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| 2. |
- Barausse, Enrico, et al.
(author)
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Prospects for fundamental physics with LISA
- 2020
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In: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
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Journal article (other academic/artistic)abstract
- In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
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- Barack, Leor, et al.
(author)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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In: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Research review (peer-reviewed)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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| 8. |
- Couch, Y., et al.
(author)
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A brief history of nearly EV-erything - The rise and rise of extracellular vesicles
- 2021
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In: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 10:14
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Journal article (peer-reviewed)abstract
- Extracellular vesicles (EVs) are small cargo-bearing vesicles released by cells into the extracellular space. The field of EVs has grown exponentially over the past two decades; this growth follows the realisation that EVs are not simply a waste disposal system as had originally been suggested by some, but also a complex cell-to-cell communication mechanism. Indeed, EVs have been shown to transfer functional cargo between cells and can influence several biological processes. These small biological particles are also deregulated in disease. As we approach the 75th anniversary of the first experiments in which EVs were unknowingly isolated, it seems right to take stock and look back on how the field started, and has since exploded into its current state. Here we review the early experiments, summarise key findings that have propelled the field, describe the growth of an organised EV community, discuss the current state of the field, and identify key challenges that need to be addressed.
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| 9. |
- Escaned, Javier, et al.
(author)
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Applied coronary physiology for planning and guidance of percutaneous coronary interventions. A clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the European Society of Cardiology
- 2023
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In: EuroIntervention. - : Europa Digital & Publishing. - 1774-024X .- 1969-6213. ; 19:6, s. 464-
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Journal article (peer-reviewed)abstract
- The clinical value of fractional flow reserve and non-hyperaemic pressure ratios are well established in determining an indication for percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). In addition, over the last 5 years we have witnessed a shift towards the use of physio-logy to enhance procedural planning, assess post-PCI functional results, and guide PCI optimisation. In this regard, clinical studies have reported compelling data supporting the use of longitudinal vessel analysis, obtained with pressure guidewire pullbacks, to better understand how obstructive CAD contributes to myocardial ischaemia, to establish the likelihood of functionally successful PCI, to identify the presence and location of residual flow-limiting stenoses and to predict long-term outcomes. The introduction of new functional coronary angiography tools, which merge angiographic information with fluid dynamic equations to deliver information equivalent to intracoronary pressure measurements, are now available and potentially also applicable to these endeavours. Furthermore, the ability of longitudinal vessel analysis to predict the functional results of stenting has played an integral role in the evolving field of simulated PCI. Nevertheless, it is important to have an awareness of the value and challenges of physiology-guided PCI in specific clinical and anatomical contexts. The main aim of this European Association of Percutaneous Cardiovascular Interventions clinical consensus statement is to offer up-to-date evidence and expert opin-ion on the use of applied coronary physiology for procedural PCI planning, disease pattern recognition and post-PCI optimisation.
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| 12. |
- Gray, I., et al.
(author)
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A novel approach for the autonomous inspection and repair of aircraft composite structures
- 2019
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In: <em>18<sup>th</sup> European Conference on Composite Materials </em>(ECCM). - : Applied Mechanics Laboratory.
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Conference paper (other academic/artistic)abstract
- The paper presents the results obtained in the first two years of the H2020 CompInnova project which deals with the development of an innovative approach for inspection and repair of damage in aeronautical composites. The development of a newly designed robotic platform for autonomous inspection using combined infrared thermography (IRT) and phased array (PA) non-destructive investigation for damage detection and characterization, while integrated with laser repair capabilities. PA and IRT are combined in order to detect near-surface and sub-surface damages. Development of a novel thermographic technique termed Pulsed Phase-informed Lock-In Thermography, enables for the first time the rapid and quantitative assessment of damage in the materials. Furthermore, the results are fused using machine learning and image processing techniques for detection and sizing in real time. This will provide the information needed for an automatic laser repair procedure capable of removing precisely ply-by-ply the material. This method allows to have a well-treated surface to apply a repair patch. The three different modules (PA, IRT and laser repair) are integrated on an autonomous robotic platform. The robot is going to be able to attach and move on surfaces of different orientations via the use of a vortex-based actuation system, thus providing the ability to autonomously access, scan and repair the different sections of an aircraft fuselage. © CCM 2020 - 18th European Conference on Composite Materials. All rights reserved.
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| 14. |
- Kalra, Hina, et al.
(author)
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Vesiclepedia : a compendium for extracellular vesicles with continuous community annotation
- 2012
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In: PLoS biology. - : Public library of science. - 1544-9173 .- 1545-7885. ; 10:12, s. e1001450-
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Journal article (peer-reviewed)abstract
- Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field.
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| 15. |
- Kostopoulos, V., et al.
(author)
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Autonomous Inspection and Repair of Aircraft Composite Structures
- 2018
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In: 18th IFAC Conference on Technology, Culture and International Stability TECIS 2018. - : Elsevier. ; , s. 554-557, s. 554-557
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Conference paper (peer-reviewed)abstract
- This paper deals with the development of an innovative approach for inspection and repair of damage in aeronautical composites that took place in the first two years of the H2020 Compinnova project which. The aim is a newly designed robotic platform for autonomous inspection using combined infrared thermography (IRT) and phased array (PA) non-destructive investigation for damage detection and characterization, while integrated with laser repaircapabilities. This will affect the increasing societal need for safer aircraft in the lowest possible cost, while new and effective techniques of inspection are needed because of the rapidly expanding use of composites in the aerospace industry.
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| 16. |
- Lahore, G. F., et al.
(author)
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Vitamin D3 receptor polymorphisms regulate T cells and T cell-dependent inflammatory diseases
- 2020
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:40, s. 24986-24997
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Journal article (peer-reviewed)abstract
- It has proven difficult to identify the underlying genes in complex autoimmune diseases. Here, we use forward genetics to identify polymorphisms in the vitamin D receptor gene (Vdr) promoter, controlling Vdr expression and T cell activation. We isolated these polymorphisms in a congenic mouse line, allowing us to study the immunomodulatory properties of VDR in a physiological context. Congenic mice overexpressed VDR selectively in T cells, and thus did not suffer from calcemic effects. VDR overexpression resulted in an enhanced antigen-specific T cell response and more severe autoimmune phenotypes. In contrast, vitamin D3-deficiency inhibited T cell responses and protected mice from developing autoimmune arthritis. Our observations are likely translatable to humans, as Vdr is overexpressed in rheumatic joints. Genetic control of VDR availability codetermines the proinflammatory behavior of T cells, suggesting that increased presence of VDR at the site of inflammation might limit the antiinflammatory properties of its ligand.
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| 17. |
- Panda, SK, et al.
(author)
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IL-4 controls activated neutrophil FcγR2b expression and migration into inflamed joints
- 2020
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 117:6, s. 3103-3113
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Journal article (peer-reviewed)abstract
- Neutrophils are the most abundant immune cells found in actively inflamed joints of patients with rheumatoid arthritis (RA), and most animal models for RA depend on neutrophils for the induction of joint inflammation. Exogenous IL-4 and IL-13 protect mice from antibody-mediated joint inflammation, although the mechanism is not understood. Neutrophils display a very strong basal expression of STAT6, which is responsible for signaling following exposure to IL-4 and IL-13. Still, the role of IL-4 and IL-13 in neutrophil biology has not been well studied. This can be explained by the low neutrophil surface expression of the IL-4 receptor α-chain (IL-4Rα), essential for IL-4– and IL-13–induced STAT6 signaling. Here we identify that colony stimulating factor 3 (CSF3), released during acute inflammation, mediates potent STAT3-dependent neutrophil IL-4Rα up-regulation during sterile inflammatory conditions. We further demonstrate that IL-4 limits neutrophil migration to inflamed joints, and that CSF3 combined with IL-4 or IL-13 results in a prominent neutrophil up-regulation of the inhibitory Fcγ receptor (FcγR2b). Taking these data together, we demonstrate that the IL-4 and CSF3 pathways are linked and play important roles in regulating proinflammatory neutrophil behavior.
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| 18. |
- Raposo, B., et al.
(author)
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Epitope-specific antibody response is controlled by immunoglobulin V(H) polymorphisms
- 2014
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 211:3, s. 405-411
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Journal article (peer-reviewed)abstract
- Autoantibody formation is essential for the development of certain autoimmune diseases like rheumatoid arthritis (RA). Anti-type II collagen (CII) antibodies are found in RA patients; they interact with cartilage in vivo and are often highly pathogenic in the mouse. Autoreactivity to CII is directed to multiple epitopes and conserved between mice and humans. We have previously mapped the antibody response to CII in a heterogeneous stock cohort of mice, with a strong association with the IgH locus. We positioned the genetic polymorphisms and determined the structural requirements controlling antibody recognition of one of the major CII epitopes. Polymorphisms at positions S31R and W33T of the associated variable heavy chain (VH) allele were identified and confirmed by gene sequencing. The Fab fragment binding the J1 epitope was crystallized, and site-directed mutagenesis confirmed the importance of those two variants for antigen recognition. Back mutation to germline sequence provided evidence for a preexisting recognition of the J1 epitope. These data demonstrate a genetic association of epitope-specific antibody responses with specific VH alleles, and it highlights the importance of germline-encoded antibodies in the pathogenesis of antibody-mediated autoimmune diseases.
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| 19. |
- Sumnik, Z., et al.
(author)
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Persistent heterogeneity in diabetes technology reimbursement for children with type 1 diabetes: The SWEET perspective
- 2019
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 20:4, s. 434-443
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Journal article (peer-reviewed)abstract
- Background: Frequent use of modern diabetes technologies increases the chance for optimal type 1 diabetes (T1D) control. Limited reimbursement influences the access of patients with T1D to these modalities and could worsen their prognosis. We aimed to describe the situation of reimbursement for insulins, glucometers, insulin pumps (CSII) and continuous glucose monitoring (CGM) for children with T1D in European countries participating in the SWEET Project and to compare data from EU countries with data from our previous study in 2009. Methods: The study was conducted between March 2017 and August 2017. First, we approached diabetes technology companies with a survey to map the reimbursement of insulins and diabetic devices. The data collected from these companies were then validated by members of the SWEET consortium. Results: We collected data from 29 European countries, whereas all types of insulins are mostly fully covered, heterogeneity was observed regarding the reimbursement of strips for glucometers (from 90 strips/month to no limit). CSII is readily available in 20 of 29 countries. Seven countries reported significant quota issues or obstacles for CSII prescription, and two countries had no CSII reimbursement. CGM is at least partially reimbursed in 17 of 29 countries. The comparison with the 2009 study showed an increasing availability of CSII and CGM across the EU. Conclusions: Although innovative diabetes technology is available, a large proportion of children with T1D still do not benefit from it due to its limited reimbursement. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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| 20. |
- Thim, Troels, et al.
(author)
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Evaluation and Management of Nonculprit Lesions in STEMI
- 2020
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In: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1936-8798. ; 13:10, s. 1145-1154
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Research review (peer-reviewed)abstract
- Nonculprit lesions are frequently observed in patients with ST-segment elevation myocardial infarction. Results from recent randomized clinical trials suggest that complete revascularization after ST-segment elevation myocardial infarction improves outcomes. In this state-of-the-art paper, the authors review these trials and consider how best to determine which nonculprit lesions require revascularization and when this should be performed.
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