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The living interface between synthetic biology and biomaterial design

Recent far-reaching advances in synthetic biology have yielded exciting tools for the creation of new materials. Conversely, advances in the fundamental understanding of soft-condensed matter, polymers and biomaterials offer new avenues to extend the reach of synthetic biology. The broad and exciting range of possible applications have substantial implications to address grand challenges in health, biotechnology and sustainability. Despite the potentially transformative impact that lies at the interface of synthetic biology and biomaterials, the two fields have, so far, progressed mostly separately. This Perspective provides a review of recent key advances in these two fields, and a roadmap for collaboration at the interface between the two communities. Here we highlight the near-term applications of this interface to the development of hierarchically structured biomaterials, from bioinspired building blocks to 'living' materials that sense and respond based on the reciprocal interactions between materials and embedded cells.

59 BASIC BIOLOGICAL SCIENCES↗

Thermoplastic Composites Parts Manufacturing Enabling High Volumes, Low Cost, Reduced Weight with Design Flexibility – Phase 2

The deliverable of this IACMI PHASE II project is an innovative thermoplastic composite parts manufacturing process that addressed some of the most challenging aspects for commercial adoption in high volume market applications with requisite design flexibility while lowering cost and weight. The collaborative 15-month joint effort built upon the collective collateral value that was validated in PHASE I, as well as the synergies of a cross- functional team members comprised & lead by DuPont, Fibrtec & Purdue. Specifically, Fibrtec’s uniquely flexible coated tow (FibrFlex®) with DuPont's Rapid Fabric Formation (RFF) technology and a proprietary DuPont polyamide resin, were used to create near net shapes, while Purdue developed new simulation tools to predict the behavior of material system preforms in molding processes. These were ultimately deployed for the manufacturing with “informed” performance of industrially-interesting CFRP parts. Experiments, modeling, and simulations have shown that this process/materials combination offers advantages for producing lower cost continuous fiber reinforced polymer (CFRP) materials that drape well during molding while maintaining outstanding physical properties. This newly deployed process is ideally suitable for adoption in the automotive and other higher volume industries because of the associated cost savings due to reduction of waste and embodied energy. Furthermore, it overcomes the drawbacks of the prevalent two other typically deployed processes; the slow speed and expensive part formation associated with the usage of the stiff and brittle UD tapes, or the release of short conductive carbon fiber strands into the environment associated by the alternate layering of fiber woven fabric with resin film.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

FY25 Electric Grid Security Annual Report

Sandia’s Electric Grid Security program advances a national vision of energy dominance and accessibility, while applying our national security -emphasis on ensuring of a secure, resilient, and affordable electric system for all users. Our achievements reflect a strategic approach combining technology development; modeling, simulation, and data analytics; and partnered demonstrations and outreach to further the adoption of advanced grid and storage technologies. Our FY25 efforts leverage the strengths of our partnerships—spanning Sandia’s core science and technology competencies as well as external technology leaders—to develop the solutions today which enable the grid of tomorrow. Key accomplishments in this report that support our strategy span our technical program areas and include: • New open-source analytical tools for systems -level planning and optimization, including significant advances to the QuESt analytical environment; • Further advancement of artificial intelligence and machine learning to enhanced grid operations and planning as we rise to the challenge of new large loads; • Development of solid-state power conversion technologies and a new medium-voltage research lab; • New technologies to assess wildfire vulnerabilities and mitigate potential impacts; • Advanced applications of new cybersecurity technologies with industry partners; • Contributions to understanding the impacts of electromagnetic pulses and geomagnetic disturbances on grid components; and • Digital twin development for hybrid microgrids with multiple generators, storage, and loads. This report indicates key areas of research and engagement and summarizes the impact of Sandia’s contributions through notable accomplishments, journal publications, patents, and technical conferences and presentations. It is provided with the hope that readers discover ways we can further team to create our modern grid and apply the outcomes of our efforts. The bulk of work described herein is funded by several offices within the U.S. Department of Energy (USDOE), including the Office of Electricity (OE); Cybersecurity, Energy Security, and Emergency Response (CESER); former offices such as the Office of Energy Efficiency and Renewable Energy (EERE), the Grid Deployment Office (GDO), the Office of Clean Energy Demonstrations (OCED), and other key programs at USDOE. As we continue to state in these annual reports, the contributors to our successes are too numerous to name here, though our team wishes to express our deep gratitude to the numerous program and project sponsors at the US Department of Energy, who often function equally as technical collaborators; our many partners in industry, academia, utilities, and other national labs; and fellow researchers and business partners at Sandia whose leadership and creativity have enabled the accomplishments described herein.

24 POWER TRANSMISSION AND DISTRIBUTION↗

NA84 Auto Aiming Tool (Final Report)

The Microsoft Hololens is capable of bi-directional communication between units. This allows many users to share a common visual experience and is the primary capability of interest due to the collaborative scenarios it may enable. One scenario pursued in the Automated Aiming Tool project is shown in figure 1 which conceptualizes the reciprocal workflow between remote team members wearing these devices. In this scenario, the down-range team member leverages the depth-scanning capability of the Hololens to scan and texture map the environment and any objects of interest. This data and any associated metadata are then packaged and transmitted to remote team members where it is then unpackaged and visualized. The remote team member can then insert computer generated imagery – a type of “virtual indicator” – within the visualized environment and that object is then rendered in the field of view of the down-range operator in real time. These virtual objects can be indicators for the placement of instrumentation, items of interest, areas from which data has been collected, etc. Pursuant to the above scenario, the primary objective has been to assess the feasibility of its implementation with current v1 hardware. Certain limitations were found to limit the degree to which the above scenario can currently be implemented. However, the future potential of this approach is clear for revolutionizing the speed and precision of multi-object registration at a single site, instrumentation placement and orientation (aiming), and for full-scene communication and coordination among two or more sites.

47 OTHER INSTRUMENTATION↗

WBS 4.2.1.31 Integrated Life Cycle Sustainability Analysis

The main objective of this project (following the 2017 BETO Program Peer-Review) is to provide BETO with a coherent methodology and modeling framework based on life cycle (LCA) and economic input-output analysis, tested and vetted with stakeholders, to better understand the effects of an expanding U.S. bioeconomy at specific levels including economic dimensions such as jobs, gross domestic product (value added), and environmental criteria such as air pollutant emissions, water and land use, ecotoxicity, and others. This supports a 2019 milestone in the BETO MYP and simultaneously addresses a gap previously identified in the BETO program and highlighted, e.g., by BETO Program Peer Reviewers in 2015 and 2017. To fill in this gap, NREL started collaborating with developers of the national level U.S. Environmentally-Extended Input-Output (USEEIO) model in FY18. This peer-reviewed, open source model is based on publicly available data, and developed and maintained by U.S. EPA where it has been the basis for EPA's Sustainable Material Management analyses and program. Also, USEEIO was initially designed for use with EPA's Tool for the Reduction and Assessment of Chemicals and Other Environmental Impacts (TRACI). It aligns well with similar efforts including the Federal LCA Commons and the Sustainable Acquisition Program at the Department of Defense (DoD). In FY18, NREL convened stakeholders from federal agencies, universities, and private sector entities to identify and form a common understanding of (1) models describing the U.S. economy and how to build off of them, (2) a bioeconomy definition for the next modeling steps, (3) the (sub)sectors that can/should be used in the framework, and (4) opportunities for collaboration and data sharing. NREL then created a first order model by disaggregating, i.e., separating the economic activities associated with and attributed to a selected product of the bioeconomy: corn ethanol. Corn ethanol is well studied and has a significant amount of public, validated economic industry information. This is important as disaggregation is a critical step in creating a representative and accurate framework. Corn ethanol served as a validation test case for the method and framework. By the end of FY18, the team was able to generate several scenarios for corn ethanol on national and selected regional levels providing results on the absolute and relative (Megajoule) effects in several environmental and economic impact categories. A second objective of the project is to inform BETO's strategic decision making, specifically its sustainability research portfolio, by engaging in, evaluating, and synthesizing selected global multi-year activities from the perspectives of a variety of complex multilateral and multi-stakeholder processes that pertain to bioenergy. This helps to (1) identify gaps, barriers, and critical areas for future BETO bioenergy and sustainability assessments; (2) identify opportunities and challenges to a sustainable U.S. bioeconomy; and (3) contribute to and disseminate BETO information to and from major global bioenergy and sustainability efforts. This project's work with multilateral organizations ensures that U.S. science-based viewpoints are considered and helps to balance the influence of the large number of countries with the same centralized philosophy. This engagement builds a more solid foundation for sustainable biomass and bioenergy systems in the U.S. and in the world. Working with multi-lateral, international platforms including IEA Bioenergy, Global Bio-Energy Partnership (GBEP), and their partner organizations also allows engagement with important stakeholders including policy makers, industry, NGOs, and academia.

09 BIOMASS FUELS↗

Understanding Part to Part Variability During Directed Energy Deposition Processes Using In Situ and Ex Situ Process Characterization

The overall goal of this technical collaboration is the use of in situ and ex situ characterization techniques to understand part to part variability in Ti-6Al-4V parts fabricated using directed energy deposition (DED) process, and subsequently qualify parts fabricated using AM. The primary goal of the Phase-1 of this CRADA was to demonstrate the feasibility of capturing the above changes using a combination of high speed stereo imaging and in situ monitoring using two wavelength pyrometers. The in situ monitoring was then correlated using ex situ characterization performed using optical microscopy. The results from phase-1 clearly show that changes to the process and shielding gases have a significant impact on the geometric conformity of the build and the build layer height. The results from phase-1 show that in addition to using IR thermography as a tool to measure the temperature and gradients, we could use it to monitor the build topography and the layer height and use the information to develop closed loop control systems. The phase-1 results show that there is a narrow zone under which the process must operate in order to be “passively stable” or autocorrect for over building. In addition, the results demonstrate that when operated within this range the build autocorrects and there is a drastic reduction in the interlayer lack of fusion defect formation.

36 MATERIALS SCIENCE↗

Enabling Sustainable Landscape Design for Continual Improvement of Operating Bioenergy Supply Systems

This unique and highly effective project catalyzed collaboration among government, university, and private sector partners through a multi-state research and technology transfer project designed to support continuous improvement of bioenergy feedstock supply systems. Conceived and built upon the foundation created by prior DOE investments in the Billion Ton Study, Sun Grant Regional Project, and many other feedstock production, harvest, storage and transportation studies, this project addressed seven tasks with more than 29 subtasks. All goals were met with key accomplishments being: (1) on-farm establishment of potential perennial plant mixtures that could not only become sustainable feedstock sources but also enhance soil health, (2) a reduction in potential wind and water erosion by improving corn stover harvest techniques and incorporating cover crops into current row-crop production systems, (3) reduced potential for surface and groundwater contamination while also increasing potential biodiversity and sustainability of Midwestern USA landscapes, and (4) development of site-specific land management, data visualization, and sustainability assessment tools. Twenty-two Case Studies highlighting accomplishments and lessons learned through this public-private partnership investment are incorporated into this final report. On-farm and replicated field plot studies were used to provide the real-world data needed to verify baseline assumptions for extensive feedstock logistic modeling and greenhouse gas (GHG) assessments needed to develop sustainable bioenergy and bio-product industries at national and international scales.

09 BIOMASS FUELS↗

Renewal: Coherent control of spin states in organic electronics – discovery and investigation of complex room-temperature magnetic quantum excitations

In the course of four funding cycles of this project, its research focused on the exploration and understanding of spin-dependent electronic processes in organic semiconductors. It aimed to investigate the potential of harnessing the spin degree of freedom in organic materials for various applications such as spin electronics, quantum information, sensors, and as well as quantum coherent spin phenomena of charge carrier states in organic semiconductors, with the aim to develop room-temperature-based quantum applications. Specifically, the project aimed to: Apply new diagnostic tools, i.e. spin spectroscopy techniques, for paramagnetic charge carrier states in organic semiconductors, based on coherent control with pulsed electron spin resonance to understand spin relaxation and spin mixing mechanisms in organic semiconductor materials and devices such as OLEDs. Explore the nature of charge carrier spin-coupling and pathways for its manipulation to control the physical behaviors of these materials. This involves investigating spin interactions through materials structure, composition, morphological dependencies, isotopic effects, and externally applied electric and magnetic fields, with the goal to manipulate electrical and optical material properties by adjusting spin-orbit, spin-dipolar, spin-exchange, as well as spin-hyperfine interactions to open up this materials class for new applications. Study spin-dependent charge carrier transport and recombination and how these observables are governed by spin-propagation, especially coherent spin propagation as well as collective spin-effects such as the spin-Dicke effect and resonant multi-photon magnetic dipole transitions. The project utilized pulsed electrically detected magnetic resonance (pEDMR) and pulsed optically detected magnetic resonance (pODMR) techniques over a wide frequency range. These techniques enabled the observation and quantification of various spin-spin coupling types, including spin-exchange, spin-dipolar, hyperfine, and spin-orbit interactions. The project will leverage low- to mid-frequency pEDMR/pODMR facilities and collaboration with the National High Magnetic Field Laboratory.

36 MATERIALS SCIENCE↗

Bridging Theory with Practice: An Exploratory Study of Visualization Use and Design for Climate Model Comparison

Evaluation methodologies in visualization have mostly focused on how well the tools and techniques cater to the analytical needs of the user. While this is important in determining the effectiveness of the tools and advancing the state-of-the-art in visualization research, a key area that has mostly been overlooked is how well established visualization theories and principles are instantiated in practice. This is especially relevant when domain experts, and not visualization researchers, design visualizations for analysis of their data or for broader dissemination of scientific knowledge. There is very little research on exploring the synergistic capabilities of cross-domain collaboration between domain experts and visualization researchers. To fill this gap, in this paper we describe the results of an exploratory study of climate data visualizations conducted in tight collaboration with a pool of climate scientists. The study analyzes a large set of static climate data visualizations for identifying their shortcomings in terms of visualization design. The outcome of the study is a classification scheme that categorizes the design problems in the form of a descriptive taxonomy. The taxonomy is a first attempt for systematically categorizing the types, causes, and consequences of design problems in visualizations created by domain experts. We demonstrate the use of the taxonomy for a number of purposes, such as, improving the existing climate data visualizations, reflecting on the impact of the problems for enabling domain experts in designing better visualizations, and also learning about the gaps and opportunities for future visualization research. We demonstrate the applicability of our taxonomy through a number of examples and discuss the lessons learnt and implications of our findings.

54 ENVIRONMENTAL SCIENCES↗

TH-A-207B-00: Shear-Wave Imaging and a QIBA US Biomarker Update

Imaging of tissue elastic properties is a relatively new and powerful approach to one of the oldest and most important diagnostic tools. Imaging of shear wave speed with ultrasound is has been added to most high-end ultrasound systems. Understanding this exciting imaging mode aiding its most effective use in medicine can be a rewarding effort for medical physicists and other medical imaging and treatment professionals. Assuring consistent, quantitative measurements across the many ultrasound systems in a typical imaging department will constitute a major step toward realizing the great potential of this technique and other quantitative imaging. This session will target these two goals with two presentations. A. Basics and Current Implementations of Ultrasound Imaging of Shear Wave Speed and Elasticity - Shigao Chen, Ph.D. Learning objectives-To understand: Introduction: Importance of tissue elasticity measurement Strain vs. shear wave elastography (SWE), beneficial features of SWE The link between shear wave speed and material properties, influence of viscosity Generation of shear waves External vibration (Fibroscan) ultrasound radiation force Point push Supersonic push (Aixplorer) Comb push (GE Logiq E9) Detection of shear waves Motion detection from pulse-echo ultrasound Importance of frame rate for shear wave imaging Plane wave imaging detection How to achieve high effective frame rate using line-by-line scanners Shear wave speed calculation Time to peak Random sample consensus (RANSAC) Cross correlation Sources of bias and variation in SWE Tissue viscosity Transducer compression or internal pressure of organ Reflection of shear waves at boundaries B. Elasticity Imaging System Biomarker Qualification and User Testing of Systems – Brian Garra, M.D. Learning objectives-To understand: Goals Review the need for quantitative medical imaging Provide examples of quantitative imaging biomarkers Acquaint the participant with the purpose of the RSNA Quantitative Imaging Biomarker Alliance and the need for such an organization Review the QIBA process for creating a quantitative biomarker Summarize steps needed to verify adherence of site, operators, and imaging systems to a QIBA profile Underlying Premise and Assumptions Objective, quantifiable results are needed to enhance the value of diagnostic imaging in clinical practice Reasons for quantification Evidence based medicine requires objective, not subjective observer data Computerized decision support tools (eg CAD) generally require quantitative input. Quantitative, reproducible measures are more easily used to develop personalized molecular medical diagnostic and treatment systems What is quantitative imaging? Definition from Imaging Metrology Workshop The Quantitative Imaging Biomarker Alliance Formation 2008 Mission Structure Example Imaging Biomarkers Being Explored Biomarker Selection Groundwork Draft Protocol for imaging and data evaluation QIBA Profile Drafting Equipment and Site Validation Technical Clinical Site and Equipment QA and Compliance Checking Ultrasound Elasticity Estimation Biomarker US Elasticity Estimation Background Current Status and Problems Biomarker Selection-process and outcome US SWS for Liver Fibrosis Biomarker Work Groundwork Literature search and analysis results Phase I phantom testing-Elastic phantoms Phase II phantom testing-Viscoelastic phantoms Digital Simulated Data Protocol and Profile Drafting Protocol: based on UPICT and existing literature and standards bodies protocols Profile-Current claims, Manufacturer specific appendices What comes after the profile Profile Validation Technical validation Clinical validation QA and Compliance Possible approaches Site Operator testing Site protocol re-evaluation Imaging system Manufacturer testing and attestation User acceptance testing and periodic QA Phantom Tests Digital Phantom Based Testing Standard QA Testing Remediation Schemes Profile Evolution Towards additional applications Towards higher accuracy and precision Supported in part by NIH contract HHSN268201300071C from NIBIB. Collaboration with GE Global Research, no personal support.; S. Chen, Some technologies described in this presentation have been licensed. Mayo Clinic and Dr. Chen have financial interests these technologies.

60 APPLIED LIFE SCIENCES↗

The GREEN ‘omics of Nutrient Feedbacks to Soil Warming

The GREEN ‘omics of Nutrient Feedbacks in Soil project advanced the DOE Biological and Environmental Research (BER) mission by developing and applying isotope-enabled ’omics tools to understand how soil microbes regulate carbon and nutrient cycling. Guided by the Growth Rate, growth Efficiency, and stoichiometry of Essential Nutrients (GREEN ’omics) framework, the project aimed to build a predictive, systems-level understanding of microbial traits that control ecosystem biogeochemistry. In a collaboration among Northern Arizona University (lead), West Virginia University, Lawrence Livermore National Laboratory, and Pacific Northwest National Laboratory, we combined quantitative stable isotope probing (qSIP), Chip-SIP, NanoSIMS, and genome-resolved metagenomics across long-term experiments in Arctic, boreal, temperate, and tropical ecosystems. The project produced three key outcomes: 1) We showed that community-weighted temperature sensitivities of bacterial growth (Q10) can predict ecosystem-scale soil respiration responses across diverse soils. 2) We provided the first in situ evidence for density-dependent population dynamics in soil bacteria and demonstrated that nutrient additions intensify competition, concentrating carbon use into fewer taxa. 3) We improved and extended isotope-enabled ’omics methods by quantifying qSIP measurement error to guide experimental design and coupling SIP with genome-resolved metagenomics to reveal cross-kingdom interactions among bacteria, fungi, and viruses. Together, these results show that a small number of microbial traits and taxa exert disproportionate control over soil carbon and nutrient cycling, providing critical data and methods to improve representation of microbial processes in Earth system models.

54 ENVIRONMENTAL SCIENCES↗

Collaborative Aerospace Research and Fellowship Program at NASA Glenn Research Center

During the summer of 2004, a 10-week activity for university faculty entitled the NASA-OAI Collaborative Aerospace Research and Fellowship Program (CFP) was conducted at the NASA Glenn Research Center in collaboration with the Ohio Aerospace Institute (OAI). This is a companion program to the highly successful NASA Faculty Fellowship Program and its predecessor, the NASA-ASEE Summer Faculty Fellowship Program that operated for 38 years at Glenn. The objectives of CFP parallel those of its companion, viz., (1) to further the professional knowledge of qualified engineering and science faculty,(2) to stimulate an exchange of ideas between teaching participants and employees of NASA, (3) to enrich and refresh the research and teaching activities of participants institutions, and (4) to contribute to the research objectives of Glenn. However, CFP, unlike the NASA program, permits faculty to be in residence for more than two summers and does not limit participation to United States citizens. Selected fellows spend 10 weeks at Glenn working on research problems in collaboration with NASA colleagues and participating in related activities of the NASA-ASEE program. This year's program began officially on June 1, 2004 and continued through August 7, 2004. Several fellows had program dates that differed from the official dates because university schedules vary and because some of the summer research projects warranted a time extension beyond the 10 weeks for satisfactory completion of the work. The stipend paid to the fellows was $1200 per week and a relocation allowance of $1000 was paid to those living outside a 50-mile radius of the Center. In post-program surveys from this and previous years, the faculty cited numerous instances where participation in the program has led to new courses, new research projects, new laboratory experiments, and grants from NASA to continue the work initiated during the summer. Many of the fellows mentioned amplifying material, both in undergraduate and graduate courses, on the basis of the summer s experience at Glenn. A number of 2004 fellows indicated that proposals to NASA will grow out of their summer research projects. In addition, some journal articles and NASA publications will result from this past summer s activities. Fellows from past summers continue to send reprints of articles that resulted from work initiated at Glenn. This report is intended primarily to summarize the research activities comprising the 2004 CFP Program at Glenn. Particular research studies include: 1) Development of an Imaging-Based, Computational Fluid Dynamics Tool to Assess Fluid Mechanics in Experimental Models that Simulate Blood Vessels; 2) Analysis of Nanomaterials Produced from Precursors; and 3) LEO Propagation Analysis Tool.

Heyward, Ann O.↗

Collaborative development of diffraction-limited beamline optical systems at US DOE light sources

An ongoing collaboration among four US Department of Energy National Laboratories has demonstrated key technology prototypes and software modeling tools required for new high-coherent flux beamline optical systems. New free electron laser (FEL) and diffraction-limited storage ring (DLSR) light sources demand wavefront preservation from source to sample to achieve and maintain optimal performance. Fine wavefront control was achieved using a novel, roomtemperature cooled mirror system called REAL (resistive element adjustable length) that combines cooling with applied, spatially variable auxiliary heating. Single-grating shearing interferometry (also called Talbot interferometry) and Hartmann wavefront sensors were developed and used for optical characterization and alignment on several beamlines, across a range of photon energies. Demonstrations of non-invasive hard x-ray wavefront sensing were performed using a thin diamond single-crystal as a beamsplitter.

Goldberg, Kenneth A.↗

TH-A-207B-01: Basics and Current Implementations of Ultrasound Imaging of Shear Wave Speed and Elasticity

Imaging of tissue elastic properties is a relatively new and powerful approach to one of the oldest and most important diagnostic tools. Imaging of shear wave speed with ultrasound is has been added to most high-end ultrasound systems. Understanding this exciting imaging mode aiding its most effective use in medicine can be a rewarding effort for medical physicists and other medical imaging and treatment professionals. Assuring consistent, quantitative measurements across the many ultrasound systems in a typical imaging department will constitute a major step toward realizing the great potential of this technique and other quantitative imaging. This session will target these two goals with two presentations. A. Basics and Current Implementations of Ultrasound Imaging of Shear Wave Speed and Elasticity - Shigao Chen, Ph.D. Learning objectives-To understand: Introduction: Importance of tissue elasticity measurement Strain vs. shear wave elastography (SWE), beneficial features of SWE The link between shear wave speed and material properties, influence of viscosity Generation of shear waves External vibration (Fibroscan) ultrasound radiation force Point push Supersonic push (Aixplorer) Comb push (GE Logiq E9) Detection of shear waves Motion detection from pulse-echo ultrasound Importance of frame rate for shear wave imaging Plane wave imaging detection How to achieve high effective frame rate using line-by-line scanners Shear wave speed calculation Time to peak Random sample consensus (RANSAC) Cross correlation Sources of bias and variation in SWE Tissue viscosity Transducer compression or internal pressure of organ Reflection of shear waves at boundaries B. Elasticity Imaging System Biomarker Qualification and User Testing of Systems – Brian Garra, M.D. Learning objectives-To understand: Goals Review the need for quantitative medical imaging Provide examples of quantitative imaging biomarkers Acquaint the participant with the purpose of the RSNA Quantitative Imaging Biomarker Alliance and the need for such an organization Review the QIBA process for creating a quantitative biomarker Summarize steps needed to verify adherence of site, operators, and imaging systems to a QIBA profile Underlying Premise and Assumptions Objective, quantifiable results are needed to enhance the value of diagnostic imaging in clinical practice Reasons for quantification Evidence based medicine requires objective, not subjective observer data Computerized decision support tools (eg CAD) generally require quantitative input. Quantitative, reproducible measures are more easily used to develop personalized molecular medical diagnostic and treatment systems What is quantitative imaging? Definition from Imaging Metrology Workshop The Quantitative Imaging Biomarker Alliance Formation 2008 Mission Structure Example Imaging Biomarkers Being Explored Biomarker Selection Groundwork Draft Protocol for imaging and data evaluation QIBA Profile Drafting Equipment and Site Validation Technical Clinical Site and Equipment QA and Compliance Checking Ultrasound Elasticity Estimation Biomarker US Elasticity Estimation Background Current Status and Problems Biomarker Selection-process and outcome US SWS for Liver Fibrosis Biomarker Work Groundwork Literature search and analysis results Phase I phantom testing-Elastic phantoms Phase II phantom testing-Viscoelastic phantoms Digital Simulated Data Protocol and Profile Drafting Protocol: based on UPICT and existing literature and standards bodies protocols Profile-Current claims, Manufacturer specific appendices What comes after the profile Profile Validation Technical validation Clinical validation QA and Compliance Possible approaches Site Operator testing Site protocol re-evaluation Imaging system Manufacturer testing and attestation User acceptance testing and periodic QA Phantom Tests Digital Phantom Based Testing Standard QA Testing Remediation Schemes Profile Evolution Towards additional applications Towards higher accuracy and precision Supported in part by NIH contract HHSN268201300071C from NIBIB. Collaboration with GE Global Research, no personal support.; S. Chen, Some technologies described in this presentation have been licensed. Mayo Clinic and Dr. Chen have financial interests these technologies.

60 APPLIED LIFE SCIENCES↗

TH-A-207B-02: QIBA Ultrasound Elasticity Imaging System Biomarker Qualification and User Testing of Systems

Imaging of tissue elastic properties is a relatively new and powerful approach to one of the oldest and most important diagnostic tools. Imaging of shear wave speed with ultrasound is has been added to most high-end ultrasound systems. Understanding this exciting imaging mode aiding its most effective use in medicine can be a rewarding effort for medical physicists and other medical imaging and treatment professionals. Assuring consistent, quantitative measurements across the many ultrasound systems in a typical imaging department will constitute a major step toward realizing the great potential of this technique and other quantitative imaging. This session will target these two goals with two presentations. A. Basics and Current Implementations of Ultrasound Imaging of Shear Wave Speed and Elasticity - Shigao Chen, Ph.D. Learning objectives-To understand: Introduction: Importance of tissue elasticity measurement Strain vs. shear wave elastography (SWE), beneficial features of SWE The link between shear wave speed and material properties, influence of viscosity Generation of shear waves External vibration (Fibroscan) ultrasound radiation force Point push Supersonic push (Aixplorer) Comb push (GE Logiq E9) Detection of shear waves Motion detection from pulse-echo ultrasound Importance of frame rate for shear wave imaging Plane wave imaging detection How to achieve high effective frame rate using line-by-line scanners Shear wave speed calculation Time to peak Random sample consensus (RANSAC) Cross correlation Sources of bias and variation in SWE Tissue viscosity Transducer compression or internal pressure of organ Reflection of shear waves at boundaries B. Elasticity Imaging System Biomarker Qualification and User Testing of Systems – Brian Garra, M.D. Learning objectives-To understand: Goals Review the need for quantitative medical imaging Provide examples of quantitative imaging biomarkers Acquaint the participant with the purpose of the RSNA Quantitative Imaging Biomarker Alliance and the need for such an organization Review the QIBA process for creating a quantitative biomarker Summarize steps needed to verify adherence of site, operators, and imaging systems to a QIBA profile Underlying Premise and Assumptions Objective, quantifiable results are needed to enhance the value of diagnostic imaging in clinical practice Reasons for quantification Evidence based medicine requires objective, not subjective observer data Computerized decision support tools (eg CAD) generally require quantitative input. Quantitative, reproducible measures are more easily used to develop personalized molecular medical diagnostic and treatment systems What is quantitative imaging? Definition from Imaging Metrology Workshop The Quantitative Imaging Biomarker Alliance Formation 2008 Mission Structure Example Imaging Biomarkers Being Explored Biomarker Selection Groundwork Draft Protocol for imaging and data evaluation QIBA Profile Drafting Equipment and Site Validation Technical Clinical Site and Equipment QA and Compliance Checking Ultrasound Elasticity Estimation Biomarker US Elasticity Estimation Background Current Status and Problems Biomarker Selection-process and outcome US SWS for Liver Fibrosis Biomarker Work Groundwork Literature search and analysis results Phase I phantom testing-Elastic phantoms Phase II phantom testing-Viscoelastic phantoms Digital Simulated Data Protocol and Profile Drafting Protocol: based on UPICT and existing literature and standards bodies protocols Profile-Current claims, Manufacturer specific appendices What comes after the profile Profile Validation Technical validation Clinical validation QA and Compliance Possible approaches Site Operator testing Site protocol re-evaluation Imaging system Manufacturer testing and attestation User acceptance testing and periodic QA Phantom Tests Digital Phantom Based Testing Standard QA Testing Remediation Schemes Profile Evolution Towards additional applications Towards higher accuracy and precision Supported in part by NIH contract HHSN268201300071C from NIBIB. Collaboration with GE Global Research, no personal support.; S. Chen, Some technologies described in this presentation have been licensed. Mayo Clinic and Dr. Chen have financial interests these technologies.

60 APPLIED LIFE SCIENCES↗

Holography, Gravity and Condensed Matter

Over the five years of funding from this grant, I produced 26 publications. These include a book-long monograph on "Holographic Quantum Matter" that is currently in press with MIT press. The remainder were mostly published in Physical Review Letters, the Journal of High Energy Physics, Nature Physics, Classical and Quantum Gravity and Physical Review B. Over this period, the field of holography applied to condensed matter physics developed from a promising theoretical approach to a mature conceptual and practical edifice, whose ideas were realized in experiments. My own work played a central role in this development. In particular, in the final year of this grant, I co-authored two experimental papers in which ideas that I had developed in earlier years were shown to usefully describe transport in strongly correlated materials — these papers were published in Science and in the Proceedings of the National Academy of Sciences (obviously my contribution to these papers was theoretical). My theoretical work in this period developed several new directions of research that have proven to be influential. These include (i) The construction of highly inhomogeneous black hole event horizons, realizing disordered fixed points and describing new regimes of classical gravity, (ii) The conjecture of a bound on diffusivities that could underpin transport in strongly interacting media — an idea which may be proven in the near future and has turned out to be intimately connected to studies of quantum chaos in black holes and strongly correlated media, (iii) The characterization of new forms of hydrodynamic transport, e.g. with phase-disordered order parameters. These studies pertain to key open questions in our understanding of how non-quasiparticle, intrinsically strongly interacting systems can behave. In addition to the interface between holography and strongly interacting condensed matter systems, I made several advances on understanding the role of entanglement in quantum gravity. These included the first computation of holographic entanglement beyond the bulk classical limit as well understanding short distance entanglement in the emergent spacetime of the c=1 matrix quantum mechanics. The objective here is ultimately to understanding how a priori non-local degrees of freedom can re-arrange themselves quantum mechanically to support emergent local dynamics. Much of work funded by this grant involved collaboration with postdocs and graduate students, several of which were directly funded by the grant. These students have now successfully graduated to postdoctoral positions and in one case to high tech industry. The ideas developed in this work have directly fed into my current research in which I am aiming to prove fundamental bounds on entropy production and transport from quantum mechanics and statistical physics. As often, as with much of my previous work, black hole physics can be an inspiration for extreme dynamics such as fundamental bounds, but ultimately one hopes to prove them using more general tools of quantum field theory.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Final Report: Modeling coupled ice sheet-ocean interactions in the Model for Prediction Across Scales (MPAS) and in DOE Earth System Models

Ice sheet-ocean interactions are involved in a potential climate tipping point in the climate system. Weakening of dynamical ocean barriers that currently hold warmer waters off the Antarctic continental shelf could lead to warming under Antarctica’s largest ice shelves, causing as much as a hundredfold increase in sub-ice-shelf melting. Increased ice-sheet melting could trigger dynamical instabilities in the ice sheet itself if sufficient buttressing from ice shelves is lost. This project developed and tested several modeling capabilities needed to investigate these phenomena. In collaboration with a number of international groups, notably the climate modeling group at Los Alamos National Laboratory (LANL), the following capabilities were added to the Energy Exascale Earth System Model (E3SM) and its ocean component (the Model for Prediction Across Scales Ocean, MPAS-Ocean): 1) a new vertical coordinate appropriate for ice-shelf cavities; 2) an initialization procedure appropriate for damping waves from imbalances in ocean pressure and that of the overlying ice shelf; 3) A suite of idealized test cases related to ice shelf-ocean interactions; 4) A set of diagnostics for tracking freshwater fluxes and heat budgets from ice-shelf melting; 5) infrastructure for computing ice sheet-ocean fluxes in the E3SM coupler; and 6) A set of analysis and visualization tools for E3SM ocean and sea-ice validation with a particular focus on Antarctic and Southern Ocean climate. Additionally, the project included participation and leadership in a number of international model intercomparison projects (MIPs). Most notably, the PI was a co-chair of the Marine Ice Sheet-Ocean Model Intercomparison Project (MISOMIP), designing the experiment, coordinating participation in the MIP and performing the bulk of the analysis. Although the project was cut short when the PI accepted a staff scientist position at LANL, the project played a role in seven publications and has segued smoothly into ongoing Department of Energy projects in the “ecosystem” surrounding E3SM.

54 ENVIRONMENTAL SCIENCES↗

Integrated Design of Ultradurable, Low CO 2 Alternative Binder Systems via Machine Learning

This ARPA-E project developed a machine learning tool to use in formulation design of cementitious binders for concrete having 50% less embodied CO 2 and possessing twice the durability compared to concrete based on ordinary portland cement (OPC) binders. The technical focus was on limestone/calcined clay cement (LC3), the leading replacement for OPC. Here, hierarchical machine learning (HML) was used to model the flowability, set time, strength, and durability of LC3 concrete. This methodology identifies latent variables derived from domain knowledge and empirical models that develop an accurate model for a response surface from small datasets. For the flowability metric, particle packing was a dominant factor, while strength and durability were both strongly determined by the fraction of metakaolin and the water:solids ratio. Under constraints of water:binder ratio, material performance metrics, embodied CO 2 , and cost per tonne of OPC, multi-objective optimization was used to design binders parameterized by the mineral composition replacing OPC, particle size distributions, and water:solids ratio. The trained algorithm was able to predict multiple mixes met these performance criteria, and experimental testing validated the predictions. The model demonstrated here is relevant for North America, where pure kaolin deposits are found broadly. The approach is being taken forward into commercial application by Ansatz AI, a materials informatics company founded by PI Washburn and co-PI Poczos. Through collaborations with the cement and concrete industry, and funding from SBIR programs, a commercial software will be developed in future research.

36 MATERIALS SCIENCE↗