| 1. |
- Garcia-Lopez, R., et al.
(författare)
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A measure of the size of the magnetospheric accretion region in TW Hydrae
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 584:7822, s. 547-550
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Tidskriftsartikel (refereegranskat)abstract
- Stars form by accreting material from their surrounding disks. There is a consensus that matter flowing through the disk is channelled onto the stellar surface by the stellar magnetic field. This is thought to be strong enough to truncate the disk close to the corotation radius, at which the disk rotates at the same rate as the star. Spectro-interferometric studies in young stellar objects show that hydrogen emission (a well known tracer of accretion activity) mostly comes from a region a few milliarcseconds across, usually located within the dust sublimation radius1–3. The origin of the hydrogen emission could be the stellar magnetosphere, a rotating wind or a disk. In the case of intermediate-mass Herbig AeBe stars, the fact that Brackett γ (Brγ) emission is spatially resolved rules out the possibility that most of the emission comes from the magnetosphere4–6 because the weak magnetic fields (some tenths of a gauss) detected in these sources7,8 result in very compact magnetospheres. In the case of T Tauri sources, their larger magnetospheres should make them easier to resolve. The small angular size of the magnetosphere (a few tenths of a milliarcsecond), however, along with the presence of winds9,10 make the interpretation of the observations challenging. Here we report optical long-baseline interferometric observations that spatially resolve the inner disk of the T Tauri star TW Hydrae. We find that the near-infrared hydrogen emission comes from a region approximately 3.5 stellar radii across. This region is within the continuum dusty disk emitting region (7 stellar radii across) and also within the corotation radius, which is twice as big. This indicates that the hydrogen emission originates in the accretion columns (funnel flows of matter accreting onto the star), as expected in magnetospheric accretion models, rather than in a wind emitted at much larger distance (more than one astronomical unit).
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| 2. |
- Koutoulaki, M., et al.
(författare)
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The GRAVITY young stellar object survey: IV. The CO overtone emission in 51 Oph at sub-au scales
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 645
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Tidskriftsartikel (refereegranskat)abstract
- Context. 51 Oph is a Herbig Ae/Be star that exhibits strong near-infrared CO ro-vibrational emission at 2.3 μm, most likely originating in the innermost regions of a circumstellar disc. Aims. We aim to obtain the physical and geometrical properties of the system by spatially resolving the circumstellar environment of the inner gaseous disc. Methods. We used the second-generation Very Large Telescope Interferometer instrument GRAVITY to spatially resolve the continuum and the CO overtone emission. We obtained data over 12 baselines with the auxiliary telescopes and derive visibilities, and the differential and closure phases as a function of wavelength. We used a simple local thermal equilibrium ring model of the CO emission to reproduce the spectrum and CO line displacements. Results. Our interferometric data show that the star is marginally resolved at our spatial resolution, with a radius of ∼10.58 ± 2.65R·. The K-band continuum emission from the disc is inclined by 63° ± 1°, with a position angle of 116° ± 1°, and 4 ± 0.8 mas (0.5 ± 0.1 au) across. The visibilities increase within the CO line emission, indicating that the CO is emitted within the dust-sublimation radius. By modelling the CO bandhead spectrum, we derive that the CO is emitted from a hot (T = 1900-2800 K) and dense (NCO = (0.9-9) × 1021 cm-2) gas. The analysis of the CO line displacement with respect to the continuum allows us to infer that the CO is emitted from a region 0.10 ± 0.02 au across, well within the dust-sublimation radius. The inclination and position angle of the CO line emitting region is consistent with that of the dusty disc. Conclusions. Our spatially resolved interferometric observations confirm the CO ro-vibrational emission within the dust-free region of the inner disc. Conventional disc models exclude the presence of CO in the dust-depleted regions of Herbig AeBe stars. Ad hoc models of the innermost disc regions, that can compute the properties of the dust-free inner disc, are therefore required.
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| 3. |
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| 4. |
- Herbst, SA, et al.
(författare)
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Proteogenomics refines the molecular classification of chronic lymphocytic leukemia
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 6226-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic-based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterize the proteome and transcriptome alongside genetic and ex-vivo drug response profiling in a clinically annotated CLL discovery cohort (n = 68). Unsupervised clustering of the proteome data reveals six subgroups. Five of these proteomic groups are associated with genetic features, while one group is only detectable at the proteome level. This new group is characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). Classifiers developed to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n = 165, n = 169) confirm that ASB-CLL comprises about 20% of CLL patients. The inferior overall survival in ASB-CLL is also independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling.
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| 5. |
- Ferrari-Souza, J. P., et al.
(författare)
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APOEε4 potentiates amyloid β effects on longitudinal tau pathology
- 2023
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Ingår i: Nature Aging. - 2662-8465. ; 3:10
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms by which the apolipoprotein E epsilon 4 (APOE epsilon 4) allele influences the pathophysiological progression of Alzheimer's disease (AD) are poorly understood. Here we tested the association of APOE epsilon 4 carriership and amyloid-beta (A beta) burden with longitudinal tau pathology. We longitudinally assessed 94 individuals across the aging and AD spectrum who underwent clinical assessments, APOE genotyping, magnetic resonance imaging, positron emission tomography (PET) for A beta ([F-18]AZD4694) and tau ([F-18]MK-6240) at baseline, as well as a 2-year follow-up tau-PET scan. We found that APOE epsilon 4 carriership potentiates A beta effects on longitudinal tau accumulation over 2 years. The APOE epsilon 4-potentiated A beta effects on tau-PET burden were mediated by longitudinal plasma phosphorylated tau at threonine 217 (p-tau217(+)) increase. This longitudinal tau accumulation as measured by PET was accompanied by brain atrophy and clinical decline. Our results suggest that the APOE epsilon 4 allele plays a key role in A beta downstream effects on the aggregation of phosphorylated tau in the living human brain.
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| 6. |
- Pearson, A. D. J., et al.
(författare)
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Paediatric Strategy Forum for medicinal product development for acute myeloid leukaemia in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration
- 2020
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 136, s. 116-129
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The current standard-of-care for front-line therapy for acute myeloid leukaemia (AML) results in short-term and long-term toxicity, but still approximately 40% of children relapse. Therefore, there is a major need to accelerate the evaluation of innovative medicines, yet drug development continues to be adult-focused. Furthermore, the large number of competing agents in rare patient populations requires coordinated prioritisation, within the global regulatory framework and cooperative group initiatives. Methods: The fourth multi-stakeholder Paediatric Strategy Forum focused on AML in children and adolescents. Results: CD123 is a high priority target and the paediatric development should be accelerated as a proof-of-concept. Efforts must be coordinated, however, as there are a limited number of studies that can be delivered. Studies of FLT3 inhibitors in agreed paediatric investigation plans present challenges to be completed because they require enrolment of a larger number of patients than actually exist. A consensus was developed by industry and academia of optimised clinical trials. For AML with rare mutations that are more frequent in adolescents than in children, adult trials should enrol adolescents and when scientifically justified, efficacy data could be extrapolated. Methodologies and definitions of minimal residual disease need to be standardised internationally and validated as a new response criterion. Industry supported, academic sponsored platform trials could identify products to be further developed. The Leukaemia and Lymphoma Society PedAL/EUpAL initiative has the potential to be a major advance in the field. Conclusion: These initiatives continue to accelerate drug development for children with AML and ultimately improve clinical outcomes. (C) 2020 Elsevier Ltd. All rights reserved.
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| 7. |
- Woo, M. S., et al.
(författare)
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Plasma pTau-217 and N-terminal tau (NTA) enhance sensitivity to identify tau PET positivity in amyloid-β positive individuals
- 2024
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 20:2, s. 1166-1174
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONWe set out to identify tau PET-positive (A+T+) individuals among amyloid-beta (A beta) positive participants using plasma biomarkers.METHODSIn this cross-sectional study we assessed 234 participants across the AD continuum who were evaluated by amyloid PET with [18F]AZD4694 and tau-PET with [18F]MK6240 and measured plasma levels of total tau, pTau-181, pTau-217, pTau-231, and N-terminal tau (NTA-tau). We evaluated the performances of plasma biomarkers to predict tau positivity in A beta+ individuals.RESULTSHighest associations with tau positivity in A beta+ individuals were found for plasma pTau-217 (AUC [CI95%] = 0.89 [0.82, 0.96]) and NTA-tau (AUC [CI95%] = 0.88 [0.91, 0.95]). Combining pTau-217 and NTA-tau resulted in the strongest agreement (Cohen's Kappa = 0.74, CI95% = 0.57/0.90, sensitivity = 92%, specificity = 81%) with PET for classifying tau positivity.DISCUSSIONThe potential for identifying tau accumulation in later Braak stages will be useful for patient stratification and prognostication in treatment trials and in clinical practice.HighlightsWe found that in a cohort without pre-selection pTau-181, pTau-217, and NTA-tau showed the highest association with tau PET positivity.We found that in A beta+ individuals pTau-217 and NTA-tau showed the highest association with tau PET positivity.Combining pTau-217 and NTA-tau resulted in the strongest agreement with the tau PET-based classification.
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| 8. |
- Breznau, Nate, et al.
(författare)
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Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
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Tidskriftsartikel (refereegranskat)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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| 9. |
- Ebersole, Charles R., et al.
(författare)
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Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
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Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
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Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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| 10. |
- Ferreira, P. C. L., et al.
(författare)
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Plasma p-tau231 and p-tau217 inform on tau tangles aggregation in cognitively impaired individuals
- 2023
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 19:10, s. 4463-4474
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONPhosphorylated tau (p-tau) biomarkers have been recently proposed to represent brain amyloid-& beta; (A & beta;) pathology. Here, we evaluated the plasma biomarkers' contribution beyond the information provided by demographics (age and sex) to identify A & beta; and tau pathologies in individuals segregated as cognitively unimpaired (CU) and impaired (CI). METHODSWe assessed 138 CU and 87 CI with available plasma p-tau231, 217(+), and 181, A & beta;42/40, GFAP and A & beta;- and tau-PET. RESULTSIn CU, only plasma p-tau231 and p-tau217(+) significantly improved the performance of the demographics in detecting A & beta;-PET positivity, while no plasma biomarker provided additional information to identify tau-PET positivity. In CI, p-tau217(+) and GFAP significantly contributed to demographics to identify both A & beta;-PET and tau-PET positivity, while p-tau231 only provided additional information to identify tau-PET positivity. DISCUSSIONOur results support plasma p-tau231 and p-tau217(+) as state markers of early A & beta; deposition, but in later disease stages they inform on tau tangle accumulation. HighlightsIt is still unclear how much plasma biomarkers contribute to identification of AD pathology across the AD spectrum beyond the information already provided by demographics (age + sex).Plasma p-tau231 and p-tau217(+) contribute to demographic information to identify brain A & beta; pathology in preclinical AD.In CI individuals, plasma p-tau231 contributes to age and sex to inform on the accumulation of tau tangles, while p-tau217(+) and GFAP inform on both A & beta; deposition and tau pathology.
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