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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Cabaleiro-Lago, Celia, et al.
(författare)
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Inhibition of IAPP and IAPP(20-29) fibrillation by polymeric nanoparticles
- 2010
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Ingår i: Langmuir. - : The American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:5, s. 3453-3461
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Tidskriftsartikel (refereegranskat)abstract
- The fibrillation process of the islet amyloid polypeptide (IAPP) and its fragment (IAPP(20-29)) was studied by means of Thioflavin T (ThT) fluorescence and transmission electron microscopy in the absence and presence of N-isopropylacrylamide:N-tert-butylacrylamide (NiPAM:BAM) copolymeric nanoparticles. The process was found to be strongly affected by the presence of the nanoparticles, which retard protein fibrillation as a function of the chemical surface properties of the nanoparticles. The NiPAM:BAM ratio was varied from 50:50 to 100:0. The nanoparticles with higher fraction of NiPAM imposed the strongest retardation of IAPP and IAPP(20-29) fibrillation. These particles have the strongest hydrogen bonding capacity due to the less bulky N-isopropyl group and thus less steric hindrance of the hydrogen-bonding groups of the nanoparticle polymer backbone. Kinetic fibrillation data, as monitored by ThT fluorescence and supported by surface plasmon resonance experiments, suggest that the peptide is strongly absorbed onto the surface of the nanoparticles. This interaction reduces the concentration of peptide free in solution available to proceed to fibrillation which results in an increased lag time of fibrillation, observed as a delayed onset of ThT fluorescence increase, plus a reduction of the amount of fibrils formed as indicated by the equilibrium values at the end of the fibrillation reaction. For the fragment (IAPP(20-29)), the presence of nanoparticles changes the mechanism of association from monomers to fibrils, by interfering with early oligomeric species along the fibrillation pathway.
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- Dawson, Andreas, et al.
(författare)
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The effect of botulinum toxin A on patients with persistent idiopathic dentoalveolar pain : A systematic review
- 2020
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 47:9, s. 1184-1191
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has been suggested that botulinum toxin A (BONT-A) is a safe and effective treatment in relieving pain in patients with persistent idiopathic dentoalveolar pain (PIDP).OBJECTIVES: This study aimed to systematically evaluate all the available studies investigating the pain-relieving effects of BONT-A in patients with PIDP.METHODS: A systematic search with specific search terms was made in PubMed, Web of Science and Scopus. Two authors screened titles and abstracts and selected eligible studies for inclusion in the systematic review. The quality of the studies was evaluated by the 12 items Quality Assessment Tool for Observational studies (Pre-Post) Studies with No Control Group, and the level of evidence was assessed according to GRADE.RESULTS: Three observational studies of 3695 identified were included (445 overlapping studies; 3247 excluded studies). All studies were uncontrolled observational studies investigating the pain-relieving effect of BONT-A in patients with PIDP. The included studies had a fair quality (moderate risk of bias) and insufficient level of evidence. The pain reducing effect by BONT-A injections was in average 50% or more in two studies, in one study 3 out of 4 patients became almost pain free.CONCLUSIONS: This systematic review shows that presently the level of scientific evidence is insufficient to evaluate the pain-relieving effect of BONT-A injections in patients with PIDP. There are indications that BONT-A injections could be a possible management option for patients with PIDP that seems to be safe and with few adverse events. There is a need for well-designed placebo-controlled, double-blind RCTs.
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- Hagberg, Henrik, 1955, et al.
(författare)
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PARP-1 gene disruption in mice preferentially protects males from perinatal brain injury
- 2004
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Ingår i: J Neurochem. ; 90:5, s. 1068-75
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Tidskriftsartikel (refereegranskat)abstract
- Poly(ADP-ribose) polymerase-1 is over-activated in the adult brain in response to ischemia and contributes to neuronal death, but its role in perinatal brain injury remains uncertain. To address this issue, 7-day-old wild-type (wt) and PARP-1 gene deficient (parp+/- and parp-/-) Sv129/CD-1 hybrid mice were subjected to unilateral hypoxia-ischemia and histologic damage was assessed 10 days later by two evaluators. Poly(ADP-ribose) polymerase-1 knockout produced moderate but significant (p < 0.05) protection in the total group of animals, but analysis by sex revealed that males were strongly protected (p < 0.05) in contrast to females in which there was no significant effect. Separate experiments demonstrated that PARP-1 was activated over 1-24 h in both females and males after the insult in neonatal wt mice and rats using immnocytochemistry and western blotting for poly(ADP-ribose). Brain levels of NAD+ were also significantly reduced, but the decrease of NAD+ during the early post-hypoxia-ischemia (HI) phase was only seen in males. The results indicate that hypoxia-ischemia activates Poly(ADP-ribose) polymerase-1 in the neonatal brain and that the sex of the animal strongly influences its role in the pathogenesis of brain injury.
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- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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- Leitão, T., et al.
(författare)
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Contaminant sampling and analysis
- 2008
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Ingår i: Water in Road Structures. - : Springer. - 9781402085611 ; , s. 147-174
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Bokkapitel (refereegranskat)
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19. |
- Lüscher, Bernhard, et al.
(författare)
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ADP-ribosyltransferases, an update on function and nomenclature
- 2022
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Ingår i: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 289:23, s. 7399-7410
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Tidskriftsartikel (refereegranskat)abstract
- ADP-ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and is involved in intra- and extracellular signaling, chromatin and transcriptional regulation, protein biosynthesis, and cell death. ADP-ribosylation is catalyzed by ADP-ribosyltransferases (ARTs), which transfer ADP-ribose from NAD+ onto substrates. The modification, which occurs as mono- or poly-ADP-ribosylation, is reversible due to the action of different ADP-ribosylhydrolases. Importantly, inhibitors of ARTs are approved or are being developed for clinical use. Moreover, ADP-ribosylhydrolases are being assessed as therapeutic targets, foremost as antiviral drugs and for oncological indications. Due to the development of novel reagents and major technological advances that allow the study of ADP-ribosylation in unprecedented detail, an increasing number of cellular processes and pathways are being identified that are regulated by ADP-ribosylation. In addition, characterization of biochemical and structural aspects of the ARTs and their catalytic activities have expanded our understanding of this protein family. This increased knowledge requires that a common nomenclature be used to describe the relevant enzymes. Therefore, in this viewpoint, we propose an updated and broadly supported nomenclature for mammalian ARTs that will facilitate future discussions when addressing the biochemistry and biology of ADP-ribosylation. This is combined with a brief description of the main functions of mammalian ARTs to illustrate the increasing diversity of mono- and poly-ADP-ribose mediated cellular processes.
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- Lynch, Iseult, et al.
(författare)
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The nanoparticle - protein complex as a biological entity; a complex fluids and surface science challenge for the 21st century
- 2007
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Ingår i: Advances in Colloid and Interface Science. - Univ Coll Dublin, Sch Chem & Chem Biol, Dublin, Ireland. Conway Inst Biomed & Biomol Res, Dublin, Ireland. Lund Univ, SE-22100 Lund, Sweden. : ELSEVIER. - 0001-8686 .- 1873-3727. ; 134-35, s. 167-174
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Tidskriftsartikel (refereegranskat)abstract
- The major aim of our current work is to develop a deep understanding of biological effects of nanoparticles and how these effects are mediated by proteins that are adsorbed on the nanoparticles under different biological circumstances. Due to their small size, nanoparticles have distinct properties compared to the bulk form of the same materials, and these properties are rapidly revolutionizing many areas of medicine and technology. However, relatively little is known about the interaction of nanoscale objects with biological systems, as this requires quite different concepts from more established nanoscience. Thus, we have argued that in a biological fluid, proteins associate with nanoparticles, and it is the amount and presentation of the proteins on the surface rather than the particles themselves that are the cause of numerous biological responses. It is this outer layer of proteins that is seen by the biological cells, and leads to their responses. We are developing novel techniques to identify and quantify the proteins that are consistently associated with nanoparticles, as a function of the nanoparticle size, shape, and surface properties, and to correlate the adsorbed protein identities with their association and dissociation rates to and from the nanoparticles. We also seek to understand the degree of conformational change that they undergo upon adsorption to the nanoparticles. In essence, we wish to create "epitope maps" of the protein corona that surrounds nanoparticles in biological solutions, as it is the particle-protein complex that is the biologically active entity. (c) 2007 Elsevier B.V. All rights reserved.
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- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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- Prendergast, Jillian, et al.
(författare)
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Ganglioside Regulation of AMPA Receptor Trafficking
- 2014
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 34:39, s. 13246-13258
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Tidskriftsartikel (refereegranskat)abstract
- Gangliosides are major cell-surface determinants on all vertebrate neurons. Human congenital disorders of ganglioside biosynthesis invariably result in intellectual disability and are often associated with intractable seizures. To probe the mechanisms of ganglioside functions, affinity-captured ganglioside-binding proteins from rat cerebellar granule neurons were identified by quantitative proteomic mass spectrometry. Of the six proteins that bound selectively to the major brain ganglioside GT1b (GT1b:GM1 > 4; p < 10−4), three regulate neurotransmitter receptor trafficking: Thorase (ATPase family AAA domain-containing protein 1), soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (γ-SNAP), and the transmembrane protein Nicalin. Thorase facilitates endocytosis of GluR2 subunit-containing AMPA-type glutamate receptors (AMPARs) in an ATPase-dependent manner; its deletion in mice results in learning and memory deficits (J. Zhang et al., 2011b). GluR2-containing AMPARs did not bind GT1b, but bound specifically to another ganglioside, GM1. Addition of noncleavable ATP (ATPγS) significantly disrupted ganglioside binding, whereas it enhanced AMPAR association with Thorase, NSF, and Nicalin. Mutant mice lacking GT1b expressed markedly higher brain Thorase, whereas Thorase-null mice expressed higher GT1b. Treatment of cultured hippocampal neurons with sialidase, which cleaves GT1b (and other sialoglycans), resulted in a significant reduction in the size of surface GluR2 puncta. These data support a model in which GM1-bound GluR2-containing AMPARs are functionally segregated from GT1b-bound AMPAR-trafficking complexes. Release of ganglioside binding may enhance GluR2-containing AMPAR association with its trafficking complexes, increasing endocytosis. Disrupting ganglioside biosynthesis may result in reduced synaptic expression of GluR2-contianing AMPARs resulting in intellectual deficits and seizure susceptibility in mice and humans.
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- Puschmann, Andreas, et al.
(författare)
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Heterozygous PINK1 p.G411S increases risk of Parkinson's disease via a dominant-negative mechanism
- 2017
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 140:1, s. 98-117
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Tidskriftsartikel (refereegranskat)abstract
- SEE GANDHI AND PLUN-FAVREAU DOI101093/AWW320 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: It has been postulated that heterozygous mutations in recessive Parkinson's genes may increase the risk of developing the disease. In particular, the PTEN-induced putative kinase 1 (PINK1) p.G411S (c.1231G>A, rs45478900) mutation has been reported in families with dominant inheritance patterns of Parkinson's disease, suggesting that it might confer a sizeable disease risk when present on only one allele. We examined families with PINK1 p.G411S and conducted a genetic association study with 2560 patients with Parkinson's disease and 2145 control subjects. Heterozygous PINK1 p.G411S mutations markedly increased Parkinson's disease risk (odds ratio = 2.92, P = 0.032); significance remained when supplementing with results from previous studies on 4437 additional subjects (odds ratio = 2.89, P = 0.027). We analysed primary human skin fibroblasts and induced neurons from heterozygous PINK1 p.G411S carriers compared to PINK1 p.Q456X heterozygotes and PINK1 wild-type controls under endogenous conditions. While cells from PINK1 p.Q456X heterozygotes showed reduced levels of PINK1 protein and decreased initial kinase activity upon mitochondrial damage, stress-response was largely unaffected over time, as expected for a recessive loss-of-function mutation. By contrast, PINK1 p.G411S heterozygotes showed no decrease of PINK1 protein levels but a sustained, significant reduction in kinase activity. Molecular modelling and dynamics simulations as well as multiple functional assays revealed that the p.G411S mutation interferes with ubiquitin phosphorylation by wild-type PINK1 in a heterodimeric complex. This impairs the protective functions of the PINK1/parkin-mediated mitochondrial quality control. Based on genetic and clinical evaluation as well as functional and structural characterization, we established p.G411S as a rare genetic risk factor with a relatively large effect size conferred by a partial dominant-negative function phenotype.
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- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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34. |
- Aad, G., et al.
(författare)
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- 2011
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Tidskriftsartikel (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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38. |
- Aad, G., et al.
(författare)
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- 2013
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swepub:Mat__t (refereegranskat)
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39. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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