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Criterion validity of wrist accelerometry for assessing energy intake via the intake-balance technique

Background: Intake-balance assessments measure energy intake (EI) by summing energy expenditure (EE) with concurrent change in energy storage (ΔES). Prior work has not examined the validity of such calculations when EE is estimated via open-source techniques for research-grade accelerometry devices. The purpose of this study was to test the criterion validity of accelerometry-based intake-balance methods for a wrist-worn ActiGraph device. Methods: Healthy adults (n = 24) completed two 14-day measurement periods while wearing an ActiGraph accelerometer on the non-dominant wrist. During each period, criterion values of EI were determined based on ΔES measured by dual X-ray absorptiometry and EE measured by doubly labeled water. A total of 11 prediction methods were tested, 8 derived from the accelerometer and 3 from non-accelerometry methods (e.g., diet recall; included for comparison). Group-level validity was assessed through mean bias, while individual-level validity was assessed through mean absolute error, mean absolute percentage error, and Bland–Altman analysis. Results: Mean bias for the three best accelerometry-based methods ranged from -167 to 124 kcal/day, versus -104 to 134 kcal/day for the non-accelerometry-based methods. The same three accelerometry-based methods had mean absolute error of 323–362 kcal/day and mean absolute percentage error of 18.1-19.3%, versus 353–464 kcal/day and 19.5-24.4% for the non-accelerometry-based methods. All 11 methods demonstrated systematic bias in the Bland–Altman analysis. Conclusions: Accelerometry-based intake-balance methods have promise for advancing EI assessment, but ongoing refinement is necessary. We provide an R package to facilitate implementation and refinement of accelerometry-based methods in future research (see paulhibbing.com/IntakeBalance).

60 APPLIED LIFE SCIENCES↗

Structural basis for antibody recognition of the proximal MUC16 ectodomain

Mucin 16 (MUC16) overexpression is linked with cancer progression, metastasis, and therapy resistance in high grade serous ovarian cancer and other malignancies. The cleavage of MUC16 forms independent bimodular fragments, the shed tandem repeat sequence which circulates as a protein bearing the ovarian cancer biomarker (CA125) and a proximal membrane-bound component which is critical in MUC16 oncogenic behavior. A humanized, high affinity antibody targeting the proximal ectodomain represents a potential therapeutic agent against MUC16 with lower antigenic potential and restricted human tissue expression. Here, we demonstrate the potential therapeutic versatility of the humanized antibody as a monoclonal antibody, antibody drug conjugate, and chimeric antigen receptor. We report the crystal structures of 4H11-scFv, derived from an antibody specifically targeting the MUC16 C-terminal region, alone and in complex with a 26-amino acid MUC16 segment resolved at 2.36 Å and 2.47 Å resolution, respectively. The scFv forms a robust interaction with an epitope consisting of two consecutive β-turns and a β-hairpin stabilized by 2 hydrogen bonds. The V H -V L interface within the 4H11-scFv is stabilized through an intricate network of 11 hydrogen bonds and a cation-π interaction. Together, our studies offer insight into antibody-MUC16 ectodomain interaction and advance our ability to design agents with potentially improved therapeutic properties over anti-CA125 moiety antibodies.

60 APPLIED LIFE SCIENCES↗

Biomarkers, Proteoforms, and Mass Spectrometry–Based Assays for Diabetes Clinical Research

Abstract The prevalence of diabetes, particularly type 2 diabetes, has reached epidemic proportions globally. The number of patients with type 1 diabetes (T1D) is also increasing rapidly. Despite advancements in understanding the pathogenesis of diabetes, the lack of circulating pancreatic biomarkers and reliable clinical-grade assays remains a major gap in diabetes research, often hindering the ability to adequately assess disease progression and therapeutic responses. This mini-review discusses emerging pancreatic biomarkers, with an emphasis on T1D, the limitations of current immunoassays, and the expanding role of mass spectrometry–based assays. Highlights include the recent work within the NIDDK-funded “Targeted Mass Spectrometry Assays for Diabetes and Obesity Research (TaMADOR)” consortium, which aims to develop robust, quantitative, and transferable assays for translational research. The review also emphasizes the importance of proteoform-specific assays for monitoring pancreatic function, including prohormone processing during disease progression or in responses to therapy.

Endocrinology & Metabolism↗

Perioperative Gemcitabine + Erlotinib Plus Pancreaticoduodenectomy for Resectable Pancreatic Adenocarcinoma: ACOSOG Z5041 (Alliance) Phase II Trial

Background: There is considerable interest in a neoadjuvant approach for resectable pancreatic ductal adenocarcinoma (PDAC). This study evaluated perioperative gemcitabine + erlotinib (G+E) for resectable PDAC. Methods: A multicenter, cooperative group, single-arm, phase II trial was conducted between April 2009 and November 2013 (ACOSOG Z5041). Patients with biopsy-confirmed PDAC in the pancreatic head without evidence of involvement of major mesenteric vessels (resectable) were eligible. Patients (n = 123) received an 8-week cycle of G+E before and after surgery. The primary endpoint was 2-year overall survival (OS), and secondary endpoints included toxicity, response, resection rate, and time to progression. Resectability was assessed retrospectively by central review. The study closed early due to slow accrual, and no formal hypothesis testing was performed. Results: Overall, 114 patients were eligible, consented, and initiated protocol treatment. By central radiologic review, 97 (85%) of the 114 patients met the protocol-defined resectability criteria. Grade 3+ toxicity was reported in 60% and 79% of patients during the neoadjuvant phase and overall, respectively. Twenty-two of 114 (19%) patients did not proceed to surgery; 83 patients (73%) were successfully resected. R0 and R1 margins were obtained in 67 (81%) and 16 (19%) resected patients, respectively, and 54 patients completed postoperative G+E (65%). The 2-year OS rate for the entire cohort (n = 114) was 40% (95% confidence interval [CI] 31–50), with a median OS of 21.3 months (95% CI 17.2–25.9). The 2-year OS rate for resected patients (n = 83) was 52% (95% CI 41–63), with a median OS of 25.4 months (95% CI 21.8–29.6). Conclusions: For resectable PDAC, perioperative G+E is feasible. Further evaluation of neoadjuvant strategies in resectable PDAC is warranted with more active systemic regimens.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A Prospective, Open-Label, Multicenter Phase 2 Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma

Background: Neoadjuvant therapy reportedly shows only marginal clinical benefit in pancreatic ductal adenocarcinoma (PDAC), especially in resectable cases. However, with more effective regimens, neoadjuvant therapy may become a standard of care for resectable cases. A prospective, open-label, multicenter phases 1 and 2 trial of neoadjuvant therapy was conducted using full-dose gemcitabine and S-1 concurrently with 50.4 Gy of radiation therapy (GSRT) for resectable PDAC. This report describes the phase 2 results. Methods: The phase 2 part of this study enrolled 57 patients with cytologically or histologically proven PDAC deemed resectable based on imaging before neoadjuvant therapy. These patients received GSRT. After reevaluation by computed tomography scan, surgical exploration was performed, followed by adjuvant therapy. According to the prescribed protocol of the clinical trial, statistical analyses included 57 phase 2 patients and 6 phase 1 patients who received the same dosage as in phase 2. Results: This trial enrolled 63 patients (42 men and 21 women) with a median age of 70 years. Leukopenia or neutropenia of grade 3 or higher occurred for 79% of the patients, but no other severe adverse events were observed. Among the 63 patients, 54 underwent surgical resection. Intention-to-treat analysis of the 63 patients showed an excellent median survival time lasting as long as 55.3 months. The patients who completed neoadjuvant therapy, surgery, and adjuvant therapy had a 5-year survival rate of 56.6%. Conclusions: This regimen showed outstanding clinical efficacy with acceptable tolerability for patients with resectable PDAC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Trends in Regional Nodal Management of Breast Cancer Patients with Low Nodal Burden

Background: American College of Surgeons Oncology Group Z0011 confirms the safety of omitting axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) in breast cancer patients with one to two positive sentinel lymph nodes (SLNs), without compromising disease-free survival (DFS) and overall survival (OS). In contrast, the NCIC MA20 trial showed improved DFS in node-positive patients undergoing ALND and RNI. We sought to examine how these data have influenced the management of patients with limited nodal burden. Methods: Using the National Cancer Database, patients diagnosed between 2010 and 2015 and who met the criteria for Z0011 were identified. Logistic regression was used to analyze factors associated with practice patterns. The Cox proportional hazards model was used to assess the association of ALND and RNI with OS. Results: Omission of ALND in Z0011-eligible patients reached 89.2% in 2015. This Z0011-compliant group was more likely to undergo RNI compared with the non-compliant group (36.4% vs. 31.3%; p < 0.05), with RNI increasing to 43.8% by 2015. Factors associated with the use of RNI included later year of diagnosis [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.6–2.1], hormone receptor-negative tumor (OR 1.2, 95% CI 1.1–1.4), grade 3 tumor (OR 1.2, 95% CI 1.1–1.3), treatment at a non-academic site (OR 1.2, 95% CI 1.1–1.3) and two versus one positive SLN (OR 2.0, 95% CI 1.8–2.2). With 43 months median follow-up, RNI was not associated with improved OS. Conclusion: Since the publication of Z0011, the omission of ALND has become widespread; however nearly half of these women now receive RNI. The optimal radiation therapy approach for this low nodal burden population warrants further study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Data for Evaluation of 1,2-Diacyl-3-Acetyl Triacylglycerol Production in Yarrowia lipolytica

Plants produce many high-value oleochemical molecules. While oil-crop agriculture is performed at industrial scales, suitable land is not available to meet global oleochemical demand. Worse, establishing new oil-crop farms often comes with the environmental cost of tropical deforestation. The field of metabolic engineering offers tools to transplant oleochemical metabolism into tractable hosts while simultaneously providing access to molecules produced by non-agricultural plants. Here, we evaluate strategies for rewiring metabolism in the oleaginous yeast Yarrowia lipolytica to synthesize a foreign lipid, 3-acetyl-1,2-diacyl-sn-glycerol (acTAG). Oils made up of acTAG have a reduced viscosity and melting point relative to traditional triacylglycerol oils making them attractive as low-grade diesels, lubricants, and emulsifiers. This manuscript describes a metabolic engineering study that established acTAG production at g/L scale, exploration of the impact of lipid bodies on acTAG titer, and a techno-economic analysis that establishes the performance benchmarks required for microbial acTAG production to be economically feasible.

Biomass Analytics↗

Data for Training and Testing Radiation Detection Algorithms in an Urban Environment

The US government routinely performs radiological response deployments to search for the presence of illicit nuclear materials (e.g., highly enriched uranium and weapons-grade plutonium) in a specified area. The deployments can be intelligence driven, in support of law enforcement, and for planned events such as WrestleMania, presidential inaugurations, or political conventions. In a typical deployment, radiation detection systems carried by human operators or mounted on vehicles move in a clearing pattern through the search area. Search teams rely on radiation detection algorithms running on these systems in real time to alert them to the presence of an illicit threat source. The detection and identification of sources is complicated by large variation of natural radiation background throughout a search area and the potential presence of localized non-threat sources such as patients undergoing treatment with medical isotopes. As a result, detection algorithms must be carefully balanced between missing real sources (false negatives) and reporting too many false alarms (false positives).The purpose of this data set is to spur innovations in detecting, identifying, and localizing nuclear materials inurban search missions.

07 ISOTOPE AND RADIATION SOURCES↗

Model America - data and models of every U.S. building

The 5-year goal of the 'Model America' concept was to generate a model of every building in the United States. This data repository delivers on that goal. Oak Ridge National Laboratory (ORNL) has developed the Automatic Building Energy Modeling (AutoBEM) software suite to process multiple types of data, extract building-specific descriptors, generate building energy models, and simulate them on High Performance Computing (HPC) resources. For more information, see AutoBEM-related publications (bit.ly/AutoBEM). There were 125,714,640 buildings detected in the United States and this dataset contains 122,930,327 (97.8%) buildings which resulted in a successful simulation. Future, annual updates have been proposed that may include additional buildings, data improvements, or other algorithmic enhancements. This dataset of 122.9 million buildings includes: Models (state_county.zip) - OpenStudio (v3.1.0) and EnergyPlus (v9.4) building energy models. Please note that the download requires the free Globus Connect Personal (https://www.globus.org/globus-connect-personal); Each model has approximately 3,000 building input descriptors that can be extracted. Please see the EnergyPlus(v9.4) 2,784-page Input/Output Reference Guide (https://energyplus.net/sites/all/modules/custom/nrel_custom/pdfs/pdfs_v9.4.0/InputOutputReference.pdf) for everything that can be retrieved or simulated from these models. These models were derived from the following metadata, which is not included in this dataset: 1. ID - unique building ID 2. County - county name 3. State - state name 4. CZ - ASHRAE Climate Zone designation 5. Clim_Zone - text label of climate zone 6. est_year - estimated year of construction 7. est_commercial - estimated building type (0=residential, 1=commercial) 8. Centroid - building center location in latitude/longitude (from Footprint2D) 9. Footprint2D - building polygon of 2D footprint (lat1/lon1_lat2/lon2_...) 10. Height - building height (meters) 11. Area2D - footprint area (ft2) 12. BuildingType - DOE prototype building designation (IECC=residential) as implemented by OpenStudio-standards 13. WWR_surfaces - percent of each facade (pair of points from Footprint2D) covered by fenestration/windows (average 14.5% for residential, 40% for commercial buildings) 14. NumFloors - number of floors (above-grade) 15. Area - estimate of total conditioned floor area (ft2) 16. Standard - building vintage. These models are made free and openly available in hopes of stimulating any simulation-informed use case. Data is provided as-is with no warranties, express or implied, regarding fitness for a particular purpose. We wish to thank our sponsors which include Oak Ridge National Laboratory (ORNL) Laboratory Directed Research and Development (LDRD), U.S. Dept. of Energy's (DOE) Building Technologies Office (BTO), Office of Electricity (OE), Biological and Environmental Research (BER), and National Nuclear Security Administration (NNSA). This research used resources of the Argonne Leadership Computing Facility, which is a DOE Office of Science User Facility supported under Contract DE-AC02-06CH11357. Please cite as: New, Joshua R., Adams, Mark, Bass, Brett, Berres, Anne, and Clinton, Nicholas (2021). 'Model America - data and models of every U.S. building. [Data set].' Constellation, doi.ccs.ornl.gov/ui/doi/339, April 14, 2021

24 POWER TRANSMISSION AND DISTRIBUTION↗

Oak Ridge National Laboratory Building Envelope Library (ORNOBEL)

The Oak Ridge National Laboratory Building Envelope Library (ORNOBEL) is a collection of dense exterior building-facade point clouds acquired using a survey-grade terrestrial laser scanner. Each file represents an individual facade from a building on the Oak Ridge National Laboratory (ORNL) campus or in Knoxville, Tennessee, with an average point-cloud resolution of approximately 3 mm. The points in each facade are semantically labeled into three classes: (1) window/door, representing openings in the building envelope; (2) wall, representing planar opaque envelope surfaces; and (3) other, representing the remaining facade-adjacent elements, architectural features, and protrusions. ORNOBEL supports the development, training, and evaluation of advanced deep-learning methods for automated building-envelope segmentation, geometric reconstruction, and building information modeling (BIM).

Maldonado Puente, Bryan [ORNL] (ORCID:000000033880↗

Thermal Neutron Scattering Law Evaluation for Zirconium Carbide and Critical Mass Calculations

Zirconium carbide (ZrC) is a candidate material for use in advanced high temperature reactors, including space nuclear thermal propulsion applications. Thermal neutron scattering laws (TSLs) are generated for carbon bound in ZrC, C(ZrC), and zirconium bound in ZrC, Zr(ZrC), using ab initio lattice dynamics methods. These evaluations are to be submitted for inclusion in ENDF/B-VIII.1 and use the incoherent approximation for inelastic scattering as well as the new mixed elastic scattering treatment. The application of disordered alloy theory is introduced to appropriately capture the isotopic composition of Zr and C in the elastic scattering cross section. Localized higher energy vibrations in the C(ZrC) phonon density of states that are separated from lower energy modes result in quantized oscillations in the inelastic contributions to the TSL with a significant likelihood of large energy down-scattering and up-scattering interactions, where the latter increases in probability with temperature. The quanta of energy transfer during neutron thermalization is substantially greater than classically expected within the thermal neutron energy range. MC21 critical mass calculations of ZrC mixtures with high-enriched uranium demonstrate an impact of the TSLs when compared to free-gas treatment for 235 U concentrations less than 0.2 g/cm 3 . Additional MC21 critical mass calculations with homogenous mixtures of ZrC and reactor-grade graphite also demonstrate sensitivity to the ZrC TSL for thermal spectrum driven fission systems.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

OPERATING EXPERIENCE AND ITS RELATIONSHIP TO EMBEDDED DIGITAL DEVICES IN SAFETY SYSTEMS

Interest in embedded digital devices (EDDs) for monitoring and providing control of components is increasing and the added functionality digital brings such as diagnostics, displays, control functions is welcomed in both the nuclear and other industries. As a result, pure analog-based components continue to disappear from the industrial I&C marketplace. Equipment with EDDs, also known by related terms such as smart devices, intelligent devices, and digital devices of limited functionality, can include sensors, breakers, priority logic modules, time delay relays, pumps, valve actuators, motor control centers, and uninterruptible power supplies. Not only is equipment consisting of analog and older digital technology being replaced with commercial grade products containing EDDs, but EDDs can also be retrofitted to work with existing components. EDDs may be installed physically within a component, such as in a relay. There are also external devices that some would not consider an EDD, but that operate in almost all technical ways identically to one internal to a component such as in a valve controller. In fact, the digital portions may be located hundreds of feet from the actual component.Due to the potential of being used in an identical manner and without alteration from their application in other industries, operating experience (OpE) for EDDs may be much more applicable than in the case of other more system level devices. Clear separation and independence of functionality provided with EDDs may also allow greater applicability of existing OpE from industry for changes that can be shown not to affect its safety function. However, OpE also demonstrates issues with different conditions between other industries and nuclear power plants, such as issues with undeclared changes or undeclared digital devices and the new failure modes they may introduce, issues with the reporting of OpE in industry, and a lack of transparency into OpE for EDDs.Understanding and addressing these issues will be key in the future use of EDDs in nuclear power plants, but failure rate data is difficult to obtain for EDDs, and lessons learned from the use of EDDs are difficult to collect and identify.Key words: embedded digital device, smart device, operating experience, failure modes

Muhlheim, Michael↗

Development of a Pulsed Slowing-Down-Time Benchmark of Neutron Thermalization in Graphite

Graphite is a classic neutronic material that has been used as both a reactor reflector and moderator in various nuclear reactor systems. The ability to accurately predict the slowing down and thermalization of neutrons in graphite can have significant implications on the safety and operation of such reactor systems. In reactors, the neutron thermalization process is quantified using the thermal scattering law (TSL) and related cross sections for a given moderator. An ideal approach to assess the validity of TSL data is using benchmark measurement based on the pulsed Slowing-Down-Time technique and its comparison with the appropriate graphite nuclear library. In this work, experimental measurement and computational Monte Carlo simulations were performed to benchmark the slowing down characteristics and thermalization of neutrons in nuclear (reactor-grade) graphite. Given the density of graphite, various graphite libraries were selected for the benchmark analysis.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Thermal compensation of molded silicone optics

Optical grade silicone has various properties that make it attractive for solar concentrators, such as excellent transmission across the solar spectrum and flexible moldability for freeform profiles. In this study, a glass–silicone lens structure is proposed to reduce the optothermal effect on the silicone lens. Experimental measurements and simulation modeling results demonstrate that the focal length sensitivity of the glass–silicone lens with respect to temperature can be reduced by a factor of 10 when compared to a silicone lens alone. This model has been extended to the simulation of a proposed two-stage silicone solar concentrator, consisting of an array of acylindrical lenslets and rows of waveguides that focus light onto microphotovoltaic cells. The optical efficiency of the solar concentration system showed a change of less than 10% compared to the efficiency at room temperature for temperature changes from − <#comment/> 10 ∘ <#comment/> C to 70°C.

Lyons, Nicholas P.↗

X-ray computed tomography using partially coherent Fresnel diffraction with application to an optical fiber

A reconstruction algorithm for partially coherent x-ray computed tomography (XCT) including Fresnel diffraction is developed and applied to an optical fiber. The algorithm is applicable to a high-resolution tube-based laboratory-scale x-ray tomography instrument. The computing time is only a few times longer than the projective counterpart. The algorithm is used to reconstruct, with projections and diffraction, a tilt series acquired at the micrometer scale of a graded-index optical fiber using maximum likelihood and a Bayesian method based on the work of Bouman and Sauer. The inclusion of Fresnel diffraction removes some reconstruction artifacts and use of a Bayesian prior probability distribution removes others, resulting in a substantially more accurate reconstruction.

Levine, Zachary H. (ORCID:000000029928276X)↗

Comparative study of spectral broadening and few-cycle compression of Yb:KGW laser pulses in gas-filled hollow-core fibers

While industrial-grade Yb-based amplifiers have become very prevalent, their limited gain bandwidth has created a large demand for robust spectral broadening techniques that allow for few-cycle pulse compression. In this work, we perform a comparative study between several atomic and molecular gases as media for spectral broadening in a hollow-core fiber geometry. Exploiting nonlinearities such as self-phase modulation, self-steepening, and stimulated Raman scattering, we explore the extent of spectral broadening and its dependence on gas pressure, the critical power for self-focusing, and the optimal regime for few-cycle pulse compression. Using a 3-mJ, 200-fs input laser pulses, we achieve 17 fs, few-cycle pulses with 80% fiber energy transmission efficiency. The optimal parameters can be scaled for higher or lower input pulse energies with appropriate gas parameters and fiber geometry.

Shalaby, Islam (ORCID:0000000332846636)↗

High efficiency glass-based VUV metasurfaces

Most advances in metaoptics have been made at visible wavelengths and above; in contrast, the vacuum ultraviolet (VUV) has barely been explored despite numerous scientific and technological opportunities. Creating metaoptic elements at this short wavelength is challenging due to the scarcity of VUV transparent materials and the small sizes of the required nanostructures. Here, we present the first transmissive VUV (175 nm) metalens. By using UV-grade silica and trading off the Nyquist requirement for subwavelength structures against feasibility of the fabrication process, we achieve a step-change in diffraction efficiencies for wavelengths shorter than 300 nm. Our large numerical aperture (NA = 0.5) metalens shows an average diffraction efficiency of (53.3 ± 1.4)%. This demonstration opens up new avenues for compact flat optic systems operating in the VUV range.

Martins, Augusto [Univ. of York (United Kingdom)] ↗

Using case-level context to classify cancer pathology reports

Individual electronic health records (EHRs) and clinical reports are often part of a larger sequence—for example, a single patient may generate multiple reports over the trajectory of a disease. In applications such as cancer pathology reports, it is necessary not only to extract information from individual reports, but also to capture aggregate information regarding the entire cancer case based off case-level context from all reports in the sequence. In this paper, we introduce a simple modular add-on for capturing case-level context that is designed to be compatible with most existing deep learning architectures for text classification on individual reports. We test our approach on a corpus of 431,433 cancer pathology reports, and we show that incorporating case-level context significantly boosts classification accuracy across six classification tasks—site, subsite, laterality, histology, behavior, and grade. We expect that with minimal modifications, our add-on can be applied towards a wide range of other clinical text-based tasks.

60 APPLIED LIFE SCIENCES↗

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