Gamma-Normal-Gamma Mixture Model for Detecting Differentially Methylated Loci in Three Breast Cancer Cell Lines

With state-of-the-art microarray technologies now available for whole genome CpG island (CGI) methylation profiling, there is a need to develop statistical models that are specifically geared toward the analysis of such data. In this article, we propose a Gamma-Normal-Gamma (GNG) mixture model for describing three groups of CGI loci: hypomethylated, undifferentiated, and hypermethylated, from a single methylation microarray. This model was applied to study the methylation signatures of three breast cancer cell lines: MCF7, T47D, and MDAMB361. Biologically interesting and interpretable results are obtained, which highlights the heterogeneity nature of the three cell lines. This underlies the premise for the need of analyzing each of the microarray slides individually as opposed to pooling them together for a single analysis. Our comparisons with the fitted densities from the Normal-Uniform (NU) mixture model in the literature proposed for gene expression analysis show an improved goodness of fit of the GNG model over the NU model. Although the GNG model was proposed in the context of single-slide methylation analysis, it can be readily adapted to analyze multi-slide methylation data as well as other types of microarray data

Super-orbital re-entry in Australia - laboratory measurement, simulation and flight observation

There are large uncertainties in the aerothermodynamic modelling of super-orbital re-entry which impact the design of spacecraft thermal protection systems (TPS). Aspects of the thermal environment of super-orbital re-entry flows can be simulated in the laboratory using arc- and plasma jet facilities and these devices are regularly used for TPS certification work [5]. Another laboratory device which is capable of simulating certain critical features of both the aero and thermal environment of super-orbital re-entry is the expansion tube, and three such facilities have been operating at the University of Queensland in recent years[10]. Despite some success, wind tunnel tests do not achieve full simulation, however, a virtually complete physical simulation of particular re-entry conditions can be obtained from dedicated flight testing, and the Apollo era FIRE II flight experiment [2] is the premier example which still forms an important benchmark for modern simulations. Dedicated super-orbital flight testing is generally considered too expensive today, and there is a reluctance to incorporate substantial instrumentation for aerothermal diagnostics into existing missions since it may compromise primary mission objectives. An alternative approach to on-board flight measurements, with demonstrated success particularly in the ‘Stardust’ sample return mission, is remote observation of spectral emissions from the capsule and shock layer [8]. JAXA’s ‘Hayabusa’ sample return capsule provides a recent super-orbital reentry example through which we illustrate contributions in three areas: (1) physical simulation of super-orbital re-entry conditions in the laboratory; (2) computational simulation of such flows; and (3) remote acquisition of optical emissions from a super-orbital re entry event

Heritable clustering and pathway discovery in breast cancer integrating epigenetic and phenotypic data

BACKGROUND: In order to recapitulate tumor progression pathways using epigenetic data, we developed novel clustering and pathway reconstruction algorithms, collectively referred to as heritable clustering. This approach generates a progression model of altered DNA methylation from tumor tissues diagnosed at different developmental stages. The samples act as surrogates for natural progression in breast cancer and allow the algorithm to uncover distinct epigenotypes that describe the molecular events underlying this process. Furthermore, our likelihood-based clustering algorithm has great flexibility, allowing for incomplete epigenotype or clinical phenotype data and also permitting dependencies among variables. RESULTS: Using this heritable clustering approach, we analyzed methylation data obtained from 86 primary breast cancers to recapitulate pathways of breast tumor progression. Detailed annotation and interpretation are provided to the optimal pathway recapitulated. The result confirms the previous observation that aggressive tumors tend to exhibit higher levels of promoter hypermethylation. CONCLUSION: Our results indicate that the proposed heritable clustering algorithms are a useful tool for stratifying both methylation and clinical variables of breast cancer. The application to the breast tumor data illustrates that this approach can select meaningful progression models which may aid the interpretation of pathways having biological and clinical significance. Furthermore, the framework allows for other types of biological data, such as microarray gene expression or array CGH data, to be integrated

Moving teaching online: cultural barriers experienced by university teachers during Covid19

This empirical study examines the experiences of academics and professional service staff in a large UK university during first weeks of the transition to online teaching and working from home during the Covid-19 pandemic. The method draws on the work by Gourlay and Oliver (2018) to explore engagement with the digital university in everyday practice. Using data from 412 survey responses and 32 interviews, the study traces varying ways staff characterised themselves during the first months of lockdown in the UK (from March to July, 2020). The findings highlight that university support services underwent a metamorphosis to support the transition to online teaching. However, insufficient attention was paid to the ‘identity crisis’ and threats perceived by academics who were used to teaching students on campus. Academics tended to focus on transferring traditional teaching practices to the online environment, rather than on changing teaching practice, leaving face-to-face teaching as the default point of reference. These cultural barriers are a persistent obstacle to a more productive engagement with digitalisation. Transitioning to online teaching involves continuing existing work while also learning new practices. Such efforts were challenging for teaching staff who did not have dedicated space at home to work and those with caring responsibilities. This, combined with gendered patterns around caring and the extra support needed by students during the crisis, added emotional labour to already-full workloads. We recommend that intersecting forms of disadvantage be acknowledged, supported and rewarded for universities to create sustainable and just futures

The Fire and Smoke Model Evaluation Experiment—A Plan for Integrated, Large Fire–Atmosphere Field Campaigns

The Fire and Smoke Model Evaluation Experiment (FASMEE) is designed to collect integrated observations from large wildland fires and provide evaluation datasets for new models and operational systems. Wildland fire, smoke dispersion, and atmospheric chemistry models have become more sophisticated, and next-generation operational models will require evaluation datasets that are coordinated and comprehensive for their evaluation and advancement. Integrated measurements are required, including ground-based observations of fuels and fire behavior, estimates of fire-emitted heat and emissions fluxes, and observations of near-source micrometeorology, plume properties, smoke dispersion, and atmospheric chemistry. To address these requirements the FASMEE campaign design includes a study plan to guide the suite of required measurements in forested sites representative of many prescribed burning programs in the southeastern United States and increasingly common high-intensity fires in the western United States. Here we provide an overview of the proposed experiment and recommendations for key measurements. The FASMEE study provides a template for additional large-scale experimental campaigns to advance fire science and operational fire and smoke models

The NEMP family supports metazoan fertility and nuclear envelope stiffness

Human genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) i