| 1. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 2. |
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| 3. |
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| 4. |
- Pfohl, J., et al.
(författare)
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Highly deformed rotational structures in 136Pm
- 2000
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Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 62:3, s. 313041-313045
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Tidskriftsartikel (refereegranskat)abstract
- Four highly deformed structures in the odd-odd nucleus 13661Pm75 were observed via the 105Pd(35Cl,2p2n) reaction at 180 and 173 MeV using the GAMMASPHERE γ-ray spectrometer and the Microball charged-particle detector array. Quadrupole moment measurements were performed on all of the bands. In contrast to lighter odd-Ζ Pm and Pr nuclei, bands based on the g9/2[404]9/2 proton orbital were not observed. Instead, the four observed sequences are assigned as a coupling of an i13/2 neutron with the low-Ω h11/2 and mixed d5/2g7/2 orbitals. Comparisons with neighboring highly deformed structures are discussed and cranked Nilsson-Strutinsky calculations for 136Pm are presented.
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| 5. |
- Priori, Silvia G., et al.
(författare)
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Task Force on Sudden Cardiac Death, European Society of Cardiology
- 2002
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 4:1, s. 3-18
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Tidskriftsartikel (refereegranskat)abstract
- The European Society of Cardiology has convened a Task Force on Sudden Cardiac Death in order to provide a comprehensive, educational document on this important topic. The main document has been published in the European Heart Journal in August 2001[1]. The Task Force has now summarized the most important clinical issues on sudden cardiac death and provided tables with recommendations for risk stratification and for prophylaxis of sudden cardiac death. The present recommendations are specifically intended to encourage the development and revision of national guidelines on prevention of sudden cardiac death. The common challenge for cardiologists, physicians of other medical specialties and health professionals throughout Europe is to realize the potential for sudden cardiac death prevention and to contribute to public health efforts to reduce its burden.
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| 6. |
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| 7. |
- Agostoni, Angelo, et al.
(författare)
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Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond
- 2004
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 114:3 Suppl, s. 51-131
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.
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| 8. |
- Astuto, Lisa M., et al.
(författare)
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Genetic heterogeneity of Usher syndrome : analysis of 151 families with Usher type 1
- 2000
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 67:6, s. 1569-1574
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A-USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher I. Of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USH1F, on chromosome 10. A HOMOG chi(2)((1)) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region.
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| 9. |
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| 10. |
- Kamali, A, et al.
(författare)
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Syndromic management of sexually-transmitted infections and behaviour change interventions on transmission of HIV-1 in rural Uganda : a community randomised trial.
- 2003
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 361:9358, s. 645-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Treatment of sexually-transmitted infections (STIs) and behavioural interventions are the main methods to prevent HIV in developing countries. We aimed to assess the effect of these interventions on incidence of HIV-1 and other sexually-transmitted infections. METHODS: We randomly allocated all adults living in 18 communities in rural Uganda to receive behavioural interventions alone (group A), behavioural and STI interventions (group B), or routine government health services and community development activities (group C). The primary outcome was HIV-1 incidence. Secondary outcomes were incidence of herpes simplex virus type 2 (HSV2) and active syphilis and prevalence of gonorrhoea, chlamydia, reported genital ulcers, reported genital discharge, and markers of behavioural change. Analysis was per protocol. FINDINGS: Compared with group C, the incidence rate ratio of HIV-1 was 0.94 (0.60-1.45, p=0.72) in group A and 1.00 (0.63-1.58, p=0.98) in group B, and the prevalence ratio of use of condoms with last casual partner was 1.12 (95% CI 0.99-1.25) in group A and 1.27 (1.02-1.56) in group B. Incidence of HSV2 was lower in group A than in group C (incidence rate ratio 0.65, 0.53-0.80) and incidence of active syphilis for high rapid plasma reagent test titre and prevalence of gonorrhoea were both lower in group B than in group C (active syphilis incidence rate ratio, 0.52, 0.27-0.98; gonorrhoea prevalence ratio, 0.25, 0.10-0.64). INTERPRETATION: The interventions we used were insufficient to reduce HIV-1 incidence in rural Uganda, where secular changes are occurring. More effective STI and behavioural interventions need to be developed for HIV control in mature epidemics.
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| 11. |
- Rioux, John D., et al.
(författare)
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Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease
- 2001
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 29:2, s. 223-228
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Tidskriftsartikel (refereegranskat)abstract
- Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease1. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10−4). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P<2×10−7) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence—each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.
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| 12. |
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| 13. |
- Balbach, John J., et al.
(författare)
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Supramolecular Structure in Full-Length Alzheimer's β-Amyloid Fibrils: Evidence for a Parallel β-Sheet Organization from Solid-State Nuclear Magnetic Resonance
- 2002
-
Ingår i: Biophysical Journal. - 0006-3495 .- 1542-0086. ; 83:2, s. 1205-1216
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Tidskriftsartikel (refereegranskat)abstract
- We report constraints on the supramolecular structure of amyloid fibrils formed by the 40-residue β-amyloid peptide associated with Alzheimer's disease (Aβ1–40) obtained from solid-state nuclear magnetic resonance (NMR) measurements of intermolecular dipole-dipole couplings between 13C labels at 11 carbon sites in residues 2 through 39. The measurements are carried out under magic-angle spinning conditions, using the constant-time finite-pulse radiofrequency-driven recoupling (fpRFDR-CT) technique. We also present one-dimensional 13C magic-angle spinning NMR spectra of the labeled Aβ1–40 samples. The fpRFDR-CT data reveal nearest-neighbor intermolecular distances of 4.8 ± 0.5 Å for carbon sites from residues 12 through 39, indicating a parallel alignment of neighboring peptide chains in the predominantly β-sheet structure of the amyloid fibrils. The one-dimensional NMR spectra indicate structural order at these sites. The fpRFDR-CT data and NMR spectra also indicate structural disorder in the N-terminal segment of Aβ1–40, including the first nine residues. These results place strong constraints on any molecular-level structural model for full-length β-amyloid fibrils.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- De Koning, H. J., et al.
(författare)
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Large-scale randomized prostate cancer screening trials : Program performances in the european randomized screening for prostate cancer trial and the prostate, lung, colorectal and ovary cancer trial
- 2002
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 97:2, s. 237-244
-
Tidskriftsartikel (refereegranskat)abstract
- Two large-scale randomized screening trials, the Prostate, Lung, Colorectal and Ovary (PLCO) cancer trial in the USA and the European Randomized Screening for Prostate Cancer (ERSPC) trial in Europe are currently under way, aimed at assessing whether screening reduces prostate cancer mortality. Up to the end of 1998, 102,691 men have been randomized to the intervention arm and 115,322 to the control arm (which represents 83% of the target sample size) from 7 European countries and 10 screening centers in the USA. The principal screening method at all centers is determination of serum prostate-specific antigen (PSA). The PLCO trial and some European centers use also digital rectal examination (DRE) as an ancillary screening test. In the core age group (55-69 years), 3,362 of 32,486 men screened (10%) had a serum PSA concentration of 4 ng/ml or greater, which is I cut-off for biopsy (performed in 84%). An additional 6% was referred for further assessment based on other criteria, with much less efficiency. Differences in PSA by country are largely attributable to the age structure of the study population. The mean age-specific PSA levels are lower in the PLCO trial (1.64 ng/ml [in the age group 55-59 years], 1.80 [60-64 years] and 2.18 [65-69 years) than in the ERSPC trial (1.28-1.71 [55-59], 1.75-2.87 [60-64] and 2.48-3.06 [65-69 years]). Detection rates at the first screen in the ERSPC trial range from II to 42/1,000 men screened and reflect underlying differences in incidence rates and screening procedures. In centers with consent to randomization design, adherence in the screening arm is 91%, but less than half of the men in the target population are enrolled in the trial. In population-based centers in which men were randomized prior to consent, all eligible subjects are enrolled, but only about two-thirds of the men in the intervention arm undergo screening. Considerable progress has been made in both trials. Enrollment will be completed in 2001. A substantial number of early prostate cancers have been detected. The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy. The trials have the power to show definitive results in 2005-2008.
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| 18. |
- d'Orgeville, Céline, et al.
(författare)
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Preliminary results of the 2001-2002 Gemini sodium monitoring campaign at Cerro Tololo, Chile
- 2003
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Ingår i: Adaptive Optical System Technologies II. Edited by Wizinowich, Peter L.; Bonaccini, Domenico. Proceedings of the SPIE, Volume 4839, pp. 492-503 (2003).. ; 4839:Part 2, s. 492-503
-
Konferensbidrag (refereegranskat)abstract
- In the near future several astronomical observatories in Chile areplanning to use sodium laser guide stars to increase the sky coverageprovided by their adaptive optics facilities. Knowledge of themesospheric sodium layer behavior is crucial to predict the performanceof future laser guide star adaptive optics systems. Whereas the sodiumlayer has been observed quite extensively at several locations, many ofthem in the Northern Hemisphere, very little measurements have been madein Chile. The Gemini Observatory therefore initiated a year-long sodiummonitoring campaign at the Cerro Tololo Inter-American Observatorylocated only a few kilometers away from the Gemini South telescope wherea conventional laser guide star facility will be offered to thecommunity in 2005, soon to be upgraded to a multi-conjugate adaptiveoptics system with five laser guide stars. This paper reports on thelaser-based sodium monitoring experimental set up and data reductiontechniques, and presents some preliminary results on the sodium columndensity and layer altitude variations observed from February 2001 toFebruary 2002. Implications for the Gemini South Adaptive Optics systemexpected performance are presented as well.
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| 19. |
- Erneman, J., et al.
(författare)
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Precipitation reactions caused by nitrogen uptake during service at high temperatures of a niobium stabilised austenitic steel
- 2004
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Ingår i: Acta Materialia. - : Elsevier BV. - 1359-6454 .- 1873-2453. ; 52:14, s. 4337-4350
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Tidskriftsartikel (refereegranskat)abstract
- Precipitation phenomena in type 347 austenitic stainless steels have been investigated after long-term heat treatment and creep in air at 700 and 800 degreesC. Nitrogen uptake was observed during long-term creep testing at 800 degreesC. No such effect was observed at 700 degreesC although times up to about 70,000 h were used. The major phases precipitated after long time exposure at 800 degreesC were primary Nb(C,N), Z-phase, Cr2N and M23C6, while primary Nb(C,N), secondary Nb(C,N) and sigma-phase were the major phases at 700 degreesC. Z-phase precipitated in both intragranular and intergranular form at 800 degreesC. Large precipitates exhibiting a core/rim structure showed a rim of Z-phase surrounding undissolved primary Nb(C,N). The microstructural evolution during creep deformation in air at 800 degreesC was modelled thermodynamically. The model satisfactorily predicts nitrogen uptake and the essential features of the evolution of the microstructure with time. The precipitation sequence could be qualitatively described, although it was not possible to model the formation of all precipitates.
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| 20. |
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| 21. |
- Kanis, John A, et al.
(författare)
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A meta-analysis of prior corticosteroid use and fracture risk.
- 2004
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Ingår i: Journal of bone and mineral research. - 0884-0431 .- 1523-4681. ; 19:6, s. 893-9
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between use of corticosteroids and fracture risk was estimated in a meta-analysis of data from seven cohort studies of approximately 42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD. INTRODUCTION: The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk. MATERIALS AND METHODS: We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patient-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. RESULTS: Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.63-1.71, and for hip fracture 4.42-2.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD. CONCLUSION: We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in case-finding strategies.
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| 22. |
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| 23. |
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| 24. |
- Kinsman, John, et al.
(författare)
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Condom awareness and intended use : gender and religious contrasts among school pupils in rural Masaka, Uganda
- 2001
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Ingår i: AIDS Care. - : Informa UK Limited. - 0954-0121 .- 1360-0451. ; 13:2, s. 215-220
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Tidskriftsartikel (refereegranskat)abstract
- A cross-sectional questionnaire survey examining knowledge, attitudes and intended use of condoms was conducted among 1,821 pupils (mean age = 14.2 years, range = 9--24) from 27 primary and secondary schools in rural south western Uganda. Condom education is not provided in Ugandan schools, but both boys and girls had relatively high overall levels of knowledge, even though boys demonstrated a higher level than girls. This suggests that respondents had successfully obtained reliable information from other sources. Boys and girls had similar and fairly positive attitudes towards condoms, although considerable shyness was expressed, both about discussing condoms with a partner and buying them. Fifty-eight per cent said that they themselves would use a condom if one were available, but girls were far less likely than boys to say so. Roman Catholics (46% of the sample) were less knowledgeable and less positive about condoms than non-Catholics, and the boys in this group, but not the girls, were also much less likely to say they would use one. Possible interventions based on these findings are discussed, and a research agenda for the delivery of assertiveness training to girls is proposed.
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| 25. |
- Kinsman, John, et al.
(författare)
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Evaluation of a comprehensive school-based AIDS education programme in rural Masaka, Uganda
- 2001
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Ingår i: Health Education Research. - : Oxford University Press (OUP). - 0268-1153 .- 1465-3648. ; 16:1, s. 85-100
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Tidskriftsartikel (refereegranskat)abstract
- A 19 activity extracurricular school-based AIDS education programme lasting 1 year was conducted in rural southwestern Uganda using specially trained teachers, and was evaluated using mutually supportive quantitative and qualitative methods. In total, 1274 students from 20 intervention schools and 803 students from 11 control schools completed questionnaires at baseline, and their classes were followed up. In addition, 93 students from five of the intervention schools participated in 12 focus group discussions. The programme had very little effect--seven of the nine key questionnaire variables showed no significant increase in score after the intervention. Data from the focus group discussions suggest that the programme was incompletely implemented, and that key activities such as condoms and the role-play exercises were covered only very superficially. The main reasons for this were a shortage of classroom time, as well as teachers' fear of controversy and the unfamiliar. We conclude that large-scale comprehensive school-based AIDS education programmes in sub-Saharan Africa may be more completely implemented if they are fully incorporated into national curricula and examined as part of life-skills education. This would require teachers to be trained in participatory teaching methods while still at training college.
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| 26. |
- Kinsman, John, et al.
(författare)
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Quantitative process evaluation of a community-based HIV/AIDS behavioural intervention in rural Uganda
- 2002
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Ingår i: Health Education Research. - : Oxford University Press (OUP). - 0268-1153 .- 1465-3648. ; 17:2, s. 253-265
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the implementation of a large community-based HIV/AIDS behavioural intervention in rural Uganda and presents 4 years' worth of quantitative process data. The intervention involved 560 field-based workers (57% male, 76% subsistence farmers, mean age 35 years), supervised by six central staff. Intervention channels included drama and video shows, Community Educators (CEs), as well as leaflet and condom distribution. Activities focused on one or more of 16 key topics. In total, 392 000 attendances (51% female) were recorded--a mean of over 6 for each of the 64 000 target adults--at 81 000 activities, with CEs attracting 71% of the total attendance; 164 000 leaflets and 242 000 condoms were also distributed. The annual cost of the intervention per target individual was approximately US$1.76. Our voluntary workforce experienced an annual attrition rate of 11%, with 'stable' workers more likely to be older, married or opinion leaders in their community than those who dropped out. We calculate that even a significant increase in the proportion of female field workers would have made little difference either to the sex ratio of attendees or to overall attendance. In spite of some initial resistance to the intervention, particularly in relation to condoms, we have demonstrated that people in rural Africa can accept and actively participate in the dissemination of HIV/AIDS prevention messages throughout their own communities.
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| 27. |
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| 28. |
- Olofsson, Henrik, 1972, et al.
(författare)
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Odin water mapping in the Orion KL region
- 2003
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L47-L54
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Tidskriftsartikel (refereegranskat)abstract
- New results from water mapping observations of the Orion KL region using the submm/mm wave satellite Odin (2.1\arcmin beam size at 557 GHz), are presented. The ortho-H2O \jkktrans{1}{1}{0}{1}{0}{1} ground state transition was observed in a 7arcminx 7arcmin rectangular grid with a spacing of 1\arcmin, while the same line of H218O was measured in two positions, Orion KL itself and 2\arcmin south of Orion KL. In the main water species, the KL molecular outflow is largely resolved from the ambient cloud and it is found to have an extension of 60\arcsec-110\arcsec. The H2O outflow profile exhibits a rather striking absorption-like asymmetry at the line centre. Self-absorption in the near (or ``blue'') part of the outflow (and possibly in foreground quiescent halo gas) is tentatively suggested to play a role here. We argue that the dominant part of the KL H218O outflow emission emanates from the compact (size ~ 15\arcsec) low-velocity flow and here estimate an H2O abundance of circa 10-5 compared to all H2 in the flow - an order of magnitude below earlier estimates of the H2O abundance in the shocked gas of the high-velocity flow. The narrow ambient cloud lines show weak velocity trends, both in the N-S and E-W directions. H218O is detected for the first time in the southern position at a level of ~ 0.15 K and we here estimate an H2O abundance of (1-8) x 10-8. Odin is a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes), and the Centre National d'Études Spatiales (CNES, France). The Swedish Space Corporation (SSC) was the industrial prime contractor and is also responsible for the satellite operation.
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| 29. |
- Schwind, M., et al.
(författare)
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sigma-phase precipitation in stabilized austenitic stainless steels
- 2000
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Ingår i: Acta Materialia. - 1359-6454 .- 1873-2453. ; 48:10, s. 2473-2481
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Tidskriftsartikel (refereegranskat)abstract
- Experimental observations of sigma-phase precipitation in two stabilized austenitic stainless steers, AISI 321 and AISI 347, aged up to 80,000 h at temperatures between 500 and 800 degrees C, are compared with the results obtained from a simple model of the process. The model is based on the assumption that diffusion of alloying elements from inside austenite grains to sigma-phase particles at grain boundaries limits the rate of formation, and this is supported by the presence of zones depleted in chromium at grain boundaries revealed by TEM/EDS. The full multicomponent thermodynamic behaviour of the system is taken into account using the DICTRA software and the influence of grain shape is discussed. The predictions of the model are in fair agreement with experimentally estimated Volume fractions of sigma-phase.
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| 30. |
- Simrén, Magnus, 1966, et al.
(författare)
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Quality of life and illness costs in irritable bowel syndrome.
- 2004
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 69:4, s. 254-61
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Tidskriftsartikel (refereegranskat)abstract
- Quality of life is reduced in patients with irritable bowel syndrome, and the costs for this disease are substantial to society. During a meeting in London, UK, the IBiS club reviewed the literature on these subjects. Drawbacks and advantages with existing instruments to assess quality of life and costs were discussed and the clinical and scientific relevance of the current knowledge was assessed. A summary from the meeting is presented in this paper.
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| 31. |
- Algers, John, et al.
(författare)
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Free volume determination of azobenzene-PMMA copolymer by a pulsed low-energy positron lifetime beam with in-situ UV illumination
- 2004
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Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 37:21, s. 8035-8042
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Tidskriftsartikel (refereegranskat)abstract
- The free volume properties of a poly(methyl methacrylate)-azobenzene copolymer were for the first time directly probed by use of a low-energy positron lifetime beam with in-situ excitation capabilities, showing that the free volume cavity size was not appreciably influenced by photoisomerization and thermal isomerization in the temperature range 34-180 degreesC. lsomerization is therefore suggested to occur without any molecular rearrangement of the glassy polymer matrix, which would also account for the lack of any shift to shorter wavelengths for the photoisomerization occurring in a glassy polymer in comparison to a chloroform solution. A decrease in the thermal isomerization rate at room temperature caused by the glassy polymer is explained in terms of a model in which only a fraction of the azobenzene is free to isomerize. The cis-azobenzene was found to be an efficient inhibitor of positronium formation, which enabled measurements of thermal isomerization rates and changes in the steady-state concentration of cis-azobenzene for an illuminated sample as a function of temperature.
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| 32. |
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| 33. |
- Allen, John, et al.
(författare)
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General discussion
- 2003
-
Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 1471-2970. ; 358:1429, s. 217-222
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 34. |
- Andersson, Bert, 1952, et al.
(författare)
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Dose-related effects of metoprolol on heart rate and pharmacokinetics in heart failure.
- 2001
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Ingår i: Journal of cardiac failure. - 1071-9164. ; 7:4, s. 311-7
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Tidskriftsartikel (refereegranskat)abstract
- The pharmacokinetics and pharmacodynamics of immediate-release (IR) metoprolol, 50 mg 3 times daily, were compared with those of different doses of controlled-release/extended-release metoprolol (CR/XL) given once daily.Fifteen patients with chronic heart failure were randomized to a 3-way crossover study to receive metoprolol IR 50 mg 3 times daily, CR/XL 100 mg once daily, and CR/XL 200 mg once daily for 7 days. On the seventh day of each treatment, serial plasma samples were drawn and standardized exercise tests and a 24-hour Holter recording were performed. Metoprolol IR 50 mg produced peak plasma levels comparable to those observed for CR/XL 200 mg (285 v 263 nmol/L). The difference in mean 24-hour heart rate between CR/XL 100 mg and IR 50 mg was 1.0 bpm (95% confidence interval [CI]), -2.9 to 4.9; NS) compared with -3.8 bpm (95% CI, -7.6 to -0.04; P = .048) between CR/XL 200 mg and IR 50 mg. Submaximal exercise heart rate was lower for patients receiving CR/XL 200 mg than those receiving IR 50 mg. No difference in tolerance or exercise performance was observed between treatment regimens.Peak plasma levels produced by metoprolol 200 mg CR/XL were similar to those of 50 mg IR. Metoprolol CR/XL 200 mg was associated with a more pronounced suppression of heart rate than metoprolol IR 50 mg. It is suggested that patients can safely be switched from multiple dosing of metoprolol IR 50 mg to a once-daily dose of metoprolol CR/XL.
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| 35. |
- Antzutkin, Oleg, et al.
(författare)
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Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of β-sheets in Alzheimer's β-amyloid fibrils
- 2000
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 97:24, s. 13045-13050
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Tidskriftsartikel (refereegranskat)abstract
- Senile plaques associated with Alzheimer's disease contain deposits of fibrils formed by 39- to 43-residue β-amyloid peptides with possible neurotoxic effects. X-ray diffraction measurements on oriented fibril bundles have indicated an extended β-sheet structure for Alzheimer's β-amyloid fibrils and other amyloid fibrils, but the supramolecular organization of the β-sheets and other structural details are not well established because of the intrinsically noncrystalline, insoluble nature of amyloid fibrils. Here we report solid-state NMR measurements, using a multiple quantum (MQ) 13C NMR technique, that probe the β-sheet organization in fibrils formed by the full-length, 40-residue β-amyloid peptide (Aβ1-40). Although an antiparallel β-sheet organization often is assumed and is invoked in recent structural models for full-length β-amyloid fibrils, the MQNMR data indicate an in-register, parallel organization. This work provides site-specific, atomic-level structural constraints on full-length β-amyloid fibrils and applies MQNMR to a significant problem in structural biology.
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| 36. |
- Antzutkin, Oleg, et al.
(författare)
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Site-Specific Identification of Non-ß-Strand Conformations in Alzheimer's ß-Amyloid Fibrils by Solid-State NMR
- 2003
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Ingår i: Biophysical Journal. - 0006-3495 .- 1542-0086. ; 84:5, s. 3326-3335
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Tidskriftsartikel (refereegranskat)abstract
- The most well-established structural feature of amyloid fibrils is the cross-ß motif, an extended ß-sheet structure formed by ß-strands oriented perpendicular to the long fibril axis. Direct experimental identification of non-ß-strand conformations in amyloid fibrils has not been reported previously. Here we report the results of solid-state NMR measurements on amyloid fibrils formed by the 40-residue ß-amyloid peptide associated with Alzheimer's disease (Aß1-40), prepared synthetically with pairs of 13C labels at consecutive backbone carbonyl sites. The measurements probe the peptide backbone conformation in residues 24-30, a segment where a non-ß-strand conformation has been suggested by earlier sequence analysis, cross-linking experiments, and molecular modeling. Data obtained with the fpRFDR-CT, DQCSA, and 2D MAS exchange solid-state NMR techniques, which provide independent constraints on the and backbone torsion angles between the labeled carbonyl sites, indicate non-ß-strand conformations at G25, S26, and G29. These results represent the first site-specific identification and characterization of non-ß-strand peptide conformations in an amyloid fibril
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| 37. |
- Antzutkin, Oleg, et al.
(författare)
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Supramolecular structural constraints on Alzheimer's β-amyloid fibrils from electron microscopy and solid-state nuclear magnetic resonance
- 2002
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 41:51, s. 15436-15450
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Tidskriftsartikel (refereegranskat)abstract
- We describe electron microscopy (EM), scanning transmission electron microscopy (STEM), and solid-state nuclear magnetic resonance (NMR) measurements on amyloid fibrils formed by the 42-residue β-amyloid peptide associated with Alzheimer's disease (Aβ1-42) and by residues 10-35 of the full-length peptide (Aβ10-35). These measurements place constraints on the supramolecular structure of the amyloid fibrils, especially the type of β-sheets present in the characteristic amyloid cross-β structural motif and the assembly of these β-sheets into a fibril. EM images of negatively stained Aβ10-35 fibrils and measurements of fibril mass per length (MPL) by STEM show a strong dependence of fibril morphology and MPL on pH. Aβ10-35 fibrils formed at pH 3.7 are single "protofilaments" with MPL equal to twice the value expected for a single cross-β layer. Aβ10-35 fibrils formed at pH 7.4 are apparently pairs of protofilaments or higher order bundles. EM and STEM data for Aβ1-42 fibrils indicate that protofilaments with MPL equal to twice the value expected for a single cross-β layer are also formed by Aβ1-42 and that these protofilaments exist singly and in pairs at pH 7.4. Solid-state NMR measurements of intermolecular distances in Aβ10-35 fibrils, using multiple-quantum 13C NMR, 13C-13C dipolar recoupling, and 15N-13C dipolar recoupling techniques, support the in-register parallel β-sheet organization previously established by Lynn, Meredith, Botto, and co-workers [Benzinger et al. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 13407-13412; Benzinger et al. (2000) Biochemistry 39, 3491-3499] and show that this β-sheet organization is present at pH 3.7 as well as pH 7.4 despite the differences in fibril morphology and MPL. Solid-state NMR measurements of intermolecular distances in Aβ1-42 fibrils, which represent the first NMR data on Aβ1-42 fibrils, also indicate an in-register parallel β-sheet organization. These results, along with previously reported data on Aβ1-40 fibrils, suggest that the supramolecular structures of Aβ10-35, Aβ1-40, and Aβ1-42 fibrils are quite similar. A schematic structural model of these fibrils, consistent with known experimental EM, STEM, and solid-state NMR data, is presented.
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| 38. |
- Armstrong, Scott A, et al.
(författare)
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FLT3 mutations in childhood acute lymphoblastic leukemia.
- 2004
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 103:9, s. 3544-3546
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Tidskriftsartikel (refereegranskat)abstract
- Activating mutations of the FLT3 receptor tyrosine kinase are common in acute myelogenous leukemia (AML) but are rare in adult acute lymphoblastic leukemia (ALL). We have recently shown that FLT3 is highly expressed and often mutated in ALLs with rearrangement of the mixed lineage leukemia (MLL) gene on chromosome 11q23. Because hyperdiploid ALL samples also show high-level expression of FLT3, we searched for the presence of FLT3 mutations in leukemic blasts from 71 patients with ALL. The data show that approximately 25% (6 of 25) of hyperdiploid ALL samples possess FLT3 mutations, whereas only 1 of 29 TEL/AML1-rearranged samples harbored mutations (P =.04, Fisher exact test). Three mutations are novel in-frame deletions within a 7-amino acid region of the receptor juxtamembrane domain. Finally, 3 samples from patients whose disease would relapse harbored FLT3 mutations. These data suggest that patients with hyperdiploid or relapsed ALL might be considered candidates for therapy with newly described small-molecule FLT3 inhibitors.
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| 39. |
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| 40. |
- Balbach, John J., et al.
(författare)
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Amyloid Fibril Formation by Aβ16-22, a Seven-Residue Fragment of the Alzheimer's β-Amyloid Peptide, and Structural Characterization by Solid State NMR
- 2000
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 39:45, s. 13748-13759
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Tidskriftsartikel (refereegranskat)abstract
- The seven-residue peptide N-acetyl-Lys-Leu-Val-Phe-Phe-Ala-Glu-NH2, called Aβ16-22 and representing residues 16-22 of the full-length β-amyloid peptide associated with Alzheimer's disease, is shown by electron microscopy to form highly ordered fibrils upon incubation of aqueous solutions. X-ray powder diffraction and optical birefringence measurements confirm that these are amyloid fibrils. The peptide conformation and supramolecular organization in Aβ16-22 fibrils are investigated by solid state 13C NMR measurements. Two-dimensional magic-angle spinning (2D MAS) exchange and constant-time double-quantum-filtered dipolar recoupling (CTDQFD) measurements indicate a β-strand conformation of the peptide backbone at the central phenylalanine. One-dimensional and two-dimensional spectra of selectively and uniformly labeled samples exhibit 13C NMR line widths of <2 ppm, demonstrating that the peptide, including amino acid side chains, has a well-ordered conformation in the fibrils. Two-dimensional 13C-13C chemical shift correlation spectroscopy permits a nearly complete assignment of backbone and side chain 13C NMR signals and indicates that the β-strand conformation extends across the entire hydrophobic segment from Leu17 through Ala21. 13C multiple-quantum (MQ) NMR and 13C/15N rotational echo double-resonance (REDOR) measurements indicate an antiparallel organization of β-sheets in the Aβ16-22 fibrils. These results suggest that the degree of structural order at the molecular level in amyloid fibrils can approach that in peptide or protein crystals, suggest how the supramolecular organization of β-sheets in amyloid fibrils can be dependent on the peptide sequence, and illustrate the utility of solid state NMR measurements as probes of the molecular structure of amyloid fibrils. Aβ16-22 is among the shortest fibril-forming fragments of full-length β-amyloid reported to date, and hence serves as a useful model system for physical studies of amyloid fibril formation.
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Brooks, Andrew J, et al.
(författare)
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The interdomain region of dengue NS5 protein that binds to the viral helicase NS3 contains independently functional importin beta 1 and importin alpha/beta-recognized nuclear localization signals
- 2002
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 277:39, s. 36399-36407
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Tidskriftsartikel (refereegranskat)abstract
- Dengue virus NS5 protein is a multifunctional RNA-dependent RNA polymerase that is essential for virus replication. We have shown previously that the 37- amino acid interdomain spacer sequence (residues (369)X(2)KKX(14)KKKX(11)RKX(3)405) of Dengue2 NS5 contains a functional nuclear localization signal (NLS). In this study, beta-galactosidase fusion proteins carrying point mutations of the positively charged residues or truncations of the interdomain linker region (residues 369-389 or residues 386-405) were analyzed for nuclear import and importin binding activities to show that the N-terminal part of the linker region (residues 369-389, a/bNLS) is critical for nuclear localization and is recognized with high affinity by the conventional NLS-binding importin alpha/beta heterodimeric nuclear import receptor. We also show that the importin beta-binding site (residues 320-368, bNLS) adjacent to the a/bNLS, previously identified by yeast two-hybrid analysis, is functional as an NLS, recognized with high affinity by importin beta, and able to target beta-galactosidase to the nucleus. Intriguingly, the bNLS is highly conserved among Dengue and related flaviviruses, implying a general role for the region and importin beta in the infectious cycle.
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| 45. |
- Carrino, David A, et al.
(författare)
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Age-related changes in the proteoglycans of human skin - Specific cleavage of decorin to yield a major catabolic fragment in adult skin
- 2003
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 278:19, s. 17566-17572
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Tidskriftsartikel (refereegranskat)abstract
- Dramatic changes occur in skin as a function of age, including changes in morphology, physiology, and mechanical properties. Changes in extracellular matrix molecules also occur, and these changes likely contribute to the overall age-related changes in the physical properties of skin. The major proteoglycans detected in extracts of human skin are decorin and versican. In addition, adult human skin contains a truncated form of decorin, whereas fetal skin contains virtually undetectable levels of this truncated decorin. Analysis of this molecule, herein referred to as decorunt, indicates that it is a catabolic fragment of decorin rather than a splice variant. With antibody probes to the core protein, decorunt is found to lack the carboxyl-terminal portion of decorin. Further analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry shows that the carboxyl terminus of decorunt is at Phe(170) of decorin. This result indicates that decorunt represents the amino-terminal 43% of the mature decorin molecule. Such a structure is inconsistent with alternative splicing of decorin and suggests that decorunt is a catabolic fragment of decorin. A neoepitope antiserum, anti-VRKVTF, was generated against the carboxyl terminus of decorunt. This antiserum does not recognize intact decorin in any skin proteoglycan sample tested on immunoblots but recognizes every sample of decorunt tested. The results with anti-VRKVTF confirm the identification of the carboxyl terminus of decorunt. Analysis of collagen binding by surface plasmon resonance indicates that the affinity of decorunt for type I collagen is 100-fold less than that of decorin. This observation correlates with the structural analysis of decorunt, in that it lacks regions of decorin previously shown to be important for interaction with type I collagen. The detection of a catabolic fragment of decorin suggests the existence of a specific catabolic pathway for this proteoglycan. Because of the capacity of decorin to influence collagen fibrillogenesis, catabolism of decorin may have important functional implications with respect to the dermal collagen network.
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| 46. |
- Cho, Eunyoung, et al.
(författare)
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Alcohol intake and colorectal cancer : a pooled analysis of 8 cohort studies
- 2004
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 140:8, s. 603-613
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiologic studies have generally reported positive associations between alcohol consumption and risk for colorectal cancer. However, findings related to specific alcoholic beverages or different anatomic sites in the large bowel have been inconsistent. OBJECTIVE: To examine the relationship of total alcohol intake and intake from specific beverages to the incidence of colorectal cancer and to evaluate whether other potential risk factors modify the association. DESIGN: Pooled analysis of primary data from 8 cohort studies in 5 countries. SETTING: North America and Europe. PARTICIPANTS: 489,979 women and men with no history of cancer other than nonmelanoma skin cancer at baseline. MEASUREMENTS: Alcohol intake was assessed in each study at baseline by using a validated food-frequency questionnaire. RESULTS: During a maximum of 6 to 16 years of follow-up across the studies, 4687 cases of colorectal cancer were documented. In categorical analyses, increased risk for colorectal cancer was limited to persons with an alcohol intake of 30 g/d or greater (approximately > or =2 drinks/d), a consumption level reported by 4% of women and 13% of men. Compared with nondrinkers, the pooled multivariate relative risks were 1.16 (95% CI, 0.99 to 1.36) for persons who consumed 30 to less than 45 g/d and 1.41 (CI, 1.16 to 1.72) for those who consumed 45 g/d or greater. No significant heterogeneity by study or sex was observed. The association was evident for cancer of the proximal colon, distal colon, and rectum. No clear difference in relative risks was found among specific alcoholic beverages. LIMITATIONS: The study included only one measure of alcohol consumption at baseline and could not investigate lifetime alcohol consumption, alcohol consumption at younger ages, or changes in alcohol consumption during follow-up. It also could not examine drinking patterns or duration of alcohol use. CONCLUSIONS: A single determination of alcohol intake correlated with a modest relative elevation in colorectal cancer rate, mainly at the highest levels of alcohol intake.
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| 47. |
- Deedwania, P. C., et al.
(författare)
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Efficacy, safety and tolerability of beta-adrenergic blockade with metoprolol CR/XL in elderly patients with heart failure
- 2004
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Ingår i: Eur Heart J. - : Oxford University Press (OUP). - 0195-668X. ; 25:15, s. 1300-9
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the efficacy and tolerability of beta-blockade in elderly patients with heart failure in the MERIT-HF study. METHODS AND RESULTS: Cox proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). Risk reduction was defined as (1-HR). In patients > or = 65 years total mortality was reduced by 37% (95% CI 17% to 52%; p=0.0008), sudden death by 43% (95% CI 17% to 61%; p=0.0032), and death from worsening heart failure by 61% (95% CI 32% to 77%; p=0.0005). Hospitalisations for worsening heart failure was reduced by 36% (p=0.0006). Elderly patients with severe heart failure (NYHA class III/IV with ejection fraction < 0.25; n=425, and patients above 75 years (n=490) showed similar risk reductions. Metoprolol CR/XL was safe and well tolerated both during initiating therapy and during long-term follow-up. CONCLUSIONS: Metoprolol CR/XL was easily instituted, safe and well tolerated in elderly patients with systolic heart failure. The data suggest that these are the patients in whom treatment will have the greatest impact as shown by number of lives saved and number of hospitalisations avoided. The time has come to overcome the barriers that physicians perceive to beta-blocker treatment, and to provide it to the large number of elderly patients with heart failure in need of this therapy.
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| 48. |
- Du, H., et al.
(författare)
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Microstructural and compositional evolution of compound layers during gaseous nitrocarburizing
- 2000
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Ingår i: Metallurgical and Materials Transactions. A. - : Springer Science and Business Media LLC. - 1073-5623 .- 1543-1940. ; 31:1, s. 195-211
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Tidskriftsartikel (refereegranskat)abstract
- Compound layers developed at 848 K during gaseous nitrocarburizing of iron and iron-carbon specimens were investigated for several combinations of N and C activities imposed at the specimen surface by gas mixtures of NH3, N-2, CO2, and CO. The microstructural evolution of the compound layer was studied by light microscopy and by X-raydiffraction analysis. Composition-depth profiles were determined by electron probe (X-ray) microanalysis. Layer growth kinetics was investigated by layer thickness measurements. The influence Of the N and C activities on the microstructural and compositional evolution and the growth kinetics of the compound layers formed is discussed for the iron substrate. The results indicate that the microstructure is governed by a fast C and a slow N absorption at the surface in an early stage of gaseous nitrocarburizing. The influence of carbon in the substrate on the microstructural and compositional evolutions and on the growth kinetics was evaluated from comparing the results obtained for: a: normalized Fe-0.8C alloy with those for iron under identical nitrocarburizing conditions.
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| 49. |
- Dunagan, John, et al.
(författare)
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FUSE:Lightweight Guaranteed Distributed Failure Notification
- 2004
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Ingår i: Proceedings of the 6th Symposium on Operating Systems Design and Implementation (OSDI). - : Association for Computing Machinery (ACM).
-
Konferensbidrag (refereegranskat)abstract
- FUSE is a lightweight failure notification service for building distributed systems. Distributed systems built with FUSE are guaranteed that failure notifications never fail. Whenever a failure notification is triggered, all live members of the FUSE group will hear a notification within a bounded period of time, irrespective of node or communication failures. In contrast to previous work on failure detection, the responsibility for deciding that afailure has occurred is shared between the FUSE service and the distributed application. This allows applications to implement their own definitions of failure. Our experience building a scalable distributed event delivery system on an overlay network has convinced us of the usefulness of this service. Our results demonstrate that the network costs of each FUSE group can be small; in particular, our overlay network implementation requires no additional liveness-verifying ping traffic beyond that already needed to maintain the overlay, making the steady state network load independent of the number of active FUSE groups.
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| 50. |
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