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

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor

Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for de novo extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures. Applying SigProfilerExtractor to 4,643 whole-genome- and 19,184 whole-exome-sequenced cancers reveals four novel signatures. Two of the signatures are confirmed in independent cohorts, and one of these signatures is associated with tobacco smoking. In summary, this report provides a reference tool for analysis of mutational signatures, a comprehensive benchmarking of bioinformatics tools for extracting signatures, and several novel mutational signatures, including one putatively attributed to direct tobacco smoking mutagenesis in bladder tissues.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Mechanical Performance of the First Two Prototype 4.5 m Long Nb$_3$Sn Low-$β$ Quadrupole Magnets for the Hi-Lumi LHC Upgrade

The U.S. High-Luminosity LHC Accelerator Upgrade Project (HL-LHC AUP) team is collaborating with CERN in the design and fabrication of the first 4.5 m long MQXFA magnets, a 150 mm aperture high-field Nb$_3$Sn quadrupole magnet that uses the aluminum shell-based bladder-and-key technology. The first two prototype magnets, MQXFAP1 and MQXFAP2, were assem-bled and tested while the first pre-series structure (MQXFA03) was in fabrication. This paper summarizes the mechanical perfor-mance of these prototype structures based on the comparison of measured strain gauge data with finite element model analyses from all load steps to powering. The MQXFAP1 magnet almost reached ultimate current before a short to ground was detected and the test was stopped. The MQXFAP2 magnet experienced a low training performance due to a fractured aluminum shell. MQXFAP1b was rebuilt with a new replacement coil, but an old coil limited the magnet from achieving the ultimate current. The mitigations and analyses of these prototype magnets are discussed in the context of the transition to pre-series production.

43 PARTICLE ACCELERATORS↗
DOE OSTI2021

Magnetic and Mechanical Analysis of a Large Aperture 15 T Cable Test Facility Dipole Magnet

The US Department of Energy (DOE) Office of Science (SC), is funding a large bore “Cable Test Facility Magnet” for testing advanced cables and inserts in high transverse field. This is a joint effort between the Office of High Energy Physics (HEP) and the Office of Fusion Energy Sciences (FES). The background field magnet for this facility is being developed at Lawrence Berkeley National Laboratory (LBNL) while the cryostat and test facility will be located and operated by Fermi National Accelerator Laboratory (FNAL). The Nb 3 Sn dipole magnet, which will provide the transverse background field, is designed to generate a field of 15 T in a 100 × 150 mm bore at 1.9 K. The conceptual design of a block-type dipole with flared ends and a structure based on key-and-bladder technology will be introduced. The results of the magnetic and mechanical analysis will be presented.

43 PARTICLE ACCELERATORS↗
DOE OSTI2023

Computation of the Strain Induced Critical Current Reduction in the 16 T Nb 3 Sn Test Facility Dipole

A test facility dipole is being developed at LBNL, targeting a 16 T field in a 144 mm wide aperture. The magnet uses a block design, with two double-pancake coils. In order to minimize motion under the large Lorentz forces, the coils are preloaded against a thick aluminum shell and iron yoke using bladder and key technology. It is then crucial to verify that the performance of the magnet is not degraded due to strain induced on the Nb 3 Sn conductor during assembly, cool-down and powering. The critical current of extracted strands was measured in a varying background magnetic field and as a function of the applied longitudinal strain. Finite element analysis was used to extract the strain state inside the superconducting strands during magnet assembly and operation. This strain was then compared to the measurements to evaluate potential reversible and irreversible effects on the magnet performances. Here the results suggest that the magnet can reach 16 T with sufficient margin, with no irreversible degradation in the high field region.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2023

A Novel Design for Improving the Control on the Stainless-Steel Vessel Welding Process for Superconducting Magnets

Stainless steel vessels see widespread use in superconducting magnets for particle accelerator applications. Their function varies in different magnet designs: they always provide the necessary liquid helium containment, but in some cases are also used to provide azimuthal prestress and can also be welded to the magnet end plate to provide additional longitudinal stiffness. A magnet designed with the bladder and key technology does not rely on the structural role of the vessel. They are structurally supported using azimuthally prestressed aluminum shells, and the longitudinal constraint by rods. In this case, the magnet designer would generally like to minimize the interaction between the magnet and the stainless-steel vessel and to minimize the coil stress variation due to the vessel. The stress state in the vessel and in the coil is a function of the circumferential interference, defined as the vessel azimuthal length minus the magnet circumference. The vessel and the magnet azimuthal length machining tolerances are relatively large resulting in significant stress variations in the superconducting coils. Here in this paper we introduce an interference-control shim, which can significantly limit the stress variation of the coils for a given variation of the interference. The effectiveness of the interference-control shim is evaluated numerically on the MQXF, the low-β quadrupole for the High Luminosity LHC.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2024

Conceptual Structural Design and Analysis of a 20 T Hybrid Cos Dipole for Future Particle Colliders

Here, to reach high collision energy for future high-energy particle colliders, like the Future Circular Collider (FCC) or the Muon Collider, it is required to achieve high field strength of the bending dipoles. Currently, the practical limit for Nb$_{\text{3}}$ Sn technology is around 16 T and, in order to further increase the magnetic field, the superconducting magnet community is considering High Temperature Superconductors (HTS), in particular Bi-2212 and REBCO conductors. However, their relevant higher cost has led the community to consider a hybrid approach where HTS materials are used in the high field region of the coils with so-called insert coils, and Low Temperature Superconductors are involved in the lower field part ($< $ 16 T) with so-called outsert coils. This paper describes the conceptual mechanical design of a 20 T hybrid cos$\theta$ dipole configuration. The high stress levels that the structure is facing due to the high magnetic field are discussed. Moreover, it presents the results of the optimization analysis of the shell-based support structure based on the key-and-bladder technology that provides the azimuthal pre-stress during room temperature assembly and cooldown to cryogenic temperatures. The aim of this work is to present a feasible design that satisfies the stress requirements.

D'Addazio, Marika [Politecnico di Torino (Italy); ↗
DOE OSTI2025

Design of B2PF: A Large Aperture Nb-Ti Dipole Magnet for the Electron-Ion Collider

Here, we present the initial design of the matching dipole B2PF, a large aperture cosine-theta magnet for the Electron-Ion Collider (EIC). First we share an optimized 2D magnet cross-section based on a double-layer design with Nb-Ti Rutherford cable. This cross-section is optimized to meet the required field quality in the 120 mm coil aperture both at the nominal operating current and considering iron saturation effects during the ramp. Next, we share a first design of the 3D coil ends optimized for windability, field quality, and minimizing the conductor peak field. Based on the resulting peak field, we evaluate the short-sample margin of the design for an operating target of 6.3 T dipole field at 1.9 K. Finally, we share an initial mechanical design study which utilizes a key-and-bladder support structure capable of adjusting magnet preload.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2022

US HL-LHC Accelerator Upgrade Project (MQXFA Final Design Report)

The MQXFA Quadrupole magnets will be installed in High Luminosity LHC to form the Q1 and Q3 inner triplet optical elements in front of the interaction points 1 (ATLAS) and 5 (CMS). A pair of MQXFA units is assembled in a stainless steel helium vessel, including the end domes, to make the Q1 Cold Mass or the Q3 Cold Mass. The US HL LHC Accelerator Upgrade Project* is responsible for the design, manufacturing and test of the Q1/Q3 Cold Masses and the complete MQXFA magnets. CERN provides the cryostat components and is responsible for integration and installation in HL LHC. The MQXFA quadrupoles have 150 mm aperture, 4.2 m magnetic length, nominal gradient of 132.2 T/m, and coil peak field of 11.3 T. They use Nb_3Sn conductor and a support structure made of segmented aluminum shells pre-loaded by using bladders and keys. This report presents the final design of the MQXFA quadrupole magnets.

43 PARTICLE ACCELERATORS↗
DOE OSTI2022

FAST Equipment Lease with Liberty University, Inc. (Cooperative Research and Development Final Report)

Liberty University, Inc. (Participant) will receive government owned equipment from NREL to evaluate and perform fatigue testing of bladders in use for small scale pumped storage hydropower. NREL is providing technical support to advance Liberty University's pumped storage hydropower (PSH) concept towards commercialization. The concept creates modular upper and lower watertight enclosures (tanks or reservoirs) connected by a series of modular pipe lengths (penstock).

13 HYDRO ENERGY↗
DOE OSTI2026

Investigating Temperature Uniformity and Accuracy in PV Module Lamination: A Verification Study

This study investigates the temperature uniformity and accuracy of a photovoltaic (PV) module lamination process by addressing inconsistencies identified in 2017 data where irregular temperature changes were observed across setpoints. The 2017 data showed a notable drop in temperature upon bladder initiation, except for the 145 degrees Celsius profile. This inconsistency indicated potential inaccuracies in manual data recording methods. To address this concern, a verification experiment was conducted to evaluate temperature uniformity across the 2014 Bent River SPL2828 laminator platen and within test samples. Thermocouples, paired with Omega data acquisition software, were deployed to measure temperatures at multiple platen locations and within test samples. The experiment compared lamination temperatures of polyethylene-co-vinyl acetate (EVA) encapsulant when paired with solite glass or TPE backsheets. The methodology included verifying temperature uniformity directly on the platen and by using a large glass/EVA/glass sample using multiple thermocouples. Smaller samples were built with glass/EVA/glass and glass/EVA/backsheet configurations with one centered thermocouple to verify and compare sample temperatures. This verification aims to refine lamination temperature profiles, enhance data accuracy and provide insights into optimal process control for uniform module lamination. Ensuring consistent and uniform lamination may improve the accuracy and reliability of research outcomes.

14 SOLAR ENERGY↗
DOE OSTI2021

Early Drug Discovery and Development of Novel Cancer Therapeutics Targeting DNA Polymerase Eta (POLH)

Polymerase eta (or Pol η or POLH) is a specialized DNA polymerase that is able to bypass certain blocking lesions, such as those generated by ultraviolet radiation (UVR) or cisplatin, and is deployed to replication foci for translesion synthesis as part of the DNA damage response (DDR). Inherited defects in the gene encoding POLH (a.k.a., XPV) are associated with the rare, sun-sensitive, cancer-prone disorder, xeroderma pigmentosum, owing to the enzyme’s ability to accurately bypass UVR-induced thymine dimers. In standard-of-care cancer therapies involving platinum-based clinical agents, e.g., cisplatin or oxaliplatin, POLH can bypass platinum-DNA adducts, negating benefits of the treatment and enabling drug resistance. POLH inhibition can sensitize cells to platinum-based chemotherapies, and the polymerase has also been implicated in resistance to nucleoside analogs, such as gemcitabine. POLH overexpression has been linked to the development of chemoresistance in several cancers, including lung, ovarian, and bladder. Co-inhibition of POLH and the ATR serine/threonine kinase, another DDR protein, causes synthetic lethality in a range of cancers, reinforcing that POLH is an emerging target for the development of novel oncology therapeutics. Using a fragment-based drug discovery approach in combination with an optimized crystallization screen, we have solved the first X-ray crystal structures of small novel drug-like compounds, i.e., fragments, bound to POLH, as starting points for the design of POLH inhibitors. The intrinsic molecular resolution afforded by the method can be quickly exploited in fragment growth and elaboration as well as analog scoping and scaffold hopping using medicinal and computational chemistry to advance hits to lead. An initial small round of medicinal chemistry has resulted in inhibitors with a range of functional activity in an in vitro biochemical assay, leading to the rapid identification of an inhibitor to advance to subsequent rounds of chemistry to generate a lead compound. Importantly, our chemical matter is different from the traditional nucleoside analog-based approaches for targeting DNA polymerases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Aristolochic acid-induced genotoxicity and toxicogenomic changes in rodents

Aristolochic acid (AA) is a group of structurally related nitrophenanthrene carboxylic acids found in many plants that are widely used by many cultures as traditional herbal medicines. AA is a causative agent for Chinese herbs nephropathy, a term replaced later by AA nephropathy. Evidence indicates that AA is nephrotoxic, genotoxic, and carcinogenic in humans; and it also induces tumors in the forestomach, kidney, renal pelvis, urinary bladder, and lung of rats and mice. Therefore, plants containing AA have been classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer. In our laboratories, we have conducted a series of genotoxicity and toxicogenomic studies in the rats exposed to AA of 0.1–10 mg/kg for 12 weeks. Our results demonstrated that AA treatments induced DNA adducts and mutations in the kidney, liver, and spleen of rats, as well as significant alteration of gene expression in both its target and nontarget tissues. AA treatments altered mutagenesis- or carcinogenesis-related microRNA expression in rat kidney and resulted in significant changes in protein expression profiling. We also applied benchmark dose (BMD) modeling to the 3-month AA-induced genotoxicity data. The obtained BMDL10 (the lower 95% confidence interval of the BMD 10 that is a 10% increase over the background level) for AA-induced mutations in the kidney of rats was about 7 μg/kg body weight per day. This review constitutes an overview of our investigations on AA-induced genotoxicity and toxicogenomic changes including gene expression, microRNA expression, and proteomics; and presents updated information focused on AA-induced genotoxicity in rodents.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Resin transfer molding systems and control logic for manufacturing fiber-reinforced composite parts

Presented are manufacturing control systems for fabricating composite-material structures, methods for making/operating such systems, and resin transfer molding techniques for ameliorating race-tracking effects in fiber-reinforced polymer panels. A method for forming a composite-material construction includes confirming, via a system electronic control unit (ECU), that a fiber-based preform is placed in a mold cavity and that opposing mold segments of the molding apparatus are sealed together. A filler, such as a compressible bladder, a cluster of spring-biased pins, or a spray-chopped fiber bed, is introduced into a void between the fiber-based preform and a tool face of one mold segment to thereby eliminate an unwanted resin race track. The system ECU commands a resin pump to inject resin through a primary gate of the molding apparatus and into the mold cavity to thereby impregnate the fiber-based preform with the resin. One or more vents operate to evacuate air from the mold.

Rodgers, William R.↗
DOE OSTI2023

A Novel Design for Improving the Control on the Stainless-Steel Vessel Welding Process for Superconducting Magnets

Stainless steel vessels see widespread use in superconducting magnets for particle accelerator applications. Their function varies in different magnet designs: they always provide the necessary liquid helium containment, but in some cases are also used to provide azimuthal prestress and can also be welded to the magnet end plate to provide additional longitudinal stiffness. A magnet designed with the bladder and key technology does not rely on the structural role of the vessel. They are structurally supported using azimuthally prestressed aluminum shells, and the longitudinal constraint by rods. In this case, the magnet designer would generally like to minimize the interaction between the magnet and the stainless-steel vessel and to minimize the coil stress variation due to the vessel. The stress state in the vessel and in the coil is a function of the circumferential interference, defined as the vessel azimuthal length minus the magnet circumference. The vessel and the magnet azimuthal length machining tolerances are relatively large resulting in significant stress variations in the superconducting coils. In this paper we introduce an interference control shim, which can significantly limit the stress variation of the coils for a given variation of the interference. The effectiveness of the interference-control shim is evaluated numerically on the MQXF, the low-β quadrupole for the High Luminosity LHC.

43 PARTICLE ACCELERATORS↗
DOE OSTI2019

Advanced urothelial cancer: a radiology update

The recent genomic characterization of urothelial carcinoma by the Cancer Genome Atlas Project, made possible by the introduction of high throughput, reduced cost, and sequence analysis, has shed new insights on the biology of advanced disease. In addition, studies on imaging of advanced urothelial carcinoma have widened the knowledge on disease presentation and on pattern of metastatic spread and their correlation with the underlying biology of urothelial carcinoma. The wide range of treatments for advanced urothelial cancer, including combined chemotherapy regimens and immune checkpoint inhibitors, each result in treatment class-specific patterns of response and adverse events. Results of studies point to the need for a reliable biomarker, perhaps with imaging, that predicts prognosis and treatment response to systemic treatment, and can be used to select the most effective treatment while minimizing toxicity. This review of advanced urothelial cancer introduces the latest advances in genetic profiling, the current role of imaging, the radiographic appearance of treatment response and their toxicities, and details potential future areas of imaging research.

62 RADIOLOGY AND NUCLEAR MEDICINE↗