Search

The cap-dependent endonuclease inhibitor baloxavir marboxil is approved in Japan for the treatment of influenza virus infection in patients >12 years of age and children In phase 3 trials, patients [...]

Background: The antigenicity of SARS‐CoV‐2 is a critical issue for the effectiveness of the vaccine, and thus, it should be phenotypically evaluated by serological assays as new field isolates emerge. The hemagglutination/hemagglutination inhibition (HA/HI) tests are well known as a representative method for antigenic analysis of influenza viruses, but SARS‐CoV‐2 does not agglutinate human or guinea pig red blood cells. Therefore, the antigenic analysis requires complicated cell‐based assays using special equipment such as plate reader or ELISPOT analyzer. Methods: Based on the HA/HI tests for influenza viruses, we developed the particle agglutination/particle agglutination inhibition (PA/PAI) test to easily and rapidly quantify the virus and antibody using human angiotensin‐converting enzyme 2 (hACE2)‐bound latex beads. The virus titers were determined by mixing the beads and the virus from culture supernatant, settling it overnight, and then observing the sedimentation/agglutination pattern (PA test). The neutralization antibody titers were determined by mixing virus‐infected hamster antisera in addition to the beads and virus (PAI test). Results: The PA titer was positively correlated with the plaque‐forming units. The PAI titer using the hamster antisera clearly revealed the antigenic difference between the omicron and previous variants. The antigenic differences were supported by the results shown in other methods. Conclusions: The PAI test is an easy and rapid method to analyze the antigenicity of SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

The practical use of cell‐based seasonal influenza vaccines is currently being considered in Japan. From the perspective of adventitious virus contamination, we assessed the suitability of NIID‐MDCK cells (NIID‐MDCK‐Cs) as a safe substrate for the isolation of influenza viruses from clinical specimens. We first established a sensitive multiplex real‐time PCR system to screen for 27 respiratory viruses and used it on 34 virus samples that were isolated by passaging influenza‐positive clinical specimens in NIID‐MDCK‐Cs. Incidentally, the limit of detection (LOD) of the system was 100 or fewer genome copies per reaction. In addition to influenza viruses, human enterovirus 68 (HEV‐D68) genomes were detected in two samples after two or three passages in NIID‐MDCK‐Cs. To further investigate the susceptibility of NIID‐MDCK‐Cs to adventitious viruses, eight common respiratory viruses were subjected to passages in NIID‐MDCK‐Cs. The genome copy numbers of seven viruses other than parainfluenza 3 decreased below the LOD by passage 4. By passaging in NIID‐MDCK‐Cs, the genome numbers of the input HEV‐D68, 1 × 108 copies, declined to 102 at passage 3 and to under the LOD at passage 4, whereas those of the other six viruses were under the LOD by passage 3. These results implied that during the process of isolating influenza viruses with NIID‐MDCK‐Cs, contaminating viruses other than parainfluenza 3 can be efficiently removed by passages in NIID‐MDCK‐Cs. NIID‐MDCK‐Cs could be a safe substrate for isolating influenza viruses that can be used to develop cell‐based influenza vaccine candidate viruses. [ABSTRACT FROM AUTHOR]

A study is conducted to investigate the effects of contact resistance between strands (bare and with Cr plate) in Cable-in-conduit conductors. The results show that the obtained results provide the fundamental data to simulate an electric circuit model of multi-stranded conductors and to estimate inter-strand coupling losses in the conductors.

Contact resistance between superconducting strands in cable-in-conduit conductors is measured and reported.

In this article, we studied a magnetic levitation system which was composed of a high-temperature superconducting (HTS) coil, HTS bulks, and a ferromagnetic material (rail). We set two magnetic levitation systems in one ferromagnetic rail. We analyzed the levitation force depending on changing the distance between HTS coils of each direction of current flowing. As a result of comparing two poles that has current flowing through its coils in one direction and two poles that has current flowing through its coils in different directions, the model which had the coils in one direction was better. A reason for this result is discussed comparing with the magnetic flux density and the stress tensor in a ferromagnetic rail. In addition, the distance between coils was also important for the magnetic interaction. We show the tendency of levitation force obtained by changing the distance between coils in each direction of current flowing and explain the reason. In this article, it is found that a greater force can be obtained by using magnetic field interaction effectively. We optimized arrangement and magnetic pole combination and we succeeded to improve the levitation property. [ABSTRACT FROM AUTHOR]

Suspension Madin–Darby canine kidney (MDCK) cells (MDCK-N), adherent MDCK cells (MDCK-C), and adherent rhesus monkey kidney LLC-MK2 cells (LLC-MK2D) were systematically evaluated for the preparation of influenza vaccine seed viruses for humans on the basis of primary virus isolation efficiency, growth ability, genetic stability of the hemagglutinin (HA) and neuraminidase (NA) genes, and antigenic properties in hemagglutination inhibition (HI) test of each virus isolate upon further passages. All the subtypes/lineages of influenza viruses (A(H1N1), A(H1N1)pdm09, A(H3N2), B-Victoria, and B-Yamagata) were successfully isolated from clinical specimens by using MDCK-N and MDCK-C, whereas LLC-MK2D did not support virus replication well. Serial passages of A(H1N1) viruses in MDCK-N and MDCK-C induced genetic mutations of HA that resulted in moderate antigenic changes in the HI test. All A(H1N1)pdm09 isolates from MDCK-C acquired amino acid substitutions at the site from K153 to N156 of the HA protein, which resulted in striking antigenic alteration. In contrast, only 30% of MDCK-N isolates showed amino acid changes at this site. The frequency of MDCK-N isolates with less than two-fold reduction in the HI titer was as high as 70%. A(H3N2) and B-Yamagata isolates showed high antigenic stability and no specific amino acid substitution during passages in MDCK-N and MDCK-C. B-Victoria isolates from MDCK-N and MDCK-C acquired genetic changes at HA glycosylation sites that greatly affected their antigenicity. When these cell isolates were applied to passages in hen eggs, A(H1N1), B-Victoria, and B-Yamagata viruses grew well in eggs, while none of the cell isolates of A(H3N2) viruses did. Thus, we demonstrate that MDCK-N might be useful for the preparation of influenza vaccine seed viruses. [ABSTRACT FROM AUTHOR]

We characterized influenza A(H1N1)pdm09 isolates from large-scale outbreaks that occurred in Nepal and India in early 2015. Although no specific viral features, which may have caused the outbreaks, were identified, an S84N substitution in hemagglutinin was frequently observed. Chronological phylogenetic analysis revealed that these Nepalese and Indian viruses possessing the S84N substitution constitute potential ancestors of the novel genetic subclade 6B.1 virus that spread globally in the following (2015/16) influenza season. Thus, active surveillance of circulating influenza viruses in the Southern Asia region, including Nepal and India, would be beneficial for detecting novel variant viruses prior to their worldwide spread. [ABSTRACT FROM AUTHOR]

We experimentally and numerically evaluated the AC loss occurred in joints of the EF coil in JT60-SA. There are two kinds of the joints (pancake joint and terminal joint) in the EF coil. Firstly, the AC losses of the joints were experimentally obtained. The experimental results showed that the AC losses in the pancake and the terminal joints were smaller than the loss in the prototype joint which was the previously designed joint and we measured the loss data in two years ago. And next, we numerically analysed the AC loss of the joints. The simulated results well agreed with the experimentally measured data. And we numerically tried to decrease the loss. The AC loss could be decreased to be half of the initial loss. [ABSTRACT FROM PUBLISHER]

5-Fluorouracil (5-FU) is broadly considered the drug of choice for treating human colorectal cancer (CRC). However, 5-FU resistance, mainly caused by the overexpression of antiapoptotic proteins such as Bcl-2, often leads ultimately to treatment failure. We here investigated the effect of Bcl-2 gene silencing, using small interfering RNA (siRNA) (siBcl-2), on the efficacy of 5-FU in CRC. Transfection of siBcl-2 by a Lipofectamine2000/siRNA lipoplex effectively downregulated Bcl-2 expression in the DLD-1 cell line (a CRC), resulting in significant cell growth inhibition in vitro upon treatment with 5-FU. For in vivo treatments, S-1, an oral formulation of Tegafur (TF), a prodrug of 5-FU, was used to mimic 5-FU infusion. The combined treatment of polyethylene glycol (PEG)-coated siBcl-2-lipoplex and S-1 showed superior tumor growth suppression in a DLD-1 xenograft model, compared to each single treatment. Surprisingly, daily S-1 treatment enhanced the accumulation of PEG-coated siBcl-2-lipoplex in tumor tissue. We propose a novel double modulation strategy in cancer treatment, in which chemotherapy enhances intratumoral siRNA delivery and the delivered siRNA enhances the chemosensitivity of tumors. Combination of siRNA-containing nanocarriers with chemotherapy may compensate for the limited delivery of siRNA to tumor tissue. In addition, such modulation strategy may be considered a promising therapeutic approach to successfully managing 5-FU-resistant tumors. [ABSTRACT FROM AUTHOR]

To examine whether Apple latent spherical virus (ALSV) has spread among apple trees in an orchard, we surveyed 21 apple trees surrounding two ALSV-infected trees for virus infection using a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA). None of the 21 trees were infected, indicating that ALSV has not spread from the infected trees to the neighboring apple trees since it was first detected in 1984. We analyzed seed embryos and seedlings derived from infected trees and detected ALSV in 10 of 223 seed embryos (4.5%) and 10 of 227 seedlings (4.4%). From these results, we conclude that ALSV is seed-transmitted at a rate of ca. 4.5% in apple. We also analyzed seed embryos and seedlings from uninfected apple trees that were hand-pollinated with pollen from infected trees. We detected ALSV in only 1 of 260 seed embryos and in none of the 227 apple seedlings. This result indicated that the seed transmission rate via infected pollen is only 0-0.38%. In situ hybridization analysis of ALSV-infected apple flower buds showed that ALSV was present inside almost all pollen grains and in all ovary and ovule tissues, including the embryo sac and inner integument. [ABSTRACT FROM AUTHOR]

Japan and EU are promoting the project that the coils in JT-60 installed in Japan Atomic Energy Agency are changed to superconducting coils. We numerically and experimentally evaluate thermal stability of a conductor joint in the planning superconducting coil (EF coil).We measured an AC loss of the prototype joint, and estimated the coupling time constant. The AC loss at the EF coils joint segment was calculated based on the coupling time constant and the magnetic field distribution. Moreover, the temperature rise due to the AC loss was numerically derived. The calculation result showed that the temperature rise was small and the coil was enough stable. [ABSTRACT FROM AUTHOR]

Abstract: Epoxomicin potently and irreversibly inhibits the catalytic activity of proteasomal subunits. Treatment of proliferating cells with epoxomicin results in cell death through accumulation of ubiquinated proteins. Thus, epoxomicin has been proposed as a potential anti-cancer drug. In the present study, the inhibitory effects of epoxomicin on the in vitro growth of bovine and equine Babesia parasites were evaluated. The inhibitory effect of epoxomicin on the in vivo growth of Babesia microti was also assessed. The in vitro growth of five Babesia species that were tested was significantly inhibited (P <0.05) by nanomolar concentrations of epoxomicin (IC50 values=21.4±0.2, 4±0.1, 39.5±0.1, 9.7±0.3, and 21.1±0.1nM for Babesia bovis, Babesia bigemina, Babesia ovata, Babesia caballi, and Babesia equi, respectively). Epoxomicin IC50 values for Babesia parasites were low when compared with diminazene aceturate and tetracycline hydrochloride. Combinations of epoxomicin with diminazene aceturate synergistically potentiated its inhibitory effects in vitro on B. bovis, B. bigemina, and B. caballi. In B. microti-infected mice, epoxomicin caused significant (P <0.05) inhibition of the growth of B. microti at the non-toxic doses of 0.05 and 0.5mg/kg BW relative to control groups. Therefore, epoxomicin might be used for treatment of babesiosis. [Copyright &y& Elsevier]

Abstract: Pt/Ni/CeO2/Al2O3 catalyst showed the high performance in the steam gasification of cedar wood at the initial stage, however, the catalyst was deactivated within 2h. According to the catalyst characterization by means of XRD and Ni K-edge EXAFS, it is found that aggregation of Ni metal particles causes the deactivation. In contrast, the Pt/Ni/CeO2/MgO/Al2O3 showed the high catalytic activity and stability. The addition of MgO to Pt/Ni/CeO2/Al2O3 decreased the reduction degree of Ni, but increased the dispersion of the Ni metal particles. As a result, the activity of Pt/Ni/CeO2/MgO/Al2O3 was comparable to that of Pt/Ni/CeO2/Al2O3. The Pt/Ni/CeO2/MgO/Al2O3 had high resistance to the aggregation, which can be related to high stability. Another important point is that the aggregated Ni particles on the Pt/Ni/CeO2/MgO/Al2O3 became re-dispersed by the catalyst regeneration (oxidation and reduction). The re-dispersion can proceed via the formation of the NiO–MgO solid solution by oxidation and the reduction of the NiO–MgO from the results of XRD and Ni K-edge EXAFS. [Copyright &y& Elsevier]