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1.	Campbell, PJ, et al. (författare) Pan-cancer analysis of whole genomes 2020 Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82- Tidskriftsartikel (refereegranskat)abstract Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
2.	Ederle, Joerg, et al. (författare) Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial 2010 Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997 Tidskriftsartikel (refereegranskat)abstract Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
3.	Ackley, K., et al. (författare) Observational constraints on the optical and near-infrared emission from the neutron star-black hole binary merger candidate S190814bv 2020 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 643 Tidskriftsartikel (refereegranskat)abstract Context. Gravitational wave (GW) astronomy has rapidly reached maturity, becoming a fundamental observing window for modern astrophysics. The coalescences of a few tens of black hole (BH) binaries have been detected, while the number of events possibly including a neutron star (NS) is still limited to a few. On 2019 August 14, the LIGO and Virgo interferometers detected a high-significance event labelled S190814bv. A preliminary analysis of the GW data suggests that the event was likely due to the merger of a compact binary system formed by a BH and a NS.Aims. In this paper, we present our extensive search campaign aimed at uncovering the potential optical and near infrared electromagnetic counterpart of S190814bv. We found no convincing electromagnetic counterpart in our data. We therefore use our non-detection to place limits on the properties of the putative outflows that could have been produced by the binary during and after the merger.Methods. Thanks to the three-detector observation of S190814bv, and given the characteristics of the signal, the LIGO and Virgo Collaborations delivered a relatively narrow localisation in low latency - a 50% (90%) credible area of 5 deg(2) (23 deg(2)) - despite the relatively large distance of 26752 Mpc. ElectromagNetic counterparts of GRAvitational wave sources at the VEry Large Telescope collaboration members carried out an intensive multi-epoch, multi-instrument observational campaign to identify the possible optical and near infrared counterpart of the event. In addition, the ATLAS, GOTO, GRAWITA-VST, Pan-STARRS, and VINROUGE projects also carried out a search on this event. In this paper, we describe the combined observational campaign of these groups.Results. Our observations allow us to place limits on the presence of any counterpart and discuss the implications for the kilonova (KN), which was possibly generated by this NS-BH merger, and for the strategy of future searches. The typical depth of our wide-field observations, which cover most of the projected sky localisation probability (up to 99.8%, depending on the night and filter considered), is r similar to 22 (resp. K similar to 21) in the optical (resp. near infrared). We reach deeper limits in a subset of our galaxy-targeted observations, which cover a total similar to 50% of the galaxy-mass-weighted localisation probability. Altogether, our observations allow us to exclude a KN with large ejecta mass M greater than or similar to 0.1 M-circle dot to a high (> 90%) confidence, and we can exclude much smaller masses in a sub-sample of our observations. This disfavours the tidal disruption of the neutron star during the merger.Conclusions. Despite the sensitive instruments involved in the campaign, given the distance of S190814bv, we could not reach sufficiently deep limits to constrain a KN comparable in luminosity to AT 2017gfo on a large fraction of the localisation probability. This suggests that future (likely common) events at a few hundred megaparsecs will be detected only by large facilities with both a high sensitivity and large field of view. Galaxy-targeted observations can reach the needed depth over a relevant portion of the localisation probability with a smaller investment of resources, but the number of galaxies to be targeted in order to get a fairly complete coverage is large, even in the case of a localisation as good as that of this event.
4.	Waszak, S. M., et al. (författare) Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort 2018 Ingår i: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 19:6, s. 785-798 Tidskriftsartikel (refereegranskat)abstract Background Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 4069) and 5-year overall survival was 65% (95% CI 5281); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.
5.	Agudo, I., et al. (författare) Panning for gold, but finding helium: Discovery of the ultra-stripped supernova SN 2019wxt from gravitational-wave follow-up observations 2023 Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 675 Tidskriftsartikel (refereegranskat)abstract We present the results from multi-wavelength observations of a transient discovered during an intensive follow-up campaign of S191213g, a gravitational wave (GW) event reported by the LIGO-Virgo Collaboration as a possible binary neutron star merger in a low latency search. This search yielded SN 2019wxt, a young transient in a galaxy whose sky position (in the 80% GW contour) and distance (∼150 Mpc) were plausibly compatible with the localisation uncertainty of the GW event. Initially, the transienta's tightly constrained age, its relatively faint peak magnitude (Mi ∼ -16.7 mag), and the r-band decline rate of ∼1 mag per 5 days appeared suggestive of a compact binary merger. However, SN 2019wxt spectroscopically resembled a type Ib supernova, and analysis of the optical-near-infrared evolution rapidly led to the conclusion that while it could not be associated with S191213g, it nevertheless represented an extreme outcome of stellar evolution. By modelling the light curve, we estimated an ejecta mass of only ∼0.1 M·, with 56Ni comprising ∼20% of this. We were broadly able to reproduce its spectral evolution with a composition dominated by helium and oxygen, with trace amounts of calcium. We considered various progenitor channels that could give rise to the observed properties of SN 2019wxt and concluded that an ultra-stripped origin in a binary system is the most likely explanation. Disentangling genuine electromagnetic counterparts to GW events from transients such as SN 2019wxt soon after discovery is challenging: in a bid to characterise this level of contamination, we estimated the rate of events with a volumetric rate density comparable to that of SN 2019wxt and found that around one such event per week can occur within the typical GW localisation area of O4 alerts out to a luminosity distance of 500 Mpc, beyond which it would become fainter than the typical depth of current electromagnetic follow-up campaigns.
6.	Sturm, D, et al. (författare) New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs 2016 Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 164:5, s. 1060-1072 Tidskriftsartikel (refereegranskat)
7.	Anand, S., et al. (författare) Optical follow-up of the neutron star–black hole mergers S200105ae and S200115j 2020 Ingår i: Nature Astronomy. - : Nature Research. - 2397-3366. Tidskriftsartikel (refereegranskat)abstract LIGO and Virgo’s third observing run revealed the first neutron star–black hole (NSBH) merger candidates in gravitational waves. These events are predicted to synthesize r-process elements1,2 creating optical/near-infrared ‘kilonova’ emission. The joint gravitational wave and electromagnetic detection of an NSBH merger could be used to constrain the equation of state of dense nuclear matter3, and independently measure the local expansion rate of the Universe4. Here, we present the optical follow-up and analysis of two of the only three high-significance NSBH merger candidates detected to date, S200105ae and S200115j, with the Zwicky Transient Facility5. The Zwicky Transient Facility observed ~48% of S200105ae and ~22% of S200115j’s localization probabilities, with observations sensitive to kilonovae brighter than −17.5 mag fading at 0.5 mag d−1 in the g- and r-bands; extensive searches and systematic follow-up of candidates did not yield a viable counterpart. We present state-of-the-art kilonova models tailored to NSBH systems that place constraints on the ejecta properties of these NSBH mergers. We show that with observed depths of apparent magnitude ~22 mag, attainable in metre-class, wide-field-of-view survey instruments, strong constraints on ejecta mass are possible, with the potential to rule out low mass ratios, high black hole spins and large neutron star radii.
8.	Waszak, S. M., et al. (författare) Germline Elongator mutations in Sonic Hedgehog medulloblastoma 2020 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 580:7803 Tidskriftsartikel (refereegranskat)abstract Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children(1,2), and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma(3). Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1 in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH. Parent-offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHH alpha subtype(4) and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U-34) position(5,6). Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems(7-9). Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.
9.	Kool, Erik C., et al. (författare) AT 2017gbl : a dust obscured TDE candidate in a luminous infrared galaxy 2020 Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 498:2, s. 2167-2195 Tidskriftsartikel (refereegranskat)abstract We present the discovery with Keck of the extremely infrared (IR) luminous transient AT 2017gbl, coincident with the Northern nucleus of the luminous infrared galaxy (LIRG) IRAS 23436+5257. Our extensive multiwavelength follow-up spans ∼900 d, including photometry and spectroscopy in the optical and IR, and (very long baseline interferometry) radio and X-ray observations. Radiative transfer modelling of the host galaxy spectral energy distribution and long-term pre-outburst variability in the mid-IR indicate the presence of a hitherto undetected dust obscured active galactic nucleus (AGN). The optical and near-IR spectra show broad ∼2000 km s−1 hydrogen, He i, and O i emission features that decrease in flux over time. Radio imaging shows a fast evolving compact source of synchrotron emission spatially coincident with AT 2017gbl. We infer a lower limit for the radiated energy of 7.3 × 1050 erg from the IR photometry. An extremely energetic supernova would satisfy this budget, but is ruled out by the radio counterpart evolution. Instead, we propose AT 2017gbl is related to an accretion event by the central supermassive black hole, where the spectral signatures originate in the AGN broad line region and the IR photometry is consistent with re-radiation by polar dust. Given the fast evolution of AT 2017gbl, we deem a tidal disruption event (TDE) of a star a more plausible scenario than a dramatic change in the AGN accretion rate. This makes AT 2017gbl the third TDE candidate to be hosted by a LIRG, in contrast to the so far considered TDE population discovered at optical wavelengths and hosted preferably by post-starburst galaxies.
10.	Ahumada, T., et al. (författare) Discovery and confirmation of the shortest gamma-ray burst from a collapsar 2021 Ingår i: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:9, s. 917-927 Tidskriftsartikel (refereegranskat)abstract Gamma-ray bursts (GRBs) are among the brightest and most energetic events in the Universe. The duration and hardness distribution of GRBs has two clusters1, now understood to reflect (at least) two different progenitors2. Short-hard GRBs (SGRBs; T90 < 2 s) arise from compact binary mergers, and long-soft GRBs (LGRBs; T90 > 2 s) have been attributed to the collapse of peculiar massive stars (collapsars)3. The discovery of SN 1998bw/GRB 980425 (ref. 4) marked the first association of an LGRB with a collapsar, and AT 2017gfo (ref. 5)/GRB 170817A/GW170817 (ref. 6) marked the first association of an SGRB with a binary neutron star merger, which also produced a gravitational wave. Here, we present the discovery of ZTF20abwysqy (AT2020scz), a fast-fading optical transient in the Fermi satellite and the Interplanetary Network localization regions of GRB 200826A; X-ray and radio emission further confirm that this is the afterglow. Follow-up imaging (at rest-frame 16.5 days) reveals excess emission above the afterglow that cannot be explained as an underlying kilonova, but which is consistent with being the supernova. Although the GRB duration is short (rest-frame T90 of 0.65 s), our panchromatic follow-up data confirm a collapsar origin. GRB 200826A is the shortest LGRB found with an associated collapsar; it appears to sit on the brink between a successful and a failed collapsar. Our discovery is consistent with the hypothesis that most collapsars fail to produce ultra-relativistic jets.
11.	Kankare, E., et al. (författare) Core-collapse supernova subtypes in luminous infrared galaxies 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649 Tidskriftsartikel (refereegranskat)abstract The fraction of core-collapse supernovae (CCSNe) occurring in the central regions of galaxies is not well constrained at present. This is partly because large-scale transient surveys operate at optical wavelengths, making it challenging to detect transient sources that occur in regions susceptible to high extinction factors. Here we present the discovery and follow-up observations of two CCSNe that occurred in the luminous infrared galaxy (LIRG) NGC 3256. The first, SN 2018ec, was discovered using the ESO HAWK-I /GRAAL adaptive optics seeing enhancer, and was classified as a Type Ic with a host galaxy extinction of AV = 2:1+0:3 0:1 mag. The second, AT 2018cux, was discovered during the course of follow-up observations of SN 2018ec, and is consistent with a subluminous Type IIP classification with an AV = 2:1 +/- 0:4 mag of host extinction. A third CCSN, PSN J10275082 4354034 in NGC 3256, was previously reported in 2014, and we recovered the source in late-time archival Hubble Space Telescope imaging. Based on template light curve fitting, we favour a Type IIn classification for it with modest host galaxy extinction of AV = 0:3+0:4 0:3 mag. We also extend our study with follow-up data of the recent Type IIb SN 2019lqo and Type Ib SN 2020fkb that occurred in the LIRG system Arp 299 with host extinctions of AV = 2:1 +0:1 0 :3 and AV = 0:4 +0:1 0 :2 mag, respectively. Motivated by the above, we inspected, for the first time, a sample of 29 CCSNe located within a projected distance of 2.5 kpc from the host galaxy nuclei in a sample of 16 LIRGs. We find, if star formation within these galaxies is modelled assuming a global starburst episode and normal IMF, that there is evidence of a correlation between the starburst age and the CCSN subtype. We infer that the two subgroups of 14 H-poor (Type IIb /Ib /Ic /Ibn) and 15 H-rich (Type II /IIn) CCSNe have di fferent underlying progenitor age distributions, with the H-poor progenitors being younger at 3 sigma significance. However, we note that the currently available sample sizes of CCSNe and host LIRGs are small, and the statistical comparisons between subgroups do not take into account possible systematic or model errors related to the estimated starburst ages.
12.	Waszak, SM, et al. (författare) Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort 2018 Ingår i: The Lancet. Oncology. - 1474-5488. ; 19:6, s. 785-798 Tidskriftsartikel (refereegranskat)
13.	Gal-Yam, A., et al. (författare) A WC/WO star exploding within an expanding carbon-oxygen-neon nebula 2022 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 601:7892, s. 201-204 Tidskriftsartikel (refereegranskat)abstract The final fate of massive stars, and the nature of the compact remnants they leave behind (black holes and neutron stars), are open questions in astrophysics. Many massive stars are stripped of their outer hydrogen envelopes as they evolve. Such Wolf-Rayet stars(1) emit strong and rapidly expanding winds with speeds greater than 1,000 kilometres per second. A fraction of this population is also helium-depleted, with spectra dominated by highly ionized emission lines of carbon and oxygen (types WC/WO). Evidence indicates that the most commonly observed supernova explosions that lack hydrogen and helium (types Ib/Ic) cannot result from massive WC/WO stars(2,3), leading some to suggest that most such stars collapse directly into black holes without a visible supernova explosion(4). Here we report observations of SN 2019hgp, beginning about a day after the explosion. Its short rise time and rapid decline place it among an emerging population of rapidly evolving transients(5-8). Spectroscopy reveals a rich set of emission lines indicating that the explosion occurred within a nebula composed of carbon, oxygen and neon. Narrow absorption features show that this material is expanding at high velocities (greater than 1,500 kilometres per second), requiring a compact progenitor. Our observations are consistent with an explosion of a massive WC/WO star, and suggest that massive Wolf-Rayet stars may be the progenitors of some rapidly evolving transients.
14.	Sollerman, Jesper, et al. (författare) The Type II supernova SN 2020jfo in M 61, implications for progenitor system, and explosion dynamics 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 655 Tidskriftsartikel (refereegranskat)abstract We present the discovery and extensive follow-up observations of SN 2020jfo, a Type IIP supernova (SN) in the nearby (14.5 Mpc) galaxy M 61. Optical light curves (LCs) and spectra from the Zwicky Transient Facility (ZTF), complemented with data from Swift/UVOT and near-infrared photometry is presented. These were used to model the 350-day duration bolometric light curve, which exhibits a relatively short (∼65 days) plateau. This implies a moderate ejecta mass (∼5 M⊙) at the time of explosion, whereas the deduced amount of ejected radioactive nickel is ∼0.025 M⊙. An extensive series of spectroscopy is presented, including spectropolarimetric observations. The nebular spectra are dominated by Hα, but also reveal emission lines from oxygen and calcium. Comparisons to synthetic nebular spectra indicate an initial progenitor mass of ∼12 M⊙. We also note the presence of stable nickel in the nebular spectrum, and SN 2020jfo joins a small group of SNe that have inferred super-solar Ni/Fe ratios. Several years of prediscovery data were examined, but no signs of precursor activity were found. Pre-explosion Hubble Space Telescope imaging reveals a probable progenitor star, detected only in the reddest band (MF814W ≈ −5.8) and it is fainter than expected for stars in the 10−15 M⊙ range. There is thus some tension between the LC analysis, the nebular spectral modeling, and the pre-explosion imaging. To compare and contrast, we present two additional core-collapse SNe monitored by the ZTF, which also have nebular Hα-dominated spectra. This illustrates how the absence or presence of an interaction with circumstellar material (CSM) affect both the LCs and in particular the nebular spectra. Type II SN 2020amv has a LC powered by CSM interaction, in particular after ∼40 days when the LC is bumpy and slowly evolving. The late-time spectra show strong Hα emission with a structure suggesting emission from a thin, dense shell. The evolution of the complex three-horn line profile is reminiscent of that observed for SN 1998S. Finally, SN 2020jfv has a poorly constrained early-time LC, but it is of interest because of the transition from a hydrogen-poor Type IIb to a Type IIn, where the nebular spectrum after the light-curve rebrightening is dominated by Hα, although with an intermediate line width.
15.	Gerlag, DM, et al. (författare) Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study 2019 Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:2, s. 179-185 Tidskriftsartikel (refereegranskat)abstract We explored the effects of B-cell directed therapy in subjects at risk of developing autoantibodypositive rheumatoid arthritis (RA), who never experienced inflammatory arthritis before, and explored biomarkers predictive of arthritis development.MethodsIndividuals positive for both anti-citrullinated peptide antibodies and rheumatoid factor but without arthritis were included in a randomised, double-blind, placebo-controlled study to receive a single infusion of 1000 mg rituximab or placebo.ResultsEighty-one individuals received treatment and were followed up for a mean of 29.0 (0–54) months, during which 30/81 (37%) individuals developed arthritis. The observed risk of developing arthritis in the placebo-treated group was 40%, which was decreased by 55% (HR 0.45, 95% CI 0.154 to 1.322) in the rituximab-treated group at 12 months. Rituximab treatment caused a delay in arthritis development of 12 months compared with placebo treatment at the point when 25% of the subjects had developed arthritis (p<0.0001). Erythrocyte sedimentation rate and the presence of anti-citrullinated α-enolase peptide 1 at baseline were significant predictors of arthritis development.ConclusionsA single infusion of 1000 mg rituximab significantly delays the development of arthritis in subjects at risk of developing RA, providing evidence for the pathogenetic role of B cells in the earliest, prearthritis stage of autoantibody positive RA.
16.	Kool, Erik C., et al. (författare) SN 2020bqj : A Type Ibn supernova with a long-lasting peak plateau 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 652 Tidskriftsartikel (refereegranskat)abstract Context. Type Ibn supernovae (SNe Ibn) are a rare class of stripped envelope supernovae interacting with a helium-rich circumstellar medium (CSM). The majority of the SNe Ibn reported in the literature display a surprising homogeneity in their fast-evolving lightcurves and are typically found in actively starforming spiral galaxies.Aims. We present the discovery and the study of SN 2020bqj (ZTF20aalrqbu), a SN Ibn with a long-duration peak plateau lasting 40 days and hosted by a faint low-mass galaxy. We aim to explain its peculiar properties using an extensive photometric and spectroscopic data set.Methods. We compare the photometric and spectral evolution of SN 2020bqj with regular SNe Ibn from the literature, as well as with other outliers in the SN Ibn subclass. We fit the bolometric and multi-band lightcurves with powering mechanism models such as radioactive decay and CSM interaction. We also model the host galaxy of SN 2020bqj.Results. The risetime, peak magnitude and spectral features of SN 2020bqj are consistent with those of most SNe Ibn, but the SN is a clear outlier in the subclass based on its bright, long-lasting peak plateau and the low mass of its faint host galaxy. We show through modeling that the lightcurve of SN 2020bqj can be powered predominantly by shock heating from the interaction of the SN ejecta and a dense CSM, combined with radioactive decay. The peculiar Type Ibn SN 2011hw is a close analog to SN 2020bqj in terms of lightcurve and spectral evolution, suggesting a similar progenitor and CSM scenario. In this scenario a very massive progenitor star in the transitional phase between a luminous blue variable and a compact Wolf-Rayet star undergoes core-collapse, embedded in a dense helium-rich CSM with an elevated opacity compared to normal SNe Ibn, due to the presence of residual hydrogen. This scenario is consistent with the observed properties of SN 2020bqj and the modeling results.Conclusions. SN 2020bqj is a compelling example of a transitional SN Ibn/IIn based on not only its spectral features, but also its lightcurve, host galaxy properties and the inferred progenitor properties. The strong similarity with SN 2011hw suggests this subclass may be the result of a progenitor in a stellar evolution phase that is distinct from those of progenitors of regular SNe Ibn.
17.	Kool, M, et al. (författare) Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas 2012 Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 123:4, s. 473-484 Tidskriftsartikel (refereegranskat)
18.	Purdum, Josiah N., et al. (författare) Time-series and Phase-curve Photometry of the Episodically Active Asteroid (6478) Gault in a Quiescent State Using APO, GROWTH, P200, and ZTF 2021 Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 911:2 Tidskriftsartikel (refereegranskat)abstract We observed the episodically active asteroid (6478) Gault in 2020 with multiple telescopes in Asia and North America and found that it is no longer active after its recent outbursts at the end of 2018 and the start of 2019. The inactivity during this apparition allowed us to measure the absolute magnitude of Gault of H ( r ) = 14.63 +/- 0.02, G ( r ) = 0.21 +/- 0.02 from our secular phase-curve observations. In addition, we were able to constrain Gault's rotation period using time-series photometric lightcurves taken over 17 hr on multiple days in 2020 August, September, and October. The photometric lightcurves have a repeating less than or similar to 0.05 mag feature suggesting that (6478) Gault has a rotation period of similar to 2.5 hr and may have a semispherical or top-like shape, much like the near-Earth asteroids Ryugu and Bennu. The rotation period of similar to 2.5 hr is near the expected critical rotation period for an asteroid with the physical properties of (6478) Gault, suggesting that its activity observed over multiple epochs is due to surface mass shedding from its fast rotation spin-up by the Yarkovsky-O'Keefe-Radzievskii-Paddack effect.
19.	Alexandrov, Ludmil B., et al. (författare) Signatures of mutational processes in human cancer 2013 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 500:7463, s. 415-421 Tidskriftsartikel (refereegranskat)abstract All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
20.	Andreoni, Igor, et al. (författare) Target-of-opportunity Observations of Gravitational-wave Events with Vera C. Rubin Observatory 2022 Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 260:1 Tidskriftsartikel (refereegranskat)abstract The discovery of the electromagnetic counterpart to the binary neutron star (NS) merger GW170817 has opened the era of gravitational-wave multimessenger astronomy. Rapid identification of the optical/infrared kilonova enabled a precise localization of the source, which paved the way to deep multiwavelength follow-up and its myriad of related science results. Fully exploiting this new territory of exploration requires the acquisition of electromagnetic data from samples of NS mergers and other gravitational-wave sources. After GW170817, the frontier is now to map the diversity of kilonova properties and provide more stringent constraints on the Hubble constant, and enable new tests of fundamental physics. The Vera C. Rubin Observatory's Legacy Survey of Space and Time can play a key role in this field in the 2020s, when an improved network of gravitational-wave detectors is expected to reach a sensitivity that will enable the discovery of a high rate of merger events involving NSs (∼tens per year) out to distances of several hundred megaparsecs. We design comprehensive target-of-opportunity observing strategies for follow-up of gravitational-wave triggers that will make the Rubin Observatory the premier instrument for discovery and early characterization of NS and other compact-object mergers, and yet unknown classes of gravitational-wave events.
21.	Casewell, Nicholas R, et al. (författare) Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals. 2019 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:51, s. 25745-25755 Tidskriftsartikel (refereegranskat)abstract Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find that KLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions.
22.	Gerlag, D, et al. (författare) THE EFFECTS OF B CELL DIRECTED THERAPY ON DISEASE RELEVANT BIOMARKERS IN SUBJECTS AT RISK OF RHEUMATOID ARTHRITIS 2017 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ Publishing Group Ltd and European League Against Rheumatism. - 0003-4967. ; 76, s. 781-781 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
23.	Huang, Miller, et al. (författare) Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis 2019 Ingår i: Cell Stem Cell. - : CELL PRESS. - 1934-5909 .- 1875-9777. ; 25:3, s. 433- Tidskriftsartikel (refereegranskat)abstract Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here, we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome patients, who are predis- posed to medulloblastoma due to germline-mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.
24.	Kasliwal, Mansi M., et al. (författare) Kilonova Luminosity Function Constraints Based on Zwicky Transient Facility Searches for 13 Neutron Star Merger Triggers during O3 2020 Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 905:2 Tidskriftsartikel (refereegranskat)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%.
25.	Kool, Erik C., et al. (författare) A radio-detected type Ia supernova with helium-rich circumstellar material 2023 Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 617:7961, s. 477-482 Tidskriftsartikel (refereegranskat)abstract Type Ia supernovae (SNe Ia) are thermonuclear explosions of degenerate white dwarf stars destabilized by mass accretion from a companion star1, but the nature of their progenitors remains poorly understood. A way to discriminate between progenitor systems is through radio observations; a non-degenerate companion star is expected to lose material through winds2 or binary interaction3 before explosion, and the supernova ejecta crashing into this nearby circumstellar material should result in radio synchrotron emission. However, despite extensive efforts, no type Ia supernova (SN Ia) has ever been detected at radio wavelengths, which suggests a clean environment and a companion star that is itself a degenerate white dwarf star4,5. Here we report on the study of SN 2020eyj, a SN Ia showing helium-rich circumstellar material, as demonstrated by its spectral features, infrared emission and, for the first time in a SN Ia to our knowledge, a radio counterpart. On the basis of our modelling, we conclude that the circumstellar material probably originates from a single-degenerate binary system in which a white dwarf accretes material from a helium donor star, an often proposed formation channel for SNe Ia (refs. 6,7). We describe how comprehensive radio follow-up of SN 2020eyj-like SNe Ia can improve the constraints on their progenitor systems.
26.	Northcott, Paul A, et al. (författare) Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. 2014 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 511:7510, s. 428-428 Tidskriftsartikel (refereegranskat)abstract Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
27.	Yang, Sheng, et al. (författare) A low-energy explosion yields the underluminous Type IIP SN 2020cxd 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 655 Tidskriftsartikel (refereegranskat)abstract Context. We present our observations and analysis of SN 2020cxd, a low-luminosity (LL), long-lived Type IIP supernova (SN). This object is a clear outlier in the magnitude-limited SN sample recently presented by the Zwicky Transient Facility’s (ZTF) Bright Transient Survey.Aims. We demonstrate that SN 2020cxd is an additional member of the group of LL SNe and we discuss the rarity of LL SNe in the context of the ZTF survey. We consider how further studies of these faintest members of the core-collapse (CC) SN family might help improve the general understanding of the underlying initial mass function for stars that explode.Methods. We used optical light curves (LCs) from the ZTF in the gri bands and several epochs of ultraviolet data from the Neil Gehrels Swift observatory as well as a sequence of optical spectra. We constructed the colour curves and a bolometric LC. Then we compared the evolution of the ejecta velocity and black-body temperature for LL SNe as well as for typical Type II SNe. Furthermore, we adopted a Monte Carlo code that fits semi-analytic models to the LC of SN 2020cxd, which allows for the estimation of the physical parameters. Using our late-time nebular spectra, we also make a comparison against SN II spectral synthesis models from the literature to constrain the progenitor properties of SN 2020cxd.Results. The LCs of SN 2020cxd show a great similarity with those of LL SNe IIP in terms of luminosity, timescale, and colours. Also, the spectral evolution of SN 2020cxd is that of a Type IIP SN. The spectra show prominent and narrow P-Cygni lines, indicating low expansion velocities. This is one of the faintest LL SNe observed, with an absolute plateau magnitude of Mr = −14.5 mag and also one with the longest plateau lengths, with a duration of 118 days. Finally, the velocities measured from the nebular emission lines are among the lowest ever seen in a SN, with an intrinsic full width at half maximum value of 478 km s−1. The underluminous late-time exponential LC tail indicates that the mass of 56Ni ejected during the explosion is much smaller than the average of normal SNe IIP, we estimate M56Ni = 0.003 M⊙. The Monte Carlo fitting of the bolometric LC suggests that the progenitor of SN 2020cxd had a radius of R0 = 1.3 × 1013 cm, kinetic energy of Ekin = 4.3 × 1050 erg, and ejecta mass of Mej = 9.5 M⊙. From the bolometric LC, we estimated the total radiated energy Erad = 1.52 × 1048 erg. Using our late-time nebular spectra, we compared these results against SN II spectral synthesis models to constrain the progenitor zero-age main sequence mass and found that it is likely to be ≲15 M⊙.Conclusions. SN 2020cxd is a LL Type IIP SN. The inferred progenitor parameters and the features observed in the nebular spectrum favour a low-energy, Ni-poor, iron CC SN from a low-mass (∼12 M⊙) red supergiant.
28.	Andreoni, Igor, et al. (författare) Constraining the Kilonova Rate with Zwicky Transient Facility Searches Independent of Gravitational Wave and Short Gamma-Ray Burst Triggers 2020 Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 904:2 Tidskriftsartikel (refereegranskat)abstract The first binary neutron star merger, GW170817, was accompanied by a radioactivity-powered optical/infrared transient called a kilonova. To date, no compelling kilonova has been found in all-sky optical surveys, independently of short gamma-ray burst and gravitational-wave triggers. In this work, we searched the first 23 months of the Zwicky Transient Facility (ZTF) data stream for candidate kilonovae in the form of rapidly evolving transients. We combined ZTF alert queries with forced point-spread-function photometry and nightly flux stacking to increase our sensitivity to faint and fast transients. Automatic queries yielded >11,200 candidates, 24 of which passed quality checks and selection criteria based on a grid of kilonova models tailored for both binary neutron star and neutron star-black hole mergers. None of the candidates in our sample was deemed a possible kilonova after thorough vetting. The sources that passed our selection criteria are dominated by Galactic cataclysmic variables. We identified two fast transients at high Galactic latitude, one of which is the confirmed afterglow of long-duration GRB.190106A, the other is a possible cosmological afterglow. Using a survey simulation code, we constrained the kilonova rate for a range of models including top-hat, linearly decaying light curves, and synthetic light curves obtained with radiative transfer simulations. For prototypical GW170817-like kilonovae, we constrain the rate to be R < 1775 Gpc(-3) yr(-1) (95% confidence). By assuming a population of kilonovae with the same geometry and composition of GW170817 observed under a uniform viewing angle distribution, we obtained a constraint on the rate of R.<.4029 Gpc(-3) yr(-1).
29.	Andreoni, Igor, et al. (författare) GROWTH on S190814bv : Deep Synoptic Limits on the Optical/Near-infrared Counterpart to a Neutron Star-Black Hole Merger 2020 Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 890:2 Tidskriftsartikel (refereegranskat)abstract On 2019 August 14, the Advanced LIGO and Virgo interferometers detected the high-significance gravitational wave (GW) signal S190814bv. The GW data indicated that the event resulted from a neutron star-black hole (NSBH) merger, or potentially a low-mass binary BH merger. Due to the low false-alarm rate and the precise localization (23 deg(2) at 90%), S190814bv presented the community with the best opportunity yet to directly observe an optical/near-infrared counterpart to an NSBH merger. To search for potential counterparts, the GROWTH Collaboration performed real-time image subtraction on six nights of public Dark Energy Camera images acquired in the 3 weeks following the merger, covering >98% of the localization probability. Using a worldwide network of follow-up facilities, we systematically undertook spectroscopy and imaging of optical counterpart candidates. Combining these data with a photometric redshift catalog, we ruled out each candidate as the counterpart to S190814bv and placed deep, uniform limits on the optical emission associated with S190814bv. For the nearest consistent GW distance, radiative transfer simulations of NSBH mergers constrain the ejecta mass of S190814bv to be M-ej < 0.04 M-circle dot at polar viewing angles, or M-ej < 0.03 M-circle dot if the opacity is kappa < 2 cm(2)g(-1). Assuming a tidal deformability for the NS at the high end of the range compatible with GW170817 results, our limits would constrain the BH spin component aligned with the orbital momentum to be chi < 0.7 for mass ratios Q < 6, with weaker constraints for more compact NSs.
30.	Archer, TC, et al. (författare) Proteomics, Post-translational Modifications, and Integrative Analyses Reveal Molecular Heterogeneity within Medulloblastoma Subgroups 2018 Ingår i: Cancer cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 34:3, s. 396- Tidskriftsartikel (refereegranskat)
31.	Bauer, CM, et al. (författare) A novel assistive therapy chair to improve trunk control during neurorehabilitation: Perceptions of physical therapists and patients 2021 Ingår i: Applied ergonomics. - : Elsevier BV. - 1872-9126 .- 0003-6870. ; 94, s. 103390- Tidskriftsartikel (refereegranskat)
32.	Bronzwaer, S.L.A.M., et al. (författare) The relationship between antimicrobial use and antimicrobial resistance in Europe. 2002 Ingår i: Emerg Infect Dis. ; 8, s. 278- Tidskriftsartikel (refereegranskat)
33.	Chagtai, Tasnim, et al. (författare) Gain of 1q as a prognostic biomarker in Wilms Tumors (WTs) treated with preoperative chemotherapy in the International Society of Paediatric Oncology (SIOP) WT 2001 trial : A SIOP renal tumours biology consortium study 2016 Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 34:26, s. 3195-3203 Tidskriftsartikel (refereegranskat)abstract Purpose: Wilms tumor (WT) is the most common pediatric renal tumor. Treatment planning under International Society of Paediatric Oncology (SIOP) protocols is based on staging and histologic assessment of response to preoperative chemotherapy. Despite high overall survival (OS), many relapses occur in patients without specific risk factors, and many successfully treated patients are exposed to treatments with significant risks of late effects. To investigate whether molecular biomarkers could improve risk stratification, we assessed 1q status and other potential copy number biomarkers in a large WT series. Materials and Methods: WT nephrectomy samples from 586 SIOP WT 2001 patients were analyzed using a multiplex ligation-dependent probe amplification (MLPA) assay that measured the copy number of 1q and other regions of interest. Results: One hundred sixty-seven (28%) of 586 WTs had 1q gain. Five-year event-free survival (EFS) was 75.0% in patients with 1q gain (95% CI, 68.5% to 82.0%) and 88.2% in patients without gain (95% CI, 85.0% to 91.4%). OS was 88.4% with gain (95% CI, 83.5% to 93.6%) and 94.4% without gain (95% CI, 92.1% to 96.7%). In univariable analysis, 1q gain was associated with poorer EFS (P < .001; hazard ratio, 2.33) and OS (P = .01; hazard ratio, 2.16). The association of 1q gain with poorer EFS retained significance in multivariable analysis adjusted for 1p and 16q loss, sex, stage, age, and histologic risk group. Gain of 1q remained associated with poorer EFS in tumor subsets limited to either intermediate-risk localized disease or nonanaplastic localized disease. Other notable aberrations associated with poorer EFS included MYCN gain and TP53 loss. Conclusion: Gain of 1q is a potentially valuable prognostic biomarker in WT, in addition to histologic response to preoperative chemotherapy and tumor stage.
34.	Chomiuk, Laura, et al. (författare) Classical Novae at Radio Wavelengths 2021 Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 257:2 Tidskriftsartikel (refereegranskat)abstract We present radio observations (1-40 GHz) for 36 classical novae, representing data from over five decades compiled from the literature, telescope archives, and our own programs. Our targets display a striking diversity in their optical parameters (e.g., spanning optical fading timescales, t (2) = 1-263 days), and we find a similar diversity in the radio light curves. Using a brightness temperature analysis, we find that radio emission from novae is a mixture of thermal and synchrotron emission, with nonthermal emission observed at earlier times. We identify high brightness temperature emission (T ( B ) > 5 x 10(4) K) as an indication of synchrotron emission in at least nine (25%) of the novae. We find a class of synchrotron-dominated novae with mildly evolved companions, exemplified by V5589 Sgr and V392 Per, that appear to be a bridge between classical novae with dwarf companions and symbiotic binaries with giant companions. Four of the novae in our sample have two distinct radio maxima (the first dominated by synchrotron and the later by thermal emission), and in four cases the early synchrotron peak is temporally coincident with a dramatic dip in the optical light curve, hinting at a common site for particle acceleration and dust formation. We publish the light curves in a machine-readable table and encourage the use of these data by the broader community in multiwavelength studies and modeling efforts.
35.	Dyberg, C, et al. (författare) Inhibition of Rho-Associated Kinase Suppresses Medulloblastoma Growth 2020 Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:1 Tidskriftsartikel (refereegranskat)abstract Medulloblastoma is one of the most common malignant brain tumor types in children, with an overall survival of 70%. Mortality is associated with metastatic relapsed tumors. Rho-associated kinases (ROCKs), important for epithelial-mesenchymal transition (EMT) and proper nervous system development, have previously been identified as a promising drug target to inhibit cancer growth and metastatic spread. Here, we show that ROCKs are expressed in medulloblastoma, with higher ROCK2 mRNA expression in metastatic compared to non-metastatic tumors. By evaluating three ROCK inhibitors in a panel of medulloblastoma cell lines we demonstrated that medulloblastoma cells were sensitive for pharmacological ROCK inhibition. The specific ROCK inhibitor RKI-1447 inhibited the tumorigenicity in medulloblastoma cells as well as impeded cell migration and invasion. Differential gene expression analysis suggested that ROCK inhibition was associated with the downregulation of signaling pathways important in proliferation and metastasis e.g., TNFα via NFκβ, TGFβ, and EMT. Expression of key proteins in these pathways such as RHOA, RHOB, JUN, and vimentin was downregulated in ROCK inhibited cells. Finally, we showed that ROCK inhibition by RKI-1447 suppressed medulloblastoma growth and proliferation in vivo. Collectively, our results suggest that ROCK inhibition presents a potential new therapeutic option in medulloblastoma, especially for children with metastatic disease.
36.	Dyberg, CH, et al. (författare) Wnt/beta-catenin signaling regulates the expression of O6-methylguanine DNA-methyltransferase in cancer cells: a new strategy to overcome resistance for DNA alkylators in cancer therapy 2012 Ingår i: CANCER RESEARCH. - 0008-5472. ; 72 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
37.	Dyberg, C, et al. (författare) Wnt/BETA-CATENIN SIGNALING REGULATES THE EXPRESSION OF O6-METHYLGUANINE DNA-METHYLTRANSFERASE IN MEDULLOBLASTOMA CELLS: A NEW STRATEGY TO INCREASE SENSITIVITY FOR DNA ALKYLATORS IN CANCER THERAPY 2012 Ingår i: NEURO-ONCOLOGY. - 1522-8517. ; 14, s. 13-14 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
38.	Hayden, JA, et al. (författare) Exercise treatment effect modifiers in persistent low back pain: an individual participant data meta-analysis of 3514 participants from 27 randomised controlled trials 2020 Ingår i: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 54:21, s. 1277- Tidskriftsartikel (refereegranskat)abstract Low back pain is one of the leading causes of disability worldwide. Exercise therapy is widely recommended to treat persistent non-specific low back pain. While evidence suggests exercise is, on average, moderately effective, there remains uncertainty about which individuals might benefit the most from exercise.MethodsIn parallel with a Cochrane review update, we requested individual participant data (IPD) from high-quality randomised clinical trials of adults with our two primary outcomes of interest, pain and functional limitations, and calculated global recovery. We compiled a master data set including baseline participant characteristics, exercise and comparison characteristics, and outcomes at short-term, moderate-term and long-term follow-up. We conducted descriptive analyses and one-stage IPD meta-analysis using multilevel mixed-effects regression of the overall treatment effect and prespecified potential treatment effect modifiers.ResultsWe received IPD for 27 trials (3514 participants). For studies included in this analysis, compared with no treatment/usual care, exercise therapy on average reduced pain (mean effect/100 (95% CI) −10.7 (−14.1 to –7.4)), a result compatible with a clinically important 20% smallest worthwhile effect. Exercise therapy reduced functional limitations with a clinically important 23% improvement (mean effect/100 (95% CI) −10.2 (−13.2 to –7.3)) at short-term follow-up. Not having heavy physical demands at work and medication use for low back pain were potential treatment effect modifiers—these were associated with superior exercise outcomes relative to non-exercise comparisons. Lower body mass index was also associated with better outcomes in exercise compared with no treatment/usual care. This study was limited by inconsistent availability and measurement of participant characteristics.ConclusionsThis study provides potentially useful information to help treat patients and design future studies of exercise interventions that are better matched to specific subgroups.Protocol publicationhttps://doi.org/10.1186/2046-4053-1-64
39.	Johnsen, J, et al. (författare) THE WNT/beta-CATENIN SIGNALING PATHWAY REGULATES MGMT GENE EXPRESSION IN CHILDHOOD NEURAL TUMORS AND INHIBITION OF WNT SIGNALING PREVENTS CHEMORESISTANCE 2015 Ingår i: PEDIATRIC BLOOD & CANCER. - 1545-5009. ; 62, s. S276-S276 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
40.	Korhonen, P, et al. (författare) Pioglitazone use and risk of bladder cancer in patients with type 2 diabetes: retrospective cohort study using datasets from four European countries 2016 Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833. ; 354, s. i3903- Tidskriftsartikel (refereegranskat)
41.	Lundqvist, Peter, et al. (författare) Radio observations of nearby Type Ia Supernovae Annan publikation (övrigt vetenskapligt/konstnärligt)
42.	Milosevic, J, et al. (författare) Expression of O6-methylguanine DNA-methyltransferase is regulated by Wnt/beta-catenin signalling in cancer cells: A new strategy for DNA alkylators in cancer therapy 2011 Ingår i: CANCER RESEARCH. - 0008-5472. ; 71 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
43.	Reynolds, T. M., et al. (författare) Energetic nuclear transients in luminous and ultraluminous infrared galaxies 2022 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 664 Tidskriftsartikel (refereegranskat)abstract Energetic nuclear outbursts have been discovered in luminous and ultraluminous infrared galaxies (U/LIRGs) at unexpectedly high rates. To investigate this population of transients, we performed a search in mid-IR data from the Wide-field Infrared Survey Explorer (WISE) satellite and its NEOWISE survey to detect and characterise luminous and smoothly evolving transients in a sample of 215 U/LIRGs. We report three new transients, all with ΔL > 1043 erg s−1, in addition to two previously known cases. Their host galaxies are all part of major galaxy mergers, and through radiative transfer model fitting we find that all have a significant contribution from an active galactic nucleus (AGN). We characterised the transients through measurements of their luminosities and resulting energetics, all of which are between 1050.9 erg and 1052.2 erg. The IR emission of the five transients was found to be consistent with re-radiation by the hot dust of emission at shorter wavelengths, presumably originating from an accretion event, onto the supermassive black hole. The corresponding transient rate of (1.6–4.6) × 10−3 yr−1 galaxy−1 is over an order of magnitude higher than the rate of large amplitude flares shown by AGN in the optical. We suggest that the observed transients are part of a dust-obscured population of tidal disruption events (TDEs) that have remained out of the reach of optical surveys due to the obscuring dust. In one case, this is supported by our radio observations. We also discuss other plausible explanations. The observed rate of events is significantly higher than optical TDE rates, which can be expected in U/LIRG hosts undergoing a major galaxy merger with increased stellar densities in the nuclear regions. Continued searches for such transients and their multi-wavelength follow-up is required to constrain their rate and nature.
44.	Sandén, Emma, et al. (författare) Establishment and characterization of an orthotopic patient-derived Group 3 medulloblastoma model for preclinical drug evaluation 2017 Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7, s. 46366- Tidskriftsartikel (refereegranskat)abstract Medulloblastomas comprise a heterogeneous group of tumours and can be subdivided into four molecular subgroups (WNT, SHH, Group 3 and Group 4) with distinct prognosis, biological behaviour and implications for targeted therapies. Few experimental models exist of the aggressive and poorly characterized Group 3 tumours. In order to establish a reproducible transplantable Group 3 medulloblastoma model for preclinical therapeutic studies, we acquired a patient-derived tumour sphere culture and inoculated low-passage spheres into the cerebellums of NOD-scid mice. Mice developed symptoms of brain tumours with a latency of 17–18 weeks. Neurosphere cultures were re-established and serially transplanted for 3 generations, with a negative correlation between tumour latency and numbers of injected cells. Xenografts replicated the phenotype of the primary tumour, including high degree of clustering in DNA methylation analysis, high proliferation, expression of tumour markers, MYC amplification and elevated MYC expression, and sensitivity to the MYC inhibitor JQ1. Xenografts maintained maintained expression of tumour-derived VEGFA and stromal-derived COX-2. VEGFA, COX-2 and c-Myc are highly expressed in Group 3 compared to other medulloblastoma subgroups, suggesting that these molecules are relevant therapeutic targets in Group 3 medulloblastoma.
45.	Slavc, I, et al. (författare) Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a "MEMMAT-like" Metronomic Antiangiogenic Approach 2022 Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:20 Tidskriftsartikel (refereegranskat)abstract Medulloblastoma (MB) recurrence is usually incurable despite intensive therapy including high-dose chemotherapy. An evolving alternative approach to conventional chemotherapy aims at interfering with tumor angiogenesis at different levels. We report on a novel combinatorial metronomic antiangiogenic approach. The study is a retrospective observational study of 29 consecutive patients with first or multiple recurrences prospectively treated according to the MEMMAT strategy (“MEMMAT-like”) before the formal protocol (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290) started. The study period was 11/2006 to 06/2016. Treatment consisted of daily oral thalidomide, fenofibrate, celecoxib, and alternating 21-day cycles of low-dose oral etoposide and cyclophosphamide supplemented by IV bevacizumab and intraventricular therapy consisting of alternating etoposide and liposomal cytarabine. Median overall survival (OS) after recurrence for the whole group was 29.5 months, OS was 48.3 ± 9.3% at three years and 34.5 ± 8.8% at five years, and progression-free survival was 42.0 ± 9.5% at three years and 29.4 ± 9% at five years. As of 07/2022, 9/29 patients are alive 86 to 164 months after the recurrence that prompted the “MEMMAT-like” therapy. Treatment was primarily out-patient and generally well-tolerated. Toxicities did occur but were manageable. In conclusion, antiangiogenic therapy according to the MEMMAT strategy increased median OS of patients with recurrent MB and may lead to long-term survival. Adherence to the protocol, including intraventricular therapy, appears important.
46.	Strongman, H, et al. (författare) Pioglitazone and risk of mortality in patients with type 2 diabetes: results from a European multidatabase cohort study 2017 Ingår i: BMJ open diabetes research & care. - : BMJ. - 2052-4897. ; 5:1, s. e000364- Tidskriftsartikel (refereegranskat)
47.	Tartaglia, Leonardo, et al. (författare) The long-lived Type IIn SN 2015da : Infrared echoes and strong interaction within an extended massive shell star star star 2020 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635 Tidskriftsartikel (refereegranskat)abstract In this paper we report the results of the first similar to four years of spectroscopic and photometric monitoring of the Type IIn supernova SN 2015da (also known as PSN J13522411+3941286, or iPTF16tu). The supernova exploded in the nearby spiral galaxy NGC 5337 in a relatively highly extinguished environment. The transient showed prominent narrow Balmer lines in emission at all times and a slow rise to maximum in all bands. In addition, early observations performed by amateur astronomers give a very well-constrained explosion epoch. The observables are consistent with continuous interaction between the supernova ejecta and a dense and extended H-rich circumstellar medium. The presence of such an extended and dense medium is difficult to reconcile with standard stellar evolution models, since the metallicity at the position of SN 2015da seems to be slightly subsolar. Interaction is likely the mechanism powering the light curve, as confirmed by the analysis of the pseudo bolometric light curve, which gives a total radiated energy greater than or similar to 10(51) erg. Modeling the light curve in the context of a supernova shock breakout through a dense circumstellar medium allowed us to infer the mass of the prexisting gas to be similar or equal to 8 M-circle dot, with an extreme mass-loss rate for the progenitor star similar or equal to 0.6 M-circle dot yr(-1), suggesting that most of the circumstellar gas was produced during multiple eruptive events. Near- and mid-infrared observations reveal a fluxexcess in these domains, similar to those observed in SN 2010jl and other interacting transients, likely due to preexisting radiatively heated dust surrounding the supernova. By modeling the infrared excess, we infer a mass greater than or similar to 0.4 x 10(-3) M-circle dot for the dust.
48.	Tazelaar, Gijs H. P., et al. (författare) Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort 2019 Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 74, s. 234.e9-234.e15 Tidskriftsartikel (refereegranskat)abstract NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8×10−5). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS.
49.	van Velzen, Sjoert, et al. (författare) Establishing accretion flares from supermassive black holes as a source of high-energy neutrinos 2024 Ingår i: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 529:3, s. 2559-2576 Tidskriftsartikel (refereegranskat)abstract The origin of cosmic high-energy neutrinos remains largely unexplained. For high-energy neutrino alerts from IceCube, a coincidence with time-variable emission has been seen for three different types of accreting black holes: (1) a gamma-ray flare from a blazar (TXS 0506+056), (2) an optical transient following a stellar tidal disruption event (TDE; AT2019dsg), and (3) an optical outburst from an active galactic nucleus (AGN; AT2019fdr). For the latter two sources, infrared follow-up observations revealed a powerful reverberation signal due to dust heated by the flare. This discovery motivates a systematic study of neutrino emission from all supermassive black hole with similar dust echoes. Because dust reprocessing is agnostic to the origin of the outburst, our work unifies TDEs and high-amplitude flares from AGN into a population that we dub accretion flares. Besides the two known events, we uncover a third flare that is coincident with a PeV-scale neutrino (AT2019aalc). Based solely on the optical and infrared properties, we estimate a significance of 3.6σ for this association of high-energy neutrinos with three accretion flares. Our results imply that at least ∼10 per cent of the IceCube high-energy neutrino alerts could be due to accretion flares. This is surprising because the sum of the fluence of these flares is at least three orders of magnitude lower compared to the total fluence of normal AGN. It thus appears that the efficiency of high-energy neutrino production in accretion flares is increased compared to non-flaring AGN. We speculate that this can be explained by the high Eddington ratio of the flares.
50.	Willems, M. C. M., et al. (författare) Assessing endovascular skills using the Simulator for Testing and Rating Endovascular Skills (STRESS) machine 2009 Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 37:4, s. 431-6 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: Endovascular techniques are an integral part of modern-day vascular surgery practice and training. Nevertheless, validated in vitro assessment tools for these skills are scarce. This study describes the development and pilot testing of the Simulator for Testing and Rating Endovascular Skills (STRESS machine). DESIGN: The design was kept straightforward and compact, without the need for contrast or fluoroscopy. A specific technical skill score was designed analogous to the Imperial College Evaluation of Procedural Skill (ICEPS), an assessment score for open surgical skill. This score was combined with an already validated global rating assessment to form the total score (TS). METHODS: A pilot study was carried out on 18 candidates of varying levels of expertise: novice, intermediate and expert, who were assessed by two independent observers to test inter-observer reliability. RESULTS: Inter-observer reliability was excellent, Cronbach's alpha coefficient of the TS was 0.94 (95% confidence interval: 0.84-0.97). A one-way analysis of variance (ANOVA) showed a significant difference between the novice and expert groups (p<0.001), between the novice and intermediate groups (p<0.01) and between the intermediate and expert groups (p<0.05). CONCLUSION: The STRESS machine, in combination with the specific technical skill score and global rating assessment, provides a reliable method of discriminating between the novice, intermediate and expert candidates with excellent inter-observer variability.

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