Remote sensing of electron precipitation mechanisms enabled by ELFIN mission operations and ADCS
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Ethan Tsai↗
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An ASIC With a Low Power Multichannel ADC for Energy and Timing Measurements
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42 ENGINEERING↗
A 12-b 5-GS/s Frontend IC for Photonic Sampling ADC System
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Engineering - Electronic and electrical engineerin↗
Improving Signal to Noise Ratios in Ion Mobility Spectrometry and Structures for Lossless Ion Manipulations (SLIM) using a High Dynamic Range Analog-to-Digital Converter
Signal digitization is a commonly overlooked part of ion mobility-mass spectrometry (IMS-MS) workflows, yet it is a significant contributor for determining signal-to-noise ratios and MS resolution. Here we report on the integration of a 2 GS/s, 14-bit ADC with a structures for lossless ion manipulations (SLIM)-IMS-MS and compare the performance to a commonly used 8-bit ADC. The 14-bit ADC provided an effective reduction in digitized noise by factor of ~6, owing largely to the use of smaller bit sizes. The low baseline allowed the threshold voltage levels to be set very close to the MCP baseline voltage, allowing for as much signal to be acquired as possible without causing overloading or excessive digitization of MCP baseline noise. Analyses of Agilent tuning mixture ions and a complex mixture of heavy labeled phosphopeptides showed that the 14-bit ADC (compared to the 8-bit ADC) provided a modest signal-to-noise increase (~1.5 to 2-fold) for high intensity ions, such as the Agilent tuning mixture ions and the 2+ and 3+ charge states of many phosphopeptide constituents. However, signal enhancements were as much as 10-fold for low intensity ions, and the 14-bit ADC enabled discernable signal intensities otherwise lost using an 8-bit digitizer. Additionally, the 14-bit ADC required ~14-fold fewer mass spectra to be averaged to produce a mass spectrum with similar S/N as the 8-bit ADC under identical conditions, potentially providing an order of magnitude higher measurement throughput. The high resolution, low baseline, and fast speed of the new 14-bit ADC enables high performance digitization of MS, IMS-MS, and SLIM-IMS-MS spectra, and allows a much fuller picture of analyte profiles in complex mixtures to be acquired.
data acquisition, digitization, ion mobility spect↗
Synthesis of site-specific antibody-drug conjugates by ADP-ribosyl cyclases
Most of the current antibody-drug conjugates (ADCs) in clinic are heterogeneous mixtures. To produce homogeneous ADCs, established procedures often require multiple steps or long reaction times. The introduced mutations or foreign sequences may cause high immunogenicity. Here, we explore a new concept of transforming CD38 enzymatic activity into a facile approach for generating site-specific ADCs. This was achieved through coupling bifunctional antibody-CD38 fusion proteins with designer dinucleotide-based covalent inhibitors with stably attached payloads. The resulting adenosine diphosphate–ribosyl cyclase–enabled ADC (ARC-ADC) with a drug-to-antibody ratio of 2 could be rapidly generated through single-step conjugation. The generated ARC-ADC targeting human epidermal growth factor receptor 2 (HER2) displays excellent stability and potency against HER2-positive breast cancer both in vitro and in vivo. This proof-of-concept study demonstrates a new strategy for production of site-specific ADCs. It may provide a general approach for the development of a novel class of ADCs with potentially enhanced properties.
59 BASIC BIOLOGICAL SCIENCES↗
Quantification of Residual Water in Spent Fuel Dry Storage Canisters Using Mass Spectrometry
The purpose of this report is to document updates on the apparatus to simulate commercial vacuum drying procedures at the Nuclear Energy Work Complex at Sandia National Laboratories. Validation of the extent of water removal in a dry spent nuclear fuel storage system based on drying procedures used at nuclear power plants is needed to close existing technical gaps. Operational conditions leading to incomplete drying may have potential impacts on the fuel, cladding, and other components in the system during subsequent storage and disposal, such as fuel degradation; cladding corrosion, embrittlement, or breaching; and the creation of a flammable environment via radiolysis of water. A general lack of data suitable for model validation of commercial nuclear canister drying processes necessitates well-designed investigations of drying process efficacy and water retention. Scaled tests that incorporate relevant physics and well-controlled boundary conditions are essential to provide insight and guidance to the simulation of prototypic systems undergoing drying processes. This report documents details on the quantification of residual water in the Advanced Drying Cycle Simulator (ADCS), an apparatus built to simulate commercial drying procedures and quantify the amount of residual water remaining in a pressurized water reactor (PWR) fuel assembly after drying. The ADCS was constructed with a prototypic 17×17 PWR fuel skeleton and waterproof heater rods to simulate decay heat. The ADCS is outfitted with thermocouples to measure the thermal response of the ADCS to simulated decay heats and internal helium fill pressures relevant to commercial drying procedures. The ADCS is also instrumented with pressure transducers to measure the pressures and vacuum levels observed during simulated commercial drying. The most unique instrumentation used for quantifying residual water in the ADCS is a Hiden Analytical HPR-30 mass spectrometer (MS), which measures gas compositions of the ADCS internal free volume, based on partial pressures calculated from relative proportions of gas molecules detected by the MS. This report details the methodology used to implement MS measurements in quantifying residual water in the ADCS. This methodology includes the calibration of the HPR-30 MS to a Buck Research Instruments CR-4 chilled mirror hygrometer, which itself is calibrated to a NIST-traceable standard. Data collected by both the MS and the chilled mirror hygrometer from water/helium mixtures ranging from 150 to 500,000 ppmv water in helium were used to generate calibration curves, establishing a source of verification of MS measured water contents. Details regarding water content measurement uncertainties are included in this report, defining the accuracy and verifiability of the HPR-30 MS in measuring residual water content in simulated dry storage canister environments.
11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
Advanced Drying Cycle Simulator Thermal Response to Commercial Drying Conditions
The purpose of this report is to document updates on testing of the apparatus built to simulate commercial drying procedures for spent nuclear fuel at the Nuclear Energy Work Complex at Sandia National Laboratories. Validation of the extent of water removal in a dry spent nuclear fuel storage system based on drying procedures used at nuclear power plants is needed to close existing technical gaps. Operational conditions leading to incomplete drying may have potential impacts on the fuel, cladding, and other components in the system during subsequent storage and disposal. A general lack of data suitable for model validation of commercial nuclear canister drying processes necessitates well-designed investigations of drying process efficacy and water retention that incorporate relevant physics and well-controlled boundary conditions. This report documents testing updates for the Advanced Drying Cycle Simulator (ADCS). This apparatus was built to simulate commercial drying procedures and quantify the amount of residual water remaining in a pressurized water reactor (PWR) fuel assembly after drying. The ADCS was constructed with a prototypic 17×17 PWR fuel skeleton and waterproof heater rods to simulate decay heat. These waterproof heaters are the next generation design to heater rods developed and tested at Sandia National Laboratories in FY20. This report describes preliminary testing of the ADCS through measurement and analysis of the thermal response of the system to a subset of commercial drying conditions that exclude the introduction of water, namely simulated decay heats and pressures relevant to commercial drying. This test series, referred to as a “dry” test series in this report, spans three uniform waterproof heater rod powers (representing spent fuel decay heats), four helium fill pressures, and six vacuum levels. This test series was conducted to cover the range of expected ADCS testing conditions for upcoming “wet” testing, where water will be introduced and a simulated commercial drying cycle will be performed. The dry test conditions were derived from the commercial drying conditions seen in the High Burnup Demonstration and the vacuum drying conditions chosen for a smaller scale Dashpot Drying Apparatus tested at Sandia National Laboratories in FY22. For a given uniform power and pressure/vacuum level, the ADCS was operated at constant power and pressure and allowed to reach steady state conditions. The thermal data obtained from these tests were analyzed, and the results can inform computational models built to simulate commercial drying processes by providing baseline thermal data prior to the introduction of water. Following the preliminary dry tests, a test plan for the ADCS will be developed to implement a drying procedure that begins with the introduction of water to the system and is based on measurements from the drying process used for the High Burnup Demonstration Project. While applying power to the simulated fuel rods, this procedure is expected to consist of filling the ADCS vessel with water, draining the water with applied pressure and multiple helium blowdowns, evacuating additional water with a vacuum drying sequence at successively lower pressures, and backfilling the vessel with helium. Additional investigations are expected to feature failed fuel rod simulators with engineered cladding defects and guide tubes with obstructed dashpots to challenge the drying system with multiple water retention sites. The data from these investigations is expected to inform the efficacy of commercial drying operations through the quantification of residual water in a prototypic-length dry storage canister.
11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
Accretion disk coronae
Recent observations of partial X-ray eclipses from 4U1822-37 have shown that the central X-ray source in this system is diffused by a large Compton-thick accretion disk corona (ADC). Another binary, 4U2129-47, also displays a partial eclipse and contains an ADC. The possible origin of an ADC is discussed and a simple hydrostatic evaporated ADC model is developed which, when applied to 4U1822-37, 4U2129+47 and Cyg X-3, can explain their temporal and spectral properties. The quasi-sinusoidal modulation of all three sources can be reconciled with the partial occultation of the ADC by a bulge at the edge of the accretion disk which is caused by the inflowing material. The height of this bulge is an order of magnitude larger than the hydrostatic disk height and is the result of turbulence in the outer region of the disk. The spectral properties of all three sources can be understood in terms of Compton scattering of the original source spectrum by the ADC. Spectral variations with epoch in Cyg X-3 are probably caused by changes in the optical depth of the corona. A consequence of our model is that any accreting neutron star X-ray source in a semi-detached binary system which is close to its Eddington limit most likely contains an optically thick ADC.
White, N. E.↗
Rapid and Simultaneous Characterization of Drug Conjugation in Heavy and Light Chains of a Monoclonal Antibody Revealed by High-Resolution Ion Mobility Separations in SLIM
Antibody-drug conjugates (ADCs) have recently gained traction in the biomedical community due to their promise for human therapeutics and an alternative to chemotherapy for cancer. Crucial metrics for ADC efficacy, safety, and selectivity are their drug-antibody ratios (DARs). However, DAR characterization (i.e., determining the average number of conjugated drugs on the antibody) through analytical methods remains challenging due to the heterogeneity of drug conjugation as well as the numerous post-translational modifications possible in the monoclonal antibody. In this work, we report on the use of high-resolution ion mobility spectrometry separations in our structures for lossless ion manipulations coupled to mass spectrometry (SLIM IMS-MS) platform for the rapid and simultaneous characterization of the drug load profile (i.e., stoichiometric distribution of the number of conjugated drugs present on the mAb), determination of the weighted average DAR in both the heavy and light chains of a model antibody-drug conjugate, and calculation of the overall DAR of the ADC. After chemical reduction of the ADC and a subsequent 31.5 meter SLIM IMS separation the various drug bound antibody species could be well resolved for both chains. Furthermore, we also show that higher resolution separations were possible with SLIM IMS as compared to ones performed on a commercially available (~1 meter) drift tube IMS-MS platform. Interestingly, additional gas-phase substructures become evident with longer path length SLIM IMS, potentially providing insight related to how drug conjugation may alter the structural properties of a monoclonal antibody and thus affect its overall potency and/or selectivity for a given antigen. We expect high-resolution SLIM IMS separations will augment the existing toolbox for ADC characterization, particularly for structural confirmation to enable the rapid optimization of DAR for a given ADC and thus better understand its potential toxicity and potency.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Update on the Investigation of Commercial Drying Cycles Using the Advanced Drying Cycle Simulator
The purpose of this report is to document updates on the apparatus to simulate commercial vacuum drying procedures at the Nuclear Energy Work Complex at Sandia National Laboratories. Validation of the extent of water removal in a dry spent nuclear fuel storage system based on drying procedures used at nuclear power plants is needed to close existing technical gaps. Operational conditions leading to incomplete drying may have potential impacts on the fuel, cladding, and other components in the system during subsequent storage and disposal. A general lack of data suitable for model validation of commercial nuclear canister drying processes necessitates well-designed investigations of drying process efficacy and water retention. Scaled tests that incorporate relevant physics and well-controlled boundary conditions are essential to provide insight and guidance to the simulation of prototypic systems undergoing drying processes. This report documents a new test apparatus, the Advanced Drying Cycle Simulator (ADCS). This apparatus was built to simulate commercial drying procedures and quantify the amount of residual water remaining in a pressurized water reactor (PWR) fuel assembly after drying. The ADCS was constructed with a prototypic 17×17 PWR fuel skeleton and waterproof heater rods to simulate decay heat. These waterproof heaters are the next generation design to heater rods developed and tested at Sandia National Laboratories in FY20. This report describes the ADCS vessel build that was completed late in FY22, including the receipt of the prototypic length waterproof heater rods and construction of the fuel basket and the pressure vessel components. In addition, installations of thermocouples, emissivity coupons, pressure and vacuum lines, pressure transducers, and electrical connections were completed. Preliminary power functionality testing was conducted to demonstrate the capabilities of the ADCS. In FY23, a test plan for the ADCS will be developed to implement a drying procedure based on measurements from the process used for the High Burnup Demonstration Project. While applying power to the simulated fuel rods, this procedure is expected to consist of filling the ADCS vessel with water, draining the water with applied pressure and multiple helium blowdowns, evacuating additional water with a vacuum drying sequence at successively lower pressures, and backfilling the vessel with helium. Additional investigations are expected to feature failed fuel rod simulators with engineered cladding defects and guide tubes with obstructed dashpots to challenge the drying system with multiple water retention sites.
11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
Astronomical catalog desk reference, 1994 edition
The Astronomical Catalog Desk Reference is designed to aid astronomers in locating machine readable catalogs in the Astronomical Data Center (ADC) archives. The key reference components of this document are as follows: A listing of shortened titles for all catalogs available from the ADC (includes the name of the lead author and year of publication), brief descriptions of over 300 astronomical catalogs, an index of ADC catalog numbers by subject keyword, and an index of ADC catalog numbers by author. The heart of this document is the set of brief descriptions generated by the ADC staff. The 1994 edition of the Astronomical Catalog Desk Reference contains descriptions for over one third of the catalogs in the ADC archives. Readers are encouraged to refer to this section for concise summaries of those catalogs and their contents.
Source record↗
Effect of inhibitors of polyamine biosynthesis on gibberellin-induced internode growth in light-grown dwarf peas
When gibberellic acid (GA3) is sprayed on 9-day-old light-brown dwarf Progress pea (Pisum sativum) seedlings, arginine decarboxylase (ADC; EC 4.1.1.9) activity increases within 3 h and peaks at about 9 h after GA3 application. This is followed by a second lower peak at about 30 h; both peaks were higher than the corresponding peaks in the controls. In contrast, no appreciable effect of GA3 on internode length was observed until about 12 h, after which time a dramatic increase in growth rate occurred and persisted for about 12 h. Specific (DL-alpha-difluoromethylarginine) and non-specific (D-arginine and L-canavanine) inhibitors of ADC strongly inhibited ADC activity and to a lesser extent internode growth. The inhibition was reversed only slightly by the addition of polyamines. Actinomycin D and cycloheximide inhibited the rise in ADC activity induced by GA3. The half-life of the enzyme was increased by GA3 treatment. The results suggest that part of the GA3-induced increase in internode growth may result from enhanced polyamine biosynthesis through the ADC pathway. Furthermore, the GA3 induced increase in ADC activity probably requires de novo synthesis of both RNA and protein.
NASA Program Space Biology↗
Approaches and Analysis for On-Focal-Plane Analog-to-Digital Conversion
This paper presents approaches for on-focal-plane analog-to-digital conversion (ADC). Common approaches and architectures for ADC and their utility for on-focal-plane integration are discussed. Candidate approaches are analyzed with respect to required amplifier gain, bandwidth, capacitance matching, noise and offsets as a function of ADC resolution. A column-parallel ADC architecture appears to be an effective compromise of chip area, power, circuit speed and ADC resolution. The discussion is valid for both infrared focal-plane arrays (FPAs) and visible image sensors.
analog-to-digital↗
Quantifying Atomically Dispersed Catalysts Using Deep Learning Assisted Microscopy
The catalytic performance of atomically dispersed catalysts (ADCs) is greatly influenced by their atomic configurations, such as atom–atom distances, clustering of atoms into dimers and trimers, and their distributions. Scanning transmission electron microscopy (STEM) is a powerful technique for imaging ADCs at the atomic scale; however, most STEM analyses of ADCs thus far have relied on human labeling, making it difficult to analyze large data sets. Here, we introduce a convolutional neural network (CNN)-based algorithm capable of quantifying the spatial arrangement of different adatom configurations. The algorithm was tested on different ADCs with varying support crystallinity and homogeneity. Results show that our algorithm can accurately identify atom positions and effectively analyze large data sets. Here, this work provides a robust method to overcome a major bottleneck in STEM analysis for ADC catalyst research. We highlight the potential of this method to serve as an on-the-fly analysis tool for catalysts in future in situ microscopy experiments.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
A New Hybrid Mass-Flux/High-Order Turbulence Closure for Ocean Vertical Mixing
While various parameterizations of vertical turbulent fluxes at different levels of complexity have been proposed, each has its own limitations. For example, simple first-order closure schemes such as the K-Profile Parameterization (KPP) lack energetic constraints; two-equation models $k-ε$ like directly solve an equation for the turbulent kinetic energy but do not account for non-diffusive fluxes, and high-order closures that include the high-order transport terms are computationally expensive. To address these, we extend the Assumed-Distribution Higher-Order Closure (ADC) framework originally proposed for the atmospheric boundary layer and apply it to the ocean surface boundary layer. By assuming a probability distribution function relationship between the vertical velocity and tracers, all second-order and higher-order moments are exactly constructed and turbulence closure is achieved in the ADC scheme. In addition, this ADC parameterization has full energetic constraints and includes non-diffusive fluxes without the computational cost of a full higher-order closure scheme. We have tested the ADC scheme against a combination of large eddy simulation (LES), KPP, and $k-ε$ for surface buoyancy-driven convective mixing and found that the ADC scheme is robust with different vertical resolutions and compares well to the LES results.
54 ENVIRONMENTAL SCIENCES↗
Enhancing Discoverability and Management of Atmospheric Data at Scale: Solutions from the ARM Data Center
The Atmospheric Radiation Measurement (ARM) is a multi-laboratory and multi-institutional U.S. Department of Energy (DOE) Office of Science National User Facility. The ARM Data Center (ADC), located at Oak Ridge National Laboratory, collects, archives, and shares vast atmospheric data crucial for climate research. The ADC manages over 7 PB of data from 460 instruments worldwide, processing it into more than 11,000 diverse data products using the Network Common Data Form (NetCDF) for machine-independent accessibility. The primary challenge addressed in this paper is the efficient management and distribution of vast and diverse datasets essential for the climate research community, enhancing accessibility through advanced tools like Data Discovery. The ADC has developed advanced infrastructure and software architecture to handle the continuous influx of heterogeneous data to enhance data discoverability, resulting in increased scientific collaboration. In 2023, users from over 34 countries downloaded and utilized ARM data, resulting in 1,455 publications. The ADC’s efforts have significantly improved the discoverability and usability of atmospheric data, fostering extensive scientific research and collaboration. This paper details the solutions implemented by the ADC team for efficient data discovery and distribution, and it demonstrates ARM’s capability of staging processed data for scientific analysis.
Shah, Chirag [ORNL] (ORCID:0000000203145737)↗
Mechanistic Insights into the Successful Development of Combination Therapy of Enfortumab Vedotin and Pembrolizumab for the Treatment of Locally Advanced or Metastatic Urothelial Cancer
Antibody–drug conjugates (ADCs) consist of an antibody backbone that recognizes and binds to a target antigen expressed on tumor cells and a small molecule chemotherapy payload that is conjugated to the antibody via a linker. ADCs are one of the most promising therapeutic modalities for the treatment of various cancers. However, many patients have developed resistance to this form of therapy. Extensive efforts have been dedicated to identifying an effective combination of ADCs with other types of anticancer therapies to potentially overcome this resistance. A recent clinical study demonstrated that a combination of the ADC enfortumab vedotin (EV) with the immune checkpoint inhibitor (ICI) pembrolizumab can achieve remarkable clinical efficacy as the first-line therapy for the treatment of locally advanced or metastatic urothelial carcinoma (la/mUC)—leading to the first approval of a combination therapy of an ADC with an ICI for the treatment of cancer patients. In this review, we highlight knowledge and understanding gained from the successful development of EV and the combination therapy of EV with ICI for the treatment of la/mUC. Using urothelial carcinoma as an example, we will focus on dissecting the underlying mechanisms necessary for the development of this type of combination therapy for a variety of cancers.
Oncology↗