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| 62. |
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| 63. |
- Asplund, Anna, et al.
(författare)
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Expression profiling of microdissected cell populations selected from basal cells in normal epidermis and basal cell carcinoma
- 2008
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 158:3, s. 527-538
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Tidskriftsartikel (refereegranskat)abstract
- Background Basal cell carcinomas (BCCs) are prevalent tumours with uniform histology that develop without any known precursor lesion. Alterations in the sonic hedgehog-patched1 signalling pathway are accepted as necessary events for tumorigenesis, and mutations in the patched1 gene are frequently present in tumours. Objectives To analyse transcript profiles in BCC. Methods We used laser-assisted microdissection to isolate and collect cell populations defined under the microscope. Peripheral cells from nests of BCC were selected to represent tumour cells, and normal keratinocytes from epidermis basal layer were used as control. Extracted RNA was amplified and hybridized on to a cDNA microarray. Results Our results show that BCC cells express a transcript signature that is significantly different from that of normal keratinocytes, and over 350 genes with various functions were identified as differentially expressed. The compiled data suggest an upregulation of the Wnt signalling pathway as a major event in BCC cells. Furthermore, tumour cells appear to have an increased sensitivity to oxygen radicals and dysregulated genes involved in antigen presentation. Results were validated at both the transcriptional level using real-time polymerase chain reaction and at the protein level using immunohistochemistry. Conclusions We show that microdissection in combination with robust strategies for RNA extraction, amplification and cDNA microarray analysis allow for reliable transcript profiling and that antibody-based proteomics provides an advantageous strategy for the analysis of corresponding differentially expressed proteins. We found that expression patterns were significantly altered in BCC cells compared with basal keratinocytes and that the Wnt signalling pathway was upregulated in tumour cells.
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| 64. |
- Benkestock, Kurt, et al.
(författare)
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Automated Nano-Electrospray Mass Spectrometry for Protein-Ligand Screening by Noncovalent Interaction Applied to Human H-FABP and A-FABP
- 2003
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Ingår i: Journal of Biomolecular Screening. - : Elsevier BV. - 1087-0571 .- 1552-454X. ; 8:3, s. 247-256
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Tidskriftsartikel (refereegranskat)abstract
- A method for ligand screening by automated nano-electrospray ionization mass spectrometry (nano-ESI/MS) is described. The core of the system consisted of a chip-based platform for automated sample delivery from a 96-well plate and subsequent analysis based on noncovalent interactions. Human fatty acid binding protein, H-FABP (heart) and A-FABP (adipose), with small potential ligands was analyzed. The technique has been compared with a previously reported method based on nuclear magnetic resonance (NMR), and excellent correlation with the found hits was obtained. In the current MS screening method, the cycle time per sample was 1.1 min, which is approximately 50 times faster than NMR for single compounds and approximately 5 times faster for compound mixtures. High reproducibility was achieved, and the protein consumption was in the range of 88 to 100 picomoles per sample. Furthermore, a novel protocol for preparation of A-FABP without the natural ligand is presented. The described screening approach is suitable for ligand screening very early in the drug discovery process before conventional high-throughput screens (HTS) are developed and/or used as a secondary screening for ligands identified by HTS.
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| 65. |
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| 66. |
- Bergström, L., et al.
(författare)
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Signals of WIMP annihilation into electrons at the galactic center
- 2005
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Ingår i: Proceedings of the 29th International Cosmic Ray Conference, Vol 4: OG 2.1, 2.2 & 2.3. - : Tata Institute of Fundamental Research. ; , s. 57-60
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Konferensbidrag (refereegranskat)abstract
- Photons from the annihilation of dark matter in the center of our Galaxy are expected to provide a promising way to find out the nature and distribution of the dark matter itself. These photons can be either produced directly and/or through successive decays of annihilation products, or radiated from electrons and positrons. This ends up in a multi-wavelength production of photons whose expected intensity can be compared to observational data. Assuming that the Lightest Supersymmetric Particle makes the dark matter, we derive the expected photon signal from a given dark matter model and compare it with present available data.
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| 67. |
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| 69. |
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