Astrophysics lies at the crossroads of big datasets (such as the Large Synoptic Survey Telescope and Gaia), open source software to visualize and interpret high dimensional datasets (such as Glue, WorldWide Telescope,...
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ABSTRACTIntroductionImmune checkpoint blockade has revolutionised cancer treatment. However, clinical outcomes are highly variable as only a proportion of cancer patients benefit from this treatment. To understand the...
ABSTRACTIntroductionImmune checkpoint blockade has revolutionised cancer treatment. However, clinical outcomes are highly variable as only a proportion of cancer patients benefit from this treatment. To understand the mechanisms that determine responses to current immunotherapies and for the design of alternative approaches, it is crucial to characterise the immune landscape of the tumour microenvironment. An in-depth understanding of anti-tumour immunity requires a comprehensive analysis of the immune cell populations that participate in the process of tumorigenesis. The aim of this study is to unravel local and systemic profiles of lymphoid and myeloid immune subsets in colorectal cancer (CRC) using high-dimensional immunophenotyping by mass cytometry. Material and methodsThe expression of 36 immune cell markers was simultaneously assessed at the single-cell level by mass cytometry in tumour tissues (n=19), tumor-associated lymph nodes (n=17), adjacent normal mucosa (n=4), and peripheral blood samples (n=9) derived from 18 CRC patients. In total, 9 million cells were included in the analysis. Cytosplore and HSNE (Hierarchical Stochastic Neighbour Embedding) analysis tools were used to identify and visualise the composition of the lymphoid and myeloid cell populations of the innate and adaptive immune compartments in the tissues. Results and discussionsWe identified 220 immune cell subsets, including tumor-resident CD8 +CD45RO +CD103 +PD-1 +, CD4 +CD45RO +CD103 +PD-1 + and CD4 +CD45RO +ICOS +CD27 - T cell populations that were not found in tumor-associated lymph nodes, adjacent normal mucosa, and peripheral blood samples of CRC patients. In addition, we identified an overrepresentation of CD3 -CD7 +CD56 +CD45RO +CD127 - intermediate innate lymphoid cells in mismatch-repair deficient cancers and an enrichment of CD14 - myeloid populations in mismatch-repair proficient cancers. Unsupervised clustering of the samples based on the composite immune profile separated the
A prototype concurrent engineering tool has been developed for the preliminary design of composite topside structures for modern navy warships. This tool, named GELS for the Concurrent Engineering of Layered Structure...
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A prototype concurrent engineering tool has been developed for the preliminary design of composite topside structures for modern navy warships. This tool, named GELS for the Concurrent Engineering of Layered Structures, provides designers with an immediate assessment of the impacts of their decisions on several disciplines which are important to the performance of a modern naval topside structure, including electromagnetic interference effects (EMI), radar cross section (RCS), structural integrity, cost, and weight. Preliminary analysis modules in each of these disciplines are integrated to operate from a common set of design variables and a common materials database. Performance in each discipline and an overall fitness function for the concept are then evaluated. A graphical user interface (GUI) is used to define requirements and to display the results from the technical analysis modules. Optimization techniques, including feasible sequential quadratic programming (FSQP) and exhaustive search are used to modify the design variables to satisfy all requirements simultaneously. The development of this tool, the technical modules, and their integration are discussed noting the decisions and compromises required to develop and integrate the modules into a prototype conceptual design tool.
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