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All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Ion transport in non-aqueous electrolyte mixtures of zinc chloride deep eutectic solvent (DES) and molecular solvents

For this work, the ion dynamics of null solvents 1ZnCl 2 :4EtG and 1ChCl:1ZnCl 2 :6EtG incorporating 1M water, propylene carbonate (PC) or acetonitrile (AcN) were investigated using 1 H NMR spectra and spin-lattice relaxation time (T 1 ) measurements combined with ionic conductivity, density, and viscosity, all as a function of temperature. Results show that the inclusion of all co-solvents increased the available free volume of the mixtures and followed the trend H 2 O ≤ PC < AcN. 1 H NMR spectra and T 1 inferred the presence of multiple ionic species with varying rates of mobilities. These dynamic heterogeneities were displayed by the broad T 1 minima – especially for the 1ZnCl 2 :4EtG mixtures – and asymmetrically broadened linewidths. T 1 results also revealed selective interaction sites between the hydrogen bond donors and acceptors, as well as with the co-solvents.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2013

Temporal trends (1989–2011) in levels of mercury and other heavy metals in feathers of fledgling great egrets nesting in Barnegat Bay, NJ

There is an abundance of data for levels of metals from a range of species, but relatively few long-term time series from the same location. In this paper I examine the levels of arsenic, cadmium, chromium, lead, manganese, mercury and selenium in feathers from fledgling great egrets (Ardea alba) collected at nesting colonies in Barnegat Bay, New Jersey from 1989 to 2011. The primary objectives were to test the null hypotheses that (1) There were no temporal differences in metal levels in feathers of fledgling great egrets, and (2) Great egrets nesting in different areas of Barnegat Bay (New Jersey) did not differ in metal levels. There were significant yearly variations in levels of all heavy metals in feathers of fledgling great egret, but levels decreased significantly from 1989 to 2011 only for lead (1470 ppb to 54.3 ppb), cadmium (277 ppb to 30.5 ppb), and manganese (only since 1996; 2669 ppb to 329 ppb)). Although mercury levels decreased from 2003–2008 (6430 ppb to 1042 ppb), there was no pattern before 2003, and levels increased after 2008 to 2610 ppb in 2011. Lead, cadmium, chromium, manganese and mercury were higher in feathers from great egrets nesting in the northern part of the bay, and selenium was highest in feathers from mid-bay. The lack of a temporal decline in mercury levels in feathers of great egrets is cause for concern, since the high levels in feathers from some years (means as high as 6430 ppb) are in the range associated with adverse effects (5000 ppb for feathers). -- Highlights: ► Metals were monitored in feathers of great egrets from Barnegat Bay, New Jersey. ► Levels of cadmium and lead decreased significantly from 1989–2011. ► Mercury levels in feathers from great egrets did not decline from 1989–2011. ► Metal levels were generally higher in great egrets and black-crowned night heron feathers than in snowy egrets.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Adverse pregnancy outcomes in women with changing patterns of exposure to the emissions of a municipal waste incinerator

Highlights: • Reproductive health outcomes are suitable for risk assessment of a waste incinerator. • Emissions from a municipal solid waste incinerator did not increase miscarriage rate. • Emissions from a municipal solid waste incinerator did not increase birth defects. Municipal solid waste incinerators emissions contain pollutants that, despite their low concentration, might adversely affect reproductive health. In the present study, we examined rates of miscarriage and birth defects among women who resided or were employed in the vicinity of a municipal solid waste incinerator plant from 2003 to 2013. In 2009, a progressive shutdown of the old incineration lines and operation of a new line caused considerably higher atmospheric release of polycyclic aromatic hydrocarbons, particularly of dioxins, due to these irregular operating conditions, technological renovation, and increased capacity. We used dioxin emission levels, based on a dispersion model, to define exposure status of the residing population to air pollutants emitted by the waste incinerator. In women who resided in areas characterized by higher emission exposures compared with a referent area, the relative risk (RR) of miscarriage was 1.04 (95% confidence interval (CI) 0.80–1.32) based on 62 cases overall, with little evidence of a dose-response relation. RRs were similarly null for both 2003–2008 and 2010–2013 periods (RR 1.12 (95% CI 0.80–1.53) and 0.98 (95% CI 0.63–1.48), respectively). Concerning birth defects in the offspring of women residing in the exposed area, no evidence of increased risk emerged, since the prevalence ratio at birth was 0.64 (95% CI 0.29–1.26), with comparable results in the 2003–2008 and 2010–2013 period. Corresponding analyses carried out in municipal residents who worked in the exposed area confirmed these findings. We also did not detect abnormally high rates of miscarriage and birth defects in the exposed cohorts in the single year 2009. Overall, these results do not suggest an effect of exposure to the emissions of the municipal solid waste incinerator we investigated on two indicators of reproductive health. However, the limited statistical stability of the estimates and the absence of individual-based information on some potential confounders suggest caution in the interpretation of study findings.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Effects of incomplete residential histories on studies of environmental exposure with application to childhood leukaemia and background radiation

Highlights: • Residential exposures are most important for many environmental carcinogens. • Direct measurement in all occupied homes is the gold standard but may be impractical. • About half of cases of childhood cancer have not moved between birth and diagnosis. • Most house movements are short-range; exposures in successive houses are correlated. • Analyses using exposure estimation from a single address are informative. When evaluating environmental exposures, residential exposures are often most relevant. In most countries, it is impossible to establish full residential histories. In recent publications, childhood leukaemia and background radiation have been studied with and without full residential histories. This paper investigates the consequences of lacking such full data. Data from a nationwide Finnish Case-Control study of Childhood Leukaemia and gamma rays were analysed. This included 1093 children diagnosed with leukaemia in Finland in 1990–2011. Each case was matched by gender and year of birth to three controls. Full residential histories were available. The dose estimates were based on outdoor background radiation measurements. The indoor dose rates were obtained with a dwelling type specific conversion coefficient and the individual time-weighted mean red bone marrow dose rates were calculated using age-specific indoor occupancy and the age and gender of the child. Radiation from Chernobyl fallout was included and a 2-year latency period assumed. The median separation between successive dwellings was 3.4 km and median difference in red bone marrow dose 2.9 nSv/h. The Pearson correlation between the indoor red bone marrow dose rates of successive dwellings was 0.62 (95% CI 0.60, 0.64). The odds ratio for a 10 nSv/h increase in dose rate with full residential histories was 1.01 (95% CI 0.97, 1.05). Similar odds ratios were calculated with dose rates based on only the first dwelling (1.02, 95% CI 0.99, 1.05) and only the last dwelling (1.00, 95% CI 0.98, 1.03) and for subjects who had lived only in a single dwelling (1.05, 95% CI 0.98, 1.10). Knowledge of full residential histories would always be the option of choice. However, due to the strong correlation between exposure estimates in successive dwellings and the uncertainty about the most relevant exposure period, estimation of overall exposure level from a single address is also informative. Error in dose estimation is likely to cause some degree of classical measurement error resulting in bias towards the null.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2018

A critical evaluation of the NCRP COMMENTARY 27 endorsement of the linear no-threshold model of radiation effects

Highlights: • The linear no-threshold (LNT) model of radiation effects has fractured the scientific community. • This paper analyzes the latest review of the LNT model, NCRP Commentary 27. • Expert reviews of the LNT model rely on institutional inertia and numerous logical fallacies. • Recommendations to advance this debate in an objective future review are provided. Regulatory policy to protect the public and the environment from radiation is universally based on the linear, no-threshold model (LNT) of radiation effects. This model has been controversial since its inception over nine decades ago, and remains so to this day, but it has proved remarkably resistant to challenge from the scientific community. The LNT model has been repeatedly endorsed by expert advisory bodies, and regulatory agencies in turn adopt policies that reflect this advice. Unfortunately, these endorsements rest on a foundation of institutional inertia and numerous logical fallacies. These include most significantly setting the LNT as the null hypothesis, and shifting the burden of proof onto LNT skeptics. Other examples include arbitrary exclusion of alternative hypotheses, ignoring criticisms of the LNT, cherry-picking evidence, and making policy judgements without foundation. This paper presents an evaluation of the National Council on Radiation Protection and Measurements’ (NCRP) Commentary 27, which concluded that recent epidemiological studies are compatible with the continued use of the LNT model for radiation protection. While this report will likely provide political cover for regulators’ continued reliance on the LNT, it is a missed opportunity to advance the scientific discussion of the effects of low dose, low dose-rate radiation exposure. Due to its Congressionally chartered mission, no organization is better positioned than the NCRP to move this debate forward, and recommendations for doing so in future reviews are provided.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Joint estimation of biogeochemical model parameters from multiple experiments: A bayesian approach applied to mercury methylation

Here, to characterize complex biogeochemical systems, results from multiple experiments, where each targets a specific subprocess, are commonly combined. The resulting datasets are interpreted through the calibration of biogeochemical models for process inference and predictions. Commonly used calibration approaches of fitting datasets from individual experiments to subprocess models one at a time is prone to missing information shared between datasets and incomplete uncertainty propagation. We propose a Bayesian joint-fitting scheme addressing the above-mentioned concerns by jointly fitting all the available datasets, thus calibrating the entire biogeochemical model in one go using Markov Chain Monte Carlo (MCMC). The identification of null spaces in the parameter distributions from MCMC guided the simplification of certain subprocess models. For example, fast kinetic sorption was replaced by equilibrium sorption, and Monod demethylation was replaced by first-order demethylation. Joint fitting of datasets resulted in complete uncertainty propagation with parameter estimates informed by all available data.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2026

Scaling open-weight large language models for hydropower regulatory information extraction: A systematic analysis

Information extraction from regulatory and technical documents using large language models (LLMs) involves practical trade-offs between extraction quality and computational cost. We evaluate eight open-weight LLMs spanning 0.6B–70B parameters on hydropower licensing documents and report deployment-oriented evidence under a unified extraction schema and evaluation protocol. Across the model set, we observe clear scale-dependent trends in both baseline extraction quality and the effectiveness of reflective reasoning (self-checking) under our fixed-prompt, no-augmentation setting. Mid-scale models often provide a favorable balance of accuracy and efficiency, whereas the smallest models show limited or inconsistent gains from the reasoning variants tested. Larger models achieve the highest overall F1 scores but incur substantially greater compute and infrastructure requirements. We further find that reliability failure modes can distort conventional metrics in this domain: in particular, high recall can coincide with systematic extraction errors when models fabricate values for fields that are absent from the source text, underscoring the importance of conservative null handling and evidence-grounded evaluation. Overall, our study provides a reproducible resource–performance comparison for open-weight LLM-based extraction in hydropower regulatory documentation and offers practical guidance for model selection under different deployment constraints.

Evaluation protocol↗
DOE OSTI2016

Results of availability imposed configuration details developed for K-DEMO

We completed a two year study using the Korean fusion demonstration reactor (K-DEMO) where we looked at key Tokamak components and configuration options in preparation of a conceptual design phase. A key part of a device configuration centers on defining an arrangement that enhances the ability to reach high availability values by defining design solutions that foster simplified maintenance operations. In order to maximize the size and minimize the number of in-vessel components enlarged TF coils were defined that incorporate a pair of windings within each coil to mitigate pressure drop issues and to reduce the cost of the coils. Furthermore, we defined a semi-permanent shield structure in order to develop labyrinth interfaces between double-null plasma contoured shield modules, provide an entity to align blanket components and provide support against disruption loads—with a load path that equilibrates blanket, TF and PF loads through a base structure. Blanket piping services and auxiliary systems that interface with in-vessel components have played a major role in defining the overall device arrangement—concept details will be presented along with general arrangement features and preliminary results obtained from disruption analysis.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2018

Conceptual design study for heat exhaust management in the ARC fusion pilot plant

The ARC pilot plant conceptual design study has been extended beyond its initial scope to explore options for managing ∼525 MW of fusion power generated in a compact, high field (B 0 = 9.2 T) tokamak that is approximately the size of JET (R 0 = 3.3 m). Taking advantage of ARC’s novel design – demountable high temperature superconductor toroidal field (TF) magnets, poloidal magnetic field coils located inside the TF, and vacuum vessel (VV) immersed in molten salt FLiBe blanket – this follow-on study has identified innovative and potentially robust power exhaust management solutions. The superconducting poloidal field coil set has been reconfigured to produce double-null plasma equilibria with a long-leg X-point target divertor geometry. Here this design choice is motivated by recent modeling which indicates that such configurations enhance power handling and may attain a passively-stable detachment front that stays in the divertor leg over a wide power exhaust window. A modified VV accommodates the divertor legs while retaining the original core plasma volume and TF magnet size. The molten salt FLiBe blanket adequately shields all superconductors, functions as an efficient tritium breeder, and, with augmented forced flow loops, serves as an effective single-phase, low-pressure coolant for the divertor, VV, and breeding blanket. Advanced neutron transport calculations (MCNP) indicate a tritium breeding ratio of ∼1.08. The neutron damage rate (DPA/year) of the remote divertor targets is ∼3–30 times lower than that of the first wall. The entire VV (including divertor and first wall) can tolerate high damage rates since the demountable TF magnets allow the VV to be replaced every 1–2 years as a single unit, employing a vertical maintenance scheme. A tungsten swirl tube FLiBe coolant channel design, similar in geometry to that used by ITER, is considered for the divertor heat removal and shown capable of exhausting divertor heat flux levels of up to 12 MW/m 2 . Several novel, neutron tolerant diagnostics are explored for sensing power exhaust and for providing feedback control of divertor conditions over long time scales. These include measurement of Cherenkov radiation emitted in FLiBe to infer DT fusion reaction rate, measurement of divertor detachment front locations in the divertor legs with microwave interferometry, and monitoring “hotspots” on the divertor chamber walls via IR imaging through the FLiBe blanket.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2020

Recent progress in the design of the K-DEMO divertor

The preliminary conceptual design of the Korean fusion demonstration reactor (K-DEMO) with a major radius of 6.8 m and the fusion power of 2200 MW has been studied since 2012. The overall configuration of the K-DEMO divetor system based on the ITER-like water-cooled tungsten technology is a double-null type symmetric divertor subdivided into 32 toroidal modules for the vertical maintenance. A detached divertor scenario with impurity seeding was considered as the primary approach for the power exhaust to reduce the peak heat flux lower than the engineering limit of 10 MW/m 2 . The power exhaust performance at the scrap off layer was estimated by using UEDGE-2D code, a two-dimensional fluid transport code for collisional edge plasma and neutral species like N, Ne, and Ar. Particle and heat flux on inboard and outboard divertor targets were calculated for the detached cased depending on parameters such as the impurity seeding rate, pumping rate, and the pedestal density. On the other hand, a magnetic solution like X-divertor, snowflake divertor, and super X-divertor to expand the plasma wet area was considered for K-DEMO since the detached divertor increasing a radiation fraction by impurity seeding might be able to be unstable. However, the extremely high current of poloidal coils was required more than the engineering limit, 20 MA, to form magnetic field lines for the alternative divertors. Based on the physical calculation of the edge plasma, engineering analyses were carried out to find out the thermal and structural reliability. The thermo-hydraulic analysis confirmed thermal stability, whether all comprising materials are operating within their allowable temperature windows when the case of the peak heat flux is set to 10 MW/m 2 on the outboard divertor target. The response surface optimization method derived two optimal design candidates employing two kinds of heat sink materials, respectively: the reduced activation ferritic martensitic (RAFM) steel and CuCrZr alloy. Additionally, the drawbacks and merits of the two materials were definite. The optimal design with applying RAFM steel was vulnerable to withstand thermal and mechanical loads since low thermal conductivity caused too thin thickness of the heat sink. On the other hand, the CuCrZr alloy has critical drawbacks in terms of activation and radioactive waste despite its high thermal conductivity. Meanwhile, preliminary electromagnetic (EM) analysis was carried out to estimate the EM loads caused by the abnormal behaviors of plasma since EM loads are one of the most critical external loads for designing a DEMO divertor.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2025

Plasma shape and position control development for NSTX-U using the GSEvolve plasma simulator

NSTX-U discharges have been reproduced using the GSEvolve plasma simulator in order to improve their control and reduce oscillations during the plasma current (Ip) ramp-up phase, and with the ultimate goal of enabling reliable H-mode access with a double-null shape at high elongation, low internal inductance, and high plasma performance. The control objective is to eliminate undesired oscillations in the plasma shape and vertical position that start when the plasma diverts during the Ip ramp-up phase, and that happened recurrently during the first NSTX-U experimental campaign. Model-based control solutions have been developed, including alternative H-mode access recipes and a Multi-Input Multi-Output (MIMO) decoupling controller. These solutions have demonstrated their capability to reduce or eliminate the aforementioned oscillations in GSEvolve simulations, enabling reproducible H-mode access. The results of this work aim to inform NSTX-U experimental operations on potential control developments to maximize its scientific output, and highlight the powerful capabilities of high-fidelity control-simulation frameworks like GSEvolve.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2013

Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

A Critical Role of the PTEN/PDGF Signaling Network for the Regulation of Radiosensitivity in Adenocarcinoma of the Prostate

Purpose: Loss or mutation of the phosphate and tensin homologue (PTEN) is a common genetic abnormality in prostate cancer (PCa) and induces platelet-derived growth factor D (PDGF D) signaling. We examined the role of the PTEN/PDGF axis on radioresponse using a murine PTEN null prostate epithelial cell model. Methods and Materials: PTEN wild-type (PTEN{sup +/+}) and PTEN knockout (PTEN{sup −/−}) murine prostate epithelial cell lines were used to examine the relationship between the PTEN status and radiosensitivity and also to modulate the PDGF D expression levels. PTEN{sup −/−} cells were transduced with a small hairpin RNA (shRNA) lentiviral vector containing either scrambled nucleotides (SCRM) or sequences targeted to PDGF D (shPDGF D). Tumorigenesis and morphogenesis of these cell lines were evaluated in vivo via subcutaneous injection of male nude mice and in vitro using Matrigel 3-dimensional (3D) culture. Effects of irradiation on clonogenic survival, cell migration, and invasion were measured with respect to the PTEN status and the PDGF D expression level. In addition, apoptosis and cell cycle redistribution were examined as potential mechanisms for differences seen. Results: PTEN{sup −/−} cells were highly tumorigenic in animals and effectively formed foci in 3D culture. Importantly, loss of PDGF D in these cell lines drastically diminished these phenotypes. Furthermore, PTEN{sup −/−} cells demonstrated increased clonogenic survival in vitro compared to PTEN{sup +/+}, and attenuation of PDGF D significantly reversed this radioresistant phenotype. PTEN{sup −/−} cells displayed greater migratory and invasive potential at baseline as well as after irradiation. Both the basal and radiation-induced migratory and invasive phenotypes in PTEN{sup −/−} cells required PDGF D expression. Interestingly, these differences were independent of apoptosis and cell cycle redistribution, as they showed no significant difference. Conclusions: We propose that PDGF D represents a potentially promising target for PCa treatment resistance in the absence of PTEN function, and warrants further laboratory evaluation and clinical study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Targeting Nucleophosmin 1 Represents a Rational Strategy for Radiation Sensitization

Purpose: To test the hypothesis that small molecule targeting of nucleophosmin 1 (NPM1) represents a rational approach for radiosensitization. Methods and Materials: Wilde-type and NPM1-deficient mouse embryo fibroblasts (MEFs) were used to determine whether radiosensitization produced by the small molecule YTR107 was NPM1 dependent. The stress response to ionizing radiation was assessed by quantifying pNPM1, γH2AX, and Rad51 foci, neutral comet tail moment, and colony formation. NPM1 levels in a human-derived non-small-cell lung cancer (NSCLC) tissue microarray (TMA) were determined by immunohistochemistry. YTR107-mediated radiosensitization was assessed in NSCLC cell lines and xenografts. Results: Use of NPM1-null MEFs demonstrated that NPM1 is critical for DNA double- strand break (DSB) repair, that loss of NPM1 increases radiation sensitivity, and that YTR107-mediated radiosensitization is NPM1 dependent. YTR107 was shown to inhibit NPM1 oligomerization and impair formation of pNPM1 irradiation-induced foci that colocalized with γH2AX foci. Analysis of the TMA demonstrated that NPM1 is overexpressed in subsets of NSCLC. YTR107 inhibited DNA DSB repair and radiosensitized NSCLC lines and xenografts. Conclusions: These data demonstrate that YTR107-mediated targeting of NPM1 impairs DNA DSB repair, an event that increases radiation sensitivity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

Purpose: To perform a prospective, multi-institutional, phase 2 study of a substantial decrease in concurrent chemoradiation therapy (CRT) intensity as primary treatment for favorable-risk, human papillomavirus–associated oropharyngeal squamous cell carcinoma. Methods and Materials: The major inclusion criteria were: (1) T0 to T3, N0 to N2c, M0; (2) human papillomavirus or p16 positive; and (3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy with concurrent weekly intravenous cisplatinum (30 mg/m{sup 2}). The primary study endpoint was pathologic complete response (pCR) rate based on required biopsy of the primary site and dissection of pretreatment positive lymph node regions, regardless of radiographic response. Power computations were performed for the null hypothesis that the pCR rate is 87% and n=40, resulting in a type 1 error of 14.2%. Secondary endpoint measures included physician-reported toxicity (Common Toxicity Terminology for Adverse Events, CTCAE), patient-reported symptoms (PRO-CTCAE), and modified barium swallow studies. Results: The study population was 43 patients. The pCR rate was 86% (37 of 43). The incidence of CTCAE grade 3/4 toxicity and PRO-CTCAE severe/very severe symptoms was as follows: mucositis 34%/45%, general pain 5%/48%, nausea 18%/52%, vomiting 5%/34%, dysphagia 39%/55%, and xerostomia 2%/75%. Grade 3/4 hematologic toxicities were 11%. Thirty-nine percent of patients required a feeding tube for a median of 15 weeks (range, 5-22 weeks). There were no significant differences in modified barium swallow studies before and after CRT. Conclusions: The pCR rate with decreased intensity of therapy with 60 Gy of IMRT and weekly low-dose cisplatinum is very high in favorable-risk oropharyngeal squamous cell carcinoma, with evidence of decreased toxicity compared with standard therapies. (ClinicalTrials.gov) ID: (NCT01530997).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Wee1 Kinase Inhibitor AZD1775 Radiosensitizes Hepatocellular Carcinoma Regardless of TP53 Mutational Status Through Induction of Replication Stress

Purpose: Wee1 kinase inhibitors are effective radiosensitizers in cells lacking a G{sub 1} checkpoint. In this study we examined the potential effect of Wee1 kinase inhibition on inducing replication stress in hepatocellular carcinoma (HCC). Methods and Materials: Five independent datasets from the Oncomine database comparing gene expression in HCC compared to normal tissue were combined and specific markers associated with Wee1 sensitivity were analyzed. We then performed a series of in vitro experiments to study the effect of Wee1 inhibition on irradiated HCC cell lines with varying p53 mutational status. Clonogenic survival assays and flow cytometry using anti-γH2AX and phospho-histone H3 antibodies with propidium iodide were performed to study the effect of AZD1775 on survival, cell cycle, and DNA repair. Additionally, nucleoside enriched medium was used to examine the effect of altering nucleotide pools on Wee1 targeted radiation sensitization. Results: Our analysis of the Oncomine database found high levels of CDK1 and other cell cycle regulators indicative of Wee1 sensitivity in HCC. In our in vitro experiments, treatment with AZD1775 radiosensitized and chemosensitized Hep3B, Huh7, and HepG2 cell lines and was associated with delayed resolution of γH2AX foci and the induction of pan-nuclear γH2AX staining. Wee1 inhibition attenuated radiation-induced G{sub 2} arrest in the Hep3B (TP53 null) and Huh7 (TP53 mutant) cell lines but not in the TP53 wild-type cell line HepG2. Supplementation with nucleosides reversed the radiation-sensitizing effect of AZD1775 and reduced the amount of cells with pan-nuclear γH2AX staining after radiation. Conclusions: Radiation sensitization with Wee1 inhibition occurs in cells regardless of their p53 mutational status. In this study we show for the first time that replication stress via the overconsumption of nucleotides plays an important role in AZD1775-induced radiation sensitization.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Contemporary Trends in Radiation Oncology Resident Research

Purpose: To test the hypothesis that recent resident research productivity might be different than a decade ago, and to provide contemporary information about resident scholarly activity. Methods and Materials: We compiled a list of radiation oncology residents from the 2 most recent graduating classes (June 2014 and 2015) using the Association of Residents in Radiation Oncology annual directories. We queried the PubMed database for each resident's first-authored publications from postgraduate years (PGY) 2 through 5, plus a 3-month period after residency completion. We abstracted corresponding historical data for 2002 to 2007 from the benchmark publication by Morgan and colleagues (Int J Radiat Oncol Biol Phys 2009;74:1567-1572). We tested the null hypothesis that these 2 samples had the same distribution for number of publications using the Wilcoxon rank-sum test. We explored the association of demographic factors and publication number using multivariable zero-inflated Poisson regression. Results: There were 334 residents publishing 659 eligible first-author publications during residency (range 0-17; interquartile range 0-3; mean 2.0; median 1). The contemporary and historical distributions were significantly different (P<.001); contemporary publication rates were higher. Publications accrued late in residency (27% in PGY-4, 59% in PGY-5), and most were original research (75%). In the historical cohort, half of all articles were published in 3 journals; in contrast, the top half of contemporary publications were spread over 10 journals—most commonly International Journal of Radiation Oncology • Biology • Physics (17%), Practical Radiation Oncology (7%), and Radiation Oncology (4%). Male gender, non-PhD status, and larger residency size were associated with higher number of publications in the multivariable analysis. Conclusion: We observed an increase in first-author publications during training compared with historical data from the mid-2000s. These contemporary figures may be useful to medical students considering radiation oncology, current residents, training programs, and prospective employers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Asymptomatic Late-phase Radiographic Changes Among Chest-Wall Patients Are Associated With a Proton RBE Exceeding 1.1

Clinical practice assumes a fixed proton relative biological effectiveness (RBE) of 1.1, but in vitro experiments demonstrate higher RBEs at the distal edge of the proton spread-out Bragg peak, that is, in a region that falls within the lung for chest-wall patients. We performed retrospective qualitative and quantitative analyses of lung-density changes—indicative of asymptomatic fibrosis—for chest-wall patients treated with protons or photons. Our null hypothesis was that, assuming a fixed RBE of 1.1, these changes would be the same for the 2 cohorts, supporting current RBE practice. Our alternative hypothesis was that radiographic abnormalities would be greater for the proton cohort, suggesting an RBE > 1.1.

62 RADIOLOGY AND NUCLEAR MEDICINE↗