| 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. |
- Cibere, Jolanda, et al.
(författare)
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Association of Biomarkers With Pre-Radiographically Defined and Radiographically Defined Knee Osteoarthritis in a Population-Based Study
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 60:5, s. 1372-1380
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate 10 biomarkers in magnetic resonance imaging (M RI)-determined, pre-radiographically defined osteoarthritis (pre-ROA) and radiographically defined OA (ROA) in a population-based cohort of subjects with symptomatic knee pain. Methods. Two hundred one white subjects with knee pain, ages 40-79 years, were classified into OA subgroups according to MRI-based cartilage (MRC) scores (range 0-4) and Kellgren/Lawrence (K/L) grades of radiographic severity (range 0-4): no OA (MRC score 0, K/L grade <2), pre-ROA (MRC score > 1, K/L grade <2), or ROA (MRC score >= 1, K/L grade >= 2). Urine and serum samples were assessed for levels of the following biomarkers: urinary biomarkers C-telopeptide of type II collagen (uCTX-II), type II and types I and II collagen cleavage neoepitopes (uC2C and uC1,2C, respectively), and N-telopeptide of type I collagen, and serum biomarkers sC1,2C, sC2C, C-propeptide of type II procollagen (sCPII), chondroitin sulfate 846 epitope, cartilage oligomeric matrix protein, and hyaluronic acid. Multicategory logistic regression was performed to evaluate the association of OA subgroup with individual biomarker levels and biomarker ratios, adjusted for age, sex, and body mass index. Results. The risk of ROA versus no OA increased with increasing levels of uCTX-II (odds ratio [OR] 3.12, 95% confidence interval [95% CI] 1.35-7.21), uC2C (OR 2.13, 95% CI 1.04-4.37), and uC1,2C (OR 2.07, 95% CI 1.06-4.04), and was reduced in association with high levels of sCPII (OR 0.53, 95% CI 0.30-0.94). The risk of pre-ROA versus no OA increased with increasing levels of uC2C (OR 2.06, 95% CI 1.05-4.01) and uC1,2C (OR 2.06, 95% CI 1.12-3.77). The ratios of type II collagen degradation markers to collagen synthesis markers were better than individual biomarkers at differentiating the OA subgroups, e.g., the ratio of [uCTX-II] [uC1,2C] to sCPII was associated with a risk of ROA versus no OA of 3.47 (95% CI 1.34-9.03) and a risk of pre-ROA versus no OA of 2.56 (95% CI 1.03-6.40). Conclusion. Different cartilage degradation markers are associated with pre-ROA than are associated with ROA, indicating that their use as diagnostic markers depends on the stage of OA. Biomarker ratios contrasting cartilage degradation with cartilage synthesis are better able to differentiate OA stages compared with levels of the individual markers.
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| 3. |
- Linder, Adam, et al.
(författare)
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Short-term organ dysfunction is associated with long-term (10-Yr) mortality of septic shock
- 2016
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Ingår i: Critical Care Medicine. - 0090-3493. ; 44:8, s. 728-736
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: As mortality of septic shock decreases, new therapies focus on improving short-term organ dysfunction. However, it is not known whether short-term organ dysfunction is associated with long-term mortality of septic shock. Design: Retrospective single-center. Setting: Mixed medical-surgical ICU. Patients: One thousand three hundred and thirty-one patients with septic shock were included from 2000-2004. To remove the bias of 28-day nonsurvivors' obvious association with long-term mortality, we determined the associations of days alive and free of ventilation, vasopressors and renal replacement therapy in 28-day and 1-year survivors with 1-, 5- and 10-year mortality in unadjusted analyses and analyses adjusted for age, gender, Acute Physiology and Chronic Health Evaluation II and presence of chronic comorbidities. Interventions: None. Measurements and Main Results: Days alive and free of ventilation, vasopressors, and renal replacement therapy were highly significantly associated with 1-, 5-, and 10-year mortality (p <0.0001). In 28-day survivors, using Bonferroni-corrected multiple logistic regression, days alive and free of ventilation (p <0.0001, p = 0.0002, and p = 0.001), vasopressors (p <0.0001, p <0.0001, and p = 0.0004), and renal replacement therapy (p = 0.0008, p = 0.0008, and p = 0.0002) were associated with increased 1-, 5-, and 10-year mortality, respectively. In 1-year survivors, none of the acute organ support and dysfunction measures were associated with 5- and 10-year mortality. Conclusions: Days alive and free of ventilation, vasopressors, and renal replacement therapy in septic shock in 28-day survivors was associated with 1-, 5-, and 10-year mortality. These associations are nullified in 1-year survivors in whom none of the acute organ support measures were associated with 5- and 10-year mortality. This suggests that therapies that decrease short-term organ dysfunction could also improve long-term outcomes of 28-day survivors of septic shock.
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| 4. |
- Singer, L. P., et al.
(författare)
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The Needle in the 100 deg2 Haystack : Uncovering Afterglows of Fermi GRBs with the Palomar Transient Factory
- 2015
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 806:1
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Tidskriftsartikel (refereegranskat)abstract
- The Fermi Gamma-Ray Space Telescope has greatly expanded the number and energy window of observations of gamma-ray bursts (GRBs). However, the coarse localizations of tens to a hundred square degrees provided by the Fermi Gamma-ray Burst Monitor (GBM) instrument have posed a formidable obstacle to locating the bursts' host galaxies, measuring their redshifts, and tracking their panchromatic afterglows. We have built a target of opportunity mode for the intermediate Palomar Transient Factory (iPTF) in order to perform targeted searches for Fermi afterglows. Here, we present the results of one year of this program: eight afterglow discoveries, two of which (GRBs 130702A and 140606B) were at low redshift (z=0.145 and 0.384 respectively) and had spectroscopically confirmed broad-line type Ic supernovae. We present our broadband follow-up including spectroscopy as well as X-ray, UV, optical, millimeter, and radio observations. We study possible selection effects in the context of the total Fermi and Swift GRB samples. We identify one new outlier on the Amati relation. We find that two bursts are consistent with a mildly relativistic shock breaking out from the progenitor star, rather than the ultra-relativistic internal shock mechanism that powers standard cosmological bursts. Finally, in the context of the Zwicky Transient Facility (ZTF), we discuss how we will continue to expand this effort to find optical counterparts of binary neutron star mergers that may soon be detected by Advanced LIGO and Virgo.
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| 5. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 6. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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