| 1. |
- Wortman, J. R., et al.
(author)
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The 2008 update of the Aspergillus nidulans genome annotation: A community effort
- 2009
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In: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
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Journal article (peer-reviewed)abstract
- The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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| 3. |
- Birney, Ewan, et al.
(author)
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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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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)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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| 4. |
- Andersson, L., et al.
(author)
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New Features of Electron Phase Space Holes Observed by the THEMIS Mission
- 2009
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:22, s. 225004-
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Journal article (peer-reviewed)abstract
- Observations of electron phase-space holes (EHs) in Earth's plasma sheet by the THEMIS satellites include the first detection of a magnetic perturbation (delta B-parallel to) parallel to the ambient magnetic field (B-0). EHs with a detectable delta B-parallel to have several distinguishing features including large electric field amplitudes, a magnetic perturbation perpendicular to B-0, high speeds (similar to 0.3c) along B-0, and sizes along B-0 of tens of Debye lengths. These EHs have a significant center potential (Phi similar to k(B)T(e)/e), suggesting strongly nonlinear behavior nearby such as double layers or magnetic reconnection.
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| 5. |
- Druker, Brian J., et al.
(author)
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Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
- 2006
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 355:23, s. 2408-2417
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Journal article (peer-reviewed)abstract
- BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events. CONCLUSIONS: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)
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| 6. |
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| 7. |
- Ergun, R. E., et al.
(author)
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Observations of Double Layers in Earth's Plasma Sheet
- 2009
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:15, s. 155002-
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Journal article (peer-reviewed)abstract
- We report the first direct observations of parallel electric fields (E-parallel to) carried by double layers (DLs) in the plasma sheet of Earth's magnetosphere. The DL observations, made by the THEMIS spacecraft, have E-parallel to signals that are analogous to those reported in the auroral region. DLs are observed during bursty bulk flow events, in the current sheet, and in plasma sheet boundary layer, all during periods of strong magnetic fluctuations. These observations imply that DLs are a universal process and that strongly nonlinear and kinetic behavior is intrinsic to Earth's plasma sheet.
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| 8. |
- Hanly, J G, et al.
(author)
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Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis
- 2008
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In: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 58:3, s. 843-853
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Journal article (peer-reviewed)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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| 9. |
- Hanly, J. G., et al.
(author)
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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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In: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 59:5, s. 721-729
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Journal article (peer-reviewed)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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| 10. |
- Lu, R, et al.
(author)
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Genetic associations of LYN with systemic lupus erythematosus
- 2009
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In: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 10:5, s. 397-403
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Journal article (peer-reviewed)abstract
- We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 x 10(-4), odds ratio (OR)=0.81 (95% confidence interval: 0.73-0.90)). This single nucleotide polymorphism (SNP) is located in the 5' untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P=1.5 x 10(-3), OR=0.75 (95% CI: 0.62-0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.
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