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- Arnborg, Stefan, et al.
(author)
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Data Mining in Schizophrenia Research - preliminary analysis
- 2002
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Conference paper (peer-reviewed)abstract
- We describe methods used and some results in a study of schizophrenia in a population of affected and unaffected participants, called patients and controls. The subjects are characterized by diagnosis, genotype, brain anatomy (MRI), laboratory tests on blood samples, and basic demographic data. The long term goal is to identify the causal chains of processes leading to disease. We describe a number of preliminary findings, which confirm earlier results on deviations of brain tissue volumes in schizophrenia patients, and also indicate new effects that are presently under further investigation. More importantly, we discuss a number of issues in selection of methods from the very large set of tools in data mining and statistics.
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| 2. |
- Driscoll, K., et al.
(author)
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Byzantine Fault Tolerance, from Theory to Reality
- 2003
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In: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1611-3349 .- 0302-9743. - 3540201262 ; 2788, s. 235-248
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Conference paper (peer-reviewed)abstract
- Since its introduction nearly 20 years ago, the Byzantine Generals Problem has been the subject of many papers having the scrutiny of the fault tolerance community. Numerous Byzantine tolerant algorithms and architectures have been proposed. However, this problem is not yet sufficiently understood by those who design, build, and maintain systems with high dependability requirements. Today, there are still many misconceptions relating to Byzantine failure, what makes a system vulnerable, and indeed the very nature and reality of Byzantine faults. This paper revisits the Byzantine problem from a practitioner's perspective. It has the intention to provide the reader with a working appreciation of the Byzantine failure from a practical as well as a theoretical perspective. A discussion of typical failure properties and the difficulties in preventing the associated failure propagation is presented. These are illustrated with real Byzantine failure observations. Finally, various architectural solutions to the Byzantine problem are presented.
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| 3. |
- Hall, Håkan
(author)
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T cell responses and NK cell function in experimental autoimmune diabetes
- 2004
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Doctoral thesis (other academic/artistic)abstract
- The immune system is regulated by several complex mechanisms to maintain self tolerance and prevent autoimmune diseases. However, genetic as well as environmental factors can increase the risk of breaking self tolerance. Autoimmune diabetes is a polygenic disorder characterized by the selective destruction of pancreatic beta cells. Self-reactive T cells mediate the disease, but other cells including B cells, macrophages, dendritic cells (DC) , natural killer (NK) cells, NKT cells and regulatory T cells have been suggested to influence disease development. The aim of this thesis has been to characterize the regulation of T cell responses and the function of NK cells in autoimmune diabetes. CD8+ T cells are major producers of IFN-gamma, a key cytokine in autoimmune diabetes. The regulation of IFN-gamma production by CD8+ T cells was studied in relation to stimulatory strength. IFN-gamma secretion in stimulated naïve CD8+ T cells varied inversely with proliferation. Low concentrations of antigenic peptide and low levels of costimulation resulted in weak T cell proliferation, but substantial IFN-gamma production. Our unpublished data showed that CD8+ T cells from NOD mice (that spontaneously develop diabetes) are predisposed to increased IFNgamma responses, suggesting a possible role for IFN-gamma produced by self-reactive CD8+ T cells in the initiation phase of autoimmune diabetes. We also evaluated the role of the signaling adapter molecule DAP12 in a CD4+ T cell transgenic diabetes mouse model. Previously, it was shown that DAP 12 knock out mice were protected from experimental autoimmune encephalitis (EAE). Protection from EAE was associated with diminished priming of autoreactive CD4+ T cells in the mutant mice. We showed that DAP12 had an adverse effect in our model of autoimmune diabetes. In the absence of a functional DAP12 molecule, both diabetes and the activation of autoreactive CD4+ T cells were increased. This increased disease pathogenicity was accompanied by reduced suppression by antigen-specific CD4+CD25+ regulatory T cells. DAP 12 mutated mice had a different composition of DC, with an increased frequency of plasmacytoid DC (pDC), suggesting an interesting link between pDC and activation of regulatory T cells. NK cells may be involved in autoimmmunity and have been suggested to serve as regulatory cells in T cell mediated autoimmune diseases. A comprehensive analysis of NK cell function in NOD mice was made. NK cells in NOD mice could be identified by the combination of two monoclonal antibodies, TMbeta-1 (recognizing the beta-chain of the IL-2 receptor) and DX5 (recognizing CD49b integrin). Using these antibodies we demonstrated that there were no abnormalities in the size of NK cell populations in NOD mice compared to non-diabetogenic strains. However, NOD NK cell functions were broadly impaired due to defects in multiple activation pathways. This NK cell deficiency could be partially restored by NK cell activation in vivo, and after IL-12 and IL-18 stimulation in vitro. Furthermore, treating NOD mice with the TMbeta-1 antibody prevented disease. We confirmed, by flow cytometry, that all NK cells were depleted by this treatment. NK cell depletion was also confirmed by the complete lack of NK killing ability in antibody treated mice. A fraction of NKT cells was also depleted. In addition, a small population of CD8+ T cells, some of which co-expressed NKG2D, disappeared after treatment. TMbeta-1 treated mice could mount a normal primary CD8+ T cell response, but it is still possible that this small population of CD8+ T cells is important for diabetes development. A particularly interesting finding in this study was that disease was blocked when the antibody was administered late in disease pathogenesis. Even when given to prediabetic mice at 15 weeks of age, most mice were protected from diabetes, suggesting that the TMbeta-1 antibody targets effector cell/s responsible for a late, perhaps direct beta cell cytotoxic, effect in disease. This finding opens up the possibility for future development of new late-acting drugs against this disease.
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| 5. |
- Hult, Roger, 1969-
(author)
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Segmentation and Visualisation of Human Brain Structures
- 2003
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Doctoral thesis (other academic/artistic)abstract
- In this thesis the focus is mainly on the development of segmentation techniques for human brain structures and of the visualisation of such structures. The images of the brain are both anatomical images (magnet resonance imaging (MRI) and autoradigraphy) and functional images that show blood flow (functional magnetic imaging (fMRI), positron emission tomography (PET), and single photon emission tomograpy (SPECT)). When working with anatomical images, the structures segmented are visible as different parts of the brain, e.g. the brain cortex, the hippocampus, or the amygdala. In functional images, the activity or the blood flow that be seen.Grey-level morphology methods are used in the segmentations to make tissue types in the images more homogenous and minimise difficulties with connections to outside tissue. A method for automatic histogram thresholding is also used. Furthermore, there are binary operations such as logic operation between masks and binary morphology operations.The visualisation of the segmented structures uses either surface rendering or volume rendering. For the visualisation of thin structures, surface rendering is the better choice since otherwise some voxels might be missed. It is possible to display activation from a functional image on the surface of a segmented cortex. A new method for autoradiographic images has been developed, which integrates registration, background compensation, and automatic thresholding to getfaster and more realible results than the standard techniques give.
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