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- Weltman, A., et al.
(författare)
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Fundamental physics with the Square Kilometre Array
- 2020
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Ingår i: Publications Astronomical Society of Australia. - : CAMBRIDGE UNIV PRESS. - 1323-3580 .- 1448-6083. ; 37
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Forskningsöversikt (refereegranskat)abstract
- The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
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| 6. |
- de Blok, W.J.G., et al.
(författare)
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an overview of the MHONGOOSE survey: Observing nearby galaxies with MeerKAT
- 2016
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Ingår i: Proceedings of Science. - 1824-8039.
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Konferensbidrag (refereegranskat)abstract
- MHONGOOSE is a deep survey of the neutral hydrogen distribution in a representative sample of 30 nearby disk and dwarf galaxies with H I masses from ∼ 106 to ∼ 1011 M, and luminosities from MR ∼ 12 to MR ∼ −22. The sample is selected to uniformly cover the available range in log(MHI). Our extremely deep observations, down to H I column density limits of well below 1018 cm−2 — or a few hundred times fainter than the typical H I disks in galaxies — will directly detect the effects of cold accretion from the intergalactic medium and the links with the cosmic web. These observations will be the first ever to probe the very low-column density neutral gas in galaxies at these high resolutions. Combination with data at other wavelengths, most of it already available, will enable accurate modeling of the properties and evolution of the mass components in these galaxies and link these with the effects of environment, dark matter distribution, and other fundamental properties such as halo mass and angular momentum. MHONGOOSE can already start addressing some of the SKA-1 science goals and will provide a comprehensive inventory of the processes driving the transformation and evolution of galaxies in the nearby universe at high resolution and over 5 orders of magnitude in column density. It will be a Nearby Galaxies Legacy Survey that will be unsurpassed until the advent of the SKA, and can serve as a highly visible, lasting statement of MeerKAT’s capabilities.
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- Bosma, A. L., et al.
(författare)
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TREatment of ATopic eczema (TREAT) Registry Taskforce : protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema
- 2020
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 182:6, s. 1423-1429
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Tidskriftsartikel (refereegranskat)abstract
- Background: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. Objectives: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. Methods: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. Conclusions: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic?. There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add?. The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.
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- Michaut, Magali, et al.
(författare)
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Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.
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| 9. |
- Billecke, N, et al.
(författare)
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Perilipin 5 mediated lipid droplet remodelling revealed by coherent Raman imaging
- 2015
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Ingår i: Integrative biology : quantitative biosciences from nano to macro. - : Oxford University Press (OUP). - 1757-9708. ; 7:4, s. 467-476
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative, label-free coherent Raman microscopy was used to show lipid droplet compositional differences in muscle upon plin5 overexpressionin vivoandin vitro.
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- Bosma, M, et al.
(författare)
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FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 11314-
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Tidskriftsartikel (refereegranskat)abstract
- FNDC4 is a secreted factor sharing high homology with the exercise-associated myokine irisin (FNDC5). Here we report that Fndc4 is robustly upregulated in several mouse models of inflammation as well as in human inflammatory conditions. Specifically, FNDC4 levels are increased locally at inflamed sites of the intestine of inflammatory bowel disease patients. Interestingly, administration of recombinant FNDC4 in the mouse model of induced colitis markedly reduces disease severity compared with mice injected with a control protein. Conversely, mice lacking Fndc4 develop more severe colitis. Analysis of binding of FNDC4 to different immune cell types reveals strong and specific binding to macrophages and monocytes. FNDC4 treatment of bone marrow-derived macrophages in vitro results in reduced phagocytosis, increased cell survival and reduced proinflammatory chemokine expression. Hence, treatment with FNDC4 results in a state of dampened macrophage activity, while enhancing their survival. Thus, we have characterized FNDC4 as a factor with direct therapeutic potential in inflammatory bowel disease and possibly other inflammatory diseases.
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- Combes, F., et al.
(författare)
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PKS 1830-211: OH and HI at z = 0.89 and the first MeerKAT UHF spectrum
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 648
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Tidskriftsartikel (refereegranskat)abstract
- The Large Survey Project (LSP) "MeerKAT Absorption Line Survey"(MALS) is a blind H I 21 cm and OH 18 cm absorption line survey in the L- and UHF-bands, primarily designed to better determine the occurrence of atomic and molecular gas in the circumgalactic and intergalactic medium, and its redshift evolution. Here we present the first results using the UHF band obtained towards the strongly lensed radio source PKS 1830-211, revealing the detection of absorption produced by the lensing galaxy. With merely 90 min of data acquired on-source for science verification and processed using the Automated Radio Telescope Imaging Pipeline (ARTIP), we detect in absorption the known H I 21 cm and OH 18 cm main lines at z = 0.89 at an unprecedented signal-to-noise ratio (4000 in the continuum, in each 6 km s-1 wide channel). For the first time we report the detection of OH satellite lines at z = 0.89, which until now have not been detected at z > 0.25. We decompose the OH lines into a thermal and a stimulated contribution, where the 1612 and 1720 MHz lines are conjugate. The total OH 1720 MHz emission line luminosity is 6100 L⊙. This is the most luminous known 1720 MHz maser line and is also among the most luminous of the OH main line megamasers. The absorption components of the different images of the background source sample different light paths in the lensing galaxy, and their weights in the total absorption spectrum are expected to vary in time on daily and monthly time scales. We compare our normalized spectra with those obtained more than 20 years ago, and find no variation. We interpret the absorption spectra with the help of a lens galaxy model derived from an N-body hydrodynamical simulation, with a morphology similar to its optical HST image. The resulting absorption lines depend mainly on the background continuum and the radial distribution of the gas surface density for each atomic and molecular species. We show that it is possible to reproduce the observations assuming a realistic spiral galaxy disk without invoking any central gas outflows. However, there are distinct and faint high-velocity features in the ALMA millimeter absorption spectra that most likely originate from high-velocity clouds or tidal features. These clouds may contribute to broaden the H I and OH spectra.
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| 16. |
- Pagnini, F, et al.
(författare)
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Erratum
- 2015
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Ingår i: Psychology & health. - 1476-8321. ; 30:5, s. I-I
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 20. |
- Severson, Tesa M, et al.
(författare)
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BRCA1-like signature in triple negative breast cancer: Molecular and clinical characterization reveals subgroups with therapeutic potential.
- 2015
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 9:8, s. 1528-1538
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Tidskriftsartikel (refereegranskat)abstract
- Triple negative (TN) breast cancers make up some 15% of all breast cancers. Approximately 10-15% are mutant for the tumor suppressor, BRCA1. BRCA1 is required for homologous recombination-mediated DNA repair and deficiency results in genomic instability. BRCA1-mutated tumors have a specific pattern of genomic copy number aberrations that can be used to classify tumors as BRCA1-like or non-BRCA1-like. BRCA1 mutation, promoter methylation, BRCA1-like status and genome-wide expression data was determined for 112 TN breast cancer samples with long-term follow-up. Mutation status for 21 known DNA repair genes and PIK3CA was assessed. Gene expression and mutation frequency in BRCA1-like and non-BRCA1-like tumors were compared. Multivariate survival analysis was performed using the Cox proportional hazards model. BRCA1 germline mutation was identified in 10% of patients and 15% of tumors were BRCA1 promoter methylated. Fifty-five percent of tumors classified as BRCA1-like. The functions of genes significantly up-regulated in BRCA1-like tumors included cell cycle and DNA recombination and repair. TP53 was found to be frequently mutated in BRCA1-like (P < 0.05), while PIK3CA was frequently mutated in non-BRCA1-like tumors (P < 0.05). A significant association with worse prognosis was evident for patients with BRCA1-like tumors (adjusted HR = 3.32, 95% CI = 1.30-8.48, P = 0.01). TN tumors can be further divided into two major subgroups, BRCA1-like and non-BRCA1-like with different mutation and expression patterns and prognoses. Based on these molecular patterns, subgroups may be more sensitive to specific targeted agents such as PI3K or PARP inhibitors.
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