544 research outputs found

    Tables of f/us, ub/ and g/us, ub/ functions for semiconductor surface calculations

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    Derivation of mathematical functions for calculating changes in semiconductor surfaces due to applied surface charg

    A Global Community of Courts? Modelling the Use of Persuasive Authority as a Complex Network

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    There is a growing discussion in the legal literature of an emerging global community of courts composed of a network of increasing judicial dialogue across national borders. We investigate the use of foreign persuasive authority in common law countries by analyzing the network of citations to case law in a corpus of over 1.5 million judgments given by the senior courts of twenty-six common law countries. Our corpus of judgments is derived from data available in the vLex Justis database. In this paper we aim to quantify the flow of jurisprudence across the countries in our corpus and to explore the factors that may influence a judge’s selection of foreign jurisprudence. Utilization of foreign case law varies across the countries in our data, with the courts of some countries presenting higher engagement with foreign jurisprudence than others. Our analysis shows that there has been an upward trend in the use of foreign case law over time, with a marked increase in citations across national borders from the 1990s onward, potentially indicating that increased digital access to foreign judgments has served to facilitate and promote comparative analysis. Not only has the use of foreign case law generally increased over time, the factors that may influence the selection of case law have also evolved, with judges gradually casting their research beyond the most influential and well-known foreign authorities. Notwithstanding that judgments emanating from the United Kingdom (chiefly from the courts of England and Wales) constitute the most frequently consulted body of jurisprudence, we find evidence that domestic courts favor citing the case law of countries that are geographically proximal

    Live Coding, Live Notation, Live Performance

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    This paper/demonstration explores relationships between code, notation including representation, visualisation and performance. Performative aspects of live coding activities are increasingly being investigated as the live coding movement continues to grow and develop. Although live instrumental performance is sometimes included as an accompaniment to live coding, it is often not a fully integrated part of the performance, relying on improvisation and/or basic indicative forms of notation with varying levels of sophistication and universality. Technologies are developing which enable the use of fully explicit music notations as well as more graphic ones, allowing more fully integrated systems of code in and as performance which can also include notations of arbitrary complexity. This itself allows the full skills of instrumental musicians to be utilised and synchronised in the process. This presentation/demonstration presents work and performances already undertaken with these technologies, including technologies for body sensing and data acquisition in the translation of the movements of dancers and musicians into synchronously performable notation, integrated by live and prepared coding. The author together with clarinetist Ian Mitchell present a short live performance utilising these techniques, discuss methods for the dissemination and interpretation of live generated notations and investigate how they take advantage of instrumental musicians’ training-related neuroplasticity skills

    Tumor Evolution in Two Patients with Basal-like Breast Cancer: A Retrospective Genomics Study of Multiple Metastases

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    Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual

    Crossing boundaries: Exploring the theory, practice and possibility of a ‘Future 3’ curriculum

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    In this article, we examine a case of innovation in curriculum and pedagogy at a new school in the UK. We begin by outlining the 3 Futures model, which we use as a methodological heuristic in the case study of the school that appears to be both knowledge‐led and learner‐engaged; characteristics of the Future 3 scenario. In considering the school's curriculum, we also draw on a number of concepts from the work of Basil Bernstein: classification, framing and the idea of open schools, and a curriculum integration model developed by us to consider the degree of epistemic emphasis in the school's predominantly interdisciplinary curriculum. Together, these concepts provide the means to examine the organising principles of practice operating in the school, as links are drawn between the 3 Futures model, Bernstein's concepts and the data. We theorise this as a form of ‘opening up’, suggesting that even within the context of an interdisciplinary curriculum, access to powerful knowledge may be maintained in a whole‐school approach where the demands of both knowledge and knowers are brought into balance. The school's approach and the theorisation we offer may provide insights for other schools embarking on a futures model for education and for twenty‐first‐century educational discourses more generally

    Improving statistical inference on pathogen densities estimated by quantitative molecular methods: malaria gametocytaemia as a case study

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    BACKGROUND: Quantitative molecular methods (QMMs) such as quantitative real-time polymerase chain reaction (q-PCR), reverse-transcriptase PCR (qRT-PCR) and quantitative nucleic acid sequence-based amplification (QT-NASBA) are increasingly used to estimate pathogen density in a variety of clinical and epidemiological contexts. These methods are often classified as semi-quantitative, yet estimates of reliability or sensitivity are seldom reported. Here, a statistical framework is developed for assessing the reliability (uncertainty) of pathogen densities estimated using QMMs and the associated diagnostic sensitivity. The method is illustrated with quantification of Plasmodium falciparum gametocytaemia by QT-NASBA. RESULTS: The reliability of pathogen (e.g. gametocyte) densities, and the accompanying diagnostic sensitivity, estimated by two contrasting statistical calibration techniques, are compared; a traditional method and a mixed model Bayesian approach. The latter accounts for statistical dependence of QMM assays run under identical laboratory protocols and permits structural modelling of experimental measurements, allowing precision to vary with pathogen density. Traditional calibration cannot account for inter-assay variability arising from imperfect QMMs and generates estimates of pathogen density that have poor reliability, are variable among assays and inaccurately reflect diagnostic sensitivity. The Bayesian mixed model approach assimilates information from replica QMM assays, improving reliability and inter-assay homogeneity, providing an accurate appraisal of quantitative and diagnostic performance. CONCLUSIONS: Bayesian mixed model statistical calibration supersedes traditional techniques in the context of QMM-derived estimates of pathogen density, offering the potential to improve substantially the depth and quality of clinical and epidemiological inference for a wide variety of pathogens

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer

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    Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate the underlying mechanisms that cause breast cancer metastasis. To address this issue, we performed DNA exome and RNA sequencing of matched primary tumors and multiple metastases from 16 patients, totaling 83 distinct specimens. We identified tumor-specific drivers by integrating known protein-protein network information with RNA expression and somatic DNA alterations and found that genetic drivers were predominantly established in the primary tumor and maintained through metastatic spreading. In addition, our analyses revealed that most genetic drivers were DNA copy number changes, the TP53 mutation was a recurrent founding mutation regardless of subtype, and that multiclonal seeding of metastases was frequent and occurred in multiple subtypes. Genetic drivers unique to metastasis were identified as somatic mutations in the estrogen and androgen receptor genes. These results highlight the complexity of metastatic spreading, be it monoclonal or multiclonal, and suggest that most metastatic drivers are established in the primary tumor, despite the substantial heterogeneity seen in the metastases

    Identification of mRNA isoform switching in breast cancer

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    Abstract Background Alternative splicing provides a major mechanism to generate protein diversity. Increasing evidence suggests a link of dysregulation of splicing associated with cancer. While previous genomic-based studies demonstrated the expression of a handful of tumor-specific isoforms, genome-wide alterations in the balance between isoforms and cancer subtypes is understudied. Result We systematically analyzed the isoform-level expression patterns and isoform switching events of 819 breast tumor and normal samples assayed by mRNA-seq from TCGA project. On average, 2.2 isoforms per gene were detected and 67.5 % of detected genes (i.e. expressed) showed 1–2 isoforms only. While the majority of isoforms for a given gene were positively correlated with each other and the overall gene level, 470 pairs of isoforms displayed an inverse correlation suggesting a switching event. Most of the isoform switching events were associated with molecular subtypes, including a Basal-like-associated switching in CTNND1. 88 genes showed switching independent of subtypes, among which the isoform pattern of PRICKLE1 was associated with a large genomic signature of biological significance. Conclusion Our results reveal that the majority of genes do not undergo complex mRNA splicing within breast cancers, and that there is a general concordance in isoform and gene expression levels in breast tumors. We identified hundreds of isoform switching events across breast tumors, most of which were associated with differences in tumor subtypes. As exemplified by the detailed analysis of CTNND1 and PRICKLE1, these isoform switching events potentially provide new insights into the post-transcriptional regulatory mechanisms of tumor subtypes and cancer biology
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