Emerging viruses and current strategies for vaccine intervention.

During the past decade several notable viruses have suddenly emerged from obscurity or anonymity to become serious global health threats, provoking concern regarding their sustained epidemic transmission in immunologically naive human populations. With each new threat comes the call for rapid vaccine development. Indeed, vaccines are considered a critical component of disease prevention for emerging viral infections because, in many cases, other medical options are limited or non-existent, or that infections result in such a rapid clinical deterioration that the effectiveness of therapeutics is limited. While classic approaches to vaccine development are still amenable to emerging viruses, the application of molecular techniques in virology has profoundly influenced our understanding of virus biology, and vaccination methods based on replicating, attenuated and non-replicating virus vector approaches have become useful vaccine platforms. Together with a growing understanding of viral disease emergence, a range of vaccine strategies and international commitment to underpin development, vaccine intervention for new and emerging viruses may become a possibility

Monte Carlo modelling of an x-ray chamber for providing inactivation exposures to viruses

The Monte Carlo radiation transport code MCNP6 has been used to model dosimetry for biological pathogen samples placed within a MultiRad 225 irradiation chamber, in order to inform virus deactivation protocols. Full characterisations of the photon spectra generated by the chamber's x-ray tube were achieved for both 190 and 220 kV potentials, with and without aluminium and copper beam filters of different thicknesses. Dose rate maps to air and water within the chamber were then derived, along with corresponding conversion coefficient data. The maps were determined for samples located both on a shelf and on a dry ice refrigeration chamber, at different distances from the source. The potential depth-dose profiles through samples were also investigated. The optimum choice of filter for use in virus inactivation procedures will rely on a compromise between dose homogeneity and dose rate

Tula orthohantavirus nucleocapsid protein is cleaved in infected cells and may sequester activated caspase-3 during persistent infection to suppress apoptosis

The family Hantaviridae mostly comprises rodent-borne segmented negative-sense RNA viruses, many of which are capable of causing devastating disease in humans. In contrast, hantavirus infection of rodent hosts results in a persistent and inapparent infection through their ability to evade immune detection and inhibit apoptosis. In this study, we used Tula hantavirus (TULV) to investigate the interplay between viral and host apoptotic responses during early, peak and persistent phases of virus infection in cell culture. Examination of early-phase TULV infection revealed that infected cells were refractory to apoptosis, as evidenced by the complete lack of cleaved caspase-3 (casp-3C) staining, whereas in non-infected bystander cells casp-3C was highly abundant. Interestingly, at later time points, casp-3C was abundant in infected cells, but the cells remained viable and able to continue shedding infectious virus, and together these observations were suggestive of a TULV-associated apoptotic block. To investigate this block, we viewed TULV-infected cells using laser scanning confocal and wide-field deconvolution microscopy, which revealed that TULV nucleocapsid protein (NP) colocalized with, and sequestered, casp-3C within cytoplasmic ultrastructures. Consistent with casp-3C colocalization, we showed for the first time that TULV NP was cleaved in cells and that TULV NP and casp-3C could be co-immunoprecipitated, suggesting that this interaction was stable and thus unlikely to be solely confined to NP binding as a substrate to the casp-3C active site. To account for these findings, we propose a novel mechanism by which TULV NP inhibits apoptosis by spatially sequestering casp-3C from its downstream apoptotic targets within the cytosol

GW170104: Observation of a 50-Solar-Mass Binary Black Hole Coalescence at Redshift 0.2

We describe the observation of GW170104, a gravitational-wave signal produced by the coalescence of a pair of stellar-mass black holes. The signal was measured on January 4, 2017 at 10: 11: 58.6 UTC by the twin advanced detectors of the Laser Interferometer Gravitational-Wave Observatory during their second observing run, with a network signal-to-noise ratio of 13 and a false alarm rate less than 1 in 70 000 years. The inferred component black hole masses are 31.2(-6.0)(+8.4) M-circle dot and 19.4(-5.9)(+5.3)M(circle dot) (at the 90% credible level). The black hole spins are best constrained through measurement of the effective inspiral spin parameter, a mass-weighted combination of the spin components perpendicular to the orbital plane, chi(eff) = -0.12(-0.30)(+0.21) . This result implies that spin configurations with both component spins positively aligned with the orbital angular momentum are disfavored. The source luminosity distance is 880(-390)(+450) Mpc corresponding to a redshift of z = 0.18(-0.07)(+0.08) . We constrain the magnitude of modifications to the gravitational-wave dispersion relation and perform null tests of general relativity. Assuming that gravitons are dispersed in vacuum like massive particles, we bound the graviton mass to m(g) \u3c= 7.7 x 10(-23) eV/c(2). In all cases, we find that GW170104 is consistent with general relativity

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of genetically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Omega(T)(0) \u3c 5.58 x 10(-8), Omega(V)(0) \u3c 6.35 x 10(-8), and Omega(S)(0) \u3c 1.08 x 10(-7) at a reference frequency f(0) = 25 Hz

GW170817: Implications for the Stochastic Gravitational-Wave Background from Compact Binary Coalescences

The LIGO Scientific and Virgo Collaborations have announced the event GW170817, the first detection of gravitational waves from the coalescence of two neutron stars. The merger rate of binary neutron stars estimated from this event suggests that distant, unresolvable binary neutron stars create a significant astrophysical stochastic gravitational-wave background. The binary neutron star component will add to the contribution from binary black holes, increasing the amplitude of the total astrophysical background relative to previous expectations. In the Advanced LIGO-Virgo frequency band most sensitive to stochastic backgrounds (near 25 Hz), we predict a total astrophysical background with amplitude Omega(GW) (f = 25 Hz) = 1.8(-1.3)(+2.7) x 10(-9) with 90% confidence, compared with Omega(GW) (f = 25 Hz) = 1.1(-0.7)(+1.2) x 10(-9) from binary black holes alone. Assuming the most probable rate for compact binary mergers, we find that the total background may be detectable with a signal-to-noise-ratio of 3 after 40 months of total observation time, based on the expected timeline for Advanced LIGO and Virgo to reach their design sensitivity

Search for Tensor Vector and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T\u3c5.58×10-8, Ω0V\u3c6.35×10-8, and Ω0S\u3c1.08×10-7 at a reference frequency f0=25 Hz

GW170817: Implications for the Stochastic Gravitational-Wave Background from Compact Binary Coalescences

The LIGO Scientific and Virgo Collaborations have announced the event GW170817, the first detection of gravitational waves from the coalescence of two neutron stars. The merger rate of binary neutron stars estimated from this event suggests that distant, unresolvable binary neutron stars create a significant astrophysical stochastic gravitational-wave background. The binary neutron star component will add to the contribution from binary black holes, increasing the amplitude of the total astrophysical background relative to previous expectations. In the Advanced LIGO-Virgo frequency band most sensitive to stochastic backgrounds (near 25 Hz), we predict a total astrophysical background with amplitude ΩGW(f=25 Hz)=1.8-1.3+2.7×10-9 with 90% confidence, compared with ΩGW(f=25 Hz)=1.1-0.7+1.2×10-9 from binary black holes alone. Assuming the most probable rate for compact binary mergers, we find that the total background may be detectable with a signal-to-noise-ratio of 3 after 40 months of total observation time, based on the expected timeline for Advanced LIGO and Virgo to reach their design sensitivity

GW170608: Observation of a 19 Solar-mass Binary Black Hole Coalescence

On 2017 June 8 at 02:01:16.49 UTC, a gravitational-wave (GW) signal from the merger of two stellar-mass blackholes was observed by the two Advanced Laser Interferometer Gravitational-Wave Observatory detectors with anetwork signal-to-noise ratio of 13. This system is the lightest black hole binary so far observed, with componentmasses of 12+7-2M⊙7+2-2 (90% credible intervals). These lie in the range of measured black hole masses inlow-mass X-ray binaries, thus allowing us to compare black holes detected through GWs with electromagneticobservations. The source\u27s luminosity distance is 340+140-140corresponding to redshift -0.07+0.03003. We verify thatthe signal waveform is consistent with the predictions of general relativity

Search for Intermediate Mass Black Hole Binaries in the First Observing Run of Advanced LIGO

During their first observational run, the two Advanced LIGO detectors attained an unprecedented sensitivity, resulting in the first direct detections of gravitational-wave signals produced by stellar-mass binary black hole systems. This paper reports on an all-sky search for gravitational waves (GWs) from merging intermediate mass black hole binaries (IMBHBs). The combined results from two independent search techniques were used in this study: the first employs a matched-filter algorithm that uses a bank of filters covering the GW signal parameter space, while the second is a generic search for GW transients (bursts). No GWs from IMBHBs were detected; therefore, we constrain the rate of several classes of IMBHB mergers. The most stringent limit is obtained for black holes of individual mass 100 M, with spins aligned with the binary orbital angular momentum. For such systems, the merger rate is constrained to be less than 0.93 Gpc-3 yr-1 in comoving units at the 90% confidence level, an improvement of nearly 2 orders of magnitude over previous upper limits