| 1. |
- Alic, I., et al.
(författare)
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Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26:10, s. 5766-5788
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Tidskriftsartikel (refereegranskat)abstract
- A population of more than six million people worldwide at high risk of Alzheimer's disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of beta-amyloid-(A beta)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar A beta deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Presence/absence of AD-like pathology was donor-specific (reproducible between individual organoids/iPSC lines/experiments). Pathology could be triggered in pathology-negative T21 organoids by CRISPR/Cas9-mediated elimination of the third copy of chromosome 21 gene BACE2, but prevented by combined chemical beta and gamma-secretase inhibition. We found that T21 organoids secrete increased proportions of A beta-preventing (A beta 1-19) and A beta-degradation products (A beta 1-20 and A beta 1-34). We show these profiles mirror in cerebrospinal fluid of people with DS. We demonstrate that this protective mechanism is mediated by BACE2-trisomy and cross-inhibited by clinically trialled BACE1 inhibitors. Combined, our data prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in similar to 30% of people with DS. We also show that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens as well as identification of natural suppressor genes for neurodegenerative diseases.
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| 2. |
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| 3. |
- Komm, M., et al.
(författare)
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Contribution to the multi-machine pedestal scaling from the COMPASS tokamak
- 2017
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Ingår i: Nuclear Fusion. - : Institute of Physics (IOP). - 0029-5515 .- 1741-4326. ; 57:5
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Tidskriftsartikel (refereegranskat)abstract
- First systematic measurements of pedestal structure during Ohmic and NBI-assisted Type I ELMy H-modes were performed on the COMPASS tokamak in two dedicated experimental campaigns during 2015 and 2016. By adjusting the NBI heating and a toroidal magnetic field, the electron pedestal temperature was increased from 200 eV up to 300 eV, which allowed reaching pedestal collisionality nu(ped)* < 1 at q(95) similar to 3. COMPASS has approached conditions for the Identity experiment done at JET & DIII-D, complementing the range of scanned rho(ped)*. The pedestal pressure was successfully reproduced by the EPED model. The dependence of pedestal pressure width on nu(ped)* and beta(pol)(ped) is discussed.
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| 4. |
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| 5. |
- Weinzettl, V., et al.
(författare)
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Dust remobilization experiments on the COMPASS tokamak
- 2017
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Ingår i: Fusion engineering and design. - : ELSEVIER SCIENCE SA. - 0920-3796 .- 1873-7196. ; 124, s. 446-449
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Tidskriftsartikel (refereegranskat)abstract
- Dust remobilization is one of the not yet fully understood mechanisms connected to the prompt erosion of material from plasma facing surfaces in fusion devices. As a part of a newly initiated cross-machine study, dust remobilization experiments have been performed on the COMPASS tokamak. Tungsten samples with well-defined deposited tungsten dust grains, prepared using a recently developed controlled pre-adhesion method, have been exposed to ELMy H-mode discharges as well as L-mode discharges with forced disruptions. Here we report on the technical aspects of the experiment realization as well as on the experimental results of dust remobilization. The latter is discussed in the light of data from other machines and a physical interpretation is suggested for the observed spatial localization of the dust remobilization activity. Evidence of rearrangement of isolated dust into clusters and strings is also presented.
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| 6. |
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| 7. |
- Bohm, P., et al.
(författare)
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Edge Thomson scattering diagnostic on COMPASS tokamak : Installation, calibration, operation, improvements
- 2014
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 85:11, s. 11E431-
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Tidskriftsartikel (refereegranskat)abstract
- The core Thomson scattering diagnostic (TS) on the COMPASS tokamak was put in operation and reported earlier. Implementation of edge TS, with spatial resolution along the laser beam up to similar to 1/100 of the tokamak minor radius, is presented now. The procedure for spatial calibration and alignment of both core and edge systems is described. Several further upgrades of the TS system, like a triggering unit and piezo motor driven vacuum window shutter, are introduced as well. The edge TS system, together with the core TS, is now in routine operation and provides electron temperature and density profiles.
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| 10. |
- Marto, João Pedro, et al.
(författare)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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