Search Results (36)

Predicting flow-induced vibration (FIV) of multiple slender structures remains a modern challenge in science and engineering due to the phenomenon’s sensitivity to layout parameters and the emergence of oscillations driven by multiple mechanisms. The present study examines the FIV of five circular cylinders with two degrees of freedom arranged in a ‘cross’ configuration and subjected to a uniform current. A computational fluid dynamics approach, solving the transient, incompressible 2D Navier–Stokes equations, is employed to analyze the influence of the spacing ratio and reduced velocity $U_r$ on the vibration response and wake dynamics. The investigation includes model verification and parametric studies for several spacing ratios. Results reveal vortex-induced vibrations (VIVs) in some of the cylinders in the arrangement and combined vortex-induced and wake-induced vibration (WIV) in others. Lock-in is observed at $U_r$ = 7 for the upstream cylinder, while the midstream and downstream cylinders exhibit the highest vibration amplitudes due to wake interference. Larger spacing ratios amplify the oscillations of the downstream cylinders, while the side-by-side cylinders display distinct frequency responses. Motion trajectories transition from figure-of-eight patterns to enclosed loops as $U_r$ increases, with specifically complex oscillations emerging at higher velocities. These findings provide insights into multi-body VIV, relevant to offshore structures, marine risers, and heat exchangers. Full article

Background/Objectives: The risk of the introduction of highly pathogenic avian influenza virus (HPAIV) in geese breeding and fattening flocks is heightened due to the necessity of free-range access to grazing grounds. This study aimed to evaluate the safety, immunogenicity, and protective efficacy of five commercial vaccines against HPAIV subtype H5N1 (clade 2.3.4.4b) in subadult fattening geese. Methods: A prime-boost vaccination trial was conducted using five commercial vaccines, including H5 expressing vaccines of novel technology (subunit, vector, RNA) and whole inactivated virus (WIV) vaccines. Based on serological results, one RNA and one WIV vaccine were selected for a homologous challenge experiment. Results: Two vaccines of novel technology (vector, RNA) required a booster dose to raise specific antibodies titers above a threshold of four log₂ using a hemagglutination inhibition (HI) assay, whereas a subunit vaccine and two WIV vaccines induced seroconversion after primary vaccination. In the challenge experiment, all unvaccinated control geese succumbed to infection by day four. In contrast, all vaccinated geese that had seroconverted exhibited full clinical protection. Although sterile immunity was not achieved, viral excretion was significantly reduced in the vaccinated groups compared to controls. Conclusions: Vaccination substantially mitigated the impact of HPAIV H5N1, clade 2.3.4.4b infection in geese, greatly improving animal welfare by preventing severe disease. Additionally, there was a significant reduction in viral burden. Further studies are necessary to verify the potential of these vaccines to reduce susceptibility to infection and virus excretion in order to achieve suppression of the between-flock reproduction number to < 1 in geese flocks at high risk of infection. Full article

Invariant natural killer T (iNKT) cells are glycolipid-reactive T cells with potent immunoregulatory properties. iNKT cells activated with the marine-sponge-derived glycolipid, α-galactosylceramide (αGC), provide a universal source of T-cell help that has shown considerable promise for a wide array of therapeutic applications. This includes harnessing iNKT-cell-mediated immune responses to adjuvant whole inactivated influenza virus (WIV) vaccines. An important concern with WIV vaccines is that under certain circumstances, they are capable of triggering vaccine-associated enhanced respiratory disease (VAERD). This immunopathological phenomenon can arise after immunization with an oil-in-water (OIW) adjuvanted WIV vaccine, followed by infection with a hemagglutinin and neuraminidase mismatched challenge virus. This elicits antibodies (Abs) that bind immunodominant epitopes in the HA2 region of the heterologous virus, which purportedly causes enhanced virus fusion activity to the host cell and increased infection. Here, we show that αGC can induce severe VAERD in pigs. However, instead of stimulating high concentrations of HA2 Abs, αGC elicits high concentrations of interferon (IFN)-γ-secreting cells both in the lungs and systemically. Additionally, we found that VAERD mediated by iNKT cells results in distinct cytokine profiles and altered adaptation of the challenge virus following infection compared to an OIW adjuvant. Overall, these results provide a cautionary note about considering the formulation of WIV vaccines with iNKT-cell agonists as a potential strategy to modulate antigen-specific immunity. Full article

H9N2 avian influenza poses a significant public health risk, necessitating effective vaccines for mass immunization. Oral inactivated vaccines offer advantages like the ease of administration, but their efficacy often requires enhancement through mucosal adjuvants. In a previous study, we established a novel complex of polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) and preliminarily demonstrated its immune-enhancing function. This work aimed to evaluate the efficacy of AMP-ZnONPs as adjuvants in an oral H9N2-inactivated vaccine and the vaccine’s impact on intestinal mucosal immunity. In this study, mice were orally vaccinated on days 0 and 14 after adapting to the environment. AMP-ZnONPs significantly improved HI titers, the levels of specific IgG, IgG1 and IgG2a in serum and sIgA in intestinal lavage fluid; increased the number of B-1 and B-2 cells and dendritic cell populations; and enhanced the mRNA expression of intestinal homing factors and immune-related cytokines. Interestingly, AMP-ZnONPs were more likely to affect B-1 cells than B-2 cells. AMP-ZnONPs showed mucosal immune enhancement that was comparable to positive control (cholera toxin, CT), but not to the side effect of weight loss caused by CT. Compared to the whole-inactivated H9N2 virus (WIV) group, the WIV + AMP-ZnONP and WIV + CT groups exhibited opposite shifts in gut microbial abundance. AMP-ZnONPs serve as an effective and safe mucosal adjuvant for oral WIV, improving cellular, humoral and mucosal immunity and microbiota in the gastrointestinal tract, avoiding the related undesired effects of CT. Full article

SARS-CoV-2 variants of concern (VOCs) show increasing transmissibility and infectivity and induce substantial injuries to human health and the ecology. Therefore, it is vital to understand the related features for controlling infection. In this study, SARS-CoV-2 WIV04 (prototype) and five VOCs (Beta, Delta, Omicron BA.1, BA.2 and BA.5 variants) were inoculated in Vero cells to observe their growth activities. Apart from evaluating the environmental stability at different temperatures, residual virus titers and infectivity at different temperatures (4 °C, room temperature (RT) and 37 °C) were measured over 7 days. The experiment also assessed the infectivity for different incubation durations. The growth capacity assay suggested that the WIV04, Beta and Delta variants replicated efficiently in Vero cells compared with Omicron Variants, and BA.2 replicated more efficiently in Vero cells than BA.1 and BA.5. In addition, all variants exhibited longer survivals at 4 °C and could remain infectious after 7 days, compared to RT’ survival after 5 days and at 37 °C after 1 day. The virus infection assay indicated that the Omicron variant had a weaker ability to infect cells compared to the WIV04, Beta and Delta strains, and a longer infection time was required for these strains, except for BA.2. Full article

Proline betaine (Pro-B) has been identified as a biomarker of dietary citrus intake, yet gaps remain in its validation as a quantitative predictor of intake during various physiological states. This study quantified sources of within-individual variation (WIV) in urinary Pro-B concentration during pregnancy and assessed its correlation with the reported usual intake of citrus fruit and juice. Pro-B concentrations were determined by ¹H-NMR spectroscopy in spot and 24-h urine specimens (n = 255) collected throughout pregnancy from women participating in the MARBLES cohort study. Adjusted linear or log mixed effects models quantified WIV and tested potential temporal predictors of continuous or elevated Pro-B concentration. Pearson or Spearman correlations assessed the relationship between averaged repeated biomarker measures and usual citrus intake reported by food frequency questionnaires. The proportion of variance in urinary Pro-B attributable to WIV ranged from 0.69 to 0.74 in unadjusted and adjusted models. Citrus season was a significant predictor of Pro-B in most analyses (e.g., adjusted β [95% CI]: 0.52 [0.16, 0.88] for non-normalized Pro-B), while gestational age predicted only non-normalized Pro-B (adjusted β [95% CI]: −0.093 [−0.18, −0.0038]). Moderate correlations (r_s of 0.40 to 0.42) were found between reported usual citrus intake and averaged repeated biomarker measurements, which were stronger compared to using a single measurement. Given the high degree of WIV observed in urinary Pro-B, multiple samples per participant are likely needed to assess associations between citrus consumption and health outcomes. Full article

The synthesis, characterization and biological activity of tungstenocenes with varying biologically active (O,O–), (S,O–) and (N,O–) chelates are described. Complexes were characterized by ¹H and ¹³C NMR, elemental analysis, ESI-mass spectrometry, FT-IR spectroscopy and X-ray diffraction analysis. The aqueous stability was studied by UV/Vis spectroscopy and the W^IV to W^V process by cyclic voltammetry. The cytotoxicity was determined by the MTT assay in A549, CH1/PA-1 and SW480 cancer cells as well as in IMR-90 human fibroblasts. Extensive biological evaluation was performed in three other human cancer cell lines (HCT116, HT29 and MCF-7) in monolayer and multicellular tumor spheroid cultures to better understand the mode of action. Lead compounds showed promising in vitro anticancer activity in all cancer cell lines. Further studies yielded important insights into apoptosis induction, ROS generation, different patterns in metal distribution (detected by LA-ICP-TOF-MS), changes in KI67 (proliferation marker) expression and DNA interactions. The results based on qualitative and quantitative research designs show that complexes containing (S,O–) chelates are more active than their (O,O–) and (N,O–) counterparts. The most striking results in spheroid models are the high antiproliferative capacity and the different distribution pattern of two complexes differing only in a W–S or W–O bond. Full article

Influenza A viruses (IAV-S) belonging to the H1 subtype are endemic in swine worldwide. Antigenic drift and antigenic shift lead to a substantial antigenic diversity in circulating IAV-S strains. As a result, the most commonly used vaccines based on whole inactivated viruses (WIVs) provide low protection against divergent H1 strains due to the mismatch between the vaccine virus strain and the circulating one. Here, a consensus coding sequence of the full-length of HA from H1 subtype was generated in silico after alignment of the sequences from IAV-S isolates obtained from public databases and was delivered to pigs using the Orf virus (ORFV) vector platform. The immunogenicity and protective efficacy of the resulting ORFV^Δ121conH1 recombinant virus were evaluated against divergent IAV-S strains in piglets. Virus shedding after intranasal/intratracheal challenge with two IAV-S strains was assessed by real-time RT-PCR and virus titration. Viral genome copies and infectious virus load were reduced in nasal secretions of immunized animals. Flow cytometry analysis showed that the frequency of T helper/memory cells, as well as cytotoxic T lymphocytes (CTLs), were significantly higher in the peripheral blood mononuclear cells (PBMCs) of the vaccinated groups compared to unvaccinated animals when they were challenged with a pandemic strain of IAV H1N1 (CA/09). Interestingly, the percentage of T cells was higher in the bronchoalveolar lavage of vaccinated animals in relation to unvaccinated animals in the groups challenged with a H1N1 from the gamma clade (OH/07). In summary, delivery of the consensus HA from the H1 IAV-S subtype by the parapoxvirus ORFV vector decreased shedding of infectious virus and viral load of IAV-S in nasal secretions and induced cellular protective immunity against divergent influenza viruses in swine. Full article

A new synthetic material, namely, (3-(((4-((5-(((S)-hydroxyhydrophosphoryl)oxy)-2-nitrobenzylidene) amino) phenyl) imino) methyl)-4-nitrophenyl hydrogen (R)-phosphonate)), was subjected to a quaternary ammonium salt and named (HNAP/QA). Several characterizations, such as FTIR spectrometry, ¹H-NMR analysis, ¹³C-NMR analysis, ³¹P-NMR Analysis, TGA analysis, and GC-MS analysis, were performed to ensure its felicitous preparation. HNAP/QA is capable of the selective adsorption of W(VI) ions from its solutions and from its rock leachate. The optimum factors controlling the adsorption of W(VI) ions on the new adsorbent were studied in detail. Furthermore, kinetics and thermodynamics were studied. The adsorption reaction fits the Langmuir model. The sorption process of the W(VI) ions is spontaneous due to the negative value of ∆G° calculated for all temperatures, while the positive value of ∆H° proves that the adsorption of the W(VI) ions adsorption on HNAP/QA is endothermic. The positive value of ∆S° suggests that the adsorption occurs randomly. Ultimately, the recovery of W(IV) from wolframite ore was conducted successfully. Full article

Importance: The protective efficacy of COVID-19 vaccinations has declined over time such that booster doses are required. Objective: To evaluate the efficacy and adverse events of booster doses of two inactivated COVID-19 vaccines. Design: This is a double-blind, randomized, placebo-controlled phase 3 trial aiming to evaluate the protective efficacy, safety, and immunogenicity of inactivated SARS-CoV-2 vaccine (Vero cells) after inoculation with booster doses of inactivated COVID-19 vaccine. Setting: Healthy volunteers were recruited in an earlier phase 3 trial of two doses of inactivated vaccine. The participants in Abu Dhabi maintained the blind state of the trial and received a booster dose of vaccine or placebo at least six months after the primary immunization. Participants: Adults aged 18 and older with no history of SARS-CoV, SARS-CoV-2, or Middle East respiratory syndrome infection (via onsite inquiry) were screened for eligibility. Interventions: A total of 9370 volunteers were screened and randomly allocated, of which 61 voluntarily withdrew from the screening stage without booster inoculation; 9309 received the booster vaccination, with 3083 in the WIV04 group, 3150 in the HB02 group, and 3076 in the alum-only group. Further, 5μg and 4μg of inactivated SARS-CoV-2 virion was adsorbed into aluminum hydroxide in a 0.5 mL aqueous suspension for WIV04 and HB02 vaccines. Main Outcomes and Measures: The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 from 14 days after the booster vaccine in the per-protocol population. A safety analysis was performed in the intention-to-treat population. Results: Symptomatic COVID-19 was identified in 36 participants in the WIV04 group (9.9 [95% CI, 7.2–13.8] per 1000 person-years), 28 in the HB02 group (7.6 [95% CI, 5.2–11.0] per 1000 person-years), and 193 in the alum-only group (55.2 [95% CI, 47.9–63.5] per 1000 person-years), resulting in a vaccine efficacy of 82.0% (95% CI, 74.2–87.8%) for WIV04 and 86.3% (95% CI, 79.6–91.1%) for HB02. One severe case of COVID-19 occurred in the alum-only group, and none occurred in the vaccine groups. Adverse reactions within seven days after vaccination occurred in 29.4% to 34.3% of participants in the three groups. Serious adverse events were rare and not related to vaccines (WIV04: 17 [0.5%]; HB02: 11 [0.4%]; alum only: 40 [1.3%]). Conclusions and Relevance: This study evaluated the safety of the booster dose, which was well tolerated by participants. Booster doses given over six months after the completion of primary immunization can help to provide more-effective protection against COVID-19 in healthy people 18 years of age or older. At the same time, the anti-SARS-CoV-2 antibodies produced by the two groups of experimental vaccines exhibited extensive cross-neutralization against representative SARS-CoV-2 variants. Trial Registration: This study is registered on ClinicalTrials.gov (NCT04510207). Full article

In a previous vaccination study in pigs, heterologous prime-boost vaccination with whole-inactivated H1N1 virus vaccines (WIV) induced superior antibody responses and protection compared to homologous prime-boost vaccination. However, no pan-H1 antibody response was induced. Therefore, to stimulate both local and systemic immune responses, we first vaccinated pigs intranasally with a pseudorabies vector vaccine expressing the pH1N1 hemagglutinin (prvCA09) followed by a homologous or heterologous WIV booster vaccine. Homologous and heterologous WIV–WIV vaccinated groups and mock-vaccinated or prvCA09 single-vaccinated pigs served as control groups. Five weeks after the second vaccination, pigs were challenged with a homologous pH1N1 or one of two heterologous H1N2 swine influenza A virus strains. A single prvCA09 vaccination resulted in complete protection against homologous challenge, and vector–WIV vaccinated groups were significantly better protected against heterologous challenge compared to the challenge control group or WIV–WIV vaccinated groups. Furthermore, vector–WIV vaccination resulted in broader hemagglutination inhibition antibody responses compared to WIV–WIV vaccination and higher numbers of antibody-secreting cells in peripheral blood, draining lymph nodes and nasal mucosa. However, even though vector–WIV vaccination induced stronger antibody responses and protection, we still failed to induce a pan-H1 antibody response. Full article

The most effective method of limiting the coronavirus disease pandemic of 2019 (COVID-19) is vaccination. For the determination of the comparative efficacy and safety of COVID-19 vaccines and their platforms during the pre-Delta era, a systematic review and network meta-analysis was conducted. The MEDLINE, Embase, and MedRxiv databases were searched, and the gray literature was manually searched up to 8 July 2021. The review includes the phase II and III randomized controlled trials (RCTs) that assessed the efficacy, immunogenicity, and safety of the COVID-19 vaccines. The network meta-analysis used a Bayesian model and used the surface under the cumulative ranking to rank the comparisons between the vaccines. All included studies were quality appraised according to their design, and the heterogeneity of the analyses was assessed using I2. In terms of vaccine efficacy, the mRNA-1273 vaccine ranked the highest, and the CoronaVac vaccine ranked the lowest. The mRNA-1273 ranked the highest for neutralizing antibody responses to live SARS-CoV-2. The WIV04 vaccine was associated with the lowest incidence of both local and systemic adverse reactions. All studies except one had a low to moderate risk of bias. The mRNA platform vaccines showed higher efficacy and more adverse reactions than the other vaccines. Full article

A new SARS-CoV-2 variant B.1.1.529 was named by the WHO as Omicron and classified as a Variant of Concern (VOC) on 26 November 2021. Because this variant has more than 50 mutations, including 30 mutations on the spike, it has generated a lot of concerns on the potential impacts of the VOC on COVID-19. Here through ELISA assays using the recombinant RBD proteins with sequences the same to that of SARS-CoV-2 WIV04 (lineage B.1), the Delta variant and the Omicron variant as the coating antigens, the binding capabilities between the RBDs and the antibodies in COVID-19 convalescent sera and vaccine sera after two doses of the inactivated vaccine produced by Sinopharm WIBP are compared with each other. The results showed that the Omicron variant may evade antibodies induced by the ancestral strain and by the inactivated vaccine, with significant reduction in the binding capability of its RBD much greater than that of the Delta variant. Full article

Intranasal immunization with whole inactivated virus (WIV) is an important strategy used for influenza prevention and control. However, a powerful mucosal adjuvant is required to improve nasal vaccine efficacy. Riboflavin, as a food additive with the advantages of being safe and low-cost, widely exists in living organisms. In this paper, the mucosal adjuvant function of riboflavin was studied. After intranasal immunization with H1N1 WIV plus riboflavin in mice, we found that the mucosal immunity based on the secretory IgA (sIgA) levels in the nasal cavity, trachea, and lung were strongly enhanced compared with H1N1 WIV alone. Meanwhile, the IgG, IgG1, and IgG2a levels in serum also showed a high upregulation and a decreased ratio of IgG1/IgG2a, which implied a bias in the cellular immune response. Moreover, riboflavin strongly improved the protection level of H1N1 inactivated vaccine from a lethal influenza challenge. Furthermore, riboflavin was found to possess the capacity to induce dendritic cell (DC) phenotypic (MHCII, CD40, CD80, and CD86) and functional maturation, including cytokine secretion (TNF-α, IL-1β, IL-12p70, and IL-10) and the proliferation of allogeneic T cells. Lastly, we found that the DC maturation induced by riboflavin was dependent on the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which plays an important role in immune regulation. Therefore, riboflavin is expected to be developed as an alternative mucosal adjuvant for influenza nasal vaccine application. Full article

This paper investigates the hybrid source localization problem using differential received signal strength (DRSS) and angle of arrival (AOA) measurements. The main advantage of hybrid measurements is to improve the localization accuracy with respect to a single sensor modality. For sufficiently short wavelengths, AOA sensors can be constructed with size, weight, power and cost (SWAP-C) requirements in mind, making the proposed hybrid DRSS-AOA sensing feasible at a low cost. Firstly the maximum likelihood estimation solution is derived, which is computationally expensive and likely to become unstable for large noise levels. Then a novel closed-form pseudolinear estimation method is developed by incorporating the AOA measurements into a linearized form of DRSS equations. This method eliminates the nuisance parameter associated with linearized DRSS equations, hence improving the estimation performance. The estimation bias arising from the injection of measurement noise into the pseudolinear data matrix is examined. The method of instrumental variables is employed to reduce this bias. As the performance of the resulting weighted instrumental variable (WIV) estimator depends on the correlation between the IV matrix and data matrix, a selected-hybrid-measurement WIV (SHM-WIV) estimator is proposed to maintain a strong correlation. The superior bias and mean-squared error performance of the new SHM-WIV estimator is illustrated with simulation examples. Full article