Hepatitis C virus vaccine: Challenges and prospects

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. The hepatitis C virus (HCV) causes both acute and chronic infection and continues to be a global problem despite advances in antiviral therapeutics. Current treatments fail to prevent reinfection and remain expensive, limiting their use to developed countries, and the asymptomatic nature of acute infection can result in individuals not receiving treatment and unknowingly spreading HCV. A prophylactic vaccine is therefore needed to control this virus. Thirty years since the discovery of HCV, there have been major gains in understanding the molecular biology and elucidating the immunological mechanisms that underpin spontaneous viral clearance, aiding rational vaccine design. This review discusses the challenges facing HCV vaccine design and the most recent and promising candidates being investigated

Redistribution of Nickel Ions Embedded within Indium Phosphide Via Low Energy Dual Ion Implantations

Transition-metal doped Indium Phosphide (InP) has been studied over several decades for utilization in optoelectronics applications. Recently, interesting magnetic properties have been reported for metal clusters formed at different depths surrounded by a high quality InP lattice. In this work, we have reported accumulation of Ni atoms at various depths in InP via implantation of Ni- followed by H– and subsequently thermal annealing. Prior to the ion implantations, the ion implant depth profile was simulated using an ion-solid interaction code SDTrimSP, incorporating dynamic changes in the target matrix during ion implantation. Initially, 50 keV Ni- ions are implanted with a fluence of 2 × 1015 atoms cm-2, with a simulated peak deposition profile approximately 42 nm from the surface. 50 keV H- ions are then implanted with a fluence of 1.5 × 1016 atoms cm-2. The simulation result indicates that the H- creates damages with a peak defect center ~400 nm below the sample surface. The sample has been annealed at 50°C in an Ar rich environment for approximately 1hr. During the annealing, H vacates the lattice, and the formed nano-cavities act as trapping sites and a gettering effect for Ni diffusion into the substrate. The distribution of Ni atoms in InP samples are estimated by utilizing Rutherford Backscattering Spectrometry and X-ray Photoelectron Spectroscopy based depth profiling while sputtering the sample with Ar-ion beams. In the sample annealed after H implantation, the Ni was found to migrate to deeper depths of 125 nm than the initial end of range of 70 nm

The PyCBC search for gravitational waves from compact binary coalescence

We describe the PyCBC search for gravitational waves from compact-object binary coalescences in advanced gravitational-wave detector data. The search was used in the first Advanced LIGO observing run and unambiguously identified two black hole binary mergers, GW150914 and GW151226. At its core, the PyCBC search performs a matched-filter search for binary merger signals using a bank of gravitational-wave template waveforms. We provide a complete description of the search pipeline including the steps used to mitigate the effects of noise transients in the data, identify candidate events and measure their statistical significance. The analysis is able to measure false-alarm rates as low as one per million years, required for confident detection of signals. Using data from initial LIGO's sixth science run, we show that the new analysis reduces the background noise in the search, giving a 30% increase in sensitive volume for binary neutron star systems over previous searches.Comment: 29 pages, 7 figures, accepted by Classical and Quantum Gravit

Evaluation of the relative potential for contact and doffing transmission of SARS-CoV-2 by a range of personal protective equipment materials

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—the causative agent of coronavirus disease 2019 (COVID-19)—has caused a global public health emergency. Personal protective equipment (PPE) is the primary defence against viral exposure in healthcare and community settings. However, the surfaces of PPE materials may trap virus for contact transmission or through laden aerosols generated during removal of PPE, through cleaning or during movement. In this study, the relative efficacy of current PPE materials in terms of virion adsorption to materials and their antiviral potency, has been evaluated on a wide range of PPE for the first time, including four polymer glove types, two types of scrubs, apron material, a mask, visor and a selection of other commercial polymers and products. Although differences in virion adsorption to the test materials were observed, none of the existing polymer-based PPE resulted in more than tenfold reduction in the SARS-CoV-2 titre within either 10min or 30min contact period. The wettability and surface chemistry of the test materials were analysed to investigate any correlations with their surface physicochemical properties. While no correlation was found between wettability and viral retention under air flow challenge, one secondary ion of m/z 101.03 (+) and three secondary ions of m/z 31.98 (−), 196.93 (−) and 394.33 (+) in ToF–SIMS data of the test materials showed positive and negative correlations with the viral retention, respectively, which was identified by PLS regression model, suggesting that the surface chemistry plays a role in determining the extent of virion adsorption. Our findings outline the material aspects that influence the efficacy of current PPE against SARS-CoV-2 transmission and give suggestions on the development of novel simple polymer-based PPE for better infection protection

A JWST NIRSpec Phase Curve for WASP-121b: Dayside Emission Strongest Eastward of the Substellar Point and Nightside Conditions Conducive to Cloud Formation

We present the first exoplanet phase curve measurement made with the JWST NIRSpec instrument, highlighting the exceptional stability of this newly-commissioned observatory for exoplanet climate studies. The target, WASP-121b, is an ultrahot Jupiter with an orbital period of 30.6 hr. We analyze two broadband light curves generated for the NRS1 and NRS2 detectors, covering wavelength ranges of 2.70-3.72 micron and 3.82-5.15 micron, respectively. Both light curves exhibit minimal systematics, with approximately linear drifts in the baseline flux level of 30 ppm/hr (NRS1) and 10 ppm/hr (NRS2). Assuming a simple brightness map for the planet described by a low-order spherical harmonic dipole, our light curve fits suggest that the phase curve peaks coincide with orbital phases $3.36 \pm 0.11$ deg (NRS1) and $2.66 \pm 0.12$ deg (NRS2) prior to mid-eclipse. This is consistent with the strongest dayside emission emanating from eastward of the substellar point. We measure planet-to-star emission ratios of $3,924 \pm 7$ ppm (NRS1) and $4,924 \pm 9$ ppm (NRS2) for the dayside hemisphere, and $136 \pm 8$ ppm (NRS1) and $630 \pm 10$ ppm (NRS2) for the nightside hemisphere. The latter nightside emission ratios translate to planetary brightness temperatures of $926 \pm 12$ K (NRS1) and $1,122 \pm 10$ K (NRS2), which are low enough for a wide range of refractory condensates to form, including enstatite and forsterite. A nightside cloud deck may be blocking emission from deeper, hotter layers of the atmosphere, potentially helping to explain why cloud-free 3D general circulation model simulations systematically over-predict the nightside emission for WASP-121b.Comment: Accepted for publication in Astrophysical Journal Letters on December 29, 202

A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C

Rabies, caused by RNA viruses in the Genus Lyssavirus, is the most fatal of all infectious diseases. This neglected zoonosis remains a major public health problem in developing countries, causing the death of an estimated 25,000-159,000 people each year, with more than half of them in children. The high incidence of human rabies in spite of effective vaccines is mainly linked to the lack of compliance with the complicated administration schedule, inadequacies of the community public health system for local administration by the parenteral route and the overall costs of the vaccine. The goal of our work was the development of a simple, affordable and effective vaccine strategy to prevent human rabies virus infection. This next generation vaccine is based on a replication-defective chimpanzee adenovirus vector belonging to group C, ChAd155-RG, which encodes the rabies glycoprotein (G). We demonstrate here that a single dose of this vaccine induces protective efficacy in a murine model of rabies challenge and elicits strong and durable neutralizing antibody responses in vaccinated non-human primates. Importantly, we demonstrate that one dose of a commercial rabies vaccine effectively boosts the neutralizing antibody responses induced by ChAd155-RG in vaccinated monkeys, showing the compatibility of the novel vectored vaccine with the current post-exposure prophylaxis in the event of rabies virus exposure. Finally, we demonstrate that antibodies induced by ChAd155-RG can also neutralize European bat lyssaviruses 1 and 2 (EBLV-1 and EBLV-2) found in bat reservoirs

Rethinking Equality in the Global Society

The future of affirmative action, especially in the area of American higher education, has been called into question by the 1996 decision of the U.S. Court of Appeals for the Fifth Circuit in Hopwood v. State of Texas, requiring race-blind admission to state universities in Texas, and the passage of Proposition 209 in California. The seemingly endless American debate on this issue almost entirely has ignored the fact that other countries faced with comparable problems of remedying the effects of past discrimination have developed programs and acquired experience from which Americans might learn. Further, the legal debate has not been adequately informed by the social science disciplines. This conference was intended to expand discussion at a critical moment by introducing these missing perspectives

KELT-25 b and KELT-26 b: A Hot Jupiter and a Substellar Companion Transiting Young A Stars Observed by TESS

We present the discoveries of KELT-25 b (TIC 65412605, TOI-626.01) and KELT-26 b (TIC 160708862, TOI-1337.01), two transiting companions orbiting relatively bright, early A stars. The transit signals were initially detected by the KELT survey and subsequently confirmed by Transiting Exoplanet Survey Satellite (TESS) photometry. KELT-25 b is on a 4.40 day orbit around the V = 9.66 star CD-24 5016 (Teff=8280-180+440 K, M ∗ = 2.18-0.11+0.12 M o˙), while KELT-26 b is on a 3.34 day orbit around the V = 9.95 star HD 134004 (Teff = 8640-240+500 K, M ∗ = 1.93-0.16+0.14 M o˙), which is likely an Am star. We have confirmed the substellar nature of both companions through detailed characterization of each system using ground-based and TESS photometry, radial velocity measurements, Doppler tomography, and high-resolution imaging. For KELT-25, we determine a companion radius of R P = 1.64-0.043+0.039 R J and a 3σ upper limit on the companion\u27s mass of ∼64 M J. For KELT-26 b, we infer a planetary mass and radius of M P = 1.41-0.51+0.43MJ and R P = 1.94-0.058+0.060 R J. From Doppler tomographic observations, we find KELT-26 b to reside in a highly misaligned orbit. This conclusion is weakly corroborated by a subtle asymmetry in the transit light curve from the TESS data. KELT-25 b appears to be in a well-aligned, prograde orbit, and the system is likely a member of the cluster Theia 449

Staphylococcus aureus α-Hemolysin Mediates Virulence in a Murine Model of Severe Pneumonia Through Activation of the NLRP3 Inflammasome

Staphylococcus aureus is a dangerous pathogen that can cause necrotizing infections characterized by massive inflammatory responses and tissue destruction. Staphylococcal α-hemolysin is an essential virulence factor in severe S. aureus pneumonia. It activates the nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 (NLRP3) inflammasome to induce production of interleukin-1β and programmed necrotic cell death. We sought to determine the role of α-hemolysin–mediated activation of NLRP3 in the pathogenesis of S. aureus pneumonia. We show that α-hemolysin activates the NLRP3 inflammasome during S. aureus pneumonia, inducing necrotic pulmonary injury. Moreover, Nlrp3−/− mice have less-severe pneumonia. Pulmonary injury induced by isolated α-hemolysin or live S. aureus is independent of interleukin-1β signaling, implicating NLRP3-induced necrosis in the pathogenesis of severe infection. This work demonstrates the exploitation of host inflammatory signaling by S. aureus and suggests the NLRP3 inflammasome as a potential target for pharmacologic interventions in severe S. aureus infections