33 research outputs found

    Design of an interactive computer system for microelectronic mask making

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    Enriched biodiversity data as a resource and service

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    Background: Recent years have seen a surge in projects that produce large volumes of structured, machine-readable biodiversity data. To make these data amenable to processing by generic, open source “data enrichment” workflows, they are increasingly being represented in a variety of standards-compliant interchange formats. Here, we report on an initiative in which software developers and taxonomists came together to address the challenges and highlight the opportunities in the enrichment of such biodiversity data by engaging in intensive, collaborative software development: The Biodiversity Data Enrichment Hackathon. Results: The hackathon brought together 37 participants (including developers and taxonomists, i.e. scientific professionals that gather, identify, name and classify species) from 10 countries: Belgium, Bulgaria, Canada, Finland, Germany, Italy, the Netherlands, New Zealand, the UK, and the US. The participants brought expertise in processing structured data, text mining, development of ontologies, digital identification keys, geographic information systems, niche modeling, natural language processing, provenance annotation, semantic integration, taxonomic name resolution, web service interfaces, workflow tools and visualisation. Most use cases and exemplar data were provided by taxonomists. One goal of the meeting was to facilitate re-use and enhancement of biodiversity knowledge by a broad range of stakeholders, such as taxonomists, systematists, ecologists, niche modelers, informaticians and ontologists. The suggested use cases resulted in nine breakout groups addressing three main themes: i) mobilising heritage biodiversity knowledge; ii) formalising and linking concepts; and iii) addressing interoperability between service platforms. Another goal was to further foster a community of experts in biodiversity informatics and to build human links between research projects and institutions, in response to recent calls to further such integration in this research domain. Conclusions: Beyond deriving prototype solutions for each use case, areas of inadequacy were discussed and are being pursued further. It was striking how many possible applications for biodiversity data there were and how quickly solutions could be put together when the normal constraints to collaboration were broken down for a week. Conversely, mobilising biodiversity knowledge from their silos in heritage literature and natural history collections will continue to require formalisation of the concepts (and the links between them) that define the research domain, as well as increased interoperability between the software platforms that operate on these concepts

    Clonal architecture of secondary acute myeloid leukemia

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    BACKGROUND: The myelodysplastic syndromes are a group of hematologic disorders that often evolve into secondary acute myeloid leukemia (AML). The genetic changes that underlie progression from the myelodysplastic syndromes to secondary AML are not well understood. METHODS: We performed whole-genome sequencing of seven paired samples of skin and bone marrow in seven subjects with secondary AML to identify somatic mutations specific to secondary AML. We then genotyped a bone marrow sample obtained during the antecedent myelodysplastic-syndrome stage from each subject to determine the presence or absence of the specific somatic mutations. We identified recurrent mutations in coding genes and defined the clonal architecture of each pair of samples from the myelodysplastic-syndrome stage and the secondary-AML stage, using the allele burden of hundreds of mutations. RESULTS: Approximately 85% of bone marrow cells were clonal in the myelodysplastic-syndrome and secondary-AML samples, regardless of the myeloblast count. The secondary-AML samples contained mutations in 11 recurrently mutated genes, including 4 genes that have not been previously implicated in the myelodysplastic syndromes or AML. In every case, progression to acute leukemia was defined by the persistence of an antecedent founding clone containing 182 to 660 somatic mutations and the outgrowth or emergence of at least one subclone, harboring dozens to hundreds of new mutations. All founding clones and subclones contained at least one mutation in a coding gene. CONCLUSIONS: Nearly all the bone marrow cells in patients with myelodysplastic syndromes and secondary AML are clonally derived. Genetic evolution of secondary AML is a dynamic process shaped by multiple cycles of mutation acquisition and clonal selection. Recurrent gene mutations are found in both founding clones and daughter subclones. (Funded by the National Institutes of Health and others.

    Drivers of Change or Cut-Throat Competitors? Challenging Cultures of Innovation of Chinese and Nigerian Migrant Entrepreneurs in West Africa

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    L'afflux remarquable des entrepreneurs migrants chinois dans diffĂ©rents pays d'Afrique occidentale au cours des derniĂšres annĂ©es a Ă©tĂ© heurtĂ©e Ă  une rĂ©sistance de plus en plus farouche par des entrepreneurs locaux Ă©tablis. Que le premiers ont un avantage concurrentiel sur ce dernier en raison de traits socio-culturels distinctifs, ou si l'efficacitĂ© supposĂ©e chinoise est juste une caractĂ©ristique de toutes les diasporas mercantiles, est ouvert Ă  la question. Cette Ă©tude exploratoire des migrants entrepreneuriales chinois et nigĂ©rians au Ghana et au BĂ©nin tente de rĂ©pondre Ă  cette question. Apparemment, les forces culturels des agents du changement migrants ne sont pas limitĂ©s Ă  des systĂšmes de valeurs hĂ©ritĂ©es ou religions, comme une Ă©thique protestante ou le confucianisme, mais ils sont adaptĂ©s en permanence et ont inventĂ© de nouveau par des rĂ©seaux transnationaux de la migration dans un monde globalisĂ©. Il n'y a aucune preuve d'une prĂ©tendue supĂ©rioritĂ© de la culture d’innovation chinois par rapport aux cultures d’innovation africains des migrants entrepreneuriales. PlutĂŽt, il existe une capacitĂ© accrue d'innovation d'une diaspora mercantile en gĂ©nĂ©ral vis Ă  vis des entrepreneurs locaux, indĂ©pendamment de l'origine de la culture nationale dans lequel il est intĂ©grĂ©. En outre, la rivalitĂ© des entrepreneurs migrants chinois et nigĂ©rians dans les marchĂ©s africains ne conduit pas nĂ©cessairement Ă  la concurrence coupe-gorge souvent suspectĂ©e sous l'impact de la mondialisation. Souvent, les deux groupes agissent plutĂŽt complĂ©mentaires. Cela contribue, sous certaines conditions, mĂȘme Ă  la rĂ©duction de la pauvretĂ© dans le pays d'accueil

    Daily magnesium fluxes regulate cellular timekeeping and energy balance

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    Circadian clocks are fundamental to the biology of most eukaryotes, coordinating behaviour and physiology to resonate with the environmental cycle of day and night through complex networks of clock-controlled genes1, 2, 3. A fundamental knowledge gap exists, however, between circadian gene expression cycles and the biochemical mechanisms that ultimately facilitate circadian regulation of cell biology4, 5. Here we report circadian rhythms in the intracellular concentration of magnesium ions, [Mg2+]i, which act as a cell-autonomous timekeeping component to determine key clock properties both in a human cell line and in a unicellular alga that diverged from each other more than 1 billion years ago6. Given the essential role of Mg2+ as a cofactor for ATP, a functional consequence of [Mg2+]i oscillations is dynamic regulation of cellular energy expenditure over the daily cycle. Mechanistically, we find that these rhythms provide bilateral feedback linking rhythmic metabolism to clock-controlled gene expression. The global regulation of nucleotide triphosphate turnover by intracellular Mg2+ availability has potential to impact upon many of the cell’s more than 600 MgATP-dependent enzymes7 and every cellular system where MgNTP hydrolysis becomes rate limiting. Indeed, we find that circadian control of translation by mTOR8 is regulated through [Mg2+]i oscillations. It will now be important to identify which additional biological processes are subject to this form of regulation in tissues of multicellular organisms such as plants and humans, in the context of health and disease

    Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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    Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
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