Machine learning methods for automatic silent speech recognition using a wearable graphene strain gauge sensor

Silent speech recognition is the ability to recognise intended speech without audio information. Useful applications can be found in situations where sound waves are not produced or cannot be heard. Examples include speakers with physical voice impairments or environments in which audio transference is not reliable or secure. Developing a device which can detect non-auditory signals and map them to intended phonation could be used to develop a device to assist in such situations. In this work, we propose a graphene-based strain gauge sensor which can be worn on the throat and detect small muscle movements and vibrations. Machine learning algorithms then decode the non-audio signals and create a prediction on intended speech. The proposed strain gauge sensor is highly wearable, utilising graphene’s unique and beneficial properties including strength, flexibility and high conductivity. A highly flexible and wearable sensor able to pick up small throat movements is fabricated by screen printing graphene onto lycra fabric. A framework for interpreting this information is proposed which explores the use of several machine learning techniques to predict intended words from the signals. A dataset of 15 unique words and four movements, each with 20 repetitions, was developed and used for the training of the machine learning algorithms. The results demonstrate the ability for such sensors to be able to predict spoken words. We produced a word accuracy rate of 55% on the word dataset and 85% on the movements dataset. This work demonstrates a proof-of-concept for the viability of combining a highly wearable graphene strain gauge and machine leaning methods to automate silent speech recognition.EP/S023046/

Conformational comparisons of Pasteurella multocida types B and E and structurally related capsular polysaccharides

Pasteurella multocida, an encapsulated gram-negative bacterium, is a significant veterinary pathogen. The P. multocida is classified into 5 serogroups (A, B, D, E, and F) based on the bacterial capsular polysaccharide (CPS), which is important for virulence. Serogroups B and E are the primary causative agents of bovine hemorrhagic septicemia that is associated with significant yearly losses of livestock worldwide, primarily in low- and middle-income countries. The P. multocida disease is currently managed by whole-cell vaccination, albeit with limited efficacy. CPS is an attractive antigen target for an improved vaccine: CPS-based vaccines have proven highly effective against human bacterial diseases and could provide longer-term protection against P. multocida. The recently elucidated CPS repeat units of serogroups B and E both comprise a N-acetyl-β-D-mannosaminuronic acid/N-acetyl-β-D-glucosamine disaccharide backbone with β-D-fructofuranose (Fruf) side chain, but differ in their glycosidic linkages, and a glycine (Gly) side chain in serogroup B. Interestingly, the Haemophilus influenzae types e and d CPS have the same backbone residues. Here, comparative modeling of P. multocida serogroups B and E and H. influenzae types e and d CPS identifies a significant impact of small structural differences on both the chain conformation and the exposed potential antibody-binding epitopes (Ep). Further, Fruf and/or Gly side chains shield the immunogenic amino-sugar CPS backbone—a possible common strategy for immune evasion in both P. multocida and H. influenzae. As the lack of common epitopes suggests limited potential for cross-reactivity, a bivalent CPS-based vaccine may be necessary to provide adequate protection against P. multocida types B and E

Modeling of pneumococcal serogroup 10 capsular polysaccharide molecular conformations provides insight into epitopes and observed cross-reactivity.

Streptococcus pneumoniae is an encapsulated gram-negative bacterium and a significant human pathogen. The capsular polysaccharide (CPS) is essential for virulence and a target antigen for vaccines. Although widespread introduction of pneumococcal conjugate vaccines (PCVs) has significantly reduced disease, the prevalence of non-vaccine serotypes has increased. On the basis of the CPS, S. pneumoniae serogroup 10 comprises four main serotypes 10A, 10B, 10C, and 10F; as well as the recently identified 10D. As it is the most prevalent, serotype 10A CPS has been included as a vaccine antigen in the next generation PCVs. Here we use molecular modeling to provide conformational rationales for the complex cross-reactivity reported between serotypes 10A, 10B, 10C, and 10F anti-sera. Although the highly mobile phosphodiester linkages produce very flexible CPS, shorter segments are conformationally defined, with exposed β-D-galactofuranose (β DGalf) side chains that are potential antibody binding sites. We identify four distinct conformational epitopes for the immunodominant β DGalf that assist in rationalizing the complex asymmetric cross-reactivity relationships. In particular, we find that strongly cross-reactive serotypes share common epitopes. Further, we show that human intelectin-1 has the potential to bind the exposed exocyclic 1,2-diol of the terminal β DGalf in each serotype; the relative accessibility of three- or six-linked β DGalf may play a role in the strength of the innate immune response and hence serotype disease prevalence. In conclusion, our modeling study and relevant serological studies support the inclusion of serotype 10A in a vaccine to best protect against serogroup 10 disease

What are shared and social values of ecosystems?

The theoretical framework outlined in this paper was developed initially through a series of expert workshops as part of the Valuing Nature Network — BRIDGE: From Values to Decisions project, funded by the UK Natural Environment Research Council (NERC). It was developed further through the follow-on phase of the UK National Ecosystem Assessment (Work Package 6: Shared, Plural and Cultural Values) funded by the UK Department of the Environment, Food and Rural Affairs (Defra), the Welsh Government, NERC, the Economic and Social Research Council (ESRC), and the Arts and Humanities Research Council (AHRC).Peer reviewedPublisher PD

Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation.

The pathogenic bacterium Shigella is a leading cause of diarrheal disease and mortality, disproportionately affecting young children in low-income countries. The increasing prevalence of antibiotic resistance in Shigella necessitates an effective vaccine, for which the bacterial lipopolysaccharide O-antigen is the primary target. S. flexneri serotype 6 has been proposed as a multivalent vaccine component to ensure broad protection against Shigella. We have previously explored the conformations of S. flexneri O-antigens from serogroups Y, 2, 3, and 5 that share a common saccharide backbone (serotype Y). Here we consider serogroup 6, which is of particular interest because of an altered backbone repeat unit with non-stoichiometric O-acetylation, the antigenic and immunogenic importance of which have yet to be established. Our simulations show significant conformational changes in serogroup 6 relative to the serotype Y backbone. We further find that O-acetylation has little effect on conformation and hence may not be essential for the antigenicity of serotype 6. This is corroborated by an in vivo study in mice, using Generalized Modules for Membrane Antigens (GMMA) as O-antigen delivery systems, that shows that O-acetylation does not have an impact on the immune response elicited by the S. flexneri serotype 6 O-antigen

Cross-reactivity of Haemophilus influenzae type a and b polysaccharides: molecular modeling and conjugate immunogenicity studies.

Haemophilus influenzae is a leading cause of meningitis disease and mortality, particularly in young children. Since the introduction of a licensed conjugate vaccine (targeting the outer capsular polysaccharide) against the most prevalent serotype, Haemophilus influenzae serotype b, the epidemiology of the disease has changed and Haemophilus influenzae serotype a is on the rise, especially in Indigenous North American populations. Here we apply molecular modeling to explore the preferred conformations of the serotype a and b capsular polysaccharides as well as a modified hydrolysis resistant serotype b polysaccharide. Although both serotype b and the modified serotype b have similar random coil behavior, our simulations reveal some differences in the polysaccharide conformations and surfaces which may impact antibody cross-reactivity between these two antigens. Importantly, we find significant conformational differences between the serotype a and b polysaccharides, indicating a potential lack of cross-reactivity that is corroborated by immunological data showing little recognition or killing between heterologous serotypes. These findings support the current development of a serotype a conjugate vaccine

Gramene: a growing plant comparative genomics resource

Gramene (www.gramene.org) is a curated resource for genetic, genomic and comparative genomics data for the major crop species, including rice, maize, wheat and many other plant (mainly grass) species. Gramene is an open-source project. All data and software are freely downloadable through the ftp site (ftp.gramene.org/pub/gramene) and available for use without restriction. Gramene's core data types include genome assembly and annotations, other DNA/mRNA sequences, genetic and physical maps/markers, genes, quantitative trait loci (QTLs), proteins, ontologies, literature and comparative mappings. Since our last NAR publication 2 years ago, we have updated these data types to include new datasets and new connections among them. Completely new features include rice pathways for functional annotation of rice genes; genetic diversity data from rice, maize and wheat to show genetic variations among different germplasms; large-scale genome comparisons among Oryza sativa and its wild relatives for evolutionary studies; and the creation of orthologous gene sets and phylogenetic trees among rice, Arabidopsis thaliana, maize, poplar and several animal species (for reference purpose). We have significantly improved the web interface in order to provide a more user-friendly browsing experience, including a dropdown navigation menu system, unified web page for markers, genes, QTLs and proteins, and enhanced quick search functions

Work Package Report 6: Shared, plural and cultural values of ecosystems – Summary

Key findings: Finding 1: Shared values resulting from deliberative, group-based valuation are different from individual values. Case study evidence suggests that they are more informed, considered, confident and reflective of participants’ deeper-held, transcendental values. Deliberated, group-based monetary values may be a better reflection of real welfare impacts than non-deliberated individual values, if derived through a carefully designed and managed process. Although more research is needed to expand the currently small evidence base on deliberative monetary methods, group deliberation has the potential to significantly enhance elicitation of values. Finding 2: The ethical, moral and justice dimensions of many environmental issues necessitate approaches that allow for the elicitation of shared and plural values. Key ethical concerns include: 1) providing a space and opportunity for people to identify values that they may find difficult to articulate (e.g. spiritual, identity); 2) recognising that some values cannot be traded without discussion and negotiation (e.g. the legal or felt rights of local people, intrinsic values of other species); and 3) understanding that it is often difficult to isolate valuation from decision-making processes because people feel there are strong ethical or moral issues at stake that need to be debated (e.g. the justice of the process, fairness in the distribution of benefits or disbenefits, responsibility, and issues of sustainability and future generations). Finding 3: Catalyst and/or conflict points can play a key role in the emergence and articulation of values at a societal or community level that have not previously been outwardly or explicitly articulated. Catalyst and conflict points can be symbolic and are often linked to wider contested issues and meanings about who is involved in decision-making, whose voice counts and who receives the benefits or disbenefits of environmental change. These catalyst points can potentially be connected to feelings of powerlessness that give rise to concern and protest. By recognising transcendental societal and communal values (the deeper-held and overarching values held by society and communities), it becomes possible to make these values explicit and incorporate them in decision-making to better anticipate and manage conflicts. Finding 4: There is a diversity of ways in which shared, plural, cultural and social values are used, but they are rarely conceptualised. The UK NEAFO provides a clear theoretical framework that distinguishes and categorises different dimensions and types of shared values. The proposed range of value types was both identifiable and distinguishable within case study results. This suggests that the framework provides a useful basis for operationalizing shared values for decision-making. Finding 5: Shared and social values in the sense of value to society is conceptualised very differently by conventional economics and other disciplines. Neoclassical economists have generally undertaken valuation by equating social value with the aggregate of individual values. They consider values as fundamentally commensurable. In contrast, literature from other disciplines consistently considers values as plural, not just in the sense that multiple things have value, but also that there are multiple dimensions to value that cannot necessarily be captured in a single metric. Within mainstream economics, the difficulties associated with commensurability and aggregating values have long been recognised, but have also been neglected. An interesting area for future debate between economic and non-economic views on values may be the normative nature of value-aggregation. Finding 6: A mixed method approach is required to elicit the multiple dimensions of shared values and to translate deeper-held, transcendental values into contextual values and preferences. Monetary valuation is limited to quantifying values. Other methods are needed to understand their meaning or content, and the communal, societal and transcendental values that underpin them. Psychometric, non-analytical and interpretive methods (e.g. storytelling) can reveal those shared values. They can be combined with deliberative-analytical methods (e.g. deliberative monetary valuation and multi-criteria analysis) to provide a comprehensive valuation that can quantify values, understand their individual and shared meanings and significance, and better include ethical dimensions. Finding 7: Deliberative and social learning processes help people to understand the values held by others; they can lead to increased sharing of values and/or to greater acceptance of the decisions emerging from such processes. Deliberation clearly affects what values participants express compared to non-deliberated processes. There is also a growing body of theoretical and empirical research suggesting that deliberation has the potential to affect how people understand and shape the values of others. Although rarely considered in the economic literature, the concept of social learning helps to explain some of the processes involved in deliberation. The extent to which deliberation or social learning helps participants express and shape values will depend upon the frequency and depth of interactions and the timescale over which interactions occur. Only a shift in cultural values (e.g. less emphasis on material wealth), reflected in other societal institutions (e.g. changes in the indicators used to measure national progress) is likely to achieve sustainable outcomes in the long-term. Finding 8: Media analysis is a promising avenue for characterising different types of shared values at a large scale, as well as assessing the conflicts between the communal values of different sectors of society. There has been a marked increase in public interest in environmental issues over the last decade, which is reflected in their increased media coverage. Media content and discourse analysis is able to distinguish and characterise the plurality of cultural, societal and transcendental values and their interrelationships, and can offer a picture of the self- and other-regarding values that underpin environmental issues and conflicts. Social media can provide a further forum for understanding societal and communal values surrounding environmental issues. Finding 9: Aesthetic and spiritual values of ecosystems have a strong non-instrumental component. While they benefit human well-being, they should not simply be classified as just ‘services’ or ‘benefits’. Many spiritual discourses about nature resist talk of consequentialist benefits and economic analysis. These discourses counter assertions of the disenchantment of the world, which is associated with an instrumental environmental ethic and the commodification of nature. Allowing the possibility of enchantment can be a richer way of understanding our experience of nature and alerts us to the limitations of using economic models for valuation and informing decisions about these profound cultural ecosystem ‘services’. Faith communities have experience of using these non-utilitarian values in their own decision-making and provide models that could be adapted for use in environmental decision-making. Finding 10: Subjective well-being measures provide a useful means of assessing ‘intangible’ cultural ecosystem services and their benefits. Different user groups associate common elements of subjective well-being with environmental settings, providing opportunities for development of standardised measures. In the UK NEAFO, key facets of well-being associated with places in nature across different user groups included: engagement with nature (incorporating elements of connectedness, getting to know nature and the beauty of nature, and taking care of a place); therapeutic benefits (including physical and mental aspects of health); place identity (including a sense of place and belonging); spiritual value (in the sense of feeling connected or responsible to something larger than oneself); social bonding with others; and transformative and memorable experiences. Further empirical work with different user groups and environmental settings would allow for the continued development of a standardised tool for large-scale non-monetary assessment of cultural ecosystem services

Bi-allelic mutations in MYL1 cause a severe congenital myopathy.

OBJECTIVE: Congenital myopathies are typically characterised by early onset hypotonia, weakness and hallmark features on biopsy. Despite the rapid pace of gene discovery, approximately 50% of patients with a congenital myopathy remain without a genetic diagnosis following screening of known disease genes. METHODS: We performed exome sequencing on two consanguineous probands diagnosed with a congenital myopathy and muscle biopsy showing selective atrophy/hypotrophy or absence of type II myofibres. RESULTS: We identified variants in the gene (MYL1) encoding the skeletal muscle fast-twitch specific myosin essential light chain in both probands. A homozygous essential splice acceptor variant (c.479-2A>G, predicted to result in skipping of exon 5 was identified in Proband 1, and a homozygous missense substitution (c.488T>G, p.(Met163Arg)) was identified in Proband 2. Protein modeling of the p.(Met163Arg) substitution predicted it might impede intermolecular interactions that facilitate binding to the IQ domain of myosin heavy chain, thus likely impacting on the structure and functioning of the myosin motor. MYL1 was markedly reduced in skeletal muscle from both probands, suggesting that the missense substitution likely results in an unstable protein. Knock down of myl1 in zebrafish resulted in abnormal morphology, disrupted muscle structure and impaired touch-evoked escape responses, thus confirming that skeletal muscle fast-twitch specific myosin essential light chain is critical for myofibre development and function. INTERPRETATION: Our data implicate MYL1 as a crucial protein for adequate skeletal muscle function and that MYL1 deficiency is associated with a severe congenital myopathy