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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 127 records · Page 7
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma

Purpose: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models. We evaluated the addition of VPA to standard radiation therapy (RT) plus temozolomide (TMZ) in patients with newly diagnosed GBM. Methods and Materials: Thirty-seven patients with newly diagnosed GBM were enrolled between July 2006 and April 2013. Patients received VPA, 25 mg/kg orally, divided into 2 daily doses concurrent with RT and TMZ. The first dose of VPA was given 1 week before the first day of RT at 10 to 15 mg/kg/day and subsequently increased up to 25 mg/kg/day over the week prior to radiation. VPA- and TMZ-related acute toxicities were evaluated using Common Toxicity Criteria version 3.0 (National Cancer Institute Cancer Therapy Evaluation Program) and Cancer Radiation Morbidity Scoring Scheme for toxicity and adverse event reporting (Radiation Therapy Oncology Group/European Organization for Research and Treatment). Results: A total of 81% of patients took VPA according to protocol. Median overall survival (OS) was 29.6 months (range: 21-63.8 months), and median progression-free survival (PFS) was 10.5 months (range: 6.8-51.2 months). OS at 6, 12, and 24 months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24 months was 70%, 43%, and 38% respectively. The most common grade 3/4 toxicities of VPA in conjunction with RT/TMZ therapy were blood and bone marrow toxicity (32%), neurological toxicity (11%), and metabolic and laboratory toxicity (8%). Younger age and class V recursive partitioning analysis (RPA) results were significant for both OS and PFS. VPA levels were not correlated with grade 3 or 4 toxicity levels. Conclusions: Addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may result in improved outcomes compared to historical data and merits further study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

Purpose: To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods: Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results: Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions: IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

Purpose: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT). Methods and Materials: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m{sup 2}) and 14 were treated with cisplatin (40 mg/m{sup 2}) plus gemcitabine (50-125 mg/m{sup 2}) (C/G). Patients underwent {sup 18}F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and 1.5 to 6.0 months after treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV of the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extrapelvic versus pelvic ABM percentage from baseline to after treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extrapelvic BM using a 2-sided paired t test. Results: We observed a significant increase in the overall extrapelvic compensatory response after CRT (0.381; 95% confidence interval [CI]: 0.312, 0.449) and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared with C/G (P=.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (P<.001) and in those receiving C/G (P<.001), whereas extrapelvic ABM percentage was increased in patients receiving cisplatin (P<.001) and C/G (P<.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (P<.001) and C/G (P<.001). The mean SUV appeared lower in extrapelvic structures after CRT in patients treated with C/G (P=.076) but not with cisplatin (P=.942). We also observed that older age and more intense chemotherapy regimens were correlated with a decreased compensatory response on multivariable analysis. In patients treated with C/G, mean pelvic bone marrow dose was found to be negatively correlated with the compensatory response. Conclusion: Patients have differing subacute compensatory responses after CRT, owing to variable recovery in unirradiated marrow. Intensive chemotherapy regimens appear to decrease the extrapelvic compensatory response, which may lead to increased hematologic toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice. • Oroxin B effectively exerts anti-lymphoma without obvious toxicity. • Oroxin B promotes tumor-suppressive DDIT3 and inhibits tumorigenic GRP78.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Using Novosphingobium aromaticivorans for Concurrent Production of Intracellular and Extracellular Products from Aromatics Extracted from Poplar Biomass

Achieving high biochemical production in biotransformations of renewable resources requires using concentrated cultures that not only generate the product of interest but also produce abundant microbial cell waste. We explored the concept of gaining value from microbial cells by producing intracellular products in tandem with a desired extracellular product. Specifically, we engineered a strain ofNovosphingobium aromaticivorans to extracellularly produce 2-pyrone-4,6-dicarboxylic acid (PDC) from aromatic substrates and to intracellularly accumulate astaxanthin along with coenzyme Q 10 , all of which are products of industrial interest. Achieving the goal of concurrent production of intracellular and extracellular products required the creative application of bioreactor engineering principles. Although a continuously fed membrane bioreactor (MBR) maximized extracellular product biosynthesis, it had a negative effect on intracellular product accumulation. However, operating the MBR as a sequencing batch reactor (MBR-SBR) with a step-feed resulted in stable concurrent production of both extracellular and intracellular products. With aromatics extracted from poplar biomass, we achieved productivities of 1.14 g of PDC/L-h for the extracellular product and 0.04 mg of astaxanthin/L-h and 0.64 mg of CoQ 10 /L-h for intracellular products, respectively. Our findings demonstrate that the mode of operation of a bioreactor impacts the simultaneous production of intracellular and extracellular products byN. aromaticivorans.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Harnessing the concurrent reaction dynamics in active Si and Ge to achieve high performance lithium-ion batteries

Advanced composite electrodes containing multiple active components are often used in lithium-ion batteries for practical applications. The performance of such heterogeneous composite electrodes can in principle be enhanced by tailoring the concurrent reaction dynamics in multiple active components for promoting their collective beneficial effects. However, the potential of this design principle has remained uncharted to date. Here we develop a composite anode of Cu/Si/Ge nanowire arrays, where each nanowire consists of a core of Cu segments and a Si/Ge bilayer shell. This unique electrode architecture exhibited a markedly improved electrochemical performance over the reference Cu/Si systems, demonstrating a stable capacity retention (81% after 3000 cycles at 2C) and doubled specific capacity at a rate of 16C (1C = 2 A g1). By using in situ transmission electron microscopy and electrochemical testing, we unravel a novel reaction mechanism of dynamic co-lithiation/co-delithiation in the active Si and Ge bilayer, which is shown to effectively alleviate the electrochemically induced mechanical degradation and thus greatly enhance the long-cycle stability of the electrode. Our findings offer insights into a rational design of high-performance lithium-ion batteries via exploiting the concurrent reaction dynamics in the multiple active components of composite electrodes. A composite anode of Cu/Si/Ge nanowire arrays grown on a porous Ni foam enables the outstanding capacity, rate capability and cycle stability of Li-ion batteries.

Environmental Molecular Sciences Laboratory↗
DOE OSTI2019

Concurrent coupling of atomistic simulation and mesoscopic hydrodynamics for flows over soft multi-functional surfaces

We develop an e?cient parallel multiscale method that bridges the atomistic and mesoscale regimes, from nanometers to microns and beyond, via concurrent coupling of atomistic simulation and mesoscopic dynamics. In particular, we combine an all-atom molecular dynamics (MD) description for specific atomistic details in the vicinity of the functional surface with a dissipative particle dynamics (DPD) approach that captures mesoscopic hydrodynamics in the domain away from the functional surface. In order to achieve a seamless transition in dynamic properties we endow the MD simulation with a DPD thermostat, which is validated against experimental results by modeling water at di?erent temperatures. We then validate the MD-DPD coupling method for transient Couette and Poiseuille flows, demonstrating that the concurrent MD-DPD coupling can resolve accurately the continuumbased analytical solutions. Subsequently, we simulate shear flows over grafted polydimethylsiloxane (PDMS) surfaces (polymer brushes) for various grafting densities, and investigate the slip flow as a function of the shear stress. We verify that a ‘‘universal’’ power law exists for the slip length, in agreement with published results. Having validated the MD-DPD coupling method, we simulate timedependent flows past an endothelial glycocalyx layer (EGL) in a microchannel. Coupled simulation results elucidate the dynamics of the EGL changing from an equilibrium state to a compressed state under shear by aligning the molecular structures along the shear direction. MD-DPD simulation results agree well with results of a single MD simulation, but with the former more than two orders of magnitude faster than the latter for system sizes above one micron.

Wang, Yuying↗
DOE OSTI2019

Land–atmosphere feedbacks exacerbate concurrent soil drought and atmospheric aridity

Compound extremes such as cooccurring soil drought (low soil moisture) and atmospheric aridity (high vapor pressure deficit) can be disastrous for natural and societal systems. Soil drought and atmospheric aridity are 2 main physiological stressors driving widespread vegetation mortality and reduced terrestrial carbon uptake. Here, we empirically demonstrate that strong negative coupling between soil moisture and vapor pressure deficit occurs globally, indicating high probability of cooccurring soil drought and atmospheric aridity. Using the Global Land Atmosphere Coupling Experiment (GLACE)-CMIP5 experiment, we further show that concurrent soil drought and atmospheric aridity are greatly exacerbated by land–atmosphere feedbacks. The feedback of soil drought on the atmosphere is largely responsible for enabling atmospheric aridity extremes. In addition, the soil moisture–precipitation feedback acts to amplify precipitation and soil moisture deficits in most regions. CMIP5 models further show that the frequency of concurrent soil drought and atmospheric aridity enhanced by land–atmosphere feedbacks is projected to increase in the 21st century. Significantly, land–atmosphere feedbacks will greatly increase the intensity of both soil drought and atmospheric aridity beyond that expected from changes in mean climate alone.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

AN INTERPRETATION OF GLE71 CONCURRENT CME-DRIVEN SHOCK WAVE

Particle accelerations in solar flares and CME-driven shocks can sometimes result in very high-energy particle events (≥1 GeV) that are known as ground level enhancements (GLEs). Recent studies on the first GLE event (GLE71 2012 May 17 01:50 UT) of solar cycle 24 suggested that CME-driven shock played a leading role in causing the event. To verify this claim, we have made an effort to interpret the GLE71 concurrent shock wave. For this, we have deduced the possible speed and height of the shock wave in terms of the frequency (MHz) of the solar radio type II burst and its drift rate (MHz min{sup –1}), and studied the temporal evolution of the particle intensity profiles at different heights of the solar corona. For a better perception of the particle acceleration in the shock, we have studied the solar radio type II burst with concurrent solar radio and electron fluxes. When the particle intensity profiles are necessarily shifted in time at ∼1 AU, it is found that the growth phases of the electron and cosmic ray intensity fluxes are strongly correlated (>0.91; ≥0.87) with the frequency drift rate of the type II burst, which is also consistent with the intensive particle accelerations at upper coronal heights (∼≥0.80 R {sub S} < 1.10 R {sub S}). Thus, we conclude that the CME-driven shock was possibly capable of producing the high-energy particle event. However, since the peaks of some flare components are found to be strongly associated with the fundamental phase of the type II burst, the preceding flare is supposed to contribute to the shock acceleration process.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2015

Locality Aware Concurrent Start for Stencil Applications

Stencil computations are at the heart of many physical simulations used in scientific codes. Thus, there exists a plethora of optimization efforts for this family of computations. Among these techniques, tiling techniques that allow concurrent start have proven to be very efficient in providing better performance for these critical kernels. Nevertheless, with many core designs being the norm, these optimization techniques might not be able to fully exploit locality (both spatial and temporal) on multiple levels of the memory hierarchy without compromising parallelism. It is no longer true that the machine can be seen as a homogeneous collection of nodes with caches, main memory and an interconnect network. New architectural designs exhibit complex grouping of nodes, cores, threads, caches and memory connected by an ever evolving network-on-chip design. These new designs may benefit greatly from carefully crafted schedules and groupings that encourage parallel actors (i.e. threads, cores or nodes) to be aware of the computational history of other actors in close proximity. In this paper, we provide an efficient tiling technique that allows hierarchical concurrent start for memory hierarchy aware tile groups. Each execution schedule and tile shape exploit the available parallelism, load balance and locality present in the given applications. We demonstrate our technique on the Intel Xeon Phi architecture with selected and representative stencil kernels. We show improvement ranging from 5.58% to 31.17% over existing state-of-the-art techniques.

Locality Aware execution, jagged tiling↗
DOE OSTI2019

Runtime Concurrency Control and Operation Scheduling for High Performance Neural Network Training

In this paper, we extend an existing runtime system (the TensorFlow runtime) to enable automatic concurrency control and scheduling of operations. We explore performance modeling to predict the performance of operations with various thread- level parallelism. Our performance model is highly accurate and lightweight. Leveraging the performance model, our runtime system employs a set of scheduling strategies that co-run opera- tions to improve hardware utilization and system throughput. Our runtime system demonstrates a significant performance benefit. Comparing with using the recommended configurations for concurrency control and operation scheduling in TensorFlow, our approach achieves 36% performance (execution time) im- provement on average (up to 49%) for four neural network models, and achieves high performance close to the optimal one manually obtained by the user.

Liu, Jiawen↗
DOE OSTI2019

Efficient Modeling of HIL Multi-Grid System for Scalability & Concurrency in CPS Security Testbed

Cyber-event-triggered power grid blackout compels utility operators to intensify cyber-aware and physics-constrained recovery and restoration process. Recently, coordinated cyber attacks on the Ukrainian grid witnessed such a cyber-event-triggered power system blackout. Various cyber-physical system (CPS) testbeds have attempted with multitude designs to analyze such interdependent events and evaluate remedy measures. However, resource constraints and modular integration designs have been significant barriers while modeling large-scale grid models (scalability) and multi-grid isolated models (concurrency) under a single real-time execution environment for the hardware-in-the-loop (HIL) CPS security testbeds. This paper proposes a meticulous design and effective modeling for simulating large-scale grid models and multi-grid isolated models in a HIL realtime digital simulator environment integrated with industry-grade hardware and software systems. We have used our existing HIL CPS security testbed to demonstrate scalability by the realtime performance of a Texas-2000 bus US synthetic grid model and concurrency by the real-time performance of simultaneous ten IEEE-39 bus grid models and an IEEE-118 bus grid model. The experiments demonstrated significant results by 100% realtime performance with zero overruns, low latency while receiving and executing control signals from SEL Relays via IEC-61850 protocol and low latency while computing and transmitting grid data streams including stability measures via IEEE C37.118 synchrophasor data protocol to SEL Phasor Data Concentrators.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2013

Effect of MLC leaf width on treatment adaptation and accuracy for concurrent irradiation of prostate and pelvic lymph nodes

Purpose: The aim of the study was to evaluate the impact of multileaf collimator (MLC) leaf width on treatment adaptation and delivery accuracy for concurrent treatment of the prostate and pelvic lymph nodes with intensity modulated radiation therapy (IMRT). Methods: Seventy-five kilovoltage cone beam CTs (KV-CBCT) from six patients were included for this retrospective study. For each patient, three different IMRT plans were created based on a planning CT using three different MLC leaf widths of 2.5, 5, and 10 mm, respectively. For each CBCT, the prostate displacement was determined by a dual image registration. Adaptive plans were created by shifting selected MLC leaf pairs to compensate for daily prostate movements. To evaluate the impact of MLC leaf width on the adaptive plan for each daily CBCT, three MLC shifted plans were created using three different leaf widths of MLCs (a total of 225 adaptive treatment plans). Selective dosimetric endpoints for the tumor volumes and organs at risk (OARs) were evaluated for these adaptive plans. Using the planning CT from a selected patient, MLC shifted plans for three hypothetical longitudinal shifts of 2, 4, and 8 mm were delivered on the three linear accelerators to test the deliverability of the shifted plans and to compare the dose accuracy of the shifted plans with the original IMRT plans. Results: Adaptive plans from 2.5 and 5 mm MLCs had inadequate dose coverage to the prostate (D99 < 97%, or D{sub mean} < 99% of the planned dose) in 6%-8% of the fractions, while adaptive plans from 10 mm MLC led to inadequate dose coverage to the prostate in 25.3% of the fractions. The average V{sub 56Gy} of the prostate over the six patients was improved by 6.4% (1.6%-32.7%) and 5.8% (1.5%-35.7%) with adaptive plans from 2.5 and 5 mm MLCs, respectively, when compared with adaptive plans from 10 mm MLC. Pelvic lymph nodes were well covered for all MLC adaptive plans, as small differences were observed for D99, D{sub mean}, and V{sub 50.4Gy}. Similar OAR sparing could be achieved for the bladder and rectum with all three MLCs for treatment adaptation. The MLC shifted plans can be accurately delivered on all three linear accelerators with accuracy similar to their original IMRT plans, where gamma (3%/3 mm) passing rates were 99.6%, 93.0%, and 92.1% for 2.5, 5, and 10 mm MLCs, respectively. The percentages of pixels with dose differences between the measurement and calculation being less than 3% of the maximum dose were 85.9%, 82.5%, and 70.5% for the original IMRT plans from the three MLCs, respectively. Conclusions: Dosimetric advantages associated with smaller MLC leaves were observed in terms of the coverage to the prostate, when the treatment was adapted to account for daily prostate movement for concurrent irradiation of the prostate and pelvic lymph nodes. The benefit of switching the MLC from 10 to 5 mm was significant (p Much-Less-Than 0.01); however, switching the MLC from 5 to 2.5 mm would not gain significant (p= 0.15) improvement. IMRT plans with smaller MLC leaf widths achieved more accurate dose delivery.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2016

WE-AB-202-02: Incorporating Regional Ventilation Function in Predicting Radiation Fibrosis After Concurrent Chemoradiotherapy for Lung Cancer

Purpose: To investigate the incorporation of pre-therapy regional ventilation function in predicting radiation fibrosis (RF) in stage III non-small-cell lung cancer (NSCLC) patients treated with concurrent thoracic chemoradiotherapy. Methods: 37 stage III NSCLC patients were retrospectively studied. Patients received one cycle of cisplatin-gemcitabine, followed by two to three cycles of cisplatin-etoposide concurrently with involved-field thoracic radiotherapy between 46 and 66 Gy (2 Gy per fraction). Pre-therapy regional ventilation images of the lung were derived from 4DCT via a density-change-based image registration algorithm with mass correction. RF was evaluated at 6-months post-treatment using radiographic scoring based on airway dilation and volume loss. Three types of ipsilateral lung metrics were studied: (1) conventional dose-volume metrics (V20, V30, V40, and mean-lung-dose (MLD)), (2) dose-function metrics (fV20, fV30, fV40, and functional mean-lung-dose (fMLD) generated by combining regional ventilation and dose), and (3) dose-subvolume metrics (sV20, sV30, sV40, and subvolume mean-lung-dose (sMLD) defined as the dose-volume metrics computed on the sub-volume of the lung with at least 60% of the quantified maximum ventilation status). Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to evaluate the predictability of these metrics for RF. Results: In predicting airway dilation, the area under the ROC curve (AUC) values for (V20, MLD), (fV20, fMLD), and (sV20, and sMLD) were (0.76, 0.70), (0.80, 0.74) and (0.82, 0.80), respectively. The logistic regression p-values were (0.09, 0.18), (0.02, 0.05) and (0.004, 0.006), respectively. With regard to volume loss, the corresponding AUC values for these metrics were (0.66, 0.57), (0.67, 0.61) and (0.71, 0.69), and p-values were (0.95, 0.90), (0.43, 0.64) and (0.08, 0.12), respectively. Conclusion: The inclusion of regional ventilation function improved predictability of radiation fibrosis. Dose-subvolume metrics provided a promising method for incorporating functional information into the conventional dose-volume parameters for outcome assessment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Concurrent Selective Lymph Node Radiotherapy and S-1 Plus Cisplatin for Esophageal Squamous Cell Carcinoma: A Phase II Study

Background: The efficacy, toxicity, and patterns of failure of esophageal squamous cell carcinoma (ESCC) treated with selective lymph node (SLN) conventional fraction radiotherapy (CFRT) and S-1 plus cisplatin (CDDP) were evaluated. Patients and Methods: 67 Patients with clinical stage II–IVa ESCC were enrolled. The total dose of SLN CFRT was 60 Gy in 30 fractions over 6 weeks. The first course of radiation covered the primary and metastatic regional tumors and high-risk lymph nodal regions, given at 2 Gy/fraction for a dose of 40 Gy. In the second course, CFRT was delivered to the boost volume for an additional 20 Gy in 10 days, using 2 Gy/fraction. Two cycles of chemotherapy were given at the beginning of radiotherapy. CDDP at 25 mg/m{sup 2}/day was given on days 1–3 and days 22–24, and S-1 at 80 mg/m{sup 2}/day on days 1–14 and days 22–35. Patients achieving objective response after concurrent chemoradiotherapy underwent two additional cycles of chemotherapy. Results: The objective response rate (ORR) was 82.5%. Grade 3 or 4 toxicities included leukopenia (23.8%), neutropenia (14.3%), thrombocytopenia (14.3%), hemoglobin (4.8%), gastrointestinal (12.7%), skin (1.6%), and esophagus fistula (1.6%). One patient died of severe pneumonia, and two died of late toxicity because of esophagus fistula. With median follow-up of 32 months, the overall survival (OS) and progression-free survival (PFS) at 1 year and 2 years were 81.0% and 73.0%, and 63.5% and 49.2%, respectively. Conclusions: SLN RT concurrent with S-1 plus CDDP may represent a better strategy for treatment of ESCC patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2025

CONCURRENT, CONDENSED STEIN VARIATIONAL GRADIENT DESCENT FOR UNCERTAINTY QUANTIFICATION OF NEURAL NETWORKS

In this work, we propose a Stein variational gradient descent (SVGD) method to concurrently sparsify, train, and provide uncertainty quantification (UQ) of a complexly parameterized model, such as a neural network (NN). It employs a graph reconciliation and condensation process to reduce complexity and increase similarity in the Stein ensemble of parameterizations. Therefore, the proposed concurrent, condensed SVGD (ccSVGD) method can provide UQ on parameters, not just outputs. Furthermore, the parameter reduction speeds up the convergence of the Stein gradient descent as it reduces the combinatorial complexity by aligning and differentiating the sensitivity to parameters. These properties are demonstrated with an illustrative example and an application to a mechanical response representation problem in solid mechanics.

42 ENGINEERING↗
DOE OSTI2020

Concurrent evaluation of autophagy induction and Burkholderia infection at the single cell level

Autophagy is a natural, regulated cellular process that "cleans up" cellular debris by degrading and recycling dysfunctional proteins. There is a high potential impact of exploiting the benefits of autophagy to complement existing treatments, but little has been done to date on bacterial pathogens of defense concern such as Burkholderia pseudomallei, a highly virulent Select Agent pathogen that is intrinsically resistant to most classes of antibiotics. Assessment of autophagy in the context of infection typically requires use of multiple technologies in combination (e.g., Western analysis paired with microscopy or flow cytometry) as applied to heterogeneous populations of cells. To address this, we have developed a dual target reporter cell line (RAW264.7 LC3-BFP:mPlum, GFP-RelA) that enables concurrent visualization of infection and autophagy induction. We assessed the effect of clinically approved small molecule inducers of autophagy on infection by Burkholderia thailendensis, a closely related but less virulent surrogate for B. pseudomallei. The reporter cells were first infected with a B. thailendensis strain that constitutively expresses GFP, then treated with one of four known autophagy inducers (rapamycin, niclosamide, bromhexine HC1, or flubendazole) for 4 hours. Confocal fluorescence imaging was used to quantify autophagy stimulation at the single cell level. Autophagy maturation was observed as a decrease in BFP LC3 puncta with a concurrent increase in mPlum LC3 puncta. B. thailendensis infection was assessed by monitoring translocation of GFP-RelA (an NFkB subunit) into the nucleus and through quantitating the intracellular bacterial presence in single cells. Preliminary results indicate that bromhexine HC1 and niclosamide may hinder B. thailendensis' ability to replicate intracellularly and reduce overall bacterial survival.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Automatically parallelizing batch inference on deep neural networks using Fiats and Fortran 2023 `do concurrent`

This paper introduces novel programming strategies that leverage features of the Fortran 2023 standard of the International Standards Organization (ISO) to automatically parallelize computations on deep neural networks. The paper focuses on the interplay of object-oriented, parallel, and functional programming paradigms in the Fiats deep learning library. We demonstrate how several infrequently used language features play a role in enabling efficient, parallel execution. Specifically, the ability to explicitly declare that a procedure is pure facilitates inference in the context of the language’s loop-parallelism construct `do concurrent`. Also, explicitly prohibiting the overriding of a parent type’s type-bound procedures eliminates the need for dynamic dispatch in performance-critical code. Finally, this paper uses batch inference calculations on a neural network surrogate for atmospheric aerosol dynamics to demonstrate that LLVM Flang compiler’s automatic parallelization of `do concurrent` achieves roughly the same performance and scalability as achieved by OpenMP compiler directives. We also demonstrate that double-precision inference costs 37–72% longer runtime than default-real precision with most values in the range 57-60%.

Rouson, Damian↗