| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 3. |
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| 4. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 5. |
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| 6. |
- Urowitz, M B, et al.
(författare)
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Clinical manifestations and coronary artery disease risk factors at diagnosis of systemic lupus erythematosus: data from an international inception cohort
- 2007
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 16:9, s. 731-735
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Tidskriftsartikel (refereegranskat)abstract
- Systemic Lupus International Collaborating Clinics (SLICC) comprises 27 centres from 11 countries. An inception cohort of 918 SLE patients has been assembled according to a standardized protocol between 2000 and 2006. Clinical features, classic coronary artery disease (CAD) risk factors, as well as other potential risk factors were collected. Of the 918 patients 89% were females, and of multi racial origin. Less than half the patients were living in a permanent relationship, 58% had post secondary education and 51% were employed. Eight percent had family history of SLE. At enrolment, with at mean age of diagnosis of 34.5 years, a significant number of patients already had CAD risk factors, such as hypertension (33%) and hypercholesterolemia (36%). Only 15% of the patients were postmenopausal, 16% were current smokers and 3.6% had diabetes at entry to the SLICC-RAS (Registry for Atherosclerosis). A number of patients in this multi-racial, multi-ethnic inception cohort of lupus patients have classic CAD risk factors within a mean of 5.4 months from diagnosis. This cohort will be increased to 1500 patients to be followed yearly for 10 years. This will provide a unique opportunity to evaluate risk factors for accelerated atherosclerosis in SLE.
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| 7. |
- Bacelar, A. M. Denis, et al.
(författare)
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Angular Momentum Population In Fragmentation Reactions
- 2009
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 40:3, s. 889-892
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Tidskriftsartikel (refereegranskat)abstract
- Neutron-deficient nuclei with N = 126 have been populated following projectile fragmentation of a U-238 beam with energy 1 GeV/A. The decay of several previously reported isomers has been measured. This will allow us to calculate high-spin isomeric ratios and compare them with model calculations to allow a better understanding of the reaction mechanism.
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| 8. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 9. |
- Hanly, J G, et al.
(författare)
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Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis
- 2008
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 58:3, s. 843-853
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To examine, in an inception cohort of systemic lupus erythematosus (SLE) patients, the association between neuropsychiatric (NP) events and anti-ribosomal P (anti-P), antiphospholipid (lupus anticoagulant [LAC], anticardiolipin), anti-beta 2-glycoprotein I, and anti-NR2 glutamate receptor antibodies. Methods. NP events were identified using the American College of Rheumatology case definitions and clustered into central/peripheral and diffuse/focal events. Attribution of NP events to SLE was determined using decision rules of differing stringency. Autoantibodies were measured without knowledge of NP events or their attribution. Results. Four hundred twelve patients were studied (87.4% female; mean +/- SD age 34.9 +/- 13.5 years, mean +/- SD disease duration 5.0 +/- 4.2 months). There were 214 NP events in 133 patients (32.3%). The proportion of NP events attributed to SLE varied from 15% to 36%. There was no association between autoantibodies and NP events overall. However, the frequency of anti-P antibodies in patients with central NP events attributed to SLE was 4 of 20 (20%), versus 3 of 107 (2.8%) in patients with other NP events and 24 of 279 (8.6%) in those with no NP events (P = 0.04). Among patients with diffuse NP events, 3 of 11 had anti-P antibodies (27%), compared with 4 of 111 patients with other NP events (3.6%) and 24 of 279 of those with no NP events (8.6%) (P 0.02). Specific clinical-serologic associations were found between anti-P and psychosis attributed to SLE (P = 0.02) and between LAC and cerebrovascular disease attributed to SLE (P = 0.038). There was no significant association between other autoantibodies and NP events. Conclusion. Clinically distinct NP events attributed to SLE and occurring around the time of diagnosis were found to be associated with anti-P antibodies and LAC. This Suggests that there are different autoimmune pathogenetic mechanisms, although low sensitivity limits the clinical application of testing for these antibodies.
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| 10. |
- Hanly, J. G., et al.
(författare)
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Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus - An international inception cohort study
- 2007
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 56:1, s. 265-273
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To describe the prevalence, characteristics, attribution, and clinical significance of neuropsychiatric (NP) events in an international inception cohort of systemic lupus erythematosus (SLE) patients. Methods. The study was conducted by the Systemic Lupus International Collaborating Clinics (SLICC). Patients were enrolled within 15 months of fulfilling the American College of Rheumatology (ACR) SLE classification criteria. All NP events within a predefined enrollment window were identified using the ACR case definitions of 19 NP syndromes. Decision rules were derived to determine the proportion of NP disease attributable to SLE. Clinical significance was determined using the Short Form 36 (SF-36) Health Survey and the SLICC/ACR Damage Index (SDI). Results. A total of 572 patients (88% female) were recruited, with a mean +/- SD age of 35 +/- 14 years. The mean +/- SD disease duration was 5.2 +/- 4.2 months. Within the enrollment window, 158 of 572 patients (28%) had at least 1 NP event. In total, there were 242 NP events that encompassed 15 of 19 NP syndromes. The proportion of NP events attributed to SLE varied from 19% to 38% using alternate attribution models and occurred in 6.1-11.7% of patients. Those with NP events, regardless of attribution, had lower scores on the SF-36 and higher SDI scores compared with patients with no NP events. Conclusion. Twenty-eight percent of SLE patients experienced at least 1 NP event around the time of diagnosis of SLE, of which only a minority were attributed to SLE. Regardless of attribution, the occurrence of NP events was associated with reduced quality of life and increased organ damage.
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| 11. |
- Hanly, J. G., et al.
(författare)
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Short-term outcome of neuropsychiatric events in systemic lupus erythematosus upon enrollment into an international inception cohort study
- 2008
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 59:5, s. 721-729
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To determine the short-term outcome of neuropsychiatric (NP) events upon enrollment into an international inception cohort of patients with systemic lupus erythematosus (SLE). Methods. The study was performed by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis and NP events were characterized using the American College of Rheumatology case definitions. Decision rules were derived to identify NP events attributable to SLE. Physician outcome scores of NP events and patient-derived mental component summary (MCS) and physical component summary (PCS) scores of the Short Form 36 were recorded. Results. There were 890 patients (88.7% female) with a mean +/- SD age of 33.8 +/- 13.4 years and mean disease duration of 5.3 +/- 4.2 months. Within the enrollment window, 271 (33.5%) of 890 patients had at least 1 NP event encompassing 15 NP syndromes. NP events attributed to SLE varied from 16.5% to 33.9% using alternate attribution models and occurred in 6.0-11.5% of patients. Outcome scores for NP events attributed to SLE were significantly better than for NP events due to non-SLE causes. Higher global disease activity was associated with worse outcomes. MCS scores were lower in patients with NP events, regardless of attribution, and were also lower in patients with diffuse and central NP events. There was a significant association between physician outcome scores and patient MCS scores only for NP events attributed to SLE. Conclusion. In SLE patients, the short-term outcome of NP events is determined by both the characteristics and attribution of the events. Conclusion. In SLE patients, the short-term outcome of NP events is determined by both the characteristics and attribution of the events.
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| 12. |
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| 13. |
- Morales, A. I., et al.
(författare)
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beta -Delayed gamma -Ray Spectroscopy of Heavy Neutron Rich Nuclei "South" of Lead
- 2009
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Ingår i: Acta Physica Polonica B. - 0587-4254. ; 40:3, s. 867-870
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Konferensbidrag (refereegranskat)abstract
- Relativistic projectile fragmentation of a Pb-208 primary beam has been used to produce neutron-rich nuclei with proton-holes relative to the Z = 82 shell closure, i.e., "south" of Pb. beta-delayed gamma-ray spectroscopy allows to investigate the structural properties of such nuclei with A similar to 195 -> 205. The current work presents transitions de-exciting excited states in Au-204, which are the first spectroscopic information on this N = 125 isotone.
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| 14. |
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| 15. |
- Ainsworth, Elizabeth A., et al.
(författare)
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Next generation of elevated [CO2] experiments with crops: a critical investment for feeding the future world
- 2008
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Ingår i: Plant, Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 31:9, s. 1317-1324
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Tidskriftsartikel (refereegranskat)abstract
- A rising global population and demand for protein-rich diets are increasing pressure to maximize agricultural productivity. Rising atmospheric [CO2] is altering global temperature and precipitation patterns, which challenges agricultural productivity. While rising [CO2] provides a unique opportunity to increase the productivity of C-3 crops, average yield stimulation observed to date is well below potential gains. Thus, there is room for improving productivity. However, only a fraction of available germplasm of crops has been tested for CO2 responsiveness. Yield is a complex phenotypic trait determined by the interactions of a genotype with the environment. Selection of promising genotypes and characterization of response mechanisms will only be effective if crop improvement and systems biology approaches are closely linked to production environments, that is, on the farm within major growing regions. Free air CO2 enrichment (FACE) experiments can provide the platform upon which to conduct genetic screening and elucidate the inheritance and mechanisms that underlie genotypic differences in productivity under elevated [CO2]. We propose a new generation of large-scale, low-cost per unit area FACE experiments to identify the most CO2-responsive genotypes and provide starting lines for future breeding programmes. This is necessary if we are to realize the potential for yield gains in the future.
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| 16. |
- Al-Dahan, N., et al.
(författare)
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Isomeric States In 208Hg And 209Tl Populated In Fragmentation Of 238U
- 2009
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 40:3, s. 871-874
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear structure of neutron-rich N > 126 nuclei has been investigated following their production via relativistic projectile fragmentation of a E/A = 1 GeV U-238 beam on a Be target. The preliminary analysis indicates the presence of previously unreported isomeric states in the N = 128 isotones Hg-208 and Tl-209.
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| 17. |
- Al-Dahan, N., et al.
(författare)
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Nuclear Structure "Southeast" of 208Pb: Isomeric states in 208Hg and 209Tl
- 2009
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:6
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear structure of neutron-rich N>126 nuclei has been investigated following their production via relativistic projectile fragmentation of a E/A=1 GeV U-238 beam. Metastable states in the N=128 isotones Hg-208 and Tl-209 have been identified. Delayed gamma-ray transitions are interpreted as arising from the decay of I-pi=(8(+)) and (17/2(+)) isomers, respectively. The data allow for the so far most comprehensive verification of the shell-model approach in the region determined by magic numbers Z < 82 and N>126.
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| 18. |
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| 19. |
- Champion, Mia D, et al.
(författare)
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Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies
- 2009
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 5:5, s. e1000459-
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Tidskriftsartikel (refereegranskat)abstract
- Tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain, including modulator of drug activity B (mdaB) (FTT0961), which encodes a known NADPH quinone reductase involved in oxidative stress resistance. We have also identified genes exhibiting sequence similarity to effectors of the Type III (T3SS) and components of the Type IV secretion systems (T4SS). One of the genes, msrA2 (FTT1797c), is disrupted in F. tularensis subsp. mediasiatica and has recently been shown to mediate bacterial pathogen survival in host organisms. Our findings suggest that in addition to the duplication of the Francisella Pathogenicity Island, and acquisition of individual loci, adaptation by gene loss in the more recently emerged tularensis, holarctica, and mediasiatica subspecies occurred and was distinct from evolutionary events that differentiated these subspecies, and the novicida subspecies, from a common ancestor. Our findings are applicable to future studies focused on variations in Francisella subspecies pathogenesis, and of broader interest to studies of genomic pathoadaptation in bacteria.
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| 20. |
- Chapin III, F.S., et al.
(författare)
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Polar Systems
- 2006
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Ingår i: Millenium Ecosystem Assessment 2005 - Current State and Trends. - 1559632283 - 9781559632287 ; 1
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 21. |
- Cox, Angela, et al.
(författare)
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A common coding variant in CASP8 is associated with breast cancer risk
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 352-358
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Tidskriftsartikel (refereegranskat)abstract
- The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.
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| 22. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 23. |
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| 24. |
- Heard-Costa, Nancy L, et al.
(författare)
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NRXN3 is a novel locus for waist circumference : a genome-wide association study from the CHARGE Consortium
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000539-
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Tidskriftsartikel (refereegranskat)abstract
- Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.
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| 25. |
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| 26. |
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| 27. |
- Regan, P. H., et al.
(författare)
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First Results from the Stopped RISING Campaign at GSI: The Mapping of Isomeric Decays in Highly Exotic Nuclei
- 2007
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Ingår i: AIP Conference Proceedings. - : AIP. - 0094-243X. - 9780735413283 ; 899, s. 19-22
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Konferensbidrag (refereegranskat)abstract
- The first results from the Stopped Beam RISING experimental campaign performed at the GSI laboratory in Darmstadt, Germany, are presented. RISING (Rare ISotope INvestigations at GSI) constitutes a major new experimental program in European nuclear structure physics research aimed at using relativistic‐energy, projectile‐fragmentation reactions to study nuclei with exotic proton‐to‐neutron ratios. This paper introduces the physics aims of the Stopped RISING collaboration and presents some technical details and initial results from experiments using the RISING array to study decays from metastable nuclear states in both proton and neutron‐rich nuclei.
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| 28. |
- Sabado, Rachel L., et al.
(författare)
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Pathways utilized by dendritic cells for binding, uptake, processing and presentation of antigens derived from HIV-1
- 2007
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 37:7, s. 1752-1763
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Tidskriftsartikel (refereegranskat)abstract
- The outcome following HIV infection depends on the nature and durability of the HIV-specific T cell response induced initially. The activation of protective T cell responses depends upon dendritic cells (DC), antigen-presenting cells which have the capacity to process and present viral antigens. DC pulsed with aldrithiol-2-inactivated HIV and delivered in vivo were reported to induce immune responses and promote virologic control in chronically HIV-1-infected subjects. To gain an understanding of this phenomenon, we characterized the steps involved in the presentation of antigens derived from aldrithiol-2-treated vs. infectious HIV-1 by DC. Antigen presentation, on both MHC class I and II, was independent of DC-specific ICAM-3-grabbing integrin, DEC-205 and macrophage mannose receptor, C-type lectins expressed by the DC. Inhibitor studies showed that presentation on MHC class I was dependent on viral fusion in a CD4/coreceptor-dependent manner, both at the cell surface and within endosomes, and access to the classical endosomal processing pathway. MHC class II presentation of HIV-associated antigens was dependent on active endocytosis, probably receptor-mediated, and subsequent degradation of virions in acidified endosomes in the DC. Our study brings forth new facts regarding the binding, uptake, and processing of chemically inactivated virions leading to efficient antigen presentation and should aid in the design of more effective HIV vaccines. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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| 29. |
- 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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| 30. |
- Alkhomashi, N., et al.
(författare)
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Beta(-)-Delayed And Isomer Spectroscopy Of Neutron-Rich Ta And W Isotopes
- 2009
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Ingår i: Acta Physica Polonica B. - 0587-4254. ; 40:3, s. 875-878
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Konferensbidrag (refereegranskat)abstract
- Decays of neutron-rich A similar to 190 nuclei have been studied following projectile fragmentation of a Pb-208 beam on a Be-9 target at the GSI Fragment Separator. Gamma-ray decays from previously reported isomeric states in Ta-188, W-190 and (192,193) Re were used as internal calibrations for the particle identification analysis, together with the identification of previously unreported isomeric decays in Ta-189 and W-191. The current work also identifies beta-delayed gamma rays following the decay of Ta-188 to W-188 for the first time.
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| 31. |
- Alkhomashi, N., et al.
(författare)
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beta(-)-delayed spectroscopy of neutron-rich tantalum nuclei: Shape evolution in neutron-rich tungsten isotopes
- 2009
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:6
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Tidskriftsartikel (refereegranskat)abstract
- The low-lying structure of W-188,W-190,W-192 has been studied following beta decays of the neutron-rich mother nuclei Ta-188,Ta-190,Ta-192 produced following the projectile fragmentation of a 1-GeV-per-nucleon Pb-208 primary beam on a natural beryllium target at the GSI Fragment Separator. The beta-decay half-lives of Ta-188, Ta-190, and Ta-192 have been measured, with gamma-ray decays of low-lying states in their respective W daughter nuclei, using heavy-ion beta-gamma correlations and a position-sensitive silicon detector setup. The data provide information on the low-lying excited states in W-188, W-190, and W-192, which highlight a change in nuclear shape at W-190 compared with that of lighter W isotopes. This evolution of ground-state structure along the W isotopic chain is discussed as evidence for a possible proton subshell effect for the A similar to 190 region and is consistent with maximization of the gamma-softness of the nuclear potential around N similar to 116.
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| 32. |
- Bentley, MA, et al.
(författare)
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High-spin spectroscopy of natural and unnatural parity states in the mirror-pair V-45/Ti-45
- 2006
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 73:2: 024304
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Tidskriftsartikel (refereegranskat)abstract
- High-spin states in the proton-rich nucleus V-45 have been identified for the first time. A comprehensive gamma-ray decay scheme has been established following an experiment performed at the Vivitron accelerator at IReS Strasbourg by using the Euroball gamma-ray detector array coupled to the Neutron Wall and Euclides detector arrays. The natural (negative-) parity scheme is identified up to the f(7/2) band termination in addition to a positive-parity collective structure based on a d(3/2) particle-hole excitation. Comparison of this scheme with that of the mirror partner, Ti-45, has yielded detailed information on the variation of Coulomb energy as a function of excitation energy and angular momentum. This is the first time that such an analysis has been performed for a collective structure built on a cross-shell excitation. Comparison of the observed Coulomb energies with those predicted by large-scale shell-model calculations is presented. In this case, unusually, the calculations do not fare as well as for heavier nuclei in the shell. In addition, stark differences between the two nuclei are observed for the decay intensities of the parity-changing E1 decays that de-excite the positive-parity deformed bands.
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| 33. |
- Bergmann, Olaf, et al.
(författare)
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Evidence for Cardiomyocyte Renewal in Humans
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 324:5923, s. 98-102
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Tidskriftsartikel (refereegranskat)abstract
- It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 25 to 0.45% at the age of 75. Fewer than 50% of cardiomyocytes are exchanged during a normal life span. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work toward the development of therapeutic strategies aimed at stimulating this process in cardiac pathologies.
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| 34. |
- Bergmann, Olaf, et al.
(författare)
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Turnover of Human Cardiomyocytes
- 2008
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Ingår i: Circulation Research. - 0009-7330. ; 103:12, s. 1494-1495
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Konferensbidrag (refereegranskat)
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| 35. |
- Beynnon, Bruce D, et al.
(författare)
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Are validated questionnaires valid?
- 2006
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Ingår i: Journal of Bone and Joint Surgery. American Volume. - 0021-9355. ; 88:2, s. 448-448
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Tidskriftsartikel (refereegranskat)
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| 36. |
- Beynnon, Bruce D, et al.
(författare)
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Rehabilitation After Anterior Cruciate Ligament Reconstruction: A Prospective, Randomized, Double-Blind Comparison of Programs Administered Over 2 Different Time Intervals.
- 2005
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Ingår i: The American journal of sports medicine. - : SAGE Publications. - 1552-3365 .- 0363-5465. ; 33:3, s. 347-359
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Tidskriftsartikel (refereegranskat)abstract
- There are adverse effects associated with immobilization of the knee after anterior cruciate ligament reconstruction, yet very little is known about how much activity will promote adequate rehabilitation without permanently elongating the graft, producing graft failure, or creating damage to articular cartilage. Hypothesis Rehabilitation with either an accelerated or nonaccelerated program produces no difference in anterior-posterior knee laxity, clinical assessment, patient satisfaction, functional performance, and the synovial fluid biomarkers of articular cartilage metabolism. Study Design Randomized controlled clinical trial; Level of evidence, 1. Methods Twenty-five patients who tore their anterior cruciate ligament were enrolled and underwent anterior cruciate ligament reconstruction. Patients were randomized to accelerated rehabilitation or nonaccelerated rehabilitation. At the time of surgery and 3, 6, 12, and 24 months later, measurements of anterior-posterior knee laxity, clinical assessment, patient satisfaction, functional performance, and cartilage metabolism were completed. Results At the 2-year follow-up, there was no difference in the increase of anterior knee laxity relative to the baseline values that were obtained immediately after surgery between the 2 groups (2.2-mm vs 1.8-mm increase relative to the normal knee). The groups were similar in terms of clinical assessment, patient satisfaction, activity level, function, and response of the bio-markers. After 1 year of healing, synthesis of collagen and turnover of aggrecan remained elevated in both groups. Conclusion Anterior cruciate ligament reconstruction with a bone-patellar tendon-bone graft followed by either accelerated or nonaccelerated rehabilitation produces the same increase of anterior knee laxity. Both programs had the same effect in terms of clinical assessment, patient satisfaction, functional performance, and the biomarkers of articular cartilage metabolism. There is concern that the cartilage biomarkers remained elevated for an extended period.
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| 37. |
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| 38. |
- Bruce, Roderik, et al.
(författare)
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Beam losses from ultraperipheral nuclear collisions between Pb-208(82+) ions in the Large Hadron Collider and their alleviation
- 2009
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Ingår i: Physical Review Special Topics. Accelerators and Beams. - 1098-4402. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Electromagnetic interactions between colliding heavy ions at the Large Hadron Collider (LHC) at CERN will give rise to localized beam losses that may quench superconducting magnets, apart from contributing significantly to the luminosity decay. To quantify their impact on the operation of the collider, we have used a three-step simulation approach, which consists of optical tracking, a Monte Carlo shower simulation, and a thermal network model of the heat flow inside a magnet. We present simulation results for the case of Pb-208(82+) ion operation in the LHC, with focus on the ALICE interaction region, and show that the expected heat load during nominal Pb-208(82+) operation is 40% above the quench level. This limits the maximum achievable luminosity. Furthermore, we discuss methods of monitoring the losses and possible ways to alleviate their effect.
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| 39. |
- Butler, Geraldine, et al.
(författare)
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Evolution of pathogenicity and sexual reproduction in eight Candida genomes.
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 459:7247, s. 657-62
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Tidskriftsartikel (refereegranskat)abstract
- Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
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| 40. |
- Caceres, L. S., et al.
(författare)
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Identification of Excited States in the N = Z Nucleus 82Nb
- 2007
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 38:4, s. 1271-1275
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Tidskriftsartikel (refereegranskat)abstract
- Information on the first excited states in the N = Z = 41 nucleus Nb-82 sheds light on the competition of isospin T = 0 and T = 1 states in the A similar to 80 region. The measurement was performed at the GSI laboratory using fragmentation of a Ag-107 primary beam at 750 MeV/u on a 4 g/cm(2) Be-9 target. The fragments were separated and identified unambiguously in the FRagment Separator. Three excited states were observed and the half-life estimate for the isomeric state was extracted. A tentative spin assignment based on the isobaric analogue states systematics in the T-z = 1 nucleus Zr-82, and transition probabilities indicate T = 1 character of the first two excited states, and T = 0 for the isomeric state.
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| 41. |
- Chang, Yu-mei, et al.
(författare)
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A pooled analysis of Melanocytic nevus phenotype and the risk of cutaneous melanoma at different latitudes
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:2, s. 420-428
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Tidskriftsartikel (refereegranskat)abstract
- An abnormal nevus phenotype is associated with an increased risk of melanoma. We report a pooled analysis conducted using individual nevus data from 15 case-control studies (5,421 melanoma cases and 6,966 controls). The aims were to quantify the risk better and to determine whether relative risk is varied by latitude. Bayesian unconditional logistic random coefficients models were employed to study the risk associated with nevus characteristics. Participants with whole body nevus counts in the highest of 4 population-based categories had a greatly increased risk of melanoma compared with those in the lowest category (pooled odds ratio (pOR) 6.9 (95% confidence interval (CI): 4.4, 1.1.2) for those aged <50 years and pOR 5.1 (95% CI: 3.6, 7.5) for those aged >= 50). The pOR for presence compared with absence of any clinically atypical nevi was 4.0 (95 % CI: 2.8, 5.8). The pORs for 1-2 and >= 3 large nevi on the body compared with none were 2.9 (95% CI: 1.9, 4.3) and 7.1 (95% CI: 4.7, 11.6), respectively. The relative heterogeneities among studies were small for most measures of nevus phenotype, except for the analysis of nevus counts on the arms, which may have been due to methodological differences among studies. The pooled analysis also suggested that an abnormal nevus phenotype is associated most with melanomas on intermittently sun-exposed sites. The presence of increased numbers of nevi, large nevi and clinically atypical nevi on the body are robust risk factors for melanoma showing little variation in relative risk among studies performed at different latitudes. (C) 2008 Wiley-Liss, Inc.
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| 42. |
- Chang, Yu-mei, et al.
(författare)
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Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls
- 2009
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 38:3, s. 814-830
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Tidskriftsartikel (refereegranskat)abstract
- Background Melanoma risk is related to sun exposure; we have investigated risk variation by tumour site and latitude. Methods We performed a pooled analysis of 15 case-control studies (5700 melanoma cases and 7216 controls), correlating patterns of sun exposure, sunburn and solar keratoses (three studies) with melanoma risk. Pooled odds ratios (pORs) and 95% Bayesian confidence intervals (CIs) were estimated using Bayesian unconditional polytomous logistic random-coefficients models. Results Recreational sun exposure was a risk factor for melanoma on the trunk (pOR 1.7; 95% CI: 1.4-2.2) and limbs (pOR 1.4; 95% CI: 1.1-1.7), but not head and neck (pOR 1.1; 95% CI: 0.8-1.4), across latitudes. Occupational sun exposure was associated with risk of melanoma on the head and neck at low latitudes (pOR 1.7; 95% CI: 1.0-3.0). Total sun exposure was associated with increased risk of melanoma on the limbs at low latitudes (pOR 1.5; 95% CI: 1.0-2.2), but not at other body sites or other latitudes. The pORs for sunburn in childhood were 1.5 (95% CI: 1.3-1.7), 1.5 (95% CI: 1.3-1.7) and 1.4 (95% CI: 1.1-1.7) for melanoma on the trunk, limbs, and head and neck, respectively, showing little variation across latitudes. The presence of head and neck solar keratoses was associated with increased risk of melanoma on the head and neck (pOR 4.0; 95% CI: 1.7-9.1) and limbs (pOR 4.0; 95% CI: 1.9-8.4). Conclusion Melanoma risk at different body sites is associated with different amounts and patterns of sun exposure. Recreational sun exposure and sunburn are strong predictors of melanoma at all latitudes, whereas measures of occupational and total sun exposure appear to predict melanoma predominately at low latitudes. Keywords Melanoma, recreational sun exposure, occupational sun exposure, total sun exposure, sunburn, solar keratoses
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| 43. |
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| 44. |
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| 45. |
- Farrelly, G. F., et al.
(författare)
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Revision of the K-Isomer in 190W
- 2009
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 40:3, s. 885-888
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Tidskriftsartikel (refereegranskat)abstract
- Gamma rays from the decay of an isomer in W-190(116) have been observed following projectile fragmentation of a 1 GeV per nucleon Pb-208 beam. An earlier experiment indicated decay from a (10(-)) isomer to the ground state rotational band. Improved statistics have enabled gamma coincidence and time-difference measurements to be made which alter the previous interpretation. Blocked BCS calculations have also been used together with reduced hindrance factors to indicate possible values of spin-parity for the isomer.
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| 46. |
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| 47. |
- Garnsworthy, A. B., et al.
(författare)
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Spectroscopy of Po-212 and At-213 using a He-8 radioactive beam and EXOGAM
- 2005
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 31:10, s. S1851-S1854
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Tidskriftsartikel (refereegranskat)abstract
- A beam of 28 MeV He-8 particles with an average intensity 2 x 10(5) ions s(-1), produced by the SPIRAL facility at GANIL, was used to initiate fusion-evaporation reactions in thick targets of Pb-201 and Bi-209. Excited states of Po-212 and At-213 were populated in (He-8,4n) reactions. The emitted gamma-rays were detected using the EXOGAM array composed of four Compton suppressed germanium Clover detectors in a close geometry configuration. Preliminary results show that Po-212 has been populated to high spin (I similar or equal to 14) with a significantly increased yield compared with our previous He-8 beam experiment. An apparently increased relative population of states up to 12(+) was observed compared with published results from a Pb-208(Be-9,alpha n)(212) Po reaction at 48 MeV. Evidence is presented for a previously unreported de-excitation pathway: 69 keV (13(-) -> 12(+)). States up to I-pi = (39/2(-)) have also been observed in At-213.
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| 48. |
- Gerstein, Mark B, et al.
(författare)
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What is a gene, post-ENCODE? : History and updated definition
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 669-681
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Tidskriftsartikel (refereegranskat)abstract
- While sequencing of the human genome surprised us with how many protein-coding genes there are, it did not fundamentally change our perspective on what a gene is. In contrast, the complex patterns of dispersed regulation and pervasive transcription uncovered by the ENCODE project, together with non-genic conservation and the abundance of noncoding RNA genes, have challenged the notion of the gene. To illustrate this, we review the evolution of operational definitions of a gene over the past century--from the abstract elements of heredity of Mendel and Morgan to the present-day ORFs enumerated in the sequence databanks. We then summarize the current ENCODE findings and provide a computational metaphor for the complexity. Finally, we propose a tentative update to the definition of a gene: A gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products. Our definition side-steps the complexities of regulation and transcription by removing the former altogether from the definition and arguing that final, functional gene products (rather than intermediate transcripts) should be used to group together entities associated with a single gene. It also manifests how integral the concept of biological function is in defining genes.
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| 49. |
- Goldhahn, Jörg, et al.
(författare)
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Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis
- 2008
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 43:2, s. 343-347
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Tidskriftsartikel (refereegranskat)abstract
- Pre-clinical studies indicate that pharmacologic agents can augment fracture union. If these pharmacologic approaches could be translated into clinical benefit and offered to patients with osteoporosis or patients with other risks for impaired fracture union (e.g. in subjects with large defects or open fractures with high complication rate), they could provide an important adjunct to the treatment of fractures. However, widely accepted guidelines are important to encourage the conduct of studies to evaluate bioactive substances, drugs, and new agents that may promote fracture union and subsequent return to normal function. A consensus process was initiated to provide recommendations for the clinical evaluation of potential therapies to augment fracture repair in patients with meta- and diaphyseal fractures. Based on the characteristics of fracture healing and fixation, the following study objectives of a clinical study may be appropriate: a) acceleration of fracture union, b) acceleration of return to normal function and c) reduction of fracture healing complications. The intended goal(s) should determine subsequent study methodology. While an acceleration of return to normal function or a reduction of fracture healing complications in and of themselves may be sufficient primary study endpoints for a phase 3 pivotal study, acceleration of fracture union alone is not. Radiographic evaluation may either occur at multiple time points during the healing process with the aim of measuring the time taken to reach a defined status (e.g. cortical bridging of three cortices or disappearance of fracture lines), or could be obtained at a single pre-determined timepoint, were patients are expected to reach a common clinical milestone (i.e. pain free full weight-bearing in weight-bearing fracture cases). Validated Patient Reported Outcomes (PRO's) measures will need to support the return to normal function co-primary endpoints. If reduction of complication rate (e.g. non-union) is the primary objective, the anticipated complications must be defined in the study protocol, along with their possible associations with the specified fracture type and fixation device. The study design should be randomized, parallel, double-blind, and placebo-controlled, and all fracture subjects should receive a standardized method of fracture fixation, defined as Standard of Care. © 2008 Elsevier Inc. All rights reserved.
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| 50. |
- Gorska, M., et al.
(författare)
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Evolution of the N=82 Shell Gap below 132Sn Inferred from Core Excited States in 131In
- 2009
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 672:4-5, s. 313-316
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Tidskriftsartikel (refereegranskat)abstract
- The gamma-ray decay of ail excited state in In-131, the one proton hole neighbor of the doubly magic (132)sn has been measured. A high-spin, core-excited isomer with T-1/2 = 630(60) us was identified following production by both relativistic fragmentation of a Xe-136 beam and fission Of a U-238 beam. This state deexcites by a single gamma-ray branch of 3782(2) keV from which direct evidence for the size of the N = 82 shell gal) is inferred. The results are discussed in comparison to a shell-model Calculation including configurations across the closed shells at N = 82 and Z = 50. (C) 2009 Elsevier B.V. All rights reserved.
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