| 1. |
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| 2. |
- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 3. |
- van Haarlem, M. P., et al.
(författare)
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LOFAR : The LOw-Frequency ARray
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 556, s. 1-53
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Tidskriftsartikel (refereegranskat)abstract
- LOFAR, the LOw-Frequency ARray, is a new-generation radio interferometer constructed in the north of the Netherlands and across europe. Utilizing a novel phased-array design, LOFAR covers the largely unexplored low-frequency range from 10–240 MHz and provides a number of unique observing capabilities. Spreading out from a core located near the village of Exloo in the northeast of the Netherlands, a total of 40 LOFAR stations are nearing completion. A further five stations have been deployed throughout Germany, and one station has been built in each of France, Sweden, and the UK. Digital beam-forming techniques make the LOFAR system agile and allow for rapid repointing of the telescope as well as the potential for multiple simultaneous observations. With its dense core array and long interferometric baselines, LOFAR achieves unparalleled sensitivity and angular resolution in the low-frequency radio regime. The LOFAR facilities are jointly operated by the International LOFAR Telescope (ILT) foundation, as an observatory open to the global astronomical community. LOFAR is one of the first radio observatories to feature automated processing pipelines to deliver fully calibrated science products to its user community. LOFAR’s new capabilities, techniques and modus operandi make it an important pathfinder for the Square Kilometre Array (SKA). We give an overview of the LOFAR instrument, its major hardware and software components, and the core science objectives that have driven its design. In addition, we present a selection of new results from the commissioning phase of this new radio observatory.
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| 4. |
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| 5. |
- Abreu, A., et al.
(författare)
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Priorities for ocean microbiome research
- 2022
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Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 7:7, s. 937-947
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Tidskriftsartikel (refereegranskat)abstract
- Studying the ocean microbiome can inform international policies related to ocean governance, tackling climate change, ocean acidification and pollution, and can help promote achievement of multiple Sustainable Development Goals. Microbial communities have essential roles in ocean ecology and planetary health. Microbes participate in nutrient cycles, remove huge quantities of carbon dioxide from the air and support ocean food webs. The taxonomic and functional diversity of the global ocean microbiome has been revealed by technological advances in sampling, DNA sequencing and bioinformatics. A better understanding of the ocean microbiome could underpin strategies to address environmental and societal challenges, including achievement of multiple Sustainable Development Goals way beyond SDG 14 'life below water'. We propose a set of priorities for understanding and protecting the ocean microbiome, which include delineating interactions between microbiota, sustainably applying resources from oceanic microorganisms and creating policy- and funder-friendly ocean education resources, and discuss how to achieve these ambitious goals.
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| 6. |
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| 7. |
- van Cappellen, W., et al.
(författare)
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Apertif: Phased array feeds for the Westerbork Synthesis Radio Telescope: System overview and performance characteristics
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
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Tidskriftsartikel (refereegranskat)abstract
- We describe the APERture Tile In Focus (Apertif) system, a phased array feed (PAF) upgrade of the Westerbork Synthesis Radio Telescope that transforms this telescope into a high-sensitivity, wide-field-of-view L-band imaging and transient survey instrument. Using novel PAF technology, up to 40 partially overlapping beams are formed on the sky simultaneously, significantly increasing the survey speed of the telescope. With this upgraded instrument, an imaging survey covering an area of 2300 deg2 is being performed that will deliver both continuum and spectral line datasets, of which the first data have been publicly released. In addition, a time domain transient and pulsar survey covering 15 000 deg2 is in progress. An overview of the Apertif science drivers, hardware, and software of the upgraded telescope is presented, along with its key performance characteristics.
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| 8. |
- Gehlot, B. K., et al.
(författare)
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The first power spectrum limit on the 21-cm signal of neutral hydrogen during the Cosmic Dawn at z=20-25 from LOFAR
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 488:3, s. 4271-4287
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Tidskriftsartikel (refereegranskat)abstract
- Observations of the redshifted 21-cm hyperfine line of neutral hydrogen from early phases of the Universe such as Cosmic Dawn and the Epoch of Reionization promise to open a new window onto the early formation of stars and galaxies. We present the first upper limits on the power spectrum of redshifted 21-cm brightness temperature fluctuations in the redshift range z = 19.8-25.2 (54-68 MHz frequency range) using 14 h of data obtained with the LOFAR-Low Band Antenna (LBA) array. We also demonstrate the application of a multiple pointing calibration technique to calibrate the LOFAR-LBA dual-pointing observations centred on the North Celestial Pole and the radio galaxy 3C220.3, We observe an unexplained excess of similar to 30-50 per cent in Stokes / noise compared to Stokes V for the two observed fields, which decorrelates on greater than or similar to 12 s and might have a physical origin. We show that enforcing smoothness of gain errors along frequency direction during calibration reduces the additional variance in Stokes I compared Stokes V introduced by the calibration on sub-band level. After subtraction of smooth foregrounds, we achieve a 2 sigma upper limit on the 21-cm power spectrum of Delta(2)(21) < (14561 mK)(2) at k similar to 0.038 h cMpc(-1) and Delta(2)(21) < (14886 mK)(2) at k 0.038 h cMpc(-1) for the 3C220 and NCP fields respectively and both upper limits are consistent with each other. The upper limits for the two fields are still dominated by systematics on most k modes.
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| 9. |
- Gerrits, E, et al.
(författare)
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Distinct amyloid-β and tau-associated microglia profiles in Alzheimer's disease
- 2021
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Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 141:5, s. 681-696
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is the most prevalent form of dementia and is characterized by abnormal extracellular aggregates of amyloid-β and intraneuronal hyperphosphorylated tau tangles and neuropil threads. Microglia, the tissue-resident macrophages of the central nervous system (CNS), are important for CNS homeostasis and implicated in AD pathology. In amyloid mouse models, a phagocytic/activated microglia phenotype has been identified. How increasing levels of amyloid-β and tau pathology affect human microglia transcriptional profiles is unknown. Here, we performed snRNAseq on 482,472 nuclei from non-demented control brains and AD brains containing only amyloid-β plaques or both amyloid-β plaques and tau pathology. Within the microglia population, distinct expression profiles were identified of which two were AD pathology-associated. The phagocytic/activated AD1-microglia population abundance strongly correlated with tissue amyloid-β load and localized to amyloid-β plaques. The AD2-microglia abundance strongly correlated with tissue phospho-tau load and these microglia were more abundant in samples with overt tau pathology. This full characterization of human disease-associated microglia phenotypes provides new insights in the pathophysiological role of microglia in AD and offers new targets for microglia-state-specific therapeutic strategies.
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| 10. |
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| 11. |
- Ghara, Raghunath, et al.
(författare)
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Constraining the intergalactic medium at z approximate to 9.1 using LOFAR Epoch of Reionization observations
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 493:4, s. 4728-4747
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Tidskriftsartikel (refereegranskat)abstract
- We derive constraints on the thermal and ionization states of the intergalactic medium (IGM) at redshift approximate to 9.1 using new upper limits on the 21-cm power spectrum measured by the LOFAR radio telescope and a prior on the ionized fraction at that redshift estimated from recent cosmic microwave background (CMB) observations. We have used results from the reionization simulation code GRIZZLY and a Bayesian inference framework to constrain the parameters which describe the physical state of the IGM. We find that, if the gas heating remains negligible, an IGM with ionized fraction greater than or similar to 0.13 and a distribution of the ionized regions with a characteristic size greater than or similar to 8 h(-1) comoving megaparsec (Mpc) and a full width at half-maximum (FWHM) greater than or similar to 16 h(-1) Mpc is ruled out. For an IGM with a uniform spin temperature T-S greater than or similar to 3 K, no constraints on the ionized component can be computed. If the large-scale fluctuations of the signal are driven by spin temperature fluctuations, an IGM with a volume fraction less than or similar to 0.34 of heated regions with a temperature larger than CMB, average gas temperature 7-160 K, and a distribution of the heated regions with characteristic size 3.5-70 h(-1) Mpc and FWHM of less than or similar to 110 h(-1) Mpc is ruled out. These constraints are within the 95 per cent credible intervals. With more stringent future upper limits from LOFAR at multiple redshifts, the constraints will become tighter and will exclude an increasingly large region of the parameter space.
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| 12. |
- McNamee, Sara E., et al.
(författare)
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Distribution, occurrence and biotoxin composition of the main shellfish toxin producing microalgae within European waters : A comparison of methods of analysis
- 2016
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Ingår i: Harmful Algae. - : Elsevier BV. - 1568-9883 .- 1878-1470. ; 55, s. 112-120
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Tidskriftsartikel (refereegranskat)abstract
- Harmful algal blooms (HABs) are a natural global phenomena emerging in severity and extent. Incidents have many economic, ecological and human health impacts. Monitoring and providing early warning of toxic HABs are critical for protecting public health. Current monitoring programmes include measuring the number of toxic phytoplankton cells in the water and biotoxin levels in shellfish tissue. As these efforts are demanding and labour intensive, methods which improve the efficiency are essential. This study compares the utilisation of a multitoxin surface plasmon resonance (multitoxin SPR) biosensor with enzyme-linked immunosorbent assay (ELISA) and analytical methods such as high performance liquid chromatography with fluorescence detection (HPLC-FLD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for toxic HAB monitoring efforts in Europe. Seawater samples (n = 256) from European waters, collected 2009-2011, were analysed for biotoxins: saxitoxin and analogues, okadaic acid and dinophysistoxins 1/2 (VDU /DTX2) and domoic acid responsible for paralytic shellfish poisoning (PSP), diarrheic shellfish poisoning (DSP) and amnesic shellfish poisoning (ASP), respectively. Biotoxins were detected mainly in samples from Spain and Ireland. France and Norway appeared to have the lowest number of toxic samples. Both the multitoxin SPR biosensor and the RNA microarray were more sensitive at detecting toxic HABs than standard light microscopy phytoplankton monitoring. Correlations between each of the detection methods were performed with the overall agreement, based on statistical 2 x 2 comparison tables, between each testing platform ranging between 32% and 74% for all three toxin families illustrating that one individual testing method may not be an ideal solution. An efficient early warning monitoring system for the detection of toxic HABs could therefore be achieved by combining both the multitoxin SPR biosensor and RNA microarray. (C) 2016 Elsevier B.V. All rights reserved.
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| 13. |
- Mertens, F. G., et al.
(författare)
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Improved upper limits on the 21 cm signal power spectrum of neutral hydrogen at z approximate to 9.1 from LOFAR
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 493:2, s. 1662-1685
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Tidskriftsartikel (refereegranskat)abstract
- A new upper limit on the 21 cm signal power spectrum at a redshift of z approximate to 9.1 is presented, based on 141 h of data obtained with the Low-Frequency Array (LOFAR). The analysis includes significant improvements in spectrally smooth gain-calibration, Gaussian Process Regression (GPR) foreground mitigation and optimally weighted power spectrum inference. Previously seen 'excess power' due to spectral structure in the gain solutions has markedly reduced but some excess power still remains with a spectral correlation distinct from thermal noise. This excess has a spectral coherence scale of 0.25-0.45 MHz and is partially correlated between nights, especially in the foreground wedge region. The correlation is stronger between nights covering similar local sidereal times. A best 2-sigma upper limit of Delta(2)(21) < (73)(2) mK(2) at k = 0.075 h cMpc(-1) is found, an improvement by a factor approximate to 8 in power compared to the previously reported upper limit. The remaining excess power could be due to residual foreground emission from sources or diffuse emission far away from the phase centre, polarization leakage, chromatic calibration errors, ionosphere, or low-level radiofrequency interference. We discuss future improvements to the signal processing chain that can further reduce or even eliminate these causes of excess power.
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| 14. |
- Oostrum, L. C., et al.
(författare)
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Repeating fast radio bursts with WSRT/Apertif
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635
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Tidskriftsartikel (refereegranskat)abstract
- Context. Repeating fast radio bursts (FRBs) present excellent opportunities to identify FRB progenitors and host environments as well as to decipher the underlying emission mechanism. Detailed studies of repeating FRBs might also hold clues as to the origin of FRBs as a population. Aims. We aim to detect bursts from the first two repeating FRBs, FRB 121102 (R1) and FRB 180814.J0422+73 (R2), and to characterise their repeat statistics. We also want to significantly improve the sky localisation of R2 and identify its host galaxy. Methods. We used the Westerbork Synthesis Radio Telescope to conduct extensive follow-up of these two repeating FRBs. The new phased-array feed system, Apertif, allows one to cover the entire sky position uncertainty of R2 with fine spatial resolution in a single pointing. The data were searched for bursts around the known dispersion measures of the two sources. We characterise the energy distribution and the clustering of detected R1 bursts. Results. We detected 30 bursts from R1. The non-Poissonian nature is clearly evident from the burst arrival times, which is consistent with earlier claims. Our measurements indicate a dispersion measure (DM) of 563.5(2) pc cm(-3), suggesting a significant increase in DM over the past few years. Assuming a constant position angle across the burst, we place an upper limit of 8% on the linear polarisation fraction for the brightest burst in our sample. We did not detect any bursts from R2. Conclusions. A single power-law might not fit the R1 burst energy distribution across the full energy range or widely separated detections. Our observations provide improved constraints on the clustering of R1 bursts. Our stringent upper limits on the linear polarisation fraction imply a significant depolarisation, either intrinsic to the emission mechanism or caused by the intervening medium at 1400 MHz, which is not observed at higher frequencies. The non-detection of any bursts from R2, despite nearly 300 h of observations, implies either a highly clustered nature of the bursts, a steep spectral index, or a combination of the two assuming that the source is still active. Another possibility is that R2 has turned off completely, either permanently or for an extended period of time.
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| 15. |
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