| 1. |
- Andreoni, Igor, et al.
(författare)
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Optimizing Cadences with Realistic Light-curve Filtering for Serendipitous Kilonova Discovery with Vera Rubin Observatory
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 258:1
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Tidskriftsartikel (refereegranskat)abstract
- Current and future optical and near-infrared wide-field surveys have the potential to find kilonovae, the optical and infrared counterparts to neutron star mergers, independently of gravitational-wave or high-energy gamma-ray burst triggers. The ability to discover fast and faint transients such as kilonovae largely depends on the area observed, the depth of those observations, the number of revisits per field in a given time frame, and the filters adopted by the survey; it also depends on the ability to perform rapid follow-up observations to confirm the nature of the transients. In this work, we assess kilonova detectability in existing simulations of the Legacy Survey of Space and Time strategy for the Vera C. Rubin Wide Fast Deep survey, with focus on comparing rolling to baseline cadences. Although currently available cadences can enable the detection of >300 kilonovae out to ∼1400 Mpc over the 10 year survey, we can expect only 3–32 kilonovae similar to GW170817 to be recognizable as fast-evolving transients. We also explore the detectability of kilonovae over the plausible parameter space, focusing on viewing angle and ejecta masses. We find that observations in redder izy bands are crucial for identification of nearby (within 300 Mpc) kilonovae that could be spectroscopically classified more easily than more distant sources. Rubin's potential for serendipitous kilonova discovery could be increased by gain of efficiency with the employment of individual 30 s exposures (as opposed to 2 × 15 s snap pairs), with the addition of red-band observations coupled with same-night observations in g or r bands, and possibly with further development of a new rolling-cadence strategy.
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| 2. |
- Andreoni, Igor, et al.
(författare)
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Target-of-opportunity Observations of Gravitational-wave Events with Vera C. Rubin Observatory
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 260:1
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of the electromagnetic counterpart to the binary neutron star (NS) merger GW170817 has opened the era of gravitational-wave multimessenger astronomy. Rapid identification of the optical/infrared kilonova enabled a precise localization of the source, which paved the way to deep multiwavelength follow-up and its myriad of related science results. Fully exploiting this new territory of exploration requires the acquisition of electromagnetic data from samples of NS mergers and other gravitational-wave sources. After GW170817, the frontier is now to map the diversity of kilonova properties and provide more stringent constraints on the Hubble constant, and enable new tests of fundamental physics. The Vera C. Rubin Observatory's Legacy Survey of Space and Time can play a key role in this field in the 2020s, when an improved network of gravitational-wave detectors is expected to reach a sensitivity that will enable the discovery of a high rate of merger events involving NSs (∼tens per year) out to distances of several hundred megaparsecs. We design comprehensive target-of-opportunity observing strategies for follow-up of gravitational-wave triggers that will make the Rubin Observatory the premier instrument for discovery and early characterization of NS and other compact-object mergers, and yet unknown classes of gravitational-wave events.
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| 3. |
- Baselli, Guido A, et al.
(författare)
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Rare ATG7 genetic variants predispose patients to severe fatty liver disease.
- 2022
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Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 77:3, s. 596-606
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci contributing to severe NAFLD by examining rare variants.We performed whole-exome sequencing in individuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n=301) and examined the enrichment of likely pathogenic rare variants vs. the general population, followed by validation at gene level.In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; OR 5.26, 2.1-12.6; p=0.003) of autophagy-related 7 (ATG7), which we characterized as a loss-of-function, vs. the general population, and an enrichment in rare variants affecting the catalytic domain (OR 13.9, 1.9-612; p=0.002). In the UK Biobank cohort, loss-of-function ATG7 variants increased the risk of cirrhosis and hepatocellular carcinoma (OR 3.30, 1.1-7.5 and OR 12.30, 2.6-36, respectively; p<0.001 for both). The low-frequency loss-of-function p.V471A variant (rs36117895 T>C) was also associated with severe NAFLD in the clinical cohort (OR=1.7, 1.2-2.5; p=0.003), predisposed to hepatocellular ballooning (p=0.007) evolving to fibrosis in a Liver biopsy cohort (n=2268), and was associated with liver injury in the UK Biobank (AST levels, p<0.001), with a larger effect in severely obese individuals where it was linked to hepatocellular carcinoma (p=0.009). ATG7 protein localized to periportal hepatocytes, more so in the presence of ballooning. In the Liver Transcriptomic cohort (n=125) ATG7 expression correlated with suppression of the TNFα pathway, which was conversely upregulated in p.V471A carriers.We identified rare and low-frequency ATG7 loss-of-function variants as modifiers of NAFLD progression by impairing autophagy and facilitating ballooning and inflammation.•We found that rare mutations in a gene called autophagy related (ATG7) increase the risk of developing severe liver disease in individuals with dysmetabolism. •These mutations cause an alteration in protein function and impairment of self-renewal of cellular content, leading to liver damage and inflammation.
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| 4. |
- Bianco, Christina, et al.
(författare)
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Genetic risk scores and personalization of care in fatty liver disease.
- 2021
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Ingår i: Current opinion in pharmacology. - : Elsevier BV. - 1471-4973 .- 1471-4892. ; 61, s. 6-11
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver diseaseis the leading cause of chronic liver disease. Genetic predisposition, lifestyle, and metabolic comorbidities concur to nonalcoholic fatty liver disease development and progression to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Improvement in risk stratification and development of effective therapies for nonalcoholic steatohepatitis are key unmet clinical needs. Knowledge emerging from genomics could meet this need. A polygenic risk score (PRS) is calculated by summing the number of trait-associated alleles carried by an individual, which can be weighted by their effectsize on the trait and captures the individual's genetic risk to develop a disease. In this review, we focalize on the potential use of PRSs for disease detection at an early stage and stratification of the risk of progression to severe forms. PRSs may represent robust instruments to implement targeted prevention programs, hepatocellular carcinoma surveillance in at-risk individuals, and to develop precision medicine therapeutic approaches.
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| 5. |
- Bianco, Cristiana, et al.
(författare)
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Predictors of controlled attenuation parameter in metabolic dysfunction
- 2024
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Ingår i: United European Gastroenterology Journal. - 2050-6406 .- 2050-6414. ; 12:3, s. 364-373
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Hepatic fat content can be non-invasively estimated by controlled attenuation parameter (CAP) during transient elastography. The aim of this study was to examine the determinants and predictors of CAP values in individuals with metabolic dysfunction. Methods: We enrolled 1230 consecutive apparently healthy individuals (Liver-Bible-2022 cohort) with ≥3 metabolic dysfunction features. CAP was measured by Fibroscan. CAP determinants and predictors were identified using backward stepwise analysis and introduced in generalized linear models. Results: Participants were predominantly males (82.9%), mean age was 53.8±6.4years, 600 (48.8%) had steatosis (CAP≥275dB/m), and 27 had liver stiffness measurement (LSM)≥8kPa. CAP values correlated with LSM (p<10−22). In multivariable analysis, fasting insulin and abdominal circumference (AC) were the main determinants of CAP (p<10−6), together with body mass index (BMI; p<10−4), age, diabetes, triglycerides, ferritin, and lower HDL and thyroid stimulating hormone (TSH; p<0.05 for all). In a subset of 592 participants with thyroid hormone measurement, we found an association between higher free triiodothyronine levels, correlating with lower TSH, and CAP values, independent of TSH and of levothyroxine treatment (p=0.0025). A clinical CAP score based on age, BMI, AC, HbA1c, ALT, and HDL predicted CAP≥275dB/m with moderate accuracy (AUROC=0.73), which was better than that of the Fatty Liver Index and of ALT (AUROC=0.70/0.61, respectively) and validated it in multiple cohorts. Conclusion: Abdominal adiposity and insulin resistance severity were the main determinants of CAP in individuals with metabolic dysfunction and may improve steatotic liver disease risk stratification. CAP values were modulated by the hypophysis-thyroid axis.
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| 6. |
- Bianco, Federica B., et al.
(författare)
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Optimization of the Observing Cadence for the Rubin Observatory Legacy Survey of Space and Time : A Pioneering Process of Community-focused Experimental Design
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 258:1
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Tidskriftsartikel (refereegranskat)abstract
- Vera C. Rubin Observatory is a ground-based astronomical facility under construction, a joint project of the National Science Foundation and the U.S. Department of Energy, designed to conduct a multipurpose 10 yr optical survey of the Southern Hemisphere sky: the Legacy Survey of Space and Time. Significant flexibility in survey strategy remains within the constraints imposed by the core science goals of probing dark energy and dark matter, cataloging the solar system, exploring the transient optical sky, and mapping the Milky Way. The survey's massive data throughput will be transformational for many other astrophysics domains and Rubin's data access policy sets the stage for a huge community of potential users. To ensure that the survey science potential is maximized while serving as broad a community as possible, Rubin Observatory has involved the scientific community at large in the process of setting and refining the details of the observing strategy. The motivation, history, and decision-making process of this strategy optimization are detailed in this paper, giving context to the science-driven proposals and recommendations for the survey strategy included in this Focus Issue.
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| 7. |
- Bianco, Federica B., et al.
(författare)
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Presto-Color : A Photometric Survey Cadence for Explosive Physics and Fast Transients
- 2019
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:1000
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Tidskriftsartikel (refereegranskat)abstract
- We identify minimal observing cadence requirements that enable photometric astronomical surveys to detect and recognize fast and explosive transients and fast transient features. Observations in two different filters within a short time window (e.g., g-and-i, or r-and-z, within <0.5 hr) and a repeat of one of those filters with a longer time window (e.g., >1.5 hr) are desirable for this purpose. Such an observing strategy delivers both the color and light curve evolution of transients on the same night. This allows the identification and initial characterization of fast transient-or fast features of longer timescale transients-such as rapidly declining supernovae, kilonovae, and the signatures of SN ejecta interacting with binary companion stars or circumstellar material. Some of these extragalactic transients are intrinsically rare and generally all hard to find, thus upcoming surveys like the Large Synoptic Survey Telescope (LSST) could dramatically improve our understanding of their origin and properties. We colloquially refer to such a strategy implementation for the LSST as the Presto-Color strategy (rapid-color). This cadence's minimal requirements allow for overall optimization of a survey for other science goals.
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| 8. |
- Fremling, Christoffer, 1984-
(författare)
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Stripped-envelope supernovae discovered by the Palomar Transient Factory
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is based on research made by the intermediate Palomar Transient Factory [(i)PTF]. The focus is on stripped-envelope (SE) supernovae (SNe) discovered by (i)PTF, and it is closely tied to the research on the SE SN iPTF13bvn, that occurred in the nearby galaxy NGC 5806. This SN was initially thought to have been the explosion of a very massive Wolf-Rayet star, but we have shown that this is very likely not the case. We suggest instead that iPTF13bvn originated from a binary system where the envelope was stripped off from the SN progenitor by tidal forces from a companion (Paper I). PTF12os exploded in the same galaxy as iPTF13bvn, and our analysis shows that PTF12os and iPTF13bvn were very similar, and that both were also remarkably similar to the Type IIb SN 2011dh, in terms of their light-curves and spectra. In Paper II, hydrodynamical models were used to constrain the explosion parameters of iPTF13bvn, PTF12os and SN 2011dh; finding 56Ni masses in the range 0.063-0.075 solar masses (Ms), ejecta masses in the range 1.85-1.91 Ms, and kinetic energies in the range 0.54-0.94 x 1051 erg. Furthermore, using nebular models and late-time spectroscopy we were able to constrain the Zero-Age Main Sequence (ZAMS) mass to ~ 12 Ms, for iPTF13bvn and ≤ 15 Ms for PTF12os. In current stellar evolution models, stars with these masses on the ZAMS cannot lose their envelopes and become SE SNe without binary interactions. In Paper III we investigate a peculiar SE SN, iPTF15dtg; this SN lacks both hydrogen and helium and shows a double-peaked LC with a broad main LC peak. Using hydrodynamical modeling we show that iPTF15dtg had a very large ejecta mass (~ 10 Ms), resulting from an explosion of a very massive star (~ 35 Ms). The initial peak in the LC can be explained by the presence of extended material around the star, likely due to an episode of strong mass-loss experienced by the progenitor prior to the explosion. In Paper IV we perform a statistical study of the spectra of all 176 SE SNe (Type IIb, Ib and Ic) discovered by (i)PTF. The spectra of Type Ic SNe show O absorption features that are both stronger and broader (indicating faster expansion velocities) compared to Type IIb and Type Ib SNe. These findings along with very weak He absorption support the traditional picture with Type Ic SNe being heavily stripped of their He envelopes prior to the explosions, and argue against alternative explanations, such as differences in explosive mixing of 56Ni among the SE SN subtypes.
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| 9. |
- Huerta, E. A., et al.
(författare)
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Enabling real-time multi-messenger astrophysics discoveries with deep learning
- 2019
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Ingår i: Nature reviews physics. - : Springer Science and Business Media LLC. - 2522-5820. ; 1:10, s. 600-608
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Forskningsöversikt (refereegranskat)abstract
- Multi-messenger astrophysics is a fast-growing, interdisciplinary field that combines data, which vary in volume and speed of data processing, from many different instruments that probe the Universe using different cosmic messengers: electromagnetic waves, cosmic rays, gravitational waves and neutrinos. In this Expert Recommendation, we review the key challenges of real-time observations of gravitational wave sources and their electromagnetic and astroparticle counterparts, and make a number of recommendations to maximize their potential for scientific discovery. These recommendations refer to the design of scalable and computationally efficient machine learning algorithms; the cyber-infrastructure to numerically simulate astrophysical sources, and to process and interpret multi-messenger astrophysics data; the management of gravitational wave detections to trigger real-time alerts for electromagnetic and astroparticle follow-ups; a vision to harness future developments of machine learning and cyber-infrastructure resources to cope with the big-data requirements; and the need to build a community of experts to realize the goals of multi-messenger astrophysics. A group of experts suggests ways in which deep learning can be used to enhance the potential for discovery in multi-messenger astrophysics.
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| 10. |
- Pipitone, Rosaria M., et al.
(författare)
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Programmed cell death 1 genetic variant and liver damage in nonalcoholic fatty liver disease
- 2023
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Ingår i: Liver International. - 1478-3223 .- 1478-3231. ; 43:8, s. 1761-71
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Programmed cell death 1/programmed cell death-ligand 1 (PD-1/PDL-1) axis has been reported to modulate liver inflammation and progression to hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). Here, we examined whether the PDCD1 variation is associated with NAFLD severity in individuals with liver biopsy. Methods: We examined the impact of PDCD1 gene variants on HCC, as robust severe liver disease phenotype in UK Biobank participants. The strongest genetic association with the rs13023138 G>C variation was subsequently tested for association with liver damage in 2889 individuals who underwent liver biopsy for suspected nonalcoholic steatohepatitis (NASH). Hepatic transcriptome was examined by RNA-Seq in a subset of NAFLD individuals (n = 121). Transcriptomic and deconvolution analyses were performed to identify biological pathways modulated by the risk allele. Results: The rs13023138 C>G showed the most robust association with HCC in UK Biobank (p = 5.28E-4, OR = 1.32, 95% CI [1.1, 1.5]). In the liver biopsy cohort, rs13023138 G allele was independently associated with severe steatosis (OR 1.17, 95% CI 1.02-1.34; p =.01), NASH (OR 1.22, 95% CI 1.09-1.37; p <.001) and advanced fibrosis (OR 1.26, 95% CI 1.06-1.50; p =.007). At deconvolution analysis, rs13023138 G>C allele was linked to higher hepatic representation of M1 macrophages, paralleled by upregulation of pathways related to inflammation and higher expression of CXCR6. Conclusions: The PDCD1 rs13023138 G allele was associated with HCC development in the general population and with liver disease severity in patients at high risk of NASH.
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| 11. |
- Sasidharan, Kavitha, et al.
(författare)
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IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids.
- 2024
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Ingår i: Cell reports. Medicine. - 2666-3791. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Steatotic liver disease (SLD) prevails as the most common chronic liver disease yet lack approved treatments due to incomplete understanding of pathogenesis. Recently, elevated hepatic and circulating interleukin 32 (IL-32) levels were found in individuals with severe SLD. However, the mechanistic link between IL-32 and intracellular triglyceride metabolism remains to be elucidated. We demonstrate invitro that incubation with IL-32β protein leads to an increase in intracellular triglyceride synthesis, while downregulation of IL32 by small interfering RNA leads to lower triglyceride synthesis and secretion in organoids from human primary hepatocytes. This reduction requires the upregulation of Phospholipase A2 group IIA (PLA2G2A). Furthermore, downregulation of IL32 results in lower intracellular type I collagen levels in di-lineage human primary hepatic organoids. Finally, we identify a genetic variant of IL32 (rs76580947) associated with lower circulating IL-32 and protection against SLD measured by non-invasive tests. These data suggest that IL32 downregulation may be beneficial against SLD.
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| 12. |
- Schulze, Steve, et al.
(författare)
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The Palomar Transient Factory Core-collapse Supernova Host-galaxy Sample. I. Host-galaxy Distribution Functions and Environment Dependence of Core-collapse Supernovae
- 2021
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 255:2
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Tidskriftsartikel (refereegranskat)abstract
- Several thousand core-collapse supernovae (CCSNe) of different flavors have been discovered so far. However, identifying their progenitors has remained an outstanding open question in astrophysics. Studies of SN host galaxies have proven to be powerful in providing constraints on the progenitor populations. In this paper, we present all CCSNe detected between 2009 and 2017 by the Palomar Transient Factory. This sample includes 888 SNe of 12 distinct classes out to redshift z approximate to 1. We present the photometric properties of their host galaxies from the far-ultraviolet to the mid-infrared and model the host-galaxy spectral energy distributions to derive physical properties. The galaxy mass function of Type Ic, Ib, IIb, II, and IIn SNe ranges from 10(5) to 10(11.5) M (circle dot), probing the entire mass range of star-forming galaxies down to the least-massive star-forming galaxies known. Moreover, the galaxy mass distributions are consistent with models of star-formation-weighted mass functions. Regular CCSNe are hence direct tracers of star formation. Small but notable differences exist between some of the SN classes. Type Ib/c SNe prefer galaxies with slightly higher masses (i.e., higher metallicities) and star formation rates than Type IIb and II SNe. These differences are less pronounced than previously thought. H-poor superluminous supernovae (SLSNe) and SNe Ic-BL are scarce in galaxies above 10(10) M (circle dot). Their progenitors require environments with metallicities of < 0.4 and < 1 solar, respectively. In addition, the hosts of H-poor SLSNe are dominated by a younger stellar population than all other classes of CCSNe. Our findings corroborate the notion that low metallicity and young age play an important role in the formation of SLSN progenitors.
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| 13. |
- Tavaglione, Federica, et al.
(författare)
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Development and Validation of a Score for Fibrotic Non-Alcoholic Steatohepatitis.
- 2023
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Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 21:6, s. 1523-1532
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive assessment of histological features of non-alcoholic fatty liver disease (NAFLD) has been an intensive research area over the last decade. Herein, we aimed to develop a simple non-invasive score using routine laboratory tests to identify, among individuals at high risk for NAFLD, those with fibrotic non-alcoholic steatohepatitis (NASH) defined as NASH, NAFLD activity score (NAS) ≥4, and fibrosis stage ≥2.The derivation cohort included 264 morbidly obese individuals undergoing intraoperative liver biopsy in Rome, Italy. The best predictive model was developed and internally validated using a bootstrapping stepwise logistic regression analysis (2000 bootstrap samples). Performance was estimated by the area under the receiver operating characteristic curve (AUROC). External validation was assessed in three independent European cohorts (Finland, n=370; Italy n=947; England n=5,368) of individuals at high risk for NAFLD.The final predictive model, designated as Fibrotic NASH Index (FNI), combined aspartate aminotransferase (AST), high-density lipoprotein (HDL) cholesterol, and hemoglobin A1c (HbA1c). The performance of FNI for fibrotic NASH was satisfactory in both derivation and external validation cohorts (AUROCs 0.78 and 0.80-0.95, respectively). In the derivation cohort, rule-out and rule-in cut-offs were 0.10 for sensitivity ≥0.89 (negative predictive value [NPV] 0.93) and 0.33 for specificity ≥0.90 (positive predictive value [PPV] 0.57), respectively. In the external validation cohorts, sensitivity ranged from 0.87 to 1 (NPV 0.99-1) and specificity from 0.73 to 0.94 (PPV 0.12-0.49) for rule-out and rule-in cut-off, respectively.FNI is an accurate, simple, and affordable non-invasive score which can be used in primary healthcare to screen for fibrotic NASH individuals with dysmetabolism.
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| 14. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t
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| 15. |
- Aad, G., et al.
(författare)
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- 2012
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Tidskriftsartikel (refereegranskat)
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| 16. |
- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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