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Sökning: WFRF:(Larsen Sören)

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1.
  • Abildgaard, Amanda B., et al. (författare)
  • HSP70-binding motifs function as protein quality control degrons
  • 2023
  • Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 80:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and thus protect cells against the accumulation of potentially toxic non-native proteins. Studies have shown that PQC degrons are hydrophobic and rarely contain negatively charged residues, features which are shared with chaperone-binding regions. Here we explore the notion that chaperone-binding regions may function as PQC degrons. When directly tested, we found that a canonical Hsp70-binding motif (the APPY peptide) functioned as a dose-dependent PQC degron both in yeast and in human cells. In yeast, Hsp70, Hsp110, Fes1, and the E3 Ubr1 target the APPY degron. Screening revealed that the sequence space within the chaperone-binding region of APPY that is compatible with degron function is vast. We find that the number of exposed Hsp70-binding sites in the yeast proteome correlates with a reduced protein abundance and half-life. Our results suggest that when protein folding fails, chaperone-binding sites may operate as PQC degrons, and that the sequence properties leading to PQC-linked degradation therefore overlap with those of chaperone binding. 
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2.
  • Barthelmie, Rebecca, et al. (författare)
  • ENDOW: Efficient Development of Offshore Windfarms
  • 2003
  • Ingår i: Proceedings from Offshore Wind Energy in Meditteranean and Other Seas OWEMES2003, Naples, Italy, 10-12 April 2003.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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  • Vergmann, Anna Stage, et al. (författare)
  • Heritability of retinal vascular fractals : A twin study
  • 2017
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 58:10, s. 3997-4002
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. METHODS. This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50º, disc-centered fundus photographs, the retinal vascular fractal dimension was measured using the box-counting method and compared within monozygotic and dizygotic twin pairs using Pearson correlation coefficients. Falconer’s formula and quantitative genetic models were used to determine the genetic component of variation. RESULTS. The mean fractal dimension did not differ statistically significantly between monozygotic and dizygotic twin pairs (1.505 vs. 1.495, P = 0.06), supporting that the study population was suitable for quantitative analysis of heritability. The intrapair correlation was markedly higher (0.505, P = 0.0002) in monozygotic twins than in dizygotic twins (0.108, P = 0.46), corresponding to a heritability h2 for the fractal dimension of 0.79. In quantitative genetic models, dominant genetic effects explained 54% of the variation and 46% was individually environmentally determined. CONCLUSIONS. In young adult twins, the branching pattern of the retinal vessels demonstrated a higher structural similarity in monozygotic than in dizygotic twin pairs. The retinal vascular fractal dimension was mainly determined by genetic factors, which accounted for 54% of the variation. The genetically predetermination of the retinal vasculature may affect the retinal response to potential vascular disease in later life.
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6.
  • Andersen, Hans Estrup, et al. (författare)
  • Identifying Hot Spots of Agricultural Nitrogen Loss Within the Baltic Sea Drainage Basin
  • 2016
  • Ingår i: Water, Air and Soil Pollution. - : Springer Science and Business Media LLC. - 0049-6979 .- 1573-2932. ; 227:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Agricultural management practices are among the major drivers of agricultural nitrogen (N) loss. Legislation and management incentives for measures to mitigate N loss should eventually be carried out at the individual farm level. Consequently, an appropriate scale to simulate N loss from a scientific perspective should be at the farm scale. A data set of more than 4000 agricultural fields with combinations of climate, soils and agricultural management which overall describes the variations found in the Baltic Sea drainage basin was constructed. The soil-vegetation-atmosphere model Daisy (Hansen et al. 2012) was used to simulate N loss from the root zone of all agricultural fields in the data set. From the data set of Daisy simulations, we identified the most important drivers for N loss by multiple regression statistics and developed a statistical N loss model. By applying this model to a basin-wide data set on climate, soils and agricultural management at a 10 x 10 km scale, we were able to calculate root-zone N losses from the entire Baltic Sea drainage basin and identify N loss hot spots in a consistent way and at a level of detail not hitherto seen for this area. Further, the root-zone N loss model was coupled to estimates of nitrogen retention in catchments separated into retention in groundwater and retention in surface waters allowing calculation of the coastal N loading.
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7.
  • Arnqvist, Johan, 1985- (författare)
  • Mean Wind and Turbulence Conditions in the Boundary Layer above Forests
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • As wind turbines have grown, new installation areas become possible. Placing wind turbines in forested landscapes introduce uncertainties to the wind resource estimation. Even though close-to-canopy processes have been studied intensively during the last thirty years, the focus has mostly been on exchange processes and the height span of the studies has been below the rotor of a modern wind turbine.This thesis contains analysis of new measurements from a 138 m high tower in a forested landscape. The previous knowledge of near-canopy processes is extended to the region above the roughness sublayer. It is shown that above the roughness sublayer, the surface layer behaves as over low vegetation, and Monin-Obukhov similarity is shown to hold for several variables. However, in stable stratification, effects that could be linked to the boundary layer depth are shown to be present in the measurements. These include wind turning with height, the behaviour of the turbulence length scale and the curvature of the wind profile.Two new analytical models are presented in the thesis. One is a flux-profile expression in the roughness sublayer, which allows for analytical integration of the wind gradient. The model suggests that the roughness-sublayer effect depends on stratification and that the aerodynamic roughness length changes with stability. A decrease of roughness length in stable stratification is confirmed with a new method to determine the roughness length using measurements from the 138 m tower.The other model determines the spectral tensor in stable stratification using analytical solution to the rapid distortion equations for stratified shear flow, with homogeneous stratification and shear. By using a formulation for the integration time of the distortions of an isotropic spectrum, a model is derived which provides the cross spectra of velocity and temperature at any two given points in space.Finally the existence of waves in the wind over forests is investigated and it is concluded that the Kelvin-Helmholtz instability can create waves which are coherent in time and exist over the entire height span of wind turbine rotors. Linear wave theory is shown to be able to explain certain features of the waves.
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8.
  • Broberg, Karin, et al. (författare)
  • Trisomy 7 accumulates with age in solid tumors and non-neoplastic synovia
  • 2001
  • Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 30:3, s. 310-315
  • Tidskriftsartikel (refereegranskat)abstract
    • Trisomy 7 is a common finding in benign and malignant solid tumors, in several non-neoplastic lesions (for example, osteoarthritis and rheumatoid arthritis), and in apparently normal tissues as well, suggesting that the occurrence of +7 might be associated with factors other than the disease process itself. To find out whether the frequency of +7 varies with a patient's age, we cytogenetically analyzed short-term-cultured synovial samples from elderly persons without signs of arthritis and from young patients affected by juvenile chronic arthritis (JCA). In normal synovia, gain of a chromosome 7 was present as a clonal change in five of 10 cases and in single cells in four of the five remaining cases. In synovia from patients with JCA, cells with +7 were detected in only one of nine cases, representing the oldest patient in the series. Furthermore, we reviewed the cytogenetic literature on tumors of the brain, breast, colon, kidney, lung, skin, thyroid, and upper aerodigestive tract. In the majority (six of eight) of these tumor types, the frequency of cases displaying a clone with +7 as the sole aberration increased with age. Taken together, the results presented here suggest that the acquisition of trisomy 7 in some neoplastic and non-neoplastic tissues might be associated with age rather than with disease. The finding of a completely different frequency distribution in two of the tumor types (tumors of the brain and the thyroid gland), however, emphasizes the heterogeneity of +7 and indicates that other, possibly tissue-specific, factors might influence the occurrence of this mutation.
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9.
  • Broberg Palmgren, Karin, et al. (författare)
  • The tumor-associated gene HMGIC is expressed in normal and osteoarthritis-affected synovia
  • 2001
  • Ingår i: Modern Pathology. - : Elsevier BV. - 1530-0285 .- 0893-3952. ; 14:4, s. 311-317
  • Tidskriftsartikel (refereegranskat)abstract
    • Chromosomal rearrangements involving chromosome bands 12q13-15 are very frequent findings in benign solid tumors, and recently, the primary molecular target for these aberrations was identified as the gene HMGIC. However, mutations in this gene have also been observed in nonneoplastic tissues. In a previous study, we reported breakpoints within HMGIC of synovia affected by osteoarthritis (OA) in two cases with 12q15 aberrations. To analyze further the role of HMGIC in this disease, we have performed cytogenetic, fluorescent in situ hybridization (FISH), RNA, and protein expression analyses on synovial samples from patients with OA and individuals without signs of the disorder. Cytogenetic analysis of short-term cultured cells revealed clonal 12q13-15 aberrations in 2/36 cases of OA synovia and no rearrangement in any of the five controls. With FISH analysis, it was shown that the chromosomal breakpoints in the two aberrant cases were located outside the HMGIC locus. In contrast, at RNA and protein expression analyses, OA-affected as well as normal synovia displayed transcription and translation of the gene. We also analyzed whether immunoreactivity for HMGIC was associated with the proliferation-specific antigen Ki-67, but no correlation between the staining patterns of these proteins was observed. From the results of the present study, it is evident that expression of HMGIC cannot simply be considered a sign of neoplasia or an effect of proliferation.
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