| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)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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| 9. |
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| 11. |
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| 13. |
- Carter, J. A., et al.
(författare)
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Ground-based and additional science support for SMILE
- 2024
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Ingår i: Earth and Planetary Physics. - : Science Press. - 2096-3955. ; 8:1, s. 275-298
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Tidskriftsartikel (refereegranskat)abstract
- The joint European Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions, and simultaneously monitor the auroral response of the Northern Hemisphere ionosphere. Combining these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILE mission. Here, we describe current community efforts to prepare for SMILE, and the benefits and context various experiments that have explicitly expressed support for SMILE can offer. A dedicated group of international scientists representing many different experiment types and geographical locations, the Ground-based and Additional Science Working Group, is facilitating these efforts. Preparations include constructing an online SMILE Data Fusion Facility, the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar, and the consideration of particular observing strategies and spacecraft conjunctions. We anticipate growing interest and community engagement with the SMILE mission, and we welcome novel ideas and insights from the solar-terrestrial community.
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| 14. |
- Jaffee, E. M., et al.
(författare)
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Future cancer research priorities in the USA: a Lancet Oncology Commission
- 2017
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Ingår i: Lancet Oncology. - 1470-2045. ; 18:11
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Forskningsöversikt (refereegranskat)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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| 15. |
- Bouchet, P., et al.
(författare)
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JWST MIRI Imager Observations of Supernova SN 1987A
- 2024
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 965:1
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Tidskriftsartikel (refereegranskat)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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| 16. |
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| 17. |
- Fransson, Claes, 1951-, et al.
(författare)
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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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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 383:6685, s. 898-903
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Tidskriftsartikel (refereegranskat)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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| 18. |
- Jones, O. C., et al.
(författare)
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Ejecta, Rings, and Dust in SN 1987A with JWST MIRI/MRS
- 2023
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 958:1
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Tidskriftsartikel (refereegranskat)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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| 19. |
- Larsson, Josefin, et al.
(författare)
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JWST NIRSpec Observations of Supernova 1987A : From the Inner Ejecta to the Reverse Shock
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 949:2
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Tidskriftsartikel (refereegranskat)abstract
- We present initial results from JWST NIRSpec integral field unit observations of the nearby supernova SN 1987A. The observations provide the first spatially resolved spectroscopy of the ejecta and equatorial ring (ER) over the 1-5 μm range. We construct 3D emissivity maps of the [Fe i] 1.443 μm line from the inner ejecta and the He i 1.083 μm line from the reverse shock (RS), where the former probes the explosion geometry and the latter traces the structure of the circumstellar medium. We also present a model for the integrated spectrum of the ejecta. The [Fe i] 3D map reveals a highly asymmetric morphology resembling a broken dipole, dominated by two large clumps with velocities of ∼2300 km s−1. We also find evidence that the Fe-rich inner ejecta have started to interact with the RS. The RS surface traced by the He i line extends from just inside the ER to higher latitudes on both sides of the ER with a half-opening angle ∼45°, forming a bubble-like structure. The spectral model for the ejecta allows us to identify the many emission lines, including numerous H2 lines. We find that the H2 is most likely excited by far-UV emission, while the metal-line ratios are consistent with a combination of collisional excitation and recombination in the low-temperature ejecta. We also find several high-ionization coronal lines from the ER, requiring a temperature ≳2 × 106 K.
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| 20. |
- Wright, Gillian, et al.
(författare)
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The Mid-infrared Instrument for JWST and Its In-flight Performance
- 2023
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Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 135:1046
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Tidskriftsartikel (refereegranskat)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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| 21. |
- Arun, K. G., et al.
(författare)
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New horizons for fundamental physics with LISA
- 2022
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Ingår i: Living Reviews in Relativity. - : Springer Science and Business Media LLC. - 1433-8351 .- 2367-3613. ; 25:1
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Forskningsöversikt (refereegranskat)abstract
- The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas.
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| 22. |
- Schweinsberg, Martin, et al.
(författare)
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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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Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Tidskriftsartikel (refereegranskat)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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| 23. |
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| 24. |
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| 25. |
- Bekris, LM, et al.
(författare)
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Glutamate cysteine ligase catalytic subunit promoter polymorphisms and associations with type 1 diabetes age-at-onset and GAD65 autoantibody levels.
- 2007
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Ingår i: Exp Clin Endocrinol Diabetes. - : Georg Thieme Verlag KG. ; 115:4, s. 221-228
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to test the hypothesis that glutamate cysteine ligase catalytic subunit (GCLC) promoter polymorphisms are susceptibility factors for type 1 diabetes (T1D), T1D age-at-onset and T1D autoantibodies. T1D patients and control subjects from the Swedish Childhood Diabetes Registry and the Swedish Diabetes Incidence Study registry were genotyped for two GCLC promoter polymorphisms; the GCLC -129 C to T single nucleotide polymorphism (GCLC -129 SNP) and the GCLC GAG trinucleotide repeat polymorphism (GCLC TNR). Glutamate decarboxylase antibody (GAD65Ab) positive T1D patients with the GCLC -129 SNP C/T genotype have increased GAD65Ab levels (p-value, <0.05) compared to the GCLC -129 SNP C/C genotype. T1D patients with an age-at-onset of 14-35 years who possess the GCLC -129 SNP T/T genotype have a higher GAD65Ab index than T1D patients with the GCLC -129 SNP C/C genotype (p-value <0.05). In addition, T1D patients with an age-at-onset of 14-35 years possess the GCLC TNR 7/8 genotype at a lower frequency than the control subjects (OR, 0.33, 95% CI, 0.13-0.82). The GCLC -129 SNP and GCLC TNR appear to be in linkage disequilibrium (p-value<0.0001). These results suggest that GCLC promoter polymorphisms may influence GAD65Ab levels and may influence the age at which T1D is diagnosed.
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| 26. |
- Brem, Jürgen, et al.
(författare)
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Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors
- 2022
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Ingår i: Nature Chemistry. - : Springer Nature. - 1755-4330 .- 1755-4349. ; 14:1, s. 15-24
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Tidskriftsartikel (refereegranskat)abstract
- Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-β-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential β-lactamase stable β-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.
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| 27. |
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| 28. |
- Gasman, Danny, et al.
(författare)
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JWST MIRI/MRS in-flight absolute flux calibration and tailored fringe correction for unresolved sources
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 673
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Tidskriftsartikel (refereegranskat)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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| 29. |
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| 30. |
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| 31. |
- Ray, T. P., et al.
(författare)
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Outflows from the youngest stars are mostly molecular
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 622, s. 48-52
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Tidskriftsartikel (refereegranskat)abstract
- The formation of stars and planets is accompanied not only by the build-up of matter, namely accretion, but also by its expulsion in the form of highly supersonic jets that can stretch for several parsecs1,2. As accretion and jet activity are correlated and because young stars acquire most of their mass rapidly early on, the most powerful jets are associated with the youngest protostars3. This period, however, coincides with the time when the protostar and its surroundings are hidden behind many magnitudes of visual extinction. Millimetre interferometers can probe this stage but only for the coolest components3. No information is provided on the hottest (greater than 1,000 K) constituents of the jet, that is, the atomic, ionized and high-temperature molecular gases that are thought to make up the jet's backbone. Detecting such a spine relies on observing in the infrared that can penetrate through the shroud of dust. Here we report near-infrared observations of Herbig-Haro 211 from the James Webb Space Telescope, an outflow from an analogue of our Sun when it was, at most, a few times 104 years old. These observations reveal copious emission from hot molecules, explaining the origin of the 'green fuzzies'4-7 discovered nearly two decades ago by the Spitzer Space Telescope8. This outflow is found to be propagating slowly in comparison to its more evolved counterparts and, surprisingly, almost no trace of atomic or ionized emission is seen, suggesting its spine is almost purely molecular. Near-infrared imagery and spectroscopy from JWST of the Herbig-Haro 211 system, an analogue of the young Sun, reveals supersonic jets of hot molecules that can explain the origin of the 'green fuzzies' phenomenon.
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| 32. |
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| 33. |
- Fullgrabe, J, et al.
(författare)
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Histone onco-modifications
- 2011
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 30:31, s. 3391-3403
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Tidskriftsartikel (refereegranskat)
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| 34. |
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| 35. |
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| 36. |
- Kavanagh, E, et al.
(författare)
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Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia
- 2014
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 5, s. e1565-
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Tidskriftsartikel (refereegranskat)abstract
- The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimer's and Parkinson's diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in terms of activity and subcellular localization. We demonstrate that counteracting the repressive effect of cIAP2 on caspase-3 activation, using small interfering RNA targeting cIAP2 or a SMAC mimetic such as the BV6 compound, reduced the pro-inflammatory activation of microglia cells and promoted their death. We propose that the different caspase-3 functions in microglia, and potentially other cell types, reside in the active caspase-3 complexes formed. These results also could indicate cIAP2 as a possible therapeutic target to modulate microglia pro-inflammatory activation and associated neurotoxicity observed in neurodegenerative disorders.
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| 37. |
- Rocha, W. R.M., et al.
(författare)
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JWST Observations of Young protoStars (JOYS+): Detecting icy complex organic molecules and ions: I. CH4, SO2, HCOO, OCN, H2CO, HCOOH, CH3CH2OH, CH3CHO, CH3OCHO, and CH3COOH
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Context. Complex organic molecules (COMs) are ubiquitously detected in the gas phase and thought to be mostly formed on icy grains. Nevertheless, there have not been any unambiguous detections of COMs larger than CH3OH in ices reported thus far. Exploring this matter in greater detail has now become possible with the unprecedented possibilities offered by the James Webb Space Telescope (JWST) within the infrared (IR) spectral range with its very high sensitivity and spectral resolution in the critical 5 10 μm range, the fingerprint region of oxygen-bearing COMs. Aims. In the JWST Observations of Young protoStars (JOYS+) program, more than 30 protostars are undergoing observation with the Medium Resolution Spectrograph (MRS) of the Mid-IR Instrument (MIRI). The goal of this study is to comprehensively explore the COMs ice signatures in one low- and one high-mass protostar: NGC 1333 IRAS 2A and IRAS 23385+6053, respectively. Methods. We performed global continuum and silicate subtractions of the MIRI-MRS spectra, followed by a local continuum subtraction in optical depth scale in the range around 6.8 and 8.6 μm, the ice COM fingerprint region. We explored different choices for the local continuum and silicate subtraction. Next, we fit the observational data with a large sample of available IR laboratory ice spectra. We used the ENIIGMA fitting tool, a genetic algorithm-based code that not only finds the best fit between the lab data and the observations, but also performs a statistical analysis of the solutions, such as deriving the confidence intervals and quantifying fit degeneracy. Results. We report the best fits for the spectral ranges between 6.8 and 8.6 μm in NGC 1333 IRAS 2A and IRAS 23385+6053, originating from simple molecules and COMs, as well as negative ions. Overall, we find that ten chemical species are needed to reproduce the astronomical data. The strongest feature in this range (7.7 μm) is dominated by CH4, with contributions from SO2 and OCN. Our results indicate that the 7.2 and 7.4 μm bands are mostly dominated by HCOO. We also find statistically robust detections of COMs based on multiple bands, most notably, CH3CHO, CH3CH2OH, and CH3OCHO. We also report a likely detection of CH3COOH. Based on the ice column density ratios between CH3CH2OH and CH3CHO of NGC 1333 IRAS 2A and IRAS 23385+6053, we find compelling evidence that these COMs are formed on icy grains. Finally, the derived ice abundances for NGC 1333 IRAS 2A correlate well with those in comet 67P/GC within a factor of 5. Conclusions. Based on the high-quality JWST (MIRI-MRS) spectra, we conclude that COMs are present in interstellar ices, thus providing additional proof for the solid-state origin of these species in star-forming regions. In addition, the good correlation between the ice abundances in comet 67P and NGC 1333 IRAS 2A is fully in line with the idea that cometary COMs may be inherited from the early protostellar phases to a significant extent.
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| 38. |
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| 39. |
- Sabado, R.L., et al.
(författare)
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In vitro priming recapitulates in vivo HIV-1 specific T cell responses, revealing rapid loss of virus reactive CD4+ T cells in acute HIV-1 infection
- 2009
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:1, s. e4256-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The requirements for priming of HIV-specific T cell responses initially seen in infected individuals remain to be defined. Activation of T cell responses in lymph nodes requires cell-cell contact between T cells and DCs, which can give concurrent activation of T cells and HIV transmission. Methodology: The study aim was to establish whether DCs pulsed with HIV-1 could prime HIV-specific T cell responses and to characterize these responses. Both infectious and aldrithiol-2 inactivated noninfectious HIV-1 were compared to establish efficiencies in priming and the type of responses elicited. Findings: Our findings show that both infectious and inactivated HIV-1 pulsed DCs can prime HIV-specific responses from na�ve T cells. Responses included several CD4+ and CD8+ T cell epitopes shown to be recognized in vivo by acutely and chronically infected individuals and some CD4+ T cell epitopes not identified previously. Follow up studies of acute and recent HIV infected samples revealed that these latter epitopes are among the earliest recognized in vivo, but the responses are lost rapidly, presumably through activation-induced general CD4+ T cell depletion which renders the newly activated HIV-specific CD4+ T cells prime targets for elimination. Conclusion: Our studies highlight the ability of DCs to efficiently prime na�ve T cells and induce a broad repertoire of HIV-specific responses and also provide valuable insights to the pathogenesis of HIV-1 infection in vivo.
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| 40. |
- Smith, Richard J.H., et al.
(författare)
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C3 glomerulopathy — understanding a rare complement-driven renal disease
- 2019
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Ingår i: Nature Reviews Nephrology. - : Springer Science and Business Media LLC. - 1759-5061 .- 1759-507X.
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Forskningsöversikt (refereegranskat)abstract
- The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy — dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) — have overlapping clinical and pathological features suggestive of a disease continuum. Dysregulation of the complement alternative pathway is fundamental to the manifestations of C3 glomerulopathy, although terminal pathway dysregulation is also common. Disease is driven by acquired factors in most patients — namely, autoantibodies that target the C3 or C5 convertases. These autoantibodies drive complement dysregulation by increasing the half-life of these vital but normally short-lived enzymes. Genetic variation in complement-related genes is a less frequent cause. No disease-specific treatments are available, although immunosuppressive agents and terminal complement pathway blockers are helpful in some patients. Unfortunately, no treatment is universally effective or curative. In aggregate, the limited data on renal transplantation point to a high risk of disease recurrence (both DDD and C3GN) in allograft recipients. Clinical trials are underway to test the efficacy of several first-generation drugs that target the alternative complement pathway.
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- Van Gelder, M. L., et al.
(författare)
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JOYS+: Mid-infrared detection of gas-phase SO 2 emission in a low-mass protostar
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 682
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Tidskriftsartikel (refereegranskat)abstract
- Context. Thanks to the Mid-InfraRed Instrument (MIRI) on the James Webb Space Telescope (JWST), our ability to observe the star formation process in the infrared has greatly improved. Due to its unprecedented spatial and spectral resolution and sensitivity in the mid-infrared, JWST/MIRI can see through highly extincted protostellar envelopes and probe the warm inner regions. An abundant molecule in these warm inner regions is SO2, which is a common tracer of both outflow and accretion shocks as well as hot core chemistry. Aims. This paper presents the first mid-infrared detection of gaseous SO2 emission in an embedded low-mass protostellar system rich in complex molecules and aims to determine the physical origin of the SO2 emission. Methods. JWST/MIRI observations taken with the Medium Resolution Spectrometer (MRS) of the low-mass protostellar binary NGC 1333 IRAS 2A in the JWST Observations of Young protoStars (JOYS+) program are presented. The observations reveal emission from the SO2 ν3 asymmetric stretching mode at 7.35 µm. Using simple slab models and assuming local thermodynamic equilibrium (LTE), we derived the rotational temperature and total number of SO2 molecules. We then compared the results to those derived from high-angular-resolution SO2 data on the same scales (∼50−100 au) obtained with the Atacama Large Millimeter/submillimeter Array (ALMA). Results. The SO2 emission from the ν3 band is predominantly located on ∼50−100 au scales around the mid-infrared continuum peak of the main component of the binary, IRAS 2A1. A rotational temperature of 92 ± 8 K is derived from the ν3 lines. This is in good agreement with the rotational temperature derived from pure rotational lines in the vibrational ground state (i.e., ν = 0) with ALMA (104 ± 5 K), which are extended over similar scales. However, the emission of the ν3 lines in the MIRI-MRS spectrum is not in LTE given that the total number of molecules predicted by a LTE model is found to be a factor of 2 × 104 higher than what is derived for the ν = 0 state from the ALMA data. This difference can be explained by a vibrational temperature that is ∼100 K higher than the derived rotational temperature of the ν = 0 state: Tvib ∼ 200 K versus Trot = 104 ± 5 K. The brightness temperature derived from the continuum around the ν3 band (∼7.35 µm) of SO2 is ∼180 K, which confirms that the ν3 = 1 level is not collisionally populated but rather infrared-pumped by scattered radiation. This is also consistent with the non-detection of the ν2 bending mode at 18−20 µm. The similar rotational temperature derived from the MIRI-MRS and ALMA data implies that they are in fact tracing the same molecular gas. The inferred abundance of SO2 , determined using the LTE fit to the lines of the vibrational ground state in the ALMA data, is 1.0 ± 0.3 × 10−8 with respect to H2, which is on the lower side compared to interstellar and cometary ices (10−8−10−7). Conclusions. Given the rotational temperature, the extent of the emission (∼100 au in radius), and the narrow line widths in the ALMA data (∼3.5 km s−1), the SO2 in IRAS 2A likely originates from ice sublimation in the central hot core around the protostar rather than from an accretion shock at the disk–envelope boundary. Furthermore, this paper shows the importance of radiative pumping and of combining JWST observations with those from millimeter interferometers such as ALMA to probe the physics on disk scales and to infer molecular abundances.
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