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  • Espinoza, Fredrik, et al. (författare)
  • Analysis of Open Answers to Survey Questions throughInteractive Clustering and Theme Extraction
  • 2018
  • Ingår i: Proceedings of Conference on Human Information Interaction & Retrieval. - ACM Digital Library. ; s. 317-320
  • Konferensbidrag (refereegranskat)abstract
    • This paper describes design principles for and the implementation of Gavagai Explorer—a new application which builds on interactive text clustering to extract themes from topically coherent text sets such as open text answers to surveys or questionnaires.An automated system is quick, consistent, and has full coverage over the study material. A system allows an analyst to analyze more answers in a given time period; provides the same initial results regardless of who does the analysis, reducing the risks of inter-rater discrepancy; and does not risk miss responses due to fatigue or boredom. These factors reduce the cost and increase the reliability of the service. The most important feature, however, is relieving the human analyst from the frustrating aspects of the coding task, freeing the effort to the central challenge of understanding themes. Gavagai Explorer is available on-line at http://explorer.gavagai.se
  • Fornander, Louise Helena, et al. (författare)
  • Using Nanofluidic Channels to Probe the Dynamics of Rad51-DNA Filaments
  • 2014
  • Ingår i: Biophysical Journal. - 0006-3495 .- 1542-0086. ; 106:2, s. 692A-693A
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Rad51 is a key protein involved in the strand exchange reaction, a reaction where genetic material is transferred between two homologous DNA strands. Strand exchange is initiated by Rad51 forming a helical filament around single-stranded DNA (ssDNA), and the strand exchange is thereafter executed with a homologous double-stranded DNA (dsDNA). The structure of Rad51-DNA filaments, and also the activity of the strand exchange reaction, is dependent on the presence of ATP and dications, where Ca2+ has been shown to promote a higher degree of strand exchange than Mg2+.
  • Fornander, Louise H., et al. (författare)
  • Visualizing the Nonhomogeneous Structure of RAD51 Filaments Using Nanofluidic Channels
  • 2016
  • Ingår i: Langmuir. - 07437463. ; 32:33, s. 8403-8412
  • Tidskriftsartikel (refereegranskat)abstract
    • RAD51 is the key component of the homologous recombination pathway in eukaryotic cells and performs its task by forming filaments on DNA. In this study we investigate the physical properties of RAD51 filaments formed on DNA using nanofluidic channels and fluorescence microscopy. Contrary to the bacterial ortholog RecA, RAD51 forms inhomogeneous filaments on long DNA in vitro, consisting of several protein patches. We demonstrate that a permanent "kink" in the filament is formed where two patches meet if the stretch of naked DNA between the patches is short. The kinks are readily seen in the present microscopy approach but would be hard to identify using conventional single DNA molecule techniques where the DNA is more stretched. We also demonstrate that protein patches separated by longer stretches of bare DNA roll up on each other and this is visualized as transiently overlapping filaments. RAD51 filaments can be formed at several different conditions, varying the cation (Mg2+ or Ca2+), the DNA substrate (single-stranded or double-stranded), and the RAD51 concentration during filament nucleation, and we compare the properties of the different filaments formed. The results provide important information regarding the physical properties of RAD51 filaments but also demonstrate that nanofluidic channels are perfectly suited to study protein-DNA complexes.
  • Friederich Persson, Malou, et al. (författare)
  • Coenzyme Q10 prevents GDP-sensitive mitochondrial uncoupling, glomerular hyperfiltration and proteinuria in kidneys from db/db mice as a model of type 2 diabetes
  • 2012
  • Ingår i: Diabetologia. - Springer Verlag (Germany). - 0012-186X. ; 55:5, s. 1535-1543
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis  Increased oxygen consumption results in kidney tissue hypoxia, which is proposed to contribute to the development of diabetic nephropathy. Oxidative stress causes increased oxygen consumption in type 1 diabetic kidneys, partly mediated by uncoupling protein-2 (UCP-2)-induced mitochondrial uncoupling. The present study investigates the role of UCP-2 and oxidative stress in mitochondrial oxygen consumption and kidney function in db/db mice as a model of type 2 diabetes. Methods  Mitochondrial oxygen consumption, glomerular filtration rate and proteinuria were investigated in db/db mice and corresponding controls with and without coenzyme Q10 (CoQ10) treatment.Results  Untreated db/db mice displayed mitochondrial uncoupling, manifested as glutamate-stimulated oxygen consumption (2.7 ± 0.1 vs 0.2 ± 0.1 pmol O2 s−1 [mg protein]−1), glomerular hyperfiltration (502 ± 26 vs 385 ± 3 μl/min), increased proteinuria (21 ± 2 vs 14 ± 1, μg/24 h), mitochondrial fragmentation (fragmentation score 2.4 ± 0.3 vs 0.7 ± 0.1) and size (1.6 ± 0.1 vs 1 ± 0.0 μm) compared with untreated controls. All alterations were prevented or reduced by CoQ10 treatment. Mitochondrial uncoupling was partly inhibited by the UCP inhibitor GDP (−1.1 ± 0.1 pmol O2 s−1 [mg protein]−1). UCP-2 protein levels were similar in untreated control and db/db mice (67 ± 9 vs 67 ± 4 optical density; OD) but were reduced in CoQ10 treated groups (43 ± 2 and 38 ± 7 OD).Conclusions/interpretation  db/db mice displayed oxidative stress-mediated activation of UCP-2, which resulted in mitochondrial uncoupling and increased oxygen consumption. CoQ10 prevented altered mitochondrial function and morphology, glomerular hyperfiltration and proteinuria in db/db mice, highlighting the role of mitochondria in the pathogenesis of diabetic nephropathy and the benefits of preventing increased oxidative stress.
  • Friederich-Persson, Malou, et al. (författare)
  • Increased kidney metabolismas a pathway to kidney tissue hypoxia and damage : effects of triiodothyronine and dinitrophenol in normoglycemic rats
  • 2013
  • Ingår i: Advances in Experimental Medicine and Biology. - 0065-2598 .- 2214-8019. - 978-1-4614-7411-1 - 978-1-4614-7256-8 ; 789, s. 9-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Intrarenal tissue hypoxia is an acknowledged common pathway to end-stage renal disease in clinically common conditions associated with development of chronic kidney disease, such as diabetes and hypertension. In diabetic kidneys, increased oxygen metabolism mediated by mitochondrial uncoupling results in decreased kidney oxygen tension (PO2) and contributes to the development of diabetic nephropathy. The present study investigated whether increased intrarenal oxygen metabolism per se can cause intrarenal tissue hypoxia and kidney damage, independently of confounding factors such as hyperglycemia and oxidative stress. Male Sprague-Dawley rats were untreated or treated with either triiodothyronine (T3, 10 g/kg bw/day, subcutaneously for 10 days) or the mitochondria uncoupler dinitrophenol (DNP, 30 mg/kg bw/day, oral gavage for 14 days), after which in vivo kidney function was evaluated in terms of glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Transonic, PAH clearance), cortical PO2 (Clark-type electrodes), kidney oxygen consumption (QO2), and proteinuria. Administration of both T3 and DNP increased kidney QO2 and decreased PO2 which resulted in proteinuria. However, GFR and RBF were unaltered by either treatment. The present study demonstrates that increased kidney metabolism per se can cause intrarenal tissue hypoxia which results in proteinuria. Increased kidney QO2 and concomitantly reduced PO2 may therefore be a mechanism for the development of chronic kidney disease and progression to end-stage renal disease.
  • Fritzsche, Joachim, et al. (författare)
  • A lipid-based passivation scheme for nanofluidics
  • 2012
  • Ingår i: Proceedings of the 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2012. - Chemical and Biological Microsystems Society. - 9780979806452 ; s. 1876-1878
  • Konferensbidrag (refereegranskat)abstract
    • Stretching DNA in nanochannels allows for direct, visual studies of genomic DNA at the single molecule level. In order to facilitate the study of the interaction of linear DNA with proteins in nanochannels, we have implemented a highly effective passivation scheme based on lipid bilayers. We show long-term passivation of nanochannel surfaces to several relevant reagents and demonstrate that the performance of the lipid bilayer is significantly better compared to standard bovine serum albumin-based passivation. Moreover, we demonstrate how the passivated devices allow us to monitor single DNA cleavage events during enzymatic degradation.
  • Frykholm, Karolin, et al. (författare)
  • Probing Physical Properties of a DNA-Protein Complex Using Nanofluidic Channels
  • 2014
  • Ingår i: Biophysical Journal. - 0006-3495 .- 1542-0086. ; 106:2, s. 428A-429A
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Nanofluidic channels have become an important tool to investigate single DNA molecules both from a fundamental polymer physics perspective as well as in e.g. optical mapping techniques. However, less effort has been made to study DNA-protein complexes. A main reason is that the extreme surface-to-volume ratio in the nanochannels causes most proteins to stick to the channel walls. We have recently overcome this problem by coating the channels with a lipid bilayer, thereby eliminating sticking.
  • Frykholm, Karolin, et al. (författare)
  • Probing Physical Properties of a DNA- Protein Complex Using Nanofluidic Channels
  • 2014
  • Ingår i: Small. - 1613-6810. ; 10:5, s. 884-887
  • Tidskriftsartikel (refereegranskat)abstract
    • A method to investigate physical properties of a DNA-protein complex in solution is demonstrated. By using tapered nanochannels and lipid passivation the persistence length of a RecA filament formed on double-stranded DNA is determined to 1.15 μm, in agreement with the literature, without attaching protein or DNA to any handles or surfaces. © 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.
  • Heyman, Fredrik, et al. (författare)
  • Has the Swedish business sector become more entrepreneurial than the US business sector?
  • 2019
  • Ingår i: Research Policy. - Elsevier. - 0048-7333. ; 48:7, s. 1809-1822
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies document a 30-year decline in various measures of entrepreneurship in the U.S. Using detailed Swedish employer-employee data over the period from 1990 to 2013, we find young firms to be more prominent in the Swedish business sector than in the U.S. business sector. Young Swedish firms, aged five years or less, account for more than half of all firms during this period. We also observe an increase in Swedish entrepreneurial activity for start-ups. However, since the mid-2000s, job destruction rates for young firms have been increasing, which implies a declining employment share for younger firms. Moreover, most of the job creation by young firms occurs in the expanding service sector. We discuss different explanations for why Sweden appears not to have the same strong decline in entrepreneurial activity as the U.S. has had during the last two decades. We argue that one important explanation is the economic reforms that were implemented in Sweden in the 1990s that mitigated several hurdles to entrepreneurship.
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