| 1. |
- Ajello, M., et al.
(författare)
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Gamma Rays from Fast Black-hole Winds
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 921:2
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Tidskriftsartikel (refereegranskat)abstract
- Massive black holes at the centers of galaxies can launch powerful wide-angle winds that, if sustained over time, can unbind the gas from the stellar bulges of galaxies. These winds may be responsible for the observed scaling relation between the masses of the central black holes and the velocity dispersion of stars in galactic bulges. Propagating through the galaxy, the wind should interact with the interstellar medium creating a strong shock, similar to those observed in supernovae explosions, which is able to accelerate charged particles to high energies. In this work we use data from the Fermi Large Area Telescope to search for the gamma-ray emission from galaxies with an ultrafast outflow (UFO): a fast (v similar to 0.1 c), highly ionized outflow, detected in absorption at hard X-rays in several nearby active galactic nuclei (AGN). Adopting a sensitive stacking analysis we are able to detect the average gamma-ray emission from these galaxies and exclude that it is due to processes other than UFOs. Moreover, our analysis shows that the gamma-ray luminosity scales with the AGN bolometric luminosity and that these outflows transfer similar to 0.04% of their mechanical power to gamma-rays. Interpreting the observed gamma-ray emission as produced by cosmic rays (CRs) accelerated at the shock front, we find that the gamma-ray emission may attest to the onset of the wind-host interaction and that these outflows can energize charged particles up to the transition region between galactic and extragalactic CRs.
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| 2. |
- Izadi, Z., et al.
(författare)
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Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19
- 2021
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Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. OBJECTIVE To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. DESIGN, SETTING, AND PARTICIPANTS This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age >= 18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. EXPOSURES Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. MAIN OUTCOMES AND MEASURES The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. RESULTS A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone. CONCLUSIONS AND RELEVANCE In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.
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| 3. |
- Hickey, J. W., et al.
(författare)
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Spatial mapping of protein composition and tissue organization : a primer for multiplexed antibody-based imaging
- 2022
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Ingår i: Nature Methods. - : Nature Research. - 1548-7091 .- 1548-7105. ; 19:3, s. 284-295
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Tidskriftsartikel (refereegranskat)abstract
- Tissues and organs are composed of distinct cell types that must operate in concert to perform physiological functions. Efforts to create high-dimensional biomarker catalogs of these cells have been largely based on single-cell sequencing approaches, which lack the spatial context required to understand critical cellular communication and correlated structural organization. To probe in situ biology with sufficient depth, several multiplexed protein imaging methods have been recently developed. Though these technologies differ in strategy and mode of immunolabeling and detection tags, they commonly utilize antibodies directed against protein biomarkers to provide detailed spatial and functional maps of complex tissues. As these promising antibody-based multiplexing approaches become more widely adopted, new frameworks and considerations are critical for training future users, generating molecular tools, validating antibody panels, and harmonizing datasets. In this Perspective, we provide essential resources, key considerations for obtaining robust and reproducible imaging data, and specialized knowledge from domain experts and technology developers.
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| 4. |
- Vaivads, Andris, et al.
(författare)
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Turbulence Heating ObserveR - satellite mission proposal
- 2016
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Ingår i: JOURNAL OF PLASMA PHYSICS. - 0022-3778. ; 82
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Tidskriftsartikel (refereegranskat)abstract
- The Universe is permeated by hot, turbulent, magnetized plasmas. Turbulent plasma is a major constituent of active galactic nuclei, supernova remnants, the intergalactic and interstellar medium, the solar corona, the solar wind and the Earth's magnetosphere, just to mention a few examples. Energy dissipation of turbulent fluctuations plays a key role in plasma heating and energization, yet we still do not understand the underlying physical mechanisms involved. THOR is a mission designed to answer the questions of how turbulent plasma is heated and particles accelerated, how the dissipated energy is partitioned and how dissipation operates in different regimes of turbulence. THOR is a single-spacecraft mission with an orbit tuned to maximize data return from regions in near-Earth space - magnetosheath, shock, foreshock and pristine solar wind - featuring different kinds of turbulence. Here we summarize the THOR proposal submitted on 15 January 2015 to the 'Call for a Medium-size mission opportunity in ESAs Science Programme for a launch in 2025 (M4)'. THOR has been selected by European Space Agency (ESA) for the study phase.
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| 5. |
- Coppejans, D. L., et al.
(författare)
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A Mildly Relativistic Outflow from the Energetic, Fast-rising Blue Optical Transient CSS161010 in a Dwarf Galaxy
- 2020
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 895:1
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Tidskriftsartikel (refereegranskat)abstract
- We present X-ray and radio observations of the Fast Blue Optical Transient CRTS-CSS161010 J045834-081803 (CSS161010 hereafter) at t = 69-531 days. CSS161010 shows luminous X-ray (L-x similar to 5 x 10(39) erg s(-1)) and radio (L-nu similar to 10(29) erg s(-1) Hz(-1)) emission. The radio emission peaked at similar to 100 days post-transient explosion and rapidly decayed. We interpret these observations in the context of synchrotron emission from an expanding blast wave. CSS161010 launched a mildly relativistic outflow with velocity Gamma beta c >= 0.55c at similar to 100 days. This is faster than the non-relativistic AT 2018cow (Gamma beta c similar to 0.1c) and closer to ZTF18abvkwla (Gamma beta c >= 0.3c at 63 days). The inferred initial kinetic energy of CSS161010 (E-k greater than or similar to 10(51) erg) is comparable to that of long gamma-ray bursts, but the ejecta mass that is coupled to the mildly relativistic outflow is significantly larger (similar to 0.01-.1 M-circle dot). This is consistent with the lack of observed gamma-rays. The luminous X-rays were produced by a different emission component to the synchrotron radio emission. CSS161010 is located at similar to 150 Mpc in a dwarf galaxy with stellar mass M-* similar to 10(7) M-circle dot and specific star formation rate sSFR similar to 0.3 Gyr(-1). This mass is among the lowest inferred for host galaxies of explosive transients from massive stars. Our observations of CSS161010 are consistent with an engine-driven aspherical explosion from a rare evolutionary path of a H-rich stellar progenitor, but we cannot rule out a stellar tidal disruption event on a centrally located intermediate-mass black hole. Regardless of the physical mechanism, CSS161010 establishes the existence of a new class of rare (rate < 0.4% of the local core-collapse supernova rate) H-rich transients that can launch mildly relativistic outflows.
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| 6. |
- Johlander, Andreas, 1990-, et al.
(författare)
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Ion Acceleration Efficiency at the Earth's Bow Shock : Observations and Simulation Results
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 914:2
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Tidskriftsartikel (refereegranskat)abstract
- Collisionless shocks are some of the most efficient particle accelerators in heliospheric and astrophysical plasmas. Here we study and quantify ion acceleration at Earth's bow shock with observations from NASA's Magnetospheric Multiscale (MMS) satellites and in a global hybrid-Vlasov simulation. From the MMS observations, we find that quasiparallel shocks are more efficient at accelerating ions. There, up to 15% of the available energy goes into accelerating ions above 10 times their initial energy. Above a shock-normal angle of similar to 50 degrees, essentially no energetic ions are observed downstream of the shock. We find that ion acceleration efficiency is significantly lower when the shock has a low Mach number (M ( A ) < 6) while there is little Mach number dependence for higher values. We also find that ion acceleration is lower on the flanks of the bow shock than at the subsolar point regardless of the Mach number. The observations show that a higher connection time of an upstream field line leads to somewhat higher acceleration efficiency. To complement the observations, we perform a global hybrid-Vlasov simulation with realistic solar-wind parameters with the shape and size of the bow shock. We find that the ion acceleration efficiency in the simulation shows good quantitative agreement with the MMS observations. With the combined approach of direct spacecraft observations, we quantify ion acceleration in a wide range of shock angles and Mach numbers.
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| 7. |
- Marien, E., et al.
(författare)
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Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:7, s. 1539-1548
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Tidskriftsartikel (refereegranskat)abstract
- Non-small cell lung cancer (NSCLC) is the leading cause of cancer death globally. To develop better diagnostics and more effective treatments, research in the past decades has focused on identification of molecular changes in the genome, transcriptome, proteome, and more recently also the metabolome. Phospholipids, which nevertheless play a central role in cell functioning, remain poorly explored. Here, using a mass spectrometry (MS)-based phospholipidomics approach, we profiled 179 phospholipid species in malignant and matched non-malignant lung tissue of 162 NSCLC patients (73 in a discovery cohort and 89 in a validation cohort). We identified 91 phospholipid species that were differentially expressed in cancer versus non-malignant tissues. Most prominent changes included a decrease in sphingomyelins (SMs) and an increase in specific phosphatidylinositols (PIs). Also a decrease in multiple phosphatidylserines (PSs) was observed, along with an increase in several phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species, particularly those with 40 or 42 carbon atoms in both fatty acyl chains together. 2D-imaging MS of the most differentially expressed phospholipids confirmed their differential abundance in cancer cells. We identified lipid markers that can discriminate tumor versus normal tissue and different NSCLC subtypes with an AUC (area under the ROC curve) of 0.999 and 0.885, respectively. In conclusion, using both shotgun and 2D-imaging lipidomics analysis, we uncovered a hitherto unrecognized alteration in phospholipid profiles in NSCLC. These changes may have important biological implications and may have significant potential for biomarker development. What's new? Cellular membranes are subject to extensive modification in cancer, often with marked alterations in phospholipid metabolism. The extent and nature of those changes are not fully known, however, particularly for non-small cell lung cancer (NSCLC). In this study, lipidomics analysis of phospholipid profiles uncovered dramatic differences between NSCLC and normal lung tissue. The differences were confirmed via 2D-imaging lipidomics in tissue sections. Lipid markers capable of discriminating between tumor and normal tissue and between different NSCLC subtypes were identified. The observed alterations in NSCLC phospholipid profiles may be biologically significant.
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| 8. |
- Groseclose, M Reid, et al.
(författare)
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Identification of proteins directly from tissue : in situ tryptic digestions coupled with imaging mass spectrometry.
- 2007
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Ingår i: Journal of Mass Spectrometry. - : Wiley. - 1076-5174 .- 1096-9888. ; 42:2, s. 254-62
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Tidskriftsartikel (refereegranskat)abstract
- A novel method for on-tissue identification of proteins in spatially discrete regions is described using tryptic digestion followed by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) with MS/MS analysis. IMS is first used to reveal the protein and peptide spatial distribution in a tissue section and then a serial section is robotically spotted with small volumes of trypsin solution to carry out in situ protease digestion. After hydrolysis, 2,5-Dihydroxybenzoic acid (DHB) matrix solution is applied to the digested spots, with subsequent analysis by IMS to reveal the spatial distribution of the various tryptic fragments. Sequence determination of the tryptic fragments is performed using on-tissue MALDI MS/MS analysis directly from the individual digest spots. This protocol enables protein identification directly from tissue while preserving the spatial integrity of the tissue sample. The procedure is demonstrated with the identification of several proteins in the coronal sections of a rat brain.
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| 9. |
- Andersson, Malin, et al.
(författare)
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Imaging mass spectrometry of proteins and peptides : 3D volume reconstruction.
- 2008
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 5:1, s. 101-8
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Tidskriftsartikel (refereegranskat)abstract
- As large genomic and proteomic datasets are generated from homogenates of various tissues, the need for information on the spatial localization of their encoded products has become more pressing. Matrix-assisted laser desorption-ionization (MALDI) imaging mass spectrometry (IMS) offers investigators the means with which to unambiguously study peptides and proteins with molecular specificity, and to determine their distribution in two and three dimensions. In the past few years, several parameters have been optimized for IMS, including sample preparation, matrix application and instrumental acquisition parameters (Box 1). These developments have resulted in a high degree of reproducibility in mass accuracy and peak intensities (Supplementary Fig. 1 online). Recently, we have optimized our protocol to be able to increase the number of molecular species analyzed by collecting two sets of sections, covering one set of sections with sinapinic acid for optimal detection of proteins and adjacent sections with 2,5-dihydroxybenzoic acid (DHB) matrix for the optimal detection of low-mass species, including peptides. Approximately 1,000 peaks can be observed in each dataset (Fig. 1). Furthermore, the sections are collected at an equal distance, 200 mum instead of 400-500 mum used previously, thus enabling the use of virtual z-stacks and three-dimensional (3D) volume renderings to investigate differential localization patterns in much smaller brain structures such as the substantia nigra and the interpeduncular nucleus. Here we present our optimized step-by-step procedure based on previous work in our laboratory, describing how to make 3D volume reconstructions of MALDI IMS data, as applied to the rat brain.
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| 10. |
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