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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 1,783 records · Page 99
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Robust constrained tension control for high-precision roll-to-roll processes

Tension control is critical for maintaining good product quality in most roll-to-roll (R2R) production systems. Previous work has primarily focused on improving the disturbance rejection performance of tension controllers. Here, a robust linear parameter-varying model predictive control (LPV-MPC) scheme is designed to enhance the tension tracking performance of a pilot R2R system for deposition of materials used in flexible thin film applications. The performance of a tension controller may degrade due to disturbances associated with model uncertainties and the slowly-changing dynamics in R2R systems. We introduce a method that separately treats these two sources of disturbance. The controller utilizes an incremental model to eliminate the errors caused by the mismatch between the nominal model and the actual system. A tube-based MPC formulation combined with scheduled parameters adequately updates models and corrects for the time-varying dynamics. Constraints on the rated motor torque are incorporated in the MPC to maintain the controller reliability and avoid machine failures. We illustrate the operation of our control algorithm through simulation of an actual R2R system. The controller outperforms the benchmarks in terms of fast transient response and offset-free tension tracking. Furthermore, it also demonstrates immunity from variations due to parametric uncertainties.

42 ENGINEERING↗
DOE OSTI2024

Epitopes recognition of SARS-CoV-2 nucleocapsid RNA binding domain by human monoclonal antibodies

Coronavirus nucleocapsid protein (NP) of SARS-CoV-2 plays a central role in many functions important for virus proliferation including packaging and protecting genomic RNA. The protein shares sequence, structure, and architecture with nucleocapsid proteins from betacoronaviruses. The N-terminal domain (NP RBD ) binds RNA and the C-terminal domain is responsible for dimerization. After infection, NP is highly expressed and triggers robust host immune response. The anti-NP antibodies are not protective and not neutralizing but can effectively detect viral proliferation soon after infection. Two structures of SARS-CoV-2 NP RBD were determined providing a continuous model from residue 48 to 173, including RNA binding region and key epitopes. Five structures of NP RBD complexes with human mAbs were isolated using an antigen-bait sorting. Complexes revealed a distinct complement-determining regions and unique sets of epitope recognition. This may assist in the early detection of pathogens and designing peptide-based vaccines. Mutations that significantly increase viral load were mapped on developed, full length NP model, likely impacting interactions with host proteins and viral RNA.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Automated 3D cytoplasm segmentation in soft X-ray tomography

Cells’ structure is key to understanding cellular function, diagnostics, and therapy development. Soft X-ray tomography (SXT) is a unique tool to image cellular structure without fixation or labeling at high spatial resolution and throughput. Fast acquisition times increase demand for accelerated image analysis, like segmentation. Currently, segmenting cellular structures is done manually and is a major bottleneck in the SXT data analysis. This paper introduces ACSeg, an automated 3D cytoplasm segmentation model. ACSeg is generated using semi-automated labels and 3D U-Net and is trained on 43 SXT tomograms of immune T cells, rapidly converging to high-accuracy segmentation, therefore reducing time and labor. Furthermore, adding only 6 SXT tomograms of other cell types diversifies the model, showing potential for optimal experimental design. ACSeg successfully segmented unseen tomograms and is published on Biomedisa, enabling high-throughput analysis of cell volume and structure of cytoplasm in diverse cell types.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Subject-specific multi-scale modeling of the fate of inhaled aerosols

Determining the fate of inhaled aerosols in the respiratory system is essential in assessing the potential toxicity of inhaled airborne materials, responses to airborne pathogens, or in improving inhaled drug delivery. The availability of high-resolution clinical lung imaging and advances in the reconstruction of lung airways from CT images have led to the development of subject-specific in-silico 3D models of aerosol dosimetry, often referred to as computational fluid-particle-dynamics (CFPD) models. As CFPD models require extensive computing resources, they are typically confined to the upper and large airways. These models can be combined with lower-dimensional models to form multiscale models that predict the transport and deposition of inhaled aerosols in the entire respiratory tract. Understanding where aerosols deposit is only the first of potentially several key events necessary to predict an outcome, being a detrimental health effect or a therapeutic response. To that end, multiscale approaches that combine CFPD with physiologically-based pharmacokinetics (PBPK) models have been developed to evaluate the absorption, distribution, metabolism, and excretion (ADME) of toxic or medicinal chemicals in one or more compartments of the human body. CFPD models can also be combined with host cell dynamics (HCD) models to assess regional immune system responses. Here, this paper reviews the state of the art of these different multiscale approaches and discusses the potential role of personalized or subject-specific modeling in respiratory health.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Structural delineation and phase-dependent activation of the costimulatory CD27:CD70 complex

CD27 is a tumor necrosis factor (TNF) receptor, which stimulates lymphocytes and promotes their differentiation upon activation by TNF ligand CD70. Activation of the CD27 receptor provides a costimulatory signal to promote T cell, B cell, and NK cell activity to facilitate antitumor and anti-infection immunity. Aberrant increased and focused expression of CD70 on many tumor cells renders CD70 an attractive therapeutic target for direct tumor killing. However, despite their use as drug targets to treat cancers, the molecular basis and atomic details of CD27 and CD70 interaction remain elusive. Here we report the crystal structure of human CD27 in complex with human CD70. Analysis of our structure shows that CD70 adopts a classical TNF ligand homotrimeric assembly to engage CD27 receptors in a 3:3 stoichiometry. By combining structural and rational mutagenesis data with reported disease-correlated mutations, we identified the key amino acid residues of CD27 and CD70 that control this interaction. We also report increased potency for plate-bound CD70 constructs compared with solution-phase ligand in a functional activity to stimulate T-cells in vitro. These findings offer new mechanistic insight into this critical costimulatory interaction.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Structural insights into protection against a SARS-CoV-2 spike variant by T cell receptor diversity

T cells play a crucial role in combatting SARS-CoV-2 and forming long-term memory responses to this coronavirus. The emergence of SARS-CoV-2 variants that can evade T cell immunity has raised concerns about vaccine efficacy and the risk of reinfection. Some SARS-CoV-2 T cell epitopes elicit clonally restricted CD8 + T cell responses characterized by T cell receptors (TCRs) that lack structural diversity. Mutations in such epitopes can lead to loss of recognition by most T cells specific for that epitope, facilitating viral escape. Here, we studied an HLA-A2–restricted spike protein epitope (RLQ) that elicits CD8 + T cell responses in COVID-19 convalescent patients characterized by highly diverse TCRs. We previously reported the structure of an RLQ-specific TCR (RLQ3) with greatly reduced recognition of the most common natural variant of the RLQ epitope (T1006I). Opposite to RLQ3, TCR RLQ7 recognizes T1006I with even higher functional avidity than the WT epitope. To explain the ability of RLQ7, but not RLQ3, to tolerate the T1006I mutation, we determined structures of RLQ7 bound to RLQ–HLA-A2 and T1006I–HLA-A2. These complexes show that there are multiple structural solutions to recognizing RLQ and thereby generating a clonally diverse T cell response to this epitope that assures protection against viral escape and T cell clonal loss.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Oral delivery of a functional algal-expressed TGF-β mimic halts colitis in a murine DSS model

Inflammatory bowel disease (IBD) is a set of immunological disorders which can generate chronic pain and fatigue associated with the inflammatory symptoms. The treatment of IBD remains a significant hurdle with current therapies being only partially effective or having significant side effects, suggesting that new therapies that elicit different modes of action and delivery strategies are required. TGM1 is a TGF-β mimic that was discovered from the intestinal helminth parasite Heligmosomoides polygyrus and is thought to be produced by the parasite to suppress the intestinal inflammation response to help evade host immunity, making it an ideal candidate to be developed as a novel anti-inflammatory bio-therapeutic. Here we utilized the expression system of the edible green algae Chlamydomonas reinhardtii in order to recombinantly produce active TGM1 in a form that could be ingested. C. reinhardtii robustly expressed TGM1, and the resultant recombinant protein is biologically active as measured by regulatory T cell induction. When delivered orally to mice, the algal expressed TGM1 is able to ameliorate weight loss, lymphadenopathy, and disease symptoms in a mouse model of DSS-induced colitis, demonstrating the potential of this biologic as a novel treatment of IBD.

09 BIOMASS FUELS↗
DOE OSTI2020

Phosphate tolerance of nitrogen-coordinated-iron-carbon (FeNC) catalysts for oxygen reduction reaction: A size-related hindrance effect

The greatest challenges facing the large – scale commercialization of the intermediate temperature phosphoric acid fuel cell (PAFC) technology are: (i) the high cost of Pt catalyst that is required to overcome the slow kinetics of oxygen reduction reaction (ORR) on the PAFC cathode, and (ii) deactivation of the Pt catalyst by exposure to the phosphoric acid electrolyte. Inexpensive carbon-based materials, particularly iron- spectroscopy is used to explore the phenomenon of phosphate poisoning nitrogen-coordinated carbon supported catalysts (FeNC), are promising cathodes for PAFCs. The higher ORR activation energy and phosphate poisoning resistance of FeNC present a clear advantage over the Pt-based commercial catalysts that are easily susceptible to deactivation after exposure to phosphate anions. While the immunity of FeNC catalysts to phosphate anion poisoning has been reported previously, this work explores the counter-intuitive and conditional nature of this poisoning resistance based on the properties of the carbon support used in the preparation of the FeNC catalyst. Additionally, a combination of electrochemical measurements with characterization experiments performed using X-ray photoelectron spectroscopy, infrared spectroscopy and in-situ X-ray absorption on FeNC catalysts synthesized from two different carbon supports. Results from these studies reveal a “size-related hindrance effect” wherein the ORR active Fe centers in FeNC remain inaccessible to larger anions such as phosphate when the Fe sites are present deeper inside the pores of a carbon support with high porosity. However, FeNC catalyst is poisoned by phosphate anions when synthesized using a carbon support with low porosity. This work helps gain insights into the nature of active sites in FeNC catalysts that will be useful in designing precious-metal free ORR catalysts for intermediate temperature fuel cell technologies.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2014

Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for global HIV-1 vaccine development

An effective vaccine against human immunodeficiency virus type 1 (HIV-1) will have to provide protection against a vast array of different HIV-1 strains. Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. Here we describe the development of a global HIV-1 peptide microarray that contains 6564 peptides from across the HIV-1 proteome and covers the majority of HIV-1 sequences in the Los Alamos National Laboratory global HIV-1 sequence database. Using this microarray, we quantified the magnitude, breadth, and depth of IgG binding to linear HIV-1 sequences in HIV-1-infected humans and HIV-1-vaccinated humans, rhesus monkeys and guinea pigs. The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. Our data suggest that the global HIV-1 peptide microarray may be a useful tool for both preclinical and clinical HIV-1 research.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Integrated lipidomic and proteomic profiling reveals metabolic network disruption by SARS-CoV-2 variants

The rapid evolution of SARS-CoV-2 has produced myriad viral strains with increasing transmissibility and capacity for immune evasion. While effective vaccination campaigns have reduced the fatalities associated with SARS-CoV-2, infections continue, and a detailed understanding of how this virus manipulates host biochemical pathways remains elusive. We asked both whether the patterns of host lipid rewiring remained consistent across variants and whether the changes in the abundance of lipid classes are related to changes in the expression of the enzymes involved in their biosynthesis. We compared global nontargeted lipidomics on A549-ACE2 cells infected with the delta variant (B.1.617.2), or the omicron (B.1.1.529) variant to our previous results of global nontargeted lipidomics on A549-ACE2 cells infected with the original WA1 strain and further performed quantitative proteomics to assess changes in the host proteome. We found that metabolic rewiring, both on the lipid and the enzymatic level, is remarkably consistent across all three variants. We further mapped changes in the expression of host metabolic enzymes, linking enzyme expression to alterations in the abundance of specific lipids during infection. This analysis identified key proteins related to virus-mediated changes in lipid abundance, including fatty acid synthase (FASN), lysosomal acid lipase (LIPA), and ORMDL, a regulator of sphingolipid biosynthesis. These integrated lipidomic and proteomic experiments shed light on the importance of the complex network of host metabolism networks that support SARS-CoV-2 infection and suggest that lipid metabolism may be a promising avenue for uncovering conserved therapeutic targets.

SARS-CoV-2↗
DOE OSTI2025

Lipid and lipoprotein metabolism in microglia: Alzheimer’s disease mechanisms and interventions

Alzheimer's disease (AD) presents a significant challenge owing to its widespread prevalence and complex neuropathogenesis, affecting millions worldwide. Current therapeutic strategies that predominantly target amyloid-beta accumulation are insufficient, particularly for ApoE4 carriers. Alterations in lipid composition are well documented in AD, characterized by reductions in phospholipids and sulfatides, along with increases in cholesterol, cholesteryl esters, and triglycerides (TGs). Microglia, the brain's resident immune cells, link dysfunctional lipid processing to AD neuropathogenesis. For example, genetic studies have pointed to microglial lipid and lipoprotein processing gene variants as some of the strongest risk factors for AD. In addition, microglial dysfunction, characterized by lipid droplet accumulation, increased cholesterol and TG levels, and altered lipid transport, may exacerbate the pathological hallmarks of AD, such as amyloid-beta and tau accumulation. Conversely, emerging studies have shown that strategies aimed at inhibiting lipid droplet accumulation in microglia, reducing TG synthesis, and promoting the activity of lipoprotein receptors expressed by microglia can improve cell functions and markers of AD pathology. This review dissects the interplay between microglial lipid metabolism and AD, highlighting the significance of lipid transport and trafficking within the CNS. Given the intrinsic link between microglial metabolism and AD progression, emerging and potential therapeutic strategies aimed at restoring lipid handling and improving microglial function are explored. This review provides a comprehensive examination of the emerging literature, detailing the current state of knowledge on microglial lipid metabolism, its genetic underpinnings, and the potential for novel interventions targeting these mechanisms to ameliorate AD pathology.

Alzheimer's disease↗
DOE OSTI2015

Structures of Human CCL18, CCL3, and CCL4 Reveal Molecular Determinants for Quaternary Structures and Sensitivity to Insulin-Degrading Enzyme

CC chemokine ligands (CCL) are 8-14 kDa signaling proteins involved in diverse immune functions. While CCLs share similar tertiary structures, oligomerization produces highly diverse quaternary structures that protect chemokines from proteolytic degradation and modulate their functions. CCL18 is closely related to CCL3 and CCL4 with respect to both protein sequence and genomic location, yet CCL18 has distinct biochemical and biophysical properties. Here in this paper, we report a crystal structure of human CCL18 and its oligomerization states in solution based on crystallographic and small angle X-ray scattering (SAXS) analyses. Our data shows that CCL18 adopts an α-helical conformation at its N-terminus that weakens its dimerization, explaining CCL18’s preference for the monomeric state. Multiple contacts between monomers allow CCL18 to reversibly form a unique open-ended oligomer different from those of CCL3, CCL4, and CCL5. Furthermore, these differences hinge on proline 8, which is conserved in CCL3 and CCL4, but is replaced by lysine in human CCL18. Our structural analyses suggest that a proline 8 to alanine mutation stabilizes a type I β-turn at the N-terminus of CCL4 to prevent dimerization but prevents dimers from making key contacts with each other in CCL3. Thus, the P8A mutation induces depolymerization of CCL3 and CCL4 by distinct mechanisms. Finally, we used structural, biochemical, and functional analyses to unravel why insulin-degrading enzyme (IDE) degrades CCL3 and CCL4 but not CCL18. Lastly, our results elucidate the molecular basis for the oligomerization of three closely related CC chemokines and suggest how oligomerization shapes CCL chemokine function.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species

Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication and antagonize the host innate immune response. The latter function involves reversing the post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon-stimulated gene product 15 (ISG15). Ub is known to be highly conserved among eukaryotes, but surprisingly, ISG15 is highly divergent among animals. The ramifications of this sequence divergence to the recognition of ISG15 by coronavirus PLPs at a structural and biochemical level are poorly understood. Therefore, the activity of PLPs from SARS-CoV, MERS–CoV, and mouse hepatitis virus was evaluated against seven ISG15s originating from an assortment of animal species susceptible, and not, to certain coronavirus infections. Excitingly, our kinetic, thermodynamic, and structural analysis revealed an array of different preferences among PLPs. Included in these studies is the first insight into a coronavirus PLP’s interface with ISG15 via SARS-CoV PLpro in complex with the principle binding domain of human ISG15 (hISG15) and mouse ISG15s (mISG15s). Here, the first X-ray structure of the full-length mISG15 protein is also reported and highlights a unique, twisted hinge region of ISG15 that is not conserved in hISG15, suggesting a potential role in differential recognition. Taken together, this new information provides a structural and biochemical understanding of the distinct specificities among coronavirus PLPs observed and addresses a critical gap of how PLPs can interact with ISG15s from a wide variety of species.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Structural Insights into the Mechanisms and Pharmacology of K 2P Potassium Channels

Leak currents, defined as voltage and time independent flows of ions across cell membranes, are central to cellular electrical excitability control. The K 2P (KCNK) potassium channel class comprises an ion channel family that produces potassium leak currents that oppose excitation and stabilize the resting membrane potential in cells in the brain, cardiovascular system, immune system, and sensory organs. Due to their widespread tissue distribution, K 2P s contribute to many physiological and pathophysiological processes including anesthesia, pain, arrythmias, ischemia, hypertension, migraine, intraocular pressure regulation, and lung injury responses. Structural studies of six homomeric K 2P s have established the basic architecture of this channel family, revealed key moving parts involved in K 2P function, uncovered the importance of asymmetric pinching and dilation motions in the K 2P selectivity filter (SF) C-type gate, and defined two K 2P structural classes based on the absence or presence of an intracellular gate. Further, a series of structures characterizing K 2P :modulator interactions have revealed a striking polysite pharmacology housed within a relatively modestly sized (~70 kDa) channel. Binding sites for small molecules or lipids that control channel function are found at every layer of the channel structure, starting from its extracellular side through the portion that interacts with the membrane bilayer inner leaflet. This framework provides the basis for understanding how gating cues sensed by different channel parts control function and how small molecules and lipids modulate K 2P activity. Such knowledge should catalyze development of new K 2P modulators to probe function and treat a wide range of disorders.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Conformational Changes of RORγ During Response Element Recognition and Coregulator Engagement

The retinoic acid receptor-related orphan receptor γ (RORγ) is a ligand-dependent transcription factor of the nuclear receptor super family that underpins metabolic activity, immune function, and cancer progression. Despite being a valuable drug target in health and disease, our understanding of the ligand-dependent activities of RORγ is far from complete. Like most nuclear receptors, RORγ must recruit coregulatory protein to enact the RORγ target gene program. To date, a majority of structural studies have been focused exclusively on the RORγ ligand-binding domain and the ligand-dependent recruitment of small peptide segments of coregulators. Herein, we examine the ligand-dependent assembly of full length RORγ:coregulator complexes on cognate DNA response elements using structural proteomics and small angle x-ray scattering. The results from our studies suggest that RORγ becomes elongated upon DNA recognition, preventing long range interdomain crosstalk. We also determined that the DNA binding domain adopts a sequence-specific conformation, and that coregulatory protein may be able to ‘sense’ the ligand- and DNA-bound status of RORγ. We propose a model where ligand-dependent coregulator recruitment may be influenced by the sequence of the DNA to which RORγ is bound. Overall, the efforts described herein will illuminate important aspects of full length RORγ and monomeric orphan nuclear receptor target gene regulation through DNA-dependent conformational changes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Harbinger of hysteresis in lithium-rich oxides: Anionic activity or defect chemistry of cation migration

In this work, we present findings on the mechanisms of hysteresis in lithium-rich cathode oxides. It is generally reported that the energy inefficiency, observed during electrochemical cycling of Li-rich electrodes, is a direct result of anion redox processes. Similarly, the coupled phenomenon of cation migration has been cited as being a mere consequence of that process with no essential ramification to hysteresis. Such works, however, have only shown correlations and not causation. Specifically, studies that clearly preclude the complete absence of either anion redox or cation migration (down to defect-level concentrations) are not reported yet. Herein, we present first principles calculations and experimental data on a bespoke Li-rich system that is indubitably immune to oxygen activity but yet exhibits significant energy inefficiency. Additionally, the results directly implicate transition metal migration as the fundamental, sole process responsible for hysteresis in this material. This study is of particular importance to the design and development of new Li-rich materials aimed at eliminating the role of oxygen and enhancing the effective cationic redox contribution to the capacity and points out the essential need to develop materials devoid of transition metal migration to interstitial sites in both layered and disordered oxides alike.

25 ENERGY STORAGE↗
DOE OSTI2017

Sepsis reconsidered: Identifying novel metrics for behavioral landscape characterization with a high-performance computing implementation of an agent-based model

Objectives: Sepsis affects nearly 1 million people in the United States per year, has a mortality rate of 28–50% and requires more than $20 billion a year in hospital costs. Over a quarter century of research has not yielded a single reliable diagnostic test or a directed therapeutic agent for sepsis. Central to this insufficiency is the fact that sepsis remains a clinical/physiological diagnosis representing a multitude of molecularly heterogeneous pathological trajectories. Advances in computational capabilities offered by High Peformance Computing (HPC) platforms call for an evolution in the investigation of sepsis to attempt to define the boundaries of traditional research (bench, clinical and computational) through the use of computational proxy models. We present a novel investigatory and analytical approach, derived from how HPC resources and simulation are used in the physical sciences, to identify the epistemic boundary con- ditions of the study of clinical sepsis via the use of a proxy agent-based model of systemic inflammation. Design: Current predictive models for sepsis use correlative methods that are limited by patient heterogeneity and data sparseness. We address this issue by using an HPC version of a system-level validated agent-based model of sepsis, the Innate Immune Response ABM (IIRBM), as a proxy system in order to identify boundary conditions for the possible behavioral space for sepsis. We then apply advanced analysis derived from the study of Random Dynamical Systems (RDS) to identify novel means for characterizing system behavior and providing insight into the tractability of traditional investigatory methods. Results: The behavior space of the IIRABM was examined by simulating over 70 million sepsis patients for up to 90 days in a sweep across the following parameters: cardio-respiratory-metabolic resilience; microbial invasiveness; microbial toxigenesis; and degree of nosocomial exposure. In addition to using established methods for describing parameter space, we developed two novel methods for characterizing the behavior of a RDS: Probabilistic Basins of Attraction (PBoA) and Stochastic Trajectory Analysis (STA). Computationally generated behavioral landscapes demonstrated attractor structures around stochastic re- gions of behavior that could be described in a complementary fashion through use of PBoA and STA. The stochasticity of the boundaries of the attractors highlights the challenge for correlative attempts to characterize and classify clinical sepsis. Conclusions: HPC simulations of models like the IIRABM can be used to generate approximations of the behavior space of sepsis to both establish “boundaries of futility” with respect to existing investi- gatory approaches and apply system engineering principles to investigate the general dynamic properties of sepsis to provide a pathway for developing control strategies. Here, the issues that bedevil the study and treatment of sepsis, namely clinical data sparseness and inadequate experimental sampling of system behavior space, are fundamental to nearly all biomedical research, manifesting in the “Crisis of Reproducibility” at all levels. HPC-augmented simulation-based research offers an investigatory strategy more consistent with that seen in the physical sciences (which combine experiment, theory and simulation), and an opportunity to utilize the leading advances in HPC, namely deep machine learning and evolutionary computing, to form the basis of an iterative scientific process to meet the full promise of Precision Medicine (right drug, right patient, right time).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

The effect of grain boundary character evolution on the intergranular corrosion behavior of advanced Al-Mg-3wt%Zn alloy with Mg variation

Highlights: • The relationship among GBCD, GBPs, IGC behavior and Mg content in the age hardenable Al-Mg-3.0wt%Zn alloy is established. • None of grain boundaries are found to be immune to the GBPs. • GBPs along low angle grain boundaries are more discontinuous than high angle grain boundaries. • The IGC mechanism of Al-Mg-3.0wt%Zn alloy is clarified. • A new method for the statistical analysis of the continuity of GBPs is used in this paper. The characteristics of grain boundary and grain boundary precipitates of Al-Mg-3wt%Zn alloy with different Mg contents were systematically investigated. Observation by optical microscopy, transmission electron microscopy, scanning transmission electron microscopy and energy-dispersive X-ray spectroscopy show that the morphology and composition of the grain boundary precipitates change little with the variation in the Mg content. Based on the statistical analysis of the spacings between two adjacent grain boundary precipitates, we find that the decrease in the Mg content reduces the continuity of the grain boundary precipitates. Comparing this result with the electron backscattered diffraction analysis, it can be concluded that the continuity of grain boundary precipitates is affected by the proportion of low angle grain boundaries. The observations of grain boundary precipitates at both low angle grain boundaries and high angle grain boundaries using transmission electron microscopy indicate that low angle grain boundaries have more discontinuous grain boundary precipitates. Combining these results with the results of the intergranular corrosion test, the microscopic features of this corrosion behavior and corrosion mechanism are revealed.

36 MATERIALS SCIENCE↗