Institution
University of Amsterdam
Education•Amsterdam, Noord-Holland, Netherlands•
About: University of Amsterdam is a education organization based out in Amsterdam, Noord-Holland, Netherlands. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 59309 authors who have published 140894 publications receiving 5984137 citations. The organization is also known as: UvA & Universiteit van Amsterdam.
Papers published on a yearly basis
Papers
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TL;DR: The use of miravirsen in patients with chronic HCV genotype 1 infection showed prolonged dose-dependent reductions in HCV RNA levels without evidence of viral resistance.
Abstract: Background The stability and propagation of hepatitis C virus (HCV) is dependent on a functional interaction between the HCV genome and liver-expressed microRNA-122 (miR-122). Miravirsen is a locked nucleic acid–modified DNA phosphorothioate antisense oligonucleotide that sequesters mature miR-122 in a highly stable heteroduplex, thereby inhibiting its function. Methods In this phase 2a study at seven international sites, we evaluated the safety and efficacy of miravirsen in 36 patients with chronic HCV genotype 1 infection. The patients were randomly assigned to receive five weekly subcutaneous injections of miravirsen at doses of 3 mg, 5 mg, or 7 mg per kilogram of body weight or placebo over a 29-day period. They were followed until 18 weeks after randomization. Results Miravirsen resulted in a dose-dependent reduction in HCV RNA levels that endured beyond the end of active therapy. In the miravirsen groups, the mean maximum reduction in HCV RNA level (log10 IU per milliliter) from baseline was 1.2 (P=...
1,978 citations
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TL;DR: This paper builds on Double Q-learning, by taking the minimum value between a pair of critics to limit overestimation, and draws the connection between target networks and overestimation bias.
Abstract: In value-based reinforcement learning methods such as deep Q-learning, function approximation errors are known to lead to overestimated value estimates and suboptimal policies. We show that this problem persists in an actor-critic setting and propose novel mechanisms to minimize its effects on both the actor and the critic. Our algorithm builds on Double Q-learning, by taking the minimum value between a pair of critics to limit overestimation. We draw the connection between target networks and overestimation bias, and suggest delaying policy updates to reduce per-update error and further improve performance. We evaluate our method on the suite of OpenAI gym tasks, outperforming the state of the art in every environment tested.
1,968 citations
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01 Jan 1992TL;DR: In most cases, the assumption that one of the variables is normally distributed with constant variance, its mean being a function of the other variables, is not always satisfied, and in most cases difficult to ascertain this paper.
Abstract: Regression analysis is usually carried out under the hypothesis that one of the variables is normally distributed with constant variance, its mean being a function of the other variables. This assumption is not always satisfied, and in most cases difficult to ascertain.
1,968 citations
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TL;DR: In this paper, the authors translate, validate, and generate normative data on the SF-36 Health Survey for use among Dutch- speaking residents of the Netherlands, followed the stepwise, iterative procedures developed by the IQOLA Project.
1,957 citations
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TL;DR: Evidence is provided that the rapid 32P-PtdOH response was primarily generated through DAG kinase (DGK), and a tentative model illustrating direct cold effects on phospholipid metabolism is presented.
Abstract: Phosphatidic acid (PtdOH) is emerging as an important signalling lipid in abiotic stress responses in plants. The effect of cold stress was monitored using 32P-labelled seedlings and leaf discs of Arabidopsis thaliana. Low, non-freezing temperatures were found to trigger a very rapid 32P-PtdOH increase, peaking within 2 and 5 min, respectively. In principle, PtdOH can be generated through three different pathways, i.e. i) via de novo phospholipid biosynthesis (through acylation of lyso-PtdOH), ii) via phospholipase D hydrolysis of structural phospholipids or iii) via phosphorylation of diacylglycerol (DAG) by DAG kinase (DGK). Using a differential 32P-labelling protocol and a PLD-transphosphatidylation assay, evidence is provided that the rapid 32P-PtdOH response was primarily generated through DGK. A simultaneous decrease in the levels of 32P-PtdInsP, correlating in time, temperature dependency and magnitude with the increase in 32P-PtdOH, suggested that a PtdInsP-hydrolyzing PLC generated the DAG in this reaction. Testing T-DNA insertion lines available for the seven DGK genes, revealed no clear changes in 32P-PtdOH responses, suggesting functional redundancy. Similarly, known cold-stress mutants were analyzed to investigate whether the PtdOH response acted downstream of the respective gene products. The hos1, los1 and fry1 mutants were found to exhibit normal PtdOH responses. Slight changes were found for ice1, snow1, and the overexpression line Super-ICE1, however, this was not cold-specific and likely due to pleiotropic effects. A tentative model illustrating direct cold effects on phospholipid metabolism is presented.
1,936 citations
Authors
Showing all 59759 results
Name | H-index | Papers | Citations |
---|---|---|---|
Richard A. Flavell | 231 | 1328 | 205119 |
Scott M. Grundy | 187 | 841 | 231821 |
Stuart H. Orkin | 186 | 715 | 112182 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
David A. Weitz | 178 | 1038 | 114182 |
Dorret I. Boomsma | 176 | 1507 | 136353 |
Brenda W.J.H. Penninx | 170 | 1139 | 119082 |
Michael Kramer | 167 | 1713 | 127224 |
Nicholas J. White | 161 | 1352 | 104539 |
Lex M. Bouter | 158 | 767 | 103034 |
Wolfgang Wagner | 156 | 2342 | 123391 |
Jerome I. Rotter | 156 | 1071 | 116296 |
David Cella | 156 | 1258 | 106402 |
David Eisenberg | 156 | 697 | 112460 |
Naveed Sattar | 155 | 1326 | 116368 |