| 1. |
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| 2. |
- Imanishi, T., et al.
(författare)
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Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
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Tidskriftsartikel (refereegranskat)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Akdis, M, et al.
(författare)
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Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells
- 2004
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 199:11, s. 1567-1575
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4(+) T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-gamma-, interleukin (IL)-4-, and IL-10-producing allergen-specific CD4(+) T cells display characteristics of T helper cell (Th)1-, Th2, and T regulatory (Tr)1-like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4-secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-beta as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.
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| 9. |
- Andreyev, A. N., et al.
(författare)
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New microsecond isomers in Bi-189,Bi-190
- 2001
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 10:2, s. 129-133
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Tidskriftsartikel (refereegranskat)abstract
- New microsecond isomers in the neutron-deficient isotopes Bi-189g,Bi-190 have been identified after in-flight separation by the velocity filter SHIP. The evaporation residues were identified on the basis of delayed recoil-gamma /X-ray, recoil-gamma /X-ray-alpha and excitation function measurements. The systematics of the [pi 1i(13/2)]13/2(+) excited states in the odd-mass Bi nuclei is discussed.
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| 10. |
- Andreyev, A. N., et al.
(författare)
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The discovery of a prolate-oblate-spherical shape triple of spin 0(+) states in the atomic nucleus Pb-186
- 2001
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474 .- 1873-1554. ; 682, s. 482C-486C
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Tidskriftsartikel (refereegranskat)abstract
- Two excited J(pi)=0(+) states in Pb-186 populated in the a-decay of Po-190 have been identified through alpha -particle/conversion electron coincidences in an experiment at the velocity filter SHIP. The parent Po-190 nuclei have been produced in the Nd-142(Cr-52,4n)Po-190 complete fusion reaction, alpha -particle energies and branching ratios have been measured and hindrance factors were deduced. The observed states have been interpreted as the band heads of the known prolate and (yet unobserved) oblate rotational bands in Pb-186.
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| 11. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 12. |
- Rengefors, Karin, et al.
(författare)
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Experimental investigation of taxon-specific response of alkaline phosphatase activity in natural freshwater phytoplankton
- 2003
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Ingår i: Limnology and Oceanography. - 1939-5590. ; 48:3, s. 1167-1175
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Tidskriftsartikel (refereegranskat)abstract
- It is widely accepted that alkaline phosphatase activity (APA) is an efficient indicator of phosphate limitation in freshwater phytoplankton communities. In this study, we investigated whether the response in APA to phosphate limitation differs among the taxa in a mixed phytoplankton assemblage. We used the new enzyme-labeled fluorescence (ELF) technique, which allows microscopic detection of phosphate limitation in individual cells of multiple species. The most prominent findings of this study were that alkaline phosphatase (AP) was induced in many, but not all taxa and that different taxa, as well as different cells within a single taxon, experienced different degrees of phosphate stress under the same environmental conditions. Our approach was to manipulate the limiting nutrient in a natural freshwater phytoplankton community by incubating lake water in the laboratory. We induced nitrogen (N) or phosphate limitation through additions of inorganic nutrients. Both the ELF assay and bulk APA indicated that the lake phytoplankton were not phosphate limited at the start of the experiment. During the experiment, several chlorophyte taxa (e.g., Eudorina and an unidentified solitary spiny coccoid) were driven to phosphate limitation when inorganic N was added, as evidenced by a higher percentage of ELF-labeled cells relative to controls, whereas other chlorophyte taxa such as Actinastrum and Dicryosphaerium were not phosphate stressed under these conditions. In the phosphate-limited treatments, little or no ELF labeling was observed in any cyanobacterial taxa. Furthermore, all taxa observed after the ELF labeling procedure (>10-mum fraction) were labeled with ELF at least on one occasion, demonstrating the wide applicability of the ELF method. By using ELF labeling in tandem with bulk APA, the resolution and analysis of phosphate limitation was increased, allowing the identification of specific phosphate-stressed taxa.
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| 13. |
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| 15. |
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| 16. |
- Bäckström, Malin, 1967, et al.
(författare)
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Recombinant MUC1 mucin with a breast cancer-like O-glycosylation produced in large amounts in Chinese-hamster ovary cells.
- 2003
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Ingår i: The Biochemical journal. - 1470-8728. ; 376:Pt 3, s. 677-86
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Tidskriftsartikel (refereegranskat)abstract
- We have developed an expression system for the production of large quantities of recombinant MUC1 mucin in CHO-K1 (Chinese-hamster ovary K1) cells. The extracellular part of human MUC1, including 16 MUC1 tandem repeats, was produced as a fusion protein with murine IgG Fc, with an intervening enterokinase cleavage site for the removal of the Fc tail. Stable MUC1-IgG-producing CHO-K1 clones were generated and were found to secrete MUC1-IgG into the culture medium. After adaptation to suspension culture in protein-free medium in a bioreactor, the fusion protein was secreted in large quantities (100 mg/l per day) into the culture supernatant. From there, MUC1 could be purified to homogeneity using a two-step procedure including enterokinase cleavage and ion-exchange chromatography. Capillary liquid chromatography MS of released oligosaccharides from CHO-K1-produced MUC1 identified the main O-glycans as Galbeta1-3GalNAc (core 1) and mono- and di-sialylated core 1. The glycans occupied on average 4.3 of the five potential O-glycosylation sites in the tandem repeats, as determined by nano-liquid chromatography MS of partially deglycosylated Clostripain-digested protein. A very similar O-glycan profile and site occupancy was found in MUC1-IgG produced in the breast carcinoma cell line T47D, which has O-glycosylation typical for breast cancer. In contrast, MUC1-IgG produced in another breast cancer cell line, MCF-7, showed a more complex pattern with both core 1- and core 2-based O-glycans. This is the first reported production of large quantities of recombinant MUC1 with a breast cancer-like O-glycosylation that could be used for the immunotherapy of breast cancer.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Hedengren-Olcott, Marika, et al.
(författare)
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Differential activation of the NF-kappaB-like factors Relish and Dif in Drosophila melanogaster by fungi and gram-positive bacteria
- 2004
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 279:20, s. 21121-7
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Tidskriftsartikel (refereegranskat)abstract
- The current model of immune activation in Drosophila melanogaster suggests that fungi and Gram-positive (G+) bacteria activate the Toll/Dif pathway and that Gram-negative (G-) bacteria activate the Imd/Relish pathway. To test this model, we examined the response of Relish and Dif (Dorsal-related immunity factor) mutants to challenge by various fungi and G+ and G- bacteria. In Relish mutants, the Cecropin A gene was induced by the G+ bacteria Micrococcus luteus and Staphylococcus aureus, but not by other G+ or G- bacteria. This Relish-independent Cecropin A induction was blocked in Dif/Relish double mutant flies. Induction of the Cecropin A1 gene by M. luteus required Relish, whereas induction of the Cecropin A2 gene required Dif. Intact peptidoglycan (PG) was necessary for this differential induction of Cecropin A. PG extracted from M. luteus induced Cecropin A in Relish mutants, whereas PGs from the G+ bacteria Bacillus megaterium and Bacillus subtilis did not, suggesting that the Drosophila immune system can distinguish PGs from various G+ bacteria. Various fungi stimulated antimicrobial peptides through at least two different pathways requiring Relish and/or Dif. Induction of Attacin A by Geotrichum candidum required Relish, whereas activation by Beauvaria bassiana required Dif, suggesting that the Drosophila immune system can distinguish between at least these two fungi. We conclude that the Drosophila immune system is more complex than the current model. We propose a new model to account for this immune system complexity, incorporating distinct pattern recognition receptors of the Drosophila immune system, which can distinguish between various fungi and G+ bacteria, thereby leading to selective induction of antimicrobial peptides via differential activation of Relish and Dif.
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| 23. |
- Kleywegt, Gerard J, et al.
(författare)
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The Uppsala Electron-Density Server
- 2004
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Ingår i: Acta Crystallographica Section D. - 0907-4449 .- 1399-0047. ; 60:Pt 12 Pt 1, s. 2240-2249
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Tidskriftsartikel (refereegranskat)abstract
- The Uppsala Electron Density Server (EDS; http://eds.bmc.uu.se/) is a web-based facility that provides access to electron-density maps and statistics concerning the fit of crystal structures and their maps. Maps are available for approximately 87% of the crystallographic Protein Data Bank (PDB) entries for which structure factors have been deposited and for which straightforward map calculations succeed in reproducing the published R value to within five percentage points. Here, an account is provided of the methods that are used to generate the information contained in the server. Some of the problems that are encountered in the map-generation process as well as some spin-offs of the project are also discussed.
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| 24. |
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| 25. |
- Leon, R., et al.
(författare)
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Effects of proton irradiation on luminescence emission and carrier dynamics of self-assembled III-V quantum dots
- 2002
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Ingår i: IEEE Transactions on Nuclear Science. - 0018-9499 .- 1558-1578. ; 49:6, s. 2844-2851
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Tidskriftsartikel (refereegranskat)abstract
- The effects of proton irradiation (1.5 MeV) on photoluminescence intensities and carrier dynamics were compared between III-V quantum dots and similar quantum well structures. A significant enhancement in radiation tolerance is seen with three-dimensional (3-D) quantum confinement.. Measurements were carried out in different quantum dot (QD) structures, varying in material (InGaAs/GaAs and InAlAS/AlGaAS), QD surface density (4 x 10(8) to 3 x 10(10) cm(-2)), and substrate orientation [(100) and (311) B]. Similar trends were observed for all QD samples. A slight increase in PL emission after low to intermediate proton doses, are also observed in InGaAs/GaAs (100) QD structures. The latter is explained in terms of more efficient carrier transfer from the wetting layer via radiation-induced defects.
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| 26. |
- Link, Thomas, et al.
(författare)
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Bioprocess development for the production of a recombinant MUC1 fusion protein expressed by CHO-K1 cells in protein-free medium
- 2004
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Ingår i: J Biotechnol. ; 110, s. 51-62
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Tidskriftsartikel (refereegranskat)abstract
- The mucin MUC1 is a candidate for use in specific immunotherapy against breast cancer, but this requires the large-scale production of a MUC1 antigen. In this study, a bioprocess for the expression of a recombinant MUC1 fusion protein with a cancer associated glycosylation in CHO-K1 cells has been developed. Cells permanently expressing parts of the extracellular portion of MUC1 fused to IgG Fc were directly transferred from adherent growth in serum-containing medium to suspension culture in the protein-free ProCHO4-CDM culture medium. Using the Cellferm-pro® system, optimal culture parameter as pH and pO2 were determined in parallel spinner flask batch cultures. A pH of 6.8–7.0 and a pO2 of 40% of air saturation was found to give best cell growth and productivity of secreted recombinant protein. Specific productivity strongly depended the pO2 and correlated with the online monitored oxygen uptake rate (OUR) of the cells, which indicates a positive influence of the rate of oxidative phosphorylation on productivity. The optimised conditions were applied to continuous perfusion culture which gave very high cell densities and space time yields of the recombinant MUC1 fusion protein, allowing production at gram scale. The product degradation was much lower in supernatants from continuous perfusion culture compared to batch mode. Antibodies reacting with cancer associated MUC1 glycoforms strongly bound to the fusion protein, indicating that the desired glycoforms were obtained and suggesting that the recombinant MUC1 protein could be tested for use in immunotherapy.
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| 27. |
- Lockwood, M, et al.
(författare)
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Coordinated Cluster and ground-based instrument observations of transient changes in the magnetopause boundary layer during an interval of predominantly northward IMF : relation to reconnection pulses and FTE signatures
- 2001
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 19:10-12, s. 1613-1640
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Forskningsöversikt (refereegranskat)abstract
- We study a series of transient entries into the low-latitude boundary layer (LLBL) of all four Cluster spacecraft during an outbound pass through the mid-afternoon magnetopause ([X(GSM), Y(GSM), Z(GSM)] approximate to [2, 7, 9] R(E)). The events take place during an interval of northward IMF, as seen in the data from the ACE satellite and lagged by a propagation delay of 75 min that is well-defined by two separate studies: (1) the magnetospheric variations prior to the northward turning (Lockwood et al., 2001, this issue) and (2) the field clock angle seen by Cluster after it had emerged into the magnetosheath (Opgenoorth et al., 2001, this issue). With an additional lag of 16.5 min, the transient LLBL events cor-relate well with swings of the IMF clock angle (in GSM) to near 90degrees. Most of this additional lag is explained by ground-based observations, which reveal signatures of transient reconnection in the pre-noon sector that then take 10-15 min to propagate eastward to 15 MLT, where they are observed by Cluster. The eastward phase speed of these signatures agrees very well with the motion deduced by the cross-correlation of the signatures seen on the four Cluster spacecraft. The evidence that these events are reconnection pulses includes: transient erosion of the noon 630 nm (cusp/cleft) aurora to lower latitudes; transient and travelling enhancements of the flow into the polar cap, imaged by the AMIE technique; and poleward-moving events moving into the polar cap, seen by the EISCAT Svalbard Radar (ESR). A pass of the DMSP-F15 satellite reveals that the open field lines near noon have been opened for some time: the more recently opened field lines were found closer to dusk where the flow transient and the poleward-moving event intersected the satellite pass. The events at Cluster have ion and electron characteristics predicted and observed by Lockwood and Hapgood (1998) for a Flux Transfer Event (FTE), with allowance for magnetospheric ion reflection at Alfvenic disturbances in the magnetopause reconnection layer. Like FTEs, the events are about 1 R(E) in their direction of motion and show a rise in the magnetic field strength, but unlike FTEs, in general, they show no pressure excess in their core and hence, no characteristic bipolar signature in the boundary-normal component. However, most of the events were observed when the magnetic field was southward, i.e. on the edge of the interior magnetic cusp, or when the field was parallel to the magnetic equatorial plane. Only when the satellite begins to emerge from the exterior boundary (when the field was northward), do the events start to show a pressure excess in their core and the consequent bipolar signature. We identify the events as the first observations of FTEs at middle altitudes.
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| 28. |
- Lockwood, M., Fazakerley, A., Opgenoorth, H., Moen, J., van Eyken, A.P., Dunlop, M., Bosqued, J.M., Lu, G., Cully, C., Eglitis, P., McCrea, I., Hapgood, M. A., Wild, M.N., Stamper, R., Denig, W., Taylor, M., . Wild, J.A., Provan, G., Amm, O., Kauristie
(författare)
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Coordinated Cluster, ground-based instrumentation and low-altitude satellite observations of transient poleward-moving events in the ionosphere and in the tail lobe
- 2001
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Ingår i: Annales Geophysicae. ; 19:10, s. 1589-1612
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Tidskriftsartikel (refereegranskat)abstract
- During the interval between 8:00–9:30 on 14 January 2001, the four Cluster spacecraft were moving from the central magnetospheric lobe, through the dusk sector mantle, on their way towards intersecting the magnetopause near 15:00 MLT and 15:00 UT. Throug
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| 29. |
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| 30. |
- Marcinkevicius, Saulius, et al.
(författare)
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Changes in carrier dynamics induced by proton irradiation in quantum dots
- 2002
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Ingår i: Physica. B, Condensed matter. - 0921-4526 .- 1873-2135. ; 314:04-jan, s. 203-206
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Tidskriftsartikel (refereegranskat)abstract
- The effects of proton irradiation on carrier dynamics were investigated by time-resolved photoluminescence on different InGaAs/GaAs quantum-dot (QD) structures varying in QD surface density and substrate orientation, as well as thin InGaAs quantum wells. The carrier lifetimes in the dots are much less affected by proton irradiation than in the wells. Decrease in lifetimes of only 40 percent at the highest proton dose are observed in some of the QDs, whereas an similar to20 to similar to40-fold decrease is observed in the wells. Similar trends were observed for all quantum dot samples.
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| 31. |
- Marcinkevičius, Saulius, et al.
(författare)
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Changes in luminescence intensities and carrier dynamics induced by proton irradiation in In_xGa_1-xAs/GaAs quantum dots
- 2002
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 66:23, s. 235314-
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Tidskriftsartikel (refereegranskat)abstract
- The effects of proton irradiation (1.5 MeV) on photoluminescence intensities and carrier dynamics were compared between InGaAs/GaAs quantum dots and similar quantum well structures. A significant enhancement in radiation tolerance is seen with three-dimensional quantum confinement. Measurements were carried out in different quantum dot structures varying in dot surface density (4x10(8)-3x10(10) cm(-2)) and substrate orientation [(100) and (311)B]. Similar trends were observed for all quantum dot samples. A slight increase in photoluminescence emission intensity after low to intermediate proton doses is observed in InGaAs/GaAs (100) quantum dot structures. The latter is explained in terms of more efficient carrier transfer from the wetting layer via radiation-induced defects.
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| 32. |
- Marklund, G.T., Ivchenko, N., Karlsson, T., Fazakerley, A., Dunlop, M., Lindqvist, P.A., Buchert, S., Owen, C., Taylor, M., Vaivalds, A., Carter, P., Andre, M. and Balogh, A.
(författare)
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Temporal evolution of the electric field accelerating electrons away from the auroral ionosphere.
- 2001
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Ingår i: Nature. ; 414:6865, s. 724-727
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Tidskriftsartikel (refereegranskat)abstract
- The bright night-time aurorae that are visible to the unaided eye are caused by electrons accelerated towards Earth by an upward-pointing electric field(1-3). On adjacent geomagnetic field lines the reverse process occurs: a downward-pointing electric fie
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| 33. |
- Marklund, Göran T., et al.
(författare)
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Temporal evolution of the electric field accelerating electrons away from the auroral ionosphere
- 2001
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 414:6865, s. 724-727
-
Tidskriftsartikel (refereegranskat)abstract
- The bright night-time aurorae that are visible to the unaided eye are caused by electrons accelerated towards Earth by an upward-pointing electric field(1-3). On adjacent geomagnetic field lines the reverse process occurs: a downward-pointing electric field accelerates electrons away from Earth(4-11). Such magnetic-field-aligned electric fields in the collisionless plasma above the auroral ionosphere have been predicted(12), but how they could be maintained is still a matter for debate(13). The spatial and temporal behaviour of the electric fields-a knowledge of which is crucial to an understanding of their nature-cannot be resolved uniquely by single satellite measurements. Here we report on the first observations by a formation of identically instrumented satellites crossing a beam of upward-accelerated electrons. The structure of the electric potential accelerating the beam grew in magnitude and width for about 200 s, accompanied by a widening of the downward-current sheet, with the total current remaining constant. The 200-s timescale suggests that the evacuation of the electrons from the ionosphere contributes to the formation of the downward-pointing magnetic-field-aligned electric fields. This evolution implies a growing load in the downward leg of the current circuit, which may affect the visible discrete aurorae.
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| 34. |
- Pavey, S, et al.
(författare)
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Microarray expression profiling in melanoma reveals a BRAF mutation signature
- 2004
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 23:23, s. 4060-4067
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Tidskriftsartikel (refereegranskat)abstract
- We have used microarray gene expression pro. ling and machine learning to predict the presence of BRAF mutations in a panel of 61 melanoma cell lines. The BRAF gene was found to be mutated in 42 samples (69%) and intragenic mutations of the NRAS gene were detected in seven samples (11%). No cell line carried mutations of both genes. Using support vector machines, we have built a classifier that differentiates between melanoma cell lines based on BRAF mutation status. As few as 83 genes are able to discriminate between BRAF mutant and BRAF wild-type samples with clear separation observed using hierarchical clustering. Multidimensional scaling was used to visualize the relationship between a BRAF mutation signature and that of a generalized mitogen-activated protein kinase ( MAPK) activation ( either BRAF or NRAS mutation) in the context of the discriminating gene list. We observed that samples carrying NRAS mutations lie somewhere between those with or without BRAF mutations. These observations suggest that there are gene-specific mutation signals in addition to a common MAPK activation that result from the pleiotropic effects of either BRAF or NRAS on other signaling pathways, leading to measurably different transcriptional changes.
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| 35. |
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| 36. |
- Saha, B., et al.
(författare)
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LEA-135 expression: its association with a lower risk of recurrence and increased overall survival of patients with lymph node-positive primary invasive breast cancer
- 2004
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Ingår i: Anticancer Res. - 0250-7005. ; 24:4, s. 2391-2400
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Tidskriftsartikel (refereegranskat)abstract
- A retrospective study was undertaken to determine and compare the prognostic significance of LEA-135 protein expression by immunohistochemistry with other prognostic pathological parameters, with respect to recurrence and overall survival. This study was conducted in freshly-frozen tissue sections from a cohort of 367 patients having primary invasive breast cancer, with axillary lymph node metastasis. The association of LEA-135 expression was compared with estrogen and progesterone receptor status, segmentectomy or radical mastectomy and hormonal therapy or chemotherapy in terms of recurrence or disease-free survival. Pathologic parameters including tumor size, histological tumor type and histological grade, as well as age of patients at the time of initial diagnosis, and the treatments, together with a median follow-up of 8.8 years were contemplated for the study. Among these parameters, tumor size and histological grade were individually and significantly associated with an increased probability of recurrence (log rank p<0.001 in both cases) and short survival (log ranks p<0.001 and p=0.002, respectively), whereas age was only significantly associated with an increased probability of recurrence (log rank p=0.002) by univariate analysis. By multivariate analysis, both tumor size and histological grade remained statistically significant for recurrence (log rank p<0.001 and p=0.013, respectively) and overall survival (log ranks p<0.001 and p=0.016, respectively). Among the prognostic biomarkers, both ER and PR expression were associated with a decreased rate of recurrence (log ranks p<0.001 and p=0.008, respectively) and overall survival (log ranks p<0.001 and p=0.002, respectively) by univariate analysis. By multivariate analysis, only the ER expression remained significantly associated with a decreased recurrence and increased overall survival (log ranks p=0.023 and p=0.002, respectively). Patients with high (>50% positive cells) or moderate (5-50% positive cells) number of LEA-135-positive cells had a lower probability (46%) of recurrence at 10 years after surgery compared to 76% in LEA-135-negative patients (log rank p<0.001) by univariate analysis. Moreover, the probability of overall survival was higher in patients with high or moderate expression of LEA-135 (46% and 47%, respectively) compared to LEA-135-negative patients (24%) by univariate analysis (log rank p=0.009). By multivariate analysis, the association remained statistically significant for recurrence (log rank p<0.001) and survival (log rank p=0.002). However, there was no significant association between LEA-135 and any of the pathological parameters, age, hormone receptor status, the mode of surgery or the form of therapy (chemo- and/or hormonal) received by this cohort of patients. The results show that an improved prognosis was directly associated with the density of LEA-135-positive cancer cells, while loss of LEA-135 expression was associated with an aggressive phenotype of cancer cells during breast cancer progression. Thus, LEA-135 expression can be implicated as a significant and independent biomarker to identify and distinguish high- from low-risk patients with lymph node-positive invasive breast cancer for an aggressive treatment. Moreover, according to the present results, LEA-135 expression appears to be associated with the tumor cells that have retained certain normal biological characteristics, leading to their lack of aggressiveness and hence a better prognosis.
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| 37. |
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| 38. |
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| 39. |
- Taylor, Thomas C, et al.
(författare)
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First crystal structure of Rubisco from a green alga, Chlamydomonas reinhardtii
- 2001
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 276:51, s. 48159-48164
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structure of Rubisco (ribulose 1,5-bisphosphate carboxylase/oxygenase) from the unicellular green alga, Chlamydomonas reinhardtii has been determined to 1.4 Angstrom resolution. Overall, the structure shows high similarity to the previously determined structures of L8S8 Rubisco enzymes. The largest difference is found in the loop between beta strands A and B of the small subunit (betaA-betaB loop), which is longer by six amino acid residues than the corresponding region in Rubisco from Spinacia. Mutations of residues in the betaA-betaB loop have been shown to affect holoenzyme stability and catalytic properties. The information contained in the Chlamydomonas structure enables a more reliable analysis of the effect of these mutations. No electron density was observed for the last 13 residues of the small subunit, which are assumed to be disordered in the crystal. Because of the high resolution of the data, some posttranslational modifications are unambiguously apparent in the structure. These include cysteine and N-terminal methylations and proline 4-hydroxylations.
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