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At least 775 records · Page 43

A multimodal and integrated approach to interrogate human kidney biopsies with rigor and reproducibility: guidelines from the Kidney Precision Medicine Project

Comprehensive and spatially mapped molecular atlases of organs at a cellular level are a critical resource to gain insights into pathogenic mechanisms and personalized therapies for diseases. The Kidney Precision Medicine Project (KPMP) is an endeavor to generate three-dimensional (3-D) molecular atlases of healthy and diseased kidney biopsies by using multiple state-of-the-art omics and imaging technologies across several institutions. Obtaining rigorous and reproducible results from disparate methods and at different sites to interrogate biomolecules at a single-cell level or in 3-D space is a significant challenge that can be a futile exercise if not well controlled. Here we describe a “follow the tissue” pipeline for generating a reliable and authentic single-cell/region 3-D molecular atlas of human adult kidney. Our approach emphasizes quality assurance, quality control, validation, and harmonization across different omics and imaging technologies from sample procurement, processing, storage, shipping to data generation, analysis, and sharing. We established benchmarks for quality control, rigor, reproducibility, and feasibility across multiple technologies through a pilot experiment using common source tissue that was processed and analyzed at different institutions and different technologies. A peer review system was established to critically review quality control measures and the reproducibility of data generated by each technology before their being approved to interrogate clinical biopsy specimens. The process established economizes the use of valuable biopsy tissue for multiomics and imaging analysis with stringent quality control to ensure rigor and reproducibility of results and serves as a model for precision medicine projects across laboratories, institutions and consortia.

59 BASIC BIOLOGICAL SCIENCES↗

The LLNL Program in Relativistic Heavy-Ion Physics: FY20 Annual Laboratory Continuation Progress Report

The LLNL Heavy-Ion Group has research interests in the features and phenomena of nuclear matter at extreme temperatures and densities. It pursues these interests through participation in two experimental collaborations (ATLAS and sPHENIX) and one joint theory/experiment topical collaboration (JETSCAPE). The group is funded through a combination of LDRD, DOE-SC NP and an award from US ATLAS Software and Computing Operations, which is ultimately funded through HEP. The group's activities in FY20 were oriented around beginning a new LDRD project and fi lling two open postdoc positions while contributing to the ATLAS jet and UPC programs as well as participating in sPHENIX. Both postdoc positions were lled, effectively doubling the side of the LLNL Heavy-Ion Group, by Qipeng Hu (starting 6/20) and Dhanush Hangal (starting 8/20).

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Big PanDa Workflow Management on Titan for High Energy and Nuclear Physics and for Future Extreme Scale Scientific Application

Over a three year period, from 2016-2019, this project demonstrated the scientific benefits of integrating the Titan supercomputer at Oak Ridge Leadership Computing Facility into traditional high throughput grid based distributed computing systems managed by PanDA, the workflow management system used for the execution of all distributed computing applications by the ATLAS experiment at the Large Hadron Collider. PanDA manages millions of batch jobs daily at hundreds of clusters worldwide on request by thousands of physicist users, and processes more than an exabyte of data annually using grid middleware. High levels of operational use of Titan was sustained by PanDA in order to meet the physics goals of ATLAS. The success of this project led to the use of other supercomputers worldwide by ATLAS, and to the adoption of PanDA by other experiments and other scientists. Multiple innovative operational and computer science research goals were achieved supporting the use of supercomputers for scientific domains with large scale distributed data and distributed processing needs.

97 MATHEMATICS AND COMPUTING↗

"Experimental Research at the Energy Frontier in High Energy Physics" (Final Technical Report)

Recent developments in particle physics and cosmology raise the exciting prospect that we are on the threshold of a major step forward in our understanding of the universe. This proposal describes a research program at the University of Illinois in experimental high-energy physics on the ATLAS experiment at CERN’s Large Hadron Collider (LHC). Our group actively collaborates with the Theory Group and other experimental efforts within the Office of Science frontiers (energy, intensity, and cosmic) to search broadly in the ATLAS data to maximize our potential for scientifc discovery. The thrust of this proposal is to search for new physics using ATLAS data. Emphasis is placed on novel use of the Higgs boson as a tool to search for new particles and interactions and development of fast particle tracking systems for use in triggering. We propose to continue our strong role in FTK commissioning and operations. To maximize the impact and vitality of the proposed physics program through the HL-LHC running, we will lead firmware efforts in the HWTT Phase-II TDAQ upgrade, leveraging our expertise acquired through development of fast tracking hardware and firmware for the FTK system.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Forward Physics Facility - Snowmass 2021 Letter of Interest

A rich physics program remains unexplored in the far-forward region at the LHC. The Forward Physics Facility (FPF) is a proposal to enlarge an existing cavern in the far-forward region of ATLAS to house a suite of experiments with groundbreaking new capabilities for neutrinos, long-lived particle searches, milli-charged particle searches, QCD, dark matter, dark sectors, and cosmic rays. The FPF will be located 500 m from the ATLAS interaction point. It is shielded from the ATLAS interaction point by 100 m of concrete and rock, creating an extremely low-background environment, ideal for many standard model studies and new physics searches. In this Letter of Interest, we describe the FPF’s location and general features, its physics potential in the HL-LHC era, and topics for further study.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

DEVELOPMENT OF AN INTEGRATED SECURITY AND SAFETY MONITORING SYSTEM FOR SPENT NUCLEAR FUEL AND HIGH-LEVEL WASTE TRANSPORTATION

This paper provides an overview of the progress to date, and discussion of the path forward, related to designing, fabricating, and testing an integrated security and safety monitoring system (ISSMS) for railcars used to transport spent nuclear fuel (SNF) and high-level radioactive waste (HLW) in the United States. The system will comply with the US Department of Energy’s (DOE) Order 460.2B “Departmental Materials Transportation Management” and the Association of American Railroads’ (AAR) standard S-2043 “Performance Specification for Trains Used to Carry High-level Radioactive Material” [1] developed specifically for railcars used to transport high-level radioactive material (HLRM). DOE is in the process of developing and testing an ISSMS that will satisfy both DOE requirements and AAR standards. DOE has already developed railcar designs for transportation of HLRM. In 2024, DOE’s Atlas railcar project completed the design, fabrication and testing of three railcar types: transportation cask-carrying, buffer, and security escort, resulting in AAR conditional approval to operate on freight rail networks in North America. DOE decided to combine the required security and safety systems into one system, and this combined system is the subject of the current effort. DOE is developing and proposes to implement the ISSMS for these railcars as part of the build out of the railcar fleet. DOE began planning for development of the ISSMS in February 2020. The project is divided into seven phases starting with conceptual design and continuing through production design, as shown in Figure 1. An earlier version of the system was tested as part of the Atlas railcar consist demonstration test run in 2023. This paper describes the design features and system testing using the Atlas project railcars, and laboratory testing completed to date. The paper will also describe the activities planned to support the DOE project to ship the High Burn-Up Research Cask (HBRC) in 2027.

Schultze, Michael [ORNL] (ORCID:0000000283205671)↗

The promising role of proteomes and metabolomes in defining the single-cell landscapes of plants

The plant community has a strong track-record of RNA sequencing technology deployment, which combined with the recent advent of spatial platforms (e.g., 10x genomics), has resulted in an explosion of outstanding single cell and nuclei datasets that can be put in an in situ context within tissues (e.g., a cell atlas)1. In the genomics era, application of proteomics technologies in the plant sciences has always trailed behind that of RNA sequencing technologies, largely due to accessibility, ease-of-use and access to expertise along with depth of analysis benefits. On the other hand, the use of early analytical tools for characterizing small molecules (metabolites) from plant systems predates nucleic acid sequencing and proteomics analysis2, as the search for plant-based natural products has played a significant role in improving human health throughout history. However, the employment of proteomics and metabolomics assays for characterizing plant cell processes now remains significantly behind transcriptional approaches, even though both provide a direct functional readout of cell states and phenotypes.

Anderton, Christopher R. [BATTELLE (PACIFIC NW LAB↗

The scientific potential and technological challenges of the High-Luminosity Large Hadron Collider program

Here, we present an overview of the High-Luminosity (HL-LHC) program at the Large Hadron Collider (LHC), its scientific potential and technological challenges for both the accelerator and detectors. The HL-LHC program is expected to start circa 2027 and aims to increase the integrated luminosity delivered by the LHC by an order of magnitude at the collision energy of 14 TeV. This requires upgrades to the injector system, accelerator complex and luminosity levelling. The two experiments, ATLAS and CMS, require substantial upgrades to most of their systems in order to cope with the increased interaction rate, and much higher radiation levels than at the current LHC. We present selected examples based on novel ideas and technologies for applications at a hadron collider. Both experiments will replace their tracking systems. We describe the ATLAS pixel detector upgrade featuring novel tilted modules, and the CMS Outer Tracker upgrade with a new module design enabling use of tracks in the level-1 trigger system. CMS will also install state-of-the-art highly segmented calorimeter endcaps. Finally, we describe new picosecond precision timing detectors of both experiments. In addition, we discuss how the upgrades will enhance the physics performance of the experiments, and solve the computing challenges posed by the expected large data sets. The physics program of the HL-LHC is focused on precision measurements probing the limits of the Standard Model (SM) of particle physics and discovering new physics. We present a selection of studies that have been carried out to motivate the HL-LHC program. A central topic of exploration will be the characterization of the Higgs boson. The large HL-LHC data samples will extend the sensitivity of searches for new particles or new interactions whose existence has been hypothesized in order to explain shortcomings of the SM. Finally, we comment on the nature of large scientific collaborations.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Correlations between azimuthal anisotropy Fourier harmonics in PbPb collisions at sNN =2.76 TeV in the HYDJET++ model and in the multiphase transport model

Correlations between azimuthal anisotropy Fourier harmonics vn (n=2,3,4) are studied using the events from PbPb collisions at sNN=2.76 TeV generated by the HYDJET++ and multiphase transport (AMPT) models, and compared to the corresponding experimental results obtained by the ATLAS Collaboration. The Fourier harmonics vn are measured over a wide centrality range using the two-particle azimuthal correlation method. The slopes of the v2-v3 correlation from both models are in a good agreement with the ATLAS data. The HYDJET++ model predicts a stronger slope for the v2-v4 and v3-v4 correlations than the ones experimentally measured, while the results from the AMPT model are in a rather good agreement with the experimental results. In contrast to the HYDJET++ predictions, the AMPT model predicts a boomeranglike shape in the structure of the correlations as found in the experimental data. © 2020 American Physical Society.

60 APPLIED LIFE SCIENCES↗

Data on temporal complementarity of hybrid renewable energy systems [SWR-23-09]

These datasets describe multiple facets of the temporal complementarity of co-located hybrid renewable energy systems throughout the United States. Several metrics characterizing the complementarity of generation profiles are provided on an annual and monthly basis (for both hourly and daily aggregations). These generation profiles are underpinned by hourly resource data (e.g., the WIND Toolkit and National Solar Radiation Database (NSRDB)) spanning the multi-year period 2007-2013. The data include complementarity results for greater than 1.76 million individual locations within the continental United States (CONUS). The data are intended to accompany two publications on the topic of temporal complementarity: 1) Harrison-Atlas, Dylan, Caitlin Murphy, Anna Schleifer, and Nicholas Grue. "Temporal complementarity and value of wind-PV hybrid systems across the United States." Renewable Energy 201 (2022): 111-123, doi:10.1016/j.renene.2022.10.060; and 2) Murphy, Caitlin, Harrison-Atlas, Dylan, Nicholas Grue, Vahan Gevorgian, Juan Gallego-Calderon, Shiloh Elliot and Thomas Mosier. “A Resource Assessment for FlexPower”. NREL Technical Report.

Harrison-Atlas, Dylan↗

Probing Naturalness with Searches for Supersymmetric Higgs Partners at the Large Hadron Collider

The discovery of the Higgs boson at the Large Hadron Collider completed the standard model of particle physics and led to the 2013 Nobel Prize. While it has been extremely successful in describing a wide variety of phenomena, the standard model cannot be the final theory of nature because it is unable to explain why the Higgs boson mass lies at the electroweak scale rather than 16 orders of magnitude larger at the Planck scale, a theoretical flaw known as the ``hierarchy problem.'' Supersymmetry is a standard model extension that could provide a natural solution to the hierarchy problem by introducing light supersymmetric Higgs partners. This proposal focused on searches that are sensitive to supersymmetric Higgs partners in data collected by the ATLAS experiment, which were carried out by the University of Illinois high-energy physics group led by PI Ben Hooberman as part of his Department of Energy Early Career Research Program award from 2017-2023. The searches were complemented by improvements to particle identification algorithms and the ATLAS trigger system that extend the sensitivity of future supersymmetry searches.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Molecular subtyping reveals immune alterations in IDH wild‐type lower‐grade diffuse glioma

Abstract Isocitrate dehydrogenase ( IDH ) wild‐type diffuse lower‐grade glioma (LGG) is usually associated with poor outcome, but there have been disputes over its clinical outcome and classification. We present here a robust gene expression‐based molecular classification of IDH wild‐type diffuse LGG into two subtypes with distinct biological and clinical features. A discovery cohort of 49 IDH wild‐type diffuse LGGs from the Chinese Glioma Genome Atlas (CGGA) was subjected to clustering and function analysis. Seventy‐three tumors from The Cancer Genome Atlas (TCGA) were used to validate our findings. Consensus clustering of transcriptional data uncovered concordant classification of two robust and prognostically significant subtypes of IDH wild‐type LGG. Subtype 1, associated with poorer outcomes, was characterized by significantly higher immune and cytolytic scores, M2 macrophages, and up‐regulation of immune exhaustion markers, while Subtype 2, which had elevated lymphocytes and plasma cells, showed relatively favorable survival. Somatic alteration analysis revealed that Subtype 1 showed more frequently deleted regions, such as the locus of CDKN2A / CDKN2B , DMRTA1 , C9orf53 , and MTAP . Furthermore, we developed and validated a five‐gene signature for better application of this acquired stratification. Our data demonstrate the biological and prognostic heterogeneity within IDH wild‐type diffuse LGGs and deepen our molecular understandi‐g of this tumor entity. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Wu, Fan↗

Projected future daily characteristics of African precipitation based on global (CMIP5, CMIP6) and regional (CORDEX, CORDEX-CORE) climate models

In this work, we provide an assessment of future daily characteristics of African precipitation by explicitly comparing the results of large ensembles of global (CMIP5, CMIP6) and regional (CORDEX, CORE) climate models, specifically highlighting the similarities and inconsistencies between them. Results for seasonal mean precipitation are not always consistent amongst ensembles: in particular, global models tend to project a wetter future compared to regional models, especially over the Eastern Sahel, Central and East Africa. However, results for other precipitation characteristics are more consistent. In general, all ensembles project an increase in maximum precipitation intensity during the wet season over all regions and emission scenarios (except the West Sahel for CORE) and a decrease in precipitation frequency (under the Representative Concentration Pathways RCP8.5) especially over the West Sahel, the Atlas region, southern central Africa, East Africa and southern Africa. Depending on the season, the length of dry spells is projected to increase consistently by all ensembles and for most (if not all) models over southern Africa, the Ethiopian highlands and the Atlas region. Discrepancies exist between global and regional models on the projected change in precipitation characteristics over specific regions and seasons. For instance, over the Eastern Sahel in July–August most global models show an increase in precipitation frequency but regional models project a robust decrease. Global and regional models also project an opposite sign in the change of the length of dry spells. CORE results show a marked drying over the regions affected by the West Africa monsoon throughout the year, accompanied by a decrease in mean precipitation intensity between May and July that is not present in the other ensembles. This enhanced drying may be related to specific physical mechanisms that are better resolved by the higher resolution models and highlights the importance of a process-based evaluation of the mechanisms controlling precipitation over the region.

54 ENVIRONMENTAL SCIENCES↗

scPlantAnnotate: an accurate and robust transformer-based model for plant cell type annotation

Accurate cell type annotation remains a major bottleneck in plant single-cell RNA sequencing (scRNA-seq), where existing tools are often adapted from animal studies and perform sub-optimally on plant data. The lack of plant-specific computational frameworks limits the construction of plant cell atlases and downstream biological discovery. We develop and evaluate scPlantAnnotate, a Transformer-based reference annotation framework tailored for plant scRNA-seq data, and benchmark it against state-of-the-art deep learning and conventional methods across multiple plant species. Species-specific scPlantAnnotate models were trained using curated datasets from Arabidopsis thaliana, Zea mays, Oryza sativa, and Glycine max. We compared scPlantAnnotate with leading baselines under both standard random-split evaluation and a more stringent leave-one-dataset-out setting, which tests robustness to completely unseen datasets and tissue types. scPlantAnnotate consistently outperforms existing approaches across all four species under random-split evaluation. In the leave-one-dataset-out setting for A. thaliana, where performance drops markedly for all methods due to strong batch effects and dataset heterogeneity, scPlantAnnotate nonetheless achieves the highest Accuracy, Macro-F1, Balanced Accuracy, and Macro-AUROC on average and ranks first on most held-out datasets. These results demonstrate improved robustness to dataset shifts, a critical yet underexplored challenge in plant scRNA-seq analysis. A freely accessible web server enables users to annotate their own datasets using pretrained models. scPlantAnnotate provides a plant-specific, Transformer-based framework for single-cell annotation that delivers state-of-the-art performance and enhanced robustness to unseen datasets. By addressing limitations of existing tools and enabling scalable reference-based annotation, scPlantAnnotate supports the development of comprehensive plant cell atlases and facilitates broader use of single-cell genomics in plant biology.

Bioinformatics↗

Layout and performance of HPK prototype LGAD sensors for the High-Granularity Timing Detector

The High-Granularity Timing Detector is a detector proposed for the ATLAS Phase II upgrade. The detector, based on the Low-Gain Avalanche Detector (LGAD) technology, will cover the pseudo-rapidity region of 2.4 < |n| < 4.0 with two end caps on each side and a total area of 6.4 m 2 . The timing performance can be improved by implanting an internal gain layer that can produce signals with a fast rising edge. It significantly improves the signal-to-noise ratio. The required average timing resolution per track for a minimum ionizing particle is 30 ps at the start and 50 ps at the end of the HL-LHC operation. This is achieved with several layers of LGAD. The innermost region of the detector would accumulate a 1MeV neutron-equivalent fluence up to 2.5 10 15 n eq /cm 2 including a safety factor of 1.5 before being replaced during the scheduled shutdowns. The addition of this new detector is expected to play an important role in the mitigation of high pile-ups at the HL-LHC. The layout and performance of the various versions of LGAD prototypes produced by Hamamatsu (HPK) have been studied by the ATLAS Collaboration. The breakdown voltages, depletion voltages, inter-pad gaps, collected charge as well as the time resolution have been measured and the production yield of large size sensors has been evaluated.

47 OTHER INSTRUMENTATION↗

Humidity sensitivity of large area silicon sensors: Study and implications

The production of large area sensors is one of the main challenges that the ATLAS collaboration faces for the new Inner-Tracker full-silicon detector. During the prototype fabrication phase for the High Luminosity Large Hadron Collider upgrade, several ATLAS institutes observed indications of humidity sensitivity of large area sensors, even at relative humidities well below the dew point. Specifically, prototype Barrel and End-Cap silicon strip sensors fabricated in 6-inch wafers manifest a prompt decrease of the breakdown voltage when operating under high relative humidity, adversely affecting the performance of the sensors. In addition to the investigation of these prototype sensors, a specific fabrication batch with special passivation is also studied, allowing for a deeper understanding of the responsible mechanisms. Here we present an extensive study of this behaviour on large area sensors. The locations of the hotspots at the breakdown voltage at high humidity are revealed using different infrared thermography techniques. Several palliative treatments are attempted, proving the influence of sensor cleaning methods, as well as baking, on the device performance, but no improvement on the humidity sensitivity was achieved. Furthermore, a study of the incidence of the sensitivity in different batches is also presented, introducing a hypothesis of the origins of the humidity sensitivity associated to the sensor edge design, together with passivation thickness and conformity. Several actions to be taken during sensor production and assembly are extracted from this study, in order to minimize the impact of humidity sensitivity on the performance of large area silicon sensors for High Energy Physics experiments.

47 OTHER INSTRUMENTATION↗

The MATHUSLA test stand

The rate of muons from LHC pp collisions reaching the surface above the ATLAS interaction point is measured as a function of the ATLAS luminosity and compared with expected rates from decays of W and Z bosons and b- and c- quark jets. In addition, data collected during periods without beams circulating in the LHC provide a measurement of the background from cosmic ray inelastic backscattering that is compared to simulation predictions. Data were recorded during 2018 in a 2.5 × 2.5 × 6.5 m 3 active volume MATHUSLA test stand detector unit consisting of two scintillator planes, one at the top and one at the bottom, which defined the trigger, and six layers of RPCs between them, grouped into three ( x, y )-measuring layers separated by 1.74 m from each other. Triggers selecting both upward-going tracks and downward-going tracks were used.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Combined analysis of HPK 3.1 LGADs using a proton beam, beta source, and probe station towards establishing high volume quality control

The upgrades of the CMS and ATLAS experiments for the high luminosity phase of the Large Hadron Collider will employ precision timing detectors based on Low Gain Avalanche Detectors (LGADs). We present a suite of results combining measurements from the Fermilab Test Beam Facility, a beta source telescope, and a probe station, allowing full characterization of the HPK type 3.1 production of LGAD prototypes developed for these detectors. We demonstrate that the LGAD response to high energy test beam particles is accurately reproduced with a beta source. Finally, we further establish that probe station measurements of the gain implant accurately predict the particle response and operating parameters of each sensor, and conclude that the uniformity of the gain implant in this production is sufficient to produce full-sized sensors for the ATLAS and CMS timing detectors.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗