ABSTRACT
Numerical models of gas inflow towards a supermassive black hole (SMBH) show that star formation may occur in such an environment through the growth of a gravitationally unstable gas disc. ...We consider the effect of nuclear activity on such a scenario. We present the first three-dimensional grid-based radiative hydrodynamic simulations of direct collisions between infalling gas streams and a 4 × 106 M⊙ SMBH, using ray-tracing to incorporate radiation consistent with an active galactic nucleus (AGN). We assume inflow masses of ≈105 M⊙ and explore radiation fields of 10 per cent and 100 per cent of the Eddington luminosity (Ledd). We follow our models to the point of central gas disc formation preceding star formation and use the Toomre Q parameter (QT) to test for gravitational instability. We find that radiation pressure from UV photons inhibits inflow. Yet, for weak radiation fields, a central disc forms on time-scales similar to that of models without feedback. Average densities of >108 cm−3 limit photoheating to the disc surface allowing for QT ≈ 1. For strong radiation fields, the disc forms more gradually resulting in lower surface densities and larger QT values. Mass accretion rates in our models are consistent with 1–60 per cent of the Eddington limit, thus we conclude that it is unlikely that radiative feedback from AGN activity would inhibit circumnuclear star formation arising from a massive inflow event.
The presence of short-lived radioisotopes (SLRs) in Solar system meteorites has been interpreted as evidence that the Solar system was exposed to a supernova shortly before or during its formation. ...Yet results from hydrodynamical models of SLR injection into the proto-solar cloud or disc suggest that gas-phase mixing may not be efficient enough to reproduce the observed abundances. As an alternative, we explore the injection of SLRs via dust grains as a way to overcome the mixing barrier. We numerically model the interaction of a supernova remnant containing SLR-rich dust grains with a nearby molecular cloud. The dust grains are subject to drag forces and both thermal and non-thermal sputtering. We confirm that the expanding gas shell stalls upon impact with the dense cloud and that gas-phase SLR injection occurs slowly due to hydrodynamical instabilities at the cloud surface. In contrast, dust grains of sufficient size ( ≳ 1 μm) decouple from the gas and penetrate into the cloud within 0.1 Myr. Once inside the cloud, the dust grains are destroyed by sputtering, releasing SLRs and rapidly enriching the dense (potentially star-forming) regions. Our results suggest that SLR transport on dust grains is a viable mechanism to explain SLR enrichment.
Unresolved anisotropies of the cosmic near-infrared background radiation are expected to have contributions from the earliest galaxies during the epoch of reionization and from faint, dwarf galaxies ...at intermediate redshifts. Previous measurements were unable to pinpoint conclusively the dominant origin because they did not sample spatial scales that were sufficiently large to distinguish between these two possibilities. Here we report a measurement of the anisotropy power spectrum from subarcminute to one-degree angular scales, and find the clustering amplitude to be larger than predicted by the models based on the two existing explanations. As the shot-noise level of the power spectrum is consistent with that expected from faint galaxies, a new source population on the sky is not necessary to explain the observations. However, a physical mechanism that increases the clustering amplitude is needed. Motivated by recent results related to the extended stellar light profile in dark-matter haloes, we consider the possibility that the fluctuations originate from intrahalo stars of all galaxies. We find that the measured power spectrum can be explained by an intrahalo light fraction of 0.07 to 0.2 per cent relative to the total luminosity in dark-matter haloes of 10(9) to 10(12) solar masses at redshifts of about 1 to 4.
In recent years, the emergence of several highly pathogenic zoonotic diseases in humans has led to a renewed emphasis on the interconnectedness of human, animal, and environmental health, otherwise ...known as One Health. For example, Hendra virus (HeV), a zoonotic paramyxovirus, was discovered in 1994, and since then, infections have occurred in 7 humans, each of whom had a strong epidemiologic link to similarly affected horses. As a consequence of these outbreaks, eradication of bat populations was discussed, despite their crucial environmental roles in pollination and reduction of the insect population. We describe the development and evaluation of a vaccine for horses with the potential for breaking the chain of HeV transmission from bats to horses to humans, thereby protecting horse, human, and environmental health. The HeV vaccine for horses is a key example of a One Health approach to the control of human disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Dry Valleys of Antarctica are one of the coldest and driest environments on Earth with paleosols in selected areas that date to the emplacement of tills by warm-based ice during the Early ...Miocene. Cited as an analogue to the martian surface, the ability of the Antarctic environment to support microbial life-forms is a matter of special interest, particularly with the upcoming NASA/ESA 2018 ExoMars mission. Lipid biomarkers were extracted and analyzed by gas chromatography--mass spectrometry to assess sources of organic carbon and evaluate the contribution of microbial species to the organic matter of the paleosols. Paleosol samples from the ice-free Dry Valleys were also subsampled and cultivated in a growth medium from which DNA was extracted with the explicit purpose of the positive identification of bacteria. Several species of bacteria were grown in solution and the genus identified. A similar match of the data to sequenced DNA showed that Alphaproteobacteria, Gammaproteobacteria, Bacteriodetes, and Actinobacteridae species were cultivated. The results confirm the presence of bacteria within some paleosols, but no assumptions have been made with regard to in situ activity at present. These results underscore the need not only to further investigate Dry Valley cryosols but also to develop reconnaissance strategies to determine whether such likely Earth-like environments on the Red Planet also contain life.
BACKGROUND: Hendra virus (HeV) is an Australian bat-borne zoonotic paramyxovirus that repeatedly spills-over to horses causing fatal disease. Human cases have all been associated with close contact ...with infected horses. METHODS: A full-length antigenome clone of HeV was assembled, a reporter gene (GFP or luciferase) inserted between the P and M genes and transfected to 293T cells to generate infectious reporter gene-encoding recombinant viruses. These viruses were then assessed in vitro for expression of the reporter genes. The GFP expressing recombinant HeV was used to challenge ferrets to assess the virulence and tissue distribution by monitoring GFP expression in infected cells. RESULTS: Three recombinant HeV constructs were successfully cloned and rescued; a wild-type virus, a GFP-expressing virus and a firefly luciferase-expressing virus. In vitro characterisation demonstrated expression of the reporter genes, with levels proportional to the initial inoculum levels. Challenge of ferrets with the GFP virus demonstrated maintenance of the fatal phenotype with disease progressing to death consistent with that observed previously with the parental wild-type isolate of HeV. GFP expression could be observed in infected tissues collected from animals at euthanasia. CONCLUSIONS: Here, we report on the first successful rescue of recombinant HeV, including wild-type virus and viruses expressing two different reporter genes encoded as an additional gene cassette inserted between the P and M genes. We further demonstrate that the GFP virus retained the ability to cause fatal disease in a well-characterized ferret model of henipavirus infection despite the genome being an extra 1290 nucleotides in length.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Family influences on the use of e-cigarettes Fite, Paula J.; Cushing, Christopher C.; Poquiz, Jonathan ...
Journal of substance use,
07/2018, Letnik:
23, Številka:
4
Journal Article
Numerical models of gas inflow towards a supermassive black hole (SMBH) show that star formation may occur in such an environment through the growth of a gravitationally unstable gas disc. We ...consider the effect of nuclear activity on such a scenario. We present the first three-dimensional grid-based radiative hydrodynamic simulations of direct collisions between infalling gas streams and a \(4 \times 10^6~\text{M}_\odot\) SMBH, using ray-tracing to incorporate radiation consistent with an active galactic nucleus (AGN). We assume inflow masses of \( \approx 10^5~\text{M}_\odot\) and explore radiation fields of 10% and 100% of the Eddington luminosity (\(L_\text{edd}\)). We follow our models to the point of central gas disc formation preceding star formation and use the Toomre Q parameter (\(Q_T\)) to test for gravitational instability. We find that radiation pressure from UV photons inhibits inflow. Yet, for weak radiation fields, a central disc forms on timescales similar to that of models without feedback. Average densities of \(> 10^{8}~\text{cm}^{-3}\) limit photo-heating to the disc surface allowing for \(Q_T\approx1\). For strong radiation fields, the disc forms more gradually resulting in lower surface densities and larger \(Q_T\) values. Mass accretion rates in our models are consistent with 1%--60% of the Eddington limit, thus we conclude that it is unlikely that radiative feedback from AGN activity would inhibit circumnuclear star formation arising from a massive inflow event.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia. Care delivery for HHT patients is impeded by the need for laborious, repeated phenotyping and gaps in ...knowledge regarding the relationships between causal DNA variants in ENG, ACVRL1, SMAD4 and GDF2, and clinical manifestations. To address this, we analyzed DNA samples from 183 previously uncharacterized, unrelated HHT and suspected HHT cases using the ThromboGenomics high-throughput sequencing platform. We identified 127 rare variants across 168 heterozygous genotypes. Applying modified American College of Medical Genetics and Genomics Guidelines, 106 variants were classified as pathogenic/likely pathogenic and 21 as nonpathogenic (variant of uncertain significance/benign). Unlike the protein products of ACVRL1 and SMAD4, the extracellular ENG amino acids are not strongly conserved. Our inferences of the functional consequences of causal variants in ENG were therefore informed by the crystal structure of endoglin. We then compared the accuracy of predictions of the causal gene blinded to the genetic data using 2 approaches: subjective clinical predictions and statistical predictions based on 8 Human Phenotype Ontology terms. Both approaches had some predictive power, but they were insufficiently accurate to be used clinically, without genetic testing. The distributions of red cell indices differed by causal gene but not sufficiently for clinical use in isolation from genetic data. We conclude that parallel sequencing of the 4 known HHT genes, multidisciplinary team review of variant calls in the context of detailed clinical information, and statistical and structural modeling improve the prognostication and treatment of HHT.
•HHT genotypes are clinically relevant but poorly predicted even by analysis of extensive physical and hematological phenotypic data.•High-throughput DNA sequencing, detailed phenotyping, and statistical and structural modeling contribute to a framework to better prognosticate and treat HHT.
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Macrophages play critical, but opposite, roles in acute and chronic inflammation and cancer. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T ...cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors. Here we show that macrophage PI 3-kinase γ controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3Kγ signalling through Akt and mTor inhibits NFκB activation while stimulating C/EBPβ activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3Kγ stimulates and prolongs NFκB activation and inhibits C/EBPβ activation, thus promoting an immunostimulatory transcriptional program that restores CD8
T cell activation and cytotoxicity. PI3Kγ synergizes with checkpoint inhibitor therapy to promote tumour regression and increased survival in mouse models of cancer. In addition, PI3Kγ-directed, anti-inflammatory gene expression can predict survival probability in cancer patients. Our work thus demonstrates that therapeutic targeting of intracellular signalling pathways that regulate the switch between macrophage polarization states can control immune suppression in cancer and other disorders.
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