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DOE OSTI2025

Competition between roughness and strength for scale-dependent surfaces

Rocks famously have scale-dependent strength, yet the actual dependence is notoriously hard to measure or incorporate into any theoretical framework. Natural rough surfaces present an opportunity to solve the problem. Surfaces sliding in shear evolve as protrusions collide. These asperities can deform or break, thus creating a new surface shape. In particular, natural surfaces have roughness at all scales as well as scale-dependent strength. Based on a scaling analysis, we have previously suggested that the scale-dependent aspect ratio of steady-state surfaces should be proportional to the scale-dependent shear strain at yield. If true, scale-dependent strength could easily be inferred from natural surfaces. Thus, moving beyond the scaling argument to a rigorous treatment of scale-dependent strength for multiscale rough surfaces in shear is important. However, analytic frameworks for analyzing multiscale problems are challenging, as conventional continuum mechanics typically involves a single value for a material property across scales. Here, in this work, we build on the formalism of Persson (2001) that presents a method to compute contact area for rough surfaces with a prescribed topographic spectrum using a stochastic differential equation. The Persson formalism allows for plastic yield under normal loading of otherwise elastic materials and leaves open the possibility of scale-dependent yield stress. In this study, we pursue this route to develop a theory and numerical results for the yielding of a rough, elastoplastic surface with scale-dependent yield stress. Here, we examine surfaces for which the power spectrum of the topography 𝐶 and yield stress 𝑌 follow power laws as a function of scale 𝜆, such that 𝐶∼𝜆 −𝑚 and 𝑌∼𝜆 −𝑛 , respectively. In this formal treatment of the problem, we focus on surfaces in contact and the resulting yield and do not impose shear. Numerical solutions show that the deviation from the elastic scaling solution is bounded as expected by the prior 1D heuristic scaling argument that anticipates the Hurst exponent as 1−𝑛. We also show that the plasticity is expected to erode the contacts if 𝑚 is lower than 𝑛−3, which corresponds to a Hurst exponent lower than 1−𝑛/2. This result is rigorously sound for 2D, i.e., realistic surfaces, and quantitatively different than the prior scaling argument. The theory now permits a correspondingly quantitative approach to interpreting natural surfaces.

elasticity↗

DOE OSTI2024

Improved Creep Testing Approach for Bentonite EBS

In the United States, the nuclear reactor contributes 18.7 percent of the nation’s total electricity generation and produces a significant amount of spent nuclear fuel (SNF) and high-level waste. Because SNF is being stored for longer periods than initially envisioned, the U.S. Department of Energy Office of Nuclear Energy, Office of Spent Fuel and Waste Science and Technology is assessing the technical performance of the SNF storage systems after extended durations. The concept of a sustainable geologic repository for SNF disposal relies heavily on the safety provided by multiple barriers, such as repository host rock, overlying rock formation, and human-made engineered barrier systems (EBS). One of the major components of EBS is bentonite-based buffer materials that isolate the nuclear-waste canisters from the host rock and fill the void left in the horizontally drilled boreholes. The resaturated bentonite has a swelling characteristic, which is useful for self-sealing the microcracks in the host rock and supporting the canister’s heavy weight. However, factors such as nonuniformity in the saturation, swelling pressure of bentonite, and the high temperature at the canister-bentonite interface may lead to instability of the waste canister inside the borehole. Therefore, evaluating the long-term deformation of bentonite-based material is necessary. RESPEC Company, LLC recently completed a preliminary study for the U.S. Department of Energy (DE SC0022804) that is attempting to understand the time-dependent deformation in the consolidated sand/bentonite (SB) specimens through triaxial creep experiments and improve the understanding of EBS performance under anticipated repository conditions. The project included developing a standard testing procedure for preparing the consolidated core specimen from a mixture of sand and bentonite in a 50:50 ratio by weight, fabricating a new pressure vessel in-house, modifying existing creep equipment to perform triaxial creep experiments on consolidated SB specimens, and performing six long-term triaxial creep experiments under low-deviatoric stress at two different temperature conditions, which is representative of hypothetical conditions that might be encountered in a geologic repository within a reasonable rate of success in completing creep experiments. The consolidated SB specimen was prepared using the novel specimen preparation procedure and had physical characteristics (e.g., moisture content and bulk density) reasonably comparable with the properties of bentonite-based buffer, which is proposed to be used in the EBS in the Swedish KBS-3H design and the Swiss design of SNF disposal in the horizontal drifts. The newly fabricated pressure vessel could withstand the confining pressure of up to 15 megapascals (MPa) while maintaining the test temperature of up to 90 degrees Celsius (°C) for long-term creep experiments. The preliminary results from the triaxial creep experiments suggested that the consolidated SB specimen may experience time-dependent deformation at a low-deviatoric stress state and room temperature condition. Based on the deformation recorded in the SB specimen from axial and radial linear variable differential transformers (LVDTs) and physical characteristic changes, it is apparent that the time-dependent deformation is a combination of consolidation and creep, which is influenced by the level of deviatoric stresses and temperature. The systematic creep testing of bentonite-based specimens helped develop a standard testing procedure applicable for analyzing the similar characteristics of shale or clay-like materials in different geologic conditions outside repository science, including in civil engineering and infrastructure projects, underground and open pit mining, and deep drilling.

58 GEOSCIENCES↗

DOE OSTI2021

Differential structure and functional gene response to geochemistry associated with the suspended and attached shallow aquifer microbiomes from the Illinois Basin, IL

Despite the clear ecological significance of the microbiomes inhabiting groundwater and connected ecosystems, our current understanding of their habitats, functionality, and the ecological processes controlling their assembly have been limited. In this study, an efficient pipeline combining geochemistry, high-throughput Fluidigm TM functional gene amplification and sequencing was developed to analyze the suspended and attached microbial communities inhabiting five groundwater monitoring wells in the Illinois Basin, USA. The dominant taxa in the suspended and the attached microbial communities exhibited significantly different spatial and temporal changes in both alpha- and beta-diversity. Further analyses of representative functional genes affiliated with N 2 fixation (nifH), methane oxidation (pmoA), and sulfate reduction (dsrB, and aprA), suggested functional redundancy within the shallow aquifer microbiomes. While more diversified functional gene taxa were observed for the suspended microbial communities than the attached ones except for pmoA, different levels of changes over time and space were observed between these functional genes. Notably, deterministic and stochastic ecological processes shaped the assembly of microbial communities and functional gene reservoirs differently. While homogenous selection was the prevailing process controlling assembly of microbial communities, the neutral processes (e.g., dispersal limitation, drift and others) were more important for the functional genes. The results suggest complex and changing shallow aquifer microbiomes, whose functionality and assembly vary even between the spatially proximate habitats and fractions. As a result, this research underscored the importance to include all the interface components for a more holistic understanding of the biogeochemical processes in aquifer ecosystems, which is also instructive for practical applications.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2022

Analyzing Data Privacy for Edge Systems

Internet-of-Things (IoT)-based streaming applications are all around us. Currently, we are transitioning from IoT processing being performed on the cloud to the edge. While moving to the edge provides significant networking efficiency benefits, IoT edge computing creates significant data privacy concerns. We propose a methodology that can successfully privacy protect the continual data streams generated by sensors on the edge device. We implement local differential privacy on streaming data and incorporate Bayesian inference and Gaussian process to evaluate the privacy policy. We demonstrate our methodology on a real-world smart meter testbed and identify the optimal privacy protection settings.

Kotevska, Olivera↗

DOE OSTI2022

Microbial Tracking-2, a metagenomics analysis of bacteria and fungi onboard the International Space Station

The International Space Station (ISS) is a unique and complex built environment with the ISS surface microbiome originating from crew and cargo or from life support recirculation in an almost entirely closed system. The Microbial Tracking 1 (MT-1) project was the first ISS environmental surface study to report on the metagenome profiles without using whole-genome amplification. The study surveyed the microbial communities from eight surfaces over a 14-month period. The Microbial Tracking 2 (MT-2) project aimed to continue the work of MT-1, sampling an additional four flights from the same locations, over another 14 months. Eight surfaces across the ISS were sampled with sterile wipes and processed upon return to Earth. DNA extracted from the processed samples (and controls) were treated with propidium monoazide (PMA) to detect intact/viable cells or left untreated and to detect the total DNA population (free DNA/compromised cells/intact cells/viable cells). DNA extracted from PMA-treated and untreated samples were analyzed using shotgun metagenomics. Samples were cultured for bacteria and fungi to supplement the above results. Staphylococcus sp. and Malassezia sp. were the most represented bacterial and fungal species, respectively, on the ISS. Overall, the ISS surface microbiome was dominated by organisms associated with the human skin. Multi-dimensional scaling and differential abundance analysis showed significant temporal changes in the microbial population but no spatial differences. The ISS antimicrobial resistance gene profiles were however more stable over time, with no differences over the 5-year span of the MT-1 and MT-2 studies. Twenty-nine antimicrobial resistance genes were detected across all samples, with macrolide/lincosamide/streptogramin resistance being the most widespread. Metagenomic assembled genomes were reconstructed from the dataset, resulting in 82 MAGs. Functional assessment of the collective MAGs showed a propensity for amino acid utilization over carbohydrate metabolism. Co-occurrence analyses showed strong associations between bacterial and fungal genera. Culture analysis showed the microbial load to be on average 3.0 × 10 5 cfu/m 2 . Utilizing various metagenomics analyses and culture methods, we provided a comprehensive analysis of the ISS surface microbiome, showing microbial burden, bacterial and fungal species prevalence, changes in the microbiome, and resistome over time and space, as well as the functional capabilities and microbial interactions of this unique built microbiome. Data from this study may help to inform policies for future space missions to ensure an ISS surface microbiome that promotes astronaut health and spacecraft integrity.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2026

Screening and qualification methodology for SiC end plug processing methods

Deployment of SiC-ceramic-based fuel cladding for light water reactors requires a hermetic end plug–to–cladding joint that can withstand neutron irradiation during normal operation and maintain integrity during design-basis accidents. Reactor experiments have shown that some SiC composite tubes with SiC end plugs can retain hermeticity after irradiation. However, achieving consistent joint performance under irradiation remains a key challenge. Resolving this issue is essential to enable integral irradiation testing and to demonstrate fuel integrity under commercial-reactor irradiation conditions. This report aims to: (1) provide guidance for designing radiation-tolerant end plug joints for SiC cladding; (2) demonstrate experimental methods to detect processing defects that are unstable under neutron irradiation at light-water-reactor-relevant temperatures and doses; and (3) outline a step-by-step approach for designing and conducting reactor experiments to screen joining methods. The resulting data will be used to improve joint processing and to define critical defect types and sizes that must be detected and eliminated through non-destructive evaluation for quality assurance. Based on prior irradiation experiments at the High Flux Isotope Reactor, differential swelling among the cladding, bonding layer, and end plug was identified as an underlying mechanism for irradiation-induced joint degradation. Accordingly, this effect must be considered in the design of radiation-tolerant joining techniques. In this work, miniature SiC end plug joint specimens irradiated during the previous project were analyzed using X-ray computed tomography to characterize the joint microstructure. Digital volume correlation of the tomography data quantified radiation-induced microstructural changes and enabled evaluation of defect-related risks. Finally, ongoing neutron irradiation efforts using larger specimen volumes are presented. These efforts aim to statistically assess joint performance and to build a microstructure–performance (e.g., leak-tightness) dataset to inform processing improvements and quality control.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

DOE OSTI2021

A KBase Case Study on Genome-wide Transcriptomics and Plant Primary Metabolism in Sorghum

A better understanding of the genetic and metabolic mechanisms that confer stress resistance and tolerance in plants is key to engineering new crops through advanced breeding technologies. This requires a systems biology approach that builds on a genome-wide understanding of the regulation of gene expression, plant metabolism, physiology and growth. In this study, we examine the response to drought stress in Sorghum, as we leverage the tools for transcriptomics and plant metabolic modeling we have implemented at the U.S. Department of Energy Systems Biology Knowledgebase (KBase). KBase enables researchers worldwide to collaborate and advance research by allowing them to upload private or public data into the KBase Narrative Interface, empowering them to analyze this data using a rich, extensible array of computational and data-analytics tools, and allows them to securely share scientific workflows and conclusions. We demonstrate how to use the current RNA-seq tools in KBase, applicable to both plants and microbes, to assemble and quantify long transcripts and identify differentially expressed genes effectively. More specifically, we demonstrate the utility of the platform by identifying key genes that are differentially expressed during drought-stress in Sorghum bicolor, which is an important sustainable production crop plant. We then show how to use KBase tools to predict the membership of genes in metabolic pathways and examine expression data in the context of metabolic subsystems. We demonstrate the power of the platform by making the data analysis and interpretation available to the biologists in the reproducible, re-usable, point-and-click format of a KBase Narrative thus promoting FAIR (Findable, Accessible, Interoperable and Reusable) guiding principles for scientific data management and stewardship.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Image-based time series analysis to establish differential disease progression for two Fusarium head blight pathogens in oat spikelets with variable resistance

Oat-based value-added products have increased their value as healthy foodstuff. Fusarium head blight (FHB) infections and the mycotoxins accumulated to the oat seeds, however, pose a challenge to oat production. The FHB infections are predicted to become more prevalent in the future changing climates and under more limited use of fungicides. Both these factors increase the pressure for breeding new resistant cultivars. Until now, however, genetic links in oats against FHB infection have been difficult to identify. Therefore, there is a great need for more effective breeding efforts, including improved phenotyping methods allowing time series analysis and the identification of molecular markers during disease progression. To these ends, dissected spikelets of several oat genotypes with different resistance profiles were studied by image-based methods during disease progression by Fusarium culmorum or F. langsethiae species. The chlorophyll fluorescence of each pixel in the spikelets was recorded after inoculation by the two Fusarium spp., and the progression of the infections was analyzed by calculating the mean maximum quantum yield of PSII (F v /F m ) values for each spikelet. The recorded values were (i) the change in the photosynthetically active area of the spikelet as percentage of its initial size, and (ii) the mean of F v /F m values of all fluorescent pixels per spikelet post inoculation, both indicative of the progression of the FHB disease. The disease progression was successfully monitored, and different stages of the infection could be defined along the time series. The data also confirmed the differential rate of disease progression by the two FHB causal agents. In addition, oat varieties with variable responses to the infections were indicated.

oats↗

DOE OSTI2022

Secure Collaborative Environment for Seamless Sharing of Scientific Knowledge

In a secure collaborative environment, tera-bytes of data generated from powerful scientific instruments are used to train secure machine learning (ML) models on exascale computing systems, which are then securely shared with internal or external collaborators as cloud-based services. Devising such a secure platform is necessary for seamless scientific knowledge sharing without compromising individual, or institute-level, intellectual property and privacy details. By enabling new computing opportunities with sensitive data, we envision a secure collaborative environment that will play a significant role in accelerating scientific discovery. Several recent technological advancements have made it possible to realize these capabilities. In this paper, we present our efforts at ORNL toward developing a secure computation platform. We present a use case where scientific data generated from complex instruments, like those at the Spallation Neutron Source (SNS), are used to train a differential privacy enabled deep learning (DL) network on Summit, which is then hosted as a secure multi-party computation (MPC) service on ORNL’s Compute and Data Environment for Science (CADES) cloud computing platform for third-party inference. In this feasibility study, we discuss the challenges involved, elaborate on leveraged technologies, analyze relevant performance results and present the future vision of our work to establish secure collaboration capabilities within and outside of ORNL.

Yoginath, Srikanth↗

DOE OSTI2020

Genomic diversifications of five Gossypium allopolyploid species and their impact on cotton improvement

Abstract Polyploidy is an evolutionary innovation for many animals and all flowering plants, but its impact on selection and domestication remains elusive. Here we analyze genome evolution and diversification for all five allopolyploid cotton species, including economically important Upland and Pima cottons. Although these polyploid genomes are conserved in gene content and synteny, they have diversified by subgenomic transposon exchanges that equilibrate genome size, evolutionary rate heterogeneities and positive selection between homoeologs within and among lineages. These differential evolutionary trajectories are accompanied by gene-family diversification and homoeolog expression divergence among polyploid lineages. Selection and domestication drive parallel gene expression similarities in fibers of two cultivated cottons, involving coexpression networks and N 6 -methyladenosine RNA modifications. Furthermore, polyploidy induces recombination suppression, which correlates with altered epigenetic landscapes and can be overcome by wild introgression. These genomic insights will empower efforts to manipulate genetic recombination and modify epigenetic landscapes and target genes for crop improvement.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

The need for multicomponent dust attenuation in modeling nebular emission: Constraints from SDSS-IV MaNGA

A fundamental assumption adopted in nearly every extragalactic study that analyzes optical emission lines is that the attenuation of different emission lines can be described by a single attenuation curve, scaled by a single reddening parameter, usually E(B - V). Here we show this assumption fails in many cases with important implications for derived results. We developed a new method to measure the differential nebular attenuation among three kinds of transitions: the Balmer lines of hydrogen; high-ionization transitions (> 13.6 eV) including [Ne III], [O III], and [S III]; and low-ionization transitions (≲13.6 eV) including [O II], [N II], and [S II]. This method bins the observed data in a multidimensional space spanned by attenuation-insensitive line ratios. Within each small bin, the variations in nebular parameters such as the metallicity and ionization parameter are negligible compared to the variation in the nebular attenuation. This allowed us to measure the nebular attenuation using both forbidden lines and Balmer lines. We applied this method to a sample of 2.4 million star-forming (SF) spaxels from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey. We found that the attenuation of high ionization lines and Balmer lines can be well described by a single Fitzpatrick (1999, PASP, 111, 63) extinction curve with R V = 3.1. However, no single attenuation curve can simultaneously account for these transitions and the derived attenuation of low-ionization lines. This strongly suggests that different lines have different effective attenuations, likely because spectroscopy at hundreds of parsecs to kiloparsecs of resolution mixes multiple physical regions that exhibit different intrinsic line ratios and different levels of attenuation. As a result, the assumption that different lines follow the same attenuation curve breaks down. Using a single attenuation curve determined by Balmer lines to correct attenuation-sensitive forbidden line ratios could bias the nebular parameters derived by 0.06–0.25 dex at A V = 1, depending on the details of the dust attenuation model. Observations of a statistically large sample of H II regions with high spatial resolutions and large spectral coverage are vital for improved modeling and deriving accurate corrections for this effect.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2021

Continued Investigations of Respirable Release Fractions for Stress Corrosion Crack-Like Geometries

The formation of a stress corrosion crack (SCC) in the canister wall of a dry cask storage system (DCSS) has been identified as a potential issue for the long-term storage of spent nuclear fuel. The presence of an SCC in a storage system could represent a through-wall flow path from the canister interior to the environment. Modern, vertical DCSSs are of particular interest due to the commercial practice of using relatively high backfill pressures (up to approximately 800 kPa) in the canister to enhance internal natural convection. This pressure differential offers a comparatively high driving potential for blowdown of any particulates that might be present in the canister. In this study, the rates of gas flow and aerosol transmission of a spent fuel surrogate through an engineered microchannel with dimensions representative of an SCC were evaluated experimentally using coupled mass flow and aerosol analyzers. The microchannel was formed by mating two gage blocks with a linearly tapering slot orifice nominally 13 μm (0.005 in.) tall on the upstream side and 25 μm (0.0010 in.) tall on the downstream side. The orifice is 12.7 mm (0.500 in.) wide by 8.89 mm (0.350 in.) long (flow length). Surrogate aerosols of cerium oxide, CeO 2 , were seeded and mixed with either helium or air inside a pressurized tank. The aerosol characteristics were measured immediately upstream and downstream of the simulated SCC at elevated and ambient pressures, respectively. These data sets are intended to demonstrate a new capability to characterize SCCs under well-controlled boundary conditions. Modeling efforts were also initiated that evaluate the depletion of aerosols in a commercial dry storage canister. These preliminary modeling and ongoing testing efforts are focused on understanding the evolution in both size and quantity of a hypothetical release of aerosolized spent fuel particles from failed fuel to the canister interior and ultimately through an SCC.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2022

Quantification of Aerosol Transmission through Stress Corrosion Crack-Like Geometries

The formation of a stress corrosion crack (SCC) in the canister wall of a dry cask storage system (DCSS) has been identified as a potential issue for the long-term storage of spent nuclear fuel. The presence of an SCC in a storage system could represent a through-wall flow path from the canister interior to the environment. Modern, vertical DCSSs are of particular interest due to the commercial practice of using more significant backfill pressures in the canister, up to approximately 800 kPa. This pressure differential offers a relatively high driving potential for blowdown of any particulates that might be present in the canister. In this study, the rates of gas flow and aerosol transmission of a spent fuel surrogate through an engineered microchannel with dimensions representative of an SCC were evaluated experimentally using coupled mass flow and aerosol analyzers. The microchannel was formed by mating two gage blocks with a linearly tapering slot orifice nominally 13 μm (0.005 in.) tall on the upstream side and 25 μm (0.0010 in.) tall on the downstream side. The orifice is 12.7 mm (0.500 in.) wide by 8.86 mm (0.349 in.) long (flow length). Surrogate aerosols of cerium oxide, CeO 2 , were seeded and mixed with either helium or air inside a pressurized tank. The aerosol characteristics were measured immediately upstream and downstream of the simulated SCC at elevated and ambient pressures, respectively. These data sets are intended to add to previous testing that characterized SCCs under well-controlled boundary conditions through the inclusion of testing improvements that establish initial conditions in a more consistent way. These ongoing testing efforts are focused on understanding the evolution in both size and quantity of a hypothetical release of aerosolized spent fuel particles from failed fuel to the canister interior and ultimately through an SCC.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

DOE OSTI2023

Testing of Microchannels and Lab-Grown Stress Corrosion Cracks for Quantification of Aerosol Transmission

The formation of a stress corrosion crack (SCC) in the canister wall of a dry cask storage system (DCSS) has been identified as a potential issue for the long-term storage of spent nuclear fuel. The presence of an SCC in a storage system could represent a through-wall flow path from the canister interior to the environment. Modern, vertical DCSSs are of particular interest due to the commercial practice of using higher backfill pressures in the canister, up to approximately 800 kPa, compared to their horizontal counterparts. This pressure differential offers a relatively high driving potential for blowdown of any particulates that might be present in the canister. In this study, the rates of gas flow and aerosol transmission of a spent fuel surrogate through an engineered microchannel with dimensions representative of an SCC were evaluated experimentally using coupled mass flow and aerosol analyzers. The microchannel was formed by mating two gage blocks with a linearly tapering slot orifice nominally 13 μm (0.005 in.) tall on the upstream side and 25 μm (0.0010 in.) tall on the downstream side. The orifice is 12.7 mm (0.500 in.) wide by 8.86 mm (0.349 in.) long (flow length). Surrogate aerosols of cerium oxide, CeO 2 , were seeded and mixed with either helium or air inside a pressurized tank. The aerosol characteristics were measured immediately upstream and downstream of the simulated SCC at elevated and ambient pressures, respectively. These data sets are intended to add to previous testing that characterized SCCs under well-controlled boundary conditions through the inclusion of testing improvements that establish initial conditions in a more consistent way. While the engineered microchannel has dimensions similar to actual SCCs, it does not reproduce the tortuous path the aerosol laden flow would have to traverse for eventual transmission. SCCs can be rapidly grown in a laboratory setting given the right conditions, and initial characterization and clean-flow testing has begun on lab grown crack samples provided to Sandia National Laboratories (SNL). Many such samples are required to produce statistically relevant transmission results, and SNL is developing a procedure to produce samples in welded steel plates. These ongoing testing efforts are focused on understanding the evolution in both size and quantity of a hypothetical release of aerosolized spent fuel particles from failed fuel to the canister interior and ultimately through an SCC.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

DOE OSTI2024

Personalized, disease-stage specific, rapid identification of immunosuppression in sepsis

Introduction Data overlapping of different biological conditions prevents personalized medical decision-making. For example, when the neutrophil percentages of surviving septic patients overlap with those of non-survivors, no individualized assessment is possible. To ameliorate this problem, an immunological method was explored in the context of sepsis. Methods Blood leukocyte counts and relative percentages as well as the serum concentration of several proteins were investigated with 4072 longitudinal samples collected from 331 hospitalized patients classified as septic (n=286), non-septic (n=43), or not assigned (n=2). Two methodological approaches were evaluated: (i) a reductionist alternative, which analyzed variables in isolation; and (ii) a non-reductionist version, which examined interactions among six (leukocyte-, bacterial-, temporal-, personalized-, population-, and outcome-related) dimensions. Results The reductionist approach did not distinguish outcomes: the leukocyte and serum protein data of survivors and non-survivors overlapped. In contrast, the non-reductionist alternative differentiated several data groups, of which at least one was only composed of survivors (a finding observable since hospitalization day 1). Hence, the non-reductionist approach promoted personalized medical practices: every patient classified within a subset associated with 100% survival subset was likely to survive. The non-reductionist method also revealed five inflammatory or disease-related stages (provisionally named ‘early inflammation, early immunocompetence, intermediary immuno-suppression, late immuno-suppression, or other’). Mortality data validated these labels: both ‘suppression’ subsets revealed 100% mortality, the ‘immunocompetence’ group exhibited 100% survival, while the remaining sets reported two-digit mortality percentages. While the ‘intermediary’ suppression expressed an impaired monocyte-related function, the ‘late’ suppression displayed renal-related dysfunctions, as indicated by high concentrations of urea and creatinine. Discussion The data-driven differentiation of five data groups may foster early and non-overlapping biomedical decision-making, both upon admission and throughout their hospitalization. This approach could evaluate therapies, at personalized level, earlier. To ascertain repeatability and investigate the dynamics of the ‘other’ group, additional studies are recommended.

Immunology↗

DOE OSTI2020

BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 are implicated in tau pathology

Background: Identified as an Alzheimer’s disease (AD) susceptibility gene by genome wide-association studies, BIN1 has 10 isoforms that are expressed in the Central Nervous System (CNS). The distribution of these isoforms in different cell types, as well as their role in AD pathology still remains unclear. Methods: Utilizing antibodies targeting specific BIN1 epitopes in human post-mortem tissue and analyzing mRNA expression data from purified microglia, we identified three isoforms expressed in neurons and astrocytes (isoforms 1, 2 and 3) and four isoforms expressed in microglia (isoforms 6, 9, 10 and 12). The abundance of selected peptides, which correspond to groups of BIN1 protein isoforms, was measured in dorsolateral prefrontal cortex, and their relation to neuropathological features of AD was assessed. Results: Peptides contained in exon 7 of BIN1’s N-BAR domain were found to be significantly associated with ADrelated traits and, particularly, tau tangles. Decreased expression of BIN1 isoforms containing exon 7 is associated with greater accumulation of tangles and subsequent cognitive decline, with astrocytic rather than neuronal BIN1 being the more likely culprit. These effects are independent of the BIN1 AD risk variant. Conclusions: Exploring the molecular mechanisms of specific BIN1 isoforms expressed by astrocytes may open new avenues for modulating the accumulation of Tau pathology in AD. Keywords: BIN1 isoforms, Alzheimer’s disease, Amyloid, Tau, Microglia, Astrocytes, Neurons

Taga, Mariko↗

DOE OSTI2023

Evolution of coupled weakly driven waves in a dissipative plasma

The nonlinear collisional dynamics of coupled driven plasma waves in the presence of background dissipation is studied analytically within kinetic theory. Sufficiently near marginal stability, phase space correlations are poorly preserved and time delays become unimportant. The system is then shown to be governed by two first-order coupled autonomous differential equations of cubic order for the wave amplitudes and two complementary first-order equations for the evolution of their phases. That system of equations can be decoupled and further simplified to a single second-order differential equation of Liénard's type for each amplitude. Numerical solutions for this equation are obtained in the general case, while analytic solutions are obtained for special cases in terms of parameters related to the spacing of the resonances of the two waves in frequency space, e.g., wave lengths and oscillation frequencies. These parameters are further analyzed to find classes of quasi-steady saturation and pulsating scenarios. To classify equilibrium points, local stability analysis is applied, and bifurcation conditions are determined. When the two waves saturate at similar amplitude levels, their combined signal is shown to invariably exhibit amplitude beating and phase jumps of nearly π. In conclusion, the obtained analytical results can be used to benchmark simulations and to interpret eigenmode amplitude measurements in fusion experiments.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2025

Threshold photoproduction of 𝐽/Ψ off light nuclei

Here, we analyze threshold photoproduction of heavy mesons off a deuteron and helium-4, using the QCD factorization method. Assuming large skewness, the production amplitude is dominated by the leading twist-2 gluonic energy-momentum tensor. We use our recent results for the gluonic gravitational form factors of light nuclei in the impulse approximation, to estimate the differential cross sections for 𝐽/Ψ production off a deuteron and helium-4 at current electron facilities.

few-body systems↗