| 1. |
- 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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| 3. |
- Rohmer, Laurence, et al.
(författare)
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Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains
- 2007
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Ingår i: Genome Biology. - : BioMed Central. - 1465-6906 .- 1474-760X. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Francisella tularensis subspecies tularensis and holarctica are pathogenic to humans, whereas the two other subspecies, novicida and mediasiatica, rarely cause disease. To uncover the factors that allow subspecies tularensis and holarctica to be pathogenic to humans, we compared their genome sequences with the genome sequence of Francisella tularensis subspecies novicida U112, which is nonpathogenic to humans. RESULTS: Comparison of the genomes of human pathogenic Francisella strains with the genome of U112 identifies genes specific to the human pathogenic strains and reveals pseudogenes that previously were unidentified. In addition, this analysis provides a coarse chronology of the evolutionary events that took place during the emergence of the human pathogenic strains. Genomic rearrangements at the level of insertion sequences (IS elements), point mutations, and small indels took place in the human pathogenic strains during and after differentiation from the nonpathogenic strain, resulting in gene inactivation. CONCLUSION: The chronology of events suggests a substantial role for genetic drift in the formation of pseudogenes in Francisella genomes. Mutations that occurred early in the evolution, however, might have been fixed in the population either because of evolutionary bottlenecks or because they were pathoadaptive (beneficial in the context of infection). Because the structure of Francisella genomes is similar to that of the genomes of other emerging or highly pathogenic bacteria, this evolutionary scenario may be shared by pathogens from other species.
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| 4. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 6. |
- Goransson, Gunnel I., et al.
(författare)
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Combining landslide and contaminant risk: a preliminary assessment
- 2009
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Ingår i: Journal of Soils and Sediments. - : Springer Science and Business Media LLC. - 1614-7480 .- 1439-0108. ; 9:1, s. 33-45
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to highlight a not yet recognized hazard for mass failure (landslides) of contaminated soils into rivers and to provide an understanding of important interactions of such events. A first effort to investigate the problem is made focusing on the south eastern part of the Gota A"lv river valley, in Sweden, by combining geographical information on potentially contaminated sites with slope stability levels on maps. The objectives of this study were to: (1) Review current Swedish risk assessment methodologies for contaminated areas and landslides, and analyze their capability to quantify the risk of contaminated areas being subject to landslides. (2) Investigate the presence of contaminated areas at landslide risk along the Gota A"lv river valley. (3) Provide an overview of the national methods for landslide risk analysis and for environmental risk classification, followed by a comparison between the methods and the results from the superposition of the two methods for the study site. (4) Make a first attempt to conceptualize the release and transport mechanisms. Environmental risk assessment data of the study site was combined with data on slope stability levels. Conceptual issues of the release and transport scenario were identified and a first conceptual model was created. Of 31 potentially contaminated sites, eight had moderate to high probability for landslide, and of these eight sites, five were classified as having a high or very high environmental risk. These findings had not been revealed when the data had only been considered separately. The 'actual' risk could hence be even higher than the highest environmental risk class actually suggests. By visualizing results from the landslide risk analysis with the results from the environmental risk classification of contaminated sites, a better understanding of the potential hazard involved is obtained. The release mechanisms as a result of a landslide into surface water were conceptualized using two time scales: the instantaneous and the long-term release. It is clear that the Swedish method for landslide risk assessment and for environmental risk assessment of contaminated soil considers hazard events that are characterized by different time scales. The method for landslide risk assessment addresses events that are rapid (occurring over minutes) with instantaneous impact and consequences. Measurements are made within a short time after the event (days to months). The environmental risk assessment is done with respect to events that are slowly evolving (over years or decades) and any possible consequence materializes after a long period of time. The combined data provided a more solid basis for decisions; however, inherent difficulties when combining data based on different methods were revealed. Separate assessment methodologies executed by different authorities may lead to incorrect assessments and inappropriate protective measures. The effects and the consequences of landslides in areas with contaminated soil need to be further investigated. The climate change expected to occur over the next hundred years will increase the probability of slope failures, such as landslides, in many parts of the world where the precipitation is predicted to increase (e.g., in Scandinavia). This will accentuate the need for methods and models to assess the impact of such events. In order to achieve established environmental quality objectives there is an urgent need for models and assessment principles (criteria) for contaminated areas that are at risk of experiencing slope failure. Knowledge of the governing processes that control the release and transport of substances under a variety of conditions, taking into account characteristic spatial and temporal scales, is required.
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| 8. |
- Larson, Keith W., et al.
(författare)
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Digiscoping Vouchers for Diet Studies in Bill-load Holding Birds
- 2006
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Ingår i: Waterbirds (De Leon Springs, Fla.). - 1524-4695 .- 1938-5390. ; 29:2, s. 198-202
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Tidskriftsartikel (refereegranskat)abstract
- We conducted an observer-based diet study of Caspian Terns (Sterna caspia) incorporating digiscoping to collect digital photographic vouchers of fish. Observer-based diet studies pose several problems, ranging from differential experience and abilities of observers to the lack of vouchers for confirming identification. One solution to these problems is to recover fish either directly from birds (i.e., trapping, shooting) or ones dropped on the colony. This may not, however, be desirable or achieve adequate sample sizes. Some species are difficult to capture or methods may cause significant disturbance and/or nest abandonment. To overcome these problems, we used a relatively inexpensive new photographic technique known as digiscoping. By holding a high-resolution point-and-shoot digital camera up to the eyepiece of a spotting scope or pair of binoculars, we could take digital photographic vouchers of fish as terns brought them into the colony. During the study, we made 16,423 observations, identifying 92% of the fish to the family (3%), genus (15%), or species (74%) level. We supported these observations with over 2,500 digital photograph vouchers. Vouchers confirmed identification of all fish taxa and allowed for later identification, by us or qualified fisheries biologists, of several species unidentifiable in the field. The ability to have independent experts confirm observations and identify previously unidentifiable observations greatly expanded our understanding of the range of fish taken by Caspian Terns.
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| 9. |
- Molina, Kathy C., et al.
(författare)
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The Winter Distribution of the Western Gull-billed Tern (Gelochelidon nilotica vanrossemi)
- 2009
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Ingår i: Western Birds. - 0160-1121. ; 40:1, s. 2-20
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We surveyed 73 sites along the Gulf of California and Pacific coasts of mainland Mexico during five nonbreeding seasons from December 1999 to January 2007 to clarify the winter status and distribution of the western North American subspecies of the Gull-billed Tern (Gelochelidon nilotica vanrossemi), a taxon of conservation concern. We located birds at 44 of the 73 sites, (60%) with the largest numbers found around coastal lagoons with extensive tidal flats in southern Sonora, Sinaloa, and extreme northern Nayarit. Local concentrations were also noted at other sites from the Colorado River delta of extreme northwestern Sonora south to Guerrero. Resightings of birds banded as chicks at California breeding colonies establish the first evidence of connectivity to specific wintering sites in Mexico as far south as southern Sonora and possibly into Nayarit.
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