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Asynchronous aging and turnover of human circulating and tissue-resident memory T cells across sites

Memory T cells are maintained in tissues as circulating effector-memory (T EM ) and tissue-resident (T RM ) populations for protective immunity, though the role of site and subset in memory persistence remains undefined. Here, in this work, we investigated age-associated dynamics of human T cells in lymphoid organs, mucosal sites, and blood over 10 decades of life using retrospective radiocarbon ( 14 C) birth dating, along with cellular, transcriptome, and epigenetic profiling. Memory T cells across peripheral sites exhibited continuous turnover with mean lifespans of 1–2 years, while the spleen contained longer-lived T cells. Over age, T EM cells expressed senescent markers and a GZMK transcriptional signature, while T RM cells maintained site-specific resident phenotypes without exhibiting features of senescence. Both T EM and T RM cells showed age-associated DNA hypomethylation, though T RM cells exhibited more epigenetically regulated genes. Together, our findings reveal asynchronous aging of human memory T cells by subset and site, as well as persistence of T RM cells without immunosenescence.

T cells

Computational ranking identifies Plexin-B2 in circulating tumor cell clustering with monocytes in breast cancer metastasis

Abstract Multicellular circulating tumor cell (CTC) clusters can be up to 50 times more efficient than single CTCs in mediating viable metastasis. Here, combining computational ranking and functional determination, we identify the transmembrane protein Plexin-B2 (PLXNB2) as one of the top molecular targets associated with unfavorable distant metastasis-free survival, showing enriched expression in CTC clusters versus single CTCs from patients with advanced breast cancer (mostly female). Loss of PLXNB2 (Plxnb2) reduces the formation of homotypic tumor cell clusters and heterotypic tumor-myeloid cell clusters, reducing spontaneous metastases in female mice bearing human (mouse) breast cancer. Interactions of PLXNB2 with its ligands SEMA4C on tumor cells and SEMA4A on myeloid cells (monocytes) promote homotypic and heterotypic CTC cluster formation, respectively, thereby driving lung metastasis. Global proteomic analysis reveals downstream effectors of the PLXNB2 pathway associated with tumor cell clustering. Thus, PLXNB2 is a therapeutic target for preventing new metastasis in breast cancer.

Science & Technology - Other Topics

Subpolar North Atlantic Mean State Affects the Response of the Atlantic Meridional Overturning Circulation to the North Atlantic Oscillation in CMIP6 Models

Abstract The Atlantic meridional overturning circulation (AMOC) plays an important role in climate, transporting heat and salt to the subpolar North Atlantic. The AMOC’s variability is sensitive to atmospheric forcing, especially the North Atlantic Oscillation (NAO). Because AMOC observations are short, climate models are a valuable tool to study the AMOC’s variability. Yet, there are known issues with climate models, like uncertainties and systematic biases. To investigate this, preindustrial control experiments from models participating in the phase 6 of Coupled Model Intercomparison Project (CMIP6) are evaluated. There is a large, but correlated, spread in the models’ subpolar gyre mean surface temperature and salinity. By splitting models into groups of either a warm–salty or cold–fresh subpolar gyre, it is shown that warm–salty models have a lower sea ice cover in the Labrador Sea and, hence, enable a larger heat loss during a positive NAO. Stratification in the Labrador Sea is also weaker in warm–salty models, such that the larger NAO-related heat loss can also affect greater depths. As a result, subsurface density anomalies are much stronger in the warm–salty models than in those that tend to be cold and fresh. As these anomalies propagate southward along the western boundary, they establish a zonal density gradient anomaly that promotes a stronger delayed AMOC response to the NAO in the warm–salty models. These findings demonstrate how model mean state errors are linked across variables and affect variability, emphasizing the need for improvement of the subpolar North Atlantic mean states in models.

54 ENVIRONMENTAL SCIENCES

RNA Splicing Events in Circulation Distinguish Individuals With and Without New-onset Type 1 Diabetes

Context: Alterations in RNA splicing may influence protein isoform diversity that contributes to or reflects the pathophysiology of certain diseases. Whereas specific RNA splicing events in pancreatic islets have been investigated in models of inflammation in vitro, how RNA splicing in the circulation correlates with or is reflective of type 1 diabetes (T1D) disease pathophysiology in humans remains unexplored. Objective: To use machine learning to investigate if alternative RNA splicing events differ between individuals with and without new-onset T1D and to determine if these splicing events provide insight into T1D pathophysiology. Methods: RNA deep sequencing was performed on whole blood samples from 2 independent cohorts: a training cohort consisting of 12 individuals with new-onset T1D and 12 age- and sex-matched nondiabetic controls and a validation cohort of the same size and demographics. Machine learning analysis was used to identify specific isoforms that could distinguish individuals with T1D from controls. Results: Distinct patterns of RNA splicing differentiated participants with T1D from unaffected controls. Notably, certain splicing events, particularly involving retained introns, showed significant association with T1D. Machine learning analysis using these splicing events as features from the training cohort demonstrated high accuracy in distinguishing between T1D subjects and controls in the validation cohort. Gene Ontology pathway enrichment analysis of the retained intron category showed evidence for a systemic viral response in T1D subjects. Conclusion: Alternative RNA splicing events in whole blood are significantly enriched in individuals with new-onset T1D and can effectively distinguish these individuals from unaffected controls. Further, our findings also suggest that RNA splicing profiles offer the potential to provide insights into disease pathogenesis.

60 APPLIED LIFE SCIENCES

Groundwater and Surface Water Flow (GSFLOW) model files to explore bedrock circulation depth and porosity in Copper Creek, Colorado

This data package contains integrated hydrological model input and output files for Copper Creek, Colorado (24 km2), a tributary of the East River located in the headwaters of the Upper Colorado River Basin. The model code is the U.S. Geological Survey (USGS) Groundwater and Surface Water Flow (GSFLOW) model. The model contains a 100-m grid resolution and a daily timestep. The land surface model is dynamically linked to a three-dimensional groundwater flow model that allows for streamflow gaining and losing conditions. The groundwater model contains 12 model layers and extends 400 m below land surface. The original Copper Creek model was modified to contain geologic layers representing saprolite, shallow bedrock, and deep bedrock. Endmember depth versus hydraulic conductivity relationships and porosity values for fractured crystalline rock are simulated. For the shallow case, median flow depths occur in the shallow saprolite at depths <8 m, while the deep case promotes a median groundwater flow depth of 100 m. With this modeling framework we compare streamflow response to a plausible worst-case drought lasting up to five years. Streamflow metrics of analysis include average streamflow, fraction of stream network that is dry, no-flow duration, average groundwater flow to streams and time to recovery following the drought. Results and implications are presented in a paper submitted to Geophysical Research Letters titled, "The role of bedrock circulation depth and porosity in mountain streamflow response to prolonged drought" by Rosemary WH. Carroll, Andrew H. Manning and Kenneth H Williams. A Readme.txt file provides instructions on how to download all model files and execute each model scenario. In addition to the GSFLOW output/prms/copper_drought.csv file containing daily basin water stores and fluxes (refer to GSFLOW manual) and the output/prms/copper_drought_statvar.dat file with output defined in the gsflow3.control file (refer to GSFLOW Manual), output files also include spatially distributed daily values of total evapotranspiration, canopy evaporation, precipitation, snowfall, infiltration, snow water equivalent, potential evapotranspiration, recharge, sublimation, soil moisture, contributing interflow, water table elevations, changes in groundwater storage, groundwater evapotranspiration, interbasin groundwater flow (limited to the alluvium below the stream outlet), and surface-groundwater exchanges within the river system.

54 ENVIRONMENTAL SCIENCES

Compaction and Morphology of Lost Circulation Materials

Lost circulation material (LCM) selection is critical to effectively and efficiently treating wellbore fluid losses in geothermal drilling where costs of treatment can be as much as 30% of the total drilling cost. We conducted several uniaxial compaction experiments on 10 different materials and several material mixtures to identify critical mechanical parameters of each. Materials degraded at 200°C were also investigated to understand how elevated temperatures in geothermal wells would degrade their compaction behavior. Granular materials tended to have lower compressibility and higher compression resistance, while more elongated and softer materials had less mechanical stiffness. Mixing materials tended to moderate the mechanical behaviors while heating universally increased the compaction of materials. Microscopy showed that particle strength tended to correlate positively with roundness and circularity and negatively with elongation of a material. Convexity of the degraded and undegraded materials showed heating may have increased the convexity or roughness of the individual particles. In conclusion, we concluded that granular materials are likely to provide the best seals in wells but that a mixture of size distribution, mechanical rigidity, and elongation is more likely to form a better seal for geothermal wells.

annular pressure drilling

Influence of Antarctic and Greenland Continental Shelf Circulation on High‐Latitude Oceans in E3SM

The science objectives of this project are to simulate and understand the impacts of both deep-basin warm-water intrusions and land-ice melt on the continental shelf circulations and sea-ice distributions around the margins of Greenland and Antarctica. As well, the role of subsurface ocean heat from the Atlantic on declining sea-ice cover in the Arctic is explored. Mesoscale processes and fine bathymetry are implicated in cross-shelf property transports around both Greenland and Antarctica. Therefore, we configured and ran an atmospheric reanalysis-forced global ocean/sea-ice simulation on a grid that reduces from 8 km at the Equator to 2 km at the poles (UH8to2) with 60 vertical levels. It was produced using the Energy Exascale Earth System Model ‘‘HiLAT’’ code (E3SMv0-HiLAT) that uses the Parallel Ocean Program (POP) and CICE5 as its ocean and sea-ice components, respectively. Two main UH8to2 simulations were carried out: one for 1975-2009 and the other for July 2016-2020 after it was initialized from a 1/25° data-assimilative ocean/sea-ice prediction system ocean/sea-ice state. The UH8to2 is not coupled to an active land-ice model. Rather, land-ice melt is represented by observationally informed freshwater fluxes (FWFs). Short (multi-year) UH8to2 simulations were conducted to understand sensitivities when Greenland ice sheet (GrIS) melt is released only at the ocean surface or when it is distributed over the upper water column in accordance with fjord melt plume behavior; these cases were compared with a no GrIS melt case. West Greenland continental shelf currents were fastest in the vertical distribution case and an increase in baroclinic conversion at the shelf break associated with increased eddy kinetic energy was found relative to the surface release case. Further, salinity is lower and meltwater volume greater in the eastern Labrador Sea in the vertical distribution case. For the Arctic, the veracity of the UH8to2 was evaluated for 2017-2020 using available observations. Simulated seasonal sea-ice thickness and concentration are realistic, but the ice is unrealistically thin in the central and eastern Arctic in the fall. Comparisons of vertical sections of ocean temperature, salinity, and buoyancy collected from Ice-Tethered Profilers (ITPs) in the eastern Arctic in the fall and winter of 2019/2020 and co-located/concurrent UH8to2 fields show the stratification over the top 100 m of the water column is too low in the model, the simulated mixed layer too deep, and the simulated subsurface Atlantic Water (AW) too warm; these biases may contribute to the sea-ice biases. A model intercomparison study using the UH8to2 and a forced 1/25° regional Arctic ocean/sea-ice (uses the HYbrid Coordinate Ocean Model and CICE5) simulation further investigates the relationship between AW and sea-ice in the eastern Arctic. The models show a mesoscale-rich pulse of Atlantic Water extending into the eastern basin that reaches maximum intensity in late winter of 2018, after which it decreases in strength. Concurrent and co-located sea-ice melt or the inhibition of sea-ice growth is seen and is attributed to halocline mesoscale eddies doming into the mixed layer with convection bringing this heat into the vicinity of the sea-ice.

58 GEOSCIENCES

Experimental Investigations into the Corrosion of Alloy 625 Using NaCl-PuCl3 Molten Salt in a Natural Circulation Microloop

Molten salt reactors (MSRs) can potentially revolutionize the nuclear industry by providing a path to a near-zero nuclear waste fuel cycle, contributing to more sustainable energy sources. As a plethora of MSR developers in the United States work toward an aggressive commercialization timeline, many of their fueled-salts—notably, chloride-based compositions—have limited operational testing with nuclear material. Licensing and operating these reactors require an understanding of corrosion effects on reactor materials of construction under operational conditions. The TerraPower Molten Chloride Fast Reactor (MCFR) is a liquid-fueled chloride-salt fast reactor which has received notable interest from the utility sector based on its desirable economic characteristics. The reactor operates at low pressure but does not require the use of highly reactive chemicals, leading to a reduced use of concrete and steel during construction. Additionally, liquid fuel allows for inherently stable behavior and natural circulation during a loss-of-site-power scenario. MCFR can be refueled while operating which makes it compatible with variable generation sources such as wind and solar. MCFR is a breed-and-burn in-situ reactor that does not implement any chemical processing or separations in the fuel cycle. Only mechanical filtration of noble metals and off-gassing of noble gases are utilized while the actinides stay mixed with the fuel at all times. The MCFR will require technology development to reach commercialization. With a breed-and-burn in-situ reactor like MCFR, the transmutation of fertile U-238 to fissile Pu-239 allows for much greater fuel utilization.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS

Measurements of TRACER pre-convective conditions and mesoscale circulations using small unmanned aircraft systems (sUAS)

Improved comprehension of the physical processes governing convective cloud formation and lifecycle are of critical importance for understanding and predicting future climate states. The influence of these clouds on the planetary energy budget, including on precipitation, is significant. Things are particularly complex in coastal regimes, where gradients in aerosol particle properties, localized circulations such as sea breezes, and large population centers are found. To date, numerical models struggle to accurately represent these critical clouds and are therefore challenged to provide a realistic view on the planetary energy budget. Through the proposed research, we deployed two uncrewed aircraft systems (UAS) equipped with a variety of instruments alongside sensors deployed by the US Department of Energy Atmospheric Radiation Measurement (ARM) program for the TRACER (Tracking Aerosol Convection Interactions Experiment) field campaign. The two small UAS platforms consisted of a CU RAAVEN fixed-wing airplane and an OU CopterSonde system, with the copter collecting frequent vertical profiles of thermodynamic and kinematic variables such as temperature, pressure, wind and humidity. At the same time, the fixed-wing captured horizontal gradients of these quantities and aerosol size distribution. These systems were deployed south of the Houston metro area, in an area that is impacted by the Gulf of Mexico sea breeze on a daily basis. These observations offer enhanced and complementary perspectives to those provided by the DOE ARM Mobile Facility (AMF) which is was deployed in southeast Houston, and an ancillary site in a more rural location west of the urban Houston area. Quality-controlled versions of the UAS data were collected and posted on the DOE ARM data archive after the conclusion of the campaign where they are accessible by the research community and general public. The UAS perspective offers revolutionary insight into key spatial and temporal effects that have not been evaluated previously.

54 ENVIRONMENTAL SCIENCES

Can general circulation models (GCMs) represent cloud liquid water path adjustments to aerosol–cloud interactions?

Abstract. General circulation models (GCMs), unlike other lines of evidence, indicate that anthropogenic aerosols cause a global-mean increase in cloud liquid water path (ℒ) and thus a negative adjustment to radiative forcing of the climate by aerosol–cloud interactions. In part 1 of this series of papers, we showed that this is true even in models that reproduce the negative correlation observed in present-day internal variability in ℒ and cloud droplet number concentration (Nd). We studied several possible confounding mechanisms that could explain the noncausal cloud–aerosol correlations in GCMs and that possibly contaminate observational estimates of radiative adjustments. Here, we perform single-column and full-atmosphere GCM experiments to investigate the causal model-physics mechanisms underlying the model radiative adjustment estimate. We find that both aerosol–cloud interaction mechanisms thought to be operating in real clouds – precipitation suppression and entrainment evaporation enhancement – are active in GCMs and behave qualitatively in agreement with physical process understanding. However, the modeled entrainment enhancement has a negligible global-mean effect. This raises the question of whether the GCM estimate is incorrect due to parametric or base-state representation errors or whether the process understanding gleaned from a limited set of canonical cloud cases is insufficiently representative of the diversity of clouds in the real climate. Regardless, even at limited resolution, the GCM physics appears able to parameterize the small-scale microphysics–turbulence interplay responsible for the entrainment enhancement mechanism. We suggest ways to resolve tension between current and future (storm-resolving) global modeling systems and other lines of evidence in synthesis climate projections.

54 ENVIRONMENTAL SCIENCES

General circulation models simulate negative liquid water path–droplet number correlations, but anthropogenic aerosols still increase simulated liquid water path

General circulation models' (GCMs) estimates of the liquid water path adjustment to anthropogenic aerosol emissions differ in sign from other lines of evidence. This reduces confidence in estimates of the effective radiative forcing of the climate by aerosol–cloud interactions (ERFaci). The discrepancy is thought to stem in part from GCMs' inability to represent the turbulence–microphysics interactions in cloud-top entrainment, a mechanism that leads to a reduction in liquid water in response to an anthropogenic increase in aerosols. In the real atmosphere, enhanced cloud-top entrainment is thought to be the dominant adjustment mechanism for liquid water path, weakening the overall ERFaci. We show that the latest generation of GCMs includes models that produce a negative correlation between the present-day cloud droplet number and liquid water path, a key piece of observational evidence supporting liquid water path reduction by anthropogenic aerosols and one that earlier-generation GCMs could not reproduce. However, even in GCMs with this negative correlation, the increase in anthropogenic aerosols from preindustrial to present-day values still leads to an increase in the simulated liquid water path due to the parameterized precipitation suppression mechanism. This adds to the evidence that correlations in the present-day climate are not necessarily causal. We investigate sources of confounding to explain the noncausal correlation between liquid water path and droplet number. These results are a reminder that assessments of climate parameters based on multiple lines of evidence must carefully consider the complementary strengths of different lines when the lines disagree.

54 ENVIRONMENTAL SCIENCES

Implications of Sea Breeze Circulations on boundary layer aerosols in the southern coastal Texas region

The Sea Breeze Circulation (SBC) influences atmospheric processes at multiple scales in coastal regions. Understanding how SBCs impact the aerosol number budget and aerosol–cloud interaction processes is essential. This study investigates sea breeze–aerosol interactions (SAIs) during 46 summertime SBC events using data from the TRacking Aerosol Convection Interactions Experiment (TRACER) field campaign across urban (main) and rural (supplemental) coastal sites in southern Texas. Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) simulations complement observations to explore spatio-temporal meteorological controls on boundary layer aerosols. During the summertime, Sea Breeze Fronts (SBF) penetrating inland transported cool, moist air over the land, introducing air masses with distinct properties compared to the preexisting continental air. These SAIs cause variability in number concentrations of up to a factor of two, with events typically lasting ∼ 5 h before returning to background conditions. SAI impact on aerosols varies with site proximity to water and the preceding sea breeze (SB) history, primarily affecting the marine-influenced accumulation mode. The main site, influenced by both Galveston Bay and the Gulf of Mexico, reflects a stronger marine influence. In contrast, a supplemental site, at a similar shoreline distance but exposed only to the Gulf of Mexico and typically upstream of the urban core, samples SB air that has traversed land and partially regained continental characteristics. Simulations show that the regional SAIs extend ∼ 50 km inland and reach up to the boundary layer height. SAIs further decrease cloud condensation nuclei relevant aerosol number concentrations in ∼ 20 % of events during SBF passage.

54 ENVIRONMENTAL SCIENCES

Surface radiation trends at North Slope of Alaska influenced by large-scale circulation and atmospheric rivers

Arctic amplification manifests as a pervasive warming trend emerging over the past century in near-surface air temperature throughout the Arctic that is double the globally averaged temperature increase throughout most of the year. It results from complex processes involving oceanic, atmospheric and terrestrial components which require detailed study to discern roles of the fundamental processes involved to improve predictions of the Arctic environment. We report on signals that are beginning to emerge, on a timescale predicted by recent satellite remote sensing studies, from the unique 25 year record of detailed surface-based radiometer measurements obtained by the US Department of Energy Atmospheric Radiation Measurement (ARM) Facility North Slope of Alaska (NSA) site at Utqiaġvik, Alaska. Statistically significant warming trends are found at the site in the boreal fall, while a decrease in net radiation occurs in late summer. This decrease is driven primarily by the decrease in shortwave radiation resulting from increasing cloud liquid water path as observed by the microwave radiometer. The magnitude of the liquid water path trends is slightly larger than the root mean square error (RMSE) due to natural variability, while the magnitude of the net radiation trends is smaller than the RMSE natural variability, emphasizing that these signals are only just emerging. Analysis of prevailing meteorological regimes linking NSA with the Arctic Ocean and subarctic latitudes, and atmospheric rivers, suggests that specific changing circulation patterns are the primary driver for these summertime trends.

Lubin, Dan [Univ. of California, San Diego, CA (Un

R&D with NREL's Davison Circulating Riser System

The Davison circulating riser (DCR) is the National Renewable Energy Laboratory's (NREL's) pilot-scale recirculating riser reactor system. Coupled with an upstream fluid-bed pyrolysis system, it permits evaluation of catalytic cracking of biogenic feedstocks, as well as coprocessing of biogenic and fossil feedstocks in a commercially relevant pilot fluid catalytic cracker.

09 BIOMASS FUELS

Investigation of the Performance and Explainability Tradeoffs for Machine-Learning Models for Predictive Maintenance of Circulating Water Systems in Nuclear Power Plants

Predictive maintenance (PdM) has shown great potential for achieving substantial cost savings and enhancing the economic competitiveness of nuclear power plants (NPPs) in today's energy market. Among the different modeling approaches that exist, machine learning (ML) tools in particular have a demonstrated ability to handle high dimensional and multivariate data and to extract hidden relationships within data in industrial environments. While ML methods show great potential, their lack of explainability---especially for black-box models---is a major hurdle to their adoption. Moreover, considering the supposed trade-off between explainability and performance challenges, careful consideration must be made as to which of these quality aspects takes precedence in light of multiple modeling options, resource availability, and domain characteristics. The present work evaluates the performance of six ML models, each with a different degree of explainability, in classifying the conditions of circulating water pumps (CWPs) by utilizing sensor data from nuclear power plants. To determine the drivers behind the trade-offs presented by this array of models, this work also tests different combinations of CWP units as the training and testing data, degrees of data imbalance, and objective functions for hyperparameter tuning. It was found that black-box models tend to afford superior performance in cases where there are far more instances of one type of labeled data than of any other type. It is recommended that a guided procedure be followed for designing and delivering an ML system that is sufficiently explainable to all involved stakeholders.

22 - GENERAL STUDIES OF NUCLEAR REACTORS

CFD modeling of natural circulation in LiCl-KCl molten salt closed loop

Characterizing flow within a molten salt closed-loop system is crucial for assessing system requirements, evaluating performance, and identifying potential flaws. Direct flow measurement using instrumentation is challenging due to extreme environmental conditions and the limitations associated with measuring molten salt flow under natural convection. Here, this study aims to provide comprehensive insights into the thermal-hydraulic behavior of a closed loop, with a particular focus on temperature distribution and velocity prediction. The Computational Fluid Dynamics (CFD) model demonstrated the capability to effectively simulate and predict both temperature distributions and flow velocities within the molten salt loop. The CFD model's predictive capability was validated by its ability to replicate temperature measurements under varying boundary conditions. The analysis revealed that the CFD model tends to underpredict temperatures in the cold leg and overpredict them in the hot leg, highlighting the need for continuous model refinement and acknowledging the limitations of using a steady-state approach. Furthermore, the potential of using external temperature measurements to estimate internal molten salt temperatures and predict flow velocity was explored, revealing that this approach could introduce up to a 5.5% error in flow velocity calculations. Line probes mapping temperature distributions across the tube's cross-section and molten salt provided valuable insights into temperature gradients, emphasizing the need for a thermal conductivity equation for molten salt with lower uncertainty to achieve more accurate temperature predictions of the system.

22 - GENERAL STUDIES OF NUCLEAR REACTORS