Peak intensity prediction in MALDI-TOF mass spectrometry: A machine learning study to support quantitative proteomics

Background  

Mass spectrometry is a key technique in proteomics and can be used to analyze complex samples quickly. One key problem with the mass spectrometric analysis of peptides and proteins, however, is the fact that absolute quantification is severely hampered by the unclear relationship between the observed peak intensity and the peptide concentration in the sample. While there are numerous approaches to circumvent this problem experimentally (e.g. labeling techniques), reliable prediction of the peak intensities from peptide sequences could provide a peptide-specific correction factor. Thus, it would be a valuable tool towards label-free absolute quantification.     

Home ranges and densities of medium-sized carnivores in south-east Finland, with special reference to rabies spread

Home ranges and densities of medium-sized carnivores were studied in south-east Finland by radio tracking. The species studied included potential vectors of rabies: the raccoon dogNyctereutes procyonoides (Gray, 1834), red foxVulpes vulpes (Linnaeus, 1758), European badgerMeles meles (Linnaeus, 1758) and domestic catFelis silvestris catus (Schreber, 1777). Home ranges of badgers were largest (mean 14.7 km²) and those of cats smallest (1.5 km²). Home ranges overlapped largely, both within and between species. Most home ranges were larger and population densities lower in south-east Finland compared with those in Western Europe. The pooled density of medium-sized carnivores with overlapping home ranges was, however, high, which may indicate a high risk of a rabies epizootic in this multi-host community. Rabies might also spread rapidly to new areas, because of the large home ranges and, consequently, long dispersal distances.     

Endothelial activation during interleukin 2 immunotherapy. A possible mechanism for the vascular leak syndrome

A major sequela of immunotherapy with interleukin 2 (IL-2) is development of a vascular leak syndrome. The pathogenesis of this toxic effect is not known. We have examined pre- and post-treatment skin biopsies from 14 patients undergoing systemic administration of IL-2 for evidence of endothelial cell activation. Specifically, we have used the immunoperoxidase technique to detect the expression of three different activation antigens: endothelial-leukocyte adhesion molecule 1, detected with monoclonal antibody H4/18; intercellular adhesion molecule 1, detected with antibody RR1/1; and histocompatibility leukocyte antigen-DQ, detected with antibody Leu 10. Each of these antigens may be induced on cultured endothelial cells by various cytokines (although not by IL-2) and is expressed during endothelial cell activation in vivo at sites of delayed hypersensitivity and other immune responses. Pretreatment biopsies from each patient showed no endothelial expression of endothelial-leukocyte adhesion molecule 1 and only weak to moderate expression of intercellular adhesion molecule 1 and histocompatibility leukocyte antigen-DQ (except for one specimen unreactive with Leu 10). After 5 days of treatment, every patient showed marked endothelial expression of all three antigens (except for the same patient who remained unreactive with Leu 10). Endothelial-leukocyte adhesion molecule-1 expression was confined to postcapillary venular endothelium whereas intercellular adhesion molecule-1 and Leu 10 also were expressed on stromal cells and mononuclear cells. Thus, we conclude that i.v. administration of IL-2 leads to endothelial cell activation. Because IL-2 fails to induce the same antigens on cultured endothelial cells, we infer that IL-2 acts in vivo by inducing the production of other cytokines (e.g., interleukin 1, tumor necrosis factor, lymphotoxin, and interferon-gamma). Finally, since endothelial cell activation at sites of cell-mediated immune responses is well known to result in vascular leakiness to macromolecules, we propose that the vascular leak syndrome accompanying IL-2 therapy may arise from widespread inappropriate endothelial cell activation.