| 1. |
- Abazov, V. M., et al.
(author)
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The upgraded DO detector
- 2006
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
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Journal article (peer-reviewed)abstract
- The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
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| 2. |
- Abazov, V. M., et al.
(author)
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Measurement of the isolated photon cross section in p(p)over-bar collisions at root s=1.96 TeV
- 2006
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In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 639:3-4, s. 151-158
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Journal article (peer-reviewed)abstract
- The cross section for the inclusive production of isolated photons has been measured in p (p) over bar collisions at root s = 1.96 TeV with the DO detector at the Fermilab Tevatron Collider. The photons span transverse momenta 23 to 300 GeV and have pseudorapidity vertical bar n vertical bar < 0.9. The cross section is compared with the results from two next-to-leading order perturbative QCD calculations. The theoretical predictions agree with the measurement within uncertainties.
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| 3. |
- Friedman, James S., et al.
(author)
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Mutations in a BTB-Kelch Protein, KLHL7, Cause Autosomal-Dominant Retinitis Pigmentosa
- 2009
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 84:6, s. 792-800
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Journal article (peer-reviewed)abstract
- Retinitis pigmentosa (RP) refers to a genetically heterogeneous group of progressive neurodegenerative diseases that result in dysfunction and/or death of rod and cone photoreceptors in the retina. So far, 18 genes have been identified for autosomal-dominant (ad) RP. Here, we describe an adRP locus (RP42) at chromosome 7p15 through linkage analysis in a six-generation Scandinavian family and identify a disease-causing mutation, c.449G -> A (p.S150N), in exon 6 of the KLHL7 gene. Mutation screening of KLHL7 in 502 retinopathy probands has revealed three different missense mutations in six independent families. KLHL7 is widely expressed, including expression in rod photoreceptors, and encodes a 75 kDa protein of the BTB-Kelch Subfamily within the BTB superfamily. BTB-Kelch proteins have been implicated in ubiquitination through Cullin E3 ligases. Notably, all three putative disease-causing KLHL7 mutations are within a conserved BACK domain; homology modeling suggests that mutant amino acid side chains can potentially fill the cleft between two helices, thereby affecting the ubiquitination complexes. Mutations in an identical region of another BTB-Kelch protein, gigaxonin, have previously been associated with giant axonal neuropathy. Our studies suggest an additional role of the ubiquitin-proteasome protein-degradation pathway in maintaining neuronal health and in disease.
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| 4. |
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| 5. |
- Holm, C, et al.
(author)
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Phosphorylation of the oestrogen receptor alpha at serine 305 and prediction of tamoxifen resistance in breast cancer
- 2009
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In: JOURNAL OF PATHOLOGY. - : Wiley. - 0022-3417 .- 1096-9896. ; 217:3, s. 372-379
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Journal article (peer-reviewed)abstract
- Phosphorylation of oestrogen receptor a at serine 305 (ER alpha S305-P) induces tamoxifen resistance in experimental studies, but does not influence response to other endocrine agents, such as fulvestrant. We evaluated ER alpha S305-P using immunohistochemistry in 377 breast carcinomas from premenopausal participants of a randomized trial (n = 248) and patients with advanced disease (n = 129). Among the premenopausal patients, adjuvant tamoxifen improved recurrence-free survival (RFS) for ER alpha S305-P-negative tumours (multivariate HR = 0.53, 95% CI 0.32-0.86, p = 0.010), but not for ER alpha S305-P-positive tumours (multivariate HR = 1.01, 95% CI 0.33-3.05, p = 0.99) (interaction p = 0.131). Notably, ER alpha S305-P was not significantly associated with RFS in patients not treated with tamoxifen (multivariate HR = 0.64, 95% CI 0.30-1.37, p = 0.248), indicating that ER alpha S305-P is a marker for treatment outcome rather than tumour progression. Given the direct experimental link between ER alpha S305-P and tamoxifen resistance and these first clinical data suggesting that premenopausal patients with ER alpha S305-P-positive breast cancer are resistant to adjuvant tamoxifen, further research is encouraged to study whether alternative endocrine treatment should be considered for this subgroup.
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| 6. |
- Strandberg, Linn S
(author)
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Ro52 antibodies and susceptibility genes in congenital heart block
- 2007
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Doctoral thesis (other academic/artistic)abstract
- Congenital heart block (CHB) develops in fetuses of Ro/SSA and La/SSB positive women. During pregnancy, the autoantibodies cross the placenta and affect the fetus in which a potentially lethal atrioventricular (AV) block may develop. This thesis is aimed at identifying clinically useful maternal serologic markers predictive of risk for CHB, and to define genes linked to susceptibility in the child. Ro52-p200 antibodies, binding amino acid 200-239 of the Ro52 protein, was recently suggested by our group as a marker for high risk pregnancies. Performing a multinational study we now show that p200 antibodies are highly relevant as a second step analysis in Ro52-positive pregnancies, and increase the positive predictive value for fetal cardiac involvement. The incidence of CHB in Ro/La positive women is 1-2%. This risk is only increased to 20% in subsequent pregnancies despite persisting antibodies, indicating that there are other factors involved in disease susceptibility than antibody specificity alone. Ro/La antibody levels and Ro52 subclass profiles were investigated longitudinally through pregnancies and revealed no significant differences between affected and healthy pregnancy outcomes. There were no significant decreases or peaks in antibody levels corresponding to or preceding the time point when CHB is usually detected. We therefore investigated differences in fetal susceptibility to CHB. Fetal genetic factors in susceptibility to CHB have been suggested, but not previously investigated experimentally, To investigate MHC and non-MHC associations of the disease, an immunization model of CHB was established in rat. Analysis of MHC and non-MHC genetic influences using congenic rat strains and an F2 cross revealed significant associations with MHC encoded genes. Maternal generation of pathogenic antibody specificity was linked to a specific MHC haplotype, whereas fetal susceptibility to development of CHB was linked to a separate MHC haplotype in the fetus. Patterns of inheritance also indicated a possible epigenetic influence in susceptibility to CHB. Our data suggest complex genetic prerequisites for susceptibility, and explain why simple associations with MHC genes have not been observed in human studies of CHB. The cellular function of the Ro52 autoantigen was also investigated. We show that Ro52 is an E3 ubiquitin ligase and using a panel of Ro52 monoclonal antibodies which was generated, we show that R52 locates predominantly to the cytoplasm. Stimulation of cells with the systemic autoimmune-related cytokine IFN-alpha induced translocation of Ro52 from the cytoplasm to the nucleus, which preceded apoptosis of the cells. In summary, we identify Ro52-p200 antibodies as a clinically useful marker for risk of CHB and show that fetal susceptibility to these pathogenic autoantibodies depend on fetal MHC-encoded genes. We also demonstrate that Ro52 is an E3 ligase, and that cytokines involved in systemic autoimmunity regulate the cellular localization of the Ro52 autoantigen.
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