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- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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- Blokland, G. A. M., et al.
(author)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Journal article (peer-reviewed)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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- Jaffee, E. M., et al.
(author)
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Future cancer research priorities in the USA: a Lancet Oncology Commission
- 2017
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In: Lancet Oncology. - 1470-2045. ; 18:11
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Research review (peer-reviewed)abstract
- We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$ 2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.
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- Schweinsberg, Martin, et al.
(author)
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Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
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In: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Journal article (peer-reviewed)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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- Wright, Gillian, et al.
(author)
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The Mid-infrared Instrument for JWST and Its In-flight Performance
- 2023
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In: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 135:1046
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Journal article (peer-reviewed)abstract
- The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI.
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- Bouchet, P., et al.
(author)
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JWST MIRI Imager Observations of Supernova SN 1987A
- 2024
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 965:1
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Journal article (peer-reviewed)abstract
- There exist very few mid-infrared (IR) observations of supernovae (SNe) in general. Therefore, SN 1987A, the closest visible SN in 400 yr, gives us the opportunity to explore the mid-IR properties of SNe, the dust in their ejecta, and the surrounding medium and to witness the birth of an SN remnant (SNR). The James Webb Space Telescope, with its high spatial resolution and extreme sensitivity, gives a new view on these issues. We report on the first imaging observations obtained with the Mid-InfraRed Instrument (MIRI). We build temperature maps and discuss the morphology of the nascent SNR. Our results show that the temperatures in the equatorial ring (ER) are quite nonuniform. This could be due to dust destruction in some parts of the ring, as had been assumed in some previous works. We show that the IR emission extends beyond the ER, illustrating the fact that the shock wave has now passed through this ring to affect the circumstellar medium on a larger scale. Finally, while submillimeter Atacama Large Millimeter Array observations have hinted at the location of the compact remnant of SN 1987A, we note that our MIRI data have found no such evidence.
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- Fransson, Claes, 1951-, et al.
(author)
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Emission lines due to ionizing radiation from a compact object in the remnant of Supernova 1987A
- 2024
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 383:6685, s. 898-903
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Journal article (peer-reviewed)abstract
- The nearby Supernova 1987A was accompanied by a burst of neutrino emission, which indicates that a compact object (a neutron star or black hole) was formed in the explosion. There has been no direct observation of this compact object. In this work, we observe the supernova remnant with JWST spectroscopy, finding narrow infrared emission lines of argon and sulfur. The line emission is spatially unresolved and blueshifted in velocity relative to the supernova rest frame. We interpret the lines as gas illuminated by a source of ionizing photons located close to the center of the expanding ejecta. Photoionization models show that the line ratios are consistent with ionization by a cooling neutron star or a pulsar wind nebula. The velocity shift could be evidence for a neutron star natal kick.
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22. |
- Gasman, Danny, et al.
(author)
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JWST MIRI/MRS in-flight absolute flux calibration and tailored fringe correction for unresolved sources
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 673
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Journal article (peer-reviewed)abstract
- Context. The Medium Resolution Spectrometer (MRS) is one of the four observing modes of JWST/MIRI. Using JWST in-flight data of unresolved (point) sources, we can derive the MRS absolute spectral response function (ASRF) starting from raw data. Spectral fringing, caused by coherent reflections inside the detector arrays, plays a critical role in the derivation and interpretation of the MRS ASRF. The fringe corrections implemented in the current pipeline are not optimal for non-extended sources, and a high density of molecular features particularly inhibits an accurate correction. Aims. In this paper, we present an alternative way to calibrate the MIRI/MRS data. Firstly, we derive a fringe correction that accounts for the dependence of the fringe properties on the MIRI/MRS pupil illumination and detector pixel sampling of the point spread function. Secondly, we derive the MRS ASRF using an absolute flux calibrator observed across the full 5- 28 µm wavelength range of the MRS. Thirdly, we apply the new ASRF to the spectrum of a G dwarf and compare it with the output of the JWST/MIRI default data reduction pipeline. Finally, we examine the impact of the different fringe corrections on the detectability of molecular features in the G dwarf and K giant. Methods. The absolute flux calibrator HD 163466 (A-star) was used to derive tailored point source fringe flats at each of the default dither locations of the MRS. The fringe-corrected point source integrated spectrum of HD 163466 was used to derive the MRS ASRF using a theoretical model for the stellar continuum. A cross-correlation was run to quantify the uncertainty on the detection of CO, SiO, and OH in the K giant and CO in the G dwarf for different fringe corrections. Results. The point-source-tailored fringe correction and ASRF are found to perform at the same level as the current corrections, beating down the fringe contrast to the sub-percent level in the G dwarf in the longer wavelengths, whilst mitigating the alteration of real molecular features. The same tailored solutions can be applied to other MRS unresolved targets. Target acquisition is required to ensure the pointing is accurate enough to apply this method. A pointing repeatability issue in the MRS limits the effectiveness of the tailored fringe flats is at short wavelengths. Finally, resulting spectra require no scaling to make the sub-bands match, and a dichroic spectral leak at 12.2 µm is removed.
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23. |
- Jones, O. C., et al.
(author)
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Ejecta, Rings, and Dust in SN 1987A with JWST MIRI/MRS
- 2023
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 958:1
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Journal article (peer-reviewed)abstract
- Supernova (SN) 1987A is the nearest supernova in ∼400 yr. Using the JWST MIRI Medium Resolution Spectrograph, we spatially resolved the ejecta, equatorial ring (ER), and outer rings in the mid-infrared 12,927 days (35.4 yr) after the explosion. The spectra are rich in line and dust continuum emission, both in the ejecta and the ring. The broad emission lines (280–380 km s−1 FWHM) that are seen from all singly-ionized species originate from the expanding ER, with properties consistent with dense post-shock cooling gas. Narrower emission lines (100–170 km s−1 FWHM) are seen from species originating from a more extended lower-density component whose high ionization may have been produced by shocks progressing through the ER or by the UV radiation pulse associated with the original supernova event. The asymmetric east–west dust emission in the ER has continued to fade, with constant temperature, signifying a reduction in dust mass. Small grains in the ER are preferentially destroyed, with larger grains from the progenitor surviving the transition from SN into SNR. The ER dust is fit with a single set of optical constants, eliminating the need for a secondary featureless hot dust component. We find several broad ejecta emission lines from [Ne ii], [Ar ii], [Fe ii], and [Ni ii]. With the exception of [Fe ii] 25.99 μm, these all originate from the ejecta close to the ring and are likely to be excited by X-rays from the interaction. The [Fe ii] 5.34 to 25.99 μm line ratio indicates a temperature of only a few hundred K in the inner core, which is consistent with being powered by 44 Ti decay.
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