We perform a semi-automated search for strong gravitational lensing systems in the 9000 deg2 Dark Energy Camera Legacy Survey (DECaLS), part of the Dark Energy Spectroscopic Instrument Legacy Imaging ...Surveys. The combination of the depth and breadth of these surveys are unparalleled at this time, making them particularly suitable for discovering new strong gravitational lensing systems. We adopt the deep residual neural network architecture developed by Lanusse et al. for the purpose of finding strong lenses in photometric surveys. We compile a training sample that consists of known lensing systems in the Legacy Surveys and the Dark Energy Survey as well as non-lenses in the footprint of DECaLS. In this paper we show the results of applying our trained neural network to the cutout images centered on galaxies typed as ellipticals in DECaLS. The images that receive the highest scores (probabilities) are visually inspected and ranked. Here we present 335 candidate strong lensing systems, identified for the first time.
Virus-host interactions determine an infection outcome. The Asian lineage of Zika virus (ZIKV), responsible for the recent epidemics, has fixed a mutation in the NS1 gene after 2012 that enhances ...mosquito infection. Here we report that the same mutation confers NS1 to inhibit interferon-β induction. This mutation enables NS1 binding to TBK1 and reduces TBK1 phosphorylation. Engineering the mutation into a pre-epidemic ZIKV strain debilitates the virus for interferon-β induction; reversing the mutation in an epidemic ZIKV strain invigorates the virus for interferon-β induction; these mutational effects are lost in IRF3-knockout cells. Additionally, ZIKV NS2A, NS2B, NS4A, NS4B, and NS5 can also suppress interferon-β production through targeting distinct components of the RIG-I pathway; however, for these proteins, no antagonistic difference is observed among various ZIKV strains. Our results support the mechanism that ZIKV has accumulated mutation(s) that increases the ability to evade immune response and potentiates infection and epidemics.
Zika virus (ZIKV) infection of pregnant women can cause a wide range of congenital abnormalities, including microcephaly, in the infant, a condition now collectively known as congenital ZIKV ...syndrome. A vaccine to prevent or significantly attenuate viremia in pregnant women who are residents of or travelers to epidemic or endemic regions is needed to avert congenital ZIKV syndrome, and might also help to suppress epidemic transmission. Here we report on a live-attenuated vaccine candidate that contains a 10-nucleotide deletion in the 3' untranslated region of the ZIKV genome (10-del ZIKV). The 10-del ZIKV is highly attenuated, immunogenic, and protective in type 1 interferon receptor-deficient A129 mice. Crucially, a single dose of 10-del ZIKV induced sterilizing immunity with a saturated neutralizing antibody titer, which no longer increased after challenge with an epidemic ZIKV, and completely prevented viremia. The immunized mice also developed a robust T cell response. Intracranial inoculation of 1-d-old immunocompetent CD-1 mice with 1 × 10
infectious focus units (IFU) of 10-del ZIKV caused no mortality, whereas infections with 10 IFU of wild-type ZIKV were lethal. Mechanistically, the attenuated virulence of 10-del ZIKV may be due to decreased viral RNA synthesis and increased sensitivity to type-1-interferon inhibition. The attenuated 10-del ZIKV was incapable of infecting mosquitoes after oral feeding of spiked-blood meals, representing an additional safety feature. Collectively, the safety and efficacy results suggest that further development of this promising, live-attenuated ZIKV vaccine candidate is warranted.
We perform a spectroscopic analysis of 492 450 galaxy spectra from the first two years of observations of the Sloan Digital Sky Survey (SDSS) III/Baryonic Oscillation Spectroscopic Survey (BOSS) ...collaboration. This data set has been released in the ninth SDSS data release, the first public data release of BOSS spectra. We show that the typical signal-to-noise ratio of BOSS spectra, despite being low, is sufficient to measure stellar velocity dispersion and emission line fluxes for individual objects. We show that the typical velocity dispersion of a BOSS galaxy is ∼240 km s−1. The typical error in the velocity dispersion measurement is 14 per cent, and 93 per cent of BOSS galaxies have velocity dispersions with an accuracy of better than 30 per cent. The distribution in velocity dispersion is redshift independent between redshifts 0.15 and 0.7, which reflects the survey design targeting massive galaxies with an approximately uniform mass distribution in this redshift interval. We show that emission lines can be measured on BOSS spectra. However, the majority of BOSS galaxies lack detectable emission lines, as is to be expected because of the target selection design towards massive galaxies. We analyse the emission line properties and present diagnostic diagrams using the emission lines O ii, Hβ, O iii, Hα and N ii (detected in about 4 per cent of the galaxies) to separate star-forming objects and active galactic nuclei (AGN). We show that the emission line properties are strongly redshift dependent and that there is a clear correlation between observed frame colours and emission line properties. Within in the low-z sample (LOWZ) around 0.15 < z < 0.3, half of the emission line galaxies have low-ionization nuclear emission-line region (LINER)-like emission line ratios, followed by Seyfert-AGN-dominated spectra, and only a small fraction of a few per cent are purely star-forming galaxies. AGN and LINER-like objects, instead, are less prevalent in the high-z sample (CMASS) around 0.4 < z < 0.7, where more than half of the emission line objects are star forming. This is a pure selection effect caused by the non-detection of weak Hβ emission lines in the BOSS spectra. Finally, we show that star-forming, AGN and emission line free galaxies are well separated in the g − r versus r − i target selection diagram.
Zika virus infection during pregnancy can cause congenital abnormities or fetal demise. The persistence of Zika virus in the male reproductive system poses a risk of sexual transmission. Here we ...demonstrate that live-attenuated Zika virus vaccine candidates containing deletions in the 3' untranslated region of the Zika virus genome (ZIKV-3'UTR-LAV) prevent viral transmission during pregnancy and testis damage in mice, as well as infection of nonhuman primates. After a single-dose vaccination, pregnant mice challenged with Zika virus at embryonic day 6 and evaluated at embryonic day 13 show markedly diminished levels of viral RNA in maternal, placental, and fetal tissues. Vaccinated male mice challenged with Zika virus were protected against testis infection, injury, and oligospermia. A single immunization of rhesus macaques elicited a rapid and robust antibody response, conferring complete protection upon challenge. Furthermore, the ZIKV-3'UTR-LAV vaccine candidates have a desirable safety profile. These results suggest that further development of ZIKV-3'UTR-LAV is warranted for humans.Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.
We investigate the cosmological implications of the latest growth of structure measurement from the Baryon Oscillation Spectroscopic Survey (BOSS) CMASS Data Release 11 with particular focus on the ...sum of the neutrino masses, ∑m
ν. We examine the robustness of the cosmological constraints from the baryon acoustic oscillation (BAO) scale, the Alcock–Paczynski effect and redshift-space distortions (D
V/r
s, F
AP, fσ8) of Beutler et al., when introducing a neutrino mass in the power spectrum template. We then discuss how the neutrino mass relaxes discrepancies between the cosmic microwave background (CMB) and other low-redshift measurements within Λ cold dark matter. Combining our cosmological constraints with 9-year Wilkinson Microwave Anisotropy Probe (WMAP9) yields ∑m
ν = 0.36 ± 0.14 eV (68 per cent c.l.), which represents a 2.6σ preference for non-zero neutrino mass. The significance can be increased to 3.3σ when including weak lensing results and other BAO constraints, yielding ∑m
ν = 0.35 ± 0.10 eV (68 per cent c.l.). However, combining CMASS with Planck data reduces the preference for neutrino mass to ∼2σ. When removing the CMB lensing effect in the Planck temperature power spectrum (by marginalizing over A
L), we see shifts of ∼1σ in σ8 and Ωm, which have a significant effect on the neutrino mass constraints. In the case of CMASS plus Planck without the A
L lensing signal, we find a preference for a neutrino mass of ∑m
ν = 0.34 ± 0.14 eV (68 per cent c.l.), in excellent agreement with the WMAP9+CMASS value. The constraint can be tightened to 3.4σ yielding ∑m
ν = 0.36 ± 0.10 eV (68 per cent c.l.) when weak lensing data and other BAO constraints are included.
Belatacept is an inhibitor of CD28/B7 costimulation that is clinically indicated as a calcineurin inhibitor (CNI) alternative in combination with mycophenolate mofetil and steroids after renal ...transplantation. We sought to develop a clinically translatable, nonlymphocyte depleting, belatacept‐based regimen that could obviate the need for both CNIs and steroids. Thus, based on murine data showing synergy between costimulation blockade and mTOR inhibition, we studied rhesus monkeys undergoing MHC‐mismatched renal allotransplants treated with belatacept and the mTOR inhibitor, sirolimus. To extend prior work on costimulation blockade‐resistant rejection, some animals also received CD2 blockade with alefacept (LFA3‐Ig). Belatacept and sirolimus therapy successfully prevented rejection in all animals. Tolerance was not induced, as animals rejected after withdrawal of therapy. The regimen did not deplete T cells. Alefecept did not add a survival benefit to the optimized belatacept and sirolimus regimen, despite causing an intended depletion of memory T cells, and caused a marked reduction in regulatory T cells. Furthermore, alefacept‐treated animals had a significantly increased incidence of CMV reactivation, suggesting that this combination overly compromised protective immunity. These data support belatacept and sirolimus as a clinically translatable, nondepleting, CNI‐free, steroid‐sparing immunomodulatory regimen that promotes sustained rejection‐free allograft survival after renal transplantation.
This study demonstrates that a therapy combining belatacept and sirolimus effectively prevents acute renal allograft rejection in rhesus monkeys, and that when these agents are optimally dosed, the addition of alefacept induction promotes cytomegalovirus reactivation and fails to improve survival. See related article by Lowe et al (page 312).
The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been ...established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus. Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted.
Display omitted
•Modified mRNA and live attenuated ZIKV vaccines protect during pregnancy in mice•High titers of neutralizing antibodies are achieved by both vaccine platforms•Vaccines block ZIKV transmission to the fetus in most animals•Damage to the placenta and fetus is prevented
Immunization of pregnant animals with Zika virus vaccines protects the fetuses against vertical transmission of the virus, placental disease, and fetal demise.
We present a new atmospheric extinction curve for Mauna Kea spanning 3200–9700 Å. It is the most comprehensive to date, being based on some 4285 standard star spectra obtained on 478 nights spread ...over a period of 7 years obtained by the Nearby SuperNova Factory using the SuperNova Integral Field Spectrograph. This mean curve and its dispersion can be used as an aid in calibrating spectroscopic or imaging data from Mauna Kea, and in estimating the calibration uncertainty associated with the use of a mean extinction curve. Our method for decomposing the extinction curve into physical components, and the ability to determine the chromatic portion of the extinction even on cloudy nights, is described and verified over the wide range of conditions sampled by our large dataset. We demonstrate good agreement with atmospheric science data obtain at nearby Mauna Loa Observatory, and with previously published measurements of the extinction above Mauna Kea.
Zika virus (ZIKV) infection causes devastating congenital abnormities and Guillain-Barré syndrome. The ZIKV envelope (E) protein is responsible for viral entry and represents a major determinant for ...viral pathogenesis. Like other flaviviruses, the ZIKV E protein is glycosylated at amino acid N154. To study the function of E glycosylation, we generated a recombinant N154Q ZIKV that lacks the E glycosylation and analyzed the mutant virus in mammalian and mosquito hosts. In mouse models, the mutant was attenuated, as evidenced by lower viremia, decreased weight loss, and no mortality; however, knockout of E glycosylation did not significantly affect neurovirulence. Mice immunized with the mutant virus developed a robust neutralizing antibody response and were completely protected from wild-type ZIKV challenge. In mosquitoes, the mutant virus exhibited diminished oral infectivity for the Aedes aegypti vector. Collectively, the results demonstrate that E glycosylation is critical for ZIKV infection of mammalian and mosquito hosts.
Display omitted
•Viral envelope glycosylation is critical for Zika virus virulence in A129 mice•Glycosylation-deficient Zika virus can protect mice from wild-type virus challenge•Envelope glycosylation is required for Zika virus infection of Aedes aegypti vector
Zika virus (ZIKV) causes devastating congenital abnormities and Guillain-Barré syndrome. Fontes-Garfias et al. showed that the glycosylation of ZIKV envelope protein plays an important role in infecting mosquito vectors and pathogenesis in mouse.