| 1. |
- Apel, Maria, et al.
(författare)
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Variants in RUNX3 Contribute to Susceptibility to Psoriatic Arthritis, Exhibiting Further Common Ground With Ankylosing Spondylitis
- 2013
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 65:5, s. 1224-1231
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Tidskriftsartikel (refereegranskat)abstract
- Objective Psoriatic arthritis (PsA) is a common inflammatory joint disease distinct from other chronic arthritides and frequently accompanied by psoriasis vulgaris. In a first genome-wide association study (GWAS), we were able to identify several genetic risk factors. However, even combined with previously identified factors, the genetic contribution to disease was not fully explained. Therefore, we undertook this study to investigate further 17 loci from our GWAS that did not reach genome-wide significance levels of association in the initial analysis. Methods Twenty-one of 22 single-nucleotide polymorphisms were successfully genotyped in independent cohorts of 1,398 PsA patients and 6,389 controls and in a group of 964 German patients with psoriasis vulgaris. Results Association with a RUNX3 variant, rs4649038, was replicated in independent patients and controls and resulted in a combined P value of 1.40 x 108 by Cochran-Mantel-Haenszel test and an odds ratio (OR) of 1.24 (95% confidence interval [95% CI] 1.151.33). Further analyses based on linkage disequilibrium (LD) at RUNX3 refined the most significant association to an LD block located in the first intron of one isoform. Weaker evidence for association was detected in German patients with psoriasis vulgaris (P = 5.89 x 102; OR 1.13 [95% CI 1.001.28]), indicating a role in the skin manifestations of psoriasis. Conclusion Our analyses identified variants in RUNX3 as susceptibility factors for PsA. RUNX3 has already been implicated in susceptibility to ankylosing spondylitis, another spondyloarthritis, although its risk allele is independent from the one for PsA. RUNX-3 is involved in CD8+ T lymphocyte differentiation and is therefore a good candidate for involvement in PsA and psoriasis vulgaris as T cellmediated diseases.
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| 2. |
- 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
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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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| 3. |
- Hüffmeier, Ulrike, et al.
(författare)
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Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 996-999
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Tidskriftsartikel (refereegranskat)abstract
- Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10⁻¹⁷). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10⁻³). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10⁻²⁰, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.
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| 4. |
- Leao, Richardson N., et al.
(författare)
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A Voltage-Sensitive Dye-Based Assay for the Identification of Differentiated Neurons Derived from Embryonic Neural Stem Cell Cultures
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:11, s. e13833-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pluripotent and multipotent stem cells hold great therapeutical promise for the replacement of degenerated tissue in neurological diseases. To fulfill that promise we have to understand the mechanisms underlying the differentiation of multipotent cells into specific types of neurons. Embryonic stem cell (ESC) and embryonic neural stem cell (NSC) cultures provide a valuable tool to study the processes of neural differentiation, which can be assessed using immunohistochemistry, gene expression, Ca2+-imaging or electrophysiology. However, indirect methods such as protein and gene analysis cannot provide direct evidence of neuronal functionality. In contrast, direct methods such as electrophysiological techniques are well suited to produce direct evidence of neural functionality but are limited to the study of a few cells on a culture plate. Methodology/Principal Findings: In this study we describe a novel method for the detection of action potential-capable neurons differentiated from embryonic NSC cultures using fast voltage-sensitive dyes (VSD). We found that the use of extracellularly applied VSD resulted in a more detailed labeling of cellular processes compared to calcium indicators. In addition, VSD changes in fluorescence translated precisely to action potential kinetics as assessed by the injection of simulated slow and fast sodium currents using the dynamic clamp technique. We further demonstrate the use of a finite element model of the NSC culture cover slip for optimizing electrical stimulation parameters. Conclusions/Significance: Our method allows for a repeatable fast and accurate stimulation of neurons derived from stem cell cultures to assess their differentiation state, which is capable of monitoring large amounts of cells without harming the overall culture.
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| 5. |
- Reis, Andre B, et al.
(författare)
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Distortion Optimized Multi-Service Scheduling for Next-Generation Wireless Mesh Networks
- 2010
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Konferensbidrag (refereegranskat)abstract
- Distributing multimedia content over wireless networks is challenging due to the limited resource availability and the unpredictability of wireless links. As more and more users demand wireless access to (real-time) multimedia services, the impact of constrained resources is different for different media types. Therefore, understanding this impact and developing mechanisms to optimize content delivery under resource constraints according to user perception will be key in improving user satisfaction. In this paper, we develop a novel scheduling algorithm for multi-hop wireless networks, which optimizes packet delivery for multiple audio, video and data flows according to user perceivable quality metrics. We formulate a multidimensional optimization problem to minimize the overall distortion while satisfying resource constraints for the wireless links. Our Quality-of-Experience (QoE)-optimized scheduler makes use of models to determine the user's perception of quality that are specific to the type of service being provided. Our experimental results, obtained with the NS-2 IEEE 802.16 MESH-mode simulator, show that distortion-aware scheduling can significantly increase the perceived quality of multimedia streaming under bandwidth constraints. As the scheduler allows the modeling of fairness constraints among multiple competing flows, we also demonstrate an improvement in fairness across different flows.
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| 6. |
- Reis, Andre B., et al.
(författare)
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Quality of Experience Optimized Scheduling in Multi-Service Wireless Mesh Networks
- 2010
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Ingår i: Proceedings of International Conference on Image Processing (ICIP) 2010. - : IEEE conference proceedings. - 9781424479948 ; , s. 3233-3236
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Konferensbidrag (refereegranskat)abstract
- A growing trend has emerged in network architecture research to switch focus from Quality of Service (QoS) to Quality of Experience (QoE) optimization. In this paper, we first present QoE models that characterize user satisfaction of video, audio, and data services over wireless networks. We then develop a novel packet scheduling algorithm for multi-hop wireless networks that jointly optimizes the delivery of multiple video, audio, and data flows according to the QoE metrics. We formulate a multidimensional optimization problem that minimizes the overall distortion across all flows for the given network resources on wireless links. Fairness constraints over the flows are also considered as part of the optimization. Our experimental results, obtained with the NS-2 IEEE 802.16 MESH-mode simulator, show that distortion-aware scheduling can significantly increase the perceived quality of different wireless services under bandwidth constraints. Additionally, improved fairness across the competing flows is demonstrated relative to conventional scheduling techniques.
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| 7. |
- Reis Teixeira, Andre Azevedo, et al.
(författare)
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Fast Proton Titration Scheme for Multiscale Modeling of Protein Solutions
- 2010
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 6:10, s. 3259-3266
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Tidskriftsartikel (refereegranskat)abstract
- Proton exchange between titratable amino acid residues and the surrounding solution gives rise to exciting electric processes in proteins. We present a proton titration scheme for studying acid-base equilibria in Metropolis Monte Carlo simulations where salt is treated at the Debye-Huckel level. The method, rooted in the Kirkwood model of impenetrable spheres, is applied on the three milk proteins alpha-lactalbumin, beta-lactoglobulin, and lactoferrin, for which we investigate the net-charge, molecular dipole moment, and charge capacitance. Over a wide range of pH and salt conditions, excellent agreement is found with more elaborate simulations where salt is explicitly included. The implicit salt scheme is orders of magnitude faster than the explicit analog and allows for transparent interpretation of physical mechanisms. It is shown how the method can be expanded to multiscale modeling of aqueous salt solutions of many biomolecules with nonstatic charge distributions. Important examples are protein-protein aggregation, protein-polyelectrolyte complexation, and protein-membrane association.
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| 8. |
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| 9. |
- Susano Pinto, André, et al.
(författare)
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Novelty detection using graphical models for semantic room classification
- 2011
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Ingår i: 15th Portuguese Conference on Artificial Intelligence, EPIA 2011. - Berlin, Heidelberg : Springer Berlin Heidelberg. ; , s. 326-339
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Konferensbidrag (refereegranskat)abstract
- This paper presents an approach to the problem of novelty detection in the context of semantic room categorization. The ability to assign semantic labels to areas in the environment is crucial for autonomous agents aiming to perform complex human-like tasks and human interaction. However, in order to be robust and naturally learn the semantics from the human user, the agent must be able to identify gaps in its own knowledge. To this end, we propose a method based on graphical models to identify novel input which does not match any of the previously learnt semantic descriptions. The method employs a novelty threshold defined in terms of conditional and unconditional probabilities. The novelty threshold is then optimized using an unconditional probability density model trained from unlabelled data.
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