| 1. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 3. |
- Wang, Xiaofeng, et al.
(författare)
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Evidence for type ia supernova diversity from ultraviolet observations with the hubble space telescope
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 749:2, s. 126-
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Tidskriftsartikel (refereegranskat)abstract
- We present ultraviolet (UV) spectroscopy and photometry of four Type Ia supernovae (SNe 2004dt, 2004ef, 2005M, and 2005cf) obtained with the UV prism of the Advanced Camera for Surveys on the Hubble Space Telescope. This data set provides unique spectral time series down to 2000 angstrom. Significant diversity is seen in the near-maximum-light spectra (similar to 2000-3500 angstrom) for this small sample. The corresponding photometric data, together with archival data from Swift Ultraviolet/Optical Telescope observations, provide further evidence of increased dispersion in the UV emission with respect to the optical. The peak luminositiesmeasured in the uvw1/F250W filter are found to correlate with the B-band light-curve shape parameter Delta m(15)(B), but with much larger scatter relative to the correlation in the broadband B band (e.g., similar to 0.4 mag versus similar to 0.2 mag for those with 0.8 mag < Delta m(15)(B) < 1.7 mag). SN 2004dt is found as an outlier of this correlation (at > 3 sigma), being brighter than normal SNe Ia such as SN 2005cf by similar to 0.9 mag and similar to 2.0 mag in the uvw1/F250W and uvm2/F220W filters, respectively. We show that different progenitor metallicity or line-expansion velocities alone cannot explain such a large discrepancy. Viewing-angle effects, such as due to an asymmetric explosion, may have a significant influence on the flux emitted in the UV region. Detailed modeling is needed to disentangle and quantify the above effects.
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| 4. |
- Speakman, John R., et al.
(författare)
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Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure
- 2023
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Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5:4, s. 579-588
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Obesity is caused by a prolonged positive energy balance(1,2). Whether reduced energy expenditure stemming from reduced activity levels contributes is debated(3,4). Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.
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| 5. |
- Quinlan, Ronald A., et al.
(författare)
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Transfer of carbon nanosheet films to nongrowth, zero thermal budget substrates
- 2011
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Ingår i: Journal of Vacuum Science & Technology B. - : American Vacuum Society. - 1071-1023 .- 1520-8567. ; 29:3, s. 030602-
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Tidskriftsartikel (refereegranskat)abstract
- Carbon-based nanostructures and materials have become a popular subject of research due to their unique thermal, mechanical, electrical, and optical properties. For example, the strong C-C bonds of graphene-based systems allow for excellent thermal conduction at room temperature and the conjugation of the sp(2) lattice enables extremely high electron mobility. However, the use of carbon nanostructures as a component in polymer composites, sensors, mirco-electro-mechanical systems, and both rigid and flexible electronics has been limited by several factors, including the incompatibility with standard photolithography techniques, the high temperatures required for the nanostructure growth, and the presence of-or complication-of removing noncarbon species. Here, the authors report on a novel method for the transfer of carbon nanosheets to a low or zero thermal budget substrate while maintaining their original morphology and electrical properties. Four-point probe measurements' post-transfer shows the retention of in-plane conductivity and scanning electron microscopy reveals the preservation of the original vertical morphology. Raman spectroscopy measurements confirm the retention of the graphitic structure of the post-transfer nanosheet film. This new transfer technique builds on the ability to conformally coat nanosheets while maintaining the original ultrahigh surface area morphology and the ability to fully incorporate nanosheets into several polymers while maintaining the original nanostructure separation. For a demonstration of the usefulness of polymer filling, carbon nanosheets were used as an ultrahigh surface area electrode for the photoactive polymer poly[2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene] in proof of principle experiments of a nanosheet-based organic photovoltaic device.
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| 6. |
- Rafat, Mehrdad, et al.
(författare)
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PEG-PLAmicroparticles for encapsulation and delivery of Tat-EGFP to retinal cells
- 2010
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Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 31:12, s. 3414-3421
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Tidskriftsartikel (refereegranskat)abstract
- The efficient and controlled delivery of genes and proteins to retinal cells remains a challenge. In this study, we evaluated polyethylene glycol-polylactic acid (PEG–PLA) microparticles for encapsulation and delivery of a Transactivator of transcription-enhanced green fluorescent protein fusion (Tat-EGFP) to retinal cells. Our main objective was to develop a microparticle system that delivers Tat-EGFP with an initial rapid release (within 24 h) followed by a sustained release. We prepared four different formulations of Tat-EGFP encapsulated PEG–PLA particles to investigate the effects of protein and polymer concentrations on particle morphology and protein release, using scanning electron microscopy (SEM) and fluorometry techniques. The optimum formulation was selected based on higher protein release, and smaller particle size. The optimum formulation was then tested in vitro for cell biocompatibility and protein internalization, and in vivo for cellular toxicity following sub-retinal injections into rat eyes. The results suggest that PEG–PLA microparticles can deliver proteins in cell culture allowing protein internalization in as little as 1 h. In vivo, protein was shown to localize within the photoreceptor layer of the retina, and persist for at least 9 weeks with no observed toxicity.
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| 7. |
- van den Berge, Simone A, et al.
(författare)
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Longterm quiescent cells in the aged human subventricular neurogenic system specifically express GFAP-delta.
- 2010
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Ingår i: Aging cell. - : Wiley. - 1474-9726 .- 1474-9718. ; 9:3, s. 313-326
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Tidskriftsartikel (refereegranskat)abstract
- Summary A main neurogenic niche in the adult human brain is the subventricular zone (SVZ). Recent data suggest that the progenitors that are born in the human SVZ migrate via the rostral migratory stream (RMS) towards the olfactory bulb (OB), similar to what has been observed in other mammals. A subpopulation of astrocytes in the SVZ specifically expresses an assembly-compromised isoform of the intermediate filament protein glial fibrillary acidic protein (GFAP-delta). To further define the phenotype of these GFAP-delta expressing cells and to determine whether these cells are present throughout the human subventricular neurogenic system, we analysed SVZ, RMS and OB sections of 14 aged brain donors (ages 74-93). GFAP-delta was expressed in the SVZ along the ventricle, in the RMS and in the OB. The GFAP-delta cells in the SVZ co-expressed the neural stem cell (NSC) marker nestin and the cell proliferation markers proliferating cell nuclear antigen (PCNA) and Mcm2. Furthermore, BrdU retention was found in GFAP-delta positive cells in the SVZ. In the RMS, GFAP-delta was expressed in the glial net surrounding the neuroblasts. In the OB, GFAP-delta positive cells co-expressed PCNA. We also showed that GFAP-delta cells are present in neurosphere cultures that were derived from SVZ precursors, isolated postmortem from four brain donors (ages 63-91). Taken together, our findings show that GFAP-delta is expressed in an astrocytic subpopulation in the SVZ, the RMS and the OB. Importantly, we provide the first evidence that GFAP-delta is specifically expressed in longterm quiescent cells in the human SVZ, which are reminiscent of NSCs.
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