| 1. |
- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Krasilnikov, A., et al.
(författare)
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Evidence of 9 Be + p nuclear reactions during 2ω CH and hydrogen minority ICRH in JET-ILW hydrogen and deuterium plasmas
- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:2
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Tidskriftsartikel (refereegranskat)abstract
- The intensity of 9Be + p nuclear fusion reactions was experimentally studied during second harmonic (2ω CH) ion-cyclotron resonance heating (ICRH) and further analyzed during fundamental hydrogen minority ICRH of JET-ILW hydrogen and deuterium plasmas. In relatively low-density plasmas with a high ICRH power, a population of fast H+ ions was created and measured by neutral particle analyzers. Primary and secondary nuclear reaction products, due to 9Be + p interaction, were observed with fast ion loss detectors, γ-ray spectrometers and neutron flux monitors and spectrometers. The possibility of using 9Be(p, d)2α and 9Be(p, α)6Li nuclear reactions to create a population of fast alpha particles and study their behaviour in non-active stage of ITER operation is discussed in the paper.
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| 3. |
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- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
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Forskningsöversikt (refereegranskat)
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| 24. |
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Overview of the JET results
- 2015
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Tidskriftsartikel (refereegranskat)
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| 25. |
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- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:9
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Tidskriftsartikel (refereegranskat)
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| 26. |
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| 27. |
- Mourikis, TP, et al.
(författare)
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Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3101-
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Tidskriftsartikel (refereegranskat)abstract
- The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.
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| 28. |
- Turkington, RC, et al.
(författare)
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Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:11, s. 1918-1927
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Tidskriftsartikel (refereegranskat)abstract
- Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.DesignTranscriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).ResultsA total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).ConclusionThe DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
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| 29. |
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| 30. |
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| 31. |
- Porth, Oliver, et al.
(författare)
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The Event Horizon General Relativistic Magnetohydrodynamic Code Comparison Project
- 2019
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Ingår i: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 243:2
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Tidskriftsartikel (refereegranskat)abstract
- Recent developments in compact object astrophysics, especially the discovery of merging neutron stars by LIGO, the imaging of the black hole in M87 by the Event Horizon Telescope, and high- precision astrometry of the Galactic Center at close to the event horizon scale by the GRAVITY experiment motivate the development of numerical source models that solve the equations of general relativistic magnetohydrodynamics (GRMHD). Here we compare GRMHD solutions for the evolution of a magnetized accretion flow where turbulence is promoted by the magnetorotational instability from a set of nine GRMHD codes: Athena++, BHAC, Cosmos++, ECHO, H-AMR, iharm3D, HARM-Noble, IllinoisGRMHD, and KORAL. Agreement among the codes improves as resolution increases, as measured by a consistently applied, specially developed set of code performance metrics. We conclude that the community of GRMHD codes is mature, capable, and consistent on these test problems.
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| 32. |
- Akiyama, Kazunori, et al.
(författare)
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First M87 Event Horizon Telescope Results. IV. Imaging the Central Supermassive Black Hole
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the first Event Horizon Telescope (EHT) images of M87, using observations from April 2017 at 1.3 mm wavelength. These images show a prominent ring with a diameter of similar to 40 mu as, consistent with the size and shape of the lensed photon orbit encircling the "shadow" of a supermassive black hole. The ring is persistent across four observing nights and shows enhanced brightness in the south. To assess the reliability of these results, we implemented a two-stage imaging procedure. In the first stage, four teams, each blind to the others' work, produced images of M87 using both an established method (CLEAN) and a newer technique (regularized maximum likelihood). This stage allowed us to avoid shared human bias and to assess common features among independent reconstructions. In the second stage, we reconstructed synthetic data from a large survey of imaging parameters and then compared the results with the corresponding ground truth images. This stage allowed us to select parameters objectively to use when reconstructing images of M87. Across all tests in both stages, the ring diameter and asymmetry remained stable, insensitive to the choice of imaging technique. We describe the EHT imaging procedures, the primary image features in M87, and the dependence of these features on imaging assumptions.
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| 33. |
- Akiyama, Kazunori, et al.
(författare)
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First M87 Event Horizon Telescope Results. V. Physical Origin of the Asymmetric Ring
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
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Tidskriftsartikel (refereegranskat)abstract
- The Event Horizon Telescope (EHT) has mapped the central compact radio source of the elliptical galaxy M87 at 1.3 mm with unprecedented angular resolution. Here we consider the physical implications of the asymmetric ring seen in the 2017 EHT data. To this end, we construct a large library of models based on general relativistic magnetohydrodynamic (GRMHD) simulations and synthetic images produced by general relativistic ray tracing. We compare the observed visibilities with this library and confirm that the asymmetric ring is consistent with earlier predictions of strong gravitational lensing of synchrotron emission from a hot plasma orbiting near the black hole event horizon. The ring radius and ring asymmetry depend on black hole mass and spin, respectively, and both are therefore expected to be stable when observed in future EHT campaigns. Overall, the observed image is consistent with expectations for the shadow of a spinning Kerr black hole as predicted by general relativity. If the black hole spin and M87's large scale jet are aligned, then the black hole spin vector is pointed away from Earth. Models in our library of non-spinning black holes are inconsistent with the observations as they do not produce sufficiently powerful jets. At the same time, in those models that produce a sufficiently powerful jet, the latter is powered by extraction of black hole spin energy through mechanisms akin to the Blandford-Znajek process. We briefly consider alternatives to a black hole for the central compact object. Analysis of existing EHT polarization data and data taken simultaneously at other wavelengths will soon enable new tests of the GRMHD models, as will future EHT campaigns at 230 and 345 GHz.
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| 34. |
- Akiyama, Kazunori, et al.
(författare)
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First M87 Event Horizon Telescope Results. VI. The Shadow and Mass of the Central Black Hole
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign. We develop and fit geometric crescent models (asymmetric rings with interior brightness depressions) using two independent sampling algorithms that consider distinct representations of the visibility data. We show that the crescent family of models is statistically preferred over other comparably complex geometric models that we explore. We calibrate the geometric model parameters using general relativistic magnetohydrodynamic (GRMHD) models of the emission region and estimate physical properties of the source. We further fit images generated from GRMHD models directly to the data. We compare the derived emission region and black hole parameters from these analyses with those recovered from reconstructed images. There is a remarkable consistency among all methods and data sets. We find that >50% of the total flux at arcsecond scales comes from near the horizon, and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole. Across all methods, we measure a crescent diameter of 42 +/- 3 mu as and constrain its fractional width to be
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| 35. |
- Cooke, Steven J., et al.
(författare)
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Searching for responsible and sustainable recreational fisheries in the Anthropocene
- 2019
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Ingår i: Journal of Fish Biology. - : John Wiley & Sons. - 0022-1112 .- 1095-8649. ; 94:6, s. 845-856
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Tidskriftsartikel (refereegranskat)abstract
- Recreational fisheries that use rod and reel (i.e., angling) operate around the globe in diverse freshwater and marine habitats, targeting many different gamefish species and engaging at least 220 million participants. The motivations for fishing vary extensively; whether anglers engage in catch-and-release or are harvest-oriented, there is strong potential for recreational fisheries to be conducted in a manner that is both responsible and sustainable. There are many examples of recreational fisheries that are well-managed where anglers, the angling industry and managers engage in responsible behaviours that both contribute to long-term sustainability of fish populations and the sector. Yet, recreational fisheries do not operate in a vacuum; fish populations face threats and stressors including harvest from other sectors as well as environmental change, a defining characteristic of the Anthropocene. We argue that the future of recreational fisheries and indeed many wild fish populations and aquatic ecosystems depends on having responsible and sustainable (R&S) recreational fisheries whilst, where possible, addressing, or at least lobbying for increased awareness about the threats to recreational fisheries emanating from outside the sector (e.g., climate change). Here, we first consider how the concepts of R&S intersect in the recreational fishing sector in an increasingly complex socio-cultural context. Next, we explore the role of the angler, angling industry and decision-makers in achieving R&S fisheries. We extend this idea further by considering the consequences of a future without recreational fisheries (either because of failures related to R&S) and explore a pertinent case study situated in Uttarakahand, India. Unlike other fisheries sectors where the number of participants is relatively small, recreational angling participants are numerous and widespread, such that if their actions are responsible, they have the potential to be a key voice for conservation and serve as a major force for good in the Anthropocene. What remains to be seen is whether this will be achieved, or if failure will occur to the point that recreational fisheries face increasing pressure to cease, as a result of external environmental threats, the environmental effects of recreational fishing and emerging ethical concerns about the welfare of angled fish.
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| 36. |
- Fisher, Rebecca E., et al.
(författare)
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Measurement of the C-13 isotopic signature of methane emissions from northern European wetlands
- 2017
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 31:3, s. 605-623
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Tidskriftsartikel (refereegranskat)abstract
- Isotopic data provide powerful constraints on regional and global methane emissions and their source profiles. However, inverse modeling of spatially resolved methane flux is currently constrained by a lack of information on the variability of source isotopic signatures. In this study, isotopic signatures of emissions in the Fennoscandian Arctic have been determined in chambers over wetland, in the air 0.3 to 3m above the wetland surface and by aircraft sampling from 100m above wetlands up to the stratosphere. Overall, the methane flux to atmosphere has a coherent delta C-13 isotopic signature of -71 +/- 1%, measured in situ on the ground in wetlands. This is in close agreement with delta C-13 isotopic signatures of local and regional methane increments measured by aircraft campaigns flying through air masses containing elevated methane mole fractions. In contrast, results from wetlands in Canadian boreal forest farther south gave isotopic signatures of -67 +/- 1%. Wetland emissions dominate the local methane source measured over the European Arctic in summer. Chamber measurements demonstrate a highly variable methane flux and isotopic signature, but the results from air sampling within wetland areas show that emissions mix rapidly immediately above the wetland surface and methane emissions reaching the wider atmosphere do indeed have strongly coherent C isotope signatures. The study suggests that for boreal wetlands (>60 degrees N) global and regional modeling can use an isotopic signature of -71 parts per thousand to apportion sources more accurately, but there is much need for further measurements over other wetlands regions to verify this.
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| 37. |
- Issaoun, S., et al.
(författare)
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The Size, Shape, and Scattering of Sagittarius A∗ at 86 GHz: First VLBI with ALMA
- 2019
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 871:1
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Tidskriftsartikel (refereegranskat)abstract
- The Galactic center supermassive black hole Sagittarius A∗ (Sgr A∗) is one of the most promising targets to study the dynamics of black hole accretion and outflow via direct imaging with very long baseline interferometry (VLBI). At 3.5 mm (86 GHz), the emission from Sgr A∗ is resolvable with the Global Millimeter VLBI Array (GMVA). We present the first observations of Sgr A∗ with the phased Atacama Large Millimeter/submillimeter Array (ALMA) joining the GMVA. Our observations achieve an angular resolution of ∼87 μas, improving upon previous experiments by a factor of two. We reconstruct a first image of the unscattered source structure of Sgr A∗ at 3.5 mm, mitigating the effects of interstellar scattering. The unscattered source has a major-axis size of 120 ±34 μas (12 ±3.4 Schwarzschild radii) and a symmetrical morphology (axial ratio of ), which is further supported by closure phases consistent with zero within 3σ. We show that multiple disk-dominated models of Sgr A∗ match our observational constraints, while the two jet-dominated models considered are constrained to small viewing angles. Our long-baseline detections to ALMA also provide new constraints on the scattering of Sgr A∗, and we show that refractive scattering effects are likely to be weak for images of Sgr A∗ at 1.3 mm with the Event Horizon Telescope. Our results provide the most stringent constraints to date for the intrinsic morphology and refractive scattering of Sgr A∗, demonstrating the exceptional contribution of ALMA to millimeter VLBI.
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| 38. |
- Pinder, Adrian C., et al.
(författare)
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Mahseer (Tor spp.) fishes of the world : status, challenges and opportunities for conservation
- 2019
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Ingår i: Reviews in Fish Biology and Fisheries. - : Springer Science and Business Media LLC. - 0960-3166 .- 1573-5184. ; 29:2, s. 417-452
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Forskningsöversikt (refereegranskat)abstract
- The mahseer fishes (Tor spp.) represent an iconic genus of large-bodied species of the Cyprinidae family. Across the 16 recognised species in the genus, individual fish can attain weights over 50kg, resulting in some species being considered as premier sport fishes. Tor species also generally have high religious and cultural significance throughout South and Southeast Asia. Despite their economic and cultural importance, the status of Tor fishes has been increasingly imperilled through their riverine habitats being impacted by anthropogenic activities, such as hydropower dam construction and exploitation. Moreover, conservation efforts have been constrained by knowledge on the genus being heavily skewed towards aquaculture, with considerable knowledge gaps on their taxonomy, autecology, distribution and population status. Whilst taxonomic ambiguity has been a major constraint on conservation efforts, this has been partially overcome by recent, robust taxonomic revisions. This has enabled revision of the IUCN Red List status of Tor fishes; three species are now assessed as Near Threatened', one Vulnerable', three Endangered' and one Critically Endangered'. However, eight species remain Data deficient'. Here, information on these 16 Tor fishes is synthesised for the first time, outlining the current state of knowledge for each species, including their known distributions and population status. For each species, the outstanding gaps in knowledge are also identified, and their population threats and conservation prospects outlined. Consequently, this review provides the basis for researchers to challenge and enhance the knowledge base necessary to conserve these freshwater icons in an era of unprecedented environmental changes.
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| 39. |
- Scholtz, J., et al.
(författare)
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Identifying the subtle signatures of feedback from distant AGN using ALMA observations and the EAGLE hydrodynamical simulations
- 2018
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 475:1, s. 1288-1305
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Tidskriftsartikel (refereegranskat)abstract
- We present sensitive 870 μm continuum measurements from our ALMA programmes of 114 X-ray selected active galactic nuclei (AGN) in the Chandra Deep Field-South and Cosmic Evolution Survey fields. We use these observations in combination with data from Spitzer and Herschel to construct a sample of 86 X-ray selected AGN, 63 with ALMA constraints at Ζ = 1.5-3.2 with stellar mass > 2 × 10 10 M ⊙ . We constructed broad-band spectral energy distributions in the infrared band (8-1000 μm) and constrain star-formation rates (SFRs) uncontaminated by the AGN. Using a hierarchical Bayesian method that takes into account the information from upper limits, we fit SFR and specific SFR (sSFR) distributions. We explore these distributions as a function of both X-ray luminosity and stellar mass. We compare our measurements to two versions of the Evolution and Assembly of GaLaxies and their Environments (EAGLE) hydrodynamical simulations: the reference model withAGNfeedback and the model without AGN. We find good agreement between the observations and that predicted by the EAGLE reference model for the modes and widths of the sSFR distributions as a function of both X-ray luminosity and stellar mass; however, we found that the EAGLE model without AGN feedback predicts a significantly narrower width when compared to the data. Overall, from the combination of the observations with the model predictions, we conclude that (1) even with AGN feedback, we expect no strong relationship between the sSFR distribution parameters and instantaneous AGN luminosity and (2) a signature of AGN feedback is a broad distribution of sSFRs for all galaxies (not just those hosting an AGN) with stellar masses above ≈10 10 M ⊙ .
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| 40. |
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| 41. |
- Akiyama, Kazunori, et al.
(författare)
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First M87 Event Horizon Telescope Results. I. the Shadow of the Supermassive Black Hole
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
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Tidskriftsartikel (refereegranskat)abstract
- When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 ±3 μas, which is circular and encompasses a central depression in brightness with a flux ratio ≈10:1. The emission ring is recovered using different calibration and imaging schemes, with its diameter and width remaining stable over four different observations carried out in different days. Overall, the observed image is consistent with expectations for the shadow of a Kerr black hole as predicted by general relativity. The asymmetry in brightness in the ring can be explained in terms of relativistic beaming of the emission from a plasma rotating close to the speed of light around a black hole. We compare our images to an extensive library of ray-traced general-relativistic magnetohydrodynamic simulations of black holes and derive a central mass of M =(6.5 ±0.7) ×10 9 M o . Our radio-wave observations thus provide powerful evidence for the presence of supermassive black holes in centers of galaxies and as the central engines of active galactic nuclei. They also present a new tool to explore gravity in its most extreme limit and on a mass scale that was so far not accessible.
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| 42. |
- Akiyama, Kazunori, et al.
(författare)
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First M87 Event Horizon Telescope Results. II. Array and Instrumentation
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
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Tidskriftsartikel (refereegranskat)abstract
- The Event Horizon Telescope (EHT) is a very long baseline interferometry (VLBI) array that comprises millimeter- and submillimeter-wavelength telescopes separated by distances comparable to the diameter of the Earth. At a nominal operating wavelength of ∼1.3 mm, EHT angular resolution (λ/D) is ∼25 μas, which is sufficient to resolve nearby supermassive black hole candidates on spatial and temporal scales that correspond to their event horizons. With this capability, the EHT scientific goals are to probe general relativistic effects in the strong-field regime and to study accretion and relativistic jet formation near the black hole boundary. In this Letter we describe the system design of the EHT, detail the technology and instrumentation that enable observations, and provide measures of its performance. Meeting the EHT science objectives has required several key developments that have facilitated the robust extension of the VLBI technique to EHT observing wavelengths and the production of instrumentation that can be deployed on a heterogeneous array of existing telescopes and facilities. To meet sensitivity requirements, high-bandwidth digital systems were developed that process data at rates of 64 gigabit s -1 , exceeding those of currently operating cm-wavelength VLBI arrays by more than an order of magnitude. Associated improvements include the development of phasing systems at array facilities, new receiver installation at several sites, and the deployment of hydrogen maser frequency standards to ensure coherent data capture across the array. These efforts led to the coordination and execution of the first Global EHT observations in 2017 April, and to event-horizon-scale imaging of the supermassive black hole candidate in M87.
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| 43. |
- Akiyama, Kazunori, et al.
(författare)
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First M87 Event Horizon Telescope Results. III. Data Processing and Calibration
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the calibration and reduction of Event Horizon Telescope (EHT) 1.3 mm radio wavelength observations of the supermassive black hole candidate at the center of the radio galaxy M87 and the quasar 3C 279, taken during the 2017 April 5-11 observing campaign. These global very long baseline interferometric observations include for the first time the highly sensitive Atacama Large Millimeter/submillimeter Array (ALMA); reaching an angular resolution of 25 μas, with characteristic sensitivity limits of ∼1 mJy on baselines to ALMA and ∼10 mJy on other baselines. The observations present challenges for existing data processing tools, arising from the rapid atmospheric phase fluctuations, wide recording bandwidth, and highly heterogeneous array. In response, we developed three independent pipelines for phase calibration and fringe detection, each tailored to the specific needs of the EHT. The final data products include calibrated total intensity amplitude and phase information. They are validated through a series of quality assurance tests that show consistency across pipelines and set limits on baseline systematic errors of 2% in amplitude and 1° in phase. The M87 data reveal the presence of two nulls in correlated flux density at ∼3.4 and ∼8.3 Gλ and temporal evolution in closure quantities, indicating intrinsic variability of compact structure on a timescale of days, or several light-crossing times for a few billion solar-mass black hole. These measurements provide the first opportunity to image horizon-scale structure in M87.
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| 44. |
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| 45. |
- Baek, Sungmin, et al.
(författare)
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The Alternative Splicing Regulator Nova2 Constrains Vascular Erk Signaling to Limit Specification of the Lymphatic Lineage
- 2019
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Ingår i: Developmental Cell. - : CELL PRESS. - 1534-5807 .- 1878-1551. ; 49:2, s. 279-292
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Tidskriftsartikel (refereegranskat)abstract
- The correct assignment of cell fate within fields of multipotent progenitors is essential for accurate tissue diversification. The first lymphatic vessels arise from pre-existing veins after venous endothelial cells become specified as lymphatic progenitors. Prox1 specifies lymphatic fate and labels these progenitors; however, the mechanisms restricting Prox1 expression and limiting the progenitor pool remain unknown. We identified a zebrafish mutant that displayed premature, expanded, and prolonged lymphatic specification. The gene responsible encodes the regulator of alternative splicing, Nova2. In zebrafish and human endothelial cells, Nova2 selectively regulates pre-mRNA splicing for components of signaling pathways and phosphoproteins. Nova2-deficient endothelial cells display increased Mapk/Erk signaling, and Prox1 expression is dynamically controlled by Erk signaling. We identify a mechanism whereby Nova2-regulated splicing constrains Erk signaling, thus limiting lymphatic progenitor cell specification. This identifies the capacity of a factor that tunes mRNA splicing to control assignment of cell fate during vascular differentiation.
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| 46. |
- Fox, Stuart, et al.
(författare)
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Airborne validation of radiative transfer modelling of ice clouds at millimetre and sub-millimetre wavelengths
- 2019
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 12:3, s. 1599-1617
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Tidskriftsartikel (refereegranskat)abstract
- The next generation of European polar orbiting weather satellites will carry a novel instrument, the Ice Cloud Imager (ICI), which uses passive observations between 183 and 664 GHz to make daily global observations of cloud ice. Successful use of these observations requires accurate modelling of cloud ice scattering, and this study uses airborne observations from two flights of the Facility for Airborne Atmospheric Measurements (FAAM) BAe 146 research aircraft to validate radiative transfer simulations of cirrus clouds at frequencies between 325 and 664 GHz using the Atmospheric Radiative Transfer Simulator (ARTS) and a state-of-the-art database of cloud ice optical properties. Particular care is taken to ensure that the inputs to the radiative transfer model are representative of the true atmospheric state by combining both remote-sensing and in situ observations of the same clouds to create realistic vertical profiles of cloud properties that are consistent with both observed particle size distributions and bulk ice mass. The simulations are compared to measurements from the International Submillimetre Airborne Radiometer (ISMAR), which is an airborne demonstrator for ICI. It is shown that whilst they are generally able to reproduce the observed cloud signals, for a given ice water path (IWP) there is considerable sensitivity to the cloud microphysics, including the distribution of ice mass within the cloud and the ice particle habit. Accurate retrievals from ICI will therefore require realistic representations of cloud microphysical properties.
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| 47. |
- Lu, Ru-Sen, et al.
(författare)
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Detection of Intrinsic Source Structure at similar to 3 Schwarzschild Radii with Millimeter-VLBI Observations of SAGITTARIUS A*
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 859:1
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Tidskriftsartikel (refereegranskat)abstract
- We report results from very long baseline interferometric (VLBI) observations of the supermassive black hole in the Galactic center, Sgr A*, at 1.3 mm (230 GHz). The observations were performed in 2013 March using six VLBI stations in Hawaii, California, Arizona, and Chile. Compared to earlier observations, the addition of the APEX telescope in Chile almost doubles the longest baseline length in the array, provides additional uv coverage in the N-S direction, and leads to a spatial resolution of similar to 30 mu as (similar to 3 Schwarzschild radii) for Sgr A*. The source is detected even at the longest baselines with visibility amplitudes of similar to 4%-13% of the total flux density. We argue that such flux densities cannot result from interstellar refractive scattering alone, but indicate the presence of compact intrinsic source structure on scales of similar to 3 Schwarzschild radii. The measured nonzero closure phases rule out point-symmetric emission. We discuss our results in the context of simple geometric models that capture the basic characteristics and brightness distributions of disk-and jet-dominated models and show that both can reproduce the observed data. Common to these models are the brightness asymmetry, the orientation, and characteristic sizes, which are comparable to the expected size of the black hole shadow. Future 1.3 mm VLBI observations with an expanded array and better sensitivity will allow more detailed imaging of the horizon-scale structure and bear the potential for a deep insight into the physical processes at the black hole boundary.
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| 48. |
- Noorani, A, et al.
(författare)
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A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy
- 2017
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 27:6, s. 902-912
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Tidskriftsartikel (refereegranskat)abstract
- The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-genome sequencing data obtained from chemo-naive and chemo-treated samples. The quality of whole-genomic sequencing data is comparable across all samples regardless of chemotherapy status. Inclusion of samples collected post-chemotherapy increased the proportion of late-stage tumors. When comparing matched pre- and post-chemotherapy samples from 10 cases, the mutational signatures, copy number, and SNV mutational profiles reflect the expected heterogeneity in this disease. Analysis of SNVs in relation to allele-specific copy-number changes pinpoints the common ancestor to a point prior to chemotherapy. For cases in which pre- and post-chemotherapy samples do show substantial differences, the timing of the divergence is near-synchronous with endoreduplication. Comparison across a large prospective cohort (62 treatment-naive, 58 chemotherapy-treated samples) reveals no significant differences in the overall mutation rate, mutation signatures, specific recurrent point mutations, or copy-number events in respect to chemotherapy status. In conclusion, whole-genome sequencing of samples obtained following neoadjuvant chemotherapy is representative of the genomic landscape of esophageal adenocarcinoma. Excluding these samples reduces the material available for cataloging and introduces a bias toward the earlier stages of cancer.
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| 49. |
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| 50. |
- Bower, Rebekah L., et al.
(författare)
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Mapping the calcitonin receptor in human brain stem
- 2016
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Ingår i: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 310:9, s. 788-793
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Tidskriftsartikel (refereegranskat)abstract
- The calcitonin receptor (CTR) is relevant to three hormonal systems: amylin, calcitonin, and calcitonin gene-related peptide (CGRP). Receptors for amylin and calcitonin are targets for treating obesity, diabetes, and bone disorders. CGRP receptors represent a target for pain and migraine. Amylin receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract, the hypoglossal nucleus, the cuneate nucleus, spinal trigeminal nucleus, the gracile nucleus, and the inferior olivary nucleus. CTR staining was also observed in the area postrema, the lateral reticular nucleus, and the pyramidal tract. The extensive expression of CTR in the medulla suggests that CTR may be involved in a wider range of functions than currently appreciated.
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