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| 2. |
- Chisholm, J., et al.
(författare)
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The far-ultraviolet continuum slope as a Lyman Continuum escape estimator at high redshift
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 517:4, s. 5104-5120
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Tidskriftsartikel (refereegranskat)abstract
- Most of the hydrogen in the intergalactic medium (IGM) was rapidly ionized at high redshifts. While observations have established that reionization occurred, observational constraints on the high-redshift ionizing emissivity remain elusive. Here, we present a new analysis of the Low-redshift Lyman Continuum Survey (LzLCS) and literature observations, a combined sample of 89 star-forming galaxies at redshifts near 0.3 with Hubble Space Telescope observations of their ionizing continua (or Lyman Continuum, LyC). We find a strong (6σ significant) inverse correlation between the continuum slope at 1550 Å (defined as Fλ ∝ λβ1550obs) and both the LyC escape fraction (fesc, LyC) and fesc, LyC times the ionizing photon production efficiency (ξion). On average, galaxies with redder continuum slopes have smaller fesc, LyC than galaxies with bluer slopes mainly due to higher dust attenuation. More than 5 per cent (20 per cent) of the LyC emission escapes galaxies with β1550obs <−2.1 (−2.6). We find strong correlations between β1550obs and the [O III]/[O II] flux ratio (at 7.5σ significance), galaxy stellar mass (at 5.9σ), the gas-phase metallicity (at 4.6σ), and the observed far-ultraviolet absolute magnitude (at 3.4σ). Using previous observations of β1550obs at high redshift, we estimate the evolution of fesc, LyC with both redshift and galaxy magnitude. The LzLCS observations suggest that fainter and lower mass galaxies dominate the ionizing photon budget at higher redshift, possibly due to their rapidly evolving metal and dust content. Finally, we use our correlation between β1550obs and fesc, LyC × ξion to predict the ionizing emissivity of galaxies during the epoch of reionization. Our estimated emissivities match IGM observations, and suggest that star-forming galaxies emit sufficient LyC photons into the IGM to exceed recombinations near redshifts of 7–8.
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| 3. |
- Marques-Chaves, R., et al.
(författare)
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No correlation of the Lyman continuum escape fraction with spectral hardness
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 663
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Tidskriftsartikel (refereegranskat)abstract
- The properties that govern the production and escape of hydrogen-ionizing photons (Lyman continuum, LyC; with energies > 13.6 eV) in star-forming galaxies are still poorly understood, but they are key to identifying and characterizing the sources that reionized the Universe. Here we empirically explore the relation between the hardness of ionizing radiation and the LyC leakage in a large sample of low-z star-forming galaxies from the recent Hubble Space Telescope Low-z Lyman Continuum Survey. Using Sloan Digital Sky Survey stacks and deep X-shooter observations, we investigate the hardness of the ionizing spectra (QHe+/QH) between 54.4 eV (He+) and 13.6 eV (H) from the optical recombination lines He II 4686 Å and Hβ 4861 Å for galaxies with LyC escape fractions spanning a wide range, fesc(LyC) ≃ 0−90%. We find that the observed intensity of He II/Hβ is primarily driven by variations in the metallicity, but is not correlated with LyC leakage. Both very strong (esc(LyC)> ≃ 0.5) and nonleakers (esc(LyC)> ≃ 0) present similar observed intensities of He II and Hβ at comparable metallicity, between ≃0.01 and ≃0.02 for 12 + log(O/H)> 8.0 and < 8.0, respectively. Our results demonstrate that QHe+/QH does not correlate with fesc(LyC), which implies that strong LyC emitters do not show harder ionizing spectra than nonleakers at similar metallicity.
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| 5. |
- Ogony, Joshua, et al.
(författare)
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Towards defining morphologic parameters of normal parous and nulliparous breast tissues by artificial intelligence
- 2022
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Ingår i: Breast Cancer Research. - : BMC. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Breast terminal duct lobular units (TDLUs), the source of most breast cancer (BC) precursors, are shaped by age-related involution, a gradual process, and postpartum involution (PPI), a dramatic inflammatory process that restores baseline microanatomy after weaning. Dysregulated PPI is implicated in the pathogenesis of postpartum BCs. We propose that assessment of TDLUs in the postpartum period may have value in risk estimation, but characteristics of these tissues in relation to epidemiological factors are incompletely described. Methods Using validated Artificial Intelligence and morphometric methods, we analyzed digitized images of tissue sections of normal breast tissues stained with hematoxylin and eosin from donors <= 45 years from the Komen Tissue Bank (180 parous and 545 nulliparous). Metrics assessed by AI, included: TDLU count; adipose tissue fraction; mean acini count/TDLU; mean dilated acini; mean average acini area; mean "capillary" area; mean epithelial area; mean ratio of epithelial area versus intralobular stroma; mean mononuclear cell count (surrogate of immune cells); mean fat area proximate to TDLUs and TDLU area. We compared epidemiologic characteristics collected via questionnaire by parity status and race, using a Wilcoxon rank sum test or Fishers exact test. Histologic features were compared between nulliparous and parous women (overall and by time between last birth and donation [recent birth: <= 5 years versus remote birth: > 5 years]) using multivariable regression models. Results Normal breast tissues of parous women contained significantly higher TDLU counts and acini counts, more frequent dilated acini, higher mononuclear cell counts in TDLUs and smaller acini area per TDLU than nulliparas (all multivariable analyses p < 0.001). Differences in TDLU counts and average acini size persisted for > 5 years postpartum, whereas increases in immune cells were most marked <= 5 years of a birth. Relationships were suggestively modified by several other factors, including demographic and reproductive characteristics, ethanol consumption and breastfeeding duration. Conclusions Our study identified sustained expansion of TDLU numbers and reduced average acini area among parous versus nulliparous women and notable increases in immune responses within five years following childbirth. Further, we show that quantitative characteristics of normal breast samples vary with demographic features and BC risk factors.
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| 6. |
- Prudencio, Mercedes, et al.
(författare)
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Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3
- 2020
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 12:566
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Tidskriftsartikel (refereegranskat)abstract
- Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.
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| 7. |
- Sherman, Mark E., et al.
(författare)
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Serum hormone levels and normal breast histology among premenopausal women
- 2022
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Ingår i: Breast Cancer Research and Treatment. - New York, NY, United States : Springer. - 0167-6806 .- 1573-7217. ; 194, s. 149-158
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Breast terminal duct lobular units (TDLUs) are the main source of breast cancer (BC) precursors. Higher serum concentrations of hormones and growth factors have been linked to increased TDLU numbers and to elevated BC risk, with variable effects by menopausal status. We assessed associations of circulating factors with breast histology among premenopausal women using artificial intelligence (AI) and preliminarily tested whether parity modifies associations.Methods Pathology AI analysis was performed on 316 digital images of H&E-stained sections of normal breast tissues from Komen Tissue Bank donors ages ≤ 45 years to assess 11 quantitative metrics. Associations of circulating factors with AI metrics were assessed using regression analyses, with inclusion of interaction terms to assess effect modification.Results Higher prolactin levels were related to larger TDLU area (p<0.001) and increased presence of adipose tissue proximate to TDLUs (p<0.001), with less significant positive associations for acini counts (p = 0.012), dilated acini (p = 0.043), capillary area (p = 0.014), epithelial area (p = 0.007), and mononuclear cell counts (p = 0.017). Testosterone levels were associated with increased TDLU counts (p<0.001), irrespective of parity, but associations differed by adipose tissue content. AI data for TDLU counts generally agreed with prior visual assessments.Conclusion Among premenopausal women, serum hormone levels linked to BC risk were also associated with quantitative features of normal breast tissue. These relationships were suggestively modified by parity status and tissue composition. We conclude that the microanatomic features of normal breast tissue may represent a marker of BC risk.
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