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- Berglund, Rasmus, et al.
(författare)
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Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation
- 2020
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Ingår i: Science Immunology. - Stockholm : Karolinska Institutet, Dept of Clinical Neuroscience. - 2470-9468.
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is a leading cause of incurable progressive disability in young adults caused by inflammation and neurodegeneration in the central nervous system (CNS). The capacity of microglia to clear tissue debris is essential for maintaining and restoring CNS homeostasis. This capacity diminishes with age, and age strongly associates with MS disease progression, although the underlying mechanisms are still largely elusive. Here, we demonstrate that the recovery from CNS inflammation in a murine model of MS is dependent on the ability of microglia to clear tissue debris. Microglia-specific deletion of the autophagy regulator Atg7, but not the canonical macroautophagy protein Ulk1, led to increased intracellular accumulation of phagocytosed myelin and progressive MS-like disease. This impairment correlated with a microglial phenotype previously associated with neurodegenerative pathologies. Moreover, Atg7-deficient microglia showed notable transcriptional and functional similarities to microglia from aged wild-type mice that were also unable to clear myelin and recover from disease. In contrast, induction of autophagy in aged mice using the disaccharide trehalose found in plants and fungi led to functional myelin clearance and disease remission. Our results demonstrate that a noncanonical form of autophagy in microglia is responsible for myelin degradation and clearance leading to recovery from MS-like disease and that boosting this process has a therapeutic potential for age-related neuroinflammatory conditions.
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- Collaud Coen, Martine, et al.
(författare)
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Multidecadal trend analysis of in situ aerosol radiative properties around the world
- 2020
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:14, s. 8867-8908
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Tidskriftsartikel (refereegranskat)abstract
- In order to assess the evolution of aerosol parameters affecting climate change, a long-term trend analysis of aerosol optical properties was performed on time series from 52 stations situated across five continents. The time series of measured scattering, backscattering and absorption coefficients as well as the derived single scattering albedo, backscattering fraction, scattering and absorption Angstrom exponents covered at least 10 years and up to 40 years for some stations. The non-parametric seasonal Mann-Kendall (MK) statistical test associated with several pre-whitening methods and with Sen's slope was used as the main trend analysis method. Comparisons with general least mean square associated with autoregressive bootstrap (GLS/ARB) and with standard least mean square analysis (LMS) enabled confirmation of the detected MK statistically significant trends and the assessment of advantages and limitations of each method. Currently, scattering and backscattering coefficient trends are mostly decreasing in Europe and North America and are not statistically significant in Asia, while polar stations exhibit a mix of increasing and decreasing trends. A few increasing trends are also found at some stations in North America and Australia. Absorption coefficient time series also exhibit primarily decreasing trends. For single scattering albedo, 52 % of the sites exhibit statistically significant positive trends, mostly in Asia, eastern/northern Europe and the Arctic, 22 % of sites exhibit statistically significant negative trends, mostly in central Europe and central North America, while the remaining 26 % of sites have trends which are not statistically significant. In addition to evaluating trends for the overall time series, the evolution of the trends in sequential 10-year segments was also analyzed. For scattering and backscattering, statistically significant increasing 10-year trends are primarily found for earlier periods (10-year trends ending in 2010-2015) for polar stations and Mauna Loa. For most of the stations, the present-day statistically significant decreasing 10-year trends of the single scattering albedo were preceded by not statistically significant and statistically significant increasing 10-year trends. The effect of air pollution abatement policies in continental North America is very obvious in the 10-year trends of the scattering coefficient - there is a shift to statistically significant negative trends in 2009-2012 for all stations in the eastern and central USA. This long-term trend analysis of aerosol radiative properties with a broad spatial coverage provides insight into potential aerosol effects on climate changes.
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- Fredricson, Harald, 1974-
(författare)
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Topology optimization of vehicle body structures : method, theory and applications
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation is concerned with topology optimization of vehicle body structures.The first part of this thesis gives a summary of the research project. A design process for complex mechanical structures is presented. This design process includes an optimization step where simplified models are optimized. These simplified models are frame structures consisting of beams and joints. Joints are modelled as a collection of sub-elements to support for a topological change during optimization. Parameterization of beams and joint is also presented and design variables are introduced.An application of this frame topology optimization method, concerning a vehicle body structure, is presented.Two extensions to the theory are also presented. First, the possibility to penalize joints to support for easily realizable results is presented. This is followed by a two-material interpolation that introduces the possibility of using a mixed material structure.This introductory part is followed by five appended papers produced within the framework of this research.
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- Fälth, Billy, 1968-, et al.
(författare)
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How does the Fault Rupture Model affect Simulated Co-Seismic Near-Fault Stress Evolution?
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The dynamic and static stress perturbations generated in an earthquake affect the stability of faults and fractures in the vicinity of the rupture. Estimates of co-seismic near-fault stress effects can be made using numerical simulations. Here, we study the co-seismic stress evolution close to an earthquake using two different models to simulate the rupture. One model is the linear slip-weakening (SW) model, where a spontaneous earthquake rupture is simulated. We compare this to a constant rupture velocity time-weakening (TW) model, which we implement in four different instances of rupture velocity Vr and strength reduction time interval Δtred. We evaluate the near-fault stress effects using the Coulomb Failure Stress (CFS), which we calculate from the stress evolution at various positions relative to the rupture plane. The results show that the TW method is capable of generating similar secondary effects as those generated by the SW model. However, the assumption of constant values of Δtred and Vr implies that there will always be locations on the rupture plane where these values are incompatible. We also see that variationsin Δtred and Vr have a significant impact on the results. Particularly, Vr is important for how the stresses around the rupture front are superimposed, and is thus important for the temporal evolution and spatial distribution of CFS around the fault. Lower Vr tends to generate a gentler near-fault stress evolution and lower peak CFS values. The results also indicate that not only the momentary value of Vr is important for the secondary stress effects at a near-fault position passed by the rupture, but also the integrated Vr-history up to that position.
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| 8. |
- Fälth, Billy, 1968-, et al.
(författare)
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Influence of Fault Roughness on Co-Seismic Near-Fault Stress Evolution
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Co-seismic displacements on fractures and faults close to large earthquakes may not contribute significantly to the shaking hazard for surface infrastructures. However, for deep geological nuclear waste repositories, such secondary displacements could, if large enough, damage intersected waste containers and constitute a significant long-term safety concern. To study how the potential for such displacements may depend on the earthquake rupture evolution, we simulate dynamic earthquake ruptures, and calculate the co-seismic evolution of Coulomb Failure Stress (CFS) on hypothetical fracture planes in the near-fault continuum. Poroelastic coupling is accounted for via Skempton’s coefficient B. We study three cases: (1) A planar fault with homogeneous properties. (2) A planar fault where the dynamic friction increases gradually along the fault edge to obtain a gentler rupture arrest. (3) An undulated fault with fractal properties. For Case 3, we consider ten different fault surface realizations. Since the undulations reduce fault slip, we also run models with adjusted dynamic friction coefficients, such that they generate seismic moments on par with that of Case 1. We observe the following: (i) The initial stress field, rather than the co-seismic stress effects, is the dominating influence on the fracture orientations that obtain the highest CFS values. (ii) Lower slip gradients and less fault slip in Case 2 reduce the maximum CFS by 10-15% relative to the reference case. (iii) Fault roughness may increase CFS locally by tens of percent. (iv) Given our reference value of B=0.5, B-value variations of ±0.5 would give CFS variations of ±20%, at most.
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| 9. |
- Fälth, Billy, 1968-
(författare)
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Simulating Earthquake Rupture and Near-Fault Fracture Response
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sweden is presently a low seismicity area where most earthquakes are small and pose no serious threat to constructions. For the long-term perspectives of safety assessments of geological repositories for spent nuclear fuel, however, the effects of large earthquakes have to be considered. For the Swedish nuclear waste storage concept, seismically induced secondary fracture shear displacements across waste canister positions could pose a long-term seismic risk to the repository.In this thesis, I present earthquake simulations with which I study the potential for near-fault secondary fracture shear displacements. As a measure I use the Coulomb Failure Stress (CFS), but also calculate explicit fracture displacements. I account for both the dynamic and quasi-static stress perturbations generated during the earthquake. As numerical tool I use the 3DEC code, whose performance I validate using Stokes closed-form solution and the Compsyn code as benchmarks. In a model of a Mw 6.4 earthquake, I investigate how fault roughness, the fault rupture propagation model and rupture velocity may impact the near-fault CFS evolution. I find that fault roughness can reduce the amount of fault slip by tens of percent, but also increase the near-fault CFS with similar amounts locally. Furthermore, different fault rupture models generate similar CFS levels. I also find that the secondary stresses scale with rupture velocity.In a model based on data from the Forsmark nuclear waste repository site, and assuming stress conditions prevailing at the end of a glaciation, I simulate several high stress drop ~Mw 5.6 earthquake scenarios on the gently dipping fault zone ZFMA2 and calculate secondary fracture displacements on 300 m diameter planar fractures. Less than 1% of the fractures at the shortest distance from ZFMA2 generate displacements exceeding the 50 mm criterion established by the Swedish Nuclear Fuel and Waste Management Co. Given the high stress drops and the assumption of fracture planarity, I consider the calculated displacements to represent upper bound estimates of possible secondary displacements at Forsmark. Hence, the results should strengthen the confidence in the safety assessment of the nuclear waste repository at the Forsmark site.
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| 10. |
- Fälth, Billy, et al.
(författare)
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Simulating earthquake rupture and off-fault fracture response : Application to the safety assessment of the Swedish nuclear waste repository
- 2015
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Ingår i: Bulletin of The Seismological Society of America (BSSA). - : Seismological Society of America (SSA). - 0037-1106 .- 1943-3573. ; 105:1, s. 134-151
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Tidskriftsartikel (refereegranskat)abstract
- To assess the long‐term safety of a deep repository of spent nuclear fuel, upper bound estimates of seismically induced secondary fracture shear displacements are needed. For this purpose, we analyze a model including an earthquake fault, which is surrounded by a number of smaller discontinuities representing fractures on which secondary displacements may be induced. Initial stresses are applied and a rupture is initiated at a predefined hypocenter and propagated at a specified rupture speed. During rupture we monitor shear displacements taking place on the nearby fracture planes in response to static as well as dynamic effects. As a numerical tool, we use the 3Dimensional Distinct Element Code (3DEC) because it has the capability to handle numerous discontinuities with different orientations and at different locations simultaneously. In tests performed to benchmark the capability of our method to generate and propagate seismic waves, 3DEC generates results in good agreement with results from both Stokes solution and the Compsyn code package. In a preliminary application of our method to the nuclear waste repository site at Forsmark, southern Sweden, we assume end‐glacial stress conditions and rupture on a shallow, gently dipping, highly prestressed fault with low residual strength. The rupture generates nearly complete stress drop and an Mw 5.6 event on the 12 km2 rupture area. Of the 1584 secondary fractures (150 m radius), with a wide range of orientations and locations relative to the fault, a majority move less than 5 mm. The maximum shear displacement is some tens of millimeters at 200 m fault‐fracture distance.
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