| 1. |
- 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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| 2. |
- Albuquerque, Daniel, et al.
(författare)
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LES simulation of oscillating natural ventilation driven by vortex shedding in isolated buildings
- 2020
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Ingår i: Proceedings of Building Simulation 2019: 16th Conference of IBPSA. - : IBPSA. - 9781775052012 ; , s. 644-649
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Konferensbidrag (refereegranskat)abstract
- A recently published study presented a new type of natural ventilation (NV) flow, named pumping ventilation. The oscilatory mechanism of vortex shedding that occurs at the wake region of an isolated building drives this new type of ventilation in rooms with two (or more) openings facing the leeward or windward side of an isolated building. This paper presents a validated Large Eddy Simulation (LES) study of oscillating/pumping NV in an isolated building using three different separations (s') between its two windows. LES is validated using an experimental database from measurements performed at the University of Gavle boundary layer wind tunnel (WT). The measurements use a cubic model with 0.45m side representing a three-story building at a 1/20 scale that allows the use of bottom-hung windows. LES results show a good agreement with the measured non-dimensional ventilation rates. A dimensionless analysis shows the dominant frequencies of the pumping flow, are close to the Strouhal frequency.
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| 3. |
- Albuquerque, Daniel P., et al.
(författare)
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Experimental and numerical investigation of pumping ventilation on the leeward side of a cubic building
- 2020
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Ingår i: Building and Environment. - : Elsevier. - 0360-1323 .- 1873-684X. ; 179
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Tidskriftsartikel (refereegranskat)abstract
- Unstable interaction between shear layers that form in the wake of an isolated building exposed to wind can drive natural pumping ventilation in windward and leeward facing rooms with two or more horizontally separated openings. This paper presents an experimental and numerical study of pumping ventilation in a three-story cubic building with two leeward openings in its middle floor. Reduced-scaled measurements were performed in the University of Gävle atmospheric-boundary-layer wind tunnel. The ventilation mechanism was investigated using smoke visualization, hot wire anemometry and particle image velocimetry. Effective ventilation rates were obtained using a tracer gas decay method. Experimental results confirmed that pumping ventilation is a 3D oscillatory unstable phenomenon with periodic behavior over several oscillation cycles. Measured flowrates show a linear relation between the effective ventilation rate and window separation. The numerical simulations used two turbulence modeling approaches: unsteady Reynolds-averaged Navier-Stokes (URANS) and large eddy simulation (LES). Both URANS and LES could predict vortex shedding frequency with an error below 5%. LES showed a good agreement with the measured ventilation rates, with an error below 10%, while URANS underestimated ventilation rates by at least 40%. The ventilation efficiency, obtained by LES, ranged between 0.60 and 0.75 (for the case with larger window separation). The results show that LES may be a suitable simulation approach for pumping ventilation. In contrast, URANS cannot simulate pumping ventilation.
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| 4. |
- Azzu, V., et al.
(författare)
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Suppression of insulin-induced gene 1 (INSIG1) function promotes hepatic lipid remodelling and restrains NASH progression
- 2021
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Non-alcoholic fatty liver disease (NAFLD) is a silent pandemic associated with obesity and the metabolic syndrome, and also increases cardiovascular- and cirrhosis-related morbidity and mortality. A complete understanding of adaptive compensatory metabolic programmes that modulate non-alcoholic steatohepatitis (NASH) progression is lacking. Methods and results: Transcriptomic analysis of liver biopsies in patients with NASH revealed that NASH progression is associated with rewiring of metabolic pathways, including upregulation of de novo lipid/cholesterol synthesis and fatty acid remodelling. The modulation of these metabolic programmes was achieved by activating sterol regulatory element-binding protein (SREBP) transcriptional networks; however, it is still debated whether, in the context of NASH, activation of SREBPs acts as a pathogenic driver of lipotoxicity, or rather promotes the biosynthesis of protective lipids that buffer excessive lipid accumulation, preventing inflammation and fibrosis. To elucidate the pathophysiological role of SCAP/SREBP in NASH and wound-healing response, we used an Insig1 deficient (with hyper-efficient SREBPs) murine model challenged with a NASH-inducing diet. Despite enhanced lipid and cholesterol biosynthesis, Insig1 KO mice had similar systemic metabolism and insulin sensitivity to Het/WT littermates. Moreover, activating SREBPs resulted in remodelling the lipidome, decreased hepatocellular damage, and improved wound-healing responses. Conclusions: Our study provides actionable knowledge about the pathways and mechanisms involved in NAFLD pathogenesis, which may prove useful for developing new therapeutic strategies. Our results also suggest that the SCAP/SREBP/INSIG1 trio governs transcriptional programmes aimed at protecting the liver from lipotoxic insults in NASH. (C) 2021 Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 5. |
- Bortolini, Giacomo, 1996-, et al.
(författare)
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The spatially resolved star formation history of the dwarf spiral galaxy NGC 5474
- 2024
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Ingår i: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 527:3, s. 5339-5355
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Tidskriftsartikel (refereegranskat)abstract
- We study the resolved stellar populations and derive the star formation history of NGC 5474, a peculiar star-forming dwarf galaxy at a distance of ∼7 Mpc, using Hubble Space Telescope Advanced Camera for Surveys data from the Legacy Extragalactic UV Survey (LEGUS) programme. We apply an improved colour–magnitude diagram fitting technique based on the code SFERA and use the latest PARSEC–COLIBRI stellar models. Our results are the following. The off-centre bulge-like structure, suggested to constitute the bulge of the galaxy, is dominated by star formation (SF) activity initiated 14 Gyr ago and lasted at least up to 1 Gyr ago. Nevertheless, this component shows clear evidence of prolonged SF activity (lasting until ∼10 Myr ago). We estimate the total stellar mass of the bulge-like structure to be (5.0 ± 0.3) × 108 M⊙. Such a mass is consistent with published suggestions that this structure is in fact an independent system orbiting around and not within NGC 5474’s disc. The stellar overdensity located to the South–West of the bulge-like structure shows a significant SF event older than 1 Gyr, while it is characterized by two recent peaks of SF, around ∼10 and ∼100 Myr ago. In the last Gyr, the behaviour of the stellar disc is consistent with what is known in the literature as ‘gasping’. The synchronized burst at 10–35 Myr in all components might hint to the recent gravitational interaction between the stellar bulge-like structure and the disc of NGC 5474.
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| 6. |
- Calzetti, Daniela, et al.
(författare)
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Revisiting Attenuation Curves : The Case of NGC 3351
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 913:1
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Tidskriftsartikel (refereegranskat)abstract
- Multiwavelength images from the far-UV (similar to 0.15 mu m) to the submillimeter of the central region of the galaxy NGC 3351 are analyzed to constrain its stellar populations and dust attenuation. Despite hosting a similar to 1 kpc circumnuclear starburst ring, NGC 3351 deviates from the IRX-beta relation, the relation between the infrared-to-UV luminosity ratio and the UV continuum slope beta that other starburst galaxies follow. To understand the reason for the deviation, we leverage the high angular resolution of archival near-UV-to-near-IR Hubble Space Telescope images to divide the ring into similar to 60-180 pc size regions and model each individually. We find that the UV slope of the combined intrinsic (dust-free) stellar populations in the central region is redder than what is expected for a young model population. This is due to the region's complex star formation history, which boosts the near-UV emission relative to the far-UV. The resulting net attenuation curve has a UV slope that lies between those of the starburst attenuation curve (Calzetti et al. 2000) and the Small Magellanic Cloud extinction curve; the total-to-selective attenuation value, R'(V) = 4.93, is larger than both. As found for other star-forming galaxies, the stellar continuum of NGC 3351 is less attenuated than the ionized gas, with E(B - V)(star) = 0.40 E(B - V)(gas). The combination of the red intrinsic stellar population and the new attenuation curve fully accounts for the location of the central region of NGC 3351 on the IRX-beta diagram. Thus, the observed characteristics result from the complex mixture of stellar populations and dust column densities in the circumnuclear region. Despite being a sample of one, these findings highlight the difficulty of defining attenuation curves of general applicability outside the regime of centrally concentrated starbursts.
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| 7. |
- Carlsson, Björn, et al.
(författare)
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Review article: the emerging role of genetics in precision medicine for patients with non-alcoholic steatohepatitis.
- 2020
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Ingår i: Alimentary pharmacology & therapeutics. - : Wiley. - 1365-2036 .- 0269-2813. ; 51:12, s. 1305-1320
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Forskningsöversikt (refereegranskat)abstract
- Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) characterised by liver fat accumulation, inflammation and progressive fibrosis. Emerging data indicate that genetic susceptibility increases risks of NAFLD, NASH and NASH-related cirrhosis.To review NASH genetics and discuss the potential for precision medicine approaches to treatment.PubMed search and inclusion of relevant literature.Single-nucleotide polymorphisms in PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13 are clearly associated with NASH development or progression. These genetic variants are common and have moderate-to-large effect sizes for development of NAFLD, NASH and hepatocellular carcinoma (HCC). The genes play roles in lipid remodelling in lipid droplets, hepatic very low-density lipoprotein (VLDL) secretion and de novo lipogenesis. The PNPLA3 I148M variant (rs738409) has large effects, with approximately twofold increased odds of NAFLD and threefold increased odds of NASH and HCC per allele. Obesity interacts with PNPLA3 I148M to elevate liver fat content and increase rates of NASH. Although the isoleucine-to-methionine substitution at amino acid position 148 of the PNPLA3 enzyme inactivates its lipid remodelling activity, the effect of PNPLA3 I148M results from trans-repression of another lipase (ATGL/PNPLA2) by sequestration of a shared cofactor (CGI-58/ABHD5), leading to decreased hepatic lipolysis and VLDL secretion. In homozygous Pnpla3 I148M knock-in rodent models of NAFLD, targeted PNPLA3 mRNA knockdown reduces hepatic steatosis, inflammation and fibrosis.The emerging genetic and molecular understanding of NASH paves the way for novel interventions, including precision medicines that can modulate the activity of specific genes associated with NASH.
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| 8. |
- Carrilho da Graça, Guilherme, et al.
(författare)
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Pumping ventilation of corner and single sided rooms with two openings
- 2021
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Ingår i: Building and Environment. - : Elsevier. - 0360-1323 .- 1873-684X. ; 205
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Tidskriftsartikel (refereegranskat)abstract
- Corner rooms with two or more open windows in perpendicular facades can be naturally ventilated in cross-ventilation or pumping ventilation. These two airflow regimes also occur in rooms with two openings in the same façade, in the form of single sided pumping or cross sided ventilation. This paper presents an experimental and numerical simulation study of the scale and occurrence of these two flow regimes for rooms in a rectangular building exposed to wind. Flow visualization and tracer gas measurement of effective airflow were performed in an atmospheric boundary layer wind tunnel using a rectangular model of a three-story building (1/20 scale) with a ventilated middle floor. Experimental results show that pumping ventilation occurs when the wind is perpendicular to the façade (single sided rooms) or aligned with the building corner (corner rooms). In addition to these two perfectly aligned wind directions, pumping also occurs for a range of incoming wind angles: ±19° for single sided; and ±9° for corner rooms. As a result, for isolated rectangular buildings that have, at least, one single sided and two corner rooms in each facade, pumping ventilation can potentially occur in two or more rooms for 62 % of incoming wind directions. To investigate the transition between steady cross-ventilation and unsteady pumping ventilation, three-dimensional computational fluid dynamics large eddy simulations were performed to obtain wind generated pressures in the ventilation openings. Results show that the transition from cross-ventilation to pumping occurs when the steady pressure becomes smaller than the unsteady component. These results are used to develop a pressure based simplified model for corner ventilation that can predict effective airflow from external wind generated pressures with an average error below 10.2 %. © 2021 Elsevier Ltd
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| 9. |
- de Bem, Andreza Fabro, et al.
(författare)
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Animal Models of Metabolic Disorders in the Study of Neurodegenerative Diseases : An Overview
- 2021
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 14
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Forskningsöversikt (refereegranskat)abstract
- The incidence of metabolic disorders, as well as of neurodegenerative diseases—mainly the sporadic forms of Alzheimer’s and Parkinson’s disease—are increasing worldwide. Notably, obesity, diabetes, and hypercholesterolemia have been indicated as early risk factors for sporadic forms of Alzheimer’s and Parkinson’s disease. These conditions share a range of molecular and cellular features, including protein aggregation, oxidative stress, neuroinflammation, and blood-brain barrier dysfunction, all of which contribute to neuronal death and cognitive impairment. Rodent models of obesity, diabetes, and hypercholesterolemia exhibit all the hallmarks of these degenerative diseases, and represent an interesting approach to the study of the phenotypic features and pathogenic mechanisms of neurodegenerative disorders. We review the main pathological aspects of Alzheimer’s and Parkinson’s disease as summarized in rodent models of obesity, diabetes, and hypercholesterolemia.
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| 10. |
- Dutta, Tanmoy, 1998, et al.
(författare)
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Mitochondrial amidoxime-reducing component 1 p.Ala165Thr increases protein degradation mediated by the proteasome.
- 2024
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Ingår i: Liver international : official journal of the International Association for the Study of the Liver. - 1478-3231.
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health concern with no effective and specific drug treatment available. The rs2642438 minor allele in mitochondrial amidoxime-reducing component 1 (MARC1) results in an aminoacidic substitution (p.Ala165Thr) and associates with protection against MASLD. However, the mechanisms behind this protective effect are unknown. In this study, we examined the consequences of this aminoacidic substitution on protein stability and subcellular localization.We overexpressed the human MARC1 A165 (wild-type) or 165T (mutant) invivo in mice and invitro in human hepatoma cells (HepG2 and HuH-7), generated several mutants at position 165 by insitu mutagenesis and then examined protein levels. We also generated HepG2 cells stably overexpressing MARC1 A165 or 165T to test the effect of this substitution on MARC1 subcellular localization.MARC1 165T overexpression resulted in lower protein levels than A165 both invivo and invitro. Similarly, any mutant at position 165 showed lower protein levels compared to the wild-type protein. We showed that the 165T mutant protein is polyubiquitinated and its degradation is accelerated through lysine-48 ubiquitin-mediated proteasomal degradation. We also showed that the 165T substitution does not affect the MARC1 subcellular localization.This study shows that alanine at position 165 in MARC1 is crucial for protein stability, and the threonine substitution at this position leads to a hypomorphic protein variant due to lower protein levels. Our result supports the notion that lowering hepatic MARC1 protein level may be a successful therapeutic strategy for treating MASLD.
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