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- Kasliwal, Mansi M., et al.
(author)
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Kilonova Luminosity Function Constraints Based on Zwicky Transient Facility Searches for 13 Neutron Star Merger Triggers during O3
- 2020
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 905:2
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Journal article (peer-reviewed)abstract
- We present a systematic search for optical counterparts to 13 gravitational wave (GW) triggers involving at least one neutron star during LIGO/Virgo's third observing run (O3). We searched binary neutron star (BNS) and neutron star black hole (NSBH) merger localizations with the Zwicky Transient Facility (ZTF) and undertook follow-up with the Global Relay of Observatories Watching Transients Happen (GROWTH) collaboration. The GW triggers had a median localization area of 4480 deg(2), a median distance of 267 Mpc, and false-alarm rates ranging from 1.5 to 10(-25) yr(-1). The ZTF coverage in the g and r bands had a median enclosed probability of 39%, median depth of 20.8 mag, and median time lag between merger and the start of observations of 1.5 hr. The O3 follow-up by the GROWTH team comprised 340 UltraViolet/Optical/InfraRed (UVOIR) photometric points, 64 OIR spectra, and three radio images using 17 different telescopes. We find no promising kilonovae (radioactivity-powered counterparts), and we show how to convert the upper limits to constrain the underlying kilonova luminosity function. Initially, we assume that all GW triggers are bona fide astrophysical events regardless of false-alarm rate and that kilonovae accompanying BNS and NSBH mergers are drawn from a common population; later, we relax these assumptions. Assuming that all kilonovae are at least as luminous as the discovery magnitude of GW170817 (-16.1 mag), we calculate that our joint probability of detecting zero kilonovae is only 4.2%. If we assume that all kilonovae are brighter than -16.6 mag (the extrapolated peak magnitude of GW170817) and fade at a rate of 1 mag day(-1) (similar to GW170817), the joint probability of zero detections is 7%. If we separate the NSBH and BNS populations based on the online classifications, the joint probability of zero detections, assuming all kilonovae are brighter than -16.6 mag, is 9.7% for NSBH and 7.9% for BNS mergers. Moreover, no more than <57% (<89%) of putative kilonovae could be brighter than -16.6 mag assuming flat evolution (fading by 1 mag day(-1)) at the 90% confidence level. If we further take into account the online terrestrial probability for each GW trigger, we find that no more than <68% of putative kilonovae could be brighter than -16.6 mag. Comparing to model grids, we find that some kilonovae must have M-ej M, X-lan > 10(-4), or > 30 degrees to be consistent with our limits. We look forward to searches in the fourth GW observing run; even 17 neutron star mergers with only 50% coverage to a depth of -16 mag would constrain the maximum fraction of bright kilonovae to <25%.
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- Svedenmark, Sara, 1971-, et al.
(author)
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Old Wine in a New Bottle? – Interpreting Gender Mainstreaming in a Municipal Reorganisation
- 2022
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In: Scandinavian Journal of Public Administration. - Göteborg : University of Gothenburg. - 2001-7405 .- 2001-7413. ; :4, s. 73-90
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Journal article (peer-reviewed)abstract
- Gender mainstreaming (GM) has been on the agenda of organisations at various levels in Sweden and worldwide since the 1990s. Research has shown that GM is difficult to apply and has yet to be clearly defined, and additionally that organisations are uncertain about how to implement it. Research also suggests that the dominance of the new public management (NPM) approach within organisations has made GM work more challenging. In this article, we examine GM in a medium-sized Swedish municipality that is reorganising itself to become gender mainstreamed while introducing trust-based governance (TBG). This municipality provides a unique opportunity to study how GM is constructed in a municipality at the intersection of NPM and TBG. Applying a critical perspective, this article analyses documents from reorganisation based on Bacchi’s (2009) policy analysis. The results demonstrate that GM is mainly translated into TBG-inspired practices and that efficiency becomes an overarching concept that entangles GM, TBG and NPM. GM becomes part of cultural change together with TBG, while NPM maintains its dominance in the structural change of the organisation.
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- Bandopadhayay, Pratiti, et al.
(author)
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BET Bromodomain Inhibition of MYC-Amplified Medulloblastoma
- 2014
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 20:4, s. 912-925
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Journal article (peer-reviewed)abstract
- Purpose:MYC-amplified medulloblastomas are highly lethal tumors. Bromodomain and extraterminal (BET) bromodomain inhibition has recently been shown to suppress MYC-associated transcriptional activity in other cancers. The compound JQ1 inhibits BET bromodomain-containing proteins, including BRD4. Here, we investigate BET bromodomain targeting for the treatment of MYC-amplified medulloblastoma.Experimental Design:We evaluated the effects of genetic and pharmacologic inhibition of BET bromodomains on proliferation, cell cycle, and apoptosis in established and newly generated patient- and genetically engineered mouse model (GEMM)-derived medulloblastoma cell lines and xenografts that harbored amplifications of MYC or MYCN. We also assessed the effect of JQ1 on MYC expression and global MYC-associated transcriptional activity. We assessed the in vivo efficacy of JQ1 in orthotopic xenografts established in immunocompromised mice.Results:Treatment of MYC-amplified medulloblastoma cells with JQ1 decreased cell viability associated with arrest at G1 and apoptosis. We observed downregulation of MYC expression and confirmed the inhibition of MYC-associated transcriptional targets. The exogenous expression of MYC from a retroviral promoter reduced the effect of JQ1 on cell viability, suggesting that attenuated levels of MYC contribute to the functional effects of JQ1. JQ1 significantly prolonged the survival of orthotopic xenograft models of MYC-amplified medulloblastoma (P < 0.001). Xenografts harvested from mice after five doses of JQ1 had reduced the expression of MYC mRNA and a reduced proliferative index.Conclusion:JQ1 suppresses MYC expression and MYC-associated transcriptional activity in medulloblastomas, resulting in an overall decrease in medulloblastoma cell viability. These preclinical findings highlight the promise of BET bromodomain inhibitors as novel agents for MYC-amplified medulloblastoma.
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- Bergström, Christel A S, et al.
(author)
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Hepatitis C virus NS3 protease inhibitors : large, flexible molecules of peptide origin show satisfactory permeability across Caco-2 cells
- 2009
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 38:5, s. 556-563
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Journal article (peer-reviewed)abstract
- The purpose of this study was to investigate the intestinal absorption of tripeptide-based compounds intended for treatment of hepatitis C virus (HCV) infection. The intestinal permeability of 11 HCV NS3 protease inhibitors (Mw 687-841, ClogD(pH 7.4) 1.2-7.3 and 10-13 hydrogen bond donors/acceptors) was measured using Caco-2 cells. Each compound was investigated in the apical to basolateral (a-b) and basolateral to apical (b-a) direction at pH 7.4. For compounds displaying efflux the experiment was repeated in the presence of 1 microM GF120918 to investigate possible involvement of P-glycoprotein (Pgp; ABCB1). All compounds displayed intermediate to high permeability. Seven of them showed extensive efflux, with 31-114-fold higher permeability in the b-a direction than the a-b direction. Addition of the Pgp inhibitor GF120918 reduced the b-a transport rate for the effluxed compounds. However, for inhibitors with a C-terminal carboxylic acid and the acidic bioisosteres thereof the efflux was still significant. Hence, the negative charge resulted in efflux by other ABC-transporters than Pgp. From this study it can be concluded that small changes in the overall structure can lead to a large variation in permeability and efflux as shown by the inhibitors herein, properties that also may influence the resulting inhibition potency of the compounds when performing cell-based pharmacological assays.
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