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Unexpected Consequences of Block Polydispersity on the Self-Assembly of ABA Triblock Copolymers

Controlled/'living' polymerizations and tandem polymerization methodologies offer enticing opportunities to enchain a wide variety of monomers into new, functional block copolymer materials with unusual physical properties. However, the use of these synthetic methods often introduces nontrivial molecular weight polydispersities, a type of chain length heterogeneity, into one or more of the copolymer blocks. While the self-assembly behavior of monodisperse AB diblock and ABA triblock copolymers is both experimentally and theoretically well understood, the effects of broadening the copolymer molecular weight distribution on block copolymer phase behavior are less well-explored. We report the melt-phase self-assembly behavior of SBS triblock copolymers (S = poly(styrene) and B = poly(1,4-butadiene)) comprised of a broad polydispersity B block (M{sub w}/M{sub n} = 1.73-2.00) flanked by relatively narrow dispersity S blocks (M{sub w}/M{sub n} = 1.09-1.36), in order to identify the effects of chain length heterogeneity on block copolymer self-assembly. Based on synchrotron small-angle X-ray scattering and transmission electron microscopy analyses of seventeen SBS triblock copolymers with poly(1,4-butadiene) volume fractions 0.27 {le} f{sub B} {le} 0.82, we demonstrate that polydisperse SBS triblock copolymers self-assemble into periodic structures with unexpectedly enhanced stabilities that greatly exceed those of equivalent monodisperse copolymers. The unprecedented stabilities of these polydisperse microphase separated melts are discussed in the context of a complete morphology diagram for this system, which demonstrates that narrow dispersity copolymers are not required for periodic nanoscale assembly.

36 MATERIALS SCIENCE↗

Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation

Purpose: To evaluate the feasibility of magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU. Methods and Materials: Mild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh were evaluated. Thermal maps obtained in 6 planes every 3.2 seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60 minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor. Results: In pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C. With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion. Conclusions: In pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30 minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-T-54: Benefits of Biological Cost Functions

Purpose: To verify the benefits of the biological cost functions. Methods: TG166 patients were used for the test case scenarios. Patients were planned using Monaco V5.0 (CMS/Elekta, St.Louis, MO) Monaco has 3 biological and 8 physical CFs. In this study the plans were optimized using 3 different scenarios. 1- Biological CFs only 2-Physical CFs only 3- Combination of Physical and Biological CFsMonaco has 3 biological CFs. Target EUD used for the targets, derived from the poisson cell kill model, has an α value that controls the cold spots inside the target. α values used in the optimization were 0.5 and 0.8. if cold spots needs to be penalized α value increased. Serial CF: it's called serial to mimic the behaviour of the serial organs, if a high k value like 12 or 14 is used it controls the maximum dose. Serial CF has a k parameter that is used to shape the whole dvh curve. K value ranges between 1–20. k:1 is used to control the mean dose, lower k value controls the mean dose, higher k value controls the higher dose, using 2 serial CFs with different k values controls the whole DVH. Paralel CF controls the percentage of the volume that tolerates higher doses than the reference dose to mimic the behaviour of the paralel organs. Results: It was possible to achive clinically accepted plans in all 3 scenarios. The benefit of the biological cost functions were to control the mean dose for target and OAR, to shape the DVH curve using one EUD value and one k value simplifies the optimization process. Using the biological CFs alone, it was hard to control the dose at a point. Conclusion: Biological CFs in Monaco doesn't require the ntcp/tcp values from the labs and useful to shape the whole dvh curve. I work as an applications support specialist for Elekta and I am a Ph.D. Student in Istanbul University for radiation therapy physics.

60 APPLIED LIFE SCIENCES↗

Benefits of adaptive radiation therapy in lung cancer as a function of replanning frequency

Purpose: To quantify the potential benefit associated with daily replanning in lung cancer in terms of normal tissue dose sparing and to characterize the tradeoff between adaptive benefit and replanning frequency. Methods: A set of synthetic images and contours, derived from weekly active breathing control images of 12 patients who underwent radiation therapy treatment for nonsmall cell lung cancer, is generated for each fraction of treatment using principal component analysis in a way that preserves temporal anatomical trends (e.g., tumor regression). Daily synthetic images and contours are used to simulate four different treatment scenarios: (1) a “no-adapt” scenario that simulates delivery of an initial plan throughout treatment, (2) a “midadapt” scenario that implements a single replan for fraction 18, (3) a “weekly adapt” scenario that simulates weekly adaptations, and (4) a “full-adapt” scenario that simulates daily replanning. An initial intensity modulated radiation therapy plan is created for each patient and replanning is carried out in an automated fashion by reoptimizing beam apertures and weights. Dose is calculated on each image and accumulated to the first in the series using deformable mappings utilized in synthetic image creation for comparison between simulated treatments. Results: Target coverage was maintained and cord tolerance was not exceeded for any of the adaptive simulations. Average reductions in mean lung dose (MLD) and volume of lung receiving 20 Gy or more (V20{sub lung}) were 65 ± 49 cGy (p = 0.000 01) and 1.1% ± 1.2% (p = 0.0006), respectively, for all patients. The largest reduction in MLD for a single patient was 162 cGy, which allowed an isotoxic escalation of the target dose of 1668 cGy. Average reductions in cord max dose, mean esophageal dose (MED), dose received by 66% of the heart (D66{sub heart}), and dose received by 33% of the heart (D33{sub heart}), were 158 ± 280, 117 ± 121, 37 ± 77, and 99 ± 120 cGy, respectively. Average incremental reductions in MLD for the midadapt, weekly adapt, and full-adapt treatments were 38, 18, and 8 cGy, respectively. Incremental reductions in MED for the same treatments were 57, 37, and 23 cGy. Reductions in MLD and MED for the full-adapt treatment were correlated with the absolute decrease in the planning target volume (r = 0.34 and r = 0.26). Conclusions: Adaptive radiation therapy for lung cancer yields clinically relevant reductions in normal tissue doses for frequencies of adaptation ranging from a single replan up to daily replanning. Increased frequencies of adaptation result in additional benefit while magnitude of benefit decreases.

60 APPLIED LIFE SCIENCES↗

waveSZ: A Hardware-Algorithm Co-Design of Efficient Lossy Compression for Scientific Data

Error-bounded lossy compression is critical to the success of extreme-scale scientific research because of ever-increasing volumes of data produced by today's high-performance computing (HPC) applications. Not only can error-controlled lossy compressors significantly reduce the I/O and storage burden but they can retain high data fidelity for post analysis. Existing state-of-the-art lossy compressors, however, generally suffer from relatively low compression and decompression throughput (up to hundreds of megabytes per second on a single CPU core), which considerably restrict the adoption of lossy compression by many HPC applications especially those with a fairly high data production rate. In this paper, we propose a highly efficient lossy compression approach based on field programmable gate arrays (FPGAs) under the state-of-the-art lossy compression model SZ. Our contributions are fourfold. (1) We adopt a wavefront memory layout to alleviate the data dependency during the prediction for higher-dimensional predictors, such as the Lorenzo predictor. (2) We propose a co-design framework named WAVESZ based on the wavefront memory layout and the characteristics of SZ algorithm and carefully implement it by using high-level synthesis. (3) We propose a hardware-algorithm co-optimization method to improve the performance. (4) We evaluate our proposed WAVESZ on three real-world HPC simulation datasets from the Scientific Data Reduction Benchmarks and compare it with other state-of-the-art methods on both CPUs and FPGAs. Experiments show that our WAVESZ can improve SZ's compression throughput by 6.9x similar to 8.7x over the production version running on a state-of-the-art CPU and improve the compression ratio and throughput by 2.1x and 5.8x on average, respectively, respectively, compared with the state-of-the-art FPGA design.

Compression Ratio↗

2013 Groundwater Monitoring Report, Central Nevada Test Area Subsurface Corrective Action Unit 443

The Central Nevada Test Area was the site of a 0.2- to 1-megaton underground nuclear test in 1968. The surface of the site has been closed, but the subsurface is still in the corrective action process. The corrective action alternative selected for the site was monitoring with institutional controls. Annual sampling and hydraulic head monitoring of the well network are conducted as part of the subsurface corrective action strategy for the site. The monitoring well network was enhanced in 2013 with the installation of a new well MV-6. The site is currently in the fifth year of the 5-year proof-of-concept monitoring period. Analytical results from the 2013 monitoring are consistent with those of previous years indicating no tritium or 14 C concentrations above the required detection limits. Water level data from new wells MV-4 and MV-5 and recompleted well HTH-1RC indicate that hydraulic heads are still recovering from installation and testing. Data from wells MV-4 and MV-5 also indicate that head levels have not yet recovered from the 2011 sampling event during which several thousand gallons of water were purged. Low-flow bladder pumps were installed during the November 2013 sampling event to reduce the well purge volumes and the impact purging has on the water levels during sampling. The new bladder pumps allow the collection of groundwater samples using the low-flow sampling method and will allow head levels to recover to steadystate conditions. Despite the lack of steady-state groundwater conditions, hydraulic head data collected from site continue to support the conceptual model that the southeast-bounding graben fault acts as a barrier to groundwater flow at the site.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

X-Ray Microanalysis and Electron Energy Loss Spectrometry in the Analytical Electron Microscope: Review and Future Directions

This paper reviews and discusses future directions in analytical electron microscopy for microchemical analysis using X-ray and Electron Energy Loss Spectroscopy (EELS). The technique of X-ray microanalysis, using the ratio method and k(sub AB) factors, is outlined. The X-ray absorption correction is the major barrier to the objective of obtaining I% accuracy and precision in analysis. Spatial resolution and Minimum Detectability Limits (MDL) are considered with present limitations of spatial resolution in the 2 to 3 microns range and of MDL in the 0.1 to 0.2 wt. % range when a Field Emission Gun (FEG) system is used. Future directions of X-ray analysis include improvement in X-ray spatial resolution to the I to 2 microns range and MDL as low as 0.01 wt. %. With these improvements the detection of single atoms in the analysis volume will be possible. Other future improvements include the use of clean room techniques for thin specimen preparation, quantification available at the I% accuracy and precision level with light element analysis quantification available at better than the 10% accuracy and precision level, the incorporation of a compact wavelength dispersive spectrometer to improve X-ray spectral resolution, light element analysis and MDL, and instrument improvements including source stability, on-line probe current measurements, stage stability, and computerized stage control. The paper reviews the EELS technique, recognizing that it has been slow to develop and still remains firmly in research laboratories rather than in applications laboratories. Consideration of microanalysis with core-loss edges is given along with a discussion of the limitations such as specimen thickness. Spatial resolution and MDL are considered, recognizing that single atom detection is already possible. Plasmon loss analysis is discussed as well as fine structure analysis. New techniques for energy-loss imaging are also summarized. Future directions in the EELS technique will be the development of new spectrometers and improvements in thin specimen preparation. The microanalysis technique needs to be simplified and software developed so that the EELS technique approaches the relative simplicity of the X-ray technique. Finally, one can expect major improvements in EELS imaging as data storage and processing improvements occur.

Goldstein, J. I.↗

SEM petrography of dispersed organic matter in black shales: A review

Organic matter (OM)-hosted pores are important constituents of the pore system of black shales and play a crucial role in determining their methane adsorption capacity and porosity. OM-hosted pores are generally observed and described with scanning electron microscope (SEM) on Ar ion-milled surfaces. However, SEM imaging is not able to reliably distinguish OM types and relate the observed pores to specific macerals. Partly because of this inability to relate organic pores to macerals, the evolution of organic porosity during thermal maturation remains poorly understood. In this paper, we review the petrographic characteristics of dispersed organic matter (DOM) in black shales under the SEM. Organic petrographic classification of DOM developed for reflected-light microscopy is so far the most practical method when describing DOM in black shales under the SEM because this classification has information on the origin of DOM. Therefore, correlative microscopy (combination of reflected-light and electron microscopy) is the most effective method to identify both OM types and OM-hosted pores. This method, however, is not readily available to most researchers. Although identifying OM on the basis of SEM observations is a challenging task, it is achievable provided there is a good understanding of the studied shales, especially their thermal maturity and original OM composition. Therefore, the overall objective of this paper is to review petrographic characteristics of DOM in black shales under the SEM to provide some guidelines for identifying DOM from SEM observations. We also review factors that control the formation and preservation of OM-hosted pores. OM-hosted pores consist of primary and secondary organic pores. Primary organic pores are pores inherited from the biological structure of the original OM. Secondary organic pores develop during hydrocarbon generation and expulsion from oil-prone OM and are hosted by solid bitumen or pyrobitumen. The development of secondary organic pores is controlled by thermal maturity and OM type, and their preservation is subject to thermal maturity, OM content, and mineralogical composition. The presented view of the evolution of micropore and mesopore characteristics of OM with thermal maturity is based on data from the literature. The specific surface area and pore volume of OM in black shales follow a parabolic pattern with increasing thermal maturity (quantified via vitrinite reflectance, R o ). The initial increase reflects development of OM-hosted pores, and the subsequent decrease is due to denser stacking of aromatic units in the macromolecular structure of OM, with maximum values (specific surface area ~ 300 m 2 /g and pore volume ~ 0.3 cm 3 /g) reached at R o values in the 2.5-3.5% range. The contribution of OM-hosted pores to the pore characteristics of black shales depends on OM content, OM type, and thermal maturity.

03 NATURAL GAS↗

Long-Term Results of Conformal Radiotherapy for Progressive Airway Amyloidosis

Purpose: To evaluate the efficacy of conformal external beam radiotherapy (RT) for local control of progressive airway amyloidosis. Methods and Materials: We conducted a retrospective review of patients with biopsy-proven progressive airway amyloidosis treated with conformal RT between 2000 and 2006 at Boston Medical Center. The patients were evaluated for performance status and pulmonary function, with computed tomography and endoscopy after RT compared with the pretreatment studies. Local control was defined as the lack of progression of airway wall thickening on computed tomography imaging and stable endobronchial deposits by endoscopy. Results: A total of 10 symptomatic airway amyloidosis patients (3 laryngeal and 7 tracheobronchial) received RT to a median total dose of 20 Gy in 10 fractions within 2 weeks. At a median follow-up of 6.7 years (range, 1.5-10.3), 8 of the 10 patients had local control. The remaining 2 patients underwent repeat RT 6 and 8.4 months after initial RT, 1 for persistent bronchial obstruction and 1 for progression of subglottic amyloid disease with subsequent disease control. The Eastern Cooperative Oncology Group performance status improved at a median of 18 months after RT compared with the baseline values, from a median score of 2 to a median of 1 (p = .035). Airflow (forced expiratory volume in 1 second) measurements increased compared with the baseline values at each follow-up evaluation, reaching a 10.7% increase (p = .087) at the last testing (median duration, 64.8 months). Acute toxicity was limited to Grade 1-2 esophagitis, occurring in 40% of patients. No late toxicity was observed. Conclusions: RT prevented progressive amyloid deposition in 8 of 10 patients, resulting in a marginally increased forced expiratory volume in 1 second, and improved functional capacity, without late morbidity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

MRI-Guided High–Dose-Rate Intracavitary Brachytherapy for Treatment of Cervical Cancer: The University of Pittsburgh Experience

Purpose: Image-based brachytherapy is increasingly used for gynecologic malignancies. We report early outcomes of magnetic resonance imaging (MRI)-guided brachytherapy. Methods and Materials: Consecutive patient cases with FIGO stage IB1 to IVA cervical cancer treated at a single institution were retrospectively reviewed. All patients received concurrent cisplatin with external beam radiation therapy along with interdigitated high–dose-rate intracavitary brachytherapy. Computed tomography or MRI was completed after each application, the latter acquired for at least 1 fraction. High-risk clinical target volume (HRCTV) and organs at risk were identified by Groupe Européen de Curiethérapie and European SocieTy for Radiotherapy and Oncology guidelines. Doses were converted to equivalent 2-Gy doses (EQD{sub 2}) with planned HRCTV doses of 75 to 85 Gy. Results: From 2007 to 2013, 128 patients, median 52 years of age, were treated. Predominant characteristics included stage IIB disease (58.6%) with a median tumor size of 5 cm, squamous histology (82.8%), and no radiographic nodal involvement (53.1%). Most patients (67.2%) received intensity modulated radiation therapy (IMRT) at a median dose of 45 Gy, followed by a median brachytherapy dose of 27.5 Gy (range, 25-30 Gy) in 5 fractions. At a median follow up of 24.4 months (range, 2.1-77.2 months), estimated 2-year local control, disease-free survival, and cancer-specific survival rates were 91.6%, 81.8%, and 87.6%, respectively. Predictors of local failure included adenocarcinoma histology (P<.01) and clinical response at 3 months (P<.01). Among the adenocarcinoma subset, receiving HRCTV D{sub 90} EQD{sub 2} ≥84 Gy was associated with improved local control (2-year local control rate 100% vs 54.5%, P=.03). Grade 3 or greater gastrointestinal or genitourinary late toxicity occurred at a 2-year actuarial rate of 0.9%. Conclusions: This study constitutes one of the largest reported series of MRI-guided brachytherapy in North America, demonstrating excellent local control with acceptable morbidity. Dose escalation may be warranted when feasible for adenocarcinomas to offset the risk of local failure.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Supranutrition of microalgal docosahexaenoic acid and calcidiol improved growth performance, tissue lipid profiles, and tibia characteristics of broiler chickens

Abstract Background Docosahexaenoic acid (DHA) and calcidiol could be enriched in chicken for improving public nutrition and health. It remains unclear if supranutritional levels of DHA and calcidiol impair growth performance or metabolism of broiler chickens. This study was to determine singular and combined effects of high levels of supplemental DHA-rich microalgal biomass or oil and calcidiol on growth performance, concentrations of triglycerides, cholesterol, and nonesterfied fatty acids in plasma, liver, breast, and thigh, and biophysical properties of tibia. Methods In Exp. 1, 144 day-old Cornish chicks were divided into 4 groups (6 cages/treatment, 6 birds/cage), and were fed a corn-soybean meal basal diet (BD), BD + 10,000 IU calcidiol/kg (BD + Cal), BD + 1% DHA-rich Aurantiochytrium (1.2 g DHA/kg; BD + DHA), and BD + Cal + DHA for 6 weeks. In Exp. 2, 180 day-old chicks were divided into 5 groups, and were fed: BD, BD + DHA (0.33% to 0.66% oil, 1.5 to 3.0 g DHA/kg), BD + DHA + EPA (1.9% to 3.8% eicosapentaenoic acid-rich Nannochloropsis sp. CO18, 0.3 to 0.6 g EPA/kg), BD + DHA + calcidiol (6000 to 12,000 IU/kg diet), and BD + DHA + EPA + Cal for 6 weeks. Results Birds fed BD + Cal diet in Exp. 1 and BD + DHA + EPA diet in Exp. 2 had higher ( P < 0.05) body weight gain (10%–11%) and gain:feed ratio (7%), and lower ( P < 0.05) total cholesterol and triglyceride concentrations in plasma (18%–54%), liver (8%–26%), breast (19%–26%), and thigh (10%–19%), respectively, over the controls. The two diets also improved ( P < 0.05) tibial breaking strength (8%–24%), total bone volume (2%–13%), and (or) bone mineral density (3%–19%) of chickens. Conclusion Supranutrition of dietary calcidiol and DHA alone or together did not produce adverse effects, but led to moderate improvements of growth performance, lipid profiles of plasma and muscle, and bone properties of broiler chickens.

60 APPLIED LIFE SCIENCES↗

Analysis of Gas Membrane Ultra-High Purification of Small Quantities of Mono-Isotopic Silane

A small quantity of high-value, crude, mono-isotopic silane is a prospective gas for a small-scale, high-recovery, ultra-high membrane purification process. This is an unusual application of gas membrane separation for which we provide a comprehensive analysis of a simple purification model. The goal is to develop direct analytic expressions for estimating the feasibility and efficiency of the method, and guide process design; this is only possible for binary mixtures of silane in the dilute limit which is a somewhat realistic case. Among the common impurities in crude silane, methane poses a special membrane separation challenge since it is chemically similar to silane. Other potential problematic surprises are: ethylene, diborane and ethane (in this order). Nevertheless, we demonstrate, theoretically, that a carefully designed membrane system may be able to purify mono-isotopic, crude silane to electronics-grade level in a reasonable amount of time and expenses. We advocate a combination of membrane materials that preferentially reject heavy impurities based on mobility selectivity, and light impurities based on solubility selectivity. We provide estimates for the purification of significant contaminants of interest. To improve the separation selectivity, it is advantageous to use a permeate chamber under vacuum, however this also requires greater control of in-leakage of impurities in the system. In this study, we suggest cellulose acetate and polydimethylsiloxane as examples of membrane materials on the basis of limited permeability data found in the open literature. We provide estimates on the membrane area needed and priming volume of the cell enclosure for fabrication purposes when using the suggested membrane materials. These estimates are largely theoretical in view of the absence of reliable experimental data for the permeability of silane. Last but not least, future extension of this work to the non-dilute limit may apply to the recovery of silane from rejected streams of natural silicon semi-conductor processes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

From tides to seasons: How cyclic tidal drivers and plant physiology interact to affect carbon cycling at the terrestrial-estuarine boundary (Final technical report)

Coastal ecosystems are among the most biologically and biogeochemically active and diverse systems on Earth. Because they act as important linkages between terrestrial ecosystems and the open ocean, their incorporation in Earth system models (ESMs) is critical to predict coastal and global responses to environmental changes. However, they vary greatly in the magnitude of tides and the volume and timing of freshwater input from land, making it challenging to model the major biogeochemical reactions that control productivity and greenhouse gas emissions across coastal terrestrial aquatic interfaces (TAIs). Our overall objective was to improve mechanistic process understanding and modeling of tidal wetland hydro-biogeochemistry in coastal TAIs. We established a new flux tower site (Ameriflux US-PLo) in the oligohaline part of the Parker River to continuously monitor ecosystem-scale carbon fluxes under temporally varying salinity conditions. The site is co-located with long-term monitoring plots of the Plum Island Ecosystems LTER project. We installed wells and redox sensors in the marsh interior and creek bank, established biomass monitoring plots and deployed novel optode sensors in both locations. We used this data to parameterize plant-mediated transport in PFLOTRAN and tested the impact of soil heterogeneity on porewater constituents and gas fluxes. We collected observations of root oxygen release with a novel planar optode system in the field. Flux data collected during the measurement period encompasses a large variation in salinity ranging from drought to record precipitation years. We developed a method to extract functional relationships from the flux data using artificial neural networks, identifying salinity thresholds for CH 4 fluxes. Finally, we are using the coupled ELM-PFLOTRAN model to test the impact of antecedent hydrological conditions on the salinity-CH 4 flux relationship. This grant contributed to the professional development of one postdoc, three research assistants and one graduate student. The sensor data has been shared with external collaborators.

54 ENVIRONMENTAL SCIENCES↗

F-18-FDG-PET Confined Radiotherapy of Locally Advanced NSCLC With Concomitant Chemotherapy: Results of the PET-PLAN Pilot Trial

Purpose: The integration of fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the process of radiotherapy (RT) planning of locally advanced non-small-cell lung cancer (NSCLC) may improve diagnostic accuracy and minimize interobserver variability compared with target volume definition solely based on computed tomography. Furthermore, irradiating only FDG-PET-positive findings and omitting elective nodal regions may allow dose escalation by treating smaller volumes. The aim of this prospective pilot trial was to evaluate the therapeutic safety of FDG-PET-based RT treatment planning with an autocontour-derived delineation of the primary tumor. Methods and Materials: Eligible patients had Stages II-III inoperable NSCLC, and simultaneous, platinum-based radiochemotherapy was indicated. FDG-PET and computed tomography acquisitions in RT treatment planning position were coregistered. The clinical target volume (CTV) included the FDG-PET-defined primary tumor, which was autodelineated with a source-to-background algorithm, plus FDG-PET-positive lymph node stations. Limited by dose restrictions for normal tissues, prescribed total doses were in the range of 66.6 to 73.8 Gy. The primary endpoint was the rate of out-of-field isolated nodal recurrences (INR). Results: As per intent to treat, 32 patients received radiochemotherapy. In 15 of these patients, dose escalation above 66.6 Gy was achieved. No Grade 4 toxicities occurred. After a median follow-up time of 27.2 months, the estimated median survival time was 19.3 months. During the observation period, one INR was observed in 23 evaluable patients. Conclusions: FDG-PET-confined target volume definition in radiochemotherapy of NSCLC, based on a contrast-oriented source-to-background algorithm, was associated with a low risk of INR. It might provide improved tumor control because of dose escalation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparison of wind-farm control strategies under realistic offshore wind conditions: wake quantities of interest

Wind-farm control strategies aim to increase the efficiency, and therefore lower the levelized cost of energy, of wind farms. This is done by using turbine settings such as the yaw angle, blade pitch angles, or generator torque to manipulate the wake that negatively affects downstream turbines in the farm. Two inherently different wind-farm control methods have been identified in the literature: wake steering (WS) and active wake mixing (AWM). As one of two companion papers focused on understanding practical aspects of these two wind-farm control strategies using large-eddy simulation (LES), we below analyze the wake quantities of interest for a single wind turbine performing WS and AWM, while the companion article (Frederik et al., 2025) focuses on turbine quantities of interest including power and structural loads for the same computational setup and also includes two-turbine arrays with full and partial wake overlap. The simulations, which are based in the LES solver AMR-Wind, are tailored to have inflow conditions representative of measurements from a site off the East Coast of the US, including with strong veer and low turbulence. The turbine, which is modeled in OpenFAST and coupled to the LES, is the IEA 15 MW, an open-source offshore design. After presenting an overview of the wake recovery for the different wake-control cases, the analysis probes the fluid-dynamic causes for the different performance of the arrays reported in the companion article by examining control volumes around the wakes and the budget of the mean-flow kinetic energy (MKE) within these volumes. In the high veer environment considered, the MKE recovery is dominated by mean convection, and this is shown to especially benefit the WS strategy when a neighboring turbine is directly downstream: there is ≈65 % more available power for a downstream turbine than in the baseline case, and this power is gained primarily through mean convection on the left-tip and top-tip faces of the control volume. However, the case with imperfect knowledge of the exact wind direction favors the pulse-type AWM strategy, largely because of ≈9 % increased turbulent entrainment from aloft versus the baseline that could be related to an apparent resistance to skewing in the pulsed wake. The general reduced effectiveness of helix-type and other individual-pitch-based AWM strategies for inflow with high veer and low turbulence as reported in the companion paper is due, in part, to low magnitudes of phase-averaged turbulent entrainment. Two main findings of this study are thus that veer has a significant impact on the effectiveness of different wake-control strategies and that pulse-type AWM may be a useful strategy when the objective is power maximization in realistic, offshore flow environments with imperfect knowledge of the exact wake overlap position on the downstream turbine.

17 WIND ENERGY↗

Heat transfer computer programs

On May 7, 1964, at the invitation of Dr. Raymond L. Bisplinghoff, Associate Administrator for Advanced Research and Technology, a confer­ence was held in NASA Headquarters, on the subject "Heat Transfer Computer Programs." The conference was one of several held in Headquarters during the first half of 1964 for review and planning of NASA's research program on space vehicle thermal radiation and temperature control. The conference brought about a useful interchange of information between the NASA Centers, including JPL, on computer programs which had been developed for the thermal design of spacecraft. The conferees concluded that in addition to our annual conference in this area, a useful con­tinuing exchange of information could be through the establishment of a quarterly newsletter issued from Headquarters describing, current efforts. Such a newsletter, on heat transfer. computer programs, has been established and it is hope that the publication of the present proceedings will be a further milestone in advancing the technology of using electronic computers as a tool in the thermal design of space vehicles. The present volume includes all of the formal presentations made by staff members of the various NASA Centers. Their cooperation, which led to a highly successful conference, is greatly appreciated.

SATELLITE↗

Down-regulation of Transducin-Like Enhancer of Split protein 4 in hepatocellular carcinoma promotes cell proliferation and epithelial-Mesenchymal-Transition

Background: Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC). Methods: The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation. Results: The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared to matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group. Conclusions: These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC. - Highlights: • TLE4 is significantly down-regulated in HCC samples. • Down regulated of TLE4 in HCC cells promotes cell proliferation. • Down regulated of TLE4 in HCC cells promotes epithelial-to-mesenchymal transition.

60 APPLIED LIFE SCIENCES↗

Inverse Relationship Between Biochemical Outcome and Acute Toxicity After Image-Guided Radiotherapy for Prostate Cancer

Purpose: Prostate cancer patients exhibit variability in normal tissue reactions and biochemical failure. With the use of image-guided radiotherapy (IGRT), there is a greater likelihood that the differences in normal tissue and tumor response are due to biological rather than physical factors. We tested the hypothesis that prospectively scored acute toxicity is associated with biochemical failure-free rate (BFFR) in prostate cancer patients treated with IGRT. Methods and Materials: We retrospectively analyzed BFFR in 362 patients with localized prostate cancer treated with IGRT. We compared BFFR with prospectively collected Radiation Therapy Oncology Group (RTOG) maximum acute gastrointestinal (GI) and genitourinary (GU) toxicity scores. Median follow-up for all patients was 58.3 months after total radiotherapy doses of 75.6-79.8 Gy. Results: Patients reporting RTOG acute GU or GI toxicity scores of {>=}2 were considered 'sensitive' (n = 141, 39%) and patients reporting scores <2 were considered 'nonsensitive' (n = 221, 61%). When calculating biochemical failure (BF) using the American Society for Therapeutic Radiology and Oncology definition at 5 years, 76% (CI 70-82%) of the 'nonsensitive' patients were failure free, compared with only 53% (CI 43-62%) of the 'sensitive' patients (log-rank test, p < 0.0001). This difference was also observed using the Phoenix definition; 'nonsensitive' 5-year BFFR was 81% (CI 74-86%) vs. 'sensitive' BFFR was 68% (CI 58-76%; log-rank test p = 0.0012). The difference in BF between cohorts remained significant when controlled for radiation dose (75.6 vs. 79.8 Gy), prognostic stratification (T category, prostate-specific antigen, and Gleason score), and prostate volume. Conclusions: This study unexpectedly shows that prostate cancer patients who develop {>=}Grade 2 RTOG acute toxicity during radiotherapy are less likely to remain BFF at 5 years. These results deserve further study and, if validated in other large IGRT cohorts, additional models would be required to study interaction between normal tissue and tumor biology in prostate cancer patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗