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- Cheng, Ran, et al.
(författare)
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In Vitro and in Vivo Evaluation of C-11-Labeled Azetidinecarboxylates for Imaging Monoacylglycerol Lipase by PET Imaging Studies
- 2018
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 61:6, s. 2278-2291
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Tidskriftsartikel (refereegranskat)abstract
- Monoacylglycerol lipase (MAGL) is the principle enzyme for metabolizing endogenous cannabinoid ligand 2-arachidonoyglycerol (2-AG). Blockade of MAGL increases 2-AG levels, resulting in subsequent activation of the endocannabinoid system, and has emerged as a novel therapeutic strategy to treat drug addiction, inflammation, and neurodegenerative diseases. Herein we report a new series of MAGL inhibitors, which were radiolabeled by site-specific labeling technologies, including C-11-carbonylation and spirocyclic iodonium ylide (SCIDY) radio fluorination. The lead compound [C-11]10 (MAGL-0519) demonstrated high specific binding and selectivity in vitro and in vivo. We also observed unexpected washout kinetics with these irreversible radiotracers, in which in vivo evidence for turnover of the covalent residue was unveiled between MAGL and azetidine carboxylates. This work may lead to new directions for drug discovery and PET tracer development based on azetidine carboxylate inhibitor scaffold.
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- Pahlm, Olle, et al.
(författare)
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Scientific MALT and STAFF meetings - past, present, and future
- 2016
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 0022-0736. ; 49:3, s. 259-262
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Forskningsöversikt (refereegranskat)abstract
- The scientific STAFF and MALT meetings were created around the turn of the century for scientists engaged in enhancing the role of the 12-lead ECG for detection and quantification of involved myocardium in patients with acute coronary syndrome. These meetings were initially focused on computer processing of data from two single-center databases. The STAFF database was collected in the mid-nineties on patients with prolonged total coronary occlusion; high-resolution 12-lead ECGs were collected before, during, and after 5 minutes of occlusion. The MALT database was created in the early years of this century on consecutive patients with chest pain admitted to a large teaching hospital. Delayed enhancement magnetic resonance imaging and electrocardiograms were recorded in these acutely ill patients. The paper highlights the first 2 decades of the STAFF and MALT meetings and details the meeting format.
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- Cartwright, S. P., et al.
(författare)
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Constitutively-stressed yeast strains are high-yielding for recombinant Fps1: implications for the translational regulation of an aquaporin
- 2017
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Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We previously selected four strains of Saccharomyces cerevisiae for their ability to produce the aquaporin Fps1 in sufficient yield for further study. Yields from the yeast strains spt3 Delta, srb5 Delta, gcn5 Delta. and yTHCBMS1 (supplemented with 0.5 mu g/mL doxycycline) that had been transformed with an expression plasmid containing 249 base pairs of 5' untranslated region (UTR) in addition to the primary FPS1 open reading frame (ORF) were 10-80 times higher than yields from wild-type cells expressing the same plasmid. One of the strains increased recombinant yields of the G protein-coupled receptor adenosine receptor 2a (A(2a)R) and soluble green fluorescent protein (GFP). The specific molecular mechanisms underpinning a high-yielding Fps1 phenotype remained incompletely described. Results: Polysome profiling experiments were used to analyze the translational state of spt3 Delta, srb5 Delta, gcn5 Delta. and yTHCBMS1 (supplemented with 0.5 mu g/mL doxycycline); all but gcn5 Delta. were found to exhibit a clear block in translation initiation. Four additional strains with known initiation blocks (rpl31a Delta., rpl22a Delta., ssf1 Delta. and nop1 Delta.) also improved the yield of recombinant Fps1 compared to wild-type. Expression of the eukaryotic transcriptional activator GCN4 was increased in spt3 Delta, srb5 Delta, gcn5 Delta. and yTHCBMS1 (supplemented with 0.5 mu g/mL doxycycline); these four strains also exhibited constitutive phosphorylation of the eukaryotic initiation factor, eIF2 alpha. Both responses are indicative of a constitutively-stressed phenotype. Investigation of the 5' UTR of FPS1 in the expression construct revealed two untranslated ORFs (uORF1 and uORF2) upstream of the primary ORF. Deletion of either uORF1 or uORF1 and uORF2 further improved recombinant yields in our four strains; the highest yields of the uORF deletions were obtained from wild-type cells. Frame-shifting the stop codon of the native uORF (uORF2) so that it extended into the FPS1 ORF did not substantially alter Fps1 yields in spt3. or wild-type cells, suggesting that high-yielding strains are able to bypass 5' uORFs in the FPS1 gene via leaky scanning, which is a known stress-response mechanism. Yields of recombinant A2aR, GFP and horseradish peroxidase could be improved in one or more of the yeast strains suggesting that a stressed phenotype may also be important in high-yielding cell factories. Conclusions: Regulation of Fps1 levels in yeast by translational control may be functionally important; the presence of a native uORF (uORF2) may be required to maintain low levels of Fps1 under normal conditions, but higher levels as part of a stress response. Constitutively-stressed yeast strains may be useful high-yielding microbial cell factories for recombinant protein production.
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- Fundana, Ketut, et al.
(författare)
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Continuous Graph Cut Segmentation with Shape Priors
- 2008
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Ingår i: 2008 19th International Conference on Pattern Recognition. - 9781424421749
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Konferensbidrag (refereegranskat)abstract
- In this paper we propose a novel prior-based variational object segmentation method in a global minimization framework which unifies image segmentation and image denoising. The idea of the proposed method is to convexify the energy functional of the Chan-Vese method in order to find a global minimizer, so called continuous graph cuts. The method is extended by adding an additional shape constraint into the convex energy functional in order to segment an object using prior information. We show that the energy functional including a shape prior term can be relaxed from optimization over characteristic functions to optimization over arbitrary functions followed by a thresholding at an arbitrarily chosen level between 0 and 1. Experimental results demonstrate the performance and robustness of the method to segment objects in real images.
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Om folkhögskolan : En särskild utbildningsform för vuxna
- 2020. - 1
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Sverige har ett unikt, väl utbyggt och förmånligt system för vuxnas studier och lärande. Vuxnas studiedeltagande är omfattande och sker i en rad olika sammanhang, bland annat folkhögskola, kommunal vuxenutbildning, yrkeshögskola, studiecirklar och högskola.Om folkhögskolan är en introducerande grundbok. Den redogör för folkhögskolans organisation, framväxt och framtida utmaningar, men även för olika pedagogiska och didaktiska begrepp med bäring på arbete inom folkhögskolan. Till exempel om folkhögskolans pedagogik och didaktik, kursutveckling, didaktisk innovation och frågor om bedömning. Blicken riktas även mot vilka som jobbar som lärare inom folkhögskolan och vilka deltagarna är.Boken vänder sig till dig som studerar på folkhögskollärarprogrammet eller andra utbildningar som kan leda till arbete inom folkhögskolan. Den är även relevant för verksamma inom folkhögskolan och personer med intresse för frågor om vuxnas studier och lärande i folkhögskolans sammanhang.
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