| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 5. |
- Maksimovic, M., et al.
(författare)
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First observations and performance of the RPW instrument on board the Solar Orbiter mission
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
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Tidskriftsartikel (refereegranskat)abstract
- The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is designed to measure in situ magnetic and electric fields and waves from the continuum up to several hundred kHz. The RPW also observes solar and heliospheric radio emissions up to 16 MHz. It was switched on and its antennae were successfully deployed two days after the launch of Solar Orbiter on February 10, 2020. Since then, the instrument has acquired enough data to make it possible to assess its performance and the electromagnetic disturbances it experiences. In this article, we assess its scientific performance and present the first RPW observations. In particular, we focus on a statistical analysis of the first observations of interplanetary dust by the instrument's Thermal Noise Receiver. We also review the electro-magnetic disturbances that RPW suffers, especially those which potential users of the instrument data should be aware of before starting their research work.
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| 6. |
- Maksimovic, M., et al.
(författare)
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The Solar Orbiter Radio and Plasma Waves (RPW) instrument
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 642
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Tidskriftsartikel (refereegranskat)abstract
- The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is described in this paper. This instrument is designed to measure in-situ magnetic and electric fields and waves from the continuous to a few hundreds of kHz. RPW will also observe solar radio emissions up to 16 MHz. The RPW instrument is of primary importance to the Solar Orbiter mission and science requirements since it is essential to answer three of the four mission overarching science objectives. In addition RPW will exchange on-board data with the other in-situ instruments in order to process algorithms for interplanetary shocks and type III langmuir waves detections.
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| 7. |
- Morosan, D. E., et al.
(författare)
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LOFAR tied-array imaging of Type III solar radio bursts
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 568, s. articl no. A67-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Sun is an active source of radio emission which is often associated with energetic phenomena such as solar flares and coronal mass ejections (CMEs). At low radio frequencies (
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| 8. |
- Hebestreit, H., et al.
(författare)
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Cardiopulmonary exercise testing provides additional prognostic information in cystic fibrosis
- 2019
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 199:8, s. 987-995
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors, is unclear. Objectives: To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake (VO 2 peak) following rigorous adjustment for other predictors. Methods: Data from 10 CF centers in Australia, Europe, and North America were collected retrospectively. A total of 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation was analyzed using Cox proportional hazards regression. In addition, phenotyping using hierarchical Ward clustering was performed to characterize high-risk subgroups. Measurements and Main Results: Cox regression showed, even after adjustment for sex, FEV1% predicted, body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model, that VO 2 peak in % predicted (hazard ratio [HR], 0.964; 95% confidence interval [CI], 0.944-0.986), peak work rate (% predicted; HR, 0.969; 95% CI, 0.951-0.988), ventilatory equivalent for oxygen (HR, 1.085; 95% CI, 1.041-1.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007-1.115) (all P < 0.05) were significant predictors of death or lung transplantation at 10-year follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high-risk cluster characterized by poor lung function, nutritional status, and exercise capacity. Conclusions: CPET provides additional prognostic information to established predictors of death/lung transplantation in CF. High-risk patients may especially benefit from regular monitoring of exercise capacity and exercise counseling. Copyright © 2019 by the American Thoracic Society.
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| 14. |
- Loke, M. H., et al.
(författare)
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Smoothness-constrained time-lapse inversion of data from 3D resistivity surveys
- 2014
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Ingår i: Near Surface Geophysics. - : Wiley. - 1873-0604 .- 1569-4445. ; 12:1, s. 5-24
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional resistivity surveys and their associated inversion models are required to accurately resolve structures exhibiting very complex geology. In the same light, 3D resistivity surveys collected at multiple times are required to resolve temporally varying conditions. In this work we present 3D data sets, both synthetic and real, collected at different times. The large spatio-temporal data sets are then inverted simultaneously using a least-squares methodology that incorporates roughness filters in both the space and time domains. The spatial roughness filter constrains the model resistivity to vary smoothly in the x-, y- and z-directions. A temporal roughness filter is also applied that minimizes changes in the resistivity between successive temporal inversion models and the L-curve method is used to determine the optimum weights for both spatial and temporal roughness filters. We show that the use of the temporal roughness filter can accurately resolve changes in the resistivity even in the presence of noise. The L1- and L2-norm constraints for the temporal roughness filter are first examined using a synthetic model. The synthetic data test shows that the L1-norm temporal constraint produces significantly more accurate results when the resistivity changes abruptly with time. The model obtained with the L1-norm temporal constraint is also less sensitive to random noise compared with independent inversions (i.e., without any temporal constraint) and the L2-norm temporal constraint. Anomalies that are common in models using independent inversions and the L2-norm and L1-norm temporal constraints are likely to be real. In contrast, anomalies present in a model using independent inversions but that are significantly reduced with the L2-norm and L1-norm constraints are likely artefacts. For field data sets, the method successfully recovered temporal changes in the subsurface resistivity from a landfill monitoring survey due to rainwater infiltration, as well as from an experiment to map the migration of sodium cyanide solution from an injection well using surface and borehole electrodes in an area with significant topography.
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| 15. |
- Morosan, D. E., et al.
(författare)
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LOFAR tied-array imaging and spectroscopy of solar S bursts
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Sun is an active source of radio emission that is often associated with energetic phenomena ranging from nanoflares to coronal mass ejections (CMEs). At low radio frequencies (<100 MHz), numerous millisecond duration radio bursts have been reported, such as radio spikes or solar S bursts (where S stands for short). To date, these have neither been studied extensively nor imaged because of the instrumental limitations of previous radio telescopes. Aims. Here, LOw Frequency ARray (LOFAR) observations were used to study the spectral and spatial characteristics of a multitude of S bursts, as well as their origin and possible emission mechanisms. Methods. We used 170 simultaneous tied-array beams for spectroscopy and imaging of S bursts. Since S bursts have short timescales and fine frequency structures, high cadence (similar to 50 ms) tied-array images were used instead of standard interferometric imaging, that is currently limited to one image per second. Results. On 9 July 2013, over 3000 S bursts were observed over a time period of similar to 8 h. S bursts were found to appear as groups of short-lived (<1 s) and narrow-bandwidth (similar to 2.5 MHz) features, the majority drifting at similar to 3.5 MHz s(-1) and a wide range of circular polarisation degrees (2-8 times more polarised than the accompanying Type III bursts). Extrapolation of the photospheric magnetic field using the potential field source surface (PFSS) model suggests that S bursts are associated with a trans-equatorial loop system that connects an active region in the southern hemisphere to a bipolar region of plage in the northern hemisphere. Conclusions. We have identified polarised, short-lived solar radio bursts that have never been imaged before. They are observed at a height and frequency range where plasma emission is the dominant emission mechanism, however, they possess some of the characteristics of electron-cyclotron maser emission.
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| 16. |
- Morosan, D. E., et al.
(författare)
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The association of a J-burst with a solar jet
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 606
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Sun is an active star that produces large-scale energetic events such as solar flares and coronal mass ejections, and numerous smaller scale events such as solar jets. These events are often associated with accelerated particles that can cause emission at radio wavelengths. The reconfiguration of the solar magnetic field in the corona is believed to be the cause of the majority of solar energetic events and accelerated particles. Aims. Here, we investigate a bright J-burst that was associated with a solar jet and the possible emission mechanism causing these two phenomena. Methods. We used data from the Solar Dynamics Observatory (SDO) to observe a solar jet and radio data from the Low Frequency Array (LOFAR) and the Nancay Radioheliograph (NRH) to observe a J-burst over a broad frequency range (33-173 MHz) on 9 July 2013 at similar to 11:06 UT. Results. The J-burst showed fundamental and harmonic components and was associated with a solar jet observed at extreme ultraviolet wavelengths with SDO. The solar jet occurred in the northern hemisphere at a time and location coincident with the radio burst and not inside a group of complex active regions in the southern hemisphere. The jet occurred in the negative polarity region of an area of bipolar plage. Newly emerged positive flux in this region appeared to be the trigger of the jet. Conclusions. Magnetic reconnection between the overlying coronal field lines and the newly emerged positive field lines is most likely the cause of the solar jet. Radio imaging provides a clear association between the jet and the J-burst, which shows the path of the accelerated electrons. These electrons travelled from a region in the vicinity of the solar jet along closed magnetic field lines up to the top of a closed magnetic loop at a height of similar to 360 Mm. Such small-scale complex eruptive events arising from magnetic reconnection could facilitate accelerated electrons to produce continuously the large numbers of Type III bursts observed at low frequencies, in a similar way to the J-burst analysed here.
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| 17. |
- Santoro, V., et al.
(författare)
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HighNESS conceptual design report: Volume I
- 2024
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Ingår i: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 85-314
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Tidskriftsartikel (refereegranskat)abstract
- The European Spallation Source, currently under construction in Lund, Sweden, is a multidisciplinary international laboratory. Once completed to full specifications, it will operate the world’s most powerful pulsed neutron source. Supported by a 3 million Euro Research and Innovation Action within the EU Horizon 2020 program, a design study (HighNESS) has been completed to develop a second neutron source located below the spallation target. Compared to the first source, designed for high cold and thermal brightness, the new source has been optimized to deliver higher intensity, and a shift to longer wavelengths in the spectral regions of cold (CN, 2–20 Å), very cold (VCN, 10–120 Å), and ultracold (UCN, >500 Å) neutrons. The second source comprises a large liquid deuterium moderator designed to produce CN and support secondary VCN and UCN sources. Various options have been explored in the proposed designs, aiming for world-leading performance in neutronics. These designs will enable the development of several new instrument concepts and facilitate the implementation of a high-sensitivity neutron-antineutron oscillation experiment (NNBAR). This document serves as the Conceptual Design Report for the HighNESS project, representing its final deliverable.
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| 18. |
- Santoro, V., et al.
(författare)
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HighNESS conceptual design report: Volume II. the NNBAR experiment.
- 2024
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Ingår i: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 315-406
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Tidskriftsartikel (refereegranskat)abstract
- A key aim of the HighNESS project for the European Spallation Source is to enable cutting-edge particle physics experiments. This volume presents a conceptual design report for the NNBAR experiment. NNBAR would exploit a new cold lower moderator to make the first search in over thirty years for free neutrons converting to anti-neutrons. The observation of such a baryon-number-violating signature would be of fundamental significance and tackle open questions in modern physics, including the origin of the matter-antimatter asymmetry. This report shows the design of the beamline, supermirror focusing system, magnetic and radiation shielding, and anti-neutron detector necessary for the experiment. A range of simulation programs are employed to quantify the performance of the experiment and show how background can be suppressed. For a search with full background suppression, a sensitivity improvement of three orders of magnitude is expected, as compared with the previous search. Civil engineering studies for the NNBAR beamline are also shown, as is a costing model for the experiment.
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| 20. |
- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 21. |
- van der Meer, Dennis, et al.
(författare)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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