1. |
- Province, M. A., et al.
(författare)
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CYP2D6 Genotype and Adjuvant Tamoxifen : Meta-Analysis of Heterogeneous Study Populations
- 2014
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Ingår i: Clinical Pharmacology and Therapeutics. - New York, USA : Nature Publishing Group. - 0009-9236 .- 1532-6535. ; 95:2, s. 216-227
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Tidskriftsartikel (refereegranskat)abstract
- The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1), CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.
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2. |
- Ackermann, M., et al.
(författare)
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MULTI-WAVELENGTH OBSERVATIONS OF BLAZAR AO 0235+164 IN THE 2008-2009 FLARING STATE
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 751:2
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Tidskriftsartikel (refereegranskat)abstract
- The blazarAO 0235+164 (z=0.94) has been one of the most active objects observed by Fermi Large Area Telescope (LAT) since its launch in Summer 2008. In addition to the continuous coverage by Fermi, contemporaneous observations were carried out from the radio to gamma-ray bands between 2008 September and 2009 February. In this paper, we summarize the rich multi-wavelength data collected during the campaign (including F-GAMMA, GASP-WEBT, Kanata, OVRO, RXTE, SMARTS, Swift, and other instruments), examine the cross-correlation between the light curves measured in the different energy bands, and interpret the resulting spectral energy distributions in the context of well-known blazar emission models. We find that the gamma-ray activity is well correlated with a series of near-IR/optical flares, accompanied by an increase in the optical polarization degree. On the other hand, the X-ray light curve shows a distinct 20 day high state of unusually soft spectrum, which does not match the extrapolation of the optical/UV synchrotron spectrum. We tentatively interpret this feature as the bulk Compton emission by cold electrons contained in the jet, which requires an accretion disk corona with an effective covering factor of 19% at a distance of 100 R-g. We model the broadband spectra with a leptonic model with external radiation dominated by the infrared emission from the dusty torus.
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3. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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4. |
- Fretwell, P., et al.
(författare)
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Bedmap2 : improved ice bed, surface and thickness datasets for Antarctica
- 2013
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Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 7:1, s. 375-393
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Tidskriftsartikel (refereegranskat)abstract
- We present Bedmap2, a new suite of gridded products describing surface elevation, ice-thickness and the seafloor and subglacial bed elevation of the Antarctic south of 60 degrees S. We derived these products using data from a variety of sources, including many substantial surveys completed since the original Bedmap compilation (Bedmap1) in 2001. In particular, the Bedmap2 ice thickness grid is made from 25 million measurements, over two orders of magnitude more than were used in Bedmap1. In most parts of Antarctica the subglacial landscape is visible in much greater detail than was previously available and the improved data-coverage has in many areas revealed the full scale of mountain ranges, valleys, basins and troughs, only fragments of which were previously indicated in local surveys. The derived statistics for Bedmap2 show that the volume of ice contained in the Antarctic ice sheet (27 million km(3)) and its potential contribution to sea-level rise (58 m) are similar to those of Bedmap1, but the mean thickness of the ice sheet is 4.6% greater, the mean depth of the bed beneath the grounded ice sheet is 72m lower and the area of ice sheet grounded on bed below sea level is increased by 10 %. The Bedmap2 compilation highlights several areas beneath the ice sheet where the bed elevation is substantially lower than the deepest bed indicated by Bedmap1. These products, along with grids of data coverage and uncertainty, provide new opportunities for detailed modelling of the past and future evolution of the Antarctic ice sheets.
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5. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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6. |
- Biermann, F., et al.
(författare)
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Navigating the Anthropocene: Improving Earth System Governance
- 2012
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 335:6074, s. 1306-1307
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The United Nations conference in Rio de Janeiro in June is an important opportunity to improve the institutional framework for sustainable development.
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7. |
- Gallagher, Michael D., et al.
(författare)
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TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 127:3, s. 407-418
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Tidskriftsartikel (refereegranskat)abstract
- Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease.
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8. |
- Golightly, Yvonne M., et al.
(författare)
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Psychometric Properties of the Foot and Ankle Outcome Score in a Community-Based Study of Adults With and Without Osteoarthritis
- 2014
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 66:3, s. 395-403
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveFoot and ankle problems are common in adults, and large observational studies are needed to advance our understanding of the etiology and impact of these conditions. Valid and reliable measures of foot and ankle symptoms and physical function are necessary for this research. This study examined psychometric properties of the Foot and Ankle Outcome Score (FAOS) subscales (pain, other symptoms, activities of daily living [ADL], sport and recreational function [sport/recreation], and foot- and ankle-related quality of life [QOL]) in a large, community-based sample of African American and white men and women ages 50 years. MethodsJohnston County Osteoarthritis Project participants (n = 1,670) completed the 42-item FAOS (mean age 69 years, 68% women, 31% African American, mean body mass index [BMI] 31.5 kg/m(2)). Internal consistency, test-retest reliability, convergent validity, and structural validity of each subscale were examined for the sample and for subgroups according to race, sex, age, BMI, presence of knee or hip osteoarthritis, and presence of knee, hip, or low back symptoms. ResultsFor the sample and each subgroup, Cronbach's alpha coefficients ranged from 0.95-0.97 (pain), 0.97-0.98 (ADL), 0.94-0.96 (sport/recreation), 0.89-0.92 (QOL), and 0.72-0.82 (symptoms). Correlation coefficients ranged from 0.24-0.52 for pain and symptoms subscales with foot and ankle symptoms and from 0.30-0.55 for ADL and sport/recreation subscales with the Western Ontario and McMaster Universities Osteoarthritis Index function subscale. Intraclass correlation coefficients for test-retest reliability ranged from 0.63-0.81. Items loaded on a single factor for each subscale except symptoms (2 factors). ConclusionThe FAOS exhibited sufficient reliability and validity in this large cohort study.
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9. |
- Hayashida, M., et al.
(författare)
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THE STRUCTURE AND EMISSION MODEL OF THE RELATIVISTIC JET IN THE QUASAR 3C 279 INFERRED FROM RADIO TO HIGH-ENERGY gamma-RAY OBSERVATIONS IN 2008-2010
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 754:2, s. 114-
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Tidskriftsartikel (refereegranskat)abstract
- We present time-resolved broadband observations of the quasar 3C 279 obtained from multi-wavelength campaigns conducted during the first two years of the Fermi Gamma-ray Space Telescope mission. While investigating the previously reported gamma-ray/optical flare accompanied by a change in optical polarization, we found that the optical emission appears to be delayed with respect to the gamma-ray emission by about 10 days. X-ray observations reveal a pair of isolated flares separated by similar to 90 days, with only weak gamma-ray/optical counterparts. The spectral structure measured by Spitzer reveals a synchrotron component peaking in the mid-infrared band with a sharp break at the far-infrared band during the gamma-ray flare, while the peak appears in the millimeter (mm)/submillimeter (sub-mm) band in the low state. Selected spectral energy distributions are fitted with leptonic models including Comptonization of external radiation produced in a dusty torus or the broad-line region. Adopting the interpretation of the polarization swing involving propagation of the emitting region along a curved trajectory, we can explain the evolution of the broadband spectra during the gamma-ray flaring event by a shift of its location from similar to 1 pc to similar to 4 pc from the central black hole. On the other hand, if the gamma-ray flare is generated instead at sub-pc distance from the central black hole, the far-infrared break can be explained by synchrotron self-absorption. We also model the low spectral state, dominated by the mm/sub-mm peaking synchrotron component, and suggest that the corresponding inverse-Compton component explains the steady X-ray emission.
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10. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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A high-resolution map of human evolutionary constraint using 29 mammals
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 478:7370, s. 476-482
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Tidskriftsartikel (refereegranskat)abstract
- The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering similar to 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for similar to 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate-and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
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11. |
- Biermann, Frank, et al.
(författare)
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Transforming governance and institutions for global sustainability : key insights from the Earth System Governance Project
- 2012
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 4:1, s. 51-60
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Tidskriftsartikel (refereegranskat)abstract
- The current institutional framework for sustainable development is by far not strong enough to bring about the swift transformative progress that is needed. This article contends that incrementalism-the main approach since the 1972 Stockholm Conference-will not suffice to bring about societal change at the level and speed needed to mitigate and adapt to earth system transformation. Instead, the article argues that transformative structural change in global governance is needed, and that the 2012 United Nations Conference on Sustainable Development in Rio de Janeiro must turn into a major stepping stone for a much stronger institutional framework for sustainable development. The article details core areas where urgent action is required. The article is based on an extensive social science assessment conducted by 32 members of the lead faculty, scientific steering committee, and other affiliates of the Earth System Governance Project. This Project is a ten-year research initiative under the auspices of the International Human Dimensions Programme on Global Environmental Change (IHDP), which is sponsored by the International Council for Science (ICSU), the International Social Science Council (ISSC), and the United Nations University (UNU).
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12. |
- Bower, G. C., et al.
(författare)
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THE ALLEN TELESCOPE ARRAY Pi GHz SKY SURVEY. I. SURVEY DESCRIPTION AND STATIC CATALOG RESULTS FOR THE BOOTES FIELD
- 2010
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 725:2, s. 1792-1804
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Tidskriftsartikel (refereegranskat)abstract
- The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array. PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky with an emphasis on synoptic observations that measure the static and time-variable properties of the sky. During the 2.5 year campaign, PiGSS will twice observe similar to 250,000 radio sources in the 10,000 deg(2) region of the sky with b > 30 degrees to an rms sensitivity of similar to 1 mJy. Additionally, sub-regions of the sky will be observed multiple times to characterize variability on timescales of days to years. We present here observations of a 10 deg(2) region in the Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The PiGSS image was constructed from 75 daily observations distributed over a 4 month period and has an rms flux density between 200 and 250 mu Jy. This represents a deeper image by a factor of 4-8 than we will achieve over the entire 10,000 deg(2). We provide flux densities, source sizes, and spectral indices for the 425 sources detected in the image. We identify similar to 100 new flat-spectrum radio sources; we project that when completed PiGSS will identify 10(4) flat-spectrum sources. We identify one source that is a possible transient radio source. This survey provides new limits on faint radio transients and variables with characteristic durations of months.
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14. |
- Distler, J. H. W., et al.
(författare)
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Is there a role for TNF-alpha antagonists in the treatment of SSc? EUSTAR expert consensus development using the Delphi technique
- 2011
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Ingår i: Clinical and Experimental Rheumatology. - 1593-098X. ; 29:2, s. 40-45
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To obtain experiences and expert opinion on treatment of SSc patients with TNF-alpha antagonists. Methods: An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-alpha antagonists. Assessment forms on the frequency of TNF-alpha inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) centres. Afterwards, a three round Delphi exercise was performed to obtain expert consensus on the use of TNF-alpha inhibitors in SSc. Results: Seventy-nine centres returned information on use of TNF-alpha antagonists in SSc patients. A total of 65 patients were treated with TNF-alpha inhibitors in 14 different centres. Forty-eight of the 65 patients treated with TNF-alpha inhibitors improved. Improvement was mainly seen in patients with arthritis, whereas the effects on fibrosis varied. In the first round of the subsequent Delphi approach, 71 out of 79 experts stated that they would use TNF-alpha antagonists in SSc. Arthritis was suggested as an indication for TNF alpha antagonists by 75% of the experts. However; after the third stage of the Delphi exercise, the acceptance for the off-label use of TNF-alpha antagonists decreased and 59% recommended that TNF-alpha antagonists should not be used or only used in clinical trials in SSc patients, while 38% of the experts suggested the use of TNF-alpha antagonists for arthritis associated with SSc. Conclusions: Most of the experts do not recommend the routine use of TNF-alpha antagonists in systemic sclerosis. Arthritis might be a potential indication in SSc, although controlled clinical trials with TNF-alpha antagonists are needed before general recommendations can be given.
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15. |
- Lindsten, Fredrik, et al.
(författare)
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A Semiparametric Bayesian Approach to Wiener System Identification
- 2012
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Ingår i: Proceedings of the 16th IFAC Symposium on System Identification. - 9783902823069 ; , s. 1137-1142
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Konferensbidrag (refereegranskat)abstract
- We consider a semiparametric, i.e. a mixed parametric/nonparametric, model of a Wiener system. We use a state-space model for the linear dynamical system and a nonparametric Gaussian process (GP) model for the static nonlinearity. The GP model is a flexible model that can describe different types of nonlinearities while avoiding making strong assumptions such as monotonicity. We derive an inferential method based on recent advances in Monte Carlo statistical methods, known as Particle Markov Chain Monte Carlo (PMCMC). The idea underlying PMCMC is to use a particle filter (PF) to generate a sample state trajectory in a Markov chain Monte Carlo sampler. We use a recently proposed PMCMC sampler, denoted particle Gibbs with backward simulation, which has been shown to be efficient even when we use very few particles in the PF. The resulting method is used in a simulation study to identify two different Wiener systems with non-invertible nonlinearities.
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16. |
- Lindsten, Fredrik, et al.
(författare)
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Particle Gibbs with Ancestor Sampling
- 2014
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Ingår i: Journal of machine learning research. - : MICROTOME PUBL. - 1532-4435 .- 1533-7928. ; 15, s. 2145-2184
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Tidskriftsartikel (refereegranskat)abstract
- Particle Markov chain Monte Carlo (PMCMC) is a systematic way of combining the two main tools used for Monte Carlo statistical inference: sequential Monte Carlo (SMC) and Markov chain Monte Carlo (MCMC). We present a new PMCMC algorithm that we refer to as particle Gibbs with ancestor sampling (PGAS). PGAS provides the data analyst with an off-the-shelf class of Markov kernels that can be used to simulate, for instance, the typically high-dimensional and highly autocorrelated state trajectory in a state-space model. The ancestor sampling procedure enables fast mixing of the PGAS kernel even when using seemingly few particles in the underlying SMC sampler. This is important as it can significantly reduce the computational burden that is typically associated with using SMC. PGAS is conceptually similar to the existing PG with backward simulation (PGBS) procedure. Instead of using separate forward and backward sweeps as in PGBS, however, we achieve the same effect in a single forward sweep. This makes PGAS well suited for addressing inference problems not only in state-space models, but also in models with more complex dependencies, such as non-Markovian, Bayesian nonparametric, and general probabilistic graphical models.
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18. |
- Orange, Jordan S, et al.
(författare)
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IL-2 induces a WAVE2-dependent pathway for actin reorganization that enables WASp-independent human NK cell function.
- 2011
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Ingår i: The Journal of clinical investigation. - 1558-8238. ; 121:4, s. 1535-48
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Tidskriftsartikel (refereegranskat)abstract
- Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency associated with an increased susceptibility to herpesvirus infection and hematologic malignancy as well as a deficiency of NK cell function. It is caused by defective WAS protein (WASp). WASp facilitates filamentous actin (F-actin) branching and is required for F-actin accumulation at the NK cell immunological synapse and NK cell cytotoxicity ex vivo. Importantly, the function of WASp-deficient NK cells can be restored in vitro after exposure to IL-2, but the mechanisms underlying this remain unknown. Using a WASp inhibitor as well as cells from patients with WAS, we have defined a direct effect of IL-2 signaling upon F-actin that is independent of WASp function. We found that IL-2 treatment of a patient with WAS enhanced the cytotoxicity of their NK cells and the F-actin content at the immunological synapses formed by their NK cells. IL-2 stimulation of NK cells in vitro activated the WASp homolog WAVE2, which was required for inducing WASp-independent NK cell function, but not for baseline activity. Thus, WAVE2 and WASp define parallel pathways to F-actin reorganization and function in human NK cells; although WAVE2 was not required for NK cell innate function, it was accessible through adaptive immunity via IL-2. These results demonstrate how overlapping cytoskeletal activities can utilize immunologically distinct pathways to achieve synonymous immune function.
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19. |
- Peters, W., et al.
(författare)
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Seven years of recent European net terrestrial carbon dioxide exchange constrained by atmospheric observations
- 2010
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 16:4, s. 1317-1337
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Tidskriftsartikel (refereegranskat)abstract
- We present an estimate of net ecosystem exchange (NEE) of CO2 in Europe for the years 2001-2007. It is derived with a data assimilation that uses a large set of atmospheric CO2 mole fraction observations (similar to 70 000) to guide relatively simple descriptions of terrestrial and oceanic net exchange, while fossil fuel and fire emissions are prescribed. Weekly terrestrial sources and sinks are optimized (i.e., a flux inversion) for a set of 18 large ecosystems across Europe in which prescribed climate, weather, and surface characteristics introduce finer scale gradients. We find that the terrestrial biosphere in Europe absorbed a net average of -165 Tg C yr-1 over the period considered. This uptake is predominantly in non-EU countries, and is found in the northern coniferous (-94 Tg C yr-1) and mixed forests (-30 Tg C yr-1) as well as the forest/field complexes of eastern Europe (-85 Tg C yr-1). An optimistic uncertainty estimate derived using three biosphere models suggests the uptake to be in a range of -122 to -258 Tg C yr-1, while a more conservative estimate derived from the a-posteriori covariance estimates is -165 +/- 437 Tg C yr-1. Note, however, that uncertainties are hard to estimate given the nature of the system and are likely to be significantly larger than this. Interannual variability in NEE includes a reduction in uptake due to the 2003 drought followed by 3 years of more than average uptake. The largest anomaly of NEE occurred in 2005 concurrent with increased seasonal cycles of observed CO2. We speculate these changes to result from the strong negative phase of the North Atlantic Oscillation in 2005 that lead to favorable summer growth conditions, and altered horizontal and vertical mixing in the atmosphere. All our results are available through http://www.carbontracker.eu.
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20. |
- Reed, R. A., et al.
(författare)
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Anthology of the Development of Radiation Transport Tools as Applied to Single Event Effects
- 2013
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Ingår i: IEEE Transactions on Nuclear Science. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9499 .- 1558-1578. ; 60:3, s. 1876-1911
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Tidskriftsartikel (refereegranskat)abstract
- This anthology contains contributions from eleven different groups, each developing and/or applying Monte Carlo-based radiation transport tools to simulate a variety of effects that result from energy transferred to a semiconductor material by a single particle event. The topics span from basic mechanisms for single-particle induced failures to applied tasks like developing websites to predict on-orbit single event failure rates using Monte Carlo radiation transport tools.
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21. |
- Schmoll, H. J., et al.
(författare)
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ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 23:10, s. 2479-2516
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.
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22. |
- Van Deerlin, Vivian M, et al.
(författare)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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