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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Chuah, L. L., et al.
(författare)
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Measurement of glomerular filtration rate in patients undergoing obesity surgery
- 2018
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Ingår i: Bmc Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMost studies on obesity surgery have measured renal function using the estimated GFR. However, due to the reduction of muscle mass, and therefore creatinine that accompanies weight loss, such measures can falsely suggest an improvement in renal function. To balance the risks of surgery versus any potential benefits on renal function, we need to be able to determine renal function using valid and reliable methodologies. In this pilot study we aimed to measure renal function in patients with CKD undergoing obesity surgery using the gold standard Cr-51-EDTA GFR clearance methodology which is independent of measures of muscle mass.MethodsNine consecutive obese patients with CKD underwent obesity surgery. Their renal function was assessed using Cr-51-EDTA GFR, cystatin C and serum creatinine as well as using eGFR equations including MDRD CKD Epi, Cockcroft Gault and CKD Epi cystatin before and 12months after surgery.ResultsRenal function using the Cr-51-EDTA measured GFR did not change significantly after surgery. Similar results were obtained when Cystatin C, CKD Epi cystatin, CKD Epi cystatin creatinine and adjusted Cockcroft Gault Creatinine clearance methods were used. In contrast there were either trends or significant improvements in renal function measured using the MDRD and CKD Epi equations.ConclusionsIn this pilot study using the gold standard Cr-51-EDTA method we found stabilisation in renal function after obesity surgery. Until further definitive data emerge it is critical to balance the risk and benefits of surgery, especially if renal function may not improve as often as previously suggested.
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- D'Odorico, Paolo, et al.
(författare)
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The global Food-Energy-Water Nexus
- 2018
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Ingår i: Reviews of geophysics. - : American Geophysical Union (AGU). - 8755-1209 .- 1944-9208. ; 56:3, s. 456-531
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Forskningsöversikt (refereegranskat)abstract
- Water availability is a major factor constraining humanity's ability to meet the future food and energy needs of a growing and increasingly affluent human population. Water plays an important role in the production of energy, including renewable energy sources and the extraction of unconventional fossil fuels that are expected to become important players in future energy security. The emergent competition for water between the food and energy systems is increasingly recognized in the concept of the "food-energy-water nexus." The nexus between food and water is made even more complex by the globalization of agriculture and rapid growth in food trade, which results in a massive virtual transfer of water among regions and plays an important role in the food and water security of some regions. This review explores multiple components of the food-energy-water nexus and highlights possible approaches that could be used to meet food and energy security with the limited renewable water resources of the planet. Despite clear tensions inherent in meeting the growing and changing demand for food and energy in the 21st century, the inherent linkages among food, water, and energy systems can offer an opportunity for synergistic strategies aimed at resilient food, water, and energy security, such as the circular economy.
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- Francis, E., et al.
(författare)
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Effect of Nb and Fe on damage evolution in a Zr-alloy during proton and neutron irradiation
- 2019
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Ingår i: Acta Materialia. - : PERGAMON-ELSEVIER SCIENCE LTD. - 1359-6454 .- 1873-2453. ; 165, s. 603-614
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Tidskriftsartikel (refereegranskat)abstract
- Detailed analysis was carried out on proton and a neutron irradiated Nb-containing Zr-alloy to study the evolution of dislocation loop size and densities as well as the formation and evolution of irradiation induced precipitation/clustering. The results obtained here have been contrasted against previously published work on a Nb-free Zr-alloy [1, 21 to investigate the mechanistic reason for the improved resistance to irradiation-induced growth of Nb-containing Zr alloys. The combined use of bright field scanning transmission electron microscopy, ultra-high-resolution energy dispersive spectroscopy and atom probe tomography analysis provides evidence of evenly distributed radiation-induced Nb dusters that have formed during the early stage of proton irradiation and Fe-rich nano-rods near Fe-containing second phase particles. The former seems to have a profound effect on loop and subsequent loop formation, keeping loop size small but number density high while loops seem to initially form at similar dose levels compared to a Nb-free alloy but loop line density does not increase during further irradiation. It is hypothesized that the formation of the Nb nano-precipitates/clusters significantly hinders mobility and growth of loops, resulting in a small size, high number density and limited ability of loops to arrange along basal traces compared to Nb-free Zr-alloys. It is suggested that it is the limited loop arrangement that slows down loop formation and the root cause for the high resistance of Nb-containing Zr-alloys to irradiation-induced growth.
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- Muser, Daniele, et al.
(författare)
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Prognostic Value of Nonischemic Ringlike Left Ventricular Scar in Patients With Apparently Idiopathic Nonsustained Ventricular Arrhythmias
- 2021
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 143:14, s. 1359-1373
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Tidskriftsartikel (refereegranskat)abstract
- Background: Left ventricular (LV) scar on late gadolinium enhancement (LGE) cardiac magnetic resonance has been correlated with life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). We investigated the prognostic significance of a specific LV-LGE phenotype characterized by a ringlike pattern of fibrosis. Methods: A total of 686 patients with apparently idiopathic nonsustained VA underwent contrast-enhanced cardiac magnetic resonance. A ringlike pattern of LV scar was defined as LV subepicardial/midmyocardial LGE involving at least 3 contiguous segments in the same short-axis slice. The end point of the study was time to the composite outcome of all-cause death, resuscitated cardiac arrest because of ventricular fibrillation or hemodynamically unstable ventricular tachycardia and appropriate implantable cardioverter defibrillator therapy. Results: A total of 28 patients (4%) had a ringlike pattern of scar (group A), 78 (11%) had a non-ringlike pattern (group B), and 580 (85%) had normal cardiac magnetic resonance with no LGE (group C). Group A patients were younger compared with groups B and C (median age, 40 vs 52 vs 45 years; P<0.01), more frequently men (96% vs 82% vs 55%; P<0.01), with a higher prevalence of family history of sudden cardiac death or cardiomyopathy (39% vs 14% vs 6%; P<0.01) and more frequent history of unexplained syncope (18% vs 9% vs 3%; P<0.01). All patients in group A showed VA with a right bundle-branch block morphology versus 69% in group B and 21% in group C (P<0.01). Multifocal VAs were observed in 46% of group A patients compared with 26% of group B and 4% of group C (P<0.01). After a median follow-up of 61 months (range, 34-84 months), the composite outcome occurred in 14 patients (50.0%) in group A versus 15 (19.0%) in group B and 2 (0.3%) in group C (P<0.01). After multivariable adjustment, the presence of LGE with ringlike pattern remained independently associated with increased risk of the composite end point (hazard ratio, 68.98 [95% CI, 14.67-324.39], P<0.01). Conclusions: In patients with apparently idiopathic nonsustained VA, nonischemic LV scar with a ringlike pattern is associated with malignant arrhythmic events.
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- Muser, Daniele, et al.
(författare)
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Risk Stratification of Patients With Apparently Idiopathic Premature Ventricular Contractions A Multicenter International CMR Registry
- 2020
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Ingår i: JACC. - : ELSEVIER. - 2405-500X .- 2405-5018. ; 6:6, s. 722-735
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES This study investigated the prevalence and prognostic significance of concealed myocardial abnormalities identified by cardiac magnetic resonance (CMR) imaging in patients with apparently idiopathic premature ventricular contractions (PVCs). BACKGROUND The rote of CMR imaging in patients with frequent PVCs and otherwise negative diagnostic workup is uncertain. METHODS This was a multicenter, international study that included 518 patients (age 44 +/- 15 years; 57% men) with frequent (>1,000/24 h) PVCs and negative routine diagnostic workup. Patients underwent a comprehensive CMR protocol including late gadolinium enhancement imaging for detection of necrosis and/or fibrosis. The study endpoint was a composite of sudden cardiac death, resuscitated cardiac arrest, and nonfatal episodes of ventricular fibrillation or sustained ventricular tachycardia that required appropriate implantable cardioverter-defibrillator therapy. RESULTS Myocardial abnormalities were found in 85 (16%) patients. Mate gender (odds ratio [OR]: 4.28; 95% confidence interval [CI]: 2.06 to 8.93; p = 0.01), family history of sudden cardiac death and/or cardiomyopathy (OR: 3.61; 95% CI: 1.33 to 9.82; p = 0.01), multifocat PVCs (OR: 11.12; 95% CI: 4.35 to 28.46; p < 0.01), and non-left bundle branch block inferior axis morphology (OR: 14.11; 95% CI: 7.35 to 27.07; p < 0.01) were alt significantly related to the presence of myocardial abnormalities. After a median follow-up of 67 months, the composite endpoint occurred in 26 (5%) patients. Subjects with myocardial abnormalities on CMR had a higher incidence of the composite outcome (n = 25; 29%) compared with those without abnormalities (n = 1; 0.2%; p < 0.01). CONCLUSIONS CMR can identify concealed myocardial abnormalities in 16% of patients with apparently idiopathic frequent PVCs. Presence of myocardial abnormalities on CMR predict worse clinical outcomes. (C) 2019 by the American College of Cardiology Foundation.
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- Spina, L., et al.
(författare)
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The GALAH survey : tracing the Galactic disc with open clusters
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 503:3, s. 3279-3296
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Tidskriftsartikel (refereegranskat)abstract
- Open clusters are unique tracers of the history of our own Galaxy's disc. According to our membership analysis based on Gala astrometry, out of the 226 potential clusters falling in the footprint of the GALactic Archaeology with HERMES (GALAH) survey or the Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey, we find that 205 have secure members that were observed by at least one of the surveys. Furthermore, members of 134 clusters have high-quality spectroscopic data that we use to determine their chemical composition. We leverage this information to study the chemical distribution throughout the Galactic disc of 21 elements, from C to Eu. The radial metallicity gradient obtained from our analysis is -0.076 +/- 0.009 dex kpc(-1), which is in agreement with previous works based on smaller samples. Furthermore, the gradient in the (Fe/Hi-guiding radius (r(guid)) plane is -0.073 +/- 0.008 dex kpc(-1). We show consistently that open clusters trace the distribution of chemical elements throughout the Galactic disc differently than field stars. In particular, at the given radius, open clusters show an age-metallicity relation that has less scatter than field stars. As such scatter is often interpreted as an effect of radial migration, we suggest that these differences are due to the physical selection effect imposed by our Galaxy: clusters that would have migrated significantly also had higher chances to get destroyed. Finally, our results reveal trends in the [X/Fe]-r(guid)-age space, which are important to understand production rates of different elements as a function of space and time.
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- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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- Feuillet, Diane K., et al.
(författare)
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Spatial variations in the Milky Way disc metallicity-age relation
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 489:2, s. 1742-1752
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Tidskriftsartikel (refereegranskat)abstract
- Stellar ages are a crucial component to studying the evolution of the Milky Way. Using Gaia DR2 distance estimates, it is now possible to estimate stellar ages for a larger volume of evolved stars through isochrone matching. This work presents [M/H]-age and [alpha/M]-age relations derived for different spatial locations in the Milky Way disc. These relations are derived by hierarchically modelling the star formation history of stars within a given chemical abundance bin. For the first time, we directly observe that significant variation is apparent in the [M/H]-age relation as a function of both Galactocentric radius and distance from the disc midplane. The [M/H]-age relations support claims that radial migration has a significant effect in the plane of the disc. Using the [M/H] bin with the youngest mean age at each radial zone in the plane of the disc, the present-day metallicity gradient is measured to be -0.059 +/- 0.010 dex kpc(-1), in agreement with Cepheids and young field stars. We find a vertically flared distribution of young stars in the outer disc, confirming predictions of models and previous observations. The mean age of the [M/H]-[alpha/M] distribution of the solar neighbourhood suggests that the high-[M/H] stars are not an evolutionary extension of the low-alpha sequence. Our observational results are important constraints to Galactic simulations and models of chemical evolution.
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- Frankel, Jeffrey A., et al.
(författare)
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Economic Structure and the Decision to Adopt a Common Currency
- 1996
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Everyone studying EMU cites the theory of Optimum Currency Areas: whether a country like Sweden should join the currency union depends on such parameters as the extent of Swedish trade with other EU members and the correlation of Sweden's income with that of other members. Few economists have focused on what we consider one of the most interesting aspects of this issue. Trade patters and income correlations are endogenous. Sweden could fail the OCA criterion for membership today, and yet, if it goes ahead and joins anyway, could, as the result of joining, pass the Optimum Currency Area (OCA) criterion in the future. (Further, even if Sweden does not enter EMU quickly, it will become more likely to satisfy the OCA criteria in the future as a result of its recent accession to the EU.) The few economists who have identified the importance of the endogeneity of trade patterns and income correlation are divided on the nature of the relationship between the two. This is an important empirical question, which may hold the key to the answer regarding whether it is in Sweden's interest to join the EMU. We review the OCA theory, highlighting the role of trade links and income links. Then we discuss and analyze the endogeneity of these parameters. We present econometric evidence suggesting strongly that if trade links between Sweden and the rest of Europe strengthen in the future, then Sweden's income will become more highly correlated with European income in the future (not less correlated, as some have claimed). This has important implications for the OCA criterion. It means that a naïve examination of historical data gives a biased picture of the effects of EMU entry on Sweden. It also means that EMU membership is more likely to make sense for Sweden in the future than it does today.
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