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ABSTRACT IMPACT: We hope to provide a more nuanced understanding of the type-III IFN system, thereby exploring its therapeutic potential in the realm of infectious diseases. OBJECTIVES/GOALS: The role of IFNLR1 receptor dynamics and plasticity in regulating the type-III IFN response is largely unknown. As a specific, powerful component of innate immunity, understanding how the type-III IFN system is regulated could lead to the development of novel therapeutic targets and strategies to face a multitude of viral illnesses. METHODS/STUDY POPULATION: To facilitate our investigation, we will generate doxycycline-inducible FLAG-tagged IFNLR1-expression plasmids representing all known transcriptional variants. These plasmids will allow us to: 1) Evaluate the effect of IFNLR1 surface abundance on the type-III IFN transcriptional profile and 2) Assess the extent of IFNLR1-FLAG co-localization with several notable intracellular structures using immunofluorescence, before and after stimulation with IFNL3. RESULTS/ANTICIPATED RESULTS: We have successfully generated three IFNLR1-FLAG transcriptional variants and confirmed inducible-expression and function in vitro. We are currently assessing the role of surface abundance, internalization, differential isoform expression, and trafficking. DISCUSSION/SIGNIFICANCE OF FINDINGS: By completing this study, we hope to provide a more nuanced understanding of the type-III IFN system, thereby exploring its therapeutic potential in the realm of infectious diseases.
We have found a class of circular radio objects in the Evolutionary Map of the Universe Pilot Survey, using the Australian Square Kilometre Array Pathfinder telescope. The objects appear in radio images as circular edge-brightened discs, about one arcmin diameter, that are unlike other objects previously reported in the literature. We explore several possible mechanisms that might cause these objects, but none seems to be a compelling explanation.
This study aimed to evaluate surgical and functional outcomes, in a tertiary referral centre, of two different types of semi-implantable transcutaneous bone conduction devices.
This study involved prospective data collection and review of patients implanted between November 2014 and December 2016. Glasgow Hearing Aid Inventory (Glasgow Hearing Aid Benefit Profile or Glasgow Hearing Aid Difference Profile) and Client Oriented Scale of Improvement were completed where appropriate. Surgical and audiological outcomes were recorded in the surgical notes.
Glasgow Hearing Aid Difference Profile and Glasgow Hearing Aid Benefit Profile showed similar mean score in the active and the passive transcutaneous bone conduction devices. Client Oriented Scale of Improvement showed improvements in listening situations. Post-operative speech reception threshold showed better mean threshold in the active transcutaneous bone conduction devices group when compared with the passive transcutaneous bone conduction devices group. No device failures or surgical complications existed in either group, with the surgical time being less in the passive transcutaneous bone conduction devices group.
Both devices are reliable semi-implantable transcutaneous bone conduction devices with excellent surgical and functional outcomes and patient satisfaction. Overall surgical time was much less in the passive transcutaneous bone conduction devices group with no necessity for pre-planning. This is much easier to remove with the possibility of conversion to other devices in the manufacturer’s portfolio and wide-ranging wireless accessories. Further studies are needed to assess the longer-term results in a bigger population.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with
15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination
made over a 288-MHz band centred at 887.5 MHz.
Vaccine effectiveness studies are subject to biases due to depletion-of-persons at risk of infection, or at especially high risk of infection, at different rates from different groups (depletion-of-susceptibles bias), a problem that can also lead to biased estimates of waning effectiveness, including spurious inference of waning when none exists. An alternative study design to identify waning is to study only vaccinated persons, and compare for each day the incidence in persons with earlier or later dates of vaccination to assess waning in vaccine protection as a function of vaccination time (namely whether earlier vaccination would result in lower subsequent protection compared to later vaccination). Prior studies suggested under what conditions this alternative would yield correct estimates of waning. Here we define the depletion-of-susceptibles process formally and show mathematically that for influenza vaccine waning studies, a randomised trial or corresponding observational study that compares incidence at a specific calendar time among individuals vaccinated at different times before the influenza season begins will not be vulnerable to depletion-of-susceptibles bias in its inference of waning as a function of vaccination time under the null hypothesis that none exists, and will – if waning does actually occur – underestimate the extent of waning. Such a design is thus robust in the sense that a finding of waning in that inference framework reflects actual waning of vaccine-induced immunity. We recommend such a design for future studies of waning, whether observational or randomised.
Consumption of sugar-sweetened beverages (SSB) by infants and young children are less explored in Asian populations. The Growing Up in Singapore Towards healthy Outcomes cohort study examined associations between SSB intake at 18 months and 5 years of age, with adiposity measures at 6 years of age. We studied Singaporean infants/children with SSB intake assessed by FFQ at 18 months of age (n 555) and 5 years of age (n 767). The median for SSB intakes is 28 (interquartile range 5·5–98) ml at 18 months of age and 111 (interquartile range 57–198) ml at 5 years of age. Association between SSB intake (100 ml/d increments and tertile categories) and adiposity measures (BMI standard deviation scores (sd units), sum of skinfolds (SSF)) and overweight/obesity status were examined using multivariable linear and Poisson regression models, respectively. After adjusting for confounders and additionally for energy intake, SSB intake at age 18 months were not significantly associated with later adiposity measures and overweight/obesity outcomes. In contrast, at age 5 years, SSB intake when modelled as 100 ml/d increments were associated with higher BMI by 0·09 (95 % CI 0·02, 0·16) sd units, higher SSF thickness by 0·68 (95 % CI 0·06, 1·44) mm and increased risk of overweight/obesity by 1·2 (95 % CI 1·07, 1·23) times at age 6 years. Trends were consistent with SSB intake modelled as categorical tertiles. In summary, SSB intake in young childhood is associated with higher risks of adiposity and overweight/obesity. Public health policies working to reduce SSB consumption need to focus on prevention programmes targeted at young children.
Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons (MIC). We identify participant-centricity and trustworthiness as the most important features of an MIC and discuss the implications for those seeking to create a sustainable, useful, and widely available collection of linked resources for research and other purposes.
Arbuscular mycorrhizal fungi (AMF) can increase plant nutrient uptake and chemical defense production, both of which can improve plants’ ability to resist insect herbivory. Cover crops—non-commercial species planted in between cash crops in a crop rotation—can naturally alter both soil nutrients and AMF. We tested whether different cover crop species alter AMF colonization, plant nutrient status and plant–insect interactions in a subsequent maize crop. Cover crop species were either non-mycorrhizal, non-leguminous (canola, forage radish), mycorrhizal non-leguminous (cereal rye, oats), mycorrhizal leguminous (clover, pea) or absent (fallow). We measured the cascading consequences of cover crop treatment on maize root AMF colonization, maize growth and performance of an herbivorous insect (European corn borer) feeding on the maize. Maize AMF colonization was greater in plots previously planted with mycorrhizal (rye, oats) than non-mycorrhizal (canola, radish) cover crops or no cover crop (fallow). AMF colonization was linked to increased plant phosphorous and nitrogen, and maize growth increased with low plant N:P. Induced jasmonic acid pathway plant defenses increased with increasing maize growth and AMF colonization. European corn borer survivorship decreased with lower plant N:P, and insect development rate decreased with increased induced plant defenses. Our data describe a cascade in which cover crop species selection can increase or decrease mycorrhizal colonization of subsequent maize crop roots, which in turn impacts phosphorus uptake and may affect herbivory resistance in the maize. These results suggest that farmers could select cover crop species to manage nutrient uptake and pest resistance, in order to amend or limit fertilizer and pesticide use.
Herbicide resistance, and in particular multiple-herbicide resistance, poses an ever-increasing threat to food security. A biotype of junglerice [Echinochloa colona (L.) Link] with resistance to four herbicides, imazamox, fenoxaprop-P-ethyl, quinclorac, and propanil, each representing a different mechanism of action, was identified in Sunflower County, MS. Dose responses were performed on the resistant biotype and a biotype sensitive to all four herbicides to determine the level of resistance. Application of a cytochrome P450 inhibitor, malathion, with the herbicides imazamox and quinclorac resulted in increased susceptibility in the resistant biotype. Differential gene expression analysis of resistant and sensitive plants revealed that 170 transcripts were upregulated in resistant plants relative to sensitive plants and 160 transcripts were upregulated in sensitive plants. In addition, 507 transcripts were only expressed in resistant plants and 562 only in sensitive plants. A subset of these transcripts were investigated further using quantitative PCR (qPCR) to compare gene expression in resistant plants with expression in additional sensitive biotypes. The qPCR analysis identified two transcripts, a kinase and a glutathione S-transferase that were significantly upregulated in resistant plants compared with the sensitive plants. A third transcript, encoding an F-box protein, was downregulated in the resistant plants relative to the sensitive plants. As no cytochrome P450s were differentially expressed between the resistant and sensitive plants, a single-nucleotide polymorphism analysis was performed, revealing several nonsynonymous point mutations of interest. These candidate genes will require further study to elucidate the resistance mechanisms present in the resistant biotype.
Postel Nunatak in the Patuxent Range has been previously mapped as Nelson Limestone but there was no biostratigraphic support for that interpretation until now. We confirm that limestone exposures at Postel Nunatak are at least partly correlated with the Nelson Limestone of the Neptune Range, 160 km north-east, and are not correlative with the lower Cambrian Schneider Hills Limestone of the Argentina Range. Upper beds have yielded the trilobites Suludella? davnii Palmer & Gatehouse, 1972 and Solenopleura pruina Palmer & Gatehouse, 1972, which provide a basis for assignment to Cambrian Series 3 (late middle Cambrian), within the Drumian or lower Guzhangian stages. Limestone beds were deposited in a shallow marine setting, ranging from supratidal to lagoonal facies with rare subtidal intervals. These settings contrast with deeper water facies of the Neptune Range. Despite limitations in sampling density, isotopic analysis indicates that a greater than +2.5‰ shift in δ13C is consistent with δ13C trends documented for the Drumian Stage. Because the upper and lower contacts at Postel Nunatak are covered by snow and ice, the relationship with rocks mapped as the Patuxent Formation in the Patuxent Range remains uncertain, but part of it may belong to the Precambrian Hannah Ridge Formation.
This letter describes an innovative spin-coating system, built from off-the-shelf components, that can easily and inexpensively be integrated into any laboratory environment. Combined with a liquid suspension of conductive polymer, such a “rotary coater” enables simple coating of planar samples to create a physical protective barrier on the sample surface. This barrier aids in charge dissipation during scanning electron microscope and focused ion beam (FIB) imaging and provides wide-scale protection of the sample surface from ion bombardment during FIB imaging and gas-assisted deposition. This polymer layer replaces the localized and time-consuming electron beam deposition step typically performed during transmission electron microscopy lamella preparation. After observation, the coating can be easily removed, if desired. The described spin-coating procedure has minimal cost while providing repeatable positive results, without the need for expensive commercial coating instrumentation.
Gamma-ray observations for Supernova remnant (SNR)-molecular cloud (MC) association systems play an important role in the research on the acceleration and propagation of cosmic-ray protons. Through the analysis of 5.6 years of Fermi-Large Area Telescope observation data, here we report on the detection of a gamma-ray emission source near the SNR Kesteven 41 with a significance of 24σ in 0.2–300 GeV. The best-fit location of the gamma-ray source is consistent with the MC with which the SNR interacts. Several hypotheses including both leptonic and hadronic scenarios are considered to investigate the origin of these gamma-rays. The gamma-ray emission can be naturally explained by the decay of neutral pions produced via the collision between high energy protons accelerated by the shock of Kesteven 41 and the adjacent MC. The electron energy budget would be too high for the SNR if the gamma-rays were produced via inverse Compton (IC) scattering off the Cosmic Microwave Background (CMB) photons.
We report detections of thermal X-ray line emission and proper motions in the supernova remnant (SNR) RX J1713.7-3946, the prototype of the small class of synchrotron dominated SNRs. Based on deep XMM-Newton observations, we find clear line features including Ne Lyα, Mg Heα, and Si Heα from the central portion of the remnant. The metal abundance ratios suggest that the thermal emission originates from core-collapse SN ejecta arising from a relatively low-mass (≲20 M⊙) progenitor. In addition, using XMM-Newton observations on a 13 yr time interval, we have measured expansion in the southeastern rim to be ~0.75″ yr−1 or ~3500 km s−1 at a distance of 1 kpc. Given this, we derive an upstream density to be ~0.01 cm−3, compatible with the lack of thermal X-rays from the shocked ambient medium. We also estimate the age of the remnant to be ~1200–1600 yr, roughly consistent with the idea that RX J1713.7-3946 is the remnant of SN 393.
In the framework of the Sardinia Radio Telescope (SRT) Early Science Program, we obtained single-dish high-resolution imaging of the Supernova Remnants IC443 and W44 at 7 GHz. By coupling them with SRT 1.5 GHz maps, we provided spatially-resolved spectral measurements that are highlighting a spread in spectral slope distribution. The observed features range from flat or slightly inverted spectra corresponding to bright radio limbs and filaments, to relatively steep spectra in fainter radio regions. Different theoretical possibilities explaining the above challenging findings are discussed. In particular, we exclude that the observed region-dependent wide spread in spectral slope distribution could be related to absorption processes. Our high-frequency results can be directly related to distinct electron populations in the SNRs including secondary hadronic electrons and resulting from different shocks conditions and/or undergoing different cooling processes. Integrated fluxes associated with the whole SNRs obtained by SRT in comparison with previous results in the literature support the evidence for a slight spectral steepening above 1 GHz for both sources, which could be related to primary electrons or more likely secondary hadronic electrons cut-offs.
In an aspherical supernova explosion, shock emergence is not simultaneous and non-radial flows develop near the stellar surface. Oblique shock breakouts tend to be easily developed in compact progenitors like stripped-envelop core collapse supernovae. According to Matzner et al. (2013), non-spherical explosions develop non-radial flows that alters the observable emission and radiation of a supernova explosion. These flows can limit ejecta speed, change the distribution of matter and heat of the ejecta, suppress the breakout flash, and most importantly engender collisions outside the star. We construct a global numerical FLASH hydrodynamic simulation in a two dimensional spherical coordinate, focusing on the non-relativistic, adiabatic limit in a polytropic envelope to see how these fundamental differences affect the early light curve of core-collapse SNe.
We present single-dish imaging of the well-known Supernova Remnants (SNRs) IC443 and W44 at 1.5 GHz and 7 GHz with the recently commissioned 64-m diameter Sardinia Radio Telescope (SRT). Our images were obtained through on-the-fly mapping techniques, providing antenna beam oversampling, automatic baseline subtraction and radio-frequency interference removal. It results in high-quality maps of the SNRs at 7 GHz, which are usually lacking and not easily achievable through interferometry at this frequency due to the very large SNR structures. SRT continuum maps of our targets are consistent with VLA maps carried out at lower frequencies (at 324 MHz and 1.4 GHz), providing a view of the complex filamentary morphology. New estimates of the total flux density are given within 3% and 5% error at 1.5 GHz and 7 GHz respectively, in addition to flux measurements in different regions of the SNRs.
In their final stages, massive stars can show large eruptions which can resemble core-collapse IIn SNe. Here we present SN 2015bh in NGC 2770, a IIn/impostor, where archival data show variabilities for at least 21 years before the main event in 2015. Serendipitous spectra during an outburst are the only SN progenitor spectra available since SN 1987A and show an LBV with a fast, dense outflow. Analogues to SN 2015bh are SN 2009ip and SNhunt 248 while the SN 2000ch impostor could be equivalent to the outburst phase of SN 2015bh. It is currently unclear whether SN 2015bh (and SN 2009ip) were final core-collapse events. Alternatively, they might be large outbursts shedding the outer envelope and creating a Wolf-Rayet star in only a matter of decades. Future large-scale high-cadence surveys such as LSST will detect many more of these events and allow us a unique insight into the largely unknown late stages of massive stellar evolution.
We investigate the relation between the emission properties of supernova shock breakout in the circumstellar matter (CSM) and the behavior of the shock. Using a Monte-Carlo method, we examine how the light curve and spectrum depends on the asphericity of the shock and bulk-Compton scattering, and compare the results with the observed properties of X-ray outburst (XRO) 080109/SN 2008D. We found that the rise and decay time of the X-ray light curve do not significantly depend on the degree of shock asphericity and the viewing angle in a steady and spherically symmetric CSM. The observed X-light curve and spectrum of XRO 080109 can be reproduced by considering the shock with a radial velocity of 60% of the speed of light, and the wind mass loss rate is about 5 × 10−4M⊙.
We carried out high resolution simulations of weakly-magnetized core-collapse supernovae in two-dimensional axisymmetry in order to see the influence of the magnetic field and rotation on the explosion. We found that the magnetic field amplified by magnetorotational instability (MRI) has a great positive impact on the explosion by enhancing the neutrino heating, provided that the progenitor has large angular momentum close to the highest value found in stellar evolution calculations. We also found that even for progenitors neither involving strong magnetic flux nor large angular momentum, the magnetic field is greatly amplified by the convection aand rotation, and this leads to the boost of the explosion again by enhancing the neutrino heating.