| 1. |
- Feroci, M., et al.
(författare)
-
LOFT - The large observatory for x-ray timing
- 2012
-
Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9780819491442 ; , s. 84432D-
-
Konferensbidrag (refereegranskat)abstract
- The LOFT mission concept is one of four candidates selected by ESA for the M3 launch opportunity as Medium Size missions of the Cosmic Vision programme. The launch window is currently planned for between 2022 and 2024. LOFT is designed to exploit the diagnostics of rapid X-ray flux and spectral variability that directly probe the motion of matter down to distances very close to black holes and neutron stars, as well as the physical state of ultradense matter. These primary science goals will be addressed by a payload composed of a Large Area Detector (LAD) and a Wide Field Monitor (WFM). The LAD is a collimated (<1 degree field of view) experiment operating in the energy range 2-50 keV, with a 10 m2 peak effective area and an energy resolution of 260 eV at 6 keV. The WFM will operate in the same energy range as the LAD, enabling simultaneous monitoring of a few-steradian wide field of view, with an angular resolution of <5 arcmin. The LAD and WFM experiments will allow us to investigate variability from submillisecond QPO's to yearlong transient outbursts. In this paper we report the current status of the project.
|
|
| 2. |
- Feroci, M., et al.
(författare)
-
The large observatory for x-ray timing
- 2014
-
Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
-
Konferensbidrag (refereegranskat)abstract
- The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
|
|
| 3. |
- Fischer, Hubertus, et al.
(författare)
-
Palaeoclimate constraints on the impact of 2 °C anthropogenic warming and beyond
- 2018
-
Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 11:7, s. 474-485
-
Tidskriftsartikel (refereegranskat)abstract
- Over the past 3.5 million years, there have been several intervals when climate conditions were warmer than during the pre-industrial Holocene. Although past intervals of warming were forced differently than future anthropogenic change, such periods can provide insights into potential future climate impacts and ecosystem feedbacks, especially over centennial-to-millennial timescales that are often not covered by climate model simulations. Our observation-based synthesis of the understanding of past intervals with temperatures within the range of projected future warming suggests that there is a low risk of runaway greenhouse gas feedbacks for global warming of no more than 2 °C. However, substantial regional environmental impacts can occur. A global average warming of 1–2 °C with strong polar amplification has, in the past, been accompanied by significant shifts in climate zones and the spatial distribution of land and ocean ecosystems. Sustained warming at this level has also led to substantial reductions of the Greenland and Antarctic ice sheets, with sea-level increases of at least several metres on millennial timescales. Comparison of palaeo observations with climate model results suggests that, due to the lack of certain feedback processes, model-based climate projections may underestimate long-term warming in response to future radiative forcing by as much as a factor of two, and thus may also underestimate centennial-to-millennial-scale sea-level rise.
|
|
| 4. |
- Huber, Maria, et al.
(författare)
-
Metabolic correlates of dopaminergic loss in dementia with lewy bodies
- 2020
-
Ingår i: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35, s. 595-605
-
Tidskriftsartikel (refereegranskat)abstract
- Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
|
|
| 5. |
- Lundquist, Pinelopi, 1975-
(författare)
-
Imaging and Quantification of Brain Serotonergic Activity using PET
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates the potential of using positron emission tomography (PET) to study the biosynthesis and release of serotonin (5HT) at the brain serotonergic neuron. As PET requires probe compounds with specific attributes to enable imaging and quantification of biological processes, emphasis was placed on the evaluation of these attributes. The experiments established that the 5HT transporter radioligand [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile, [11C]DASB, is suitable for imaging and quantification of transporters in rats and rhesus monkeys. In addition, the binding of [11C]DASB in brain tissue is decreased when 5HT concentrations are increased by tranylcypromine administration. The sensitivity of [11C]DASB binding, under these experimental conditions, to increased endogenous 5HT concentrations demonstrates the potential of in vivo monitoring of 5HT release in rat and monkey models. The irreversible binding of 5-hydroxy-L-[β-11C]tryptophan, [11C]HTP, in the monkey brain was lower in the presence of NSD1015, which was used to inhibit the decarboxylase step in 5HT synthesis. [11C]HTP seems thus to have potential for tracking changes in the activity of this biosynthesis enzyme. In contrast, the accumulation of [11C]HTP was unaffected by clorgyline, which was used to inhibit metabolism of the probe in the brain. This appears to indicate that elimination of the main metabolite from the brain could be negligible and thus will not alter [11C]HTP quantification. The extent and distribution of the irreversible binding of a substrate for the first enzyme in 5HT formation, α-[11C]methyl-L-tryptophan, [11C]AMT, was different from those for [11C]HTP. This suggests that the two studied probe compounds provide estimates related to the enzyme activity of different steps in the 5HT biosynthesis pathway. A reference tissue version of the Patlak method for the analysis of data obtained by PET was also developed. This approach takes into account irreversible binding in the reference region and appears, therefore, to yield more reliable parameter estimates than the conventional reference Patlak analysis. The method is recommended for parameter estimation of [11C]HTP data when no metabolite-corrected plasma curve is available. Knowledge of altered 5HT synthesis and release in disease states and the consequences for effective pharmacotherapy can improve our knowledge of the aetiology of certain psychiatric and neurological diseases and enhance our ability to design more effective drugs.
|
|
| 6. |
- Marton, Janos, et al.
(författare)
-
NMR Analysis of a Series of 6,14-Ethenomorphinan Derivatives as PET Precursors and Reference Substances**
- 2021
-
Ingår i: CHEMISTRYSELECT. - : Wiley. - 2365-6549. ; 6:24, s. 5994-6005
-
Tidskriftsartikel (refereegranskat)abstract
- The new semisynthetic oripavine derivative 3-O-trityl-6-O-desmethyl-dihydroetorphine was synthesized from the poppy alkaloid thebaine in a six-step procedure. This compound can be applied as precursor for the radiosynthesis of [6-O-methyl-C-11]-dihydroetorphine ([C-11]DHE). We present a detailed description of H-1 and C-13 NMR data of reference standards and precursors for [6-O-methyl-C-11]- and [6-O-(2-[F-18]fluoroethyl]orvinols. This includes the complete assignment for 19 oripavine derivatives examined in 1D and 2D NMR experiments. We also investigated the molecular basis for regioselectivity of fluoroalkylation of 3-O-trityl-6-O-desmethyl-phenethyl-orvinol (TDPEO) using computational methods.
|
|
| 7. |
- Mörtberg, Erik, et al.
(författare)
-
A PET study of regional cerebral blood flow after experimental cardiopulmonary resuscitation
- 2007
-
Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 75:1, s. 98-104
-
Tidskriftsartikel (refereegranskat)abstract
- Cerebral blood flow (CBF) during cardiopulmonary resuscitation and after restoration of spontaneous circulation (ROSC) from cardiac arrest has previously been measured with the microspheres and laser Doppler techniques. We used positron emission tomography (PET) with [15O]--water to map the haemodynamic changes after ROSC in nine young pigs. After the baseline PET recording, ventricular fibrillation of 5 min duration was induced, followed by closed-chest cardiopulmonary resuscitation (CPR) in conjunction with IV administration of three bolus doses of adrenaline (epinephrine). After CPR, external defibrillatory shocks were applied to achieve ROSC. CBF was measured at intervals during 4h after ROSC. Relative to the mean global CBF at baseline (32+/-5 ml hg(-1)min(-1)), there was a substantial global increase in CBF at 10 min, especially in the diencephalon. This was followed by an interval of cortical hypoperfusion and a subsequent gradual return to baseline values.
|
|
| 8. |
- Mörtberg, Erik, et al.
(författare)
-
Cerebral metabolic rate of oxygen (CMRO2) in pig brain determined by PET after resuscitation from cardiac arrest
- 2009
-
Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 80:6, s. 701-706
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: To assess the regional vulnerability to ischemic damage and perfusion/metabolism mismatch of reperfused brain following restoration of spontaneous circulation (ROSC) after cardiac arrest. METHOD: We used positron emission tomography (PET) to map cerebral metabolic rate of oxygen (CMRO(2)), cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in brain of young pigs at intervals after resuscitation from cardiac arrest. After obtaining baseline PET recordings, ventricular fibrillation of 10 min duration was induced, followed by mechanical closed-chest cardiopulmonary resuscitation (CPR) in conjunction with i.v. administration of 0.4 U/kg of vasopressin. After CPR, external defibrillatory shocks were applied to achieve restoration of spontaneous circulation (ROSC). CBF and CMRO(2) were mapped and voxelwise maps of OEF were calculated at times of 60, 180, and 300 min after ROSC. RESULTS: There was hypoperfusion throughout the telencephalon at 60 min, with a return towards baseline values at 300 min. In contrast, there was progressively increasing CBF in cerebellum throughout the observation period. The magnitude of CMRO(2) decreased globally after ROSC, especially in cerebral cortex. The magnitude of OEF in cerebral cortex was 60% at baseline, tended to increase at 60 min after ROSC, and declined to 50% thereafter, thus suggesting transition to an ischemic state. CONCLUSION: The cortical regions tended most vulnerable to the ischemic insult with an oligaemic pattern and a low CMRO(2) whereas the cerebellum instead showed a pattern of luxury perfusion.
|
|
| 9. |
- Rieb, Jesse T., et al.
(författare)
-
When, Where, and How Nature Matters for Ecosystem Services : Challenges for the Next Generation of Ecosystem Service Models
- 2017
-
Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 67:9, s. 820-833
-
Tidskriftsartikel (refereegranskat)abstract
- Many decision-makers are looking to science to clarify how nature supports human well-being. Scientists' responses have typically focused on empirical models of the provision of ecosystem services (ES) and resulting decision-support tools. Although such tools have captured some of the complexities of ES, they can be difficult to adapt to new situations. Globally useful tools that predict the provision of multiple ES under different decision scenarios have proven challenging to develop. Questions from decision-makers and limitations of existing decision-support tools indicate three crucial research frontiers for incorporating cutting-edge ES science into decision-support tools: (1) understanding the complex dynamics of ES in space and time, (2) linking ES provision to human well-being, and (3) determining the potential for technology to substitute for or enhance ES. We explore these frontiers in-depth, explaining why each is important and how existing knowledge at their cutting edges can be incorporated to improve ES decision-making tools.
|
|
| 10. |
- Rominger, Axel, et al.
(författare)
-
Validation of the Octamouse for Simultaneous 18F-Fallypride Small-Animal PET Recordings from 8 Mice
- 2010
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 51:10, s. 1576-1583
-
Tidskriftsartikel (refereegranskat)abstract
- Data collection in preclinical small-animal PET studies has been hindered by the small number of recordings typically obtained for a single radiosynthesis. Therefore, we tested procedures for obtaining 8 simultaneous small-animal PET recordings from the brains of 8 mice using an acrylic anesthesia distributor (the Octamouse), with the dopamine D-2/3 ligand F-18-fallypride serving as a test substance for brain receptor imaging. Methods: The effect of scatter correction on the small-animal PET recordings was first evaluated in phantom studies in which sources of different radioactivity concentration were placed within the chambers of the Octamouse. Next, potential effects of mass on the F-18-fallypride binding potential (BPND) in the striatum were tested in groups of mice receiving F-18-fallypride at 2 different specific activities (140 and 50 GBq/mu mol), with and without scatter correction. Finally, the relationship between BPND and injected dose of F-18-fallypride (3.5-17 MBq/mouse) was tested. Results: Scatter correction improved the contrast between sources and air space within the Octamouse phantom. The magnitude of F-18-fallypride BPND in mouse striatum was invariant across the tested range of specific activities, and scatter correction increased BPND by a mean of 6%; covariances of the inter-and intraoperator variability of BPND were 10%. There was a positive correlation between radiochemical dose and BPND with (R-2 = 0.53) and without (R-2 = 0.63) scatter correction, which was driven by increasing area under the percentage injected dose curve in the striatum. Conclusion: The quantitation of emission sources placed within the Octamouse is linear over a wide range of source activities. In the striatum of living mice, the magnitude of F-18-fallypride BPND was highly reproducible between operators and was constant over a 3-fold range of specific activities, indicating a lack of significant occupancy. Scatter correction improved quantitation but did not entirely correct for the dependence of BPND on injected dose, which was deemed to arise because of effects propagating from detector dead time when the total radiochemical dose in the field of view exceeded 50 MBq. Given this consideration, we were still able to quantify F-18-fallypride BPND in 16 mice from a single radiosynthesis, an economy that should be generalizable to brain studies of diverse radioligands.
|
|
| 11. |
- Stockbauer, Anna, et al.
(författare)
-
Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission
- 2024
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 51:4, s. 1023-1034
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA).Methods FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level.Results Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R2 = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912).Conclusion Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset.
|
|
