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| 12. |
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| 13. |
- Clendenning, M, et al.
(författare)
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A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome
- 2008
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 45:6, s. 340-345
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Tidskriftsartikel (refereegranskat)abstract
- Background: When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within PMS2 has been limited (<2% of all identified mutations), yet the immunohistochemical analysis of tumour samples indicates that approximately 5% of Lynch syndrome cases are caused by PMS2. This disparity is primarily due to complications in the study of this gene caused by interference from pseudogene sequences. Methods: Using a recently developed method for detecting PMS2 specific mutations, we have screened 99 patients who are likely candidates for PMS2 mutations based on immunohistochemical analysis. Results: We have identified a frequently occurring frame-shift mutation (c.736_741del 6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in PMS2, n = 61). These individuals all display the rare allele (population frequency <0.05) at a single nucleotide polymorphism (SNP) in exon 11, and have been shown to possess a short common haplotype, allowing us to calculate that the mutation arose around 1625 years ago (65 generations; 95% confidence interval 22 to 120). Conclusion: Ancestral analysis indicates that this mutation is enriched in individuals with British and Swedish ancestry. We estimate that there are >10 000 carriers of this mutation in the USA alone. The identification of both the mutation and the common haplotype in one Swedish control sample (n = 225), along with evidence that Lynch syndrome associated cancers are rarer than expected in the probands' families, would suggest that this is a prevalent mutation with reduced penetrance.
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| 14. |
- Kuldkepp, Matias, et al.
(författare)
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Motional Stark effect diagnostic pilot experiment for MAST
- 2006
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 77:10, s. 10E905-
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Tidskriftsartikel (refereegranskat)abstract
- Exploiting the motional Stark effect (MSE) in the low magnetic fields of spherical tokamaks such as MAST is complicated by the Doppler smearing of the relatively closely spaced Stark components. Extensive modeling of MSE spectra and the subsequent polarized fraction (similar to 20%) of spectrally filtered light and signal to noice ratios have been performed taking account of real experimental conditions including neutral beam parameters, port sizes, optical losses, filter characteristics, etc. A design is selected which uses high throughput interference filters (0.1 nm bandpass ) for separation of the spectral components. An accuracy of similar to 0.5 degrees S compared with typically 15 degrees is estimated for field angle measurements. The design allows for early implementation, starting with a pilot two chord system, and for an economic expansion to a multiplicity of chords. Matching the Doppler shifted D-alpha from the beam neutrals will be accomplished by a combination of filter selection and fine-tuning of the beam voltage. Avoiding filter tuning in the design greatly simplifies the diagnostic. Calibration results of the diagnostic support the calculations.
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| 15. |
- Ingesson, L. C., et al.
(författare)
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Progress on common aspects of the EU-supplied ITER diagnostics and prediction of diagnostic performance
- 2006
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 77:10, s. 10F502-
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Tidskriftsartikel (refereegranskat)abstract
- The European Union will supply a number of diagnostics for ITER. Significant progress has been made on the design and integration of these diagnostics. Specific topics, in common for several of the diagnostics, discussed are port-plug integration, simplification of labyrinths against neutron streaming, and design measures to protect and to be able to replace sensitive optical components. Performance analysis to predict the likely capability of the diagnostics to meet the ITER measurement requirements will be an important aspect of the design process. The interpretation of the measurement requirements, specifically of spatial resolution in the case of indirect measurements, is discussed on the basis of two examples, and methods of performance analysis are compared.
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| 16. |
- Klyubin, Igor, et al.
(författare)
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Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization.
- 2008
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Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 28:16, s. 4231-7
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Tidskriftsartikel (refereegranskat)abstract
- The current development of immunotherapy for Alzheimer's disease is based on the assumption that human-derived amyloid beta protein (Abeta) can be targeted in a similar manner to animal cell-derived or synthetic Abeta. Because the structure of Abeta depends on its source and the presence of cofactors, it is of great interest to determine whether human-derived oligomeric Abeta species impair brain function and, if so, whether or not their disruptive effects can be prevented using antibodies. We report that untreated ex vivo human CSF that contains Abeta dimers rapidly inhibits hippocampal long-term potentiation in vivo and that acute systemic infusion of an anti-Abeta monoclonal antibody can prevent this disruption of synaptic plasticity. Abeta monomer isolated from human CSF did not affect long-term potentiation. These results strongly support a strategy of passive immunization against soluble Abeta oligomers in early Alzheimer's disease.
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| 17. |
- Walsh, Nicolas E., et al.
(författare)
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Standards of care for acute and chronic musculoskeletal pain: The bone and joint decade (2000-2010)
- 2008
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Ingår i: Archives of Physical Medicine and Rehabilitation. - : Elsevier BV. - 0003-9993. ; 89:9, s. 1830-1845
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Tidskriftsartikel (refereegranskat)abstract
- Musculoskeletal conditions often manifest with the onset of pain and the resulting physical limitations. Musculoskeletal pain is almost inevitable in in individual's lifetime. It is one of the most common reasons for self-medication and entry into the health care system. Musculoskeletal pain affects in 4 adults and is the Most commons Source of serious long-term pain and physical disability. The Monumental impact Of musculoskeletal conditions is now recognized by the United Nations, the World Health Organization, World Bank, and numerous governments throughout the World through Support of the Bone and Joint Decade 2000 to 2010 initiative. Individuals With musculoskeletal pain concerns are regularly ignored. their complaints often Misunderstood by health care providers, and accordingly they do not receive timely or effective treatment. The standards of care in this document are designed to provide generic guidelines for appropriate care of people with acute or chronic musculoskeletal pain, This document was developed over a 4-year period using Multiple international meetings and a Task Force of the Bone and Joint Decade for developing international standards for the care of acute and chronic musculoskeletal pain. The final document is a product of the World Health Organization Collaborating Centre for Evidence-Based Health Care ill Musculoskeletal Disorders.
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| 19. |
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| 20. |
- Sun, Jielin, et al.
(författare)
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Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12
- 2008
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Ingår i: Nature Genetics. - London : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 40:10, s. 1153-1155
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, 26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 10-9 for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP.
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