| 1. |
- Bakali, Amin, et al.
(författare)
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Crystal structure of YegS, a homologue to the mammalian diacylglycerol kinases, reveals a novel regulatory metal binding site
- 2007
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 282:27, s. 19644-19652
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Tidskriftsartikel (refereegranskat)abstract
- The human lipid kinase family controls cell proliferation, differentiation, and tumorigenesis and includes diacylglycerol kinases, sphingosine kinases, and ceramide kinases. YegS is an Escherichia coli protein with significant sequence homology to the catalytic domain of the human lipid kinases. We have solved the crystal structure of YegS and shown that it is a lipid kinase with phosphatidylglycerol kinase activity. The crystal structure reveals a two-domain protein with significant structural similarity to a family of NAD kinases. The active site is located in the interdomain cleft formed by four conserved sequence motifs. Surprisingly, the structure reveals a novel metal binding site composed of residues conserved in most lipid kinases.
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| 2. |
- Berglund, Eva Caroline, et al.
(författare)
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A Study Protocol for Validation and Implementation of Whole-Genome and -Transcriptome Sequencing as a Comprehensive Precision Diagnostic Test in Acute Leukemias
- 2022
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Ingår i: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media SA. - 2296-858X. ; 9, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS), with the ability to provide comprehensive genomic information, have become the focal point of research interest as novel techniques that can support precision diagnostics in routine clinical care of patients with various cancer types, including hematological malignancies. This national multi-center study, led by Genomic Medicine Sweden, aims to evaluate whether combined application of WGS and WTS (WGTS) is technically feasible and can be implemented as an efficient diagnostic tool in patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In addition to clinical impact assessment, a health-economic evaluation of such strategy will be performed. Methods and Analysis: The study comprises four phases (i.e., retrospective, prospective, real-time validation, and follow-up) including approximately 700 adult and pediatric Swedish AML and ALL patients. Results of WGS for tumor (90×) and normal/germline (30×) samples as well as WTS for tumors only will be compared to current standard of care diagnostics. Primary study endpoints are diagnostic efficiency and improved diagnostic yield. Secondary endpoints are technical and clinical feasibility for routine implementation, clinical utility, and health-economic impact. Discussion: Data from this national multi-center study will be used to evaluate clinical performance of the integrated WGTS diagnostic workflow compared with standard of care. The study will also elucidate clinical and health-economic impacts of a combined WGTS strategy when implemented in routine clinical care. Clinical Trial Registration: [https://doi.org/10.1186/ISRCTN66987142], identifier [ISRCTN66987142].
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| 3. |
- Bjerke, Maria, 1977, et al.
(författare)
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Subcortical vascular dementia biomarker pattern in mild cognitive impairment.
- 2009
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:4, s. 348-56
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mild cognitive impairment (MCI) is an etiologically unclear disorder. Cerebrospinal fluid (CSF) biomarkers are potentially useful for the differentiation between various MCI etiologies. AIM: The aim of the study was to assess whether baseline CSF hyperphosphorylated tau (P-tau), total tau (T-tau), amyloid beta 1-42 (Abeta(42)) and neurofilament light (NF-L) in patients with MCI could predict subcortical vascular dementia (SVD) and Alzheimer's disease (AD) at follow-up. METHODS: Biomarker levels were assessed by Luminex xMAP technology and ELISA. RESULTS: Increased baseline concentrations of NF-L significantly separated MCI-SVD from stable MCI. The MCI-SVD patients were inseparable from stable MCI but separable from patients developing AD (MCI-AD) on the basis of Abeta(42,) T-tau and P-tau(181) levels. CONCLUSION: A combination of the biomarkers Abeta(42), T-tau, P-tau(181) and NF-L has the potential to improve the clinical separation of MCI-SVD patients from stable MCI and MCI-AD patients.
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| 4. |
- Brandenburg, Axel, et al.
(författare)
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Astrophysical turbulence modeling
- 2011
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Ingår i: Reports on progress in physics (Print). - : IOP Publishing. - 0034-4885 .- 1361-6633. ; 74:4, s. 046901-
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Forskningsöversikt (refereegranskat)abstract
- The role of turbulence in various astrophysical settings is reviewed. Among the differences to laboratory and atmospheric turbulence we highlight the ubiquitous presence of magnetic fields that are generally produced and maintained by dynamo action. The extreme temperature and density contrasts and stratifications are emphasized in connection with turbulence in the interstellar medium and in stars with outer convection zones, respectively. In many cases turbulence plays an essential role in facilitating enhanced transport of mass, momentum, energy and magnetic fields in terms of the corresponding coarse-grained mean fields. Those transport properties are usually strongly modified by anisotropies and often completely new effects emerge in such a description that have no correspondence in terms of the original (non-coarse-grained) fields.
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| 5. |
- De Pontieu, B., et al.
(författare)
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Rapid Temporal Variability of Faculae: High-Resolution Observations and Modeling
- 2006
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Ingår i: The Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 646:2, s. 1405-1420
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Tidskriftsartikel (refereegranskat)abstract
- We present high-resolution G-band observations (obtained with the Swedish 1 m Solar Telescope) of the rapid temporal variability of faculae, which occurs on granular timescales. By combining these observations with magnetoconvection simulations of a plage region, we show that much of this variability is not intrinsic to the magnetic field concentrations that are associated with faculae, but rather a phenomenon associated with the normal evolution and splitting of granules. We also show examples of facular variability caused by changes in the magnetic field, with movies of dynamic behavior of the striations that dominate much of the facular appearance at 0.1" resolution. Examples of these dynamics include merging, splitting, rapid motion, apparent fluting, and possibly swaying.
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| 6. |
- Eckerström, Carl, et al.
(författare)
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A Combination of Neuropsychological, Neuroimaging, and Cerebrospinal Fluid Markers Predicts Conversion from Mild Cognitive Impairment to Dementia.
- 2013
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 36:3, s. 421-431
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mild cognitive impairment (MCI) is a condition with increased risk for further cognitive decline. A considerable challenge lies in predicting which patients will eventually convert to dementia. Objective: To study prediction of dementia in MCI using neuropsychological tests, commonly used cerebrospinal fluid (CSF) biomarkers, and hippocampal volume. Methods: Twenty-one MCI patients converting to dementia, 21 stable MCI patients, and 26 controls were included in the study with a follow-up time of two years. The study participants underwent comprehensive examinations at inclusion: a neuropsychological assessment comprising 20 tests, MRI scanning with subsequent hippocampal volumetry, and CSF analyses of T-tau, P-tau, and Aβ42. Results: Neuropsychological tests, hippocampal volume, and the CSF markers Aβ42, P-tau, and T-tau all predicted conversion from MCI to dementia. A combination of all classes of markers was the most successful at predicting dementia (AUC 0.96) with a memory test (RAVLT) as the best individual predictor (AUC 0.93). Similar findings are reported for the prediction of Alzheimer's disease. Conclusion: Neuropsychological tests were the best individual predictors of dementia. A combination of markers improved the predictive ability with the combination of neuropsychological tests, CSF, and hippocampal volume as the best predictors of dementia.
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| 7. |
- Gudiksen, Boris Vilhelm, et al.
(författare)
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An ab Initio Approach to Solar Coronal Loops
- 2005
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Ingår i: Astrophysical Journal. - : The American Astronomical Society. - 0004-637X .- 1538-4357. ; 618:2, s. 1031-1038
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Tidskriftsartikel (refereegranskat)abstract
- Data from recent numerical simulations of the solar corona and transition region are analyzed, and the magnetic field connections between the low corona and the photosphere are found to be close to those of a potential field. The field line-to-field line displacements follow a power-law distribution with typical displacements of just a few Mm. Three loops visible in simulated TRACE filters are analyzed in detail and found to have significantly different heating rates and distributions thereof, one of them showing a small-scale heating event. The dynamical structure is complicated, even though all the loops are visible in a single filter along most of their lengths. The loops are nonstatic and are in the process of evolving into loops with very different characteristics. Differential emission measure (DEM) curves along one of the loops illustrate that DEM curves have to be treated carefully if physical characteristics are to be extracted.
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| 8. |
- Gudiksen, Boris Vilhelm, et al.
(författare)
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An Ab Initio Approach to the Solar Coronal Heating Problem
- 2005
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Ingår i: Astrophysical Journal. - : The American Astronomical Society. - 0004-637X .- 1538-4357. ; 618:2, s. 1020-1030
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Tidskriftsartikel (refereegranskat)abstract
- We present an ab initio approach to the solar coronal heating problem by modeling a small part of the solar corona in a computational box using a three-dimensional MHD code including realistic physics. The observed solar granular velocity pattern and its amplitude and vorticity power spectra, as reproduced by a weighted Voronoi tessellation method, are used as a boundary condition that generates a Poynting flux in the presence of a magnetic field. The initial magnetic field is a potential extrapolation of a SOHO/MDI high-resolution magnetogram, and a standard stratified atmosphere is used as a thermal initial condition. Except for the chromospheric temperature structure, which is kept nearly fixed, the initial conditions are quickly forgotten because the included Spitzer conductivity and radiative cooling function have typical timescales much shorter than the time span of the simulation. After a short initial start-up period, the magnetic field is able to dissipate (3-4) × 106 ergs cm-2 s-1 in a highly intermittent corona, maintaining an average temperature of ~106 K, at coronal density values for which simulated images of the TRACE 171 and 195 Å passbands reproduce observed photon count rates.
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| 9. |
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| 10. |
- Johansen, Anders, et al.
(författare)
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Transport, destruction, and growth of pebbles in the gas envelope of a protoplanet
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 903:2
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Tidskriftsartikel (refereegranskat)abstract
- We analyze the size evolution of pebbles accreted into the gaseous envelope of a protoplanet growing in a protoplanetary disk, taking into account collisions driven by the relative sedimentation speed as well as the convective gas motion. Using a simple estimate of the convective gas speed based on the pebble accretion luminosity, we find that the speed of the convective gas is higher than the sedimentation speed for all particles smaller than 1 mm. This implies that both pebbles and pebble fragments are strongly affected by the convective gas motion and will be transported by large-scale convection cells both toward and away from the protoplanet's surface. We present a simple scheme for evolving the characteristic size of the pebbles, taking into account the effects of erosion, mass transfer, and fragmentation. Including the downwards motion of convective cells for the transport of pebbles with an initial radius of 1 mm, we find pebble sizes between 100 μm and 1 mm near the surface of the protoplanet. These sizes are generally amenable to accretion at the base of the convection flow. Small protoplanets far from the star (>30 au) nevertheless erode their pebbles to sizes below 10 μm; future hydrodynamical simulations will be needed to determine whether such small fragments can detach from the convection flow and become accreted by the protoplanet.
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