Immunostimulatory Motifs Enhance Antiviral siRNAs Targeting Highly Pathogenic Avian Influenza H5N1

Highly pathogenic avian influenza (HPAI) H5N1 virus is endemic in many regions around the world and remains a significant pandemic threat. To date H5N1 has claimed almost 300 human lives worldwide, with a mortality rate of 60% and has caused the death or culling of hundreds of millions of poultry since its initial outbreak in 1997. We have designed multi-functional RNA interference (RNAi)-based therapeutics targeting H5N1 that degrade viral mRNA via the RNAi pathway while at the same time augmenting the host antiviral response by inducing host type I interferon (IFN) production. Moreover, we have identified two factors critical for maximising the immunostimulatory properties of short interfering (si)RNAs in chicken cells (i) mode of synthesis and (ii) nucleoside sequence to augment the response to virus. The 5-bp nucleoside sequence 5′-UGUGU-3′ is a key determinant in inducing high levels of expression of IFN -α, -β, -λ and interleukin 1- β in chicken cells. Positioning of this 5′-UGUGU-3′ motif at the 5′- end of the sense strand of siRNAs, but not the 3′- end, resulted in a rapid and enhanced induction of type I IFN. An anti-H5N1 avian influenza siRNA directed against the PB1 gene (PB1-2257) tagged with 5′-UGUGU-3′ induced type I IFN earlier and to a greater extent compared to a non-tagged PB1-2257. Tested against H5N1 in vitro, the tagged PB1-2257 was more effective than non-tagged PB1-2257. These data demonstrate the ability of an immunostimulatory motif to improve the performance of an RNAi-based antiviral, a finding that may influence the design of future RNAi-based anti-influenza therapeutics

Evidence for a population of high-redshift submillimeter galaxies from interferometric imaging

We have used the Submillimeter Array to image a flux-limited sample of seven submillimeter galaxies, selected by the AzTEC camera on the JCMT at 1.1 mm, in the COSMOS field at 890 μ m with ~2\u27\u27 resolution. All of the sources—two radio-bright and five radio-dim—are detected as single point sources at high significance (\u3e6 σ), with positions accurate to ~0.2\u27\u27 that enable counterpart identification at other wavelengths observed with similarly high angular resolution. All seven have IRAC counterparts, but only two have secure counterparts in deep HST ACS imaging. As compared to the two radio-bright sources in the sample, and those in previous studies, the five radio-dim sources in the sample (1) have systematically higher submillimeter-to-radio flux ratios, (2) have lower IRAC 3.6-8.0 μ m fluxes, and (3) are not detected at 24 μ m . These properties, combined with size constraints at 890 μ m (θ 1.2\u27\u27), suggest that the radio-dim submillimeter galaxies represent a population of very dusty starbursts, with physical scales similar to local ultraluminous infrared galaxies, with an average redshift higher than radio-bright sources

Global epidemiology of podoconiosis: a systematic review

Background Podoconiosis is one of the few diseases that could potentially be eliminated within one generation. Nonetheless, the global distribution of the disease remains largely unknown. The global atlas of podoconiosis was conceived to define the epidemiology and distribution of podoconiosis through dedicated surveys and assembling the available epidemiological data. Methods We have synthesized the published literature on the epidemiology of podoconiosis. Through systematic searches in SCOPUS and MEDLINE from inception to February 14, 2018, we identified observational and population-based studies reporting podoconiosis. To establish existence of podoconiosis, we used case reports and presence data. For a study to be included in the prevalence synthesis, it needed to be a population-based survey that involved all residents within a specific area. Studies that did not report original data were excluded. We undertook descriptive analyses of the extracted data. This study is registered with PROSPERO, number CRD42018084959. Results We identified 3,260 records, of which 27 studies met the inclusion criteria. Podoconiosis was described to exist or be endemic in 32 countries, 18 from the African Region, 3 from Asia and 11 from Latin America. Overall, podoconiosis prevalence ranged from 0·10% to 8.08%, was highest in the African region, and was substantially higher in adults than in children and adolescents. The highest reported prevalence values were in Africa (8.08% in Cameroon, 7.45% in Ethiopia, 4.52% in Uganda, 3.87% in Kenya and 2.51% in Tanzania). In India, a single prevalence of 0.21% was recorded from Manipur, Mizoram and Rajasthan states. None of the Latin American countries reported prevalence data. Conclusion Our data suggest that podoconiosis is more widespread in the African Region than in the rest of the regions, although this could be related to the fact that most podoconiosis epidemiological research has been focused in the African continent. The assembled dataset confirms that comprehensive podoconiosis control strategies such as promotion of footwear and personal hygiene are urgently needed in endemic parts of Africa. Mapping, active surveillance and a systematic approach to the monitoring of disease burden must accompany the implementation of podoconiosis control activities

Gain through losses in nonlinear optics

Instabilities of uniform states are ubiquitous processes occurring in a variety of spatially extended nonlinear systems. These instabilities are at the heart of symmetry breaking, condensate dynamics, self-organization, pattern formation and noise amplification across diverse disciplines, including physics, chemistry, engineering and biology. In nonlinear optics, modulation instabilities are generally linked to the so-called parametric amplification process, which occurs when certain phase-matching or quasi-phase-matching conditions are satisfied. In the present review article, we summarize the principle results on modulation instabilities and parametric amplification in nonlinear optics, with special emphasis on optical fibres. We then review state-of-the-art research about a peculiar class of modulation instabilities and signal amplification processes induced by dissipation in nonlinear optical systems. Losses applied to certain parts of the spectrum counterintuitively lead to the exponential growth of the damped mode themselves, causing gain through losses. We discuss the concept of imaging of losses into gain, showing how to map a given spectral loss profile into a gain spectrum. We demonstrate with concrete examples that dissipation-induced modulation instability, apart from being of fundamental theoretical interest, may pave the way towards the design of a new class of tuneable fibre-based optical amplifiers, optical parametric oscillators, frequency comb sources and pulsed lasers

Syndromic Autism: progressing beyond current levels of description

Genetic syndrome groups at high risk of autism comorbidity, like Down syndrome and fragile X syndrome, have been presented as useful models for understanding risk and protective factors involved in the emergence of autistic traits. Yet despite reaching clinical thresholds, these ‘syndromic’ forms of autism appear to differ in significant ways from the idiopathic or ‘non-syndromic’ autism profile. We explore alternative mechanistic explanations for these differences and propose a developmental interpretation of syndromic autism that takes into account the character of the genetic disorder. This interpretation anticipates syndrome-specific autism phenotypes, since the neurocognitive and behavioural expression of the autism is coloured by syndromically defined atypicalities. To uncover the true nature of comorbidities and of autism per se, we argue that it is key to extend definitions of autism to include the perceptual and neurocognitive characteristics of the disorder and then apply this multilevel conceptualization to the study of syndromic autism profiles

Measuring the halo mass of z similar to 3 damped Ly alpha absorbers from the absorber-galaxy cross-correlation

We test the reliability of a method to measure the mean halo mass of absorption-line systems such as damped Lyα absorbers (DLAs). The method is based on measuring the ratio of the cross-correlation between DLAs and galaxies to the autocorrelation of the galaxies themselves, which is (in linear theory) the ratio of their bias factor . We show that the ratio of the projected cross- and autocorrelation functions [wdg(rθ)/wgg(rθ)] is also the ratio of their bias factor, irrespective of the galaxy distribution, provided that one uses the same galaxies for wdg(rθ) and wgg(rθ). Thus, the method requires only multiband imaging of DLA fields and is applicable to all redshifts. Here, we focus on z = 3 DLAs. We demonstrate that the method robustly constrains the mean DLA halo mass using smoothed particle hydrodynamics (SPH) cosmological simulations that resolve DLAs and galaxies in halos of mass Mh 5.2 × 1010 M. If we use the bias formalism of Mo & White with the DLA and galaxy mass distributions of these simulations, we predict an amplitude ratio wdg/wgg of 0.771. Direct measurement of these correlation functions from the simulations yields wdg/wgg = DLA/gal = 0.73 ± 0.08, in excellent agreement with that prediction. Equivalently, inverting the measured correlation ratio to infer the (logarithmically) averaged DLA halo mass yields log MDLA(M) = 11.13, in excellent agreement with the true value in the simulations: log MDLA(M) = 11.16 is the probability-weighted mean mass of the DLA host halos in the simulations. The cross-correlation method thus appears to yield a robust estimate of the average host halo mass, even though the DLAs and the galaxies occupy a broad mass spectrum of halos and massive halos contain multiple galaxies with DLAs. If we consider subsets of the simulated galaxies with high star formation rates (representing Lyman break galaxies [LBGs]), then both correlations are higher, but their ratio still implies the same DLA host mass, irrespective of the galaxy subsamples, i.e., the cross-correlation technique is also reliable. The inferred mean DLA halo mass, log MDLA = 11.13, is an upper limit, since the simulations do not resolve halos less massive than ~1010.5 M. Thus, our results imply that the correlation length between DLAs and LBGs is predicted to be at most ~2.85 h-1 Mpc, given that z = 3 LBGs have a correlation length of r0 4 h-1 Mpc. While the small size of current observational samples does not allow strong conclusions, future measurements of this cross-correlation can definitively distinguish models in which many DLAs reside in low-mass halos from those in which DLAs are massive disks occupying only high-mass halos

Speciated PM10 Emission Inventory for Delhi, India

Emission inventories can serve as a basis for air quality management programs. The focus has been mainly on building inventories for criteria pollutants including particulate matter (PM). Control efforts in developing countries are mostly limited to total suspended particles (TSP) and/or PM10. Since the adverse effects of PM10 depend on its chemical composition, it is important to control emissions of toxic species. The first step is to identify key pollution sources and estimate quantities of various chemical species in emissions. This paper presents a speciated PM10 emission inventory for Delhi, the capital and one of the most polluted cities in India. An established PM10 inventory for Delhi in conjunction with source profiles was used to estimate emissions of major PM10 components including organic and elemental carbon (OC and EC, respectively), sulphates (SO42-), and nitrates (NO3-), as well as selected toxic trace metals (i.e., Pb, Ni, V, As, and Hg), some of which are subject to India&#39;s National Ambient Air Quality Standards (NAAQS). For the base year of 2007, emission estimates for PM10 mass, OC, EC, SO42-, and NO3- are 140, 22, 6.4, 2.8, and 2.1 tonnes/day (TPD; 1 tonne = 1000 kg), respectively. Emissions of Pb, Ni, V, As, and Hg are estimated to be 203, 43, 37, 26, and 9.4 kg/day, respectively. This inventory underestimated Pb and Hg emissions because sources of PM10 from unorganized secondary lead smelters are not specifically identified and gas-to-particle conversion of Hg is not accounted for.</p

Spitzer IRAC infrared colours of submillimetre-bright galaxies

High-redshift submillimetre-bright galaxies identified by blank field surveys at millimetre and submillimetre wavelengths appear in the region of the Infra Red Array Camera (IRAC) colour–colour diagrams previously identified as the domain of luminous active galactic nuclei (AGNs). Our analysis using a set of empirical and theoretical dusty starburst spectral energy distribution (SED) models shows that power-law continuum sources associated with hot dust heated by young (≲100 Myr old), extreme starbursts at z \u3e 2 also occupy the same general area as AGNs in the IRAC colour–colour plots. A detailed comparison of the IRAC colours and SEDs demonstrates that the two populations are distinct from each other, with submillimetre-bright galaxies having a systematically flatter IRAC spectrum (≳1 mag bluer in the observed [4.5]–[8.0] colour). Only about 20 per cent of the objects overlap in the colour–colour plots, and this low fraction suggests that submillimetre galaxies powered by a dust-obscured AGN are not common. The red infrared colours of the submillimetre galaxies are distinct from those of the ubiquitous foreground IRAC sources, and we propose a set of infrared colour selection criteria for identifying SMG counterparts that can be used even in the absence of radio or Multiband Imaging Photometer for Spitzer (MIPS) 24 μm data

PM(2.5) source profiles for black and organic carbon emission inventories

Emission inventories for black or elemental (BC or EC) and organic (OC) carbon can be derived by multiplying PM(2.5) emission estimates by mass fractions of these species in representative source profiles. This study examines the variability of source profiles and its effect on EC emission estimates. An examination of available profiles shows that EC and OC ranged from 6-13% and 35-40% for agricultural burning, 4-33% and 22-68% for residential wood combustion, 6-38% and 24-75% for on-road gasoline vehicles, and 33-74% and 20-47% for on-road heavy-duty diesel vehicles, respectively. Source profiles from the U.S. EPA SPECIATE data base were applied to PM(2.5) emissions from the U.S. EPA National Emissions Inventory for 2005. The total estimated EC emissions of 432 Gg yr(-1) was apportioned as 42.5% from biomass burning, 35.4% from non-road mobile sources, 15% from on-road mobile sources, 5.4% from fossil fuel (e.g., coal, oil, and natural gas) combustion in stationary sources, 1% from other stationary industrial sources, and 0.5% from fugitive dust. Considering the variability in available source profiles, BC emission estimates for major sources such as open fires and non-road diesels ranged from 42 to 133 (a factor of 3) and 25 to 100 (a factor of 4) Gg yr(-1), respectively. The choice of source profiles can be a major source of uncertainty in national and global BC/EC emission inventories.</p

AzTEC Millimetre Survey of the COSMOS field - II. Source count overdensity and correlations with large-scale structure

We report an overdensity of bright submillimetre galaxies (SMGs) in the 0.15 deg2 AzTEC/COSMOS survey and a spatial correlation between the SMGs and the optical-IR galaxy density at z≲ 1.1. This portion of the COSMOS field shows a ∼3σ overdensity of robust SMG detections when compared to a background, or ‘blank-field’, population model that is consistent with SMG surveys of fields with no extragalactic bias. The SMG overdensity is most significant in the number of very bright detections (14 sources with measured fluxes S1.1 mm \u3e 6 mJy), which is entirely incompatible with sample variance within our adopted blank-field number densities and infers an overdensity significance of ≫ 4σ. We find that the overdensity and spatial correlation to optical-IR galaxy density are most consistent with lensing of a background SMG population by foreground mass structures along the line of sight, rather than physical association of the SMGs with the z≲ 1.1 galaxies/clusters. The SMG positions are only weakly correlated with weak-lensing maps, suggesting that the dominant sources of correlation are individual galaxies and the more tenuous structures in the survey region, and not the massive and compact clusters. These results highlight the important roles cosmic variance and large-scale structure can play in the study of SMGs