| 1. |
- Abellán, C., et al.
(författare)
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Challenging Local Realism with Human Choices
- 2018
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 557, s. 212-216
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Tidskriftsartikel (refereegranskat)abstract
- A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings. Although technology can satisfy the first two of these requirements, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons, single atoms, atomic ensembles and superconducting devices. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bi-partite and tri-partite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties), the utilization of video-game methods for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.
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| 2. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 4. |
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| 5. |
- Kyriazis, Angelos, et al.
(författare)
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Dynamic ventilation He-3 MRI for the quantification of disease in the rat lung
- 2012
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Ingår i: IEEE Transactions on Biomedical Engineering. - 0018-9294 .- 1558-2531. ; 59, s. 777-786
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary diseases are known to be largely inhomogeneous. To evaluate such inhomogeneities, we are testing an image-based method to measure gas flow in the lung regionally. Dynamic, spin-density-weighted hyperpolarized He MR images performed during slow inhalation of this gas were analyzed to quantify regional inflation rate. This parameter was measured in regions of interest (ROIs) that were defined by a rectangular grid that covered the entire rat lung and grew dynamically with it during its inflation. We used regional inflation rate to quantify elastase-induced emphysema and to differentiate healthy ( n8) from elastase-treated ( n9) rat lungs as well as healthy from elastase-treated areas of one rat unilaterally treated with elastase in the left lung. Emphysema was also assessed by gold standard morphological and well-established hyperpolarized He MRI diffusion measurements. Mean values of regional inflation rates were significantly different for healthy and elastase-treated animals and correlated well with the apparent diffusion coefficient of He and morphological measurements. The image-based biomarker inflation rate may be useful for the assessment of regional lung ventilation. © 2011 IEEE.
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| 6. |
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| 7. |
- Contessotto, P., et al.
(författare)
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Elastin-like recombinamers-based hydrogel modulates post-ischemic remodeling in a non-transmural myocardial infarction in sheep
- 2021
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:581
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Tidskriftsartikel (refereegranskat)abstract
- Ischemic heart disease is a leading cause of mortality due to irreversible damage to cardiac muscle. Inspired by the post-ischemic microenvironment, we devised an extracellular matrix (ECM)-mimicking hydrogel using catalyst-free click chemistry covalent bonding between two elastin-like recombinamers (ELRs). The resulting customized hydrogel included functional domains for cell adhesion and protease cleavage sites, sensitive to cleavage by matrix metalloproteases overexpressed after myocardial infarction (MI). The scaffold permitted stromal cell invasion and endothelial cell sprouting in vitro. The incidence of non-transmural infarcts has increased clinically over the past decade, and there is currently no treatment preventing further functional deterioration in the infarcted areas. Here, we have developed a clinically relevant ovine model of non-transmural infarcts induced by multiple suture ligations. Intramyocardial injections of the degradable ELRs-hydrogel led to complete functional recovery of ejection fraction 21 days after the intervention. We observed less fibrosis and more angiogenesis in the ELRs-hydrogel-treated ischemic core region compared to the untreated animals, as validated by the expression, proteomic, glycomic, and histological analyses. These findings were accompanied by enhanced preservation of GATA4(+) cardiomyocytes in the border zone of the infarct. We propose that our customized ECM favors cardiomyocyte preservation in the border zone by modulating the ischemic core and a marked functional recovery. The functional benefits obtained by the timely injection of the ELRs-hydrogel in a clinically relevant MI model support the potential utility of this treatment for further clinical translation.
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| 8. |
- Cruz, Raquel, et al.
(författare)
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Novel genes and sex differences in COVID-19 severity
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 9. |
- Florentin, M., et al.
(författare)
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Al-implanted on-axis 4H-SiC MOSFETs
- 2017
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Ingår i: Semiconductor Science and Technology. - : IOP PUBLISHING LTD. - 0268-1242 .- 1361-6641. ; 32:3
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, the impact of temperature and time stress on gate oxide stability of several multi-implanted and epitaxied 4H-SiC nMOSFET is presented. The oxide layer was processed under a rapid thermal process (RTP) furnace. The variation of the main electrical parameters is shown. We report the high quality and stability of such implanted MOSFETs, and point out the very low roughness effect of the on-axis-cut sample. Particularly, in the best case, effective channel mobility (mu(fe)) overcomes 20 cm(2). V-1. s(-1) at 300 degrees C for a channel length of 12 mu m, which is very encouraging for implantation technology. Starting from 200 degrees C, the apparent increase of the mu(fe) peak of the MOSFET ceases and tends to saturate with further temperature increase. This is an indication of the potential of MOSFETs built on on-axis substrates. Thus, starting from the real case of an implanted MOSFET, the global purpose is to show that the electrical performance of such an on-axis-built device can tend to reach that of the ideal case, i.e. epitaxied MOSFET, and even overcome its electrical limitation, e.g. in terms of threshold voltage stability at high temperature.
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| 10. |
- Garcia-Cabello, E., et al.
(författare)
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The Cognitive Connectome in Healthy Aging
- 2021
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Cognitive aging has been extensively investigated using both univariate and multivariate analyses. Sophisticated multivariate approaches such as graph theory could potentially capture unknown complex associations between multiple cognitive variables. The aim of this study was to assess whether cognition is organized into a structure that could be called the "cognitive connectome," and whether such connectome differs between age groups. Methods: A total of 334 cognitively unimpaired individuals were stratified into early-middle-age (37-50 years, n = 110), late-middle-age (51-64 years, n = 106), and elderly (65-78 years, n = 118) groups. We built cognitive networks from 47 cognitive variables for each age group using graph theory and compared the groups using different global and nodal graph measures. Results: We identified a cognitive connectome characterized by five modules: verbal memory, visual memory-visuospatial abilities, procedural memory, executive-premotor functions, and processing speed. The elderly group showed reduced transitivity and average strength as well as increased global efficiency compared with the early-middle-age group. The late-middle-age group showed reduced global and local efficiency and modularity compared with the early-middle-age group. Nodal analyses showed the important role of executive functions and processing speed in explaining the differences between age groups. Conclusions: We identified a cognitive connectome that is rather stable during aging in cognitively healthy individuals, with the observed differences highlighting the important role of executive functions and processing speed. We translated the connectome concept from the neuroimaging field to cognitive data, demonstrating its potential to advance our understanding of the complexity of cognitive aging.
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| 11. |
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| 12. |
- Jensen, Maja, 1978, et al.
(författare)
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High-resolution macromolecular crystallography at the FemtoMAX beamline with time-over-threshold photon detection
- 2021
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Ingår i: Journal of Synchrotron Radiation. - 1600-5775 .- 0909-0495. ; 28, s. 64-70
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Tidskriftsartikel (refereegranskat)abstract
- Protein dynamics contribute to protein function on different time scales. Ultrafast X-ray diffraction snapshots can visualize the location and amplitude of atom displacements after perturbation. Since amplitudes of ultrafast motions are small, high-quality X-ray diffraction data is necessary for detection. Diffraction from bovine trypsin crystals using single femtosecond X-ray pulses was recorded at FemtoMAX, which is a versatile beamline of the MAX IV synchrotron. The time-over-threshold detection made it possible that single photons are distinguishable even under short-pulse low-repetition-rate conditions. The diffraction data quality from FemtoMAX beamline enables atomic resolution investigation of protein structures. This evaluation is based on the shape of the Wilson plot, cumulative intensity distribution compared with theoretical distribution, I/σ, Rmerge /Rmeas and CC1/2 statistics versus resolution. The FemtoMAX beamline provides an interesting alternative to X-ray free-electron lasers when studying reversible processes in protein crystals.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Söderlund, Z, et al.
(författare)
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Controlled release of growth factors using synthetic glycosaminoglycans in a modular macroporous scaffold for tissue regeneration
- 2022
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Healthy regeneration of tissue relies on a well-orchestrated release of growth factors. Herein, we show the use of synthetic glycosaminoglycans for controlled binding and release of growth factors to induce a desired cellular response. First, we screened glycosaminoglycans with growth factors of interest to determine kon (association rate constant), koff (dissociation rate constant), and Kd (equilibrium rate constant). As proof-of-concept, we functionalized an elastin-like recombinamer (ELR) hydrogel with a synthetic glycosaminoglycan and immobilized fibroblast growth factor 2 (FGF2), demonstrating that human umbilical vein endothelial cells cultured on top of ELR hydrogel differentiated into tube-like structures. Taking this concept further, we developed a tunable macroporous ELR cryogel material, containing a synthetic glycosaminoglycan and FGF2 that showed increased blood vessel formation and reduced immune response compared to control when implanted in a subcutaneous mouse model. These results demonstrated the possibility for specific release of desired growth factors in/from a modular 3D scaffold in vitro and in vivo.
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| 18. |
- Amselem, Elias, et al.
(författare)
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Experimental fully contextual correlations
- 2012
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 108:20, s. 200405-
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Tidskriftsartikel (refereegranskat)abstract
- Quantum correlations are contextual yet, in general, nothing prevents the existence of even more contextual correlations. We identify and test a noncontextuality inequality in which the quantum violation cannot be improved by any hypothetical postquantum theory, and use it to experimentally obtain correlations in which the fraction of noncontextual correlations is less than 0.06. Our correlations are experimentally generated from the results of sequential compatible tests on a four-state quantum system encoded in the polarization and path of a single photon.
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| 19. |
- Areitioaurtena, Maialen, et al.
(författare)
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Influence of induction hardening residual stresses on rolling contact fatigue lifetime
- 2022
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Ingår i: International Journal of Fatigue. - : Elsevier. - 0142-1123 .- 1879-3452. ; 159
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Tidskriftsartikel (refereegranskat)abstract
- Rolling contact fatigue is a unique mode of fatigue that components under cyclic contact loading experience. In this work, the impact of induction hardening residual stresses in rolling contact fatigue lifetime is investigated experimentally and numerically using the Dang Van multiaxial criterion. Various residual stress fields from induction hardening are simulated using the finite element method and are mapped into a classical monocontact finite element model. The impact of induction hardened residual stresses on the lifetime of a component has been investigated, and the importance of incorporating the residual stress profile into fatigue life assessments is affirmed.
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| 20. |
- Areitioaurtena, Maialen, et al.
(författare)
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Numerical and experimental investigation of residual stresses during the induction hardening of 42CrMo4 steel
- 2022
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Ingår i: European journal of mechanics. A, Solids. - : Elsevier. - 0997-7538 .- 1873-7285. ; 96
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Tidskriftsartikel (refereegranskat)abstract
- The usage of induction hardening in the industry has increased in the last years due to its efficiency and repeatability. Induction hardening produces a hard martensitic layer on the specimen surface, which is accompanied by the generation of compressive residual stresses in the hardened case and tensile stresses in the untreated core. Residual stresses generated by induction hardening greatly impact on fatigue performance, as they act as crack growth retardants. In this work, a multiphysical coupled finite element model is developed to simulate induction hardening and compute the final residual stress state of the specimens along the microstructural transformations and hardness evolution. The impact of the transformation induced plasticity strain in the stress-state of the specimen during the process is also studied. The experimental validation shows that considering the transformation induced plasticity in induction hardening simulations improves the residual stress predictions, concluding that this effect should be included to achieve good residual stress predictions, especially in the subsurface region.
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| 21. |
- Areitioaurtena, Maialen, et al.
(författare)
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Numerical and experimental investigation on the residual stresses generated by scanning induction hardening
- 2022. - C
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Ingår i: Procedia CIRP. - : Elsevier BV. - 2212-8271. ; 108, s. 827-832
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Konferensbidrag (refereegranskat)abstract
- Induction hardening is widely used in the industry as a surface heat treatment that improves the surface and the subsurface hardness of components greatly. The hardened case, which usually is a few mm, highly impacts the surface and structural integrity of the component. In this work, we simulate the scanning induction hardening process by means of finite element modeling. The computed hardness, microstructure, and residual stress profile are compared with experimentally measured data using several surface and subsurface characterization techniques. A very good agreement is found between the simulated and experimentally measured residual stresses, which were characterized by the incremental hole drilling technique.
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| 22. |
- Cabello, Adan, et al.
(författare)
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Quantum social networks
- 2012
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Ingår i: Journal of Physics A. - : IOP Publishing. - 1751-8113 .- 1751-8121. ; 45:28, s. 285101-
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Tidskriftsartikel (refereegranskat)abstract
- We introduce a physical approach to social networks (SNs) in which each actor is characterized by a yes-no test on a physical system. This allows us to consider SNs beyond those originated by interactions based on pre-existing properties, as in a classical SN (CSN). As an example of SNs beyond CSNs, we introduce quantum SNs (QSNs) in which actor i is characterized by a test of whether or not the system is in a quantum state |psi(i)>. We show that QSNs outperform CSNs for a certain task and some graphs. We identify the simplest of these graphs and show that graphs in which QSNs outperform CSNs are increasingly frequent as the number of vertices increases. We also discuss more general SNs and identify the simplest graphs in which QSNs cannot be outperformed.
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| 23. |
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| 24. |
- Gomez-Cabello, D, et al.
(författare)
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CtIP-dependent nascent RNA expression flanking DNA breaks guides the choice of DNA repair pathway
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 5303-
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Tidskriftsartikel (refereegranskat)abstract
- The RNA world is changing our views about sensing and resolution of DNA damage. Here, we develop single-molecule DNA/RNA analysis approaches to visualize how nascent RNA facilitates the repair of DNA double-strand breaks (DSBs). RNA polymerase II (RNAPII) is crucial for DSB resolution in human cells. DSB-flanking, RNAPII-generated nascent RNA forms RNA:DNA hybrids, guiding the upstream DNA repair steps towards favouring the error-free Homologous Recombination (HR) pathway over Non-Homologous End Joining. Specific RNAPII inhibitor, THZ1, impairs recruitment of essential HR proteins to DSBs, implicating nascent RNA in DNA end resection, initiation and execution of HR repair. We further propose that resection factor CtIP interacts with and helps re-activate RNAPII when paused by the RNA:DNA hybrids, collectively promoting faithful repair of chromosome breaks to maintain genomic integrity.
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| 25. |
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| 26. |
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| 27. |
- Lauque, Dominique, et al.
(författare)
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Length-of-Stay in the Emergency Department and In-Hospital Mortality : A Systematic Review and Meta-Analysis
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:1
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Forskningsöversikt (refereegranskat)abstract
- The effect of emergency department (ED) length of stay (EDLOS) on in-hospital mortality (IHM) remains unclear. The aim of this systematic review and meta-analysis was to determine the association between EDLOS and IHM. We searched the PubMed, Medline, Embase, Web of Science, Cochrane Controlled Register of Trials, CINAHL, PsycInfo, and Scopus databases from their inception until 14-15 January 2022. We included studies reporting the association between EDLOS and IHM. A total of 11,337 references were identified, and 52 studies (total of 1,718,518 ED patients) were included in the systematic review and 33 in the meta-analysis. A statistically significant association between EDLOS and IHM was observed for EDLOS over 24 h in patients admitted to an intensive care unit (ICU) (OR = 1.396, 95% confidence interval [CI]: 1.147 to 1.701; p < 0.001, I2 = 0%) and for low EDLOS in non-ICU-admitted patients (OR = 0.583, 95% CI: 0.453 to 0.745; p < 0.001, I2 = 0%). No associations were detected for the other cut-offs. Our findings suggest that there is an association between IHM low EDLOS and EDLOS exceeding 24 h and IHM. Long stays in the ED should not be allowed and special attention should be given to patients admitted after a short stay in the ED.
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| 28. |
- Lopez-Saavedra, A, et al.
(författare)
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A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12364-
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Tidskriftsartikel (refereegranskat)abstract
- There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways; in this study we took advantage of the SeeSaw Reporter, in which the repair of double-strand breaks by homology-independent or -dependent mechanisms is distinguished by the accumulation of green or red fluorescence, respectively. Using a genome-wide human esiRNA (endoribonuclease-prepared siRNA) library, we isolate genes that control the recombination/end-joining ratio. Here we report that two distinct sets of genes are involved in the control of the balance between NHEJ and HR: those that are required to facilitate recombination and those that favour NHEJ. This last category includes CCAR2/DBC1, which we show inhibits recombination by limiting the initiation and the extent of DNA end resection, thereby acting as an antagonist of CtIP.
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| 29. |
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| 30. |
- Marsico, G., et al.
(författare)
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Elastin-like hydrogel stimulates angiogenesis in a severe model of critical limb ischemia (CLI): An insight into the glyco-host response
- 2021
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612. ; 269
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Tidskriftsartikel (refereegranskat)abstract
- Critical limb ischemia (CLI) is characterized by the impairment of microcirculation, necrosis and inflammation of the muscular tissue. Although the role of glycans in mediating inflammation has been reported, changes in the glycosylation following muscle ischemia remains poorly understood. Here, a murine CLI model was used to show the increase of high mannose, alpha-(2, 6)-sialic acid and the decrease of hybrid and bisected N-glycans as glycosylation associated with the ischemic environment. Using this model, the efficacy of an elastin-like recombinamers (ELR) hydrogel was assessed. The hydrogel modulates key angiogenic signaling pathways, resulting in capillary formation, and ECM remodeling. Arterioles formation, reduction of fibrosis and anti-inflammatory macrophage polarization wa also induced by the hydrogel administration. Modulation of glycosylation was observed, suggesting, in particular, a role for mannosylation and sialylation in the mediation of tissue repair. Our study elucidates the angiogenic potential of the ELR hydrogel for CLI applications and identifies glycosylation alterations as potential new therapeutic targets.
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| 31. |
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| 32. |
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| 33. |
- Schunemann, Holger J., et al.
(författare)
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Methods for Development of the European Commission Initiative on Breast Cancer Guidelines Recommendations in the Era of Guideline Transparency
- 2019
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 171:4, s. 273-280
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Tidskriftsartikel (refereegranskat)abstract
- Neither breast cancer prevention and early-detection programs, nor their outcomes, are uniform across Europe. This article describes the rationale, methods, and process for development of the European Commission ( EC) Initiative on Breast Cancer Screening and Diagnosis Guidelines. To be consistent with standards set by the Institute of Medicine and others, the EC followed 6 general principles. First, the EC selected, via an open call, a panel with broad representation of areas of expertise. Second, it ensured that all recommendations were supported by systematic reviews. Third, the EC separately considered important subgroups of women, included patient advocates in the guidelines development group, and focused on good communication to inform women's decisions. Fourth, EC rules on conflicts of interest were followed and the GRADE ( Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests. Fifth, it focused its recommendations on outcomes that matter to women, and certainty of the evidence is rated for each. Sixth, the EC elicited stakeholder feedback to ensure that the recommendations remain up to date and relevant to practice. This article describes the approach and highlights ways of disseminating and adapting the recommendations both within and outside Europe, using innovative information technology tools.
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| 34. |
- Visse, Edward, et al.
(författare)
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The MAP kinases are differently utilized by CD28 and CD2 adhesion pathways in superantigen-activated Jurkat T cells
- 2003
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Ingår i: Biological Research. - 0717-6287. ; 36:2, s. 263-278
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Tidskriftsartikel (refereegranskat)abstract
- To mimic the two-signal requirements for T cell activation mediated by ligands, we exposed the superantigens SEA or SEE (signal 1) to T cells incubated with HLA-DR/LFA-3 or HLA-DR/137-1-CHO transfected cells (signal 2). LFA-3 costimulation was able to induce T cell proliferation as well as IFN-gamma and IL-4 production at similar levels as in cells induced by B7-1. Analysis of the CD28RE of the IL-2 promoter showed specific transcription factor recruitment at the CD28RE element upon induction by B7-1/SEE. Further functional Studies with an IL-2 enhancer-promoter carrying either wild type or mutated versions of the CD28RE site revealed that this element is necessary for full activation upon B7-1 costimulation. While both CD28/B7-1 and CD2/LFA-3 costimulation resulted in the up-regulation of IL-4 and IFN-gamma promoters, IL-2 promoter activity and production of IL-2 were only seen after B7-1 costimulation. However, contrary to what has been previously proposed, we show that costimulation with either B7-1 or LFA-3 further enhanced the ERK-2 activity and strongly activated the p38 MAPK pathway, but only B7-1 costiniulation induced high levels of JNK-1 activity. These data Suggest that the differential effect of CD28 vs. CD2 can be related to the difference in the ability of the two pathways to induce JNK-1 activity.
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| 35. |
- Wu, Lijuan, et al.
(författare)
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The Association between Emergency Department Length of Stay and In-Hospital Mortality in Older Patients Using Machine Learning : An Observational Cohort Study
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:14
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Tidskriftsartikel (refereegranskat)abstract
- The association between emergency department (ED) length of stay (EDLOS) with in-hospital mortality (IHM) in older patients remains unclear. This retrospective study aims to delineate the relationship between EDLOS and IHM in elderly patients. From the ED patients (n = 383,586) who visited an urban academic tertiary care medical center from January 2010 to December 2016, 78,478 older patients (age ≥60 years) were identified and stratified into three age subgroups: 60-74 (early elderly), 75-89 (late elderly), and ≥90 years (longevous elderly). We applied multiple machine learning approaches to identify the risk correlation trends between EDLOS and IHM, as well as boarding time (BT) and IHM. The incidence of IHM increased with age: 60-74 (2.7%), 75-89 (4.5%), and ≥90 years (6.3%). The best area under the receiver operating characteristic curve was obtained by Light Gradient Boosting Machine model for age groups 60-74, 75-89, and ≥90 years, which were 0.892 (95% CI, 0.870-0.916), 0.886 (95% CI, 0.861-0.911), and 0.838 (95% CI, 0.782-0.887), respectively. Our study showed that EDLOS and BT were statistically correlated with IHM (p < 0.001), and a significantly higher risk of IHM was found in low EDLOS and high BT. The flagged rate of quality assurance issues was higher in lower EDLOS ≤1 h (9.96%) vs. higher EDLOS 7 h
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