| 1. |
- Rozenblum, E, et al.
(författare)
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A genomic map of a 6-Mb region at 13q21-q22 implicated in cancer development: identification and characterization of candidate genes
- 2002
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 1432-1203 .- 0340-6717. ; 110:2, s. 111-121
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal region 13q21-q22 harbors a putative breast cancer susceptibility gene and has been implicated as a common site for somatic deletions in a variety of malignant tumors. We have built a complete physical clone contig for a region between D13S1308 and AFM220YE9 based on 18 yeast artificial chromosome and 81 bacterial artificial chromosome (BAC) clones linked together by 22 genetic markers and 61 other sequence tagged sites. Combining data from 47 sequenced BACs (as of June 2001), we have assembled in silico an integrated 5.7-Mb genomic map with 90% sequence coverage. This area contains eight known genes, two hypothetical proteins, 24 additional Unigene clusters, and approximately 100 predicted genes and exons. We have determined the cDNA and genomic sequence, and tissue expression profiles for the KIAA1008 protein (homologous to the yeast mitotic control protein dis3+), KLF12 (AP-2 repressor), progesterone induced blocking factor 1, zinc finger transcription factor KLF5, and LIM domain only-7, and for the hypothetical proteins FLJ22624 and FLJ21869. Mutation screening of the five known genes in 19 breast cancer families has revealed numerous polymorphisms, but no deleterious mutations. These data provide a basis and resources for further analyses of this chromosomal region in the development of cancer.
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| 2. |
- Kainu, T, et al.
(författare)
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Somatic deletions in hereditary breast cancers implicate 13q21 as a putative novel breast cancer susceptibility locus
- 2000
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Ingår i: Proceedings of the National Academy of Sciences. - 1091-6490. ; 97:17, s. 9603-9608
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Tidskriftsartikel (refereegranskat)abstract
- A significant proportion of familial breast cancers cannot be explained by mutations in the BRCA1 or BRCA2 genes. We applied a strategy to identify predisposition loci for breast cancer by using mathematical models to identify early somatic genetic deletions in tumor tissues followed by targeted linkage analysis. Comparative genomic hybridization was used to study 61 breast tumors from 37 breast cancer families with no identified BRCA1 or BRCA2 mutations. Branching and phylogenetic tree models predicted that loss of 13q was one of the earliest genetic events in hereditary cancers. In a Swedish family with five breast cancer cases, all analyzed tumors showed distinct 13q deletions, with the minimal region of loss at 13q21-q22. Genotyping revealed segregation of a shared 13q21 germ-line haplotype in the family. Targeted linkage analysis was carried out in a set of 77 Finnish, Icelandic, and Swedish breast cancer families with no detected BRCA1 and BRCA2 mutations. A maximum parametric two-point logarithm of odds score of 2.76 was obtained for a marker at 13q21 (D13S1308, theta = 0.10). The multipoint logarithm of odds score under heterogeneity was 3.46. The results were further evaluated by simulation to assess the probability of obtaining significant evidence in favor of linkage by chance as well as to take into account the possible influence of the BRCA2 locus, located at a recombination fraction of 0.25 from the new locus. The simulation substantiated the evidence of linkage at D13S1308 (P < 0.0017). The results warrant studies of this putative breast cancer predisposition locus in other populations.
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| 3. |
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| 4. |
- Tovesson, Fredrik, et al.
(författare)
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233Pa(n, f) cross section up to En=8.5 MeV
- 2004
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474 .- 1873-1554. ; 733:1-2, s. 3-19
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Tidskriftsartikel (refereegranskat)abstract
- The energy dependence of the neutron-induced fission cross section of 233Pa has been measured directly for the first time from the fission threshold up to En=8.5 MeV. This reaction plays an important role in the thorium-uranium fuel cycle, and is thus of interest for the design and modeling of advanced reactor and transmutation facilities. The existing information in the ENDF/B-VI and JENDL-3.3 evaluated nuclear data files differ by a factor of two for the 233Pa(n, f) cross section values and show different fission threshold energies. Our new experimental data give lower cross section values than both evaluations and resolves the question about the threshold energy. In addition to the experimental investigation, also a new theoretical calculation of the reaction cross section has been performed with the statistical model code STATIS, showing a good agreement with the experimental data.
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| 5. |
- Borgehammar, Stephan, et al.
(författare)
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A Monastic Conception of the Liturgical Year
- 2001
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Ingår i: The Liturgy of the Medieval Church. - 158044007X ; , s. 13-44
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The chapter presents the liturgical year, in particular the interpretation(s) of the liturgical year found in sermons and Biblical commentaries from the Benedictine abbey of Admont in the twelfth century.
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| 6. |
- Grimm, T, et al.
(författare)
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Genomic organization and embryonic expression of Suppressor of Fused, a candidate gene for the split-hand/split-foot malformation type 3
- 2001
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Ingår i: FEBS Letters. - 0014-5793 .- 1873-3468. ; 505:1, s. 13-17
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Tidskriftsartikel (refereegranskat)abstract
- The genes for human and mouse Suppressor of Fused (SU(FU)/Su(Fu)) in the Hedgehog signaling pathway were characterized and found to contain 12 exons. Human SU(FU) localized on chromosome 10q24-25 between the markers D10S192 and AFM183XB12. We detected three additional SU(FU) isoforms, two of which have lost their ability to interact with the transcription factor GLI1. Expression analysis using whole mount in situ hybridization revealed strong expression of Su(Fu) in various mouse embryonic tissues. SU(FU) was considered a candidate gene for the split-hand/split-foot malformation type 3 (SHFM3). However, no alterations in the SU(FU) gene were found in SHFM3 patients.
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| 7. |
- Kintscher, Ulrich, et al.
(författare)
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PPARalpha inhibits TGF-beta-induced beta5 integrin transcription in vascular smooth muscle cells by interacting with Smad4
- 2002
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 91:11, s. e35-e44
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Tidskriftsartikel (refereegranskat)abstract
- Integrins play an important role in vascular smooth muscle cell (VSMC) migration, a crucial event in the development of restenosis and atherosclerosis. Transforming growth factor-beta (TGF-beta) is highly expressed in restenotic and atherosclerotic lesions, and known to induce integrin expression. Peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily, regulates gene expression in a variety of vascular cells. We investigated the effects of PPARalpha ligands on TGF-beta-induced beta3 and beta5 integrin expression and potential interaction between PPARalpha and TGF-beta signaling. PPARalpha ligands WY-14643 (100 micromol/L) and 5,8,11,14-eicosatetranoic acid (ETYA, 50 micromol/L) inhibited TGF-beta-induced beta5 integrin protein expression by 72+/-6.8% and 73+/-7.1%, respectively (both P<0.05). TGF-beta-stimulated beta3 integrin expression was not affected by PPARalpha ligands. Both PPARalpha ligands also suppressed TGF-beta-induced beta5 integrin mRNA levels. PPARalpha ligands inhibited TGF-beta-inducible transcription of beta5 integrin by an interaction with a TGF-beta response element between nucleotides -63 and -44, which contains a Sp1/Sp3 transcription factor binding site. Nuclear complexes binding to the TGF-beta response region contained Sp1/Sp3 and TGF-beta-regulated Smad 2, 3, and 4 transcription factors. TGF-beta-stimulated Sp1/Smad4 nuclear complex formation was inhibited by WY-14643 and ETYA with a parallel induction of PPARalpha/Smad4 interactions. However, in vitro pull-down experiments failed to demonstrate direct binding between PPARalpha/Smad4. Both PPARalpha ligands blocked PDGF-directed migration of TGF-beta-pretreated VSMCs, a process mediated, in part, by beta5 integrins. The present study demonstrates that PPARalpha activators inhibit TGF-beta-induced beta5 integrin transcription in VSMCs through a novel indirect interaction between ligand-activated PPARalpha and the TGF-beta-regulated Smad4 transcription factors.
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| 8. |
- Prokofiev, A, et al.
(författare)
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A New Neutron Facility for Single-Event Effect Testing
- 2004
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Ingår i: Proceedings of the 6th International Workshop on Radiation Effects on Semiconductor Devices for Space Application. ; , s. 160-162
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Tovesson, Fredrik, et al.
(författare)
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Neutron-induced fission cross section of 233Pa between 1.0 and 3.0 MeV
- 2002
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 88:6, s. 062502-
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Tidskriftsartikel (refereegranskat)abstract
- The energy dependent neutron-induced fission cross section of 233Pa has for the first time been measured directly with monoenergetic neutrons. This nuclide is an important intermediary in a thorium based fuel cycle, and its fission cross section is a key parameter in the modeling of future advanced fuel and reactor concepts. A first experiment resulted in four cross section values between 1.0 and 3.0 MeV, establishing a fission threshold in excess of 1 MeV. Significant discrepancies were found with a previous indirect experimental determination and with model estimates.
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| 10. |
- Tovesson, Fredrik, et al.
(författare)
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The Pa-233 fission cross section
- 2002
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Ingår i: Journal of Nuclear Science and Technology. - : Informa UK Limited. - 0022-3131 .- 1881-1248. ; 39:Supplement 2, s. 210-213
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Tidskriftsartikel (refereegranskat)abstract
- The energy dependent neutron-induced fission cross section of 233Pa has for the first time been measured directly with mono-energetic neutrons. This isotope is produced in the thorium fuel cycle and serves as an intermediate step between the 232Th source material and the 233U fuel material. Four neutron energies between 1.0 and 3.0 MeV have been measured in a first campaign. Some preliminary results are presented and compared to literature.
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