The Herschel view of the environment of the radio galaxy 4C+41.17 at z = 3.8

We present Herschel observations at 70, 160, 250, 350 and 500 μm of the environment of the radio galaxy 4C+41.17 at z = 3.792. About 65 per cent of the extracted sources are securely identified with mid-infrared sources observed with the Spitzer Space Telescope at 3.6, 4.5, 5.8, 8 and 24 μm. We derive simple photometric redshifts, also including existing 850 and 1200 μm data, using templates of active galactic nuclei, starburst-dominated systems and evolved stellar populations. We find that most of the Herschel sources are foreground to the radio galaxy and therefore do not belong to a structure associated with 4C+41.17. We do, however, find that the spectral energy distribution (SED) of the closest (∼25 arcsec offset) source to the radio galaxy is fully consistent with being at the same redshift as 4C+41.17. We show that finding such a bright source that close to the radio galaxy at the same redshift is a very unlikely event, making the environment of 4C+41.17 a special case. We demonstrate that multiwavelength data, in particular on the Rayleigh–Jeans side of the SED, allow us to confirm or rule out the presence of protocluster candidates that were previously selected by single wavelength data setsPeer reviewe

Optimization of Surface Display of DENV2 e Protein on a Nanoparticle to Induce Virus Specific Neutralizing Antibody Responses

The dengue virus (DENV) causes over 350 million infections, resulting in ∼25,000 deaths per year globally. An effective dengue vaccine requires generation of strong and balanced neutralizing antibodies against all four antigenically distinct serotypes of DENV. The leading live-attenuated tetravalent dengue virus vaccine platform has shown partial efficacy, with an unbalanced response across the four serotypes in clinical trials. DENV subunit vaccine platforms are being developed because they provide a strong safety profile and are expected to avoid the unbalanced immunization issues associated with live multivalent vaccines. Subunit vaccines often lack immunogenicity, requiring either a particulate or adjuvanted formulation. Particulate formulations adsorbing monomeric DENV-E antigen to the particle surface incite a strong immune response, but have no control of antigen presentation. Highly neutralizing epitopes are displayed by DENV-E quaternary structures. To control the display of DENV-E and produce quaternary structures, particulate formulations that covalently attach DENV-E to the particle surface are needed. Here we develop a surface attached DENV2-E particulate formulation, as well as analysis tools, using PEG hydrogel nanoparticles created with particle replication in nonwetting templates (PRINT) technology. We found that adding Tween-20 to the conjugation buffer controls DENV-E adsorption to the particle surface during conjugation, improving both protein stability and epitope display. Immunizations with the anionic but not the cationic DENV2-E conjugated particles were able to produce DENV-specific and virus neutralizing antibody in mice. This work optimized the display of DENV-E conjugated to the surface of a nanoparticle through EDC/NHS chemistry, establishing a platform that can be expanded upon in future work to fully control the display of DENV-E

Oligomeric state of the ZIKV E protein defines protective immune responses

The current leading Zika vaccine candidates in clinical testing are based on live or killed virus platforms, which have safety issues, especially in pregnant women. Zika subunit vaccines, however, have shown poor performance in preclinical studies, most likely because the antigens tested do not display critical quaternary structure epitopes present on Zika E protein homodimers that cover the surface of the virus. Here, we produce stable recombinant E protein homodimers that are recognized by strongly neutralizing Zika specific monoclonal antibodies. In mice, the dimeric antigen stimulate strongly neutralizing antibodies that target epitopes that are similar to epitopes recognized by human antibodies following natural Zika virus infection. The monomer antigen stimulates low levels of E-domain III targeting neutralizing antibodies. In a Zika challenge model, only E dimer antigen stimulates protective antibodies, not the monomer. These results highlight the importance of mimicking the highly structured flavivirus surface when designing subunit vaccines

Physiological temperatures reduce dimerization of dengue and Zika virus recombinant envelope proteins

The spread of dengue (DENV) and Zika virus (ZIKV) is a major public health concern. The primary target of antibodies that neutralize DENV and ZIKV is the envelope (E) glycoprotein, and there is interest in using soluble recombinant E (sRecE) proteins as subunit vaccines. However, the most potent neutralizing antibodies against DENV and ZIKV recognize epitopes on the virion surface that span two or more E proteins. Therefore, to create effective DENV and ZIKV vaccines, presentation of these quaternary epitopes may be necessary. The sRecE proteins from DENV and ZIKV crystallize as native-like dimers, but studies in solution suggest that these dimers are marginally stable. To better understand the challenges associated with creating stable sRecE dimers, we characterized the thermostability of sRecE proteins from ZIKV and three DENV serotypes, DENV2– 4. All four proteins irreversibly unfolded at moderate temperatures (46 –53 °C). At 23 °C and low micromolar concentrations, DENV2 and ZIKV were primarily dimeric, and DENV3– 4 were primarily monomeric, whereas at 37 °C, all four proteins were predominantly monomeric. We further show that the dissociation constant for DENV2 dimerization is very temperature-sensitive, ranging from <1 M at 25 °C to 50 M at 41 °C, due to a large exothermic enthalpy of binding of 79 kcal/mol. We also found that quaternary epitope antibody binding to DENV2– 4 and ZIKV sRecE is reduced at 37 °C. Our observation of reduced sRecE dimerization at physiological temperature highlights the need for stabilizing the dimer as part of its development as a subunit vaccine

Pd-Ir alloy as an anode material for borohydride oxidation

A Pd-Ir alloy (1:1) coated on microfibrous carbon (11 μm diameter) supported on a titanium plate was evaluated as an electrode for the anodic oxidation of borohydride. The hydrogen generated, due to the parallel reaction of borohydride hydrolysis, was measured during the electrolysis obtaining less than 0.1 cm 3 min -1 H 2 between -1 and 0 V vs. Hg/HgO (-0.86 and 0.14 V vs. SHE), while the current densities for the oxidation of borohydride were up to 367 mA cm -2 in 0.5 mol dm -3 NaBH 4 + 3 mol dm -3 NaOH. The low rate of hydrogen generation suggests that Pd-Ir could be a promising catalyst for borohydride oxidation. However, higher rates of hydrogen were generated at the open circuit potential, which is inconvenient in the direct borohydride fuel cell. Cyclic voltammetry allowed analysis of the oxidation peaks due to the borohydride oxidation. To obtain a further understanding of the borohydride oxidation mechanism at Pd-Ir electrodes, density functional theory (DFT) was used to examine the reaction mechanism at Pd 2 -Ir 1 (111) and Pd 2 -Ir 2 (111) surfaces. The competition between borohydride oxidation and hydrogen evolution on the Pd-Ir alloys is compared with that on pure Pd(111), suggesting that the presence of Ir favors borohydride oxidation rather than hydrogen evolution. © 2014 Elsevier B.V. All rights reserved

Unmasking the history of 3C 293 with LOFAR sub-arcsecond imaging

Galaxie

Supermassive Binaries and Extragalactic Jets

Some quasars show Doppler shifted broad emission line peaks. I give new statistics of the occurrence of these peaks and show that, while the most spectacular cases are in quasars with strong radio jets inclined to the line of sight, they are also almost as common in radio-quiet quasars. Theories of the origin of the peaks are reviewed and it is argued that the displaced peaks are most likely produced by the supermassive binary model. The separations of the peaks in the 3C 390.3-type objects are consistent with orientation-dependent "unified models" of quasar activity. If the supermassive binary model is correct, all members of "the jet set" (astrophysical objects showing jets) could be binaries.Comment: 31 pages, PostScript, missing figure is in ApJ 464, L105 (see http://www.aas.org/ApJ/v464n2/5736/5736.html

Cosmic evolution of low-excitation radio galaxies in the LOFAR two-metre sky survey deep fields

Galaxie