. However, immunization of aged mice with a high dose of influenza VLPs induced antibody responses with high avidity similar to those in young mice. Furthermore, all vaccinated animals survived a lethal challenge by a mouse-adapted influenza virus (A/PR/8/34), indicating that influenza VLPs are highly efficacious for protection against influenza virus infection in both young and aged mice. [Copyright &y& Elsevier]

Online forumpost evaluationis an effective way for instructors to assess students' knowledge understanding and writing mechanics. Manually evaluating massive posts costs a lot of time. Automatically grading online posts could significantly alleviate instructors' burden. Similar text assessment tasks like Automated Text Scoring evaluate the writing quality of independent texts or relevance between text and prompt. And Automatic Short Answer Grading measures the semantic matching of short answers according to given problems and correct answers. Different from existing tasks, we propose a novel task, Automated Post Scoring (APS), which grades all online discussion posts in each thread of each student with given topics and quoted posts. APS evaluates not only the writing quality of posts automatically but also the relevance to topics. To measure the relevance, we model the semantic consistency between posts and topics. Supporting arguments are also extracted from quoted posts to enhance posts evaluation. Specifically, we propose a mixture model including a hierarchical text model to measure the writing quality, a semantic matching model to model topic relevance, and a semantic representation model to integrate quoted posts. We also construct a new dataset called Online Discussion Dataset containing 2,542 online posts from 694 students of a social science course. The proposed models are evaluated on the dataset with correlation and residual based evaluation metrics. Compared with measuring posts alone, experimental results demonstrate that incorporating topics and quoted posts could improve the performance of APS by a large margin, more than 9 percent on QWK. [ABSTRACT FROM AUTHOR]

The continuous emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) variants and the increasing number of breakthrough infection cases among vaccinated people support the urgent need for research and development of antiviral drugs. Viral entry is an intriguing target for antiviral drug development. We found that diltiazem, a blocker of the L-type calcium channel Cav1.2 pore-forming subunit (Cav1.2 α1c) and an FDA-approved drug, inhibits the binding and internalization of SARS-CoV-2, and decreases SARS-CoV-2 infection in cells and mouse lung. Cav1.2 α1c interacts with SARS-CoV-2 spike protein and ACE2, and affects the attachment and internalization of SARS-CoV-2. Our finding suggests that diltiazem has potential as a drug against SARS-CoV-2 infection and that Cav1.2 α1c is a promising target for antiviral drug development for COVID-19. Author summary: The emergence of variants of SARS-CoV-2 and the breakthrough infections that have occurred in recipients of approved SARS-CoV-2 vaccines raise doubts about the effectiveness of the vaccines and highlight the importance of antiviral drugs. An ideal drug to treat COVID-19 should be safe, affordable, and accessible. However, remdesivir remains the only authorized drug approved by the US FDA for emergency use, and it appears to have little effect on hospitalized COVID-19 patients. Therefore, identifying drugs to treat SARS-CoV-2 infections remains extremely important and urgent. In this study, we found that the calcium channel blocker diltiazem, which has been approved in the US since 1982 and is cheap and widely used in clinical practice for many indications, inhibits the binding and internalization of SARS-CoV-2, and decreases SARS-CoV-2 infection in cells and mouse lung. The L-type calcium channel Cav1.2 pore-forming subunit (Cav1.2 α1c), the main target of diltiazem, interacts and colocalizes with SARS-CoV-2 spike protein and ACE2, thereby affecting cell attachment and internalization of SARS-CoV-2. Our finding suggests that diltiazem could be candidate COVID-19 treatment and that Cav1.2 α1c may be a promising target for anti-SARS-CoV-2 drugs. [ABSTRACT FROM AUTHOR]

In this paper, we consider the eigenvalue problem of the Schrödinger operator with an integrable potential. Our first result states that each eigenvalue is continuously depending on the potential in the weak topology of some Lebesgue space. Furthermore, if potentials are convergent weakly in the Lebesgue space, then for each m ≥ 1 the m -th normalized eigenfunction is strongly convergent to the eigen-space of the m -th eigenvalue. Our second result obtains the convergence rate of eigenvalues, provided the potential is a cubic periodic integrable function. [ABSTRACT FROM AUTHOR]

The problem in this paper is motivated by physical problems concerned with the case when a class of continuous and equimeasurable densities of a string is given then how to find minimal frequencies among these given densities, that is, what kind of densities minimize the frequencies. By taking Dirichlet eigenvalues into account, given a certain weight function ω, we will show the minimizer of the mth eigenvalue is the m-degree continuous symmetrical decreasing rearrangement of ω. The main result of this paper can be viewed as complementary to Schwarz’s work (Schwarz in J. Math. Mech. 10:401-422, 1961). [ABSTRACT FROM AUTHOR]

Ebola viruses (EBOVs) are zoonotic pathogens that cause EBOV disease (EVD) with high case fatality in humans. Currently, EVD vaccines are still under development in several countries. Here, we generated two recombinant rabies viruses (RABVs), rERAG 333E /ZGP and rERAG 333E /SGP, expressing the Zaire EBOV glycoprotein (ZGP) or Sudan EBOV glycoprotein (SGP) gene based on a modified ERA vaccine strain (rERAG 333E ) vector platform. The recombinant RABVs retained growth properties similar to those of the vector virus in BSR cell culture and efficiently expressed ZGP or SGP. After intracerebral ( i.c. ) inoculation with rERAG 333E /ZGP or rERAG 333E /SGP, all adult mice showed no signs of disease or weight loss and suckling mice maintained similar survivorship curve as those mice inoculated with control vector rERAG 333E , demonstrating that ZGP or SGP expression did not increase the virulence of the vector. Mouse immunization studies showed that vaccination with rERAG 333E /ZGP and rERAG 333E /SGP induced Zaire or Sudan EBOV neutralizing antibody (VNA) responses and IgG, IgG2a responses to ZGP or SGP, suggesting their potential as oral or inactivated bivalent vaccines against rabies and EVD. Most importantly, all dogs immunized orally with rERAG 333E /ZGP developed long-lasting ZEBOV and RABV VNA responses with or without previous rabies vaccine immunization history. Live rERAG 333E with EBOV GP thus appear to have the potential to be oral vaccines for free-roaming animals in endemic areas of EVD and rabies, and may serve as inactivated vaccines for use in humans. [ABSTRACT FROM AUTHOR]

Bovine ephemeral fever (BEF) is caused by the arthropod-borne bovine ephemeral fever virus (BEFV), which is a member of the family Rhabdoviridae and the genus Ephemerovirus. BEFV causes an acute febrile infection in cattle and water buffalo. In this study, a recombinant Newcastle disease virus (NDV) expressing the glycoprotein (G) of BEFV (rL-BEFV-G) was constructed, and its biological characteristics in vitro and in vivo, pathogenicity, and immune response in mice and cattle were evaluated. BEFV G enabled NDV to spread from cell to cell. rL-BEFV-G remained nonvirulent in poultry and mice compared with vector LaSota virus. rL-BEFV-G triggered a high titer of neutralizing antibodies against BEFV in mice and cattle. These results suggest that rL-BEFV-G might be a suitable candidate vaccine against BEF. [ABSTRACT FROM AUTHOR]

Gossypol Broadly Inhibits Coronaviruses by Targeting RNA-Dependent RNA Polymerases (Adv. Sci. 35/2022) B RNA-Dependent RNA Polymerase b In article number 2203499, Zhigao Bu, Lingbo Qu, Maozhi Ren, Fuguang Li, and co-workers report that gossypol, a natural product from cotton plant, can efficiently inhibit SARS-CoV-2 variants by targeting RNA-dependent RNA polymerase (RdRp). Moreover, the RdRp inhibitor gossypol shows broad-spectrum antiviral activity against the examined coronaviruses from the four main phylogenetic branches alphacoronaviruses, betacoronaviruses, gammacoronaviruses, and deltacoronaviruses. [Extracted from the article]

Chemical flooding plays an important role in enhancing oil recovery due to many reasons, including the viscosity-increment effect of polymer, wettability alteration effect of surfactant, and the formation of emulsions, which have been known to effectively increase the swept area and oil displacement efficiency, hence increasing heavy oil recovery. Laboratory tests and pilot trials of alkali–surfactant–polymer (ASP) injection show that the oil recovery of the emulsified system is 5% more than the cases where no emulsions existed. Therefore, it is of great significance to study heavy oil emulsions and its field application for enhanced heavy oil recovery. This paper discusses a thorough overview of the most fundamental ASP flooding mechanisms, along with some examples of laboratory experiments and field trials. In addition, the formation conditions and the interfacial characteristics of heavy oil emulsions are also discussed, mainly ASP flooding, and then the seepage mechanisms of these emulsions are investigated. The relationship between the formation of heavy oil emulsions and the enhanced heavy oil recovery effect by chemical flooding is discussed through core flooding experiments at the reservoir temperature and some field pilots to reach the optimum heavy oil recovery. [ABSTRACT FROM AUTHOR]

[Display omitted] • By depositing Al/a-Al 2 O 3 /Al tri-layer coating on depleted uranium, diffusion pathways of corrosion medium are elongated with misalignment of columar grain boundaries in Al coatings. • The a-Al 2 O 3 interlayer can suppress accumulation and facilitate outgassing of Ar bubbles as major growth defects in Al coatings. • Introduction of intermixing layers between Al- and UO 2 -rich interfacial regions can enhance anti-corrosion stability of Al/a-Al 2 O 3 /Al tri-layer coating. As important energy materials, uranium and its alloys have been widely used in the fields of material sciences and nuclear industrial applications. Applying metal and/or ceramic surface protective coatings can effectively retard easy corrosion of uranium with extremely high chemical activity. In principle, ideal surface protective coatings should possess (1) lowered density of elongated diffusion pathways (i.e. grain boundaries and growth defects) and (2) improved interfacial bonding to substrate by preventing corrosion medium from reacting with uranium. In this work, we have demonstrated that by magnetron-sputtering amorphous Al 2 O 3 (a-Al 2 O 3) interlayers within Al coatings on depleted uranium (DU), the corrosion resistance is significantly improved as indicated by corrosion potential datum DU substrate (−645 mV), DU with mono-layer Al coating (−610 mV) and DU with Al/a-Al 2 O 3 /Al tri-layer coating (−550 mV). Diffusion pathways are elongated with misalignment of columnar grain boundaries in Al coatings around a-Al 2 O 3 interlayers. Meanwhile, density of diffusion pathways is lowered since a-Al 2 O 3 does not contain conventional crystal defects, and can suppress accumulation and facilitate outgassing of Ar bubbles as major growth defects. The effect of coating/substrate interfacial bonding on corrosion behavior is investigated by introduction of intermixing layers between Al- and UO 2 -rich interfacial regions. A strategy to improve anti-corrosion stability of Al/a-Al 2 O 3 /Al tri-layer coating by optimizing degree of intermixing is proposed. The present findings may shed lights on compositional and microstructural design of anti-corrosion coatings on uranium and its alloys. [ABSTRACT FROM AUTHOR]

• Phase separation into niobium-rich and depleted regions were evident after aging for half an hour in the U-13 at.% Nb subjected to aging at 450 °C. • A lath-shaped Nb-rich phase was identified to be more discriminable than the α precipitate in a smaller size, supposing prior precipitation of γ to α. • Applying several recent thermodynamic assessments, a spinodal decomposition mechanism seems unlikely. • The non-classical nucleation theory is suggested to be responsible for the initial precipitation of the Nb-rich phase. Phase separation of the U-Nb (13 at.%) alloy at an aging temperature of 723 K was investigated through transmission electron microscopy. Chemical redistribution initiated from a supersaturated state was identified after aging for half an hour before the discontinuous precipitation (DP) process. Such redistribution was accompanied by a fine two-phase structure and non-lamellar morphology. Among the decomposition products at this early stage, a lath-shaped Nb-rich phase was confirmed to be the bcc (γ) phase, with Nb content in the range of 35∼45 at.%. Meanwhile, discrete regions of much smaller size were detected to bare an Nb content approaching the equilibrium of the α phase. It is envisaged that the γ precipitation was a preceding event of the α. Thermodynamic estimation was carried out to reveal the decomposition mechanism responsible for this unexpected behavior. The results were in favor of a nucleation and growth mechanism over the spinodal decomposition. These results provide a deeper understanding and a new sight into the aging phenomenon of U-13Nb alloys, which are also worth consideration in other binary systems slightly outside the coherent spinodal regions such as Fe-20Cr. [Display omitted] [ABSTRACT FROM AUTHOR]

Minks are raised in many countries and have transmitted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans. However, the biologic properties of SARS-CoV-2 in minks are largely unknown. Here, we investigated and found that SARS-CoV-2 replicates efficiently in both the upper and lower respiratory tracts, and transmits efficiently in minks via respiratory droplets; pulmonary lesions caused by SARS-CoV-2 in minks are similar to those seen in humans with COVID-19. We further found that a spike protein-based subunit vaccine largely prevented SARS-CoV-2 replication and lung damage caused by SARS-CoV-2 infection in minks. Our study indicates that minks are a useful animal model for evaluating the efficacy of drugs or vaccines against COVID-19 and that vaccination is a potential strategy to prevent minks from transmitting SARS-CoV-2. [ABSTRACT FROM AUTHOR]

• The recombinant rabies viruses expressing the NiV G or F protein were generated. • NiV G or F protein expression did not increase the virulence of the vector. • The recombinant RABVs are safe and immunogenic as oral vaccines in mice and pigs. Nipah virus (NiV) is a re-emerging zoonotic pathogen that causes high mortality in humans and pigs. Oral immunization in free-roaming animals is one of the most practical approaches to prevent NiV pandemics. We previously generated a recombinant rabies viruses (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain, rERAG 333E , which contains a mutation from arginine to glutamic acid at residue 333 of glycoprotein (G 333E) and serves as an oral vaccine for dog rabies. In this study, we generated two recombinant RABVs, rERAG 333E /NiVG and rERAG 333E /NiVF, expressing the NiV Malaysian strain attachment glycoprotein (NiV-G) or fusion glycoprotein (NiV-F) gene based on the rERAG 333E vector platform. Both rERAG 333E /NiVG and rERAG 333E /NiVF displayed growth properties similar to those of rERAG 333E and caused marked syncytia formation after co-infection in BSR cell culture. Adult and suckling mice intracerebrally inoculated with the recombinant RABVs showed NiV-G and NiV-F expression did not increase the virulence of rERAG 333E. Oral vaccination with rERAG 333E /NiVG either singularly or combined with rERAG 333E /NiVF induced significant NiV neutralizing antibody against NiV and RABV, and IgG to NiV-G or NiV-F in mice and pigs. rERAG 333E /NiVG and rERAG 333E /NiVF thus appeared to be suitable candidates for further oral vaccines for potential animal targets in endemic areas of NiV disease and rabies. [ABSTRACT FROM AUTHOR]

Rabies virus (RABV) invades the central nervous system and nearly always causes fatal disease in humans. How RABV interacts with host neuron membrane receptors to become internalized and cause rabid symptoms is not yet fully understood. Here, we identified a novel receptor of RABV, which RABV uses to infect neurons. We found that metabotropic glutamate receptor subtype 2 (mGluR2), a member of the G protein-coupled receptor family that is abundant in the central nervous system, directly interacts with RABV glycoprotein to mediate virus entry. RABV infection was drastically decreased after mGluR2 siRNA knock-down in cells. Antibodies to mGluR2 blocked RABV infection in cells in vitro. Moreover, mGluR2 ectodomain soluble protein neutralized the infectivity of RABV cell-adapted strains and a street strain in cells (in vitro) and in mice (in vivo). We further found that RABV and mGluR2 are internalized into cells and transported to early and late endosomes together. These results suggest that mGluR2 is a functional cellular entry receptor for RABV. Our findings may open a door to explore and understand the neuropathogenesis of rabies. [ABSTRACT FROM AUTHOR]

Middle East respiratory syndrome coronavirus (MERS-CoV) has been a highly threatening zoonotic pathogen since its outbreak in 2012. Similar to SARS-CoV, MERS-CoV belongs to the coronavirus family and can induce severe respiratory symptoms in humans, with an average case fatality rate of 35% according to the World Health Organization. Spike (S) protein of MERS-CoV is immunogenic and can induce neutralizing antibodies, thus is a potential major target for vaccine development. Here we constructed a chimeric virus based on the vesicular stomatitis virus (VSV) in which the G gene was replaced by MERS-CoV S gene (VSVΔG-MERS). The S protein efficiently incorporated into the viral envelope and mediated cell entry through binding its receptor, human DPP4. Knockdown of clathrin expression by siRNA drastically abrogated the infection of VSVΔG-MERS in Vero cells. Furthermore, in animal studies, the recombinant virus induced neutralizing antibodies and T cell responses in rhesus monkeys after a single intramuscular or intranasal immunization dose. Our findings indicate the potential of the chimeric VSVΔG-MERS as a rapid response vaccine candidate against emerging MERS-CoV disease. [ABSTRACT FROM AUTHOR]

Oral immunization in free-roaming dogs is one of the most practical approaches to prevent rabies for developing countries. The safe, efficient and long-lasting protective oral rabies vaccine for dogs is highly sought. In this study, rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain wild-type (rERA) and a genetically modified type (rERAG 333E ) containing a mutation from arginine to glutamic acid at residue 333 of glycoprotein (G 333E ) were generated by reverse genetic. The recombinant virus rERAG 333E retained growth properties of similar to the parent strain rERA in BHK-21 cell culture. The G 333E mutation showed genetic stability during passage into neuroblastoma cells and in the brains of suckling mice and was significantly reduced the virulence of rERA in mice. rERAG 333E was immunogenic in dogs by intramuscular inoculation. Mice orally vaccinated with rERAG 333E induced strong and one year longer virus neutralizing antibodies (VNA) to RABV, and were completely protected from challenge with lethal street virus at 12 months after immunization. Dogs received oral vaccination with rERAG 333E induced strong protective RABV VNA response, which lasted for over 3 years, and moderate saliva RABV-specific IgA. Moreover, sizeable booster responses to RABV VNA were induced by a second oral dose 1 year after the first dose. These results demonstrated that the genetically modified ERA vaccine strain has the potential to serve as a safe and efficient oral live vaccine against rabies in dogs. [ABSTRACT FROM AUTHOR]

Canine Distemper Virus (CDV) infects many carnivores and cause several high-mortality disease outbreaks. The current CDV live vaccine cannot be safely used in some exotic species, such as mink and ferret. Here, we generated recombinant lentogenic Newcastle disease virus (NDV) LaSota expressing either envelope glycoproyein, heamagglutinine (H) or fusion protein (F), named as rLa-CDVH and rLa-CDVF, respectively. The feasibility of these recombinant NDVs to serve as live virus-vectored CD vaccine was evaluated in minks. rLa-CDVH induced significant neutralization antibodies (NA) to CDV and provided solid protection against virulent CDV challenge. On the contrast, rLa-CDVF induced much lower NA to CDV and fail to protected mink from virulent CDV challenge. Results suggest that recombinant NDV expressing CDV H is safe and efficient candidate vaccine against CDV in mink, and maybe other host species. [ABSTRACT FROM AUTHOR]

Highlights: [•] rLaC30L-VP2 is a chimeric vector-based vaccine. [•] The vaccine was further evaluated and shown to be safe for 18-day SPF embryos and to be effective for18-day broiler embryos. [•] Single in-ovo vaccination with the vaccine in low dose provided full protection from NDV and vvIBDV. [•] Anti-NDV and anti-IBDV antibodies did not affect its efficacy. [•] This new in-ovo vaccine provided a simple and safe solution for mass immunization of poultry in a wide variety of disease settings. [Copyright &y& Elsevier]

Abstract: A CHO cell clone (CHO-PoIFN-β) with stable porcine IFN-β expression under control of CMV promoter was selected under G418 pressure. In a 25cm2 cell culture flask (5ml culture medium), the cumulative protein yield of recombinant PoIFN-β reached 2.3×106 IU/ml. This cells clone maintained stable expression for at least 20 generations even in the absence of G418 selection pressure. The expressed recombinant PoIFN-β could induce the expression of porcine Mx protein in PK15 cells, and activate the chicken Mx promoter-controlled luciferase reporter gene expression, confirming that the recombinant PoIFN-β has the biological activity of natural porcine type-I interferon. In addition, the recombinant PoIFN-β fully protected PK15 cells against 1000 TCID50 of porcine transmissible gastroenteritis virus and pseudo-rabies virus infection, demonstrating its high potential in therapeutic applications. This is the first report of establishing a mammalian cell line with stable expression of porcine IFN-β. [Copyright &y& Elsevier]

Influenza prophylaxis would benefit from a simple method to administer influenza vaccine into skin without the need for hypodermic needles. In this study, solid metal microneedle arrays (MNs) were investigated as a system for cutaneous vaccine delivery using influenza virus antigen. The MNs with 5 monument-shaped microneedles per array were produced and coated with in activated influenza virus A/PR/8/34 (llV). As much as 10 μg of viral proteins could be coated onto an array of 5 microneedles. and the coated IIV was delivered into skin at high efficiency within minutes. The coated MNs were used to immunize mice in comparison with conventional intramuscular injection at the same dose. Analysis of immune responses showed that a single immunization with IIV-coated MNs induced strong antibody responses against influenza virus, with significant levels of hemagglutination inhibition activities (>1:40), which were comparable to those induced by conventional intramuscular immunization. Moreover, mice immunized by a single dose of IIV coated on MN5 were effectively protected against lethal challenge by a high dose of mouse-adapted influenza virus A/PR/8/34. These results show that MNs are highly effective as a simple method of vaccine delivery to elicit protective immune responses against virus infection. [ABSTRACT FROM AUTHOR]

Abstract: Ebola virus-like particles (VLPs) were produced in insect cells using a recombinant baculovirus expression system and their efficacy for protection against Ebola virus infection was investigated. Two immunizations with 50 μg Ebola VLPs (high dose) induced a high level of antibodies against Ebola GP that exhibited strong neutralizing activity against GP-mediated virus infection and conferred complete protection of vaccinated mice against lethal challenge by a high dose of mouse-adapted Ebola virus. In contrast, two immunizations with 10 μg Ebola VLPs (low dose) induced 5-fold lower levels of antibodies against GP and these mice were not protected against lethal Ebola virus challenge, similar to control mice that were immunized with 50 μg SIV Gag VLPs. However, the antibody responses against GP were boosted significantly after a third immunization with 10 μg Ebola VLPs to similar levels as those induced by two immunizations with 50 μg Ebola VLPs, and vaccinated mice were also effectively protected against lethal Ebola virus challenge. Furthermore, serum viremia levels in protected mice were either below the level of detection or significantly lower compared to the viremia levels in control mice. These results show that effective protection can be achieved by immunization with Ebola VLPs produced in insect cells, which give high production yields, and lend further support to their development as an effective vaccine strategy against Ebola virus. [Copyright &y& Elsevier]

Rabies virus (RABV) invades the central nervous system and nearly always causes fatal disease in humans. RABV enters cells via clathrin-mediated endocytosis upon receptor binding. The detailed mechanism of this process and how it is regulated are not fully understood. Here, we carried out a high-through-put RNAi analysis and identified AP2-associated kinase 1 (AAK1), a serine/threonine kinase, as an important cellular component in regulating the entry of RABV. AAK1 knock-down greatly inhibits RABV infection of cells, and AAK1-induced phosphorylation of threonine 156 of the μ subunit of adaptor protein 2 (AP2M1) is found to be required for RABV entry. Inhibition of AAK1 kinase activity by sunitinib blocked AP2M1 phosphorylation, significantly inhibiting RABV infection and preventing RABV from entering early endosomes. In vivo studies revealed that sunitinib prolongs the survival of mice challenged with RABV street virus. Our findings indicate that AAK1 is a potential drug target for postexposure prophylaxis against rabies. [ABSTRACT FROM AUTHOR]