Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza A virus infection

Kim, M.C.,Lee, J.S.,Kwon, Y.M.,O, E.,Lee, Y.J.,Choi, J.G.,Wang, B.Z.,Compans, R.W.,Kang, S.M. Elsevier/North-Holland 2013 Antiviral research Vol.99 No.3

The influenza M2 ectodomain (M2e) is poorly immunogenic and has some amino acid changes among isolates from different host species. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Immunization of mice with M2e5x VLPs induced protective antibodies cross-reactive to antigenically different influenza A viruses and conferred cross protection. Anti-M2e antibodies induced by heterologous M2e5x VLPs showed a wider range of cross reactivity to influenza A viruses at higher levels than those by live virus infection, homologous M2e VLPs, or M2e monoclonal antibody 14C2. Fc receptors were found to be important for mediating protection by immune sera from M2e5x VLP vaccination. The present study provides evidence that heterologous recombinant M2e5x VLPs can be more effective in inducing protective M2e immunity than natural virus infection and further supports an approach for developing an effective universal influenza vaccine.

Supplemented vaccination with tandem repeat M2e virus-like particles enhances protection against homologous and heterologous HPAI H5 viruses in chickens

Song, B.M.,Kang, H.M.,Lee, E.K.,Jung, S.C.,Kim, M.C.,Lee, Y.N.,Kang, S.M.,Lee, Y.J. Butterworths ; Elsevier Science Ltd 2016 Vaccine Vol.34 No.5

Highly pathogenic avian influenza (HPAI) H5 viruses derived from A/Goose/Guangdong/1/96 have been continuously circulating globally, severely affecting the public health and poultry industries. The matrix 2 protein ectodomain (M2e) is considered a promising candidate for a universal cross-protective influenza vaccine that provides more effective control over HPAI H5 viruses harboring variant hemagglutinin (HA)-antigens. Here, we evaluated the protective efficacy of a tandem repeat construct of heterologous M2e presented on virus-like particles (M2e5x VLPs) either alone or as a supplement against HPAI H5 viruses in a chicken model. Chickens immunized with M2e5x VLPs alone induced M2e-specific antibodies but were not protected against HPAI H5. The homo- and cross-protective efficacy of M2e5x VLP-supplemented vaccination of chickens was also examined. Importantly, supplementation with M2e5x VLPs induced significantly higher levels of antibodies specific for M2e and different viruses as well as provided improved protection against homologous and heterologous HPAI H5 viruses. Considering the limited efficacy of inactivated vaccines, supplement vaccination with M2e5x VLPs may be an effective measure for preventing outbreaks of HPAI viruses that have the ability to constantly change their antigenic properties in poultry.

Impact of thermal and chemical treatment on the mechanical properties of E110 and E110G cladding tubes

M. Kir aly,Z. Hozer,M. Horvath,T. Novotny,E. Perez-Fero,N. Ver 한국원자력학회 2019 Nuclear Engineering and Technology Vol.51 No.2

The mechanical and corrosion behavior of the Russian zirconium fuel cladding alloy E110, predominantlyused in VVERs, has been investigated for many decades. The recent commercialization of a new, optimizedE110 alloy, produced on a sponge zirconium basis, gave the opportunity to compare the mechanicalproperties of the old and the new E110 fuel claddings. Axial and tangential tensile test experiments were performed with samples from both claddings in theMTA EK. Due to the anisotropy of the cladding tubes, the axial tensile strength was 10e15% higher thanthe tangential (measured by ring tensile tests). The tensile strength of the new E110G alloy was 11%higher than that of the E110 cladding at room temperature. Some samples underwent chemical treatment e slight oxidation in steam or hydrogenation e or heattreatment e in argon atmosphere at temperatures between 600 and 1000 C. The heat treatment duringthe oxidation had more significant effect on the tensile strength of the claddings than the oxidation itself,which lowered the tensile strength as the thickness of the metal decreased. The hydrogenation of thecladding samples slightly lowered the tensile strength and the samples but they remained ductile even atroom temperature.

Measurement of the top quark mass in the dileptonic tt¯ decay channel using the mass observables Mbℓ , MT2 , and Mbℓν in pp collisions at s=8 TeV

Sirunyan, A. M.,Tumasyan, A.,Adam, W.,Asilar, E.,Bergauer, T.,Brandstetter, J.,Brondolin, E.,Dragicevic, M.,Erö,, J.,Flechl, M.,Friedl, M.,Frü,hwirth, R.,Ghete, V. M.,Hartl, C.,Hö,rmann, N American Physical Society 2017 Physical Review D Vol.96 No.3

<P>A measurement of the top quark mass (M-t) in the dileptonic t (t) over bar decay channel is performed using data from proton-proton collisions at a center-of-mass energy of 8 TeV. The data was recorded by the CMS experiment at the LHC and corresponds to an integrated luminosity of 19.7 +/- 0.5 fb(-1). Events are selected with two oppositely charged leptons (l = e, mu) and two jets identified as originating from b quarks. The analysis is based on three kinematic observables whose distributions are sensitive to the value of Mt. An invariant mass observable, M-bl, and a 'stransverse mass' observable, M-T2, are employed in a simultaneous fit to determine the value of M-t and an overall jet energy scale factor (JSF). A complementary approach is used to construct an invariant mass observable, M-blv, that is combined with M-T2 to measure M-t. The shapes of the observables, along with their evolutions in M-t and JSF, are modeled by a nonparametric Gaussian process regression technique. The sensitivity of the observables to the value of M-t is investigated using a Fisher information density method. The top quark mass is measured to be 172.22 +/- 0.18(stat)(-0.93)(+0.89) (syst) GeV.</P>

Supplementation of oil-based inactivated H9N2 vaccine with M2e antigen enhances resistance against heterologous H9N2 avian influenza virus infection

Park, J.K.,Lee, D.H.,Cho, C.H.,Yuk, S.S.,To, E.O.,Kwon, J.H.,Noh, J.Y.,Kim, B.Y.,Choi, S.W.,Shim, B.S.,Song, M.K.,Lee, J.B.,Park, S.Y.,Choi, I.S.,Song, C.S. Elsevier Scientific Pub. Co 2014 Veterinary microbiology Vol.169 No.3

Avian influenza virus (AIV) subtype H9N2 has been evolving rapidly and vaccine escape variants have been reported to cause circulation of infections and economic losses. In the present study, we developed and evaluated ectodomain of the AIV matrix 2 (M2e) protein as a supplementing antigen for oil-based inactivated H9N2 vaccine to increase resistance against vaccine escape variants. AIV H9N2 M2e antigen was expressed in Escherichia coli and supplemented to inactivated H9N2 oil emulsion vaccine. Specific pathogen-free chickens received a single injection of inactivated H9N2 oil emulsion vaccines with or without M2e supplementation. At three weeks post vaccination, hemagglutination inhibition tests and enzyme-linked immunosorbent assays were performed to determine serological immune responses. Challenge study using a vaccine escape H9N2 variant was performed to evaluate the efficacy of M2e supplementation. M2e antigen supplemented in oil emulsion vaccine was highly immunogenic, and a single M2e-supplemented vaccination reduced challenge virus replication and shedding more effectively than non-supplemented vaccination.

GLOBULAR CLUSTER POPULATIONS: RESULTS INCLUDING S⁴G LATE-TYPE GALAXIES

Zaritsky, Dennis,McCabe, Kelsey,Aravena, Manuel,Athanassoula, E.,Bosma, Albert,Comeró,n, Sé,bastien,Courtois, Helene M.,Elmegreen, Bruce G.,Elmegreen, Debra M.,Erroz-Ferrer, Santiago,Gadot American Astronomical Society 2016 The Astrophysical journal Vol.818 No.1

<P>Using 3.6 and 4.5 mu m images of 73 late-type, edge-on galaxies from the S(4)G survey, we compare the richness of the globular cluster populations of these galaxies to those of early-type galaxies that we measured previously. In general, the galaxies presented here fill in the distribution for galaxies with lower stellar mass, M-*, specifically log(M-*/M-circle dot) < 10, overlap the results for early-type galaxies of similar masses, and, by doing so, strengthen the case for a dependence of the number of globular clusters per 10(9)M(circle dot) of galaxy stellar mass, T-N, on M-*. For 8.5 < log(M-*/M-circle dot) < 10.5 we find the relationship can be satisfactorily described as T-N = (M-*/10(6.7))(-0.56) M-* is expressed in solar masses. The functional form of the relationship is only weakly constrained, and extrapolation outside this range is not advised. Our late-type galaxies, in contrast to our early types, do not show the tendency for low-mass galaxies to split into two T-N families. Using these results and a galaxy stellar mass function from the literature, we calculate that, in a volume-limited, local universe sample, clusters are most likely to be found around fairly massive galaxies (M-* similar to 10(10.8)M(circle dot)) and present a fitting function for the volume number density of clusters as a function of parent-galaxy stellar mass. We find no correlation between T-N and large-scale environment, but we do find a tendency for galaxies of fixed M-* to have larger T-N if they have converted a larger proportion of their baryons into stars.</P>

A novel chimeric promoter that is highly responsive to hypoxia and metals

Lee, J-Y,Lee, Y-S,Kim, J-M,Kim, K L,Lee, J-S,Jang, H-S,Shin, I-S,Suh, W,Jeon, E-S,Byun, J,Kim, D-K Nature Publishing Group 2006 Gene Therapy Vol.13 No.10

To develop a potent hypoxia-inducible promoter, we evaluated the usefulness of chimeric combinations of the (Egr-1)-binding site (EBS) from the Egr-1 gene, the metal-response element (MRE) from the metallothionein gene, and the hypoxia-response element (HRE) from the phosphoglycerate kinase 1 gene. In transient transfection assays, combining three copies of HRE (3 × HRE) with either EBS or MRE significantly increased hypoxia responsiveness. When a three-enhancer combination was tested, the EBS–MRE-3 × HRE (E–M–H) gave a hypoxia induction ratio of 69. The expression induced from E–M–H-pGL3 was 2.4-fold higher than that induced from H-pGL3 and even surpassed the expression from a human cytomegalovirus promoter-driven vector. The high inducibility of E–M–H was confirmed by validation studies in different cells and by expressing other cDNAs. Gel shift assays together with functional overexpression studies suggested that increased levels of hypoxia-inducible factor 1α, metal transcription factor-1 and Egr-1 may be associated with the high inducibility of the E–M–H chimeric promoter. E–M–H was also induced by hypoxia mimetics such as Co<SUP>2+</SUP> and deferoxamine (DFX) and by hydrogen peroxide. Gene expression from the E–M–H was reversible as shown by the reduced expression of the transgene upon removal of inducers such as hypoxia and DFX. In vivo evaluation of the E–M–H in ischemic muscle revealed that erythropoietin secretion and luciferase and LacZ expression were significantly higher in the E–M–H group than in a control or H group. With its high induction capacity and versatile means of modulation, this novel chimeric promoter should find wide application in the treatment of ischemic diseases and cancer.Gene Therapy (2006) 13, 857–868. doi:10.1038/sj.gt.3302728; published online 9 February 2006

Cosmic evolution of stellar quenching by AGN feedback: clues from the Horizon-AGN simulation

Beckmann, R. S.,Devriendt, J.,Slyz, A.,Peirani, S.,Richardson, M. L. A.,Dubois, Y.,Pichon, C.,Chisari, N. E.,Kaviraj, S.,Laigle, C.,Volonteri, M. Oxford University Press 2017 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.472 No.1

<P>The observed massive end of the galaxy stellar mass function is steeper than its predicted dark matter halo counterpart in the standard Lambda cold dark matter paradigm. In this paper, we investigate the impact of active galactic nuclei (AGN) feedback on star formation in massive galaxies. We isolate the impact of AGN by comparing two simulations from the HORIZON suite, which are identical except that one also includes supermassive black holes (SMBHs) and related feedback models. This allows us to cross-identify individual galaxies between simulations and quantify the effect of AGN feedback on their properties, including stellar mass and gas outflows. We find that massive galaxies (M-* >= 10(11) M-circle dot) are quenched by AGN feedback to the extent that their stellar masses decrease by up to 80 per cent at z = 0. SMBHs affect their host halo through a combination of outflows that reduce their baryonic mass, particularly for galaxies in the mass range 10(9) M-circle dot <= M-* <= 10(11) M-circle dot, and a disruption of central gas inflows, which limits in situ star formation. As a result, net gas inflows on to massive galaxies, M-* >= 10(11) M-circle dot, drop by up to 70 per cent. We measure a redshift evolution in the stellar mass ratio of twin galaxies with and without AGN feedback, with galaxies of a given stellar mass showing stronger signs of quenching earlier on. This evolution is driven by a progressive flattening of the M-SMBH-M-* relation with redshift, particularly for galaxies with M-* <= 10(10) M-circle dot. M-SMBH/M-* ratios decrease over time, as falling average gas densities in galaxies curb SMBH growth.</P>

The SAURON project – XIX. Optical and near‐infrared scaling relations of nearby elliptical, lenticular and Sa galaxies

Falcó,n‐,Barroso, J.,van de Ven, G.,Peletier, R. F.,Bureau, M.,Jeong, H.,Bacon, R.,Cappellari, M.,Davies, R. L.,de Zeeuw, P. T.,Emsellem, E.,Krajnović,, D.,Kuntschner, H.,McDermid, R. Blackwell Publishing Ltd 2011 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.417 No.3

<P><B>ABSTRACT</B></P><P>We present ground‐based MDM Observatory <I>V</I>‐band and <I>Spitzer</I>/InfraRed Array Camera 3.6‐<IMG src='/wiley-blackwell_img/equation/MNR_19372_mu1.gif' alt ='inline image'/>m‐band photometric observations of the 72 representative galaxies of the SAURON survey. Galaxies in our sample probe the elliptical E, lenticular S0 and spiral Sa populations in the nearby Universe, both in field and cluster environments. We perform aperture photometry to derive homogeneous structural quantities. In combination with the SAURON stellar velocity dispersion measured within an effective radius (σ<SUB>e</SUB>), this allows us to explore the location of our galaxies in the colour–magnitude, colour–σ<SUB>e</SUB>, Kormendy, Faber–Jackson and Fundamental Plane scaling relations. We investigate the dependence of these relations on our recent kinematical classification of early‐type galaxies (i.e. slow/fast rotators) and the stellar populations. Slow rotator and fast rotator E/S0 galaxies do not populate distinct locations in the scaling relations, although slow rotators display a smaller intrinsic scatter. We find that Sa galaxies deviate from the colour–magnitude and colour–σ<SUB>e</SUB> relations due to the presence of dust, while the E/S0 galaxies define tight relations. Surprisingly, extremely young objects do not display the bluest (<I>V</I>−[3.6]) colours in our sample, as is usually the case in optical colours. This can be understood in the context of the large contribution of thermally pulsing asymptotic giant branch stars to the infrared, even for young populations, resulting in a very tight (<I>V</I>−[3.6])–σ<SUB>e</SUB> relation that in turn allows us to define a strong correlation between metallicity and σ<SUB>e</SUB>. Many Sa galaxies appear to follow the Fundamental Plane defined by E/S0 galaxies. Galaxies that appear offset from the relations correspond mostly to objects with extremely young populations, with signs of ongoing, extended star formation. We correct for this effect in the Fundamental Plane, by replacing luminosity with stellar mass using an estimate of the stellar mass‐to‐light ratio, so that all galaxies are part of a tight, single relation. The new estimated coefficients are consistent in both photometric bands and suggest that differences in stellar populations account for about half of the observed tilt with respect to the virial prediction. After these corrections, the slow rotator family shows almost no intrinsic scatter around the best‐fitting Fundamental Plane. The use of a velocity dispersion within a small aperture (e.g. <I>R</I><SUB>e</SUB>/8) in the Fundamental Plane results in an increase of around 15 per cent in the intrinsic scatter and an average 10 per cent decrease in the tilt away from the virial relation.</P>

NMR study of hydrogen exchange during the B-Z transition of a DNA duplex induced by the Zα domains of yatapoxvirus E3L

Lee, E.H.,Seo, Y.J.,Ahn, H.C.,Kang, Y.M.,Kim, H.E.,Lee, Y.M.,Choi, B.S.,Lee, J.H. North-Holland Pub ; Elsevier Science Ltd 2010 FEBS letters Vol.584 No.21

The Yaba-like disease viruses (YLDV) are members of the Yatapoxvirus family and have double-stranded DNA genomes. The E3L protein, which is essential for pathogenesis in the vaccinia virus, consists of two domains: an N-terminal Z-DNA binding domain and a C-terminal RNA binding domain. The crystal structure of the E3L orthologue of YLDV (yabZα<SUB>E3L</SUB>) bound to Z-DNA revealed that the overall structure of yabZα<SUB>E3L</SUB> and its interaction with Z-DNA are very similar to those of hZα<SUB>ADAR1</SUB>. Here we have performed NMR hydrogen exchange experiments on the complexes between yabZα<SUB>E3L</SUB> and d(CGCGCG)<SUB>2</SUB> with a variety of protein-to-DNA molar ratios. This study revealed that yabZα<SUB>E3L</SUB> could efficiently change the B-form helix of the d(CGCGCG)<SUB>2</SUB> to left-handed Z-DNA via the active-mono B-Z transition pathway like hZα<SUB>ADAR1</SUB>1.