| 1. |
- Hultdin, Magnus, et al.
(författare)
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Association between telomere length and V-H gene mutation status in chronic lymphocytic leukaemia : clinical and biological implications
- 2003
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Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 88:4, s. 593-598
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Tidskriftsartikel (refereegranskat)abstract
- The immunoglobulin V-H gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V-H genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated VH genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and VH gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between VH gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 63 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months), Furthermore, the I-g gene sequence data revealed that samples with high mutations frequency (> 6%) had long telomeres (similar to 8 kbp). Thus, both the telomere and VH gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction. (C) 2003 Cancer Research UK.
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| 2. |
- Hultdin, Magnus, et al.
(författare)
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Replication timing of human telomeric DNA and other repetitive sequences analyzed by fluorescence in situ hybridization and flow cytometry
- 2001
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Ingår i: Experimental Cell Research. - : Elsevier. - 0014-4827. ; 271, s. 223-229
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Tidskriftsartikel (refereegranskat)abstract
- The replication timing of telomeres seems to differ between species. Yeast telomeres are late replicating, whereas limited data from very few human cell lines have indicated telomere replication throughout S phase. In the present study a series of permanent cell lines and patient samples was investigated using a flow cytometric approach for telomere length determination based on in situ hybridization using peptide nucleic acid probes and DNA staining. This method permits selective analysis of cells in specific phases of the cell cycle without perturbation of the cell cycle machinery. The timing of replication of telomeric C(3)TA(2) and T(2)AG(3) repeats was found to differ between individual samples and could precede or be concomitant with the replication of bulk DNA. Replication of the T(2)AG(3) strand seemed to occur somewhat later than that of the C(3)TA(2) strand in some samples. (GTG)(n) and other repetitive sequences generally showed a replication pattern similar to that of the bulk of DNA with slightly individual differences, whereas centromeric DNA repeats consistently replicated within a short time frame in late S phase. The apparent variability in replication timing seen for telomeric DNA might suggest individual differences in firing of replication origins.
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| 3. |
- Johannesson, T, et al.
(författare)
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Reliability of Protection Systems - Operational Experiences 1976-2002
- 2004
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Ingår i: 8th International Conference on Development in Power System Protection. - 0863413854 ; 1, s. 303-306
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Konferensbidrag (refereegranskat)abstract
- This paper presents the results of an extensive survey on incorrect protection operations performed in Sweden on an electric power system owned by Sydkraft. The survey is based on disturbance reports and special investigation reports for the period 1976-2002. The results indicate the occurrence of the major types and causes of incorrect protection operations that have been revealed at disturbances in the electric power system under study.
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| 4. |
- Norrback, Karl-Fredrik, et al.
(författare)
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Telomerase regulation and telomere dynamics in germinal centers
- 2001
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Ingår i: European Journal of Haematology. - : Blackwell Munksgaard. - 0902-4441 .- 1600-0609. ; 67:5-6, s. 309-317
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Tidskriftsartikel (refereegranskat)abstract
- Telomere length maintenance, usually executed by telomerase, is a prerequisite for an extended or infinite division potential. Nevertheless most telomerase positive normal cells exhibit telomere shortening. This study details the telomerase expression and telomere dynamics in purified tonsil B cell subsets during the germinal center (GC) reaction. Significant telomere lengthening was observed as naive B cells matured to centroblasts and when centroblasts matured further to centrocytes, resulting in an increase in telomere length of about 4 kbp determined by Southern blotting. Immunopurified cell populations were also studied by fluorescence in situ hybridization and flow cytometry (flow-FISH) confirming that the GC B cells exhibited lengthened telomeres. These data were further verified in unpurified tonsil cells by combining flow-FISH and immunophenotyping using selected surface markers. Centroblasts expressed high levels of telomerase activity, which was increased in centrocytes, whereas resting naive, activated naive and memory B cells were telomerase activity negative. Expression levels of the catalytic subunit (hTERT) RNA paralleled the telomerase activity levels. The unique telomere elongation in GC B cells permits extensive proliferation during the GC reaction and provides the memory cells with a substantial increase in division potential. Understanding the telomere biology of GC cells is important in defining requirements for telomere elongation in vivo, with implications for the normal immune system as well as for lymphomas, and could provide insights into how the division potential of cells can be manipulated in vitro.
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| 5. |
- Remes, K, et al.
(författare)
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Telomere length and telomerase activity in malignant lymphomas at diagnosis and relapse
- 2000
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 82:3, s. 601-607
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Tidskriftsartikel (refereegranskat)abstract
- Telomere length maintenance, in the vast majority of cases executed by telomerase, is a prerequisite for long-term proliferation. Most malignant tumours, including lymphomas, are telomerase-positive and this activity is a potential target for future therapeutic interventions since inhibition of telomerase has been shown to result in telomere shortening and cell death in vitro. One prerequisite for the suitability of anti-telomerase drugs in treating cancer is that tumours exhibit shortened telomeres compared to telomerase-positive stem cells. A scenario is envisioned where the tumour burden is reduced using conventional therapy whereafter remaining tumour cells are treated with telomerase inhibitors. In evaluating the realism of such an approach it is essential to know the effects on telomere status by traditional therapeutic regimens. We have studied the telomere lengths in 47 diagnostic lymphomas and a significant telomere shortening was observed compared to benign lymphoid tissues. In addition, telomere length and telomerase activity were studied in consecutive samples from patients with relapsing non-Hodgkin's lymphomas. Shortened, unchanged and elongated telomere lengths were observed in the relapse samples. The telomere length alterations found in the relapsing lymphomas appeared to be independent of telomerase and rather represented clonal selection random at the telomere length level. These data indicate that anti-telomerase therapy would be suitable in only a fraction of malignant lymphomas.
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| 6. |
- Roos, Fredrik, et al.
(författare)
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Distribution System Component Failure Rates and Repair Times - An Overview
- 2004
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Konferensbidrag (refereegranskat)abstract
- This paper presents the results of a literature search for publications containing failure rates and repair times, based on operational experience, for distribution system components that are critical to the reliability of a distribution system. Furthermore, component failure rates found are compared with the conclusions drawn from a previously conducted literature search.
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| 7. |
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| 8. |
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| 9. |
- Roos, Fredrik, et al.
(författare)
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Towards a design and optimization methodology for automotive mechatronics
- 2004
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Konferensbidrag (refereegranskat)abstract
- The number of mechatronic sub-systems in road vehicles is growing fast. Auxiliary systems that traditionally have been driven by the combustion engine via, for instance, gears, belts or hydraulics are being replaced with electric systems. This development is primarily driven by new and improved functionality, but it is also necessary for the transition to electric and hybrid-electric drive trains. A mechatronic sub-system can be very complex to design and especially to optimize, mainly due to the multi domain characteristics of mechatronics. Usually, in traditional methodologies for mechatronic design, the mechanical structure is determined separate from the controller and also from the electric motor design. To improve the results from the mechatronic development process, a more holistic approach is necessary. The foreseen very large production volumes of mechatronic actuation modules for the automotive industry enable such a holistic approach, where all constituent components can be designed and optimized in one common process. The problem that is being approached in this research is delimited to a methodology for conceptual design and optimization of mechatronic actuation modules. Such modules will be the low level corner stones to achieve advanced functionality such as vehicle stability control and collision avoidance. The goal with the methodology is to capture all relevant system design parameters and properties, from all involved engineering domains, in one single evaluation and optimization process. Some previous work has been done in this area, and many different research groups are working on new methods for mechatronics design. Most of the work is however concentrated on design of system dynamics from a control perspective, i.e. optimization of a system’s dynamic performance. The goal with this research project is to find methods that combine the structure design (statics & dynamics) with the controller design (dynamics). Further, the goal is to derive optimization methods that can find the most optimal system configuration and parameter set with respect to both static and dynamic criteria.
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