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- Gräslund, Torbjörn, et al.
(författare)
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Exploring strategies for the design of artificial transcription factors
- 2005
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 280:5, s. 3707-3714
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Tidskriftsartikel (refereegranskat)abstract
- Artificial transcription factors can be engineered to interact with specific DNA sequences to modulate endogenous gene expression within cells. A significant hurdle to implementation of this approach is the selection of the appropriate DNA sequence for targeting. We reasoned that a good target site should be located in chromatin, where it is accessible to DNA-binding proteins, and it should be, in the close vicinity of known transcriptional regulators of the gene. Here we have explored the efficacy of these criteria to guide our selection of potential regulators of gamma-globin expression. Several zinc finger-based transcriptional activators were designed to target the sites proximal to the -117-position of the gamma-globin promoter. This region is proximal to the binding sites of known and potential natural transcription factors. Design and study of three transcription factors identified the potent transcriptional activator, ggl-VP64-RA. This transcription factor was able to interact directly with the gamma-globin promoter and up-regulate expression of reporter gene constructs as well as the endogenous gene in a selective manner. Transfection of a gg1-VP64-RA expression vector or retroviral delivery of this transcription factor into the erythroleukemia cell line K562 resulted in an increase of fetal hemoglobin. The gamma-globin content of cells expressing gg1-vp64-HA showed up to 16-fold higher levels of fetal hemoglobin than the native K562 cell line. These transcriptional activators constitute a novel class of regulators of the globin locus that may be suitable for treatment of diseases arising from mutations in this locus such as sickle cell disease and thalassemic diseases.
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- Egron, E., et al.
(författare)
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Single-dish and VLBI observations of Cygnus X-3 during the 2016 giant flare episode
- 2017
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 471:3, s. 2703-2714
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Tidskriftsartikel (refereegranskat)abstract
- In 2016 September, the microquasar Cygnus X-3 underwent a giant radio flare, which was monitored for 6 d with the Medicina Radio Astronomical Station and the Sardinia Radio Telescope. Long observations were performed in order to follow the evolution of the flare on an hourly scale, covering six frequency ranges from 1.5 to 25.6 GHz. The radio emission reached a maximum of 13.2 +/- 0.7 Jy at 7.2 GHz and 10 +/- 1 Jy at 18.6 GHz. Rapid flux variations were observed at high radio frequencies at the peak of the flare, together with rapid evolution of the spectral index: a steepened from 0.3 to 0.6 (with S-nu alpha nu(-alpha)) within 5 h. This is the first time that such fast variations are observed, giving support to the evolution from optically thick to optically thin plasmons in expansion moving outward from the core. Based on the Italian network (Noto, Medicina and SRT) and extended to the European antennas (Torun, Yebes, Onsala), very long baseline interferometry (VLBI) observations were triggered at 22 GHz on five different occasions, four times prior to the giant flare, and once during its decay phase. Flux variations of 2 h duration were recorded during the first session. They correspond to a mini-flare that occurred close to the core 10 d before the onset of the giant flare. From the latest VLBI observation we infer that 4 d after the flare peak the jet emission was extended over 30 mas.
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- Grasselli, Giacomo, et al.
(författare)
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ESICM guidelines on acute respiratory distress syndrome : definition, phenotyping and respiratory support strategies
- 2023
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Ingår i: Intensive Care Medicine. - : Springer Nature. - 0342-4642 .- 1432-1238. ; 49, s. 727-759
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Tidskriftsartikel (refereegranskat)abstract
- The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
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