Recent epidemics of Zika virus (ZIKV) have been associated with congenital malformation during pregnancy and Guillain-Barré syndrome. There are two ZIKV lineages (African and Asian) that share >95% ...amino acid identity. Little is known regarding the ability of neutralizing antibodies elicited against one lineage to protect against the other. We investigated the breadth of the neutralizing antibody response following ZIKV infection by measuring the sensitivity of six ZIKV strains to neutralization by ZIKV-confirmed convalescent human serum or plasma samples. Contemporary Asian and early African ZIKV strains were similarly sensitive to neutralization regardless of the cellular source of virus. Furthermore, mouse immune serum generated after infection with African or Asian ZIKV strains was capable of neutralizing homologous and heterologous ZIKV strains equivalently. Because our study only defines a single ZIKV serotype, vaccine candidates eliciting robust neutralizing antibody responses should inhibit infection of both ZIKV lineages, including strains circulating in the Americas.
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•Neutralization studies with convalescent ZIKV-immune sera identify a single serotype•Infection with a single ZIKV strain elicits broadly neutralizing antibodies•Strain selection may not be a critical parameter for ZIKV vaccine development
Dowd et al. investigate the breadth of the neutralizing antibody response to ZIKV. They demonstrate that contemporary South American, Asian, and early African ZIKV strains are similarly sensitive to neutralization by ZIKV-confirmed convalescent human serum.
Zika virus (ZIKV) is a flavivirus that has emerged as a global health threat due in part to its association with congenital abnormalities. Other globally relevant flaviviruses include dengue virus ...(DENV) and West Nile virus (WNV). High-resolution structures of ZIKV reveal many similarities to DENV and suggest some differences, including an extended glycan loop (D. Sirohi, Z. Chen, L. Sun, T. Klose, T. C. Pierson, et al., 352:467-470, 2016, http://dx.doi.org/10.1126/science.aaf5316) and unique interactions among envelope (E) protein residues that were proposed to confer increased virion stability and contribute mechanistically to the distinctive pathobiology of ZIKV (V. A. Kostyuchenko, E. X. Lim, S. Zhang, G. Fibriansah, T. S. Ng, et al., Nature 533:425-428, 2016, http://dx.doi.org/10.1038/nature17994). However, in the latter study, virus stability was inferred by measuring the loss of infectivity following a short incubation period. Here, we rigorously assessed the relative stability of ZIKV, DENV, and WNV by measuring changes in infectivity following prolonged incubation at physiological temperatures. At 37°C, the half-life of ZIKV was approximately twice as long as the half-life of DENV (11.8 and 5.2 h, respectively) but shorter than that of WNV (17.7 h). Incubation at 40°C accelerated the loss of ZIKV infectivity. Increasing virion maturation efficiency modestly increased ZIKV stability, as observed previously with WNV and DENV. Finally, mutations at E residues predicted to confer increased stability to ZIKV did not affect virion half-life. Our results demonstrate that ZIKV is not uniquely stable relative to other flaviviruses, suggesting that its unique pathobiology is explained by an alternative mechanism.
Zika virus (ZIKV) belongs to the Flavivirus genus, which includes other clinically relevant mosquito-borne pathogens such as dengue virus (DENV) and West Nile virus (WNV). Historically, ZIKV infection was characterized by a self-limiting, mild disease, but recent outbreaks have been associated with severe clinical complications, including Guillain-Barré syndrome and microcephaly, which are atypical of other flavivirus infections. Moreover, ZIKV has been detected in saliva, urine, and semen, and it may be sexually transmitted. Analysis of a high-resolution cryo-electron microscopic reconstruction of ZIKV hypothesized that the unusual stability of this virus contributes to its distinctive pathobiology. Here, we directly compared the stability of ZIKV to that of other flaviviruses following prolonged incubation in solution at physiological temperatures. We found that the stability of multiple ZIKV strains, including those from recent outbreaks, is intermediate between that of DENV and WNV, suggesting an alternative explanation for the unique clinical manifestations of ZIKV infection.
The synthesis and SAR studies of benzoxazepines as a novel EGFR kinase inhibitor class are reported.
A novel class of pyrimido4,5-b-1,4-benzoxazepines is described as inhibitors of epidermal growth ...factor receptor (EGFR) tyrosine kinase. Two compounds display potent EGFR inhibitory activity of less than 1μM in cellular phosphorylation assays (IC50 0.47–0.69μM) and are highly selective against a small kinase panel. Such compounds demonstrate anti-EGFR activity within a class that is different from any known EGFR inhibitor scaffolds. They also provide a basis for the design of kinase inhibitors with the desired selectivity profile.
We present a near-infrared spectral sequence of the electromagnetic counterpart to the binary neutron star merger GW170817 detected by Advanced Laser Interferometer Gravitational-wave Observatory ...(LIGO)/Virgo. Our data set comprises seven epochs of J+H spectra taken with FLAMINGOS-2 on Gemini-South between 1.5 and 10.5 days after the merger. In the initial epoch, the spectrum is dominated by a smooth blue continuum due to a high-velocity, lanthanide-poor blue kilonova component. Starting the following night, all of the subsequent spectra instead show features that are similar to those predicted in model spectra of material with a high concentration of lanthanides, including spectral peaks near 1.07 and 1.55 m. Our fiducial model with 0.04 M of ejecta, an ejection velocity of v = 0.1c, and a lanthanide concentration of Xlan = 10−2 provides a good match to the spectra taken in the first five days, although it over-predicts the late-time fluxes. We also explore models with multiple fitting components, in each case finding that a significant abundance of lanthanide elements is necessary to match the broad spectral peaks that we observe starting at 2.5 days after the merger. These data provide direct evidence that binary neutron star mergers are significant production sites of even the heaviest r-process elements.
Abstract
We present panchromatic observations and modeling of supernova (SN) 2020tlf, the first normal Type II-P/L SN with confirmed precursor emission, as detected by the Young Supernova Experiment ...transient survey. Pre-SN activity was detected in
riz
-bands at −130 days and persisted at relatively constant flux until first light. Soon after discovery, “flash” spectroscopy of SN 2020tlf revealed narrow, symmetric emission lines that resulted from the photoionization of circumstellar material (CSM) shed in progenitor mass-loss episodes before explosion. Surprisingly, this novel display of pre-SN emission and associated mass loss occurred in a red supergiant (RSG) progenitor with zero-age main-sequence mass of only 10–12
M
⊙
, as inferred from nebular spectra. Modeling of the light curve and multi-epoch spectra with the non-LTE radiative-transfer code CMFGEN and radiation-hydrodynamical code HERACLES suggests a dense CSM limited to
r
≈ 10
15
cm, and mass-loss rate of 10
−2
M
⊙
yr
−1
. The luminous light-curve plateau and persistent blue excess indicates an extended progenitor, compatible with an RSG model with
R
⋆
= 1100
R
⊙
. Limits on the shock-powered X-ray and radio luminosity are consistent with model conclusions and suggest a CSM density of
ρ
< 2 × 10
−16
g cm
−3
for distances from the progenitor star of
r
≈ 5 × 10
15
cm, as well as a mass-loss rate of
M
̇
<
1.3
×
10
−
5
M
☉
yr
−
1
at larger distances. A promising power source for the observed precursor emission is the ejection of stellar material following energy disposition into the stellar envelope as a result of gravity waves emitted during either neon/oxygen burning or a nuclear flash from silicon combustion.
ABSTRACT We present observations of SN 2015bn (=PS15ae = CSS141223-113342+004332 = MLS150211-113342+004333), a Type I superluminous supernova (SLSN) at redshift z = 0.1136. As well as being one of ...the closest SLSNe I yet discovered, it is intrinsically brighter ( ) and in a fainter galaxy ( ) than other SLSNe at . We used this opportunity to collect the most extensive data set for any SLSN I to date, including densely sampled spectroscopy and photometry, from the UV to the NIR, spanning −50 to +250 days from optical maximum. SN 2015bn fades slowly, but exhibits surprising undulations in the light curve on a timescale of 30-50 days, especially in the UV. The spectrum shows extraordinarily slow evolution except for a rapid transformation between +7 and +20-30 days. No narrow emission lines from slow-moving material are observed at any phase. We derive physical properties including the bolometric luminosity, and find slow velocity evolution and non-monotonic temperature and radial evolution. A deep radio limit rules out a healthy off-axis gamma-ray burst, and places constraints on the pre-explosion mass loss. The data can be consistently explained by a M stripped progenitor exploding with erg kinetic energy, forming a magnetar with a spin-down timescale of ∼20 days (thus avoiding a gamma-ray burst) that reheats the ejecta and drives ionization fronts. The most likely alternative scenario-interaction with ∼20 M of dense, inhomogeneous circumstellar material-can be tested with continuing radio follow-up.
The ratio of branching fractions R ( D * − ) ≡ B ( B 0 → D * − τ + ν τ ) / B ( B 0 → D * − μ + ν μ ) is measured using a data sample of proton-proton collisions collected with the LHCb detector at ...center-of-mass energies of 7 and 8 TeV, corresponding to an integrated luminosity of 3 fb − 1 . For the first time, R ( D * − ) is determined using the τ -lepton decays with three charged pions in the final state. The B 0 → D * − τ + ν τ yield is normalized to that of the B 0 → D * − π + π − π + mode, providing a measurement of B ( B 0 → D * − τ + ν τ ) / B ( B 0 → D * − π + π − π + ) = 1.97 ± 0.13 ± 0.18 , where the first uncertainty is statistical and the second systematic. The value of B ( B 0 → D * − τ + ν τ ) = ( 1.42 ± 0.094 ± 0.129 ± 0.054 ) % is obtained, where the third uncertainty is due to the limited knowledge of the branching fraction of the normalization mode. Using the well-measured branching fraction of the B 0 → D * − μ + ν μ decay, a value of R ( D * − ) = 0.291 ± 0.019 ± 0.026 ± 0.013 is established, where the third uncertainty is due to the limited knowledge of the branching fractions of the normalization and B 0 → D * − μ + ν μ modes. This measurement is in agreement with the standard model prediction and with previous results.
Observation of the Doubly Charmed Baryon Ξ++cc Alfonso Albero, Alejandro; Badalov, Alexey; Calvo Gómez, Míriam ...
Physical review letters,
09/2017, Letnik:
119, Številka:
11
Journal Article
Recenzirano
Odprti dostop
A highly significant structure is observed in the Λc+K-π+π+ mass spectrum, where the Λc+ baryon is reconstructed in the decay mode p K-π+. The structure is consistent with originating from a weakly ...decaying particle, identified as the doubly charmed baryon Ξcc ++. The difference between the masses of the Ξcc ++ and Λc+ states is measured to be 1334.94 ±0.72 (stat.) ±0.27 (syst. ) MeV /c2 , and the Ξcc ++ mass is then determined to be 3621.40 ±0.72 (stat.) ±0.27 (syst. ) ±0.14 (Λc+) MeV /c2 , where the last uncertainty is due to the limited knowledge of the Λc+ mass. The state is observed in a sample of proton-proton collision data collected by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.7 fb-1, and confirmed in an additional sample of data collected at 8 TeV.
We evaluated the performance of the MinION DNA sequencer in-flight on the International Space Station (ISS), and benchmarked its performance off-Earth against the MinION, Illumina MiSeq, and PacBio ...RS II sequencing platforms in terrestrial laboratories. Samples contained equimolar mixtures of genomic DNA from lambda bacteriophage, Escherichia coli (strain K12, MG1655) and Mus musculus (female BALB/c mouse). Nine sequencing runs were performed aboard the ISS over a 6-month period, yielding a total of 276,882 reads with no apparent decrease in performance over time. From sequence data collected aboard the ISS, we constructed directed assemblies of the ~4.6 Mb E. coli genome, ~48.5 kb lambda genome, and a representative M. musculus sequence (the ~16.3 kb mitochondrial genome), at 100%, 100%, and 96.7% consensus pairwise identity, respectively; de novo assembly of the E. coli genome from raw reads yielded a single contig comprising 99.9% of the genome at 98.6% consensus pairwise identity. Simulated real-time analyses of in-flight sequence data using an automated bioinformatic pipeline and laptop-based genomic assembly demonstrated the feasibility of sequencing analysis and microbial identification aboard the ISS. These findings illustrate the potential for sequencing applications including disease diagnosis, environmental monitoring, and elucidating the molecular basis for how organisms respond to spaceflight.
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