Virtual testing and design of barrier coating systems

The development of coating systems for high temperatures has two central challenges: (i) the selection of materials and layer architectures that are resistant to cracking and chemical attack, and (ii) the identification of active failure mechanisms and their dependency on the system’s intrinsic properties. This talk will describe two modeling frameworks that are tailored to meet these challenges. In the first framework, an automated system for analyzing delamination and mud-cracking in complex multilayers; this enables system developers to consider a broad range of materials and architectures and in turn rapidly identify promising material systems. The impact of CMAS penetration on coating reliability will be briefly discussed to illustrate potential applications of the framework. In the second framework, distributed cohesive zone models are used to develop a virtual testing framework: the framework is capable of predicting a broad range of cracking modes without a priori assumptions regarding the evolution of damage. The simulation framework exploits highly parallel computing approaches that enable simulations covering a broad range of parameter space; this enables the construction of “durability regime maps”, which indicate likely failure mechanisms as a function of material properties. Simulations will be presented illustrating the transition between crack penetration, kinking and delamination; the results demonstrate that crack kinking can occur even in the absence of a putative kink crack, and that in certain situations, cohesive strength plays a critical role in governing brittle failure modes (i.e. the relative toughness of the constituents alone is insufficient). The implications of these simulations for developing tough, CMAS resistant coatings will be discussed, with a particular focus on the role of microstructure in ceramic coatings

Virtual simulation and design of barrier coatings for ceramic composites

The development of environmental barrier coating systems for ceramic composites has two central challenges: (i) the selection of materials and layer architectures that are resistant to cracking, volatilization, and chemical attack, and (ii) the identification of active failure mechanisms and their dependency on the system’s intrinsic properties. This talk will describe two modeling frameworks that are tailored to these two objectives. In the first framework, an automated approach for analyzing delamination and mud-cracking in complex multilayers enables developers to consider a broad range of materials and architectures and in turn rapidly identify promising material systems. The opportunities created by this framework will be demonstrated by illustrating the likely failure modes of environmental barrier coatings comprising multiple layers of rare earth silicates on silicon carbide substrates. These map illustrate combinations of material properties (e.g. coating thickness and thermal expansion coefficients) that avoid penetrating mud cracks and delamination cracks. Maps will also be presented that quantify the likelihood of crack kinking, i.e. the transition of a penetrating crack to a delamination crack that leads to coating failure. In the second framework, distributed cohesive zone models are used to develop a virtual testing framework: the framework is capable of predicting a broad range of cracking modes without a priori assumptions regarding the failure mode and without phenomenological criteria for the evolution of damage. In this framework, cracks emerge from defects in the structure according to classical brittle fracture theory. The simulation framework exploits highly parallel computing approaches that enable simulations covering a broad range of parameter space; this enables the construction of “durability regime maps”, which indicate likely failure mechanisms as a function of material properties. This framework has been used to identify whether or not interface cracks will travel along an interface or kink into the coating (leading to spallation), as a function of interface toughness, film toughness, mixed mode loading, and interface waviness. The results shed new light on the physics of crack kinking, which plays a fundamental role in coating durability. Further, the results provide insights regarding the role of interface waviness between coatings and substrates, such as would occur with a coated woven textile composite

GPU-based simulations of fracture in idealized brick and mortar composites

Stiff ceramic platelets (or bricks) that are aligned and bonded to a second ductile phase with low volume fraction (mortar) are a promising pathway to produce stiff, high-toughness composites. For certain ranges of constituent properties, including those of some synthetic analogs to nacre, one can demonstrate that the deformation is dominated by relative brick motions. This paper describes simulations of fracture that explicitly track the motions of individual rigid bricks in an idealized microstructure; cohesive tractions acting between the bricks introduce elastic, plastic and rupture behaviors. Results are presented for the stresses and damage near macroscopic cracks with different brick orientations relative to the loading orientation. The anisotropic macroscopic initiation toughness is computed for small-scale yielding conditions and is shown to be independent of specimen geometry and loading configuration. The results are shown to be in agreement with previously published experiments on synthetic nacre

An experimentally-validated computational framework for CMAS degradation of environmental barrier coatings

The work addresses reactions between silicate deposits, generically known as CMAS, and yttrium disilicate (YDS), a candidate environmental barrier coating (EBC) for SiC/SiC composites. The primary goal is to elucidate effects of deposit composition, exposure temperature and time on the extent of YDS recession as well as the associated compositional and morphological evolution of reacting phases. Phase equilibrium calculations are used to assess deposits of twelve different compositions at 1300°C and 1400°C; experimental observations of YDS recession are reported for three of these compositions at both temperatures. The results show that recession depths reach terminal values for exposure times ≥ 100h. Terminal recession depths are sensitive to deposit composition but only weakly affected by temperature. Deposits with high initial Ca:Si ratio react most severely with YDS, forming a thick layer containing an apatite reaction product interpenetrated by residual melt. The severity of the reaction decreases with decreasing Ca:Si ratio, and is least severe for deposits with insufficient Ca:Si ratio to produce apatite. Please click Additional Files below to see the full abstract

Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria–nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25–26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria–cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to environmental stressors. Citation: Shaughnessy DT, McAllister K, Worth L, Haugen AC, Meyer JN, Domann FE, Van Houten B, Mostoslavsky R, Bultman SJ, Baccarelli AA, Begley TJ, Sobol RW, Hirschey MD, Ideker T, Santos JH, Copeland WC, Tice RR, Balshaw DM, Tyson FL. 2014. Mitochondria, energetics, epigenetics, and cellular responses to stress. Environ Health Perspect 122:1271–1278; http://dx.doi.org/10.1289/ehp.140841

Paths Explored, Paths Omitted, Paths Obscured: Decision Points & Selective Reporting in End-to-End Data Analysis

Drawing reliable inferences from data involves many, sometimes arbitrary, decisions across phases of data collection, wrangling, and modeling. As different choices can lead to diverging conclusions, understanding how researchers make analytic decisions is important for supporting robust and replicable analysis. In this study, we pore over nine published research studies and conduct semi-structured interviews with their authors. We observe that researchers often base their decisions on methodological or theoretical concerns, but subject to constraints arising from the data, expertise, or perceived interpretability. We confirm that researchers may experiment with choices in search of desirable results, but also identify other reasons why researchers explore alternatives yet omit findings. In concert with our interviews, we also contribute visualizations for communicating decision processes throughout an analysis. Based on our results, we identify design opportunities for strengthening end-to-end analysis, for instance via tracking and meta-analysis of multiple decision paths

The Vitamin B1 Metabolism of Staphylococcus aureus Is Controlled at Enzymatic and Transcriptional Levels

Vitamin B1 is in its active form thiamine pyrophosphate (TPP), an essential cofactor for several key enzymes in the carbohydrate metabolism. Mammals must salvage this crucial nutrient from their diet in order to complement the deficiency of de novo synthesis. In the human pathogenic bacterium Staphylococcus aureus, two operons were identified which are involved in vitamin B1 metabolism. The first operon encodes for the thiaminase type II (TenA), 4-amino-5-hydroxymethyl-2-methylpyrimidine kinase (ThiD), 5-(2-hydroxyethyl)-4-methylthiazole kinase (ThiM) and thiamine phosphate synthase (ThiE). The second operon encodes a phosphatase, an epimerase and the thiamine pyrophosphokinase (TPK). The open reading frames of the individual operons were cloned, their corresponding proteins were recombinantly expressed and biochemically analysed. The kinetic properties of the enzymes as well as the binding of TPP to the in vitro transcribed RNA of the proposed operons suggest that the vitamin B1 homeostasis in S. aureus is strongly regulated at transcriptional as well as enzymatic levels

LabKey Server: An open source platform for scientific data integration, analysis and collaboration

<p>Abstract</p> <p>Background</p> <p>Broad-based collaborations are becoming increasingly common among disease researchers. For example, the Global HIV Enterprise has united cross-disciplinary consortia to speed progress towards HIV vaccines through coordinated research across the boundaries of institutions, continents and specialties. New, end-to-end software tools for data and specimen management are necessary to achieve the ambitious goals of such alliances. These tools must enable researchers to organize and integrate heterogeneous data early in the discovery process, standardize processes, gain new insights into pooled data and collaborate securely.</p> <p>Results</p> <p>To meet these needs, we enhanced the LabKey Server platform, formerly known as CPAS. This freely available, open source software is maintained by professional engineers who use commercially proven practices for software development and maintenance. Recent enhancements support: (i) Submitting specimens requests across collaborating organizations (ii) Graphically defining new experimental data types, metadata and wizards for data collection (iii) Transitioning experimental results from a multiplicity of spreadsheets to custom tables in a shared database (iv) Securely organizing, integrating, analyzing, visualizing and sharing diverse data types, from clinical records to specimens to complex assays (v) Interacting dynamically with external data sources (vi) Tracking study participants and cohorts over time (vii) Developing custom interfaces using client libraries (viii) Authoring custom visualizations in a built-in R scripting environment.</p> <p>Diverse research organizations have adopted and adapted LabKey Server, including consortia within the Global HIV Enterprise. Atlas is an installation of LabKey Server that has been tailored to serve these consortia. It is in production use and demonstrates the core capabilities of LabKey Server. Atlas now has over 2,800 active user accounts originating from approximately 36 countries and 350 organizations. It tracks roughly 27,000 assay runs, 860,000 specimen vials and 1,300,000 vial transfers.</p> <p>Conclusions</p> <p>Sharing data, analysis tools and infrastructure can speed the efforts of large research consortia by enhancing efficiency and enabling new insights. The Atlas installation of LabKey Server demonstrates the utility of the LabKey platform for collaborative research. Stable, supported builds of LabKey Server are freely available for download at <url>http://www.labkey.org</url>. Documentation and source code are available under the Apache License 2.0.</p

REVERBa couples the circadian clock to hepatic glucocorticoid action.

The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day. Temporal segregation of GC action was underpinned by a physical interaction of GR with the circadian transcription factor REVERBa and co-binding with liver-specific hepatocyte nuclear transcription factors (HNFs) on chromatin. REVERBa promoted efficient GR recruitment to chromatin during the day, acting in part by maintaining histone acetylation, with REVERBa-dependent GC responses providing segregation of carbohydrate and lipid metabolism. Importantly, deletion of Reverba inverted circadian liver GC sensitivity and protected mice from hepatosteatosis induced by chronic GC administration. Our results reveal a mechanism by which the circadian clock acts through REVERBa in liver on elements bound by HNF4A/HNF6 to direct GR action on energy metabolism