A wave of apoptosis (programmed cell death) occurs normally in pancreatic beta-cells of newborn mice. We previously showed that macrophages from non-obese diabetic (NOD) mice become activated more slowly and engulf apoptotic cells at a lower rate than macrophages from control (Balb/c) mice. It has been hypothesized that this low clearance could result in secondary necrosis, escalating inflammation and self-antigen presentation that later triggers autoimmune, Type 1 diabetes (T1D). We here investigate whether this hypothesis could offer a reasonable and parsimonious explanation for onset of T1D in NOD mice. We quantify variants of the Copenhagen model (Freiesleben De Blasio et al. 1999 Diabetes 48, 1677), based on parameters from NOD and Balb/c experimental data. We show that the original Copenhagen model fails to explain observed phenomena within a reasonable range of parameter values, predicting an unrealistic all-or-none disease occurrence for both strains. However, if we take into account that, in general, activated macrophages produce harmful cytokines only when engulfing necrotic (but not apoptotic) cells, then the revised model becomes qualitatively and quantitatively reasonable. Further, we show that known differences between NOD and Balb/c mouse macrophage kinetics are large enough to account for the fact that an apoptotic wave can trigger escalating inflammatory response in NOD, but not Balb/c mice. In Balb/c mice, macrophages clear the apoptotic wave so efficiently, that chronic inflammation is prevented.

With the fast global adoption of the Materials Genome Initiative (MGI), scientists and engineers are faced with the need to conduct sophisticated data analytics on large datasets to extract knowledge that can be used in modeling the behavior of materials. This raises a new problem for materials scientists: how to create and foster interoperability and share developed software tools and generated datasets. A microstructure-informed cloud-based platform (MiCloud™) has been developed that addresses this need, enabling users to easily access and insert microstructure informatics into computational tools that predict performance of engineering products by accounting for microstructural dependencies on manufacturing provenance. The platform extracts information from microstructure data by employing algorithms including signal processing, machine learning, pattern recognition, computer vision, predictive analytics, uncertainty quantification, and data visualization. The interoperability capabilities of MiCloud and its various web-based applications are demonstrated in this case study by analyzing Ti6AlV4 microstructure data via automatic identification of various features of interest and quantifying its characteristics that are used in extracting correlations and causations for the associated mechanical behavior (e.g., yield strength, cold-dwell debit, etc.). The data were recorded by two methods: (1) backscattered electron (BSE) imaging for extracting spatial and morphological information about alpha and beta phases and (2) electron backscatter diffraction (EBSD) for extracting spatial, crystallographic, and morphological information about microtextured regions (MTRs) of the alpha phase. Extracting reliable knowledge from generated information requires data analytics of a large amount of multiscale microstructure data which necessitates the development of efficient algorithms (and the associated software tools) for data recording, analysis, and visualization. The interoperability of these tools and superior effectiveness of the cloud computing approach are validated by featuring several examples of its use in alpha/beta titanium alloys and Ni-based superalloys, reflecting the anticipated computational cost and time savings via the use of web-based applications in implementations of microstructure-informed integrated computational materials engineering (ICME).

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