2,018 research outputs found

    Quantum networks reveal quantum nonlocality

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    The results of local measurements on some composite quantum systems cannot be reproduced classically. This impossibility, known as quantum nonlocality, represents a milestone in the foundations of quantum theory. Quantum nonlocality is also a valuable resource for information processing tasks, e.g. quantum communication, quantum key distribution, quantum state estimation, or randomness extraction. Still, deciding if a quantum state is nonlocal remains a challenging problem. Here we introduce a novel approach to this question: we study the nonlocal properties of quantum states when distributed and measured in networks. Using our framework, we show how any one-way entanglement distillable state leads to nonlocal correlations. Then, we prove that nonlocality is a non-additive resource, which can be activated. There exist states, local at the single-copy level, that become nonlocal when taking several copies of it. Our results imply that the nonlocality of quantum states strongly depends on the measurement context.Comment: 4 + 3 pages, 4 figure

    Using place-based public engagement to improve social and environmental sustainability: Lessons from partnership working in Cornwall, UK

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    This is the final version. Available on open access from Elsevier via the DOI in this recordPublic engagement with research and innovation is often inversely related to socio-economic status, with significant implications for realising positive solutions to pressing concerns, such as the biodiversity and climate crises. This paper reports on the use of place-based public workshops focusing on co-design of urban green spaces to understand: the extent to which public workshops can engage local people in relatively poor locations; the degree to which working with self-organised groups or newly-engaged publics impacts levels of engagement and outcomes; and how universities can play a role in developing locally relevant practical solutions to transdisciplinary issues such as the climate and biodiversity crises. We report on an action research project that involved facilitated co-design workshops in three towns in Cornwall, UK. The research methods included a survey of participants and follow up interviews with key stakeholders. We found that the workshops were successful in engaging local people, including those with less interest in the environment. Independent follow-on activities from aligned self-organised groups were greater than for newly engaged publics but this was partly dependent on the knowledge and skills of those involved. The role of the university as a neutral partner, in providing expertise and seed funding, was seen to be positive, with short-term timescales, communication and the ability to retain longer term involvement reported as hindrances to successful collaboration.UK Research and InnovationUniversity of ExeterSouth Kerrier Alliance Community Interest Company (SKACIC)Cornwall's Voluntary Sector Foru

    Conformational activation of ADAMTS13

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    A disintegrin and metalloprotease with thrombospondin motifs 13 (ADAMTS13) is a metalloprotease that regulates von Willebrand factor (VWF) function. ADAMTS13-mediated proteolysis is determined by conformational changes in VWF, but also may depend on its own conformational activation. Kinetic analysis of WT ADAMTS13 revealed ∼2.5-fold reduced activity compared with ADAMTS13 lacking its C-terminal tail (MDTCS) or its CUB1-2 domains (WTΔCUB1-2), suggesting that the CUB domains naturally limit ADAMTS13 function. Consistent with this suggestion, WT ADAMTS13 activity was enhanced ∼2.5-fold by preincubation with either an anti-CUB mAb (20E9) or VWF D4CK (the natural binding partner for the CUB domains). Furthermore, the isolated CUB1-2 domains not only bound MDTCS, but also inhibited activity by up to 2.5-fold. Interestingly, a gain-of-function (GoF) ADAMTS13 spacer domain variant (R568K/F592Y/R660K/Y661F/Y665F) was ∼2.5-fold more active than WT ADAMTS13, but could not be further activated by 20E9 mAb or VWF D4CK and was unable to bind or to be inhibited by the CUB1-2 domains, suggesting that the inhibitory effects of the CUB domains involve an interaction with the spacer domain that is disrupted in GoF ADAMTS13. Electron microscopy demonstrated a “closed” conformation of WT ADAMTS13 and suggested a more “open” conformation for GoF ADAMTS13. The cryptic spacer domain epitope revealed by conformational unfolding also represents the core antigenic target for autoantibodies in thrombotic thrombocytopenic purpura. We propose that ADAMTS13 circulates in a closed conformation, which is maintained by a CUB–spacer domain binding interaction. ADAMTS13 becomes conformationally activated on demand through interaction of its C-terminal CUB domains with VWF, making it susceptible to immune recognition

    Phylogenetic inferences of Atelinae (Platyrrhini) based on multi-directional chromosome painting in Brachyteles arachnoides, Ateles paniscus paniscus and Ateles b. marginatus

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    We performed multi-directional chromosome painting in a comparative cytogenetic study of the three Atelinae species Brachyteles arachnoides, Ateles paniscus paniscus and Ateles belzebuth marginatus, in order to reconstruct phylogenetic relationships within this Platyrrhini subfamily. Comparative chromosome maps between these species were established by multi-color fluorescence in situ hybridization ( FISH) employing human, Saguinus oedipus and Lagothrix lagothricha chromosome-specific probes. The three species included in this study and four previously analyzed species from all four Atelinae genera were subjected to a phylogenetic analysis on the basis of a data matrix comprised of 82 discrete chromosome characters. The results confirmed that Atelinae represent a monophyletic clade with a putative ancestral karyotype of 2n = 62 chromosomes. Phylogenetic analysis revealed an evolutionary branching sequence \{Alouatta \{Brachyteles \{Lagothrix and Ateles\}\}\} in Atelinae and \{Ateles belzebuth marginatus \{Ateles paniscus paniscus \{Ateles belzebuth hybridus and Ateles geoffroyi\}\}\} in genus Ateles. The chromosomal data support a re-evaluation of the taxonomic status of Ateles b. hybridus. Copyright (C) 2005 S. Karger AG, Basel

    Alginate inhibits iron absorption from ferrous gluconate in a randomized controlled trial and reduces iron uptake into Caco-2 cells

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    Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n=15) were given a test meal of 200g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p=0.003). Sub-group B (n=9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p=0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p=0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p=0.009) and 35% (p=0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p<0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification

    Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

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    To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

    Engaging with community researchers for exposure science: lessons learned from a pesticide biomonitoring study

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    A major challenge in biomonitoring studies with members of the general public is ensuring their continued involvement throughout the necessary length of the research. The paper presents evidence on the use of community researchers, recruited from local study areas, as a mechanism for ensuring effective recruitment and retention of farmer and resident participants for a pesticides biomonitoring study. The evidence presented suggests that community researchers' abilities to build and sustain trusting relationships with participants enhanced the rigour of the study as a result of their on-the-ground responsiveness and flexibility resulting in data collection beyond targets expected

    COVID-19 mortality among people with diagnosed HIV compared to those without during the first wave of the COVID-19 pandemic in England

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    Objectives: We describe COVID-19 mortality among people with and without HIV during the first wave of the pandemic in England. / Methods: National surveillance data on adults (aged ≥ 15 years) with diagnosed HIV resident in England were linked to national COVID-19 mortality surveillance data (2 March 2020–16 June 2020); HIV clinicians verified linked cases and provided information on the circumstances of death. We present COVID-19 mortality rates by HIV status, using negative binomial regression to assess the association between HIV and mortality, adjusting for gender, age and ethnicity. / Results: Overall, 99 people with HIV, including 61 of black ethnicity, died of/with COVID-19 (107/100 000) compared with 49 483 people without HIV (109/100 000). Compared to people without HIV, higher COVID-19 mortality rates were observed in people with HIV of black (188 vs. 122/100 000) and Asian (131 vs. 77.0/100 000) ethnicity, and in both younger (15–59 years: 58.3 vs. 10.2/100 000) and older (≥ 60 years: 434 vs. 355/100 000) people. After adjustment for demographic factors, people with HIV had a higher COVID-19 mortality risk than those without (2.18; 95% CI: 1.76–2.70). Most people with HIV who died of/with COVID-19 had suppressed HIV viraemia (91%) and at least one comorbidity reported to be associated with poor COVID-19 outcomes (87%). / Conclusions: In the first wave of the pandemic in England, COVID-19 mortality among people with HIV was low, but was higher than in those without HIV, after controlling for demographic factors. This supports the strategy of prioritizing COVID-19 vaccination for people with HIV and strongly encouraging its uptake, especially in those of black and Asian ethnicity

    Upregulation of p16INK4A and Bax in p53 wild/p53-overexpressing crypts in ulcerative colitis-associated tumours

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    In ulcerative colitis (UC)-associated tumours, p53 gene mutations and p53 protein overexpression are frequently found in early stages, but the two types of alteration do not always coincide. To clarify this discrepancy, p53 mutations and expression of p53-associated molecules were analysed in UC-associated dysplasias by a combination of microdissection, polymerase chain reaction-direct sequencing and immunohistochemistry at the single crypt level. Mismatch of p53 protein overexpression (+)/mutation (−) or p53 overexpression (−)/gene mutation (+) was found in nine crypts in regenerative mucosa (19 crypts), in 27 in low-grade dysplasia (41), in one in high-grade dysplasia (5) and in 12 in invasive carcinomas (17). Regarding these mismatched crypts of the first type, significant increase in p16INK4A and Bax expression was found. The Ki-67 labelling index was depressed in such p53-diffusely positive lesions with the wild-type p53 gene, compared to their p53-diffusely positive and mutant type counterparts. p16INK4A was upregulated indirectly as part of the negative feedback, and increase in Bax, directly controlled by wild-type p53, indicates upregulation of apoptosis. No significant relation with p53-related gene products was detected with the p53 protein overexpression (−)/p53 mutation (+) mismatch. Therefore, a tumorigenesis pathway independent of p53 dysfunction appears to exist in association with ulcerative colitis
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