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DOE OSTI2026

The birth of a field through a marriage of scales: urban meteorological modeling meets regional climate modeling

Urban meteorological modeling and regional climate modeling developed largely independently, with each discipline addressing different aspects of atmospheric processes across space and time. In this review, I show that urban climate modeling did not arise as a simple scaling extension of urban meteorological modeling or an add-on to regional climate modeling, but instead emerged through the selective inheritance of complementary strengths from its parents after both disciplines reached sufficient methodological maturity. By tracing the parallel evolution of these disciplines, I demonstrate that urban climate modeling inherited the physically explicit treatment of the built environment developed within urban meteorological modeling, and the hierarchical scale translation and climatological framing that matured within regional climate modeling, allowing urban effects to influence climate-relevant outcomes. Building on this synthesis, I propose an objective, and methodologically-grounded definition of urban climate modeling that distinguishes it from urban meteorological modeling. This distinction is increasingly important as urban climate data informs decisions with long-lived societal consequences, and as ambiguity in terminology risks conflating fundamentally different modeling frameworks with distinct physical meaning and decision relevance. In addition to a clarifying definition, this review outlines a research framework for advancing urban climate modeling through scale-aware coupling strategies that preserve physically consistent urban-atmosphere interactions.

regional climate↗

NASA NTRS2014

Using Concurrent Cardiovascular Information to Augment Survival Time Data from Orthostatic Tilt Tests

Orthostatic Intolerance (OI) is the propensity to develop symptoms of fainting during upright standing. OI is associated with changes in heart rate, blood pressure and other measures of cardiac function. Problem: NASA astronauts have shown increased susceptibility to OI on return from space missions. Current methods for counteracting OI in astronauts include fluid loading and the use of compression garments. Multivariate trajectory spread is greater as OI increases. Pairwise comparisons at the same time within subjects allows incorporation of pass/fail outcomes. Path length, convex hull area, and covariance matrix determinant do well as statistics to summarize this spread Missing data problems Time series analysis need many more time points per OTT session treatment of trend? how incorporate survival information?

Feiveson, Alan H.↗

DOE OSTI2023

Halted-pendulum Relaxation: Application to White Dwarf Binary Initial Data

Studying compact-star binaries and their mergers is integral to determining progenitors for observable transients. Today, compact-star mergers are typically studied via state-of-the-art computational fluid dynamics codes. One such numerical technique, smoothed particle hydrodynamics (SPH), is frequently chosen for its excellent mass, energy, and momentum conservation. The natural treatment of vacuum and the ability to represent highly irregular morphologies make SPH an excellent tool for the study of compact-star binaries and mergers. For many scenarios, including binary systems, the outcome of simulations is only as accurate as the initial conditions. For SPH, it is essential to ensure that the particles are distributed regularly, representing the initial density profile but without long-range correlations. Particle noise in the form of high-frequency local motion and low-frequency global dynamics must be damped out. Damping the latter can be as computationally intensive as the actual simulation. We discuss a new and straightforward relaxation method, halted-pendulum relaxation (HPR), to remove global oscillation modes of SPH particle configurations. In combination with effective external potentials representing gravitational and orbital forces, we show that HPR has an excellent performance in efficiently relaxing SPH particles to the desired density distribution and removing global oscillation modes. We compare the method to frequently used relaxation approaches and test it on a white dwarf binary model at its Roche-lobe overflow limit. We highlight the importance of our method in achieving accurate initial conditions and its effect on achieving circular orbits and realistic accretion rates when compared with other general relaxation methods.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2026

Combined Nitrogen and Phosphorous Recovery via Electrochemical Technology Integration into Municipal Wastewater Treatment Plants

This project developed electroN-P, an electrochemical technology for recovering nitrogen and phosphorus as a fertilizer product from anaerobic digester centrate, targeting an advancement from TRL 4 to 6. The reactor was scaled 220× from a 250 mL batch cell to a continuous 4-channel system treating 55 L of wastewater, recovering >80% of phosphorus. Energy consumption under constant-voltage operation was lower than the embedded energy of conventional fertilizers, while constant-current operation produced a cost-competitive product with a smaller reactor footprint. TEA and LCA outcomes were highly sensitive to the magnesium source; alternative magnesium salt configurations projected reduced costs and embedded energy compared to sacrificial rods, but at the expense of significantly longer operation times. The recovered fertilizer performed comparably to diammonium phosphate and triple superphosphate in soil and plant trials. Integrating the technology into a whole-plant model reduced aeration energy by nearly 50%, lowering the levelized cost of water treatment from $0.668/m 3 to $0.648/m 3 . Results support targeting commercialization at smaller (≤1 MGD) facilities with high-strength digester streams. Further investigation into the transport and corrosion kinetics governing sacrificial anode wear is recommended to support continuous, longer-term operation.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

NASA NTRS2025

Assessment of Model Outcomes Between the Integrated Medical Model (IMM) and the Medical Extensible Dynamic Probabilistic Risk Assessment Tool (MEDPRAT)

The Medical Extensible Dynamic Probabilistic Risk Assessment Tool (MEDPRAT) is a computational model that provides human health and medical risk predictions for crewed spaceflight missions. MEDPRAT utilizes discrete event modeling and dynamic probabilistic simulation to predict critical mission outcomes (total medical events, crew health index, quality time lost, loss of crew life, removal to definitive care), condition occurrences, and resource consumption. Input parameters for MEDPRAT include crew attributes (e.g., sex), types of mission activities (e.g., whether and where crew members perform an extravehicular activity (EVA)), available resources, treatment information, and probability distributions for medical conditions. As an evolution of the Integrated Medical Model (IMM), MEDPRAT provides enhanced capabilities and higher fidelity, and incorporates more appropriate assumptions for long-duration spaceflight. IMM is the currently accepted standard for quantifying spaceflight mission medical risk in NASA operations that uses a probabilistic risk assessment (PRA) approach. MEDPRAT builds on the same logical foundation as IMM but implements the model architecture through highly optimized Monte Carlo sampling methods. An analysis is performed comparing the outputs from IMM with those from MEDPRAT V1.0 and V2.0 for the same reference missions in order to quantify similarities and differences in the model outcomes. The juxtaposition between IMM and MEDPRAT V1.0 and 2.0 shown in this report demonstrates that these two models generate very similar results; where differences in outcomes are shown, these are in accordance with the underlying assumptions and differences in the model architectures. This validation effort further establishes the credibility and reliability of the MEDPRAT software.

Matthew T Prelich↗

NASA NTRS2015

Prioritizing Medical Resources for Exploration Missions

Long duration missions beyond low Earth orbit introduce new constraints to the medical system. Factors such as the inability to evacuate to Earth in a timely manner, communication delay, limitations in available medical equipment, and the clinical background of the crew will all have an impact on the assessment and treatment of medical conditions. The Exploration Medical Capability (ExMC) Element of NASAs Human Research Program seeks to improve the way the element derives its mitigation strategies for the risk of "Unacceptable Health and Mission Outcomes Due to Limitation of In‐flight Medical Capabilities."

Shah, R. V.↗

NASA NTRS2001

Recovery from vestibular ototoxicity

OBJECTIVE: Determine whether subjects with documented vestibular ototoxicity recover vestibular function and, if so, investigate the recovery dynamics. STUDY DESIGN: Prospective and retrospective reviews and repeated measures. SETTING: Clinical research and technology center. SUBJECTS: Twenty-eight subjects who received vestibulotoxic medications were followed for at least 12 months after initial treatment. CONTROLS: Our subject sample was compared with a published database of normal individuals. INTERVENTIONS: All 28 subjects received systemically administered medications known to be ototoxic. The subjects' treating physicians controlled medication, dosage, and administration schedules. MAIN OUTCOME MEASURES: Tests of horizontal canal vestibulo-ocular function were performed. Subjects' auditory and vestibular symptoms were recorded. RESULTS: Eleven subjects (39%) showed changes in horizontal canal vestibulo-ocular gain constant (GC) and/or time constant (TC) consistent with vestibular ototoxicity. When tested 1 year after ototoxic drug administration, eight of the nine subjects who experienced ototoxic decrease in GC showed a recovery of GC to normal limits. Only one of the eight subjects who experienced ototoxic decrease in TC showed recovery of TC to within normal limits. Ototoxicity onset and recovery were independent of baseline vestibular function, and ototoxicity onset did not correlate with cumulative dose of ototoxic medication. There was no relationship between subjective symptoms and ototoxicity onset. CONCLUSIONS: Recovery of GC after vestibular ototoxicity is more commonly observed than recovery of TC. Because ototoxic changes developed and continued in an unpredictable time and manner in relation to ototoxic drug administration, we propose that once ototoxic changes in vestibulo-ocular reflex are detected, ototoxic medications should be discontinued as soon as possible.

NASA Discipline Neuroscience↗

NASA NTRS2009

The Integrated Medical Model - Optimizing In-flight Space Medical Systems to Reduce Crew Health Risk and Mission Impacts

The Integrated Medical Model (IMM) is a decision support tool used by medical system planners and designers as they prepare for exploration planning activities of the Constellation program (CxP). IMM provides an evidence-based approach to help optimize the allocation of in-flight medical resources for a specified level of risk within spacecraft operational constraints. Eighty medical conditions and associated resources are represented in IMM. Nine conditions are due to Space Adaptation Syndrome. The IMM helps answer fundamental medical mission planning questions such as What medical conditions can be expected? What type and quantity of medical resources are most likely to be used?", and "What is the probability of crew death or evacuation due to medical events?" For a specified mission and crew profile, the IMM effectively characterizes the sequence of events that could potentially occur should a medical condition happen. The mathematical relationships among mission and crew attributes, medical conditions and incidence data, in-flight medical resources, potential clinical and crew health end states are established to generate end state probabilities. A Monte Carlo computational method is used to determine the probable outcomes and requires up to 25,000 mission trials to reach convergence. For each mission trial, the pharmaceuticals and supplies required to diagnose and treat prevalent medical conditions are tracked and decremented. The uncertainty of patient response to treatment is bounded via a best-case, worst-case, untreated case algorithm. A Crew Health Index (CHI) metric, developed to account for functional impairment due to a medical condition, provides a quantified measure of risk and enables risk comparisons across mission scenarios. The use of historical in-flight medical data, terrestrial surrogate data as appropriate, and space medicine subject matter expertise has enabled the development of a probabilistic, stochastic decision support tool capable of optimizing in-flight medical systems based on crew and mission parameters. This presentation will illustrate how to apply quantitative risk assessment methods to optimize the mass and volume of space-based medical systems for a space flight mission given the level of crew health and mission risk.

Kerstman, Eric↗

DOE OSTI2024

Sex Differences in Odds of Brain Metastasis and Outcomes by Brain Metastasis Status after Advanced Melanoma Diagnosis

Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011–30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

A Novel Anatomic Reconstruction for Posterior Tibialis Tendon in Treatment of Flexible Adult‐Acquired Flatfoot Deformity

Objective To present a novel approach for the anatomic reconstruction of the posterior tibialis tendon (PTT) in restoring plantar insertions and evaluate its efficiency in treating flexible adult‐acquired flatfoot deformity (AAFD) caused by PTT dysfunction. Methods For AAFD treatment, a novel PTT reconstruction method was presented. The current study involved 16 patients, including three men, and 13 women, from August 2017 to July 2019. The mean age was 43.2 ± 15.1 years (21–64 years). The innovative PTT repair method was used on all patients. The treatment involved performing a traditional Flexor Digitorum Longus (FDL) transfer in the navicular tuberosity and suturing the plantar insertions to FDL as tension was applied to tighten the plantar structures of the foot. The results were retrospectively analyzed. The clinical outcome was assessed using the pain visual analogue scale (VAS), the satisfaction VAS, and the American Orthopedic Foot and Ankle Society ankle–hindfoot scale (AOFAS‐AH). Isokinetic testing was performed using a dynamometer at 60°/s and 120°/s for inversion/eversion and plantarflexion/dorsiflexion, respectively, to determine the mean peak torque. Radiographic measurements were employed to assess the outcomes. Results Bone surgeries combined with the modified anatomic PTT reconstruction were performed on patients with medializing calcaneal osteotomy in 12 (75%) patients and subtalar joint fusion in four (25%) patients. The branch linking to the plantar insertions was detected in every case, with an average width of 3.5 ± 0.8 mm (3.1–4.3 mm). All patients were followed up for the mean of 16.8 ± 1.8 months (range, 15–20 months). The average postoperative functional scores, including pain VAS, satisfaction VAS, total AOFAS‐AH, and all AOFAS‐AH sub‐scales, steadily improved during the follow‐up. In the last follow‐up, isokinetic testing revealed no loss of plantarflexion strength ( p = 0.350 and 0.098) and significant improvement in the inversion strength ( p = 0.007 and 0.008) in the operated ankles at 60°/s and 120°/s. Radiographic outcomes, particularly the talar head uncovering, improved significantly after more than a year ( p < 0.001 for all). Conclusions The novel technique for PTT reconstruction in restoring the plantar insertions serves as an effective procedure in treating AAFD caused by PTT dysfunction in terms of delivering a consistent improvement in ankle inversion strength, medial longitudinal arch restoring, and satisfactory clinical outcomes.

Hu, Yong↗

NASA NTRSDate not supplied

Microgravity Game Changers: Recent Accomplishments of Microgravity Assisted Materials Experiments on the ISS

This paper discusses important new materials, devices and technology produced in low-Earth orbit (LEO) that have been developed with funding from NASA’s In Space Production Applications (InSPA) Portfolio. In coordination with the International Space Station (ISS) National Laboratory, InSPA supports innovative small businesses and other research & development organizations to develop microgravity-assisted applications that make significant impacts in a wide variety of industries on Earth. These technology development efforts are using the microgravity of orbital space to overcome gravity-induced defects on Earth to create high-value products for terrestrial markets in the areas of semiconductors, pharmaceuticals, and communications. Through 24/7/365 operation on ISS for 25 years, coupled with commercial space transportation and services to, in, and from orbit, the microgravity environment has enabled pioneering science and significant commercial applications, including novel medical advances. World-leading researchers, innovators, and space payload developers provide compelling evidence through demonstrations on the ISS that materials processing in microgravity improves outcomes for a wide range of materials and products at all levels of the organization of matter, from quantum entities such as Bose-Einstein condensates, to crystals, alloys, composites, thin films, and photonics, to stem cells, medical diagnoses, medical treatments, and medical devices for humans. As of 2026, numerous examples proved by demonstration on ISS show the potential of these technologies in various fields. In this paper, a summary of four important experiments is presented.

microgravity medical devices↗

DOE OSTI2024

The influence of microbial colonization on inflammatory versus pro-healing trajectories in combat extremity wounds

A combination of improved body armor, medical transportation, and treatment has led to the increased survival of warfighters from combat extremity injuries predominantly caused by blasts in modern conflicts. Despite advances, a high rate of complications such as wound infections, wound failure, amputations, and a decreased quality of life exist. To study the molecular underpinnings of wound failure, wound tissue biopsies from combat extremity injuries had RNA extracted and sequenced. Wounds were classified by colonization (colonized vs. non-colonized) and outcome (healed vs. failed) status. Differences in gene expression were investigated between timepoints at a gene level, and longitudinally by multi-gene networks, inferred proportions of immune cells, and expression of healing-related functions. Differences between wound outcomes in colonized wounds were more apparent than in non-colonized wounds. Colonized/healed wounds appeared able to mount an adaptive immune response to infection and progress beyond the inflammatory stage of healing, while colonized/failed wounds did not. Although, both colonized and non-colonized failed wounds showed increasing inferred immune and inflammatory programs, non-colonized/failed wounds progressed beyond the inflammatory stage, suggesting different mechanisms of failure dependent on colonization status. Overall, these data reveal gene expression profile differences in healing wounds that may be utilized to improve clinical treatment paradigms.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program

The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n = 35) or hospitalization (n = 42) due to severe COVID-19 using genome-wide association summary data from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the ABO locus (rs495828, rs505922) associated with the largest number of phenotypes (n rs495828 = 53 and n rs505922 = 59); strongest association with venous embolism, odds ratio (OR rs495828 1.33 (p = 1.32 x 10 –199 ), and thrombosis OR rs505922 1.33, p = 2.2 x10 -265 . Among 67 respiratory conditions tested, 11 had significant associations including MUC5B locus (rs35705950) with increased risk of idiopathic fibrosing alveolitis OR 2.83, p = 4.12 × 10 –191 ; CRHR1 (rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p = 2.26× 10 –12 . The TYK2 locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p = 6.48 x10 -23 , lupus OR 0.84, p = 3.97 x 10 –06 . PheWAS stratified by ancestry demonstrated differences in genotype-phenotype associations. LMNA (rs581342) associated with neutropenia OR 1.29 p = 4.1 x 10 –13 among Veterans of African and Hispanic ancestry but not European. Overall, we observed a shared genetic architecture between COVID-19 severity and conditions related to underlying risk factors for severe and poor COVID-19 outcomes. Differing associations between genotype-phenotype across ancestries may inform heterogenous outcomes observed with COVID-19. Divergent associations between risk for severe COVID-19 with autoimmune inflammatory conditions both respiratory and non-respiratory highlights the shared pathways and fine balance of immune host response and autoimmunity and caution required when considering treatment targets.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2026

Biochar–polymer composites for 3D printing: a review

Biochar, a bio-based co-product of biofuel production via thermochemical conversion, holds potential as a filler for polymer composites to reduce costs, improve thermomechanical properties, and aid in environmental remediation. 3D-printed biochar composites have received growing interest over the past few years but have experienced difficulties such as poor layer adhesion and nozzle clogging. Currently, no literature review examines 3D-printed biochar composites and related biochar properties in-depth. This work summarizes and discusses recent studies on 3D-printed polymer and biochar composites and examines their mechanical, thermal, and additional properties that result from each study. Technical challenges in printability, such as nozzle clogging from particle size and biochar aggregation, are also discussed. Furthermore, this work discusses the variability of biochar properties resulting from the pyrolysis conditions and feedstock choice in relation to potential 3D printing outcomes. In particular, several studies reported that high lignin feedstocks could be candidates for 3D printing. The post-processing approaches of the biochar via physical and chemical methods are also introduced. Ball milling appears to hold the most promise for physical treatments due to its tunability of particle size, surface area, and functional groups, while chemical treatments with acids or alkalis are used to tailor biochar porosity and wettability. Overall, it was determined that future research needs to be done relating biochar production and post-processing methods to resulting 3D printing parameters as the number of studies is limited.

Day, Rachel [Auburn University, Auburn, AL]↗

NASA NTRS2001

Effects of 2.0-g 1.75-g and 1.5-g Hypergravity on Pregnancy Outcome in Rats (Rattus norvegicus)

In 1995, ten pregnant female rats were launched on the Space Shuttle (STS-70) on Gestational day(G) 11 of their 22-day pregnancy as part of the NASA/NIH.Rodent (R)2 Experiment. Following landing on G20, fetuses were harvested from half of the dams, while the remaining five dams underwent birth. Spaceflight did not interrupt pregnancy, alter litter sizes, or affect body weights or gender ratios of the fetuses or neonates. In the present study we used the NASA/NIH.R2 experimental paradigm to analyze the effects of hypergravity on pregnancy outcome. On G10, time-bred Sprague-Dawley rat dams were assigned to either G20 or Birth conditions, then further assigned to Hypergravity (HG) 2.0-g, HG 1.75-g, HG 1.5-g, Rotational Control (RC, 1.03), or Stationary Control (SC, 1.0-g) treatments. Dams were exposed to continuous centrifugation from G11 through G20, with brief daily stops for animal health checks and maintenance. For both the G20 and Birth dams, comparable litter sizes and litter gender ratios were observed across gravity conditions. However, centrifugation-exposed (HG and RC) fetuses and neonates showed significantly lower body masses (p less than 0.05) relative to SC offspring. HG 2.0-g offspring weighed significantly less than those in all other gravity conditions (p less than 0.05). The observed reductions in offspring body mass at 1.5-g and 1.75-g, can be attributed to the rotational component of centrifugation, rather than to increased gravitational load, whereas 2.0-g hypergravity exposure further exacerbated the gravity centrifugation effect on offspring body mass. Pregnant dams exposed to centrifugation weighed significantly less than SC dams (p less than 0.05), suggesting that centrifugation effects on maternal body mass may contribute to reduced size of the developing offspring. These findings are consistent with previous reports of non-pregnant adult animals suggesting that, whereas spaceflight has virtually no effect on body mass, centrifugation is associated with changes in body weight regulation.

Mills, Nicole A.↗

DOE OSTI2020

Determining the impacts of venoarterial extracorporeal membrane oxygenation on cerebral oxygenation using a one-dimensional blood flow simulator

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a mechanical system that provides rapid and short-term support for patients with cardiac failure. In many patients, pulmonary function is also impaired, resulting in poorly-oxygenated cardiac outflow competing against well-oxygenated VA-ECMO outflow, a condition known as North-South syndrome. North-South syndrome is a primary concern because of its potential to cause cerebral hypoxia, which has a critical influence on neurological complications often seen in this patient population. In order to reduce ischemic neurological complications, it is important to understand how clinical decisions regarding VA-ECMO parameters influence blood oxygenation. In our work, we studied the impacts of flow rate and cannulation site on oxygenation using a one-dimensional (1D) model to simulate blood flow. Our model was initially tested by comparing blood flow results to those observed from experimental work in VA-ECMO patients. The 1D model was combined with a two-phase flow model to simulate oxygenation. Additionally, the influence of various other clinician-tunable parameters on oxygenation in the common carotid arteries (CCAs) were tested, including, blood viscosity, cannula position within the insertion artery, heart rate, and systemic vascular resistance (SVR), as well as geometrical changes such as arterial radius and length. Our results indicated that blood oxygenation to the brain strongly depended on the cannula insertion site and the VA-ECMO flow rate with a weaker but potentially significant dependence on arterial radius. During femoral cannulation, VA-ECMO flow rates greater than ~4.9 L/min were needed to perfuse the CCAs. However, axillary and central cannulation began to perfuse the CCAs at significantly lower flow (~1 L/min). These results may help explain the incidence of cerebral hypoxia in this patient population and the common need to change cannulation strategies during treatment to address this clinical problem. While this work describes patient-averaged results, determining these relationships between VA-ECMO parameters and cerebral hypoxia is an important step towards future work to develop patient-specific models that clinicians can use to improve outcomes.

1D blood flow↗

DOE OSTI2026

Pulsed Electric Field Processing of Apples

Pulsed electric field (PEF) processing is a nonthermal technology that has the potential to improve the efficiency of apple processing, particularly for firm cultivars that are growing in popularity. This study evaluated the effects of PEF pretreatment on the processability and product quality of Cosmic Crisp apples, a modern cultivar known for its firmness. Apples were treated with PEF and assessed for tissue softening, mechanical energy requirements, particle size reduction, browning tendencies, and juice yield. PEF treatment significantly softened the apple tissue, as demonstrated by reduced compression forces in Instron testing, and this softening translated to decreased grinding energy during applesauce production. There were no changes to the particle size distribution of the resulting applesauce. PEF treatment also altered browning behavior and produced higher juice yields following mechanical disruption, suggesting enhanced membrane permeability and mass transfer. Together, these results show that PEF pretreatment can reduce mechanical energy demands and increase extractability without reducing product quality in firm apple varieties. These outcomes highlight the potential of PEF to increase the value recovered from processing-grade apples and to support more efficient and sustainable apple processing operations.

32 - ENERGY CONSERVATION, CONSUMPTION, AND UTILIZA↗

DOE OSTI2021

Screening and Validation of Molecular Targeted Radiosensitizers

The development of molecular targeted drugs with radiation and chemotherapy is critically important for improving the outcomes of patients with hard-to-treat, potentially curable cancers. However, too many preclinical studies have not translated into successful radiation oncology trials. Major contributing factors to this insufficiency include poor reproducibility of preclinical data, inadequate preclinical modeling of intertumoral genomic heterogeneity that influences treatment sensitivity in the clinic, and a reliance on tumor growth delay instead of local control (TCD50) endpoints. There exists an urgent need to overcome these barriers to facilitate successful clinical translation of targeted radiosensitizers. To this end, we have used 3-dimensional (3D) cell culture assays to better model tumor behavior in vivo. Examples of successful prediction of in vivo effects with these 3D assays include radiosensitization of head and neck cancers by inhibiting epidermal growth factor receptor or focal adhesion kinase signaling, and radioresistance associated with oncogenic mutation of KRAS. To address the issue of tumor heterogeneity, we leveraged institutional resources that allow high-throughput 3D screening of radiation combinations with small-molecule inhibitors across genomically characterized cell lines from lung, head and neck, and pancreatic cancers. This high-throughput screen is expected to uncover genomic biomarkers that will inform the successful clinical translation of targeted agents from the National Cancer Institute Cancer Therapy Evaluation Program portfolio and other sources. Screening “hits” need to be subjected to refinement studies that include clonogenic assays, addition of disease-specific chemotherapeutics, target/biomarker validation, and integration of patient-derived tumor models. The chemoradiosensitizing activities of the most promising drugs should be confirmed in TCD50 assays in xenograft models with or without relevant biomarker and using clinically relevant radiation fractionation. We predict that appropriately validated and biomarker-directed targeted therapies will have a higher likelihood than past efforts of being successfully incorporated into the standard management of hard-to-treat tumors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗