53 research outputs found

    Demonstrating Immersive Media Delivery on 5G Broadcast and Multicast Testing Networks

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    This work presents eight demonstrators and one showcase developed within the 5G-Xcast project. They experimentally demonstrate and validate key technical enablers for the future of media delivery, associated with multicast and broadcast communication capabilities in 5th Generation (5G). In 5G-Xcast, three existing testbeds: IRT in Munich (Germany), 5GIC in Surrey (UK), and TUAS in Turku (Finland), have been developed into 5G broadcast and multicast testing networks, which enables us to demonstrate our vision of a converged 5G infrastructure with fixed and mobile accesses and terrestrial broadcast, delivering immersive audio-visual media content. Built upon the improved testing networks, the demonstrators and showcase developed in 5G-Xcast show the impact of the technology developed in the project. Our demonstrations predominantly cover use cases belonging to two verticals: Media & Entertainment and Public Warning, which are future 5G scenarios relevant to multicast and broadcast delivery. In this paper, we present the development of these demonstrators, the showcase, and the testbeds. We also provide key findings from the experiments and demonstrations, which not only validate the technical solutions developed in the project, but also illustrate the potential technical impact of these solutions for broadcasters, content providers, operators, and other industries interested in the future immersive media delivery.Comment: 16 pages, 22 figures, IEEE Trans. Broadcastin

    A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research

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    The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science

    Vitamin D and cause-specific vascular disease and mortality:a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults

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    Towards an appreciation of ethics in social enterprise business models

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    How can a critical analysis of entrepreneurial intention inform an appreciation of ethics in social enterprise business models? In answering this question, we consider the ethical commitments that inform entrepreneurial action (inputs) and the hybrid organisations that emerge out of these commitments and actions (outputs). Ethical theory can be a useful way to re-orient the field of social enterprise so that it is more critical of bureaucratic (charitable) and market-driven (business) enterprises connected to neo-liberal doctrine. Social enterprise hybrid business models are therefore reframed as outcomes of both ethical and entrepreneurial intentions. We challenge the dominant conceptualisation of social enterprise as a hybrid blend of mission and market (purpose-versus-resource) by reframing hybridity in terms of the moral choice of economic system (redistribution, reciprocity and market) and social value orientation (personal, mutual or public benefit). We deconstruct the political foundations of charitable trading activities (CTAs), co-operative and mutual enterprises (CMEs) and socially responsible businesses (SRBs) by examining the rationalities (formal, social and substantive) and ethical commitments (utilitarian, communitarian, pragmatic) that underpin them. Whilst conceptual modelling of social enterprise is not new, this paper contributes to knowledge by developing a theory of social enterprise ethics based on the moral/political choices that are made by entrepreneurs (knowingly and unknowingly) when choosing between systems of economic exchange and social value orientation, then expressing it through a legal form

    Multidimensional signals and analytic flexibility: Estimating degrees of freedom in human speech analyses

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    Recent empirical studies have highlighted the large degree of analytic flexibility in data analysis which can lead to substantially different conclusions based on the same data set. Thus, researchers have expressed their concerns that these researcher degrees of freedom might facilitate bias and can lead to claims that do not stand the test of time. Even greater flexibility is to be expected in fields in which the primary data lend themselves to a variety of possible operationalizations. The multidimensional, temporally extended nature of speech constitutes an ideal testing ground for assessing the variability in analytic approaches, which derives not only from aspects of statistical modeling, but also from decisions regarding the quantification of the measured behavior. In the present study, we gave the same speech production data set to 46 teams of researchers and asked them to answer the same research question, resulting insubstantial variability in reported effect sizes and their interpretation. Using Bayesian meta-analytic tools, we further find little to no evidence that the observed variability can be explained by analysts’ prior beliefs, expertise or the perceived quality of their analyses. In light of this idiosyncratic variability, we recommend that researchers more transparently share details of their analysis, strengthen the link between theoretical construct and quantitative system and calibrate their (un)certainty in their conclusions

    SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

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    Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

    Stroke genetics informs drug discovery and risk prediction across ancestries

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    Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

    Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

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    Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

    Human-Robot Interaction in Passive Assistive Lower Limb Robotic Exoskeletons

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    Exoskeletons are external structures with joints and links corresponding to the human body. The exoskeleton transfers force to the human body to assist, enhance, or rehabilitate a user. Exoskeletons and the human body create a bi-directional system built up of multiple interactive layers. This research focuses on passive lower limb assistive exoskeletons. At the core of exoskeleton design is cognitive and physical interaction, forming human-robot interaction. Cognitive interaction involves control system user intent detection and how the user interprets information from the exoskeleton. Physical interaction concerns the transmission of power to the user. The physical interface is affected by several factors such as soft tissue movement, joint misalignment, and robot inertia. It is postulated that improving exoskeleton-user attachment can improve system efficiency and user comfort. A drawback of current exoskeleton design is a lack of consideration for the human aspect of human-exoskeleton interaction, through simplification to kinematic design and system contact points. Limited work exists on human-exoskeleton interaction focusing on the effect on the human, aside from metabolic output. A review of 103 exoskeleton designs highlighted the need to standardise exoskeleton attachment. In addition, a framework for exoskeleton assessment was set out. Two passive lower limb exoskeletons were developed for assessing human-robot interaction. The first six degrees of freedom system conformed to common mechanical joint simplifications when replicating human anatomy, resulting in a minimalist design. The second fourteen degrees of freedom sought to minimise exoskeleton joint simplification, using only those required for full user mobility. Passive systems highlight the base exoskeleton-user impedance. Preliminary work suggested that the kinematic constraints of the minimalist system resulted in greater interaction forces, with the higher degree of freedom system experiencing a 12% force reduction. A novel sleeve-based attachment system is proposed in conjunction with traditional cuff-based attachment systems. Multiple design elements were taken through an iterative process before reaching a final design. Proof of concept attachment sleeve testing showed a reduction of 43% compared to the traditional attachment cuff. A flexible force tracking array was developed for human-exoskeleton interface integration. An array of 30 force-sensitive resistors (FSR406) were implemented, achieving post-calibration (0 - 60N) linearity greater than R2 = 0.95 in all sensors. The soft sensing sleeves is capable of assessing multiple attachment methodologies. Due to the extensive testing required to assess all possible attachment scenarios, an in-silico model was developed within the OpenSim and HyFyDy environment. Implementing a linear spring-damper system to represent soft tissue interaction between human and exoskeleton through closed kinematic chains. The model provides a promising and novel method for investigating human-exoskeleton interaction and exoskeleton performance assessment. Validated against human gait trials, the model achieved a 70% response agreement with the flexible force tracking system and aligned with responses documented in the academic literature. Given soft tissue’s non-linear viscoelastic properties, 70% agreement was deemed sufficient. The biomechanically accurate model was driven by muscle excitation through a forward shooting optimisation control (SCONE), driving a novel approach to exoskeleton assessment. This research found no clear link between knee alignment and joint load (R2 = 0.150). A higher density of shank attachment points is beneficial to exoskeleton stability characterised in desirable response shifts in all metrics assessed. The physical human-exoskeleton interaction presented a decrease in the normal force of 55.9% (±2.6%) and a 63.1% (±5.2%) reduction in shear. Alignment changes of 45mm to 24.5mm (46%) were observed between configurations. Gait analysis saw a similar response with a 21-31% gait deviation compared to the baseline model. Significant shifts in each metric in a passive system highlight the need for further research in this area. Thigh attachment configuration had no clear effect on performance, giving researchers more freedom in the thigh attachment. Increasing the exoskeleton joint degrees of freedom (additional pelvis-exoskeleton joint) greatly affected shank normal and shear forces, highlighting the influence of exoskeleton joint kinematics on human-robot interaction and the need for its consideration in future human-centred design
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