| 1. |
- Oliveira, F., et al.
(författare)
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Data driven diagnostic classification in Alzheimer's disease based on different reference regions for normalization of PiB-PET images and correlation with CSF concentrations of A beta species
- 2018
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Ingår i: Neuroimage-Clinical. - : Elsevier BV. - 2213-1582. ; 20, s. 603-610
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Tidskriftsartikel (refereegranskat)abstract
- Positron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B (PiB) is widely used to assess amyloid plaque burden. Standard quantification approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous studies suggested similar pons and white-matter uptake in Alzheimer's disease (AD) and healthy controls (HC), but lack exhaustive comparison of normalization across the three regions, with data-driven diagnostic classification. We aimed to compare the impact of distinct reference regions in normalization, measured by data-driven statistical analysis, and correlation with cerebrospinal fluid (CSF) amyloid beta (A beta) species concentrations. 243 individuals with clinical diagnosis of AD, HC, mild cognitive impairment (MCI) and other dementias, from the Biomarkers for Alzheimer's/Parkinson's Disease (BIOMARKAPD) initiative were included. PiB-PET images and CSF concentrations of A beta(38), A beta(40) and A beta(42) were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF A beta concentrations were calculated. Normalization by cerebellar gray matter and pons yielded identical classification accuracy of AD (accuracy-96%, sensitivity-96%, specificity-95%), and significantly higher than A beta concentrations (best accuracy 91%). Normalization by the white-matter showed decreased extent of statistically significant multivoxel patterns and was the only method not outperforming CSF biomarkers, suggesting statistical inferiority. A beta(38) and A beta(40) correlated negatively with PiB-PET images normalized by the white-matter, corroborating previous observations of correlations with non-AD-specific subcortical changes in white-matter. In general, when using the pons as reference region, higher voxel-wise group differences and stronger correlation with A beta(42), the A beta(42)/A beta(40) or A beta(42)/A beta(38) ratios were found compared to normalization based on cerebellar gray matter.
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| 2. |
- Leloudas, G., et al.
(författare)
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The superluminous transient ASASSN-15lh as a tidal disruption event from a Kerr black hole
- 2016
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Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 1:1
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Tidskriftsartikel (refereegranskat)abstract
- When a star passes within the tidal radius of a supermassive black hole, it will be torn apart1. For a star with the mass of the Sun (M-circle dot) and a non-spinning black hole with a mass <10(8)M(circle dot), the tidal radius lies outside the black hole event horizon2 and the disruption results in a luminous flare(3-6). Here we report observations over a period of ten months of a transient, hitherto interpreted(7) as a superluminous supernova(8). Our data show that the transient rebrightened substantially in the ultraviolet and that the spectrum went through three different spectroscopic phases without ever becoming nebular. Our observations are more consistent with a tidal disruption event than a superluminous supernova because of the temperature evolution(6), the presence of highly ionized CNO gas in the line of sight(9) and our improved localization of the transient in the nucleus of a passive galaxy, where the presence of massive stars is highly unlikely(10,11). While the supermassive black hole has a mass >10(8)M(circle dot)(12,13), a star with the same mass as the Sun could be disrupted outside the event horizon if the black hole were spinning rapidly(14). The rapid spin and high black hole mass can explain the high luminosity of this event.
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| 3. |
- Schnadt, J., Schiessling, J., O'Shea, J.N., Gray, S.M., Patthey, L., Johansson, M.K.J., Shi, M., Krepansky, J., Åhlund, J., Karlsson, P.G., Persson, P., Mårtensson, N., and Brühwiler, P.A.
(författare)
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Structural study of adsorption of isonicotinic acid and related molecules on rutile TiO2(110). I: XAS and STM
- 2003
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Ingår i: Surface Science. ; 540, s. 39-
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Badala, A, et al.
(författare)
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Subthreshold production of low momentum K+ in p+C at 1.2 GeV
- 1998
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Ingår i: PHYSICAL REVIEW LETTERS. - : AMERICAN PHYSICAL SOC. - 0031-9007. ; 80:22, s. 4863-4866
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Tidskriftsartikel (refereegranskat)abstract
- The double differential cross section of low momentum kaons (less than or equal to 0.3 GeV/c) from p + C collisions at subthreshold bombarding energies has been for the first time measured by the use of the CLAMSUD magnetic spectrometer installed at the C
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| 5. |
- Noveir, S. D., et al.
(författare)
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Effect of the ABCA1 agonist CS-6253 on amyloid-β and lipoprotein metabolism in cynomolgus monkeys
- 2022
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inducing brain ATP-binding cassette 1 (ABCA1) activity in Alzheimer’s disease (AD) mouse models is associated with improvement in AD pathology. The purpose of this study was to investigate the effects of the ABCA1 agonist peptide CS-6253 on amyloid-β peptides (Aβ) and lipoproteins in plasma and cerebrospinal fluid (CSF) of cynomolgus monkeys, a species with amyloid and lipoprotein metabolism similar to humans. Methods: CS-6253 peptide was injected intravenously into cynomolgus monkeys at various doses in three different studies. Plasma and CSF samples were collected at several time points before and after treatment. Levels of cholesterol, triglyceride (TG), lipoprotein particles, apolipoproteins, and Aβ were measured using ELISA, ion-mobility analysis, and asymmetric-flow field-flow fractionation (AF4). The relationship between the change in levels of these biomarkers was analyzed using multiple linear regression models and linear mixed-effects models. Results: Following CS-6253 intravenous injection, within minutes, small plasma high-density lipoprotein (HDL) particles were increased. In two independent experiments, plasma TG, apolipoprotein E (apoE), and Aβ42/40 ratio were transiently increased following CS-6253 intravenous injection. This change was associated with a non-significant decrease in CSF Aβ42. Both plasma total cholesterol and HDL-cholesterol levels were reduced following treatment. AF4 fractionation revealed that CS-6253 treatment displaced apoE from HDL to intermediate-density- and low density-lipoprotein (IDL/LDL)-sized particles in plasma. In contrast to plasma, CS-6253 had no effect on the assessed CSF apolipoproteins or lipids. Conclusions: Treatment with the ABCA1 agonist CS-6253 appears to favor Aβ clearance from the brain.
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| 6. |
- Wannberg, Gudmund, et al.
(författare)
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EISCAT_3D - a next-generation European radar system for upper atmosphere and geospace research
- 2010
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Ingår i: Radio Science Bulletin. - 1024-4530. ; :333, s. 75-88
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Tidskriftsartikel (refereegranskat)abstract
- The EISCAT Scientifi c Association, together with a number of collaborating institutions, has recently completed a feasibility and design study for an enhanced performance research radar facility to replace the existing EISCAT UHF and VHF systems. This study was supported by EU Sixth-Framework funding. The new radar retains the powerful multi-static geometry of the EISCAT UHF, but will employ phased arrays, direct-sampling receivers, and digital beamforming and beam steering. Design goals include, inter alia, a tenfold improvement in temporal and spatial resolution, an extension of the instantaneous measurement of full-vector ionospheric drift velocities from a single point to the entire altitude range of the radar, and an imaging capability to resolve small-scale structures. Prototype receivers and beamformers are currently being tested on a 48-element, 224 MHz array (the "Demonstrator") erected at the Kiruna EISCAT site, using the EISCAT VHF transmitter as an illuminator.
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| 7. |
- Zlomanczuk, J, et al.
(författare)
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Near-threshold pion production in pN collisions at CELSIUS
- 1998
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Ingår i: ACTA PHYSICA POLONICA B. - : ACTA PHYSICA POLONICA B, JAGELLONIAN UNIV, INST PHYSICS. ; , s. 3141-3148
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Konferensbidrag (refereegranskat)abstract
- The pp --> pp pi(o) and pn --> pp pi(-) reactions have been measured at 310, 320 and 340 MeV using the CELSIUS proton beam and H-1 and H-2 internal cluster-jet targets. The pi(o) production at 310 MeV has been fully analyzed and a significant deviation fr
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| 8. |
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| 9. |
- Chen, G., et al.
(författare)
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Abilities of the BRICHOS domain to prevent neurotoxicity and fibril formation are dependent on a highly conserved Asp residue
- 2022
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Ingår i: RSC Chemical Biology. - : Royal Society of Chemistry (RSC). - 2633-0679. ; 3:11, s. 1342-1358
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Tidskriftsartikel (refereegranskat)abstract
- Proteins can self-assemble into amyloid fibrils or amorphous aggregates and thereby cause disease. Molecular chaperones can prevent both these types of protein aggregation, but to what extent the respective mechanisms are overlapping is not fully understood. The BRICHOS domain constitutes a disease-associated chaperone family, with activities against amyloid neurotoxicity, fibril formation, and amorphous protein aggregation. Here, we show that the activities of BRICHOS against amyloid-induced neurotoxicity and fibril formation, respectively, are oppositely dependent on a conserved aspartate residue, while the ability to suppress amorphous protein aggregation is unchanged by Asp to Asn mutations. The Asp is evolutionarily highly conserved in >3000 analysed BRICHOS domains but is replaced by Asn in some BRICHOS families. The conserved Asp in its ionized state promotes structural flexibility and has a pKa value between pH 6.0 and 7.0, suggesting that chaperone effects can be differently affected by physiological pH variations.
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| 10. |
- Chen, G., et al.
(författare)
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Augmentation of Bri2 molecular chaperone activity against amyloid-β reduces neurotoxicity in mouse hippocampus in vitro
- 2020
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Ingår i: Communications Biology. - : Nature Research. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Molecular chaperones play important roles in preventing protein misfolding and its potentially harmful consequences. Deterioration of molecular chaperone systems upon ageing are thought to underlie age-related neurodegenerative diseases, and augmenting their activities could have therapeutic potential. The dementia relevant domain BRICHOS from the Bri2 protein shows qualitatively different chaperone activities depending on quaternary structure, and assembly of monomers into high-molecular weight oligomers reduces the ability to prevent neurotoxicity induced by the Alzheimer-associated amyloid-β peptide 1-42 (Aβ42). Here we design a Bri2 BRICHOS mutant (R221E) that forms stable monomers and selectively blocks a main source of toxic species during Aβ42 aggregation. Wild type Bri2 BRICHOS oligomers are partly disassembled into monomers in the presence of the R221E mutant, which leads to potentiated ability to prevent Aβ42 toxicity to neuronal network activity. These results suggest that the activity of endogenous molecular chaperones may be modulated to enhance anti-Aβ42 neurotoxic effects.
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