A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated ...polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest.
Abstract
We present Atacama Large Millimeter/sub-millimeter Array Cycle-2 observations of the HBC 494 molecular outflow and envelope. HBC 494 is an FU Ori-like object embedded in the Orion A cloud ...and is associated with the reflection nebulae Re50 and Re50N. We use 12CO, 13CO and C18O spectral line data to independently describe the outflow and envelope structures associated with HBC 494. The moment-1 map of the 12CO emission shows the widest outflow cavities in a Class I object known to date (opening angle ∼150°). The morphology of the wide outflow is likely to be due to the interaction between winds originating in the inner disc and the surrounding envelope. The low-velocity blueshifted and redshifted 13CO and C18O emission trace the rotation and infall motion of the circumstellar envelope. Using molecular line data and adopting standard methods for correcting optical depth effects, we estimate its kinematic properties, including an outflow mass of the order of 10−1 M⊙. Considering the large estimated outflow mass for HBC 494, our results support recent theoretical work suggesting that wind-driven processes might dominate the evolution of protoplanetary discs via energetic outflows.
ABSTRACT We present key results from the Herschel Orion Protostar Survey: spectral energy distributions (SEDs) and model fits of 330 young stellar objects, predominantly protostars, in the Orion ...molecular clouds. This is the largest sample of protostars studied in a single, nearby star formation complex. With near-infrared photometry from 2MASS, mid- and far-infrared data from Spitzer and Herschel, and submillimeter photometry from APEX, our SEDs cover 1.2-870 m and sample the peak of the protostellar envelope emission at ∼100 m. Using mid-IR spectral indices and bolometric temperatures, we classify our sample into 92 Class 0 protostars, 125 Class I protostars, 102 flat-spectrum sources, and 11 Class II pre-main-sequence stars. We implement a simple protostellar model (including a disk in an infalling envelope with outflow cavities) to generate a grid of 30,400 model SEDs and use it to determine the best-fit model parameters for each protostar. We argue that far-IR data are essential for accurate constraints on protostellar envelope properties. We find that most protostars, and in particular the flat-spectrum sources, are well fit. The median envelope density and median inclination angle decrease from Class 0 to Class I to flat-spectrum protostars, despite the broad range in best-fit parameters in each of the three categories. We also discuss degeneracies in our model parameters. Our results confirm that the different protostellar classes generally correspond to an evolutionary sequence with a decreasing envelope infall rate, but the inclination angle also plays a role in the appearance, and thus interpretation, of the SEDs.
We present a far-IR survey of the entire Mon R2 giant molecular cloud (GMC) with Herschel-Spectral and Photometric Imaging REceiver cross-calibrated with Planck-High Frequency Instrument data. We fit ...the spectral energy distributions of each pixel with a greybody function and an optimal beta value of 1.8. We find that mid-range column densities obtained from far-IR dust emission and near-IR extinction are consistent. For the entire GMC, we find that the column density histogram, or column density probability distribution function (N-PDF), is lognormal below ~10 super( 21) cm super( -2). Above this value, the distribution takes a power law form with an index of -2.15. We analyse the gas geometry, N-PDF shape, and young stellar object (YSO) content of a selection of subregions in the cloud. We find no regions with pure lognormal N-PDFs. The regions with a combination of lognormal and one power-law N-PDF have a YSO cluster and a corresponding centrally concentrated gas clump. The regions with a combination of lognormal and two power-law N-PDF have significant numbers of typically younger YSOs but no prominent YSO cluster. These regions are composed of an aggregate of closely spaced gas filaments with no concentrated dense gas clump. We find that for our fixed scale regions, the YSO count roughly correlates with the N-PDF power-law index. The correlation appears steeper for single power-law regions relative to two power-law regions with a high column density cut-off, as a greater dense gas mass fraction is achieved in the former. A stronger correlation is found between embedded YSO count and the dense gas mass among our regions.
Patients with coronavirus disease (COVID-19) are described as exhibiting oxygen levels incompatible with life without dyspnea. The pairing-dubbed happy hypoxia but more precisely termed silent ...hypoxemia-is especially bewildering to physicians and is considered as defying basic biology. This combination has attracted extensive coverage in media but has not been discussed in medical journals. It is possible that coronavirus has an idiosyncratic action on receptors involved in chemosensitivity to oxygen, but well-established pathophysiological mechanisms can account for most, if not all, cases of silent hypoxemia. These mechanisms include the way dyspnea and the respiratory centers respond to low levels of oxygen, the way the prevailing carbon dioxide tension (Pa
) blunts the brain's response to hypoxia, effects of disease and age on control of breathing, inaccuracy of pulse oximetry at low oxygen saturations, and temperature-induced shifts in the oxygen dissociation curve. Without knowledge of these mechanisms, physicians caring for patients with hypoxemia free of dyspnea are operating in the dark, placing vulnerable patients with COVID-19 at considerable risk. In conclusion, features of COVID-19 that physicians find baffling become less strange when viewed in light of long-established principles of respiratory physiology; an understanding of these mechanisms will enhance patient care if the much-anticipated second wave emerges.
With advances in exfoliation and synthetic techniques, atomically thin films of semiconducting transition metal dichalcogenides have recently been isolated and characterized. Their two-dimensional ...structure, coupled with a direct band gap in the visible portion of the electromagnetic spectrum, suggests suitability for digital electronics and optoelectronics. Toward that end, several classes of high-performance devices have been reported along with significant progress in understanding their physical properties. Here, we present a review of the architecture, operating principles, and physics of electronic and optoelectronic devices based on ultrathin transition metal dichalcogenide semiconductors. By critically assessing and comparing the performance of these devices with competing technologies, the merits and shortcomings of this emerging class of electronic materials are identified, thereby providing a roadmap for future development.
Binary and multiple star systems are a frequent outcome of the star formation process and as a result almost half of all stars with masses similar to that of the Sun have at least one companion star. ...Theoretical studies indicate that there are two main pathways that can operate concurrently to form binary/multiple star systems: large-scale fragmentation of turbulent gas cores and filaments or smaller-scale fragmentation of a massive protostellar disk due to gravitational instability. Observational evidence for turbulent fragmentation on scales of more than 1,000 astronomical units has recently emerged. Previous evidence for disk fragmentation was limited to inferences based on the separations of more-evolved pre-main sequence and protostellar multiple systems. The triple protostar system L1448 IRS3B is an ideal system with which to search for evidence of disk fragmentation as it is in an early phase of the star formation process, it is likely to be less than 150,000 years old and all of the protostars in the system are separated by less than 200 astronomical units. Here we report observations of dust and molecular gas emission that reveal a disk with a spiral structure surrounding the three protostars. Two protostars near the centre of the disk are separated by 61 astronomical units and a tertiary protostar is coincident with a spiral arm in the outer disk at a separation of 183 astronomical units. The inferred mass of the central pair of protostellar objects is approximately one solar mass, while the disk surrounding the three protostars has a total mass of around 0.30 solar masses. The tertiary protostar itself has a minimum mass of about 0.085 solar masses. We demonstrate that the disk around L1448 IRS3B appears susceptible to disk fragmentation at radii between 150 and 320 astronomical units, overlapping with the location of the tertiary protostar. This is consistent with models for a protostellar disk that has recently undergone gravitational instability, spawning one or two companion stars.
ABSTRACT We present a multiplicity study of all known protostars (94) in the Perseus molecular cloud from a Karl G. Jansky Very Large Array survey at Ka-band (8 mm and 1 cm) and C-band (4 and 6.6 ...cm). The observed sample has a bolometric luminosity range between 0.1 L and ∼33 L , with a median of 0.7 L . This multiplicity study is based on the Ka-band data, having a best resolution of ∼0 065 (15 au) and separations out to ∼43″ (10,000 au) can be probed. The overall multiplicity fraction (MF) is found to be 0.40 0.06 and the companion star fraction (CSF) is 0.71 0.06. The MF and CSF of the Class 0 protostars are 0.57 0.09 and 1.2 0.2, and the MF and CSF of Class I protostars are both 0.23 0.08. The distribution of companion separations appears bi-modal, with a peak at ∼75 au and another peak at ∼3000 au. Turbulent fragmentation is likely the dominant mechanism on >1000 au scales and disk fragmentation is likely to be the dominant mechanism on <200 au scales. Toward three Class 0 sources we find companions separated by <30 au. These systems have the smallest separations of currently known Class 0 protostellar binary systems. Moreover, these close systems are embedded within larger (50-400 au) structures and may be candidates for ongoing disk fragmentation.
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