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| 2. |
- Galluzzi, L, et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
- 2009
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In: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 16:8, s. 1093-107
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Research review (peer-reviewed)abstract
- Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
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| 5. |
- Maeda, Y., et al.
(author)
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Differential cross section and analyzing power measurements for (n)over-right-arrowd elastic scattering at 248 MeV
- 2007
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 76:1, s. 014004-
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Journal article (peer-reviewed)abstract
- The differential cross sections and vector analyzing powers for nd elastic scattering at E-n=248 MeV were measured for 10 degrees-180 degrees in the center-of-mass (c.m.) system. To cover the wide angular range, the experiments were performed separately by using two different setups for forward and backward angles. The data are compared with theoretical results based on Faddeev calculations with realistic nucleon-nucleon (NN) forces such as AV18, CD Bonn, and Nijmegen I and II, and their combinations with the three-nucleon forces (3NFs), such as Tucson-Melbourne 99 (TM99), Urbana IX, and the coupled-channel potential with Delta-isobar excitation. Large discrepancies are found between the experimental cross sections and theory with only 2N forces for theta(c.m.)>90 degrees. The inclusion of 3NFs brings the theoretical cross sections closer to the data but only partially explains this discrepancy. For the analyzing power, no significant improvement is found when 3NFs are included. Relativistic corrections are shown to be small for both the cross sections and the analyzing powers at this energy. For the cross sections, these effects are mostly seen in the very backward angles. Compared with the pd cross section data, quite significant differences are observed at all scattering angles that cannot be explained only by the Coulomb interaction, which is usually significant at small angles.
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| 10. |
- Jaderstrom, H., et al.
(author)
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200 and 300 MeV/nucleon nuclear reactions responsible for single-event effects in microelectronics
- 2008
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 77:4, s. 44601-
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Journal article (peer-reviewed)abstract
- An experimental study of nuclear reactions between Si-28 nuclei at 200 and 300 MeV/nucleon and hydrogen or deuterium target nuclei was performed at the CELSIUS storage ring in Uppsala, Sweden, to collect information about the reactions responsible for single-event effects in microelectronics. Inclusive data on Si-28 fragmentation, as well as data on correlations between recoils and spectator protons or alpha particles are compared to predictions from the Dubna cascade model and the Japan Atomic Energy Research Institute version of the quantum molecular dynamics model. The comparison shows satisfactory agreement for inclusive data except for He fragments where low-energy sub-barrier fragments and recoiling fragments with very large momenta are produced much more frequently than predicted. The yield of exclusive data are also severely underestimated by the models whereas the charge distributions of recoils in these correlations compare well. The observed enhancement in He emission, which may well be important for the description of single-event effects, is most likely to be attributed to alpha clustering in Si-28 nuclei.
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| 12. |
- Lindblom, P, et al.
(author)
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Tesaglitazar, a dual PPAR-α/γ agonist, hamster carcinogenicity, investigative animal and clinical studies
- 2012
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In: Toxicologic pathology. - : SAGE Publications. - 1533-1601 .- 0192-6233. ; 40:1, s. 18-32
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Journal article (peer-reviewed)abstract
- Tesaglitazar was developed as a dual peroxisome proliferator–activated receptor (PPARα/γ). To support the clinical program, a hamster carcinogenicity study was performed. The only neoplastic findings possibly related to treatment with tesaglitazar were low incidences of hemangioma and hemangiosarcoma in the liver of male animals. A high-power, two-year investigative study with interim necropsies was performed to further elucidate these findings. Treatment with tesaglitazar resulted in changes typical for exaggerated PPARα pharmacology in rodents, such as hepatocellular hypertrophy and hepatocellular carcinoma, but not an increased frequency of hemangiosarcomas. At the highest dose level, there was an increased incidence of sinusoidal dilatation and hemangiomas. No increased endothelial cell (EC) proliferation was detected in vivo, which was confirmed by in vitro administration to ECs. Immunohistochemistry and gene expression analyses indicated increased cellular stress and vascular endothelial growth factor (VEGF) expression in the liver, which may have contributed to the sinusoidal dilatation. A two-fold increase in the level of circulating VEGF was detected in the hamster at all dose levels, whereas no effect on VEGF was observed in patients treated with tesaglitazar. In conclusion, investigations have demonstrated that tesaglitazar does not produce hemangiosarcomas in hamster despite a slight effect on vascular morphology in the liver.
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| 13. |
- Murin, Y, et al.
(author)
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SEE-Related Studies at CELSIUS
- 2005
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In: Proc. 6th Int. Conf. on Nuclear Physics at Storage Rings (STORI’05), Bonn. ; , s. 153-
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Conference paper (peer-reviewed)
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| 14. |
- Saliba-Gustafsson, P., et al.
(author)
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Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Journal article (peer-reviewed)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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| 16. |
- Bi, D., et al.
(author)
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The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy
- 2014
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In: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 11
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Journal article (peer-reviewed)abstract
- Background: The relationship between genetic factors and the development of cerebral palsy (CP) has recently attracted much attention. Polymorphisms in the genes encoding proinflammatory cytokines have been shown to be associated with susceptibility to perinatal brain injury and development of CP. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a pivotal role in neonatal brain injury, but conflicting results have been reported regarding the association between IL-6 single nucleotide polymorphisms (SNPs) and CP. The purpose of this study was to analyze IL-6 gene polymorphisms and protein expression and to explore the role of IL-6 in the Chinese CP population. Methods: A total of 753 healthy controls and 713 CP patients were studied to detect the presence of five SNPs (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL-6 locus. Of these, 77 healthy controls and 87 CP patients were selected for measurement of plasma IL-6 by Luminex assay. The SHEsis program was used to analyze the genotyping data. For all comparisons; multiple testing on each individual SNP was corrected by the SNPSpD program. Results: There were no differences in allele or genotype frequencies between the overall CP patients and controls among the five genetic polymorphisms. However, subgroup analysis found significant sex-related differences in allele and genotype frequencies. Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837. Plasma IL-6 levels were higher in CP patients than in the controls, and this difference was more robust in full-term male spastic CP patients. Furthermore, the genotype has an effect on IL-6 synthesis. Conclusions: The influence of IL-6 gene polymorphisms on IL-6 synthesis and the susceptibility to CP is related to sex and gestational age.
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| 17. |
- Blomgren, E. M.V., et al.
(author)
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Grey-box modeling for hot-spot temperature prediction of oil-immersed transformers in power distribution networks
- 2023
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In: Sustainable Energy, Grids and Networks. - 2352-4677. ; 34
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Journal article (peer-reviewed)abstract
- Power transformers are one of the most costly assets in power grids. Due to increasing electricity demand and levels of distributed generation, they are more and more often loaded above their rated limits. Transformer ratings are traditionally set as static limits, set in a controlled environment with conservative margins. Through dynamic transformer rating, the rating is instead adapted to the actual working conditions of the transformers. This can help distribution system operators (DSOs) to unlock unused capacity and postpone costly grid investments. To this end, real-time information of the transformer operating conditions, and in particular of its hot-spot and oil temperature, is required. This work proposes a grey-box model that can be used for online estimation and forecasting of the transformer temperature. It relies on a limited set of non-intrusive measurements and was developed using experimental data from a DSO in Jutland, Denmark. The thermal model has proven to be able to predict the temperature of the transformers with a high accuracy and low computational time, which is particularly relevant for online applications. With a six-hour prediction horizon the mean average error was 0.4–0.6 °C. By choosing a stochastic data-driven modeling approach we can also provide prediction intervals and account for the uncertainty.
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| 22. |
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| 23. |
- Murin, Yu., et al.
(author)
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A detector system for studying nuclear reactions relevant to Single Event Effects
- 2007
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576 .- 0167-5087. ; 578:2, s. 385-398
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Journal article (peer-reviewed)abstract
- We describe a device to study reactions relevant for the Single Event Effect (SEE) in microelectronics by means of 200A and 300AMeV, inverse kinematics, Si + H and Si + D reactions. The work is focused on the possibility to measure Z = 2-14 projectile fragments as efficiently as possible. During commissioning and first experiments the fourth quadrant of the CELSIUS storage ring acted as a spectrometer to register fragments in two planes of Si strip detectors in the angular region 0 degrees-0.6 degrees. A combination of ring-structured and sector-structured Si strip detector planes operated at angles 0.6 degrees-1.1 degrees. For specific event tagging a Si+ phoswich scintillator wall operated in the range 3.9 degrees-11.7 degrees and Si Delta E-E telescopes of CHICSi type operated at large angles.
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| 25. |
- Oberg, M, et al.
(author)
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Subchronic toxicity of Baltic herring oil and its fractions in the rat I: Fractionation and levels of organohalogen pollutants
- 2002
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In: Pharmacology and Toxicology. - : Wiley. - 1600-0773 .- 0901-9928. ; 91:5, s. 220-231
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Journal article (peer-reviewed)abstract
- Baltic herring (Clupea harengus) oil was extracted and fractionated. To examine the contribution to toxicity and biological effects of different halogenated organic pollutants, the herring oil and the fractions were mixed into pelleted food and given to Sprague-Dawley female rats at three levels, corresponding to a human intake of 1.6, 8.2 and 34.4 kg fish per week. Herring oil, its fractions, as well as liver tissues from exposed rats, were analyzed for: eight chlorinated biphenyls, all 2,3,7,8-substituted chlorinated dibenzo-p-dioxins and dibenzofurans, hexachlorocyclohexanes, hexachlorobenzene, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), DDT-metabolites, three brominated diphenylethers as well as extractable organically bound chlorine and halogenated fatty acids. A bioassay (EROD) was used for measuring the dioxin-like enzyme induction activity. Nordic Sea lodda (Mallotus villosus) oil was used as a nutritionally equivalent control, with much lower levels of halogenated organic pollutants. A full toxicological subchronic examination is reported in the following paper (Stern et al. 2002). In this study, we report that the fractionation procedure resulted in a substantial reduction of most of the pollutants in the triacylglycerol fraction, and a pronounced enrichment of most of the pollutants into the two other fractions. However, all contaminants were present at some levels in all of the fractions. The concentrations of organoltalogens found in this study were representative for Baltic herring during the mid-1990s. Rat liver tissue showed similar residue patterns as the diet, with the exception of chlorinated dibenzo-p-dioxin and dibenzofuran congeners that had a higher liver retention than pesticides, chlorinated biphenyls and brominated diphenylethers.
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