| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
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| 4. |
- Veres, P., et al.
(författare)
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Observation of inverse Compton emission from a long gamma-ray burst
- 2019
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 575:7783, s. 459-
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Tidskriftsartikel (refereegranskat)abstract
- Long-duration gamma-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectron volt-to-mega electronvoltband, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission(1,2). Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands(1-6). The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock(7-9). Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C(10,11). Here we report multifrequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 x 10(-6) to 10(12) electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.
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| 5. |
- Heywood, I., et al.
(författare)
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Inflation of 430-parsec bipolar radio bubbles in the Galactic Centre by an energetic event
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 573:7773, s. 235-237
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Tidskriftsartikel (refereegranskat)abstract
- The Galactic Centre contains a supermassive black hole with a mass of four million Suns1 within an environment that differs markedly from that of the Galactic disk. Although the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings2. Also, although the levels of star formation in the Galactic Centre have been approximately constant over the past few hundred million years, there is evidence of increased short-duration bursts3, strongly influenced by the interaction of the black hole with the enhanced gas density present within the ring-like central molecular zone4 at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200-parsec region is characterized by large amounts of warm molecular gas5, a high cosmic-ray ionization rate6, unusual gas chemistry, enhanced synchrotron emission7,8, and a multitude of radio-emitting magnetized filaments9, the origin of which has not been established. Here we report radio imaging that reveals a bipolar bubble structure, with an overall span of 1 degree by 3 degrees (140 parsecs × 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 × 1052 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities.
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| 6. |
- Russell, T. D., et al.
(författare)
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Disk-Jet Coupling in the 2017/2018 Outburst of the Galactic Black Hole Candidate X-Ray Binary MAXI J1535-571
- 2019
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 883:2
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Tidskriftsartikel (refereegranskat)abstract
- MAXI J1535-571 is a Galactic black hole candidate X-ray binary that was discovered going into outburst in 2017 September. In this paper, we present comprehensive radio monitoring of this system using the Australia Telescope Compact Array, as well as the MeerKAT radio observatory, showing the evolution of the radio jet during its outburst. Our radio observations show the early rise and subsequent quenching of the compact jet as the outburst brightened and then evolved toward the soft state. We constrain the compact jet quenching factor to be more than 3.5 orders of magnitude. We also detected and tracked (for 303 days) a discrete, relativistically moving jet knot that was launched from the system. From the motion of the apparently superluminal knot, we constrain the jet inclination (at the time of ejection) and speed to = 0.69 c, respectively. Extrapolating its motion back in time, our results suggest that the jet knot was ejected close in time to the transition from the hard intermediate state to soft intermediate state. The launching event also occurred contemporaneously with a short increase in X-ray count rate, a rapid drop in the strength of the X-ray variability, and a change in the type-C quasi-periodic oscillation (QPO) frequency that occurs >2.5 days before the first appearance of a possible type-B QPO.
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| 7. |
- Heywood, W. E., et al.
(författare)
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Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay
- 2015
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Ingår i: Molecular Neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Currently there are no effective treatments for many neurodegenerative diseases. Reliable biomarkers for identifying and stratifying these diseases will be important in the development of future novel therapies. Lewy Body Dementia (LBD) is considered an under diagnosed form of dementia for which markers are needed to discriminate LBD from other forms of dementia such as Alzheimer's Disease (AD). This work describes a Label-Free proteomic profiling analysis of cerebral spinal fluid (CSF) from non-neurodegenerative controls and patients with LBD. Using this technology we identified several potential novel markers for LBD. These were then combined with other biomarkers from previously published studies, to create a 10 min multiplexed targeted and translational MRM-LC-MS/MS assay. This test was used to validate our new assay in a larger cohort of samples including controls and the other neurodegenerative conditions of Alzheimer's and Parkinson's disease (PD). Results: Thirty eight proteins showed significantly (p < 0.05) altered expression in LBD CSF by proteomic profiling. The targeted MRM-LC-MS/MS assay revealed 4 proteins that were specific for the identification of AD from LBD: ectonucleotide pyrophosphatase/phosphodiesterase 2 (p < 0.0001), lysosome-associated membrane protein 1 (p < 0.0001), pro-orexin (p < 0.0017) and transthyretin (p < 0.0001). Nineteen proteins were elevated significantly in both AD and LBD versus the control group of which 4 proteins are novel (malate dehydrogenase 1, serum amyloid A4, GM2-activator protein, and prosaposin). Protein-DJ1 was only elevated significantly in the PD group and not in either LBD or AD samples. Correlations with Alzheimer-associated amyloid beta-42 levels, determined by ELISA, were observed for transthyretin, GM2 activator protein and IGF2 in the AD disease group (r(2) >= 0.39, p <= 0.012). Cystatin C, ubiquitin and osteopontin showed a strong significant linear relationship (r(2) >= 0.4, p <= 0.03) with phosphorylated-tau levels in all groups, whilst malate dehydrogenase and apolipoprotein E demonstrated a linear relationship with phosphorylated-tau and total-tau levels in only AD and LBD disease groups. Conclusions: Using proteomics we have identified several potential and novel markers of neurodegeneration and subsequently validated them using a rapid, multiplexed mass spectral test. This targeted proteomic platform can measure common markers of neurodegeneration that correlate with existing diagnostic makers as well as some that have potential to show changes between AD from LBD.
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| 8. |
- Heslegrave, A. J., et al.
(författare)
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A Selected reaction monitoring protocol for the measurement of sTREM2 in cerebrospinal fluid
- 2018
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Ingår i: Biomarkers for Preclinical Alzheimer’s Disease. Perneczky R. (red.). - New York, NY : Springer. - 0893-2336. - 9781493976744 ; , s. 169-177
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Bokkapitel (refereegranskat)abstract
- Mass spectrometry plays an increasingly important role in the biomarker field with the advent of targeted proteomics. Tryptic peptides from a protein of interest can be used to create a targeted assay to interrogate cerebrospinal fluid (CSF) for biomarkers. Since heterozygous mutations in the TREM2 gene have been associated with an increased risk of Alzheimer’s disease, measuring this soluble protein in CSF has become a priority. This chapter demonstrates the development, optimization, and validation of a method to measure soluble TREM2 using a single reaction monitoring (SRM) targeted mass spectrometry assay. © 2018, Springer Science+Business Media, LLC.
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| 9. |
- Heywood, Wendy E, et al.
(författare)
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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status.
- 2016
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Ingår i: Journal of visualized experiments : JoVE. - : MyJove Corporation. - 1940-087X. ; :116
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Tidskriftsartikel (refereegranskat)abstract
- Many neurodegenerative diseases arestill lacking effective treatments. Reliable biomarkers for identifying and classifying these diseases will be important in the development of future novel therapies. Oftenpotential new biomarkers do not make itinto the clinicdue to limitationsin their development andhigh costs.However,targeted proteomics using Multiple Reaction Monitoring Liquid Chromatography-tandem/Mass Spectrometry (MRM LC-MS/MS), specifically using triple quadrupole mass spectrometers, is one method that can be used to rapidly evaluate and validate biomarkersfor clinical translation into diagnostic laboratories. Traditionally, this platform has been used extensively for measurement of small moleculesin clinical laboratories, but it is the potential to analyze proteins, that makes it an attractive alternative to ELISA (Enzyme-Linked Immunosorbent Assay)-based methods. We describe here how targeted proteomics can be used to measure multiplexed markers of dementia, including the detection and quantitation of the known risk factor apolipoprotein E isoform 4 (ApoE4). In order to make the assay suitable for translation, it is designed to be rapid, simple, highly specific and cost effective. To achieve this, every step in the development of the assay must be optimized for the individual proteins and tissues they are analyzed in. This method describes a typical workflow including various tips and tricks to developing a targeted proteomics MRM LC-MS/MS for translation. The method development is optimized using custom synthesized versions of tryptic quantotypic peptides, which calibratethe MS for detection and then spiked into CSF to determine correct identification of the endogenous peptide in the chromatographic separation prior to analysis in the MS. To achieve absolute quantitation, stable isotope-labeled internal standard versions of the peptides with short amino acid sequence tags and containing a trypsin cleavage site, are included in the assay.
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| 10. |
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| 11. |
- Mallett, H. K. W., et al.
(författare)
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Variation in the Distribution and Properties of Circumpolar Deep Water in the Eastern Amundsen Sea, on Seasonal Timescales, Using Seal-Borne Tags
- 2018
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276. ; 45:10, s. 4982-4990
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Tidskriftsartikel (refereegranskat)abstract
- In the Amundsen Sea, warm saline Circumpolar Deep Water (CDW) crosses the continental shelf toward the vulnerable West Antarctic ice shelves, contributing to their basal melting. Due to lack of observations, little is known about the spatial and temporal variability of CDW, particularly seasonally. A new data set of 6,704 seal tag temperature and salinity profiles in the easternmost trough between February and December 2014 reveals a CDW layer on average 49dbar thicker in late winter (August to October) than in late summer (February to April), the reverse seasonality of that seen at moorings in the western trough. This layer contains more heat in winter, but on the 27.76 kg/m(3) density surface CDW is 0.32 degrees C warmer in summer than in winter, across the northeastern Amundsen Sea, which may indicate that wintertime shoaling offshelf changes CDW properties onshelf. In Pine Island Bay these seasonal changes on density surfaces are reduced, likely by gyre circulation. Plain Language Summary In the Amundsen Sea, Antarctica, warm salty water crosses the continental shelf from the deep open ocean, toward the vulnerable West Antarctic ice shelves, bringing heat to help melt them from underneath. Due to lack of observations, little is known about how this flow of warm water varies in space and time, particularly seasonally. Between February and December 2014, in a trough in the eastern Amundsen Sea, 6,704 profiles were collected by sensors attached to seals, measuring temperature and salinity as the seals return from dives up to 1,200m deep. These data showed that this warm (similar to 1 degrees C) deep layer is on average similar to 50m thicker in late winter (August to October) than in late summer (February to April), the reverse seasonality of that seen within a trough in the western Amundsen Sea. This warm layer contains more heat in winter but on a surface of constant density is 0.32 degrees C warmer in summer than in winter, across the northeastern Amundsen Sea. This may indicate that in winter the deep waters offshelf rise, allowing different water onto the continental shelf. In Pine Island Bay these seasonal changes on density surfaces are reduced, probably because here the water circulates and mixes.
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| 12. |
- Paterson, R W, et al.
(författare)
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A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer's disease pathology.
- 2016
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is the most common cause of dementia. Biomarkers are required to identify individuals in the preclinical phase, explain phenotypic diversity, measure progression and estimate prognosis. The development of assays to validate candidate biomarkers is costly and time-consuming. Targeted proteomics is an attractive means of quantifying novel proteins in cerebrospinal and other fluids, and has potential to help overcome this bottleneck in biomarker development. We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. Individuals were classified as 'AD' or 'non-AD' on the basis of their CSF T-tau and amyloid Aβ1-42 profile measured using enzyme-linked immunosorbent assay; biomarkers of interest were compared using univariate and multivariate analyses. In all, 35/31 individuals in Cohort 1 and 46/36 in Cohort 2 fulfilled criteria for AD/non-AD profile CSF, respectively. After adjustment for multiple comparisons, five proteins were elevated significantly in AD CSF compared with non-AD CSF in both cohorts: malate dehydrogenase; total APOE; chitinase-3-like protein 1 (YKL-40); osteopontin and cystatin C. In an independent multivariate orthogonal projection to latent structures discriminant analysis (OPLS-DA), these proteins were also identified as major contributors to the separation between AD and non-AD in both cohorts. Independent of CSF Aβ1-42 and tau, a combination of these biomarkers differentiated AD and non-AD with an area under curve (AUC)=0.88. This targeted proteomic multiple reaction monitoring (MRM)-based assay can simultaneously and rapidly measure multiple candidate CSF biomarkers. Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility.
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| 13. |
- Testor, Pierre, et al.
(författare)
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OceanGliders: A component of the integrated GOOS
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Forskningsöversikt (refereegranskat)abstract
- The OceanGliders program started in 2016 to support active coordination and enhancement of global glider activity. OceanGliders contributes to the international efforts of the Global Ocean Observation System (GOOS) for Climate, Ocean Health and Operational Services. It brings together marine scientists and engineers operating gliders around the world: (1) to observe the long-term physical, biogeochemical, and biological ocean processes and phenomena that are relevant for societal applications; and, (2) to contribute to the GOOS through real-time and delayed mode data dissemination. The OceanGliders program is distributed across national and regional observing systems and significantly contributes to integrated, multi-scale and multi-platform sampling strategies. OceanGliders shares best practices, requirements, and scientific knowledge needed for glider operations, data collection and analysis. It also monitors global glider activity and supports the dissemination of glider data through regional and global databases, in real-time and delayed modes, facilitating data access to the wider community. OceanGliders currently supports national, regional and global initiatives to maintian and expand the capabilities and application of gliders to meet key global challenges such as improved measurement of ocean boundary currents, water transformation and storm forecast.
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| 14. |
- Webber, B. G. M., et al.
(författare)
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The Impact of Overturning and Horizontal Circulation in Pine Island Trough on Ice Shelf Melt in the Eastern Amundsen Sea
- 2019
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Ingår i: Journal of Physical Oceanography. - : American Meteorological Society. - 0022-3670 .- 1520-0485. ; 49:1, s. 63-83
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Tidskriftsartikel (refereegranskat)abstract
- The ice shelves around the Amundsen Sea are rapidly melting as a result of the circulation of relatively warm ocean water into their cavities. However, little is known about the processes that determine the variability of this circulation. Here we use an ocean circulation model to diagnose the relative importance of horizontal and vertical (overturning) circulation within Pine Island Trough, leading to Pine Island and Thwaites ice shelves. We show that melt rates and southward Circumpolar Deep Water (CDW) transports covary over large parts of the continental shelf at interannual to decadal time scales. The dominant external forcing mechanism for this variability is Ekman pumping and suction on the continental shelf and at the shelf break, in agreement with previous studies. At the continental shelf break, the southward transport of CDW and heat is predominantly barotropic. Farther south within Pine Island Trough, northward and southward barotropic heat transports largely cancel, and the majority of the net southward temperature transport is facilitated by baroclinic and overturning circulations. The overturning circulation is related to water mass transformation and buoyancy gain on the shelf that is primarily facilitated by freshwater input from basal melting.
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