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- Holmberg, J. -E, et al.
(författare)
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Nordic experience and experiments of modeling digital I&C systems in PSA
- 2012
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Ingår i: 8th International Topical Meeting on Nuclear Plant Instrumentation, Control, and Human-Machine Interface Technologies 2012, NPIC and HMIT 2012. ; , s. 278-290
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Konferensbidrag (refereegranskat)abstract
- The OECD/NEA CSNI Working Group on Risk Assessment (WGRisk) has set up a task group called DIGREL to develop a taxonomy of failure modes of digital components for the purposes of probabilistic safety assessment (PSA). A parallel Nordic activity carried out a prestudy where a comparison of Nordic experiences and a literature review were performed. The study showed a wide range of approaches and solutions to the challenges given by digital I&C, and also indicated that no state-of-the-art currently exists. An existing simplified PSA model has been complemented with fault tree models for a four-redundant distributed protection system in order to study and demonstrate the effect of design features and modelling approaches. The model has been used to test the effect of CCF modelling, fail-safe principle and voting logic. The example shows that even rather simple I&C design leads to rather complex model despite of the fact that many things have been simplified and only a few protection signals are considered. One lesson from the example is that the Alpha factor model should be used to model CCF: s instead of the Beta factor model. Two options were developed to the comparison of different fail-safe principles. The role of detectable and undetectable failure modes with respect to the failed versus spurious actuations can be clearly seen in the results, showing the importance to model these features in PSA.
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| 3. |
- Holmberg, J, et al.
(författare)
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SoxB1 transcription factors and Notch signaling use distinct mechanisms to regulate proneural gene function and neural progenitor differentiation
- 2008
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 135:10, s. 1843-1851
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Tidskriftsartikel (refereegranskat)abstract
- The preservation of a pool of neural precursors is a prerequisite for proper establishment and maintenance of a functional central nervous system(CNS). Both Notch signaling and SoxB1 transcription factors have been ascribed key roles during this process, but whether these factors use common or distinct mechanisms to control progenitor maintenance is unsettled. Here, we report that the capacity of Notch to maintain neural cells in an undifferentiated state requires the activity of SoxB1 proteins, whereas the mechanism by which SoxB1 block neurogenesis is independent of Notch signaling. A common feature of Notch signaling and SoxB1 proteins is their ability to inhibit the activity of proneural bHLH proteins. Notch represses the transcription of proneural bHLH genes, while SoxB1 proteins block their neurogenic capacity. Moreover, E-proteins act as functional partners of proneural proteins and the suppression of E-protein expression is an important mechanism by which Notch counteracts neurogenesis. Interestingly, in contrast to the Hes-dependent repression of proneural genes, suppression of E-protein occurs in a Hes-independent fashion. Together, these data reveal that Notch signaling and SoxB1 transcription factors use distinct regulatory mechanisms to control proneural protein function and to preserve neural cells as undifferentiated precursors.
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| 5. |
- Nordström, Birgitta, et al.
(författare)
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The Geneva-Copenhagen survey of the Solar neighbourhood. Ages, metallicities, and kinematic properties of ∼14 000 F and G dwarfs
- 2004
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 418:3, s. 989-1019
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Forskningsöversikt (refereegranskat)abstract
- We present and discuss new determinations of metallicity, rotation, age,kinematics, and Galactic orbits for a complete, magnitude-limited, andkinematically unbiased sample of 16 682 nearby F and G dwarf stars. Our∼63 000 new, accurate radial-velocity observations for nearly 13 500stars allow identification of most of the binary stars in the sampleand, together with published uvbyβ photometry, Hipparcosparallaxes, Tycho-2 proper motions, and a few earlier radial velocities,complete the kinematic information for 14 139 stars. These high-qualityvelocity data are supplemented by effective temperatures andmetallicities newly derived from recent and/or revised calibrations. Theremaining stars either lack Hipparcos data or have fast rotation. Amajor effort has been devoted to the determination of new isochrone agesfor all stars for which this is possible. Particular attention has beengiven to a realistic treatment of statistical biases and errorestimates, as standard techniques tend to underestimate these effectsand introduce spurious features in the age distributions. Our ages agreewell with those by Edvardsson et al. (cite{edv93}), despite severalastrophysical and computational improvements since then. We demonstrate,however, how strong observational and theoretical biases cause thedistribution of the observed ages to be very different from that of thetrue age distribution of the sample. Among the many basic relations ofthe Galactic disk that can be reinvestigated from the data presentedhere, we revisit the metallicity distribution of the G dwarfs and theage-metallicity, age-velocity, and metallicity-velocity relations of theSolar neighbourhood. Our first results confirm the lack of metal-poor Gdwarfs relative to closed-box model predictions (the ``G dwarfproblem''), the existence of radial metallicity gradients in the disk,the small change in mean metallicity of the thin disk since itsformation and the substantial scatter in metallicity at all ages, andthe continuing kinematic heating of the thin disk with an efficiencyconsistent with that expected for a combination of spiral arms and giantmolecular clouds. Distinct features in the distribution of the Vcomponent of the space motion are extended in age and metallicity,corresponding to the effects of stochastic spiral waves rather thanclassical moving groups, and may complicate the identification ofthick-disk stars from kinematic criteria. More advanced analyses of thisrich material will require careful simulations of the selection criteriafor the sample and the distribution of observational errors.Based on observations made with the Danish 1.5-m telescope at ESO, LaSilla, Chile, and with the Swiss 1-m telescope at Observatoire deHaute-Provence, France.Complete Tables 1 and 2 are only available in electronic form at the CDSvia anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or viahttp://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/418/989
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| 8. |
- Westerlund, I, et al.
(författare)
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Combined epigenetic and differentiation-based treatment inhibits neuroblastoma tumor growth and links HIF2α to tumor suppression
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 114:30, s. E6137-E6146
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Tidskriftsartikel (refereegranskat)abstract
- High-risk neuroblastoma remains a therapeutic challenge, and adjuvant retinoic acid (RA) treatment shows poor efficacy. We demonstrate that combined treatment with 5-Aza-deoxycytidine (AZA) and RA impedes neuroblastoma growth and induces a transcriptional response characterized by high levels of the HIF2α transcription factor. This approach targets high-risk neuroblastoma that responds poorly to RA. In addition, genome-wide analysis of treated tumors and patient data links HIF2α to tumor suppression, which is supported by a HIF2α-specific small molecule inhibitor-mediated block of the tumor response to AZA+RA treatment.
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