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At least 289 records · Page 16

Science & Technology Review May 2019

Lawrence Livermore’s “brain-on-a-chip” is designed to predict the effects of potentially harmful chemicals, viruses, and drugs on humans without relying on animal or human test subjects. In conjunction with an artificial blood–brain barrier, the device simulates the central nervous system by recording activity from brain cells grown onto a small platform embedded with microelectrode arrays. The brain-on-a-chip holds significant promise for national security and broader applications. For example, the device could be used to determine how soldiers are affected by exposure to chemical and biological weapons and the effectiveness of potential countermeasures and prophylactic pretreatments. The technology could also help predict the effects on the brain from promising drugs designed to treat neurological disorders. The brain-on-a-chip is the latest iteration of the Laboratory’s iCHIP (in vitro chip-based human investigational platform) project—a broad initiative at Livermore to advance human health with a focus on understanding, diagnosing, and potentially treating human neural problems and diseases.

36 MATERIALS SCIENCE↗

AI-supported mini-labs: combining smartphone-based experiments and multimodal AI

Multimedia learning has always been a topic in physics education—whether through specialized digital data acquisition systems, simulations, or animations. Due to increasing digitalization, more and more media from our everyday lives have also found their way into education in recent decades. This contribution introduces a conceptual framework and illustrative examples for AI-supported experimentation in physics education. It does not yet present empirical data but outlines directions for forthcoming classroom studies evaluating learning outcomes and engagement.

generative AI↗

Report on DOE support for GSC13 travel award

Consortium. The 3-day conference was held at the Kingkey Palace Hotel, Shenzhen, China, on March 5-7th, 2012, and was hosted by the Beijing Genomics Institute (BGI). The meeting was entitled ‘From Genomes to Interactions to Communities to Models’ and aimed to be a scientific meeting that highlighted the role of data standards associated with genomic, metagenomic and amplicon sequence data, and the contextual information associated with the sample that data was generated from. To this end the meeting focused on genomic projects for animals, plants, fungi and viruses, metagenomic studies in host-microbe interactions, and community dynamics in microbial communities. In addition the meeting hosted a Genomic Observatories Network session, a GSC biodiversity working group session, and a Microbiology of the Built Environment session sponsored by the Alfred P. Sloan Foundation. The meeting was very well organized by the local hosts at BGI, and all attendees reported that they were very happy with the outcome, service and quality of the science presented. Highlights were keynotes by Rita Colwell, Mitch Sogin and Jim Tiedje. The 5 attendees paid for by the DOE award were Daniel Smith and Jared Wilkening (University of Chicago); Patrick Chain (Los Alamos National Laboratory), Austin Davis-Richardson (University of Florida) and Greg Caporoaso (University of Northern Arizona). Each attendee was able to either present or become involved with the attending scientists, and each reported that they had got something significant out of the meeting. Here are detailed their personal accounts of the GSC13 meeting. We thank DOE for the helping to fund this valuable outreach initiative, and for supporting the attendance of these bright young scientists at this important meeting.

59 BASIC BIOLOGICAL SCIENCES↗

Multi-resolution, Multi-scale Modeling for Scalable Macroalgae Production

Macroalgae harvested along coastlines and in the open ocean has traditionally been used as food for human consumption, animal feed, and fertilizer. The U.S. ARPA-E MARINER Program estimates that the nation has suitable conditions and geography to produce at least 500 million dry metric tons of macroalgae per year, yielding approximately 2.7 quadrillion BTUs of energy in the form of liquid fuel, which is roughly 10% of the nation’s annual transportation energy demand. Adverse environmental effects of nutrient overload and ocean acidification may also be reduced by large-scale macroalgae cultivation in many coastal ocean regions. However, the successful deployment of large-scale marine macroalgae farms for fuel production depends on ambient hydrodynamic conditions and nutrient availability, as well as their interactions with macroalgae farm structures. Pacific Northwest National Laboratory led an ARPA-E MARINER project to develop a set of numerical modeling tools capable of simulating ocean hydrodynamic and biogeochemical processes, macroalgae trajectories for free-floating systems, macroalgae growth and biomass yields, and hydrodynamic load on macroalgae canopies and farm structures using a multi-resolution and multi-scale approach. This set of modeling tools provides a suite of information essential for system design, optimal project siting, risk analysis, and management of macroalgae production systems in the ocean. Better clarity can also help macroalgae system developers reduce deployment costs, operational risk, and potential impacts on the local marine environment.

59 BASIC BIOLOGICAL SCIENCES↗

Xenorhabdus bovienii Strain Diversity Impacts Coevolution and Symbiotic Maintenance with Steinernema spp. Nematode Hosts

Microbial symbionts provide benefits that contribute to the ecology and fitness of host plants and animals. Therefore, the evolutionary success of plants and animals fundamentally depends on long-term maintenance of beneficial associations. Most work investigating coevolution and symbiotic maintenance has focused on species-level associations, and studies are lacking that assess the impact of bacterial strain diversity on symbiotic associations within a coevolutionary framework. Here, we demonstrate that fitness in mutualism varies depending on bacterial strain identity, and this is consistent with variation shaping phylogenetic patterns and maintenance through fitness benefits. Through genome sequencing of nine bacterial symbiont strains and cophylogenetic analysis, we demonstrate diversity among Xenorhabdus bovienii bacteria. Further, we identified cocladogenesis between Steinernema feltiae nematode hosts and their corresponding X. bovienii symbiont strains, indicating potential specificity within the association. To test the specificity, we performed laboratory crosses of nematode hosts with native and nonnative symbiont strains, which revealed that combinations with the native bacterial symbiont and closely related strains performed significantly better than those with more divergent symbionts. Through genomic analyses we also defined potential factors contributing to specificity between nematode hosts and bacterial symbionts. These results suggest that strain-level diversity (e.g., subspecies-level differences) in microbial symbionts can drive variation in the success of host-microbe associations, and this suggests that these differences in symbiotic success could contribute to maintenance of the symbiosis over an evolutionary time scale.

59 BASIC BIOLOGICAL SCIENCES↗

California GAMA Special Study: Stable Isotopic Composition of Boron in Groundwater - San Diego County Domestic Well Data

The Groundwater Ambient Monitoring and Assessment (GAMA) Program is a comprehensive groundwater quality monitoring program for the state of California. Managed by the California State Water Resources Control Board (SWRCB), the goals of the Program are twofold: to improve statewide groundwater monitoring, and to increase the availability of groundwater quality information to the public. The Domestic Well Project has sampled 137 wells in San Diego County in an effort to assess the quality of these unregulated domestic use water sources. Lawrence Livermore National Laboratory (LLNL) performed isotopic analyses of domestic well water samples for the SWRCB; this study summarizes the results of measurements of the isotopic composition of dissolved boron in groundwater in 56 wells, and provides some interpretations regarding the significance of these findings. These data, in conjunction with water and nitrate isotopic composition data (Singleton et al., 2010), are useful for determining the source(s) of nitrate in potentially-contaminated San Diego County groundwater reservoirs. The isotopic composition of dissolved boron (δ 11 B) in sampled San Diego County groundwaters varies from -0.8 to +64.4 ‰. Most sampled groundwaters (44 of 56) have δ 11 B values between +20 and +50 ‰, within the isotopic composition range characteristic of animal manure. These samples tend to have high nitrate concentrations (>50 mg/L as NO 3 ) These results are consistent with isotopic composition of nitrogen in nitrate (δ 15 N) data from Singleton et al. (2010), indicating that animal manure is a primary source of nitrate in most groundwaters measured in this study. Seven samples have δ 11 B values less than +20 ‰, outside of the animal manure δ 11 B range. These groundwaters tend to have low nitrate concentrations(<10 mg/L as NO 3 ), although two have nitrate concentrations greater than 10 mg/L, suggesting that wastewater may partially contribute to their nitrate budget. No samples measured in this study have boron or nitrate isotopic compositions consistent with a mineral fertilizer nitrate source. Five sampled groundwaters have δ 11 B values greater than +50 ‰, significantly higher than any known anthropogenic boron source. More work is needed to assess the source of nitrate and boron in the greater than +50 ‰ groundwaters.

07 ISOTOPE AND RADIATION SOURCES↗

The Importance of Dosimetry Standardization in Radiobiology

Radiation dose is central to much of radiobiological research. Precision and accuracy of dose measurements and reporting of the measurement details should be sufficient to allow the work to be interpreted and repeated and to allow valid comparisons to be made, both in the same laboratory and by other laboratories. Despite this, a careful reading of published manuscripts suggests that measurement and reporting of radiation dosimetry and setup for radiobiology research is frequently inadequate, thus undermining the reliability and reproducibility of the findings. To address these problems and propose a course of action, the National Cancer Institute (NCI), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Standards and Technology (NIST) brought together representatives of the radiobiology and radiation physics communities in a workshop in September, 2011. The workshop participants arrived at a number of specific recommendations as enumerated in this paper and they expressed the desirability of creating dosimetry standard operating procedures (SOPs) for cell culture and for small and large animal experiments. It was also felt that these SOPs would be most useful if they are made widely available through mechanism(s) such as the web, where they can provide guidance to both radiobiologists and radiation physicists, be cited in publications, and be updated as the field and needs evolve. Other broad areas covered were the need for continuing education through tutorials at national conferences, and for journals to establish standards for reporting dosimetry. This workshop did not address issues of dosimetry for studies involving radiation focused at the sub-cellular level, internally-administered radionuclides, biodosimetry based on biological markers of radiation exposure, or dose reconstruction for epidemiological studies.

61 RADIATION PROTECTION AND DOSIMETRY↗

Policy support and technology development trajectory for renewable natural gas in the U.S.

Renewable natural gas (RNG) is a clean alternative to fossil natural gas, which can be used as transportation fuel, among other applications. This study projects the development trajectory of RNG and evaluates its impacts on the future U.S. transportation market using a hybrid computable general equilibrium model. This analysis considers various factors and uncertainties affecting RNG production, such as technology development, market conditions, competition with other advanced biofuels, and national and state policies. In 2050, RNG production will grow to 2.7 billion gallons (10 billion liters), mostly from swine manure, under current policy provisions. This will lead to a reduction in greenhouse gas (GHG) emissions by 58.56 million metric tonne of CO 2e in 2050. Analysis of different technology cases finds RNG from animal manure to be predominant, while RNG from corn stover and cellulosic ethanol are less competitive. Furthermore, a high mandatory target of 1 billion gallons will drive RNG production higher by 8–18 %, while an extended 2 nd -generation biofuel production tax credit will mostly increase cellulosic ethanol production. The model also finds RNG production being affected by uncertainties in market conditions, such as GDP growth, fossil fuel prices, and oil and gas supply.

Biomethane↗

Translation of DNA Damage Response Inhibitors as Chemoradiation Sensitizers From the Laboratory to the Clinic

Combination therapies with agents targeting the DNA damage response (DDR) offer an opportunity to selectively enhance the therapeutic index of chemoradiation or eliminate use of chemotherapy altogether. The successful translation of DDR inhibitors to clinical use requires investigating both their direct actions as (chemo)radiosensitizers and their potential to stimulate tumor immunogenicity. Beginning with high-throughput screening using both viability and DNA damage-reporter assays, followed by validation in gold-standard radiation colony-forming assays and in vitro assessment of mechanistic effects on the DDR, we describe proven strategies and methods leading to the clinical development of DDR inhibitors both with radiation alone and in combination with chemoradiation. Beyond these in vitro studies, we discuss the impact of key features of human xenograft and syngeneic mouse models on the relevance of in vivo tumor efficacy studies, particularly with regard to the immunogenic effects of combined therapy with radiation and DDR inhibitors. Finally, we describe recent technological advances in radiation delivery (using the small animal radiation research platform) that allow for conformal, clinically relevant radiation therapy in mouse models. This overall approach is critical to the successful clinical development and ultimate Food and Drug Administration approval of DDR inhibitors as (chemo)radiation sensitizers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Phase contrast tomography of the mouse cochlea at microfocus x-ray sources

We present phase contrast x-ray tomography of functional soft tissue within the bony cochlear capsule of mice, carried out at laboratory microfocus sources with well-matched source, detector, geometry, and reconstruction algorithms at spatial resolutions down to 2 μm. Contrast, data quality and resolution enable the visualization of thin membranes and nerve fibers as well as automated segmentation of surrounding bone. By complementing synchrotron radiation imaging techniques, a broad range of biomedical applications becomes possible as demonstrated for optogenetic cochlear implant research.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Animal-associated jumbo phages as widespread and active modulators of gut microbiome ecology and metabolism

Huge phages are widespread in the biosphere, yet their prevalence and ecology in the human gut remain poorly characterized. Here, we report Jug (jumbo gut) phages with genomes of 360 to 402 kilobase pairs that comprise ~1.1% of the reads in human gut metagenomes, and are predicted to infect Bacteroides and/or Phocaeicola. Although three of the four major groups of Jug phages shared >90% genome-wide sequence identity, their large terminase subunits exhibited only 38 to 57% identity, suggesting horizontal acquisition from other phages. Over 1500 genomes of Jug phages were recovered from human and animal gut metagenomes, revealing their broad distribution, with largely shared gene content suggestive of frequent cross-animal-host transmission. Jug phages displayed high gene transcription activities, including the gene for a calcium-translocating P-type ATPase not detected previously in phages. These findings broaden our understanding of huge phages and highlight Jug phages as potential major players in gut microbiome ecology.

Chen, LinXing [University of Science and Technolog↗

A Critical Role of the PTEN/PDGF Signaling Network for the Regulation of Radiosensitivity in Adenocarcinoma of the Prostate

Purpose: Loss or mutation of the phosphate and tensin homologue (PTEN) is a common genetic abnormality in prostate cancer (PCa) and induces platelet-derived growth factor D (PDGF D) signaling. We examined the role of the PTEN/PDGF axis on radioresponse using a murine PTEN null prostate epithelial cell model. Methods and Materials: PTEN wild-type (PTEN{sup +/+}) and PTEN knockout (PTEN{sup −/−}) murine prostate epithelial cell lines were used to examine the relationship between the PTEN status and radiosensitivity and also to modulate the PDGF D expression levels. PTEN{sup −/−} cells were transduced with a small hairpin RNA (shRNA) lentiviral vector containing either scrambled nucleotides (SCRM) or sequences targeted to PDGF D (shPDGF D). Tumorigenesis and morphogenesis of these cell lines were evaluated in vivo via subcutaneous injection of male nude mice and in vitro using Matrigel 3-dimensional (3D) culture. Effects of irradiation on clonogenic survival, cell migration, and invasion were measured with respect to the PTEN status and the PDGF D expression level. In addition, apoptosis and cell cycle redistribution were examined as potential mechanisms for differences seen. Results: PTEN{sup −/−} cells were highly tumorigenic in animals and effectively formed foci in 3D culture. Importantly, loss of PDGF D in these cell lines drastically diminished these phenotypes. Furthermore, PTEN{sup −/−} cells demonstrated increased clonogenic survival in vitro compared to PTEN{sup +/+}, and attenuation of PDGF D significantly reversed this radioresistant phenotype. PTEN{sup −/−} cells displayed greater migratory and invasive potential at baseline as well as after irradiation. Both the basal and radiation-induced migratory and invasive phenotypes in PTEN{sup −/−} cells required PDGF D expression. Interestingly, these differences were independent of apoptosis and cell cycle redistribution, as they showed no significant difference. Conclusions: We propose that PDGF D represents a potentially promising target for PCa treatment resistance in the absence of PTEN function, and warrants further laboratory evaluation and clinical study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Modeling Early Galaxies Using Radiation Hydrodynamics

This simulation uses a flux-limited diffusion solver to explore the radiation hydrodynamics of early galaxies, in particular, the ionizing radiation created by Population III stars. At the time of this rendering, the simulation has evolved to a redshift of 3.5. The simulation volume is 11.2 comoving megaparsecs, and has a uniform grid of 10243 cells, with over 1 billion dark matter and star particles. This animation shows a combined view of the baryon density, dark matter density, radiation energy and emissivity from this simulation. The multi-variate rendering is particularly useful because is shows both the baryonic matter ("normal") and dark matter, and the pressure and temperature variables are properties of only the baryonic matter. Visible in the gas density are "bubbles", or shells, created by the radiation feedback from young stars. Seeing the bubbles from feedback provides confirmation of the physics model implemented. Features such as these are difficult to identify algorithmically, but easily found when viewing the visualization. Simulation was performed on Kraken at the National Institute for Computational Sciences. Visualization was produced using resources of the Argonne Leadership Computing Facility at Argonne National Laboratory.

79 ASTRONOMY AND ASTROPHYSICS↗

New molecular components of high and low affinity iron import systems in Drosophila

The high abundance and molecular versatility of iron have led to its universal presence in biological systems, yet its absorption is exceptionally challenging. Animals and yeasts use divalent metal transporters to import iron, but yeasts also employ the multicopper oxidase Fet3p for high-affinity iron uptake when iron-starved. Using long-term iron depletion in Drosophila, we identified four components involved in iron absorption: Multicopper oxidase-4 (Mco4), a Fet3p ortholog, is essential for surviving iron starvation, whereas the cytochrome b561 enzymes Fire (Ferric Iron Reductase) and Fire-like, as well as cytochrome b5 protein Firewood, are required for iron absorption under normal conditions. This study reports the presence of a high-affinity iron uptake system in an animal, a cytochrome b5 electron donor for ferric iron reduction, and intestinal ferric reductases, and provides a valuable resource for further exploration of genes involved in iron homeostasis, transport, and absorption.

Iron↗

Viral Dynamic Models During COVID‐19: Are We Ready for the Next Pandemic?

Mathematical models have been used for about 30 years to improve our understanding of virus-host interaction, in particular during chronic infections. During the COVID-19 pandemic, these models have been used to provide insights into the natural history of acute SARS-CoV-2 infection, optimize antiviral treatment strategies, understand factors associated with transmission, and optimize surveillance systems. The impact of modeling has been accelerated by the availability of unprecedented multidimensional immune data from animal and human systems, which enhanced partnerships between experimentalists and theorists and led to exciting new modeling and statistical developments. In this mini review, we examine the lessons learned from the COVID-19 pandemic and discuss the main insights provided by mathematical models of viral dynamics at the different stages of the outbreak. Although we focus on respiratory infection, we also consider the new areas for development in anticipation of future acute infections from new or reemerging pathogens.

59 BASIC BIOLOGICAL SCIENCES↗

Mapping Nitrogen Pathways in Organic Manure through GCAM

As the world has become more and more globalized, a need for a comprehensive and extensive modelling system that maps out the vast majority of processes and items around the world and can display how interdependent they are. Furthermore, such a model should be able to predict future processes and values such that it can guide scientific thinking and policy. This is where the importance of GCAM becomes so apparent. GCAM, the Global Change Analysis Model, that incorporates many different fields and can predict such a wide variety of processes. As the model expands and encompasses more fields and goes into greater detail, there is a need for previously incorporated processes to be further fleshed out. My project is dedicated to creating the organic nitrogen fertilizer pathway, such that there are two nitrogen fertilizer pathways, synthetic and organic (manure). Previously, only synthetic fertilizer was included, with all organic fertilizer (manure) being omitted from the model. Developing the synthetic path is relatively easy, as the process for creating synthetic fertilizer is an industrial process that has been perfected over decades, and thus has a very precise input/output coefficient of nitrogen, but determining that same coefficient for organic manure is much harder, because, well, digestion is not an industrial process, especially considering the many different types of animals have different processes, and a good amount of the manure they produce won’t be applied to the soil. I obtained data from the UN’s FAO on manure nitrogen applied to soil, and filled in the gaps and created many different visualizations to help comprehend the data. These findings will foster a greater understanding of nitrogen flows, which is crucial to fields like industrial agriculture, polluting runoff, and nitrifying bacteria and archaea in the soil.

54 ENVIRONMENTAL SCIENCES↗

Comprehensive Evaluation of Agrivoltaics Research: Breadth, Depth, and Insights for Future Research

Agrivoltaics integrates agricultural production with solar energy generation to address challenges related to land use, food security, and renewable energy development. This study provides the most comprehensive evaluation to date of global agrivoltaic research, aiming to classify the literature, identify strengths and gaps, and guide future work. We systematically screened over 3000 English-language publications through 2023 for relevant agrivoltaic publications. A total of 670 studies were categorized in the InSPIRE Data Portal across five agrivoltaic activities and multiple hierarchical themes, including physical, biological, technological, social, and crosscutting domains. We found that research was concentrated on crop production, microclimate dynamics, and PV performance, with gaps in areas like human health, wildlife, policy, and standardized methodologies. Although the U.S. emphasizes animal grazing and habitat-based systems in practice, most U.S.-based studies focused disproportionately on crop production. The analysis revealed uneven geographic and topical representation and highlighted a lack of integrated, interdisciplinary approaches. This study concludes that while agrivoltaic research has grown rapidly, more coordinated efforts could support standardized data collection, address overlooked ecological and social impacts, and align research focus with real-world system implementation, ultimately improving the scalability and successful deployment of agrivoltaic systems.

14 SOLAR ENERGY↗

Use of Unmanned Aerial Systems for Post-closure Waste Site Maintenance and Surveillance - 20143

The P- and R-Area Reactor buildings, located at SRS near Aiken, SC, were in-situ decommissioned by grouting below-grade portions of the buildings and demolishing some above-grade structures to grade level. Other reactor building structures were left above-grade and sealed to prevent human or animal access. Because the above grade-structures are expected to continue in their present state for hundreds of years, the condition of the building roofs is critical to mitigate rainwater intrusion. For this reason, building roof areas were strengthened with high strength concrete to ensure the long-term integrity of the roof structure. Periodic inspections of the roof structures are required to ensure that the roofs are functioning properly and to identify damage areas. The traditional method of inspecting closed reactor buildings requires the use of a helicopter and photographer to generate photographs and videos for review. This method proved sufficient but lacked the resolution and clarity that is required for a thorough inspection of the building structure. Fortunately, the Savannah River National Laboratory (SRNL) has established a Small Unmanned Aircraft System (sUAS) program using commercially available and custom-built remote-controlled aircraft. EC and ACP contacted the SRNL program to evaluate whether the sUAS technology could be employed for periodic reactor building inspections. The sUAS can fly within a few meters of the reactor buildings and hover, allowing for a more thorough aerial inspection. The initial sUAS inspection of the P-Area Reactor building was completed in February 2018 and at the R-Area Reactor building in August 2018 and were successful in providing higher resolution photos and videos. The sUAS inspections also revealed that vegetation had begun to grow on the roofs that could potentially damage the structure integrity. SRNL partnered with Virginia Polytechnic Institute and State University to build a custom heavy lift sUAS that could be equipped with herbicides to remotely treat the vegetative growth. Herbicides were successfully applied to the R-Area Reactor building roof using the custom sUAS in September 2018. The use of unmanned aircraft systems at SRS to perform aerial inspections and herbicide treatment in otherwise inaccessible areas has proven to be an efficient and cost-effective technology that provides high value, increases knowledge of facility conditions, and provides for early detection of damage. Periodic inspections of the reactor building roofs using sUAS technology are performed safely, efficiently, and at a significant cost and schedule savings while reducing emissions, noise, and fossil fuel use. The use of sUAS equipment for building inspections and herbicide application at SRS is unique within the DOE complex. The goal of SRS is to apply this remote technology to other waste unit operations and maintenance activities in the future. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗