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- Edelson, R. A., et al.
(författare)
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Multiwavelength observations of short-timescale variability in NGC 4151. IV. Analysis of multiwavelength continuum variability
- 1996
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 470:1, s. 364-377377
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Tidskriftsartikel (refereegranskat)abstract
- For pt.III see ibid., vol.470, no.1, p.349-63 (1996). Combines data from the three preceding papers in order to analyze the multi wave-band variability and spectral energy distribution of the Seyfert 1 galaxy NGC 4151 during the 1993 December monitoring campaign. The source, which was near its peak historical brightness, showed strong, correlated variability at X-ray, ultraviolet, and optical wavelengths. The strongest variations were seen in medium-energy (~1.5 keV) X-rays, with a normalized variability amplitude (NVA) of 24%. Weaker (NVA=6%) variations (uncorrelated with those at lower energies) were seen at soft gamma-ray energies of ~100 keV. No significant variability was seen in softer (0.1-1 keV) X-ray bands. In the ultraviolet/optical regime, the NVA decreased from 9% to 1% as the wavelength increased from 1275 to 6900 Aring. These data do not probe extreme ultraviolet (1200 Aring to 0.1 keV) or hard X-ray (250 keV) variability. The phase differences between variations in different bands were consistent with zero lag, with upper limits of lsim0.15 day between 1275 Aring and the other ultraviolet bands, lsim0.3 day between 1275 Aring and 1.5 keV, and lsim1 day between 1275 and 5125 Aring. These tight limits represent more than an order of magnitude improvement over those determined in previous multi-wave-band AGN monitoring campaigns. The ultraviolet fluctuation power spectra showed no evidence for periodicity, but were instead well fitted with a very steep, red power law (ales-2.5)
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| 2. |
- Lerche, S., et al.
(författare)
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CSF Protein Level of Neurotransmitter Secretion, Synaptic Plasticity, and Autophagy in PD and DLB
- 2021
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:11, s. 2595-2604
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Tidskriftsartikel (refereegranskat)abstract
- Background Molecular pathways associated with alpha-synuclein proteostasis have been detected in genetic studies and in cell models and include autophagy, ubiquitin-proteasome system, mitochondrial homeostasis, and synaptic plasticity. However, we lack biomarkers that are representative for these pathways in human biofluids. Objective The objective of this study was to evaluate CSF protein profiles of pathways related to alpha-synuclein proteostasis. Methods We assessed CSF protein profiles associated with neurotransmitter secretion, synapse plasticity, and autophagy in 2 monocentric cohorts with alpha-synucleinopathy (385 PD patients and 67 DLB patients). We included 80 PD patients and 17 DLB patients with variants in the glucocerebrosidase gene to serve as proxy for accelerated alpha-synuclein pathology with pronounced clinical trajectories. Results (1) Proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy were lower in PD and DLB patients compared with healthy controls. (2) These patterns were more pronounced in DLB than in PD patients, accentuated by GBA variant status in both entities. (3) CSF levels of these proteins were positively associated with CSF levels of total alpha-synuclein, with lower levels of proteostasis proteins related to lower levels of total alpha-synuclein. (4) These findings could be confirmed longitudinally. PD patients with low CSF profiles of proteostasis proteins showed lower CSF levels of alpha-synuclein longitudinally compared with PD patients with a normal proteostasis profile. Conclusion CSF proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy might serve as biomarkers related to alpha-synuclein proteostasis in PD and DLB. (c) 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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| 3. |
- Brockmann, K., et al.
(författare)
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Association between CSF alpha-synuclein seeding activity and genetic status in Parkinson's disease and dementia with Lewy bodies
- 2021
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The clinicopathological heterogeneity in Lewy-body diseases (LBD) highlights the need for pathology-driven biomarkers in-vivo. Misfolded alpha-synuclein (alpha-Syn) is a lead candidate based on its crucial role in disease pathophysiology. Real-time quaking-induced conversion (RT-QuIC) analysis of CSF has recently shown high sensitivity and specificity for the detection of misfolded alpha-Syn in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In this study we performed the CSF RT-QuIC assay in 236 PD and 49 DLB patients enriched for different genetic forms with mutations in GBA, parkin, PINK1, DJ1, and LRRK2. A subgroup of 100 PD patients was also analysed longitudinally. We correlated kinetic seeding parameters of RT-QuIC with genetic status and CSF protein levels of molecular pathways linked to alpha-Syn proteostasis. Overall, 85% of PD and 86% of DLB patients showed positive RT-QuIC alpha-Syn seeding activity. Seeding profiles were significantly associated with mutation status across the spectrum of genetic LBD. In PD patients, we detected positive alpha-Syn seeding in 93% of patients carrying severe GBA mutations, in 78% with LRRK2 mutations, in 59% carrying heterozygous mutations in recessive genes, and in none of those with bi-allelic mutations in recessive genes. Among PD patients, those with severe GBA mutations showed the highest seeding activity based on RT-QuIC kinetic parameters and the highest proportion of samples with 4 out of 4 positive replicates. In DLB patients, 100% with GBA mutations showed positive alpha-Syn seeding compared to 79% of wildtype DLB. Moreover, we found an association between alpha-Syn seeding activity and reduced CSF levels of proteins linked to alpha-Syn proteostasis, specifically lysosome-associated membrane glycoprotein 2 and neurosecretory protein VGF. These findings highlight the value of alpha-Syn seeding activity as an in-vivo marker of Lewy-body pathology and support its use for patient stratification in clinical trials targeting alpha-Syn.
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| 4. |
- Rieth, M., et al.
(författare)
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Review on the EFDA programme on tungsten materials technology and science
- 2011
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 417:1-3, s. 463-467
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Tidskriftsartikel (refereegranskat)abstract
- All the recent DEMO design studies for helium cooled divertors utilize tungsten materials and alloys, mainly due to their high temperature strength, good thermal conductivity, low erosion, and comparably low activation under neutron irradiation. The long-term objective of the EFDA fusion materials programme is to develop structural as well as armor materials in combination with the necessary production and fabrication technologies for future divertor concepts. The programmatic roadmap is structured into four engineering research lines which comprise fabrication process development, structural material development, armor material optimization, and irradiation performance testing, which are complemented by a fundamental research programme on "Materials Science and Modeling". This paper presents the current research status of the EFDA experimental and testing investigations, and gives a detailed overview of the latest results on fabrication, joining, high heat flux testing, plasticity, modeling, and validation experiments.
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