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

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

PyZebrascope: An Open-Source Platform for Brain-Wide Neural Activity Imaging in Zebrafish

Understanding how neurons interact across the brain to control animal behaviors is one of the central goals in neuroscience. Recent developments in fluorescent microscopy and genetically-encoded calcium indicators led to the establishment of whole-brain imaging methods in zebrafish, which record neural activity across a brain-wide volume with single-cell resolution. Pioneering studies of whole-brain imaging used custom light-sheet microscopes, and their operation relied on commercially developed and maintained software not available globally. Hence it has been challenging to disseminate and develop the technology in the research community. Here, we present PyZebrascope, an open-source Python platform designed for neural activity imaging in zebrafish using light-sheet microscopy. PyZebrascope has intuitive user interfaces and supports essential features for whole-brain imaging, such as two orthogonal excitation beams and eye damage prevention. Its camera module can handle image data throughput of up to 800 MB/s from camera acquisition to file writing while maintaining stable CPU and memory usage. Its modular architecture allows the inclusion of advanced algorithms for microscope control and image processing. As a proof of concept, we implemented a novel automatic algorithm for maximizing the image resolution in the brain by precisely aligning the excitation beams to the image focal plane. PyZebrascope enables whole-brain neural activity imaging in fish behaving in a virtual reality environment. Thus, PyZebrascope will help disseminate and develop light-sheet microscopy techniques in the neuroscience community and advance our understanding of whole-brain neural dynamics during animal behaviors.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease

We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers. We retrospectively included 150 participants, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [ 18 F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy. bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvAD bvFTD, area under the curve [AUC] range 0.85–0.91, all p < 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD>tAD), MRI anterior-DMN-ratios (bvAD<tAD), FDG anterior-DMN-ratios (bvAD<tAD, AUC range 0.71–0.84, all p < 0.05). Subtle frontoinsular hypometabolism and anterior DMN involvement may underlie the prominent behavioral phenotype in bvAD.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Controlled synthesis of highly-branched plasmonic gold nanoparticles through peptoid engineering

Inspired by peptide- and protein-controlled formation of hierarchical inorganic nanostructures in nature, herein we report the design of sequence-defined peptoids for biomimetic synthesis of flower-like gold nanosuperstruc-tures. We demonstrate that the peptoid-induced morphosyn-thesis of gold nanoflowers is sequence-dependent. By varying the hydrophobicity, number of carboxylate and amino groups, and side-chain positions of peptoids, we develop a rule of thumb for designing peptoids that yield gold nanoflowers. Through a combination of hyperspectral UV-Vis absorption micro-spectroscopy (H-UVVIS-AMS) and three-photon photoemission electron microscopy (TP-PEEM), we measured the plasmonic properties of individual nanoflowers. Whereas H-UVVIS-AMS experiments revealed well-defined plasmon resonances centered at ~528 nm, TP-PEEM measurements showed an unprecedented plasmonic enhancement as high as 105 for a single nanoflower. A com-bination of the unique plasmonic property and the high sta-bility endows the peptoid-engineered nanoflowers with po-tential applications in chemical and biological imaging. FY, YC, HJ and C-LC acknowledge support by the Materials Synthesis and Simulation Across Scales (MS3) Initiative, through the Laboratory Directed Research & Development (LDRD) fund at Pacific Northwest National Laboratory (PNNL). FY was also partially supported by fellowships from Shandong Provincial Education Association for International Exchanges. YG was supported by the US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. PZE acknowledges support from the Laboratory Directed Research and Development Program through a Linus Pauling Fellowship at PNNL. PNNL is multi-program national laboratory operated for the Department of Energy by Battelle under Contracts No. DE-AC05-76RL01830. The authors are most grateful to Alan Joly and Wayne Hess (PNNL) for their support with the PEEM measurements and several useful discussions.

Yan, Feng↗
DOE OSTI2020

An international laboratory comparison of dissolved organic matter composition by high resolution mass spectrometry: Are we getting the same answer?

Since the first detailed compositional analysis of dissolved organic matter (DOM) in 1995, high resolution mass spectrometry (HRMS) has become a vital tool for DOM characterization. While the upward trend in HRMS for molecular level analysis of DOM continues, so do the challenges of data comparison and interpretation between laboratories operating instruments of differing performance and user operating conditions. It is therefore essential that the community establishes whether data and trends can be compared robustly between research groups. To this end, 4 identically prepared DOM samples were each studied by 16 laboratories, representing 17 commercially-purchased instruments located across 8 countries, using positive- and negative-mode electrospray ionization (ESI) HRMS analysis. Despite the widely reported sensitivity of ESI experiments to sample matrix, preparation, ion source operation and instrument tuning parameters, the instruments used in this study showed relatively low variability between results for the same samples, particularly H/C and AI metrics. The variation in O/C and m/z metrics was relatively higher, although z-score graphs and %BCD demonstrated that the relative difference in general chemical composition between samples was the same for each instrument included in the study. As such, these metrics can be used for fingerprinting of DOM samples and as a benchmark for quality control in participating laboratories, with future strides in environmental science building upon these efforts.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

Unconventional Oil and Gas Energy Systems: An Unidentified Hotspot of Antimicrobial Resistance?

Biocides used in unconventional oil and gas (UOG) practices, such as hydraulic fracturing, control microbial growth. Unwanted microbial growth can cause gas souring, pipeline clogging, and microbial-induced corrosion of equipment and transportation pipes. However, optimizing biocide use has not been a priority. Moreover, biocide efficacy has been questioned because microbial surveys show an active microbial community in hydraulic fracturing produced and flowback water. Hydraulic fracturing produced and flowback water increases risks to surface aquifers and rivers/lakes near the UOG operations compared with conventional oil and gas operations. While some biocides and biocide degradation products have been highlighted as chemicals of concern because of their toxicity to humans and the environment, the selective antimicrobial pressure they cause has not been considered seriously. This perspective article aims to promote research to determine if antimicrobial pressure in these systems is cause for concern. UOG practices could potentially create antimicrobial resistance hotspots under-appreciated in the literature, practice, and regulation arena, hotspots that should not be ignored. The article is distinctive in discussing antimicrobial resistance risks associated with UOG biocides from a biological risk, not a chemical toxicology, perspective. We outline potential risks and highlight important knowledge gaps that need to be addressed to properly incorporate antimicrobial resistance emergence and selection into UOG environmental and health risk assessments.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Fast and accurate influenza forecasting in the United States with Inferno

Infectious disease forecasting is an emerging field and has the potential to improve public health through anticipatory resource allocation, situational awareness, and mitigation planning. By way of exploring and operationalizing disease forecasting, the U.S. Centers for Disease Control and Prevention (CDC) has hosted FluSight since the 2013/14 flu season, an annual flu forecasting challenge. Since FluSight’s onset, forecasters have developed and improved forecasting models in an effort to provide more timely, reliable, and accurate information about the likely progression of the outbreak. While improving the predictive performance of these forecasting models is often the primary objective, it is also important for a forecasting model to run quickly, facilitating further model development and improvement while providing flexibility when deployed in a real-time setting. In this vein I introduce Inferno, a fast and accurate flu forecasting model inspired by Dante, the top performing model in the 2018/19 FluSight challenge. When pseudoprospectively compared to all models that participated in FluSight 2018/19, Inferno would have placed 2nd in the national and regional challenge as well as the state challenge, behind only Dante. Inferno, however, runs in minutes and is trivially parallelizable, while Dante takes hours to run, representing a significant operational improvement with minimal impact to performance. Forecasting challenges like FluSight should continue to monitor and evaluate how they can be modified and expanded to incentivize the development of forecasting models that benefit public health.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2023

Genomes to ecosystem function: Targeting critical knowledge gaps in methanogenesis and translation to updated global biogeochemical models

Natural freshwater temperate wetland systems currently represent the largest natural source of atmospheric methane, but are relatively understudied using systems biology tools (e.g. meta-omics) compared to other high producing methane systems (e.g. peat, tropical, or reconstructed wetlands). Using field investigations at the NOAA operated sentinel site on Lake Erie, methane producing activities and responses to geochemical conditions will be determined along seasonal and spatial gradients (Objective 1). Here, a combination of high-throughput activity and gas measurements, combined with high-resolution systems biology and analytical methods, will provide in depth knowledge of the microbiological, chemical, and physical constraints on methane production in wetlands. Using laboratory microcosms, the formation of anoxic microsites and their capacity to facilitate methane production in wetland soils will be simulated (Objective 2). This objective will validate the findings from the field investigations, offering a more controlled environment for teasing out the role of different yet interrelated variables. Lastly, these field and laboratory data will be used for multi-scale, process-level evaluation of an ecosystem biogeochemical model that accommodates these newly identified processes and parameterizes representation of these processes along relevant environmental gradients (Objective 3).This research will identify multiple interacting geochemical, ecological, and metabolic constraints that are poorly understood, oversimplified, or missing in global biogeochemical methane models. This proposal targets the role of oxygen limitation on methane processes in soil domains, to improve reactive transport models of microbial carbon cycling across terrestrial-aquatic soils and generate data on nutrient cycling activities in Great Lake wetlands. This information could provide new insights into the microbial controllers of Lake Erie eutrophication.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Integration of pH Control into Chi.Bio Reactors and Demonstration with Small-Scale Enzymatic Poly(ethylene terephthalate) Hydrolysis

Small-scale bioreactors that are affordable and accessible would be of major benefit to the research community. In previous work, an open-source, automated bioreactor system was designed to operate up to the 30 mL scale with online optical monitoring, stirring, and temperature control, and this system, dubbed Chi.Bio, is now commercially available at a cost that is typically 1–2 orders of magnitude less than commercial bioreactors. In this work, we further expand the capabilities of the Chi.Bio system by enabling continuous pH monitoring and control through hardware and software modifications. For hardware modifications, we sourced low-cost, commercial pH circuits and made straightforward modifications to the Chi.Bio head plate to enable continuous pH monitoring. For software integration, we introduced closed-loop feedback control of the pH measured inside the Chi.Bio reactors and integrated a pH-control module into the existing Chi.Bio user interface. We demonstrated the utility of pH control through the small-scale depolymerization of the synthetic polyester, poly(ethylene terephthalate) (PET), using a benchmark cutinase enzyme, and compared this to 250 mL bioreactor hydrolysis reactions. The results in terms of PET conversion and rate, measured both by base addition and product release profiles, are statistically equivalent, with the Chi.Bio system allowing for a 20-fold reduction of purified enzyme required relative to the 250 mL bioreactor setup. Through inexpensive modifications, the ability to conduct pH control in Chi.Bio reactors widens the potential slate of biochemical reactions and biological cultivations for study in this system, and may also be adapted for use in other bioreactor platforms.

09 BIOMASS FUELS↗
DOE OSTI2021

Microbial diversity analysis of two full-scale seawater desalination treatment trains provides insights into detrimental biofilm formation

Detrimental biofilms on RO membranes remain a crucial challenge for seawater desalination. Comparative analysis of 16S rRNA gene amplicon sequencing data revealed differences and commonalities of biofilm communities associated with unit operations in the two largest seawater desalination facilities in the U.S., the Claude "Bud" Lewis Carlsbad Desalination Plant and the Tampa Bay Seater Desalination facility. At both plants, feedwater collected at a single time point was a poor indicator of the RO membrane communities, which showed far greater taxa diversity. The analysis of prefilter cartridges from the Carlsbad plant revealed similarly high taxon diversity as the RO module biofilms, with relevant differences. Algal sequences were enriched on the prefilter cartridges as were sequences representing Bdellovibrionota, which are predatory bacteria. Sequences representing opportunistic Gammaproteobacteria (i.e., Shewanella, Woesia) were present in significantly higher relative abundance on the RO membranes than in the prefilter cartridges, suggesting growth of certain taxa in the RO modules. Untargeted metabolomics distinguished intra- and inter-desalination plant biofilm samples, highlighting the potential value of this tool for biofilm monitoring. These findings underscore the value of omics tools for effective microbial monitoring, to understand biofouling dynamics within RO desalination plants, and to provide insight for the development of ecologically-informed biofilm control measures.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Evaluation of sterol-o-acyl transferase 1 and cholesterol ester levels in plasma, peritoneal fluid and tumor tissue of patients with endometrial cancer: A pilot study

Endometrial cancer (EC) is the most prevalent gynecological malignancy. Abnormal accumulation of sterol-O-acyl transferase 1 (SOAT1) and SOAT1-mediated cholesterol ester (CE) contributes to cancer progression in various malignancies, including ovarian cancer. Therefore, it was hypothesized that similar molecular changes may occur in EC. The present study aimed to evaluate the diagnostic and/or prognostic potential of SOAT1 and CE in EC by: i) Determining SOAT1 and CE levels in plasma, peritoneal fluid and endometrial tissue from patients with EC and control subjects; ii) performing receiver operating characteristic curve analysis to determine diagnostic performance; iii) comparing SOAT1 and CE expression to that of the tumor proliferation marker Ki67; and iv) assessing the association between SOAT1 expression and survival. Enzyme-linked immunosorbent assay was used to determine the levels of SOAT1 protein in tissue, plasma and peritoneal fluid. The mRNA and protein expression levels of SOAT1 and Ki67 in tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively. CE levels were determined colorimetrically in plasma and peritoneal fluid. SOAT1-associated survival data from the cBioPortal cancer genomics database were used to assess prognostic relevance. The results revealed that SOAT1 and CE levels were significantly elevated in tumor tissue and peritoneal fluid samples collected from the EC group. By contrast, the plasma levels of SOAT1 and CE in the EC and control groups were similar. Significant positive associations between CE and SOAT1, SOAT1/CE and Ki67, and SOAT1/CE and poor overall survival in patients with EC suggested that SOAT1/CE may be associated with malignancy, aggressiveness and poor prognosis. In conclusion, SOAT1 and CE may serve as potential biomarkers for prognosis and target-specific treatment of EC.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Detection of Head and Neck Cancer Based on Longitudinal Changes in Serum Protein Abundance

Head and Neck Squamous Cell Carcinoma (HNSCC) is significantly represented in the military population with substantial impact on military operations. Two-thirds of new HNSCC cases are first diagnosed at advanced stage III or IV with lymph node metastases. Thus, there is an urgent need of biomarkers for early detection and risk stratification. Archived serum samples from the Department of Defense Serum Repository provide a unique resource for longitudinal studies of HNSCC in the military and the identification of early detection biomarkers. Methods: We identified 175 patients diagnosed with HNSCC with 175 matched healthy controls and retrieved a total of 978 serum samples drawn at the time of diagnosis, 2 and 4 years prior to diagnosis, and 2 years after diagnosis. Following immunoaffinity depletion, serum samples were analyzed by targeted proteomics assays for multiplexed quantification of a panel of 146 candidate protein biomarkers from the curated literature. Results: We derived a 13-protein signature that distinguishes case versus controls based on longitudinal changes in serum protein concentration. The abundances of each of the 13 proteins remain constant over time in control subjects. The area under the curve for the derived random forest classifier was 0.90. Conclusions: This 13-protein classifier is highly promising for detection of HNSCC prior to overt symptoms. Impact: Use of longitudinal samples has significant potential to identify biomarkers for detection and risk stratification.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

CICART Center For Integrated Computation And Analysis Of Reconnection And Turbulence

CICART is a partnership between the University of New Hampshire (UNH) and Dartmouth College. CICART addresses two important science needs of the DoE: the basic understanding of magnetic reconnection and turbulence that strongly impacts the performance of fusion plasmas, and the development of new mathematical and computational tools that enable the modeling and control of these phenomena. The principal participants of CICART constitute an interdisciplinary group, drawn from the communities of applied mathematics, astrophysics, computational physics, fluid dynamics, and fusion physics. It is a main premise of CICART that fundamental aspects of magnetic reconnection and turbulence in fusion devices, smaller-scale laboratory experiments, and space and astrophysical plasmas can be viewed from a common perspective, and that progress in understanding in any of these interconnected fields is likely to lead to progress in others. The establishment of CICART has strongly impacted the education and research mission of a new Program in Integrated Applied Mathematics in the College of Engineering and Applied Sciences at UNH by enabling the recruitment of a tenure-track faculty member, supported equally by UNH and CICART, and the establishment of an IBM-UNH Computing Alliance. The proposed areas of research in magnetic reconnection and turbulence in astrophysical, space, and laboratory plasmas include the following topics: (A) Reconnection and secondary instabilities in large high-Lundquist-number plasmas, (B) Particle acceleration in the presence of multiple magnetic islands, (C) Gyrokinetic reconnection: comparison with fluid and particle-in-cell models, (D) Imbalanced turbulence, (E) Ion heating, and (F) Turbulence in laboratory (including fusion-relevant) experiments. These theoretical studies make active use of three high-performance computer simulation codes: (1) The Magnetic Reconnection Code, based on extended two-fluid (or Hall MHD) equations, in an Adaptive Mesh Refinement (AMR) framework, (2) the Particle Simulation Code, a fully electromagnetic 3D Particle-In-Cell (PIC) code that includes a collision operator, and (3) GS2, an Eulerian, electromagnetic, kinetic code that is widely used in the fusion program, and simulates the nonlinear gyrokinetic equations, together with a self-consistent set of Maxwell’s equations.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2024

The military gear microbiome: risk factors surrounding the warfighter

ABSTRACT Combat extremity wounds are highly susceptible to contamination from surrounding environmental material. This bioburden could be partially transferred from materials in immediate proximity to the wound, including fragments of the uniform and gear. However, the assessment of the microbial bioburden present on military gear during operational conditions of deployment or training is relatively unexplored. Opportunistic pathogens that can survive on gear represent risk factors for infection following injury, especially following combat blasts, where fibers and other materials are embedded in wounded tissue. We utilized 16S rRNA sequencing to assess the microbiome composition of different military gear types (boot, trouser, coat, and canteen) from two operational environments (training in Hawai’i and deployed in Indonesia) across time (days 0 and 14). We found that microbiome diversity, stability, and composition were dependent on gear type, training location, and sampling timepoint. At day 14, species diversity was significantly higher in Hawai’i samples compared to Indonesia samples for boot, coat, and trouser swabs. In addition, we observed the presence of potential microbial risk factors, as opportunistic pathogenic species, such as Acinetobacter , Pseudomonas, and Staphylococcus , were found to be present in all sample types and in both study sites. These study outcomes will be used to guide the design of antimicrobial materials and uniforms and for infection control efforts following combat blasts and other injuries, thereby improving treatment guidance during military training and deployment. IMPORTANCE Combat extremity wounds are vulnerable to contamination from environments of proximity to the warfighter, leading to potential detrimental outcomes such as infection and delayed wound healing. Therefore, microbial surveillance of such environments is necessary to aid the advancement of military safety and preparedness through clinical diagnostics, treatment protocols, and uniform material design.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

The Design and Implementation of a Secure Datastore Based on Ethereum Smart Contract

In this paper, we present a secure datastore based on an Ethereum smart contract. Our research is guided by three research questions. First, we will explore to what extend a smart-contract-based datastore should resemble a traditional database system. Second, we will investigate how to store the data in a smart-contract-based datastore for maximum flexibility while minimizing the gas consumption. Third, we seek answers regarding whether or not a smart-contract-based datastore should incorporate complex processing such as data encryption and data analytic algorithms. The proposed smart-contract-based datastore aims to strike a good balance between several constraints: (1) smart contracts are publicly visible, which may create a confidentiality concern for the data stored in the datastore; (2) unlike traditional database systems, the Ethereum smart contract programming language (i.e., Solidity) offers very limited data structures for data management; (3) all operations that mutate the blockchain state would incur financial costs and the developers for smart contracts must make sure sufficient gas is provisioned for every smart contract call, and ideally, the gas consumption should be minimized. Our investigation shows that although it is essential for a smart-contract-based datastore to offer some basic data query functionality, it is impractical to offer query flexibility that resembles that of a traditional database system. Furthermore, we propose that data should be structured as tag-value pairs, where the tag serves as a non-unique key that describes the nature of the value. We also conclude that complex processing should not be allowed in the smart contract due to the financial burden and security concerns. The tag-based secure datastore designed this way also defines its applicative perimeter, i.e., only applications that align with our strategy would find the proposed datastore a good fit. Those that would rather incur higher financial cost for more data query flexibility and/or less user burden on data pre- and post-processing would find the proposed database too restrictive.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2023

Viral infections likely mediate microbial controls on ecosystem responses to global warming

Abstract Climate change is affecting how energy and matter flow through ecosystems, thereby altering global carbon and nutrient cycles. Microorganisms play a fundamental role in carbon and nutrient cycling and are thus an integral link between ecosystems and climate. Here, we highlight a major black box hindering our ability to anticipate ecosystem climate responses: viral infections within complex microbial food webs. We show how understanding and predicting ecosystem responses to warming could be challenging—if not impossible—without accounting for the direct and indirect effects of viral infections on different microbes (bacteria, archaea, fungi, protists) that together perform diverse ecosystem functions. Importantly, understanding how rising temperatures associated with climate change influence viruses and virus-host dynamics is crucial to this task, yet is severely understudied. In this perspective, we (i) synthesize existing knowledge about virus-microbe-temperature interactions and (ii) identify important gaps to guide future investigations regarding how climate change might alter microbial food web effects on ecosystem functioning. To provide real-world context, we consider how these processes may operate in peatlands—globally significant carbon sinks that are threatened by climate change. We stress that understanding how warming affects biogeochemical cycles in any ecosystem hinges on disentangling complex interactions and temperature responses within microbial food webs.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Unlocking the magic in mycelium: Using synthetic biology to optimize filamentous fungi for biomanufacturing and sustainability

Filamentous fungi drive carbon and nutrient cycling across our global ecosystems, through its interactions with growing and decaying flora and their constituent microbiomes. The remarkable metabolic diversity, secretion ability, and fiber-like mycelial structure that have evolved in filamentous fungi have been increasingly exploited in commercial operations. The industrial potential of mycelial fermentation ranges from the discovery and bioproduction of enzymes and bioactive compounds, the decarbonization of food and material production, to environmental remediation and enhanced agricultural production. Despite its fundamental impact in ecology and biotechnology, molds and mushrooms have not, to-date, significantly intersected with synthetic biology in ways comparable to other industrial cell factories (e.g. Escherichia coli,Saccharomyces cerevisiae, and Komagataella phaffii). In this review, we summarize a suite of synthetic biology and computational tools for the mining, engineering and optimization of filamentous fungi as a bioproduction chassis. A combination of methods across genetic engineering, mutagenesis, experimental evolution, and computational modeling can be used to address strain development bottlenecks in established and emerging industries. These include slow mycelium growth rate, low production yields, non-optimal growth in alternative feedstocks, and difficulties in downstream purification. In the scope of biomanufacturing, we then detail previous efforts in improving key bottlenecks by targeting protein processing and secretion pathways, hyphae morphogenesis, and transcriptional control. Bringing synthetic biology practices into the hidden world of molds and mushrooms will serve to expand the limited panel of host organisms that allow for commercially-feasible and environmentally-sustainable bioproduction of enzymes, chemicals, therapeutics, foods, and materials of the future.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome

Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)–associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology. To validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS. This multicohort study with 6, 12, and 24-month follow-up recruited adult participants between January 2011 and September 2020 from 8 tertiary care centers in the 4RT Neuroimaging Initiative (4RTNI). All participants with CBS (n = 113), PSP-RS (n = 121), and nfvPPA (n = 39) were included; other diagnoses were excluded due to rarity (n = 29). Individuals with PET-confirmed AD (n = 54) and PET-negative cognitively normal control individuals (n = 59) were evaluated at University of California San Francisco. Operators were blinded to the cohort. Plasma p-tau217, measured by Meso Scale Discovery electrochemiluminescence, was validated against amyloid-β (Aβ) and flortaucipir (FTP) PET. Imaging analyses used voxel-based morphometry and bayesian linear mixed-effects modeling. Clinical biomarker associations were evaluated using longitudinal mixed-effect modeling. Of 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years. Plasma p-tau217 was elevated in patients with CBS with positive Aβ PET results (mean [SD], 0.57 [0.43] pg/mL) or FTP PET (mean [SD], 0.75 [0.30] pg/mL) to concentrations comparable to control individuals with AD (mean [SD], 0.72 [0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control. Within CBS, p-tau217 had excellent diagnostic performance with area under the receiver operating characteristic curve (AUC) for Aβ PET of 0.87 (95% CI, 0.76-0.98; P < .001) and FTP PET of 0.93 (95% CI, 0.83-1.00; P < .001). At baseline, individuals with CBS-AD (n = 12), defined by a PET-validated plasma p-tau217 cutoff 0.25 pg/mL or greater, had increased temporoparietal atrophy at baseline compared to individuals with CBS-FTLD (n = 39), whereas longitudinally, individuals with CBS-FTLD had faster brainstem atrophy rates. Individuals with CBS-FTLD also progressed more rapidly on a modified version of the PSP Rating Scale than those with CBS-AD (mean [SD], 3.5 [0.5] vs 0.8 [0.8] points/year; P = .005). In this cohort study, plasma p-tau217 had excellent diagnostic performance for identifying Aβ or FTP PET positivity within CBS with likely underlying AD pathology. Plasma P-tau217 may be a useful and inexpensive biomarker to select patients for CBS clinical trials.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Evaluating Movement Patterns of the Rattlesnake Hills Elk Herd on Hanford for Calendar Years 2019-2024

Biologists first documented elk on the Hanford Site in 1972; since then, the elk herd known as the Rattlesnake Hills Elk Herd (RHEH) has grown substantially (PNNL-13331, Population Characteristics and Seasonal Movement Patterns of the Rattlesnake Hills Elk Herd: Status Report 2000). Through the 1990s, the core range of the RHEH was focused on the portion of the Hanford Reach National Monument known as the Fitzner-Eberhardt Arid Lands Ecology (ALE) Reserve. More recently, larger numbers of elk have been occupying the U.S. Department of Energy (DOE), Hanford Field Office (HFO), formerly the DOE, Richland Operations Office managed portion- of the Hanford Site, known as central Hanford (Figure 1-1). This began with bachelor groups of bulls occupying the site intermittently, and the herd has grown to resident herds, including bulls, cows, and calves. The Washington Department of Fish and Wildlife (WDFW) established a target herd size for the RHEH of less than 350 animals to minimize damages on adjacent private agricultural lands (Washington State Elk Herd Plan–Yakima Elk Herd [WDFW 2002]). Attempts to control the RHEH population through hunting on private lands and a relocation effort during 2000 have failed to limit growth of the population toward the WDFW target, and the herd exceeds 1,600 according to recent counts (PNNL-13331; DOE/RL- 2023-20, Hanford Annual Site Environmental Report for Calendar Year 2022). Although elk are present on central Hanford year-round, they continue to move between areas offsite, the ALE Reserve, and central Hanford throughout the year, and it is these movements that result in many of the elk-vehicle collisions (EVC) that occur along Hanford Site roads and on the Washington State highways bordering the site. In addition, changes in management strategies on the ALE Reserve, including recent and potential future tribal elk hunts, may alter herd behavior and result in additional animals transiting onto and off central Hanford.

54 ENVIRONMENTAL SCIENCES↗