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At least 955 records · Page 53

Pressurized DNA state inside herpes capsids—A novel antiviral target

Drug resistance in viruses represents one of the major challenges of healthcare. As part of an effort to provide a treatment that avoids the possibility of drug resistance, we discovered a novel mechanism of action (MOA) and specific compounds to treat all nine human herpesviruses and animal herpesviruses. The novel MOA targets the pressurized genome state in a viral capsid, “turns off” capsid pressure, and blocks viral genome ejection into a cell nucleus, preventing viral replication. This work serves as a proof-of-concept to demonstrate the feasibility of a new antiviral target—suppressing pressure-driven viral genome ejection —that is likely impervious to developing drug resistance. This pivotal finding presents a platform for discovery of a new class of broad-spectrum treatments for herpesviruses and other viral infections with genome-pressure-dependent replication. A biophysical approach to antiviral treatment such as this is also a vital strategy to prevent the spread of emerging viruses where vaccine development is challenged by high mutation rates or other evasion mechanisms.

59 BASIC BIOLOGICAL SCIENCES↗

Dynamic metabolic reprogramming in dendritic cells: An early response to influenza infection that is essential for effector function

Infection with the influenza virus triggers an innate immune response that initiates the adaptive response to halt viral replication and spread. However, the metabolic response fueling the molecular mechanisms underlying changes in innate immune cell homeostasis remain undefined. Although influenza increases parasitized cell metabolism, it does not productively replicate in dendritic cells. To dissect these mechanisms, we compared the metabolism of dendritic cells to that of those infected with active and inactive influenza A virus and those treated with toll-like receptor agonists. Using quantitative mass spectrometry, pulse chase substrate utilization assays and metabolic flux measurements, we found global metabolic changes in dendritic cells 17 hours post infection, including significant changes in carbon commitment via glycolysis and glutaminolysis, as well as mitochondrial respiration. Influenza infection of dendritic cells led to a metabolic phenotype distinct from that induced by TLR agonists, with significant resilience in terms of metabolic plasticity. We identified c-Myc as one transcription factor modulating this response. Restriction of c-Myc activity or mitochondrial substrates significantly changed the immune functions of dendritic cells, such as reducing motility and T cell activation. Transcriptome analysis of inflammatory dendritic cells isolated following influenza infection showed similar metabolic reprogramming occurs in vivo. Thus, early in the infection process, dendritic cells respond with global metabolic restructuring, that is present in inflammatory lung dendritic cells after infection, and this is important for effector function. These findings suggest metabolic switching in dendritic cells plays a vital role in initiating the immune response to influenza infection.

59 BASIC BIOLOGICAL SCIENCES↗

Soil chemistry data across a catena in the Luquillo Experimental Forest, Puerto Rico

Landscape topography can influence biogeochemical processes across the wet tropical forest soils. This dataset contains soil chemistry data such as pH and dissolved organic carbon (DOC) from April 1, 2017 to May 1, 2018 across a catena in the Luquillo Experimental Forest, Puerto Rico. The attached CSV file contains information on sampling date, location (El Verde field station) in LEF, topographic positions (ridge, slope, and valley, respectively), field replicate number, laboratory replicate number, water extractable pH, CaCl2 extractable pH, and DOC (unit: mg/g). Overall, soil pH values were highest in the valley, followed by slope, and lowest in the ridge topographic positions. However, DOC values followed the opposite trend: ridge>slope>valley. This dataset can facilitate our understanding of the biogeochemical cycling of carbon and nutrient associated with complex topography in wet tropical forest soils.

54 ENVIRONMENTAL SCIENCES↗

Data for: A Synoptic System for Capturing Ecosystem Control Points Across Terrestrial-Aquatic Interfaces

The investigation of how climate change and water level fluctuations impact variable and interconnected ecosystems, like the interfaces between terrestrial and aquatic environments, requires the collection and integration of many data types. We describe an integrative and autonomous environmental monitoring approach that uses environmental sensors and data loggers to monitor surface water, groundwater, soil, and vegetation changes and generate essential data for predictive models. We established the network at seven sites along the Chesapeake Bay and Lake Erie coastlines, including a large-scale flood manipulation experiment, collectively generating over three million observations per month. Such sensor networks hold great promise for tracking and comprehending environmental changes where land and water intersect. The sensor system and overall approach to sensor management that we have designed is intended to be widely accessible for research teams spanning in size from an individual investigator to large multi-institution projects. This dataset shows example data generated by the sensor network described above. Data output for data loggers connected to groundwater water quality sondes measuring dissolved oxygen, pH, oxidative redox potential (ORP), groundwater elevation, groundwater salinity and temperature, and groundwater elevation; replicate soil moisture and conductivity probes installed at 10 and 30 cm below the ground surface; rainfall and solar radiation; and mean sap flow from 8 replicate probes. Sensors are installed at upland forest (UP), wetlands (W), and transitional locations between these ecosystems (TR). Example datasets are from Goodwin Islands in the Chesapeake Bay and Portage River along the Lake Erie coastline.

54 ENVIRONMENTAL SCIENCES↗

Thermal dissipation sensors enter a new age: Navigating frontiers in transpiration and hydrologic function

Thermal dissipation (TD) sensors have been used extensively for a wide array of sap flow applications, and yet recently several limitations of this approach have been identified, including a tendency to underestimate absolute flows, especially in small stems with very high flows. However, when used properly, the TD method remains the most cost effective and reliable approach for determining relative flows in comparison studies. Major advantages of this method include the ability to replicate maximally within trees, across trees of different sizes, and across multiple species to capture the full range of natural variation in the study system. From early studies, such variation has been deemed a major challenge for representing stand-level dynamics. In a series of recent comparison studies, we determined mean sap flux density dynamics within and among groups of trees. These studies were conducted within temperate coniferous forest (n=46), temperate oak savanna (n=36), temperate pine forest (n=49), temperate bottomland hardwood forest (n=23), tropical premontane rainforest (n=43), semiarid subtropical shrubland (n=25), and tropical dry forest (n=15), with a total of 237 sensors. Two study sites were also equipped with eddy covariance systems for determination of stand-level evapotranspiration. Sites subject to high background thermal gradients used the transient thermal dissipation method. Comparisons varied between studies but tended to focus on relative flow differences between species, between wetter and drier microsites, between understory and overstory components, or between wetter and drier periods of the growing season. Except for the shrubland sites, study trees tended to be at least 15-cm diameter and frequently exceeded 50-cm diameter. Results of this cross-site comparison highlight the inherent variation in natural stands and the importance of using large sample sizes. The TD approach remains a valuable and preferred method for the future determination of water use in trees. However, sensor replication can fundamentally impact a study's outcomes and should be more carefully considered in study design. Customized error mitigation strategies are best to address the sources of variation most problematic for a particular study. In conclusion, the development of “smart” calibration approaches that correct for fundamental effects of radial variation inherent in thermal dissipation studies is discussed.

59 BASIC BIOLOGICAL SCIENCES↗

Accelerated epigenetic aging as a risk factor for chronic obstructive pulmonary disease and decreased lung function in two prospective cohort studies

Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up – baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.

60 APPLIED LIFE SCIENCES↗

High and low dose radiation effects on mammary adenocarcinoma cells – an epigenetic connection

The successful treatment of cancer, including breast cancer, depends largely on radiation therapy and proper diagnostics. The effect of ionizing radiation on cells and tissues depends on the radiation dose and energy level, but there is insufficient evidence concerning how tumor cells respond to the low and high doses of radiation that are often used in medical diagnostic and treatment modalities. The purpose of this study was to investigate radiation-induced gene expression changes in the MCF7 breast adenocarcinoma cell line. Using microarray technology tools, we were able to screen the differential gene expressions profiles between various radiation doses applied to MCF-7 cells. Here, we report the substantial alteration in the expression level of genes after high-dose treatment. In contrast, no dramatic gene expression alterations were noticed after the application of low and medium doses of radiation. In response to a high radiation dose, MCF-7 cells exhibited down-regulation of biological pathways such as cell cycle, DNA replication, and DNA repair and activation of the p53 pathway. Similar dose-dependent responses were seen on the epigenetic level, which was tested by a microRNA expression analysis. MicroRNA analysis showed dose-dependent radiation-induced microRNA expression alterations that were associated with cell cycle arrest and cell death. An increased rate of apoptosis was determined by an Annexin V assay. The results of this study showed that high doses of radiation affect gene expression genetically and epigenetically, leading to alterations in cell cycle, DNA replication, and apoptosis.

59 BASIC BIOLOGICAL SCIENCES↗

Small-Scale Experiments.10-gallon drum experiment summary

A series of sub-scale (10-gallon) drum experiments were conducted to characterize the reactivity, heat generation, and gas generation of mixtures of chemicals believed to be present in the drum (68660) known to have breached in association with the radiation release event at the Waste Isolation Pilot Plant (WIPP) on February 14, 2014, at a scale expected to be large enough to replicate the environment in that drum but small enough to be practical, safe, and cost effective. These tests were not intended to replicate all the properties of drum 68660 or the event that led to its breach, or to validate a particular hypothesis of the release event. They were intended to observe, in a controlled environment and with suitable diagnostics, the behavior of simple mixtures of chemicals in order to determine if they could support reactivity that could result in ignition or if some other ingredient or event would be necessary. There is a significant amount of uncertainty into the exact composition of the barrel; a limited sub-set of known components was identified, reviewed with Technical Assessment Team (TAT) members, and used in these tests. This set of experiments was intended to provide a framework to postulate realistic, data-supported hypotheses for processes that occur in a “68660-like” configuration, not definitively prove what actually occurred in 68660.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Controlling Energy Performance on the Big Stage - The New York Times Company

The Times partnered with the U.S. Department of Energy (DOE) as part of DOE’s Commercial Building Partnerships (CBP) Program to develop a post-occupancy evaluation (POE) of three EEMs that were implemented during the construction of The Times building between 2004-2006. With aggressive goals to reduce energy use and carbon emissions at a national level, one strategy of the US Department of Energy is looking to exemplary buildings that have already invested in new approaches to achieving the energy performance goals that are now needed at scale. The Times building incorporated a number of innovative technologies, systems and processes that make their project a model for widespread replication in new and existing buildings. The measured results from the post occupancy evaluation study, the tools and processes developed, and continuous improvements in the performance and cost of the systems studied suggest that these savings are scalable and replicable in a wide range of commercial buildings nationwide.

99 GENERAL AND MISCELLANEOUS↗

Solar Energy Technology Office Portfolio Review: Promotion of PV Soft Cost Reductions in the Southeastern US

From 2016-2021, the installed solar capacity in South Carolina will mushroom from less than 20 megawatts to more than 300 megawatts. Concurrently, the number of customer-sited, load-centered solar generation is expected to grow from less than 500 statewide to as many as 10,000 by 2021. This growth is anticipated to be the direct result of a landmark state policy initiative, Act 236, passed by the South Carolina General Assembly and signed into law by the Governor in June of 2014. Local policy makers in South Carolina are ill-equipped to handle the onslaught of solar permitting and zoning requests expected over the next five years. Similarly, the state’s building inspectors, first responders, and tax assessors know little about photovoltaic (PV) technology and best practices. Finally, South Carolina’s workforce and workforce trainers are underprepared to benefit from the tremendous opportunity created by the passage of Act 236. Each of these deficits in knowledge of and preparedness for solar PV translates into higher “soft costs” of installed solar PV in South Carolina. Currently, we estimate that the installed costs of residential rooftop solar are as much as 25 percent higher than the national average. The Savannah River National Laboratory (SRNL), together with almost a dozen electricity stakeholders in the Southeast, proposes to create a replicable model for solar PV soft cost reduction in South Carolina through human capacity-building at the local level and direct efforts to harmonize policy at the inter-county or regional level. The primary goal of this effort is to close the gap between South Carolina installed costs of residential rooftop solar and national averages. The secondary goal is to develop a portable and replicable model that can be applied to other jurisdictions in the Southeastern US.

14 SOLAR ENERGY↗

Sun Grant/DOE Regional Feedstock Partnership: Final Technical Report

The U.S. Department of Energy (DOE) and the Sun Grant Initiative initiated the Regional Feedstock Partnership (referred to as the Partnership) in 2007 primarily to address information gaps associated with the likelihood for realization of the sustainable and reliable production of a billion-tons of biomass annually to support the U.S. bioenergy industry by the year 2030. Publication of The Technical Feasibility of a Billion-Ton Annual Supply (Perlack et al., 2005) in 2005, with its associated yield assumptions, led to the realization that the yield goals and assumptions utilized in that analysis required careful validation. To achieve the overall goal of validating key yield assumptions, the following objectives were developed: 1. Establishment of replicated field trials across regions to determine the impact of crop residue removal (primarily corn and small grains) on future grain yields and soil health. 2. Establishment of replicated field trials of some of the most promising dedicated energy crops (herbaceous annuals and perennials, as well as woody perennials) to demonstrate the potential performance of these feedstocks across the U.S. 3. Assessment of feedstock resources to be used to estimate a sustainable national supply potential. Teams composed of representatives from Land Grant Universities, USDA ARS, DOE National Laboratories, industry, and other federal agencies were identified and assembled to address each of these objectives. For Objective 1, members of the USDA ARS’ Resilient Economic Agricultural Practices (REAP) team combined with university personnel to leverage on-going work and established new trials to determine sustainable corn residue removal rates. In addition, universities across the continental U.S. conducted surveys of published past research to define parameters for the use of cereal grain residue (primarily wheat) as a biomass feedstock. For Objective 2, and based on input from DOE, USDA, Land Grant university scientists, and others, several herbaceous and woody energy crop species were selected for new or further evaluation across wide geographic areas as cellulosic feedstock sources. Species teams were organized to assess the yield potential of candidate herbaceous feedstocks including sorghum, energycane, Miscanthus x giganteus (hereafter referred to as miscanthus), switchgrass, and mixed perennial species (primarily grasses and some legumes) on Conservation Reserve Program (CRP) land. Woody species will be critical components of the bioenergy sector; therefore, species teams were also organized for shrub willow and hybrid poplar (Populus spp.). Field trials of each species were utilized to determine yield potential across the U.S. For Objective 3, a GIS resource team was organized with representatives from each of the five Sun Grant regions. While some regional assessments were made, the multi-institutional team decided that the group from Oregon State University would utilize their PRISM ELM model to estimate national yield potential of the various species evaluated. The following are key outcomes and impacts • The Partnership demonstrated the production potential of diverse herbaceous and woody feedstocks across much of the U.S. for 5-7 consecutive growing seasons. Long-term studies such as this are not commonly possible due to limitations in funding cycles. • Long-term field trials were valuable in demonstrating the importance of agronomic management practices and genetic resources to yield of sorghum, switchgrass, miscanthus, energycane, CRP mixed perennial grasses, poplar, and willow. • National yield potential maps were developed for all species evaluated in the Partnership. • Sustainable corn stover removal rates were quantified for use by producers, harvesters, and commercial lignocellulosic biorefineries. • Data from the Partnership field trials not only validated initial Billion Ton estimates, but were instrumental in developing both the Billion Ton Update in 2011, and especially the 2016 Billion Ton Report. • The Partnership provided the opportunity to assemble and conserve a poplar germplasm collection that contains more than 20,000 clones for use in breeding programs. New clones resulting from crosses made using this germplasm collection have resulted in significantly improved cultivars that could be scaled up and deployed. • Further validation of improved yields of new varieties/cultivars of biomass sorghum, energycane, hybrid poplars, and shrub willows was produced by the Partnership. • The Partnership demonstrated the potential of energycane in northern parts of the southeastern U.S., particularly in relation to sugarcane varieties. • For certain feedstocks (e.g., CRP mixed grasses, switchgrass, willow, and poplar), production economics were ascertained through Partnership field trials. • Biomass samples collected as part of the Partnership are also being used to populate Idaho National Laboratory’s Bioenergy Feedstock Library. • Because of the size and scope of the Partnership, workforce development was a key component and outcome. Numerous undergraduate students (25), graduate students (15 MS and 8 PhD), and postdoctoral researchers (7) were trained by Partnership participants. This will help to prepare individuals for careers in the emerging fields of plant breeding, biomass production, feedstock supply logistics, and biomass conversion processes. • More than 130 scientific publications have been authored by Partnership team members. Numerous other presentations, outreach publications, book chapters, and websites have also been developed to further the continued development of the bioeconomy.

09 BIOMASS FUELS↗

Validation Study of the Spacecraft Background Activation using RHESSI Data

This document serves as a brief writeup of the work done to validate CINDER2008 and the Activation Analysis Tools in the Activation in Accelerator Radiation Environments (AARE) distribution that are used to calculate the activation of spacecraft material while in orbit [1{3]. The validation study involves replicating the decay gamma spectrum as observed onboard the RHESSI spacecraft in the high-purity germanium (HPGe) detectors after crossing the South Atlantic Anomaly (SAA) [4]. The tools involved are a suite of Python scripts, the transmutation code CINDER2008 accompanied with a suite of scripts distributed with AARE,MCNPX, and MCNP6.2 [2,5{7]. Figure 1 shows the gamma ray spectrum this study replicates as the spectrum designated \Difference".

42 ENGINEERING↗

Toward a Compatible Reproducibility Taxonomy for Computational and Computing Sciences

Reproducibility is an essential ingredient of the scientific enterprise. The ability to reproduce results builds trust that we can rely on the results as foundations for future scientific exploration. Presently, the fields of computational and computing sciences provide two opposing definitions of reproducible and replicable. In computational sciences, reproducible research means authors provide all necessary data and computer codes to run analyses again, so others can re-obtain the results (J. Claerbout et al., 1992). The concept was adopted and extended by several communities, where it was distinguished from replication: collecting new data to address the same question, and arriving at consistent findings (Peng et al. 2006). The Association of Computing Machinery (ACM), representing computer science and industry professionals, recently established a reproducibility initiative, adopting essentially opposite definitions. The purpose of this report is to raise awareness of the opposite definitions and propose a path to a compatible taxonomy.

97 MATHEMATICS AND COMPUTING↗

Investigation of thermolytic hydrogen generation rate of tank farm simulated and actual waste

To support resolution of Potential Inadequacies in the Safety Analysis for the Savannah River Site (SRS) Tank Farm, Savannah River National Laboratory conducted research to determine the thermolytic hydrogen generation rate (HGR) with simulated and actual waste. Gas chromatography methods were developed and used with air-purged flow systems to quantify hydrogen generation from heated simulated and actual waste at rates applicable to the Tank Farm Documented Safety Analysis (DSA). Initial simulant tests with a simple salt solution plus sodium glycolate demonstrated the behavior of the test apparatus by replicating known HGR kinetics. Additional simulant tests with the simple salt solution excluding organics apart from contaminants provided measurement of the detection and quantification limits for the apparatus with respect to hydrogen generation. Testing included a measurement of HGR on actual SRS tank waste from Tank 38. A final series of measurements examined HGR for a simulant with the most common SRS Tank Farm organics at temperatures up to 140 °C. The following conclusions result from this testing. HGR was measured for an actual-waste Tank 38 sample. The HGR measurements at 80, 90, 100, and 110 °C were 1.7×10 -7 , 4.7×10 -7 , 5.9×10 -7 , and 2.6×10 -6 ft 3 hr -1 gal -1 , respectively. The Limit of Detection and Limit of Quantification for the HGR measurements were 2.6×10-8 ft3 hr-1 gal-1 and 5.1×10 -8 ft 3 hr -1 gal -1 , respectively. HGR was measured in a high boiling point (HBP) simulant with major known SRS Tank Farm organic compounds. Testing used fresh organics and did not simulate the long-term exposure of these organics already experienced in the waste. Hence, testing is expected to provide high bias to the hydrogen generation rates. The final HGR measurements at 75, 100, and 140 °C were 6.2×10 -7 , 3.0×10 -6 , and 8.1×10 -5 ft 3 hr -1 gal -1 , respectively. Decreases in the HGR were noted at isothermal conditions with steady gas tracer concentration, which clouds development of a temperature dependent correlation for generation rate. While the simulant contains high concentrations of major SRS organics tested at high temperatures found in the 3H Evaporator, this limited data set may not fully bound values under all possible operating conditions. The HGR measurement apparatus was successfully employed to replicate hydrogen production rate experiments. Simulant without deliberately added organic carbon was found to contain approximately 200 mg/L of organic carbon from tramp organics in the reagents used to prepare the solution. The tests using such simulant generated hydrogen at rates consistent with, but somewhat lower than, those predicted at equivalent carbon and aluminum loadings by methods used at the Hanford Site. Prior to identifying the organic contaminants, potential sources of hydrogen in simulants without deliberately added organic carbon were examined. Testing determined that this hydrogen is not due to caustic reaction of organic materials of construction within the reaction vessel, electrolysis due to current leak, anode/cathode reactions, corrosion, or the method of heating employed in the experiment. During the HBP and Tank 38 testing, a peak was identified at a retention time greater than the retention time of the inert tracer of krypton. This peak has been identified as methane, and the data have been reexamined to obtain methane concentrations. For the HBP testing, methane concentration was constant at the highest temperature studied (140 °C) and higher than hydrogen. At the lower temperatures (100 and 75 °C), methane and hydrogen tracked closely, with methane concentration generally lower than hydrogen. For Tank 38, methane concentration was approximately 1/3 of the hydrogen concentration during testing (100 and 110 °C). At lower temperatures for Tank 38 testing (90, 80, and 27 °C), methane fell below the quantification range.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Resilience Roadmap: A Collaborative Approach to Multi-Jurisdictional Resilience Planning

Extreme weather and aging infrastructure are creating unprecedented challenges in the United States and around the globe. Many communities have suffered damages from a variety of weather-related events, such as severe weather such as hurricanes, droughts, increasing temperatures, wildfires, and storm surges. Numerous efforts exist to improve resilience to protect national security, energy and water security, economic well-being, and quality of life. As severe weather events increase in frequency and severity, many cities, states, tribes, and federal agencies are addressing the impacts through resilience planning and measures. In an effort to support communities with resilience planning, the White House Council on Environmental Quality (CEQ) initiated preparedness pilot projects designed to showcase community resilience planning in the City of Houston and the State of Colorado. This publication is the full, technical document, for the Colorado pilot project. The process is also summarized in a user-friendly web-version on NREL's website (visit www.nrel.gov/resilience-planning-roadmap) for easier access and replicability. NASA's pilot project with the City of Houston is summarized separately (visit https://toolkit.climate.gov/case-studies/climate-resilience to learn more). water security, economic well-being, and quality of life. As severe weather events increase in frequency and severity, many cities, states, tribes, and federal agencies are addressing the impacts through resilience planning and measures. In an effort to support communities with resilience planning, the White House Council on Environmental Quality (CEQ) initiated preparedness pilot projects designed to showcase community resilience planning in the City of Houston and the State of Colorado. This publication is the full, technical document, for the Colorado pilot project. The process is also summarized in a user-friendly web-version on NREL's website (visit www.nrel.gov/resilience-planning-roadmap) for easier access and replicability. NASA's pilot project with the City of Houston is summarized separately (visit https://toolkit.climate.gov/case-studies/climate-resilience to learn more).

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Investigating the role of innate immunity in viral encephalitis caused by Rift Valley fever virus

Rift Valley Fever Virus (RVFV) is a category A biodefense pathogen due to its potential for intentional spread by aerosols and the lack of a licensed vaccine or antiviral therapeutic. Although the brain is a major target of viral replication and tissue damage following aerosol infection, little is known about innate immune responses to RVFV in the brain. We are investigating the responses of resident innate immune cells of the brain (microglia and astrocytes) during RVFV infection, in order to identify how these cells are capable of controlling RVFV replication. Microglia mount a robust response to RVFV that is dependent upon mitochondrial antiviral-signaling protein (MAVS) and independent of toll-like receptors 3 and 7. Mice genetically modified to have nonfunctional MAVS (MAVS "knock out" or KO mice) have significantly higher viral loads in the brain following intranasal infection, but surprisingly, many markers of immune activity were similarly upregulated in the brains of MAVS KO and wild type (WT, or “normal”) mice. This is in contrast to the in vitro response, where microglia and astrocytes derived from MAVS KO mice were unresponsive to RVFV infection. RNA-sequencing analysis of infected brain tissue revealed that key antiviral genes are not activated in the MAVS KO animals. These results are an important step towards understanding the molecular pathways responsible for controlling RVFV infection in the brain and lay the groundwork for the development of targeted therapies for the prevention of RVFV encephalitis.

59 BASIC BIOLOGICAL SCIENCES↗

Municipal Portfolio Performance and Policy Opportunities

A wide range of policy tools are in place to enhance energy efficiency in the built environment. However, the lion’s share of today’s energy savings opportunities have to do with energy consumption in existing buildings currently in operation. Many of the policy tools in play, including energy codes, have little to no effect on these existing buildings. New tools and resources are needed to bring existing buildings up to higher levels of energy performance. This project was focused on building a replicable framework, complete with open-source software tools and resources, to empower cities around the country to significantly enhance the energy performance of their own existing buildings and identify opportunities for future improvements. These issues were addressed through the evaluation of the performance of the municipal building stock and policy environments of four mid-size cities: Eugene, Oregon; Providence, Rhode Island; Grand Rapids, Michigan; and Tacoma, Washington. The project team worked closely with these cities to help city staff lead by example and create actionable, implementation-focused strategic energy plans for their own municipal building portfolios and to evaluate and improve city policies. A major focus throughout has been replicability and knowledge transfer (“teaching them to fish” rather than doing the work for the city).

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Further Support of the Development of Advanced Multilayer Optics Coatings for X-Ray Imaging

SAO is working with LLNL to develop Wolter-I optics for x-ray imaging applications at energies of 15-50 keV and above at NNSA facilities. Our work includes R&D on advanced multilayer coatings as well as fabrication and testing of Wolter-I multilayer coated optics. It also includes delivery of custom 3.05-meter focal length Wolter optics with response at energies of interest to Sandia National Laboratories and LLNL. The mandrels for the custom optics are fabricated at MSFC. In previous contracts, SAO delivered several optics to LLNL with response at various energies. During this present contract period two tasks were carried out. Task1: the coating, replication and characterization of a custom optic with peak response at 22.8 keV, using the custom-designed SANZ mandrels. Task2: carrying out modifications to the coating chamber at SAO to accommodate new, longer, custom-designed mandrels (SANZlong) that will be fabricated at NASA MSFC in FY2020. The longer mandrels are necessary to mitigate end effects observed in the replication process for the small optics currently being fabricated.

36 MATERIALS SCIENCE↗