1. |
- 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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2. |
- Antoniou, Antonis C., et al.
(författare)
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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
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3. |
- Blum, Matthias, et al.
(författare)
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A comprehensive resource for retrieving, visualizing, and integrating functional genomics data
- 2020
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Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The enormous amount of freely accessible functional genomics data is an invaluable resource for interrogating the biological function of multiple DNA-interacting players and chromatin modifications by large-scale comparative analyses. However, in practice, interrogating large collections of public data requires major efforts for (i) reprocessing available raw reads, (ii) incorporating quality assessments to exclude artefactual and low-quality data, and (iii) processing data by using high-performance computation. Here, we present qcGenomics, a user-friendly online resource for ultrafast retrieval, visualization, and comparative analysis of tens of thousands of genomics datasets to gain new functional insight from global or focused multidimensional data integration. © 2019 Blum et al.
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4. |
- Blum, Matthias, et al.
(författare)
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A Sustainable Century? : Genuine Savings in developing and developed countries, 1900-2000
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This chapter traces the long-run development of Genuine Savings (GS) using a panel of eleven countries during the twentieth century. This panel covers a number of developed countries (Great Britain, Germany,Switzerland, France, the US, and Australia) as well as a set of resource-abundant countries in Latin America(Argentina, Brazil, Chile, Colombia, and Mexico). These countries represent approximately 50 percentof the world’s output in terms of Gross Domestic Product (GDP) by 1950, and include large economies and small open economies, and resource-rich and resource-scarce countries, thus allowing us to compare their historical experiences. Components of GS considered include physical and human capital as well asresource extraction and pollution damages. Generally, we find evidence of positive GS over the course of the twentieth century, although the two World Wars and the Great Depression left considerable marks. Also, we found striking differences between Latin American and developed countries when Total Factor Productivity(TFP) is included; this could be a signal of natural resource curse or technological gaps unnoticed in previous works
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5. |
- Blum, Matthias, et al.
(författare)
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A sustainable century : genuine savings in developing and developed countries, 1900-2000
- 2017
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Ingår i: National wealth. - Oxford : Oxford University Press. - 9780198803720 - 9780191844119 ; , s. 89-113
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Bokkapitel (refereegranskat)abstract
- This chapter traces the long-run development of genuine savings (GS) during the twentieth century using a panel of developed countries (Great Britain, Germany, Switzerland, France, the US, and Australia) and resource-abundant countries in Latin America (Argentina, Brazil, Chile, Colombia, and Mexico) representing approximately 50% of the world’s output in terms of GDP by 1950. It includes large economies and small open economies, and resource-rich and resource-scarce countries, allowing comparison of their historical experiences. Components of GS considered include physical and human capital as well as resource extraction and pollution damages. Generally, there is evidence of positive GS over the course of the twentieth century, although the two world wars and the Great Depression left considerable marks, but also striking differences between Latin American and developed countries when total factor productivity is included; this could be a signal of natural resource curse or technological gaps unnoticed in previous works.
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6. |
- Ducoing, Cristian, et al.
(författare)
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A Sustainable Century?: Genuine Savings in Developing and Developed Countries, 1900-2000
- 2017
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Ingår i: National Wealth: What is Missing, Why it Matters. - 9780198803720
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Bokkapitel (refereegranskat)abstract
- This chapter traces the long-run development of Genuine Savings (GS) using a panel of eleven countries during the twentieth century. This panel covers a number of developed countries (Great Britain, Germany,Switzerland, France, the US, and Australia) as well as a set of resource-abundant countries in Latin America(Argentina, Brazil, Chile, Colombia, and Mexico). These countries represent approximately 50 percent of the world’s output in terms of Gross Domestic Product (GDP) by 1950, and include large economies and small open economies, and resource-rich and resource-scarce countries, thus allowing us to compare their historical experiences. Components of GS considered include physical and human capital as well asresource extraction and pollution damages. Generally, we find evidence of positive GS over the course of the twentieth century, although the two World Wars and the Great Depression left considerable marks. Also, we found striking differences between Latin American and developed countries when Total Factor Productivity(TFP) is included; this could be a signal of natural resource curse or technological gaps unnoticed in previous works.
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7. |
- Lejaeghere, Kurt, et al.
(författare)
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Reproducibility in density functional theory calculations of solids.
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 351:6280, s. 1415-1422
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Tidskriftsartikel (refereegranskat)abstract
- The widespread popularity of density functional theory has given rise to an extensive range of dedicated codes for predicting molecular and crystalline properties. However, each code implements the formalism in a different way, raising questions about the reproducibility of such predictions. We report the results of a community-wide effort that compared 15 solid-state codes, using 40 different potentials or basis set types, to assess the quality of the Perdew-Burke-Ernzerhof equations of state for 71 elemental crystals. We conclude that predictions from recent codes and pseudopotentials agree very well, with pairwise differences that are comparable to those between different high-precision experiments. Older methods, however, have less precise agreement. Our benchmark provides a framework for users and developers to document the precision of new applications and methodological improvements.
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8. |
- Mintzer, Scott, et al.
(författare)
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Effects of adjunctive eslicarbazepine acetate on serum lipids in patients with partial-onset seizures: Impact of concomitant statins and enzyme-inducing antiepileptic drugs.
- 2018
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Ingår i: Epilepsy research. - : Elsevier BV. - 1872-6844 .- 0920-1211. ; 141, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences.We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period.In total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1mg/dL and +1.8mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; -5.0mg/dL) was observed between the ESL 400mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800mg QD (<6mg/dL) and ESL 1200mg QD (<10mg/dL). ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small.These results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations.
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9. |
- Shelukhin, V, et al.
(författare)
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Observation of periodic pi-phase shifts in ferromagnet-superconductor multilayers
- 2006
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Ingår i: Physical Review B. ; 73, s. 174506-
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Tidskriftsartikel (refereegranskat)abstract
- We report complementary studies of the critical temperature and the critical current in ferromagnet (Ni) - superconductor (Nb) multilayers. The observed oscillatory behavior of both quantities upon variation of the thickness of the ferromagnetic layer is found to be in good agreement with theory. The length scale of oscillations is identical for both quantities and is set by the magnetic length corresponding to an exchange field of 200 meV in Ni. The consistency between the behavior of the two quantities provides strong evidence for periodic pi phase shifts in these devices.
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10. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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