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- Abi-Dargham, A, et al.
(författare)
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Measurement of striatal and extrastriatal dopamine D1 receptor binding potential with [11C]NNC 112 in humans: validation and reproducibility
- 2000
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Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X. ; 20:2, s. 225-243
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the postulated role of extrastriatal D1 receptors in human cognition and psychopathology requires an accurate and reliable method for quantification of these receptors in the living human brain. [11C]NNC 112 is a promising novel radiotracer for positron emission tomography imaging of the D1 receptor. The goal of this study was to develop and evaluate methods to derive D1 receptor parameters in striatal and extrastriatal regions of the human brain with [11C]NNC 112. Six healthy volunteers were studied twice. Two methods of analysis (kinetic and graphical) were applied to 12 regions (neocortical, limbic, and subcortical regions) to derive four outcome measures: total distribution volume, distribution volume ratio, binding potential (BP), and specific-to-nonspecific equilibrium partition coefficient ( k3/ k4). Both kinetic and graphic analyses provided BP and k3/ k4 values in good agreement with the known distribution of D1 receptors (striatum > limbic regions = neocortical regions > thalamus). The identifiability of outcome measures derived by kinetic analysis was excellent. Time-stability analysis indicated that 90 minutes of data collection generated stable outcome measures. Derivation of BP and k3/ k4 by kinetic analysis was highly reliable, with intraclass correlation coefficients (ICCs) of 0.90 ± 0.06 (mean ± SD of 12 regions) and 0.84 ± 0.11, respectively. The reliability of these parameters derived by graphical analysis was lower, with ICCs of 0.72 ± 0.17 and 0.58 ± 0.21, respectively. Noise analysis revealed a noise-dependent bias in the graphical but not the kinetic analysis. In conclusion, kinetic analysis of [11C]NNC 112 uptake provides an appropriate method with which to derive D1 receptor parameters in regions with both high (striatal) and low (extrastriatal) D1 receptor density.
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| 5. |
- Christiansen, H. H., et al.
(författare)
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The Thermal State of Permafrost in the Nordic Area during the International Polar Year 2007-2009
- 2010
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Ingår i: Permafrost and Periglacial Processes. - : Wiley. - 1099-1530 .- 1045-6740. ; 21:2, s. 156-181
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Tidskriftsartikel (refereegranskat)abstract
- This paper provides a snapshot of the permafrost thermal state in the Nordic area obtained during the International Polar Year (IPY) 2007-2009. Several intensive research campaigns were undertaken within a variety of projects in the Nordic countries to obtain this snapshot. We demonstrate for Scandinavia that both lowland permafrost in palsas and peat plateaus, and large areas of permafrost in the mountains are at temperatures close to 0 degrees C, which makes them sensitive to climatic changes. In Svalbard and northeast Greenland, and also in the highest parts of the mountains in the rest of the Nordic area, the permafrost is somewhat colder, but still only a few degrees below the freezing point. The observations presented from the network of boreholes, more than half of which were established during the IPY, provide an important baseline to assess how future predicted climatic changes may affect the permafrost thermal state in the Nordic area. Time series of active-layer thickness and permafrost temperature conditions in the Nordic area, which are generally only 10 years in length, show generally increasing active-layer depths and risings permafrost temperatures. Copyright (C) 2010 John Wiley & Sons, Ltd.
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| 6. |
- Farde, L, et al.
(författare)
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PET study of the M1-agonists [11C]xanomeline and [11C]butylthio-TZTP in monkey and man
- 1996
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Ingår i: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 7:4, s. 187-195
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Tidskriftsartikel (refereegranskat)abstract
- Xanomeline, a substituted TZTP, is a new M<sub>1</sub> selective muscarinic agonist in clinical trials for Alzheimer''s disease. The brain uptake of [<sup>11</sup>C]xanomeline and the analog [<sup>11</sup>C]butylthio-TZTP was examined by positron emission tomography (PET). Radioactivity accumulated most markedly in the neocortex and the striatum. Pharmacological characterization in vitro and in cynomolgus monkeys in vivo by PET indicated specific [<sup>11</sup>C]butylthio-TZTP binding to muscarinic receptors and to sigma-1 recognition sites. More than 5% of the radioactivity was in the human brain 5 min after i.v. injection of [<sup>11</sup>C]xanomeline or [<sup>11</sup>C]butylthio-TZTP. This high brain uptake may be clinically advantageous in the sense that substituted TZTP may induce central muscarinic agonist effects at a dose level for which there is a low risk of peripheral side-effects.
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| 9. |
- Meier, P., et al.
(författare)
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Hydrogeophysical investigations in the western and north-central Okavango Delta (Botswana) based on helicopter and ground-based transient electromagnetic data and electrical resistance tomography
- 2014
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Ingår i: Geophysics. - : Society of Exploration Geophysicists. - 0016-8033 .- 1942-2156. ; 79:5, s. B201-B211
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Tidskriftsartikel (refereegranskat)abstract
- The Okavango Delta is a huge alluvial megafan in northwestern Botswana. Despite numerous geologic, geochemical, geophysical, and hydrologic investigations over the past half-century, the sedimentary units underlying the delta are largely unknown. To address this issue, helicopter transient electromagnetic data (HTEM) have been collected across the entire delta and coincident ground-based electrical resistance tomographic (ERT) and transient electromagnetic (TEM) data have been acquired at two locations, one along the delta’s western margin and one in its north-central region. Inversions of the HTEM data have yielded three-layer resistivity models in which a relatively homogeneous conductive layer is sandwiched between two resistive layers. The three-layer HTEM model is reproduced in models obtained from independently and jointly inverting the ground-based data. The conductive layer’s low resistivities and depths to its upper and lower boundaries are practically equal in the HTEM and ground-based models. Resistivities of the upper resistive layer are similar in the various models, with the ground-based estimates being somewhat higher than those of the HTEM model at one site and somewhat lower at the other site. For the basal resistive layer, it can only be concluded that its resistivity must be substantially higher than that of the overlying conductive layer. An interpretation of the HTEM and ground-based resistivity models in the delta’s north-central region, appropriately constrained by the surface geology, high-resolution seismic refraction-reflection models, and borehole logs suggests the following structure: basement overlain at progressively shallower depths by freshwater-saturated sand and gravel that represent the remnants of a Paleo Okavango Megafan, saline-water-saturated sand, and lacustrine clay originally deposited in Paleo Lake Makgadikgadi, and freshwater-saturated megafan and fluvial sediments of the current Okavango Delta.
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| 11. |
- Rodrigues, Letícia, et al.
(författare)
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Immune responses induced by nano-self-assembled lipid adjuvants based on a monomycoloyl glycerol analogue after vaccination with the Chlamydia trachomatis major outer membrane protein.
- 2018
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 285, s. 12-22
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Tidskriftsartikel (refereegranskat)abstract
- Nanocarriers based on inverse hexagonal liquid crystalline phases (hexosomes) show promising potential as vaccine delivery systems. Their unique internal structure, composed of both lipophilic domains and water-containing channels, renders them capable of accommodating immunopotentiating compounds and antigens. However, their adjuvant properties are poorly understood. We hypothesized that the supramolecular structure of the lyotropic liquid crystalline phase influences the immunostimulatory activity of lipid-based nanocarriers. To test this, hexosomes were designed containing the lipid phytantriol (Phy) and the immunopotentiator monomycoloyl glycerol-1 (MMG-1). Self-assembly of Phy and MMG-1 into nanocarriers featuring an internal hexagonal phase was confirmed by small-angle X-ray scattering and cryogenic transmission electron microscopy. The effect of the nanostructure on the adjuvant activity was studied by comparing the immunogenicity of Phy/MMG-1 hexosomes with MMG-1-containing lamellar liquid crystalline nanoparticles (liposomes, CAF04). The quality and magnitude of the elicited immune responses were determined after vaccination of CB6/F1 mice using the Chlamydia trachomatis major outer membrane protein (MOMP) as antigen. MMG-1-based hexosomes potentiated significantly stronger MOMP-specific humoral responses than CAF04 liposomes. The liposome-based vaccine formulation induced a much stronger MOMP-specific cell-mediated immune response compared to hexosome-adjuvanted MOMP, which elicited minimal MOMP-specific T-cell stimulation after vaccination. Hence, our data demonstrates that hexosomal and liposomal adjuvants activate the immune system via different mechanisms. Our work provides valuable insights into the adjuvant potential of hexosomes and emphasizes that engineering of the supramolecular structure can be used to design adjuvants with customized immunological properties.
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