| 1. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 2. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 3. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 4. |
- Freitag, Daniel F., et al.
(författare)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Tidskriftsartikel (refereegranskat)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 5. |
- Karyotaki, Eirini, et al.
(författare)
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Internet-Based Cognitive Behavioral Therapy for Depression : A Systematic Review and Individual Patient Data Network Meta-analysis
- 2021
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 78:4, s. 361-371
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Forskningsöversikt (refereegranskat)abstract
- IMPORTANCE: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them.OBJECTIVE: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information.DATA SOURCES: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019.STUDY SELECTION: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization.DATA EXTRACTION AND SYNTHESIS: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression.MAIN OUTCOMES AND MEASURES: Patient Health Questionnaire-9 (PHQ-9) scores.RESULTS: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9.CONCLUSIONS AND RELEVANCE: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.
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| 6. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 7. |
- Nava, Veronica, et al.
(författare)
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Plastic debris in lakes and reservoirs
- 2023
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 619:7969, s. 317-322
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Tidskriftsartikel (refereegranskat)abstract
- Plastic debris is thought to be widespread in freshwater ecosystems globally(1). However, a lack of comprehensive and comparable data makes rigorous assessment of its distribution challenging(2,3). Here we present a standardized cross-national survey that assesses the abundance and type of plastic debris (>250 mu m) in freshwater ecosystems. We sample surface waters of 38 lakes and reservoirs, distributed across gradients of geographical position and limnological attributes, with the aim to identify factors associated with an increased observation of plastics. We find plastic debris in all studied lakes and reservoirs, suggesting that these ecosystems play a key role in the plastic-pollution cycle. Our results indicate that two types of lakes are particularly vulnerable to plastic contamination: lakes and reservoirs in densely populated and urbanized areas and large lakes and reservoirs with elevated deposition areas, long water-retention times and high levels of anthropogenic influence. Plastic concentrations vary widely among lakes; in the most polluted, concentrations reach or even exceed those reported in the subtropical oceanic gyres, marine areas collecting large amounts of debris(4). Our findings highlight the importance of including lakes and reservoirs when addressing plastic pollution, in the context of pollution management and for the continued provision of lake ecosystem services.
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| 8. |
- Brout, Dillon, et al.
(författare)
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The Pantheon+ analysis : cosmological constraints
- 2022
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Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 938:2
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Tidskriftsartikel (refereegranskat)abstract
- We present constraints on cosmological parameters from the Pantheon+ analysis of 1701 light curves of 1550 distinct Type Ia supernovae (SNe Ia) ranging in redshift from z = 0.001 to 2.26. This work features an increased sample size from the addition of multiple cross-calibrated photometric systems of SNe covering an increased redshift span, and improved treatments of systematic uncertainties in comparison to the original Pantheon analysis, which together result in a factor of 2 improvement in cosmological constraining power. For a flat ΛCDM model, we find ΩM = 0.334 ± 0.018 from SNe Ia alone. For a flat w0CDM model, we measure w0 = −0.90 ± 0.14 from SNe Ia alone, H0 = 73.5 ± 1.1 km s−1 Mpc−1 when including the Cepheid host distances and covariance (SH0ES), and w0 = -0.978-+0.0310.024 when combining the SN likelihood with Planck constraints from the cosmic microwave background (CMB) and baryon acoustic oscillations (BAO); both w0 values are consistent with a cosmological constant. We also present the most precise measurements to date on the evolution of dark energy in a flat w0waCDM universe, and measure wa = -0.1-+2.00.9 from Pantheon+ SNe Ia alone, H0 = 73.3 ± 1.1 km s−1 Mpc−1 when including SH0ES Cepheid distances, and wa = -0.65-+0.320.28 when combining Pantheon+ SNe Ia with CMB and BAO data. Finally, we find that systematic uncertainties in the use of SNe Ia along the distance ladder comprise less than one-third of the total uncertainty in the measurement of H0 and cannot explain the present “Hubble tension” between local measurements and early universe predictions from the cosmological model.
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| 9. |
- D'Andrea, Chris B., et al.
(författare)
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Type II-P Supernovae from the SDSS-II Supernova Survey and the Standardized Candle Method
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 708:1, s. 661-674
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Tidskriftsartikel (refereegranskat)abstract
- We apply the Standardized Candle Method (SCM) for Type II Plateau supernovae (SNe II-P), which relates the velocity of the ejecta of a SN to its luminosity during the plateau, to 15 SNe II-P discovered over the three season run of the Sloan Digital Sky Survey-II Supernova Survey. The redshifts of these SNe—0.027 < z < 0.144—cover a range hitherto sparsely sampled in the literature; in particular, our SNe II-P sample contains nearly as many SNe in the Hubble flow (z > 0.01) as all of the current literature on the SCM combined. We find that the SDSS SNe have a very small intrinsic I-band dispersion (0.22 mag), which can be attributed to selection effects. When the SCM is applied to the combined SDSS-plus-literature set of SNe II-P, the dispersion increases to 0.29 mag, larger than the scatter for either set of SNe separately. We show that the standardization cannot be further improved by eliminating SNe with positive plateau decline rates, as proposed in Poznanski et al. We thoroughly examine all potential systematic effects and conclude that for the SCM to be useful for cosmology, the methods currently used to determine the Fe II velocity at day 50 must be improved, and spectral templates able to encompass the intrinsic variations of Type II-P SNe will be needed. Based in part on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan.
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| 10. |
- Furukawa, Toshi A., et al.
(författare)
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How can we estimate QALYs based on PHQ-9 scores? Equipercentile linking analysis of PHQ-9 and EQ-5D
- 2021
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Ingår i: Evidence-Based Mental Health. - : BMJ. - 1362-0347 .- 1468-960X. ; 24:3, s. 97-101
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Tidskriftsartikel (refereegranskat)abstract
- Background: Quality-adjusted life years (QALYs) are widely used to measure the impact of various diseases on both the quality and quantity of life and in their economic valuations. It will be clinically important and informative if we can estimate QALYs based on measurements of depression severity. Objective: To construct a conversion table from the Patient Health Questionnaire-9 (PHQ-9), the most frequently used depression scale in recent years, to the Euro-Qol Five Dimensions Three Levels (EQ-5D-3L), one of the most commonly used instruments to assess QALYs. Methods: We obtained individual participant data of randomised controlled trials of internet cognitive-behavioural therapy which had administered depression severity scales and the EQ-5D-3L at baseline and at end of treatment. Scores from depression scales were all converted into the PHQ-9 according to the validated algorithms. We used equipercentile linking to establish correspondences between the PHQ-9 and the EQ-5D-3L. Findings: Individual-level data from five trials (total N=2457) were available. Subthreshold depression (PHQ-9 scores between 5 and 10) corresponded with EQ-5D-3L index values of 0.9-0.8, mild major depression (10-15) with 0.8-0.7, moderate depression (15-20) with 0.7-0.5 and severe depression (20 or higher) with 0.6-0.0. A five-point improvement in PHQ-9 corresponded approximately with an increase in EQ-5D-3L score by 0.03 and a ten-point improvement by approximately 0.25. Conclusions and Clinical Implications: The conversion table between the PHQ-9 and the EQ-5D-3L scores will enable fine-grained assessment of burden of depression at its various levels of severity and of impacts of its various treatments.
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| 11. |
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| 12. |
- Benkner, Siegfried, et al.
(författare)
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PEPPHER : Efficient and Productive Usage of Hybrid Computing Systems
- 2011
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Ingår i: IEEE Micro. - : IEEE Institute of Electrical and Electronics. - 0272-1732 .- 1937-4143. ; 31:5, s. 28-41
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Tidskriftsartikel (refereegranskat)abstract
- PEPPHER, a three-year European FP7 project, addresses efficient utilization of hybrid (heterogeneous) computer systems consisting of multicore CPUs with GPU-type accelerators. This article outlines the PEPPHER performance-aware component model, performance prediction means, runtime system, and other aspects of the project. A larger example demonstrates performance portability with the PEPPHER approach across hybrid systems with one to four GPUs.
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| 13. |
- Dale, Nell, et al.
(författare)
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A dialog between authors and teachers
- 2002
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Ingår i: Proc. ACM SIGCSE ITiCSE'02 7th Annual Conf. on Information Technology in Computer Science Education, Aarhus, Denmark, June 2002.'. - New York : ACM. - 1581134991
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Konferensbidrag (refereegranskat)
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| 14. |
- Dilday, Benjamin, et al.
(författare)
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A Measurement of the Rate of Type Ia Supernovae in Galaxy Clusters from the SDSS-II Supernova Survey
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 715, s. 1021-1035
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the Type Ia supernova (SN) rate in galaxy clusters based on data from the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey. The cluster SN Ia rate is determined from 9 SN events in a set of 71 C4 clusters at z <= 0.17 and 27 SN events in 492 maxBCG clusters at 0.1 <= z <= 0.3. We find values for the cluster SN Ia rate of (0.37+0.17+0.01 -0.12-0.01) SNur h 2 and (0.55+0.13+0.02 -0.11-0.01) SNur h 2 (SNux = 10-12 L -1 xsun yr-1) in C4 and maxBCG clusters, respectively, where the quoted errors are statistical and systematic, respectively. The SN rate for early-type galaxies is found to be (0.31+0.18+0.01 -0.12-0.01) SNur h 2 and (0.49+0.15+0.02 -0.11-0.01) SNur h 2 in C4 and maxBCG clusters, respectively. The SN rate for the brightest cluster galaxies (BCG) is found to be (2.04+1.99+0.07 -1.11-0.04) SNur h 2 and (0.36+0.84+0.01 -0.30-0.01) SNur h 2 in C4 and maxBCG clusters, respectively. The ratio of the SN Ia rate in cluster early-type galaxies to that of the SN Ia rate in field early-type galaxies is 1.94+1.31+0.043 -0.91-0.015 and 3.02+1.31+0.062 -1.03-0.048, for C4 and maxBCG clusters, respectively. The SN rate in galaxy clusters as a function of redshift, which probes the late time SN Ia delay distribution, shows only weak dependence on redshift. Combining our current measurements with previous measurements, we fit the cluster SN Ia rate data to a linear function of redshift, and find rL = [(0.49+0.15 -0.14)+(0.91+0.85 -0.81) × z] SNuB h 2. A comparison of the radial distribution of SNe in cluster to field early-type galaxies shows possible evidence for an enhancement of the SN rate in the cores of cluster early-type galaxies. With an observation of at most three hostless, intra-cluster SNe Ia, we estimate the fraction of cluster SNe that are hostless to be (9.4+8.3 -5.1)%.
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| 15. |
- Dilday, Benjamin, et al.
(författare)
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Measurements of the Rate of Type Ia Supernovae at Redshift lsim0.3 from the Sloan Digital Sky Survey II Supernova Survey
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 713, s. 1026-1036
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Tidskriftsartikel (refereegranskat)abstract
- We present a measurement of the volumetric Type Ia supernova (SN Ia) rate based on data from the Sloan Digital Sky Survey II (SDSS-II) Supernova Survey. The adopted sample of supernovae (SNe) includes 516 SNe Ia at redshift z <~ 0.3, of which 270(52%) are spectroscopically identified as SNe Ia. The remaining 246 SNe Ia were identified through their light curves; 113 of these objects have spectroscopic redshifts from spectra of their host galaxy, and 133 have photometric redshifts estimated from the SN light curves. Based on consideration of 87 spectroscopically confirmed non-Ia SNe discovered by the SDSS-II SN Survey, we estimate that 2.04+1.61 -0.95% of the photometric SNe Ia may be misidentified. The sample of SNe Ia used in this measurement represents an order of magnitude increase in the statistics for SN Ia rate measurements in the redshift range covered by the SDSS-II Supernova Survey. If we assume an SN Ia rate that is constant at low redshift (z < 0.15), then the SN observations can be used to infer a value of the SN rate of rV = (2.69+0.34+0.21 -0.30-0.01)×10-5 SNe yr-1 Mpc-3 (H 0/(70 km s-1 Mpc-1))3 at a mean redshift of ~0.12, based on 79 SNe Ia of which 72 are spectroscopically confirmed. However, the large sample of SNe Ia included in this study allows us to place constraints on the redshift dependence of the SN Ia rate based on the SDSS-II Supernova Survey data alone. Fitting a power-law model of the SN rate evolution, rV (z) = Ap × ((1 + z)/(1 + z 0))ν, over the redshift range 0.0 < z < 0.3 with z 0 = 0.21, results in Ap = (3.43+0.15 -0.15) × 10-5 SNe yr-1 Mpc-3 (H 0/(70 km s-1 Mpc-1))3 and ν = 2.04+0.90 -0.89.
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| 16. |
- Francis, C. W., et al.
(författare)
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Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12months : the DALTECAN Study
- 2015
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 13:6, s. 1028-1035
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTreatment of venous thromboembolism (VTE) in patients with cancer has a high rate of recurrence and bleeding complications. Guidelines recommend low-molecular-weight heparin (LMWH) for at least 3-6months and possibly indefinitely for patients with active malignancy. There are, however, few data supporting treatment with LMWH beyond 6months. The primary aim of the DALTECAN study (NCT00942968) was to determine the safety of dalteparin between 6 and 12months in cancer-associated VTE. MethodsPatients with active cancer and newly diagnosed VTE were enrolled in a prospective, multicenter study and received subcutaneous dalteparin for 12months. The rates of bleeding and recurrent VTE were evaluated at months 1, 2-6 and 7-12. FindingsOf 334 patients enrolled, 185 and 109 completed 6 and 12months of therapy; 49.1% had deep vein thrombosis (DVT); 38.9% had pulmonary embolism (PE); and 12.0% had both on presentation. The overall frequency of major bleeding was 10.2% (34/334). Major bleeding occurred in 3.6% (12/334) in the first month, and 1.1% (14/1237) and 0.7% (8/1086) per patient-month during months 2-6 and 7-12, respectively. Recurrent VTE occurred in 11.1% (37/334); the incidence rate was 5.7% (19/334) for month 1, 3.4% (10/296) during months 2-6, and 4.1% (8/194) during months 7-12. One hundred and sixteen patients died, four due to recurrent VTE and two due to bleeding. ConclusionMajor bleeding was less frequent during dalteparin therapy beyond 6months. The risk of developing major bleeding complications or VTE recurrence was greatest in the first month of therapy and lower over the subsequent 11 months.
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| 17. |
- Gutman, Boris A, et al.
(författare)
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A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 352-372
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.
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| 18. |
- Hayden, Brian T., et al.
(författare)
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The Rise and Fall of Type Ia Supernova Light Curves in the SDSS-II Supernova Survey
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 712:1, s. 350-366
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Tidskriftsartikel (refereegranskat)abstract
- We analyze the rise and fall times of Type Ia supernova (SN Ia) light curves discovered by the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey. From a set of 391 light curves k-corrected to the rest-frame B and V bands, we find a smaller dispersion in the rising portion of the light curve compared to the decline. This is in qualitative agreement with computer models which predict that variations in radioactive nickel yield have less impact on the rise than on the spread of the decline rates. The differences we find in the rise and fall properties suggest that a single "stretch" correction to the light curve phase does not properly model the range of SN Ia light curve shapes. We select a subset of 105 light curves well observed in both rise and fall portions of the light curves and develop a "2-stretch" fit algorithm which estimates the rise and fall times independently. We find the average time from explosion to B-band peak brightness is 17.38 ± 0.17 days, but with a spread of rise times which range from 13 days to 23 days. Our average rise time is shorter than the 19.5 days found in previous studies; this reflects both the different light curve template used and the application of the 2-stretch algorithm. The SDSS-II supernova set and the local SNe Ia with well-observed early light curves show no significant differences in their average rise-time properties. We find that slow-declining events tend to have fast rise times, but that the distribution of rise minus fall time is broad and single peaked. This distribution is in contrast to the bimodality in this parameter that was first suggested by Strovink from an analysis of a small set of local SNe Ia. We divide the SDSS-II sample in half based on the rise minus fall value, tr - tf <= 2 days and tr - tf > 2 days, to search for differences in their host galaxy properties and Hubble residuals; we find no difference in host galaxy properties or Hubble residuals in our sample.
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| 19. |
- Hudson, Lawrence N., et al.
(författare)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
-
Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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| 20. |
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| 21. |
- Kessler, Christoph W., et al.
(författare)
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Program Composition and Optimization: An Introduction
- 2010
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Ingår i: Proceedings (abstracts collection) of the Dagstuhl Seminar 10191. - Dagstuhl, Germany : Schloss Dagstuhl - Leibniz-Zentrum fuer Informatik.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 22. |
- Kessler, Jan H., et al.
(författare)
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Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes
- 2010
-
Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 12:1, s. 45-53
-
Tidskriftsartikel (refereegranskat)abstract
- Cytotoxic T lymphocytes (CTLs) recognize peptides presented by HLA class I molecules on the cell surface. The C terminus of these CTL epitopes is considered to be produced by the proteasome. Here we demonstrate that the cytosolic endopeptidases nardilysin and thimet oligopeptidase (TOP) complemented proteasome activity. Nardilysin and TOP were required, either together or alone, for the generation of a tumor-specific CTL epitope from PRAME, an immunodominant CTL epitope from Epstein-Barr virus protein EBNA3C, and a clinically important epitope from the melanoma protein MART-1. TOP functioned as C-terminal trimming peptidase in antigen processing, and nardilysin contributed to both the C-terminal and N-terminal generation of CTL epitopes. By broadening the antigenic peptide repertoire, nardilysin and TOP strengthen the immune defense against intracellular pathogens and cancer.
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| 23. |
- Kessler, Richard, et al.
(författare)
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First-Year Sloan Digital Sky Survey-II Supernova Results : Hubble Diagram and Cosmological Parameters
- 2009
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 185:1, s. 32-84
-
Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the Hubble diagram for 103 Type Ia supernovae (SNe) with redshifts 0.04 < z < 0.42, discovered during the first season (Fall 2005) of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey. These data fill in the redshift "desert" between low- and high-redshift SN Ia surveys. Within the framework of the MLCS2K2 light-curve fitting method, we use the SDSS-II SN sample to infer the mean reddening parameter for host galaxies, RV = 2.18 ± 0.14stat ± 0.48syst, and find that the intrinsic distribution of host-galaxy extinction is well fitted by an exponential function, P(AV ) = exp(-AV /τV), with τV = 0.334 ± 0.088 mag. We combine the SDSS-II measurements with new distance estimates for published SN data from the ESSENCE survey, the Supernova Legacy Survey (SNLS), the Hubble Space Telescope (HST), and a compilation of Nearby SN Ia measurements. A new feature in our analysis is the use of detailed Monte Carlo simulations of all surveys to account for selection biases, including those from spectroscopic targeting. Combining the SN Hubble diagram with measurements of baryon acoustic oscillations from the SDSS Luminous Red Galaxy sample and with cosmic microwave background temperature anisotropy measurements from the Wilkinson Microwave Anisotropy Probe, we estimate the cosmological parameters w and ΩM, assuming a spatially flat cosmological model (FwCDM) with constant dark energy equation of state parameter, w. We also consider constraints upon ΩM and ΩΛ for a cosmological constant model (ΛCDM) with w = -1 and non-zero spatial curvature. For the FwCDM model and the combined sample of 288 SNe Ia, we find w = -0.76 ± 0.07(stat) ± 0.11(syst), ΩM = 0.307 ± 0.019(stat) ± 0.023(syst) using MLCS2K2 and w = -0.96 ± 0.06(stat) ± 0.12(syst), ΩM = 0.265 ± 0.016(stat) ± 0.025(syst) using the SALT-II fitter. We trace the discrepancy between these results to a difference in the rest-frame UV model combined with a different luminosity correction from color variations; these differences mostly affect the distance estimates for the SNLS and HST SNe. We present detailed discussions of systematic errors for both light-curve methods and find that they both show data-model discrepancies in rest-frame U band. For the SALT-II approach, we also see strong evidence for redshift-dependence of the color-luminosity parameter (β). Restricting the analysis to the 136 SNe Ia in the Nearby+SDSS-II samples, we find much better agreement between the two analysis methods but with larger uncertainties: w = -0.92 ± 0.13(stat)+0.10 -0.33(syst) for MLCS2K2 and w = -0.92 ± 0.11(stat)+0.07 -0.15 (syst) for SALT-II.
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| 24. |
- Kessler, Richard, et al.
(författare)
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Photometric Estimates of Redshifts and Distance Moduli for Type Ia Supernovae
- 2010
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 717:1, s. 40-57
-
Tidskriftsartikel (refereegranskat)abstract
- Large planned photometric surveys will discover hundreds of thousands of supernovae (SNe), outstripping the resources available for spectroscopic follow-up and necessitating the development of purely photometric methods to exploit these events for cosmological study. We present a light curve fitting technique for type Ia supernova (SN Ia) photometric redshift (photo-z) estimation in which the redshift is determined simultaneously with the other fit parameters. We implement this "LCFIT+Z" technique within the frameworks of the MLCS2K2 and SALTII light curve fit methods and determine the precision on the redshift and distance modulus. This method is applied to a spectroscopically confirmed sample of 296 SNe Ia from the Sloan Digital Sky Survey-II (SDSS-II) SN Survey and 37 publicly available SNe Ia from the Supernova Legacy Survey (SNLS). We have also applied the method to a large suite of realistic simulated light curves for existing and planned surveys, including the SDSS, SNLS, and the Large Synoptic Survey Telescope. When intrinsic SN color fluctuations are included, the photo-z precision for the simulation is consistent with that in the data. Finally, we compare the LCFIT+Z photo-z precision with previous results using color-based SN photo-z estimates.
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| 25. |
- Kessler, Richard, et al.
(författare)
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Results from the Supernova Photometric Classification Challenge
- 2010
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 122:898, s. 1415-1431
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Tidskriftsartikel (refereegranskat)abstract
- We report results from the Supernova Photometric Classification Challenge (SNPhotCC), a publicly released mix of simulated supernovae (SNe), with types (Ia, Ibc, and II) selected in proportion to their expected rates. The simulation was realized in the griz filters of the Dark Energy Survey (DES) with realistic observing conditions (sky noise, point-spread function, and atmospheric transparency) based on years of recorded conditions at the DES site. Simulations of non-Ia-type SNe are based on spectroscopically confirmed light curves that include unpublished non-Ia samples donated from the Carnegie Supernova Project (CSP), the Supernova Legacy Survey (SNLS), and the Sloan Digital Sky Survey-II (SDSS-II). A spectroscopically confirmed subset was provided for training. We challenged scientists to run their classification algorithms and report a type and photo-z for each SN. Participants from 10 groups contributed 13 entries for the sample that included a host-galaxy photo-z for each SN and nine entries for the sample that had no redshift information. Several different classification strategies resulted in similar performance, and for all entries the performance was significantly better for the training subset than for the unconfirmed sample. For the spectroscopically unconfirmed subset, the entry with the highest average figure of merit for classifying SNe Ia has an efficiency of 0.96 and an SN Ia purity of 0.79. As a public resource for the future development of photometric SN classification and photo-z estimators, we have released updated simulations with improvements based on our experience from the SNPhotCC, added samples corresponding to the Large Synoptic Survey Telescope (LSST) and the SDSS-II, and provided the answer keys so that developers can evaluate their own analysis.
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| 26. |
- Längin, Matthias, et al.
(författare)
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Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation
- 2021
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Ingår i: Xenotransplantation. - : Wiley. - 0908-665X .- 1399-3089. ; 28:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Successful preclinical transplantations of porcine hearts into baboon recipients are required before commencing clinical trials. Despite years of research, over half of the orthotopic cardiac xenografts were lost during the first 48 hours after transplantation, primarily caused by perioperative cardiac xenograft dysfunction (PCXD). To decrease the rate of PCXD, we adopted a preservation technique of cold non-ischemic perfusion for our ongoing pig-to-baboon cardiac xenotransplantation project. Methods: Fourteen orthotopic cardiac xenotransplantation experiments were carried out with genetically modified juvenile pigs (GGTA1- KO/hCD46/hTBM) as donors and captive-bred baboons as recipients. Organ preservation was compared according to the two techniques applied: cold static ischemic cardioplegia (IC; n = 5) and cold non-ischemic continuous perfusion (CP; n = 9) with an oxygenated albumin-containing hyperoncotic cardioplegic solution containing nutrients, erythrocytes and hormones. Prior to surgery, we measured serum levels of preformed anti-non-Gal-antibodies. During surgery, hemodynamic parameters were monitored with transpulmonary thermodilution. Central venous blood gas analyses were taken at regular intervals to estimate oxygen extraction, as well as lactate production. After surgery, we measured troponine T and serum parameters of the recipient’s kidney, liver and coagulation functions. Results: In porcine grafts preserved with IC, we found significantly depressed systolic cardiac function after transplantation which did not recover despite increasing inotropic support. Postoperative oxygen extraction and lactate production were significantly increased. Troponin T, creatinine, aspartate aminotransferase levels were pathologically high, whereas prothrombin ratios were abnormally low. In three of five IC experiments, PCXD developed within 24 hours. By contrast, all nine hearts preserved with CP retained fully preserved systolic function, none showed any signs of PCXD. Oxygen extraction was within normal ranges; serum lactate as well as parameters of organ functions were only mildly elevated. Preformed anti-non-Gal-antibodies were similar in recipients receiving grafts from either IC or CP preservation. Conclusions: While standard ischemic cardioplegia solutions have been used with great success in human allotransplantation over many years, our data indicate that they are insufficient for preservation of porcine hearts transplanted into baboons: Ischemic storage caused severe impairment of cardiac function and decreased tissue oxygen supply, leading to multi-organ failure in more than half of the xenotransplantation experiments. In contrast, cold non-ischemic heart preservation with continuous perfusion reliably prevented early graft failure. Consistent survival in the perioperative phase is a prerequisite for preclinical long-term results after cardiac xenotransplantation.
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| 27. |
- Längin, Matthias, et al.
(författare)
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Consistent success in life-supporting porcine cardiac xenotransplantation
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 564:7736, s. 430-433
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Tidskriftsartikel (refereegranskat)abstract
- Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1–3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.
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| 28. |
- Längin, Matthias, et al.
(författare)
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Xenografts Show Signs of Concentric Hypertrophy and Dynamic Left Ventricular Outflow Tract Obstruction after Orthotopic Pig-to-baboon Heart Transplantation
- 2023
-
Ingår i: Transplantation. - 0041-1337. ; 107:12, s. 328-338
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Orthotopic cardiac xenotransplantation has seen substantial advancement in the last years and the initiation of a clinical pilot study is close. However, donor organ overgrowth has been a major hurdle for preclinical experiments, resulting in loss of function and the decease of the recipient. A better understanding of the pathogenesis of organ overgrowth after xenotransplantation is necessary before clinical application. Methods. Hearts from genetically modified (GGTA1-KO, hCD46/hTBM transgenic) juvenile pigs were orthotopically transplanted into male baboons. Group I (control, n = 3) received immunosuppression based on costimulation blockade, group II (growth inhibition, n = 9) was additionally treated with mechanistic target of rapamycin inhibitor, antihypertensive medication, and fast corticoid tapering. Thyroid hormones and insulin-like growth factor 1 were measured before transplantation and before euthanasia, left ventricular (LV) growth was assessed by echocardiography, and hemodynamic data were recorded via a wireless implant. Results. Insulin-like growth factor 1 was higher in baboons than in donor piglets but dropped to porcine levels at the end of the experiments in group I. LV mass increase was 10-fold faster in group I than in group II. This increase was caused by nonphysiological LV wall enlargement. Additionally, pressure gradients between LV and the ascending aorta developed, and signs of dynamic left ventricular outflow tract (LVOT) obstruction appeared. Conclusions. After orthotopic xenotransplantation in baboon recipients, untreated porcine hearts showed rapidly progressing concentric hypertrophy with dynamic LVOT obstruction, mimicking hypertrophic obstructive cardiomyopathy in humans. Antihypertensive and antiproliferative drugs reduced growth rate and inhibited LVOT obstruction, thereby preventing loss of function.
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| 29. |
- Nikpay, Majid, et al.
(författare)
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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
-
Tidskriftsartikel (refereegranskat)abstract
- Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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| 30. |
- Pereira, Susana, et al.
(författare)
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Is the fetus fit for labor? Introducing fast-and-frugal trees (FFTrees) to simplify triage of women for STAN monitoring : An interobserver agreement comparison with traditional classification
- 2024
-
Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - 0001-6349. ; 103:1, s. 68-76
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: It is a shortcoming of traditional cardiotocography (CTG) classification table formats that CTG traces are frequently classified differently by different users, resulting in poor interobserver agreements. A fast-and-frugal tree (FFTree) flow chart may help provide better concordance because it is straightforward and has clearly structured binary questions with understandable “yes” or “no” responses. The initial triage to determine whether a fetus is suitable for labor when utilizing fetal ECG ST analysis (STAN) is very important, since a fetus with restricted capacity to respond to hypoxic stress may not generate STAN events and therefore may become falsely negative. This study aimed to compare physiology-focused FFTree CTG interpretation with FIGO classification for assessing the suitability for STAN monitoring. Material and methods: A retrospective study of 36 CTG traces with a high proportion of adverse outcomes (17/36) selected from a European multicenter study database. Eight experienced European obstetricians evaluated the initial 40 minutes of the CTG recordings and judged whether STAN was a suitable fetal surveillance method and whether intervention was indicated. The experts rated the CTGs using the FFTree and FIGO classifications at least 6 weeks apart. Interobserver agreements were calculated using proportions of agreement and Fleiss’ kappa (κ). Results: The proportions of agreement for “not suitable for STAN” were for FIGO 47% (95% confidence interval [CI] 42%–52%) and for FFTree 60% (95% CI 56–64), ie a significant difference; the corresponding figures for “yes, suitable” were 74% (95% CI 71–77) and 70% (95% CI 67–74). For “intervention needed” the figures were 52% (95% CI 47–56) vs 58% (95% CI 54–62) and for “expectant management” 74% (95% CI 71–77) vs 72% (95% CI 69–75). Fleiss’ κ agreement on “suitability for STAN” was 0.50 (95% CI 0.44–0.56) for the FIGO classification and 0.57 (95% CI 0.51–0.63) for the FFTree classification; the corresponding figures for “intervention or expectancy” were 0.53 (95% CI 0.47–0.59) and 0.57 (95% CI 0.51–0.63). Conclusions: The proportion of agreement among expert obstetricians using the FFTree physiological approach was significantly higher compared with the traditional FIGO classification system in rejecting cases not suitable for STAN monitoring. That might be of importance to avoid false negative STAN recordings. Other agreement figures were similar. It remains to be shown whether the FFTree simplicity will benefit less experienced users and how it will work in real-world clinical scenarios.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Reichart, Bruno, et al.
(författare)
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Pig-to-non-human primate heart transplantation : The final step toward clinical xenotransplantation?
- 2020
-
Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 39:8, s. 751-757
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The demand for donated human hearts far exceeds the number available. Xenotransplantation of genetically modified porcine organs provides an alternative. In 2000, an Advisory Board of the International Society for Heart and Lung Transplantation set the benchmark for commencing clinical cardiac xenotransplantation as consistent 60% survival of non-human primates after life-supporting porcine heart transplantations. Recently, we reported the stepwise optimization of pig-to-baboon orthotopic cardiac xenotransplantation finally resulting in consistent success, with 4 recipients surviving 90 (n = 2), 182, and 195 days. Here, we report on 4 additional recipients, supporting the efficacy of our procedure. Results: The first 2 additional recipients succumbed to porcine cytomegalovirus (PCMV) infections on Days 15 and 27, respectively. In 2 further experiments, PCMV infections were successfully avoided, and 3-months survival was achieved. Throughout all the long-term experiments, heart, liver, and renal functions remained within normal ranges. Post-mortem cardiac diameters were slightly increased when compared with that at the time of transplantation but with no detrimental effect. There were no signs of thrombotic microangiopathy. The current regimen enabled the prolonged survival and function of orthotopic cardiac xenografts in altogether 6 of 8 baboons, of which 4 were now added. These results exceed the threshold set by the Advisory Board of the International Society for Heart and Lung Transplantation. Conclusions: The results of our current and previous experimental cardiac xenotransplantations together fulfill for the first time the pre-clinical efficacy suggestions. PCMV-positive donor animals must be avoided.
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| 35. |
- Sako, Masao, et al.
(författare)
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The Data Release of the Sloan Digital Sky Survey-II Supernova Survey
- 2018
-
Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 130:988
-
Tidskriftsartikel (refereegranskat)abstract
- This paper describes the data release of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey conducted between 2005 and 2007. Light curves, spectra, classifications, and ancillary data are presented for 10,258 variable and transient sources discovered through repeat ugriz imaging of SDSS Stripe 82, a 300 deg(2) area along the celestial equator. This data release is comprised of all transient sources brighter than r similar or equal to 22.5 mag with no history of variability prior to 2004. Dedicated spectroscopic observations were performed on a subset of 889 transients, as well as spectra for thousands of transient host galaxies using the SDSS-III BOSS spectrographs. Photometric classifications are provided for the candidates with good multi-color light curves that were not observed spectroscopically, using host galaxy redshift information when available. From these observations, 4607 transients are either spectroscopically confirmed, or likely to be, supernovae, making this the largest sample of supernova candidates ever compiled. We present a new method for SN host-galaxy identification and derive host-galaxy properties including stellar masses, star formation rates, and the average stellar population ages from our SDSS multi-band photometry. We derive SALT2 distance moduli for a total of 1364 SN. Ia with spectroscopic redshifts as well as photometric redshifts for a further 624 purely photometric SN. Ia candidates. Using the spectroscopically confirmed subset of the three-year SDSS-II SN. Ia sample and assuming a flat.CDM cosmology, we determine Omega(M) = 0.315 +/- 0.093 (statistical error only) and detect a non-zero cosmological constant at 5.7 sigma.
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| 36. |
- Samii, Rouzbeh, et al.
(författare)
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Synthesis and Thermal Study of Hexacoordinated Aluminum(III) Triazenides for Use in Atomic Layer Deposition
- 2021
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Ingår i: Inorganic Chemistry. - : American Chemical Society. - 0020-1669 .- 1520-510X. ; 60:7, s. 4578-4587
-
Tidskriftsartikel (refereegranskat)abstract
- Amidinate and guanidinate ligands have been used extensively to produce volatile and thermally stable precursors for atomic layer deposition. The triazenide ligand is relatively unexplored as an alternative ligand system. Herein, we present six new Al(III) complexes bearing three sets of a 1,3-dialkyltriazenide ligand. These complexes volatilize quantitatively in a single step with onset volatilization temperatures of similar to 150 degrees C and 1 Torr vapor pressures of similar to 134 degrees C. Differential scanning calorimetry revealed that these Al(III) complexes exhibited exothermic events that overlapped with the temperatures of their mass loss events in thermogravimetric analysis. Using quantum chemical density functional theory computations, we found a decomposition pathway that transforms the relatively large hexacoordinated Al(III) precursor into a smaller dicoordinated complex. The pathway relies on previously unexplored interligand proton migrations. These new Al(III) triazenides provide a series of alternative precursors with unique thermal properties that could be highly advantageous for vapor deposition processes of Al containing materials.
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| 37. |
- Samii, Rouzbeh, et al.
(författare)
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Synthesis, characterisation and reactivity of a zinc triazenide for potential use in vapour deposition
- 2024
-
Ingår i: Dalton Transactions. - : ROYAL SOC CHEMISTRY. - 1477-9226 .- 1477-9234. ; 53:13, s. 5911-5916
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we synthesised and characterised a new zinc(ii) triazenide for potential use in vapour deposition of zinc sulphide thin films. The compound is volatile and quantitatively sublimes at 80 degrees C under vacuum (0.5 mbar). Thermogravimetric analysis showed a one-step volatilisation with an onset temperature at similar to 125 degrees C and 5% residual mass. The compound also reacted with 2 or 4 molar equivalents of triphenylsilanethiol to give dimeric and monomeric zinc thiolates, respectively. The high volatility, thermal stability, and reactivity with sterically hindered thiols makes this compound a potential candidate for use in vapour deposition of zinc containing thin films. Herein, we synthesise and characterise a new volatile and thermally stable Zn(ii) triazenide. We also react it with a bulky thiol to give two different Zn(ii) thiolates. This new triazenide shows high promise as a precursor for vapour deposition of ZnS thin films.
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| 38. |
- Samii, Rouzbeh, et al.
(författare)
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Synthesis, Characterization, and Thermal Study of Divalent Germanium, Tin, and Lead Triazenides as Potential Vapor Deposition Precursors
- 2021
-
Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 60:17, s. 12759-12765
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Tidskriftsartikel (refereegranskat)abstract
- Only a few M-N bonded divalent group 14 precursors are available for vapor deposition, in particular for Ge and Pb. A majority of the reported precursors are dicoordinated with the Sn(II) amidinates, the only tetracoordinated examples. No Ge(II) and Pb(II) amidinates suitable for vapor deposition have been demonstrated. Herein, we present tetracoordinated Ge(II), Sn(II), and Pb(II) complexes bearing two sets of chelating 1,3-di-tert-butyltriazenide ligands. These compounds are thermally stable, sublime quantitatively between 60 and 75 degrees C (at 0.5 mbar), and show ideal single-step volatilization by thermogravimetric analysis.
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| 39. |
- Schuette, Moritz, et al.
(författare)
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Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling 44,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.
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| 40. |
- Schuettpelz, Eric, et al.
(författare)
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A community-derived classification for extant lycophytes and ferns
- 2016
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Ingår i: Journal of Systematics and Evolution. - : Wiley. - 1674-4918 .- 1759-6831. ; 54:6, s. 563-603
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Tidskriftsartikel (refereegranskat)abstract
- Phylogeny has long informed pteridophyte classification. As our ability to infer evolutionary trees has improved, classifications aimed at recognizing natural groups have become increasingly predictive and stable. Here, we provide a modern, comprehensive classification for lycophytes and ferns, down to the genus level, utilizing a community-based approach. We use monophyly as the primary criterion for the recognition of taxa, but also aim to preserve existing taxa and circumscriptions that are both widely accepted and consistent with our understanding of pteridophyte phylogeny. In total, this classification treats an estimated 11 916 species in 337 genera, 51 families, 14 orders, and two classes. This classification is not intended as the final word on lycophyte and fern taxonomy, but rather a summary statement of current hypotheses, derived from the best available data and shaped by those most familiar with the plants in question. We hope that it will serve as a resource for those wanting references to the recent literature on pteridophyte phylogeny and classification, a framework for guiding future investigations, and a stimulus to further discourse.
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| 41. |
- Shapiguzov, Alexey, et al.
(författare)
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The PPH1 phosphatase is specifically involved in LHCII dephosphorylation and state transitions in Arabidopsis
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:10, s. 4782-4787
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Tidskriftsartikel (refereegranskat)abstract
- The ability of plants to adapt to changing light conditions depends on a protein kinase network in the chloroplast that leads to the reversible phosphorylation of key proteins in the photosynthetic membrane. Phosphorylation regulates, in a process called state transition, a profound reorganization of the electron transfer chain and remodeling of the thylakoid membranes. Phosphorylation governs the association of the mobile part of the light-harvesting antenna LHCII with either photosystem I or photosystem II. Recent work has identified the redox-regulated protein kinase STN7 as a major actor in state transitions, but the nature of the corresponding phosphatases remained unknown. Here we identify a phosphatase of Arabidopsis thaliana, called PPH1, which is specifically required for the dephosphorylation of light-harvesting complex II (LHCII). We show that this single phosphatase is largely responsible for the dephosphorylation of Lhcb1 and Lhcb2 but not of the photosystem II core proteins. PPH1, which belongs to the family of monomeric PP2C type phosphatases, is a chloroplast protein and is mainly associated with the stroma lamellae of the thylakoid membranes. We demonstrate that loss of PPH1 leads to an increase in the antenna size of photosystem I and to a strong impairment of state transitions. Thus phosphorylation and dephosphorylation of LHCII appear tobe specifically mediated by the kinase/phosphatase pair STN7 and PPH1. These two proteins emerge as key players in the adaptation of the photosynthetic apparatus to changes in light quality and quantity.
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| 42. |
- Smith, Mathew, et al.
(författare)
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THE SDSS-II SUPERNOVA SURVEY : PARAMETERIZING THE TYPE Ia SUPERNOVA RATE AS A FUNCTION OF HOST GALAXY PROPERTIES
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 755:1, s. 61-
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Tidskriftsartikel (refereegranskat)abstract
- Using data from the Sloan Digital Sky Supernova Survey-II (SDSS-II SN Survey), we measure the rate of Type Ia supernovae (SNe Ia) as a function of galaxy properties at intermediate redshift. A sample of 342 SNe Ia with 0.05 < z < 0.25 is constructed. Using broadband photometry and redshifts, we use the PEGASE. 2 spectral energy distributions to estimate host galaxy stellar masses and recent star formation rates (SFRs). We find that the rate of SNe Ia per unit stellar mass is significantly higher (by a factor of similar to 30) in highly star-forming galaxies compared to passive galaxies. When parameterizing the SN Ia rate (SNRIa) based on host galaxy properties, we find that the rate of SNe Ia in passive galaxies is not linearly proportional to the stellar mass; instead an SNRIa proportional to M-0.68 is favored. However, such a parameterization does not describe the observed SNRIa in star-forming galaxies. The SNRIa in star-forming galaxies is well fitted by SNRIa = (0.41 +/- 0.15) x 10(-10) M0.72+/-0.15 + (0.65 +/- 0.25) x 10(-3) SFR1.01+/-0.22 (statistical errors only), where M is the host galaxy stellar mass (in M-circle dot) and SFR is the SFR (in M-circle dot yr(-1)). We show that our results, for SNe Ia in passive galaxies, are consistent with those at higher redshifts (favoring SNRIa proportional to M) when accounting for the difference in the ages of our galaxies. This suggests that the rate of SNe Ia is correlated with the age of the stellar population. The MLCS extinction parameter, A(V), is similar in passive and moderately star-forming galaxies, but we find indications that it is smaller, on average, in highly star-forming galaxies. This result appears to be driven by a deficit of the reddest (A(V) > 0.15) SNe Ia in highly star-forming galaxies. We consider that the high levels of dust in these systems may be obscuring the reddest and faintest SNe Ia.
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| 43. |
- Stitziel, Nathan O., et al.
(författare)
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Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease
- 2016
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
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| 44. |
- Tannous, Bakhos A., et al.
(författare)
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Effects of the Selective MPS1 Inhibitor MPS1-IN-3 on Glioblastoma Sensitivity to Antimitotic Drugs
- 2013
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 105:17, s. 1322-1331
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Tidskriftsartikel (refereegranskat)abstract
- Background Glioblastomas exhibit a high level of chemotherapeutic resistance, including to the antimitotic agents vincristine and taxol. During the mitotic agent-induced arrest, glioblastoma cells are able to perform damage-control and self-repair to continue proliferation. Monopolar spindle 1 (MPS1/TTK) is a checkpoint kinase and a gatekeeper of the mitotic arrest.Methods We used glioblastoma cells to determine the expression of MPS1 and to determine the effects of MPS1 inhibition on mitotic errors and cell viability in combination with vincristine and taxol. The effect of MPS1 inhibition was assessed in different orthotopic glioblastoma mouse models (n = 3-7 mice/group). MPS1 expression levels were examined in relation to patient survival.Results Using publicly available gene expression data, we determined that MPS1 overexpression corresponds positively with tumor grade and negatively with patient survival (two-sided t test, P < .001). Patients with high MPS1 expression (n = 203) had a median and mean survival of 487 and 913 days (95% confidence intervals [CI] = 751 to 1075), respectively, and a 2-year survival rate of 35%, whereas patients with intermediate MPS1 expression (n = 140) had a median and mean survival of 858 and 1183 days (95% CI = 1177 to 1189), respectively, and a 2-year survival rate of 56%. We demonstrate that MPS1 inhibition by RNAi results in sensitization to antimitotic agents. We developed a selective small-molecule inhibitor of MPS1, MPS1-IN-3, which caused mitotic aberrancies in glioblastoma cells and, in combination with vincristine, induced mitotic checkpoint override, increased aneuploidy, and augmented cell death. MPS1-IN-3 sensitizes glioblastoma cells to vincristine in orthotopic mouse models (two-sided log-rank test, P < .01), resulting in prolonged survival without toxicity.Conclusions Our results collectively demonstrate that MPS1, a putative therapeutic target in glioblastoma, can be selectively inhibited by MPS1-IN-3 sensitizing glioblastoma cells to antimitotic drugs.
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| 45. |
- Taylor, Matt, et al.
(författare)
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THE CORE COLLAPSE SUPERNOVA RATE FROM THE SDSS-II SUPERNOVA SURVEY
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 792:2, s. 135-
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Tidskriftsartikel (refereegranskat)abstract
- We use the Sloan Digital Sky Survey II Supernova Survey (SDSS-II SNS) data to measure the volumetric core collapse supernova (CCSN) rate in the redshift range (0.03 < z < 0.09). Using a sample of 89 CCSN, we find a volume-averaged rate of 1.06 +/- 0.19 x 10(-4)((h/0.7)(3)/(yr Mpc(3))) at a mean redshift of 0.072 +/- 0.009. We measure the CCSN luminosity function from the data and consider the implications on the star formation history.
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| 46. |
- Treydte, Kerstin, et al.
(författare)
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Recent human-induced atmospheric drying across Europe unprecedented in the last 400 years
- 2024
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Ingår i: NATURE GEOSCIENCE. - 1752-0894 .- 1752-0908. ; 17, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- The vapor pressure deficit reflects the difference between how much moisture the atmosphere could and actually does hold, a factor that fundamentally affects evapotranspiration, ecosystem functioning, and vegetation carbon uptake. Its spatial variability and long-term trends under natural versus human-influenced climate are poorly known despite being essential for predicting future effects on natural ecosystems and human societies such as crop yield, wildfires, and health. Here we combine regionally distinct reconstructions of pre-industrial summer vapor pressure deficit variability from Europe's largest oxygen-isotope network of tree-ring cellulose with observational records and Earth system model simulations with and without human forcing included. We demonstrate that an intensification of atmospheric drying during the recent decades across different European target regions is unprecedented in a pre-industrial context and that it is attributed to human influence with more than 98% probability. The magnitude of this trend is largest in Western and Central Europe, the Alps and Pyrenees region, and the smallest in southern Fennoscandia. In view of the extreme drought and compound events of the recent years, further atmospheric drying poses an enhanced risk to vegetation, specifically in the densely populated areas of the European temperate lowlands. The atmosphere has dried across most regions of Europe in recent decades, a trend that can be attributed primarily to human impacts, according to tree ring records spanning 400 years and Earth system model simulations.
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| 47. |
- Wilson, Samuel T., et al.
(författare)
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Ideas and perspectives : A strategic assessment of methane and nitrous oxide measurements in the marine environment
- 2020
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 17:22, s. 5809-5828
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Tidskriftsartikel (refereegranskat)abstract
- In the current era of rapid climate change, accurate characterization of climate-relevant gas dynamics – namely production, consumption, and net emissions – is required for all biomes, especially those ecosystems most susceptible to the impact of change. Marine environments include regions that act as net sources or sinks for numerous climate-active trace gases including methane (CH4) and nitrous oxide (N2O). The temporal and spatial distributions of CH4 and N2O are controlled by the interaction of complex biogeochemical and physical processes. To evaluate and quantify how these mechanisms affect marine CH4 and N2O cycling requires a combination of traditional scientific disciplines including oceanography, microbiology, and numerical modeling. Fundamental to these efforts is ensuring that the datasets produced by independent scientists are comparable and interoperable. Equally critical is transparent communication within the research community about the technical improvements required to increase our collective understanding of marine CH4 and N2O. A workshop sponsored by Ocean Carbon and Biogeochemistry (OCB) was organized to enhance dialogue and collaborations pertaining to marine CH4 and N2O. Here, we summarize the outcomes from the workshop to describe the challenges and opportunities for near-future CH4 and N2O research in the marine environment.
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