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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 829 records · Page 46

Study of LANDSAT-D thematic mapper performance as applied to hydrocarbon exploration

Two fully processed test tapes were enhanced and evaluated at scales up to 1:10,000, using both hardcopy output and interactive screen display. A large scale, the Detroit, Michigan scene shows evidence of an along line data slip every sixteenth line in TM channel 2. Very large scale products generated in false color using channels 1,3, and 4 should be very acceptable for interpretation at scales up to 1:50,000 and useful for change mapping probably up to scale 1:24,000. Striping visible in water bodies for both natural and color products indicates that the detector calibration is probably performing below preflight specification. For a set of 512 x 512 windows within the NE Arkansas scene, the variance-covariance matrices were computed and principal component analyses performed. Initial analysis suggests that the shortwave infrared TM 5 and 6 channels are a highly significant data source. The thermal channel (TM 7) shows negative correlation with TM 1 and 4.

Everett, J. R.↗

Prediction of Research/Motor Octane Number and Octane Sensitivity Using Artificial Neural Networks

Octane sensitivity (OS), dfined as the research octane number (RON) minus the motor octane number (MON) of a given fuel, has gained interest among researchers due to its apparent ffect on knocking conditions in internal combustion engines. Compounds with a high OS enable higher efficiencies, especially with respect to advanced compression ignition engines. RON/MON must be experimentally tested to determine OS; however, the experimental methods utilized require a substantial amount of time, a significant monetary investment, and specialized equipment. To this end, predictive computational models trained with existing experimental data and molecular properties would allow for the preemptive screening of compounds prior to performing these experiments. The present work proposes two methods for predicting the OS of a given compound: using artficial neural networks (ANNs) trained with quantitative structure-property relationship (QSPR) descriptors to predict RON and MON individually to compute OS from RON/MON predictions (derived octane sensitivity, dOS), and using an ANN trained with QSPR descriptors to directly predict OS. ANNs trained to predict RON and MON achieved test set root-mean-square errors (RMSEs) of 10.499 and 7.551 respectively. dOS calculations were found to have a test set RMSE of 6.432 while predicting OS directly resulted in a test set RMSE of 7.019, showing it is more bene cial to obtain OS from RON/MON predictions than predicting it directly. Furthermore, relationships between individual QSPR descriptors and RON/MON/OS are discussed, highlighting correlations between specfic molecular features and these properties.

09 BIOMASS FUELS↗

Metrics of Balance Control for Use in Screening Tests of Vestibular Function

Decrements in balance control have been documented in astronauts after space flight. Reliable measures of balance control are needed for use in postflight field tests at remote landing sites. Diffusion analysis (DA) is a statistical mechanical tool that shows the average difference of the dependent variable on varying time scales. These techniques have been shown to measure differences in open-loop and closed-loop postural control in astronauts and elderly subjects. The goal of this study was to investigate the reliability of these measures of balance control. Eleven subjects were tested using the Clinical Test of Sensory Interaction on Balance: the subject stood with feet together and arms crossed on a stable or compliant surface, with eyes open or closed and with or without head movements in the pitch or yaw plane. Subjects were instrumented with inertial motion sensors attached to their trunk segment. The DA curves for linear acceleration measures were characterized by linear fits measuring open- (Ds) and closed-loop (Dl) control, and their intersection point (X-int, Y-int). Ds and Y-int showed significant differences between the test conditions. Additionally, Ds was correlated with the root mean square (RMS) of the signal, indicating that RMS was dominated by open-loop events (< 0.5 seconds). The Y-int was found to be correlated with the average linear velocity of trunk movements. Thus DA measures could be applied to derive reliable metrics of balance stability during field tests.

Fiedler, Matthew↗

Calculation of electron-ion temperature equilibration rates and friction coefficients in plasmas and liquid metals using quantum molecular dynamics

In this work, we discuss a method to calculate with quantum molecular dynamics simulations the rate of energy exchanges between electrons and ions in two-temperature plasmas, liquid metals, and hot solids. Promising results from this method were recently reported for various materials and physical conditions. Like other ab initio calculations, the approach offers a very useful comparison with the experimental measurements and permits an extension into conditions not covered by the experiments. The energy relaxation rate is related to the friction coefficients felt by individual ions due to their nonadiabatic interactions with electrons. Each coefficient satisfies a Kubo relation given by the time integral of the autocorrelation function of the interaction force between an ion and the electrons. These Kubo relations are evaluated using the output of quantum molecular dynamics calculations in which electrons are treated in the framework of finite-temperature density functional theory. The calculation presents difficulties that are unlike those encountered with the Kubo formulas for the electrical and thermal conductivities. In particular, the widely used Kubo-Greenwood approximation is inapplicable here. Indeed, the friction coefficients and the energy relaxation rate diverge in this approximation since it does not properly account for the electronic screening of electron-ion interactions. The inclusion of screening effects considerably complicates the calculations. We discuss the physically motivated approximations we applied to deal with these complications in order to investigate a widest range of materials and physical conditions. Unlike the standard method used for the electronic conductivities, the Kubo formulas are evaluated directly in the time domain and not in the energy domain, which spares one from needing to introduce an extraneous undetermined numerical parameter to account for the discrete character of the numerical density of states. We highlight interesting properties of the energy relaxation rate not shared by other electronic properties, in particular its self-averaging character. We then present a detailed parametric and convergence study with the numerical parameters, including the system size, the number of bands and k-points, and the physical approximations for the dielectric function and the exchange-correlation energy.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Cooperative Testing of Rocket Injectors That Use Gaseous Oxygen and Hydrogen

Gaseous oxygen and hydrogen propellants used in a special engine energy cycle called Full-Flow Staged Combustion are believed to significantly increase the lifetime of a rocket engine's pumps. The cycle can also reduce the operating temperatures of the engine. Improving the lifetime of the hardware reduces its overall maintenance and operations costs, and is critical to reducing costs for the joint NASA/industry Reusable Launch Vehicle (RLV). The work in this project will demonstrate the performance and lifetime of one-element and many-element combustors with gaseous O2/H2 injectors. This work supporting the RLV program is a cooperative venture of the NASA Lewis Research Center, the NASA Marshall Space Flight Center, Rocketdyne, and the Pennsylvania State University. Information about gas-gas rocket injector performance with O2/H2 is very limited. Because of this paucity of data, new testing is needed to improve the knowledge base for testing and designing new injectors for the RLV and to improve computer models that predict the combusting gas flows of new injector designs. Therefore, detailed observations and measurements of the combusting flow from many-element injectors in a rocket engine are being sought. These observations and measurements will be done with three different tools: schlieren photography, ultraviolet imaging, and Raman spectroscopy. The schlieren system will take photos of the density differences in combusting flow, the ultraviolet movies will determine the location of the hydroxyl (OH) radical in the combustion flow, and the Raman spectroscopic measurements will provide the combustion temperature and amount of water (H2O), hydrogen (H2), and oxygen (O2) in the combustor. Marshall is providing overall program management, design and computational fluid dynamics (CFD) analyses, as well as funding for the work at Penn State. An existing, windowed combustor and several injectors will be provided by Rocketdyne--two injectors for the initial screening tests and one with an optimized design based on the best design found in the screening tests. Lewis will provide a nozzle and several injectors for the screening test program. The configuration of the injectors will be based on a design chosen by all the participants, and their elements will be based on the coaxial and impinging flow. Lewis also will provide the instrumentation for the flow-field measurements: schlieren, ultraviolet imaging, and Raman spectroscopy. In addition, thermocouples will measure heat flow on the injector face. Other traditional measurements of rocket performance will be made as well: chamber pressure, mass flow of each propellant, purge flow, and the barrier cooling gas flow. Penn State will conduct single-element testing with the injector elements from both the Rocketdyne and the jointly designed injectors. A wide variety of traditional and nontraditional injector designs will be tested in this program. The results will be valuable in computational fluid dynamics code validation and overall rocket combustion efficiency measurements. Correlations between combustion efficiency, laser measurements of species, and ultraviolet and visible light photography will also be made. Thus far, several different single-element injectors have been tested at Penn State and Lewis. The experimental setup of a rocket engine with a viewing window is shown. The combusting flow is shown. The results are helping engineers design the many element injectors.

Source record↗

Identification of a pharmacological approach to reduce ACE2 expression and development of an in vitro COVID-19 viral entry model

Because of rapid emergence and circulation of the SARS-CoV-2 variants, especially Omicron which shows increased transmissibility and resistant to antibodies, there is an urgent need to develop novel therapeutic drugs to treat COVID-19. In this study we developed an in vitro cellular model to explore the regulation of ACE2 expression and its correlation with ACE2-mediated viral entry. We examined ACE2 expression in a variety of human cell lines, some of which are commonly used to study SARS-CoV-2. Using the developed model, we identified a number of inhibitors which reduced ACE2 protein expression. The greatest reduction of ACE2 expression was observed when CK869, an inhibitor of the actin-related protein 2/3 (ARP2/3) complex, was combined with 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), an inhibitor of sodium-hydrogen exchangers (NHEs), after treatment for 24 h. Using pseudotyped lentivirus expressing the SARS-CoV-2 full-length spike protein, we found that ACE2-dependent viral entry was inhibited in CK869 + EIPA-treated Calu-3 and MDA-MB-468 cells. This study provides an in vitro model that can be used for the screening of novel therapeutic candidates that may be warranted for further pre-clinical and clinical studies on COVID-19 countermeasures.

59 BASIC BIOLOGICAL SCIENCES↗

Corrosivity Screening of Pyrolysis Bio-Oils by Short-Term Alloy Exposures. Laboratory Analytical Procedure (LAP), Issue Date: May 12, 2022

Bio-oils contain organic acids and oxygenated compounds that can lead to corrosion issues during bio-oil processing and storage. This Laboratory Analytical Procedure (LAP) allows for rapid screening of a bio-oil's corrosivity without the need for complex equipment and long-term exposures. A robust and repeatable method for assessing the corrosivity of bio-oils is necessary in order to remove materials degradation as an obstacle to research, upgrading, use and storage of bio-oils. This LAP involves the incubation of a representative alloy, 410 stainless steel (410 SS), specimen in bio-oil over a period of 48 hours at 50 degrees C in a sealed container. The corrosive species in the bio-oil react with and deplete alloy elements such as iron (Fe) and/or chromium (Cr) from the specimen into the bio-oil solution. The depletion of Fe and Cr from the specimen results in a significant mass loss that can be recorded. The mass loss is directly correlated to the corrosivity of a bio-oil. Examples of bio-oils in scope include the ones produced by fast pyrolysis and catalytic fast pyrolysis, as well as liquids produced from hydrothermal liquefaction.

09 BIOMASS FUELS↗

Terra MODIS Sees Solar Eclipses: Analysis of Reflective Solar Band Response at Multiple Radiance Levels

The MODIS imaging spectroradiometer instruments on-board NASA's Terra and Aqua satellites have 20 reflective solar bands (RSB) covering a wavelength range from 400 to 2200 nm. Radiance is calculated from processing raw signals with background, temperature, and electronic contamination corrected. Measured gain is calibrated with a fully Sunlit solar diffuser (SD) at a stable radiance level, considering a slowly changing SD reflectance degradation. These measurements provide time-dependent gain adjustment factors, and the calibration assumes a linear response for each band and detector. Hence, an analysis of the dependence on different radiance levels is warranted. The MODIS design has no mechanism for varying radiance levels, except for an attenuator screen. However, it has been in static configuration for Terra since mid-2003. An external source of radiance attenuation can be utilized during solar eclipse events, while maintaining high stability and accuracy of solar calibration standards. Due to its long mission lifetime, Terra has seen several Sun-Moon near-conjunction events when it coincides with the orbit path where the SD is directly illuminated. As of August 2020, we have identified 7 viable partial solar eclipses in the Terra mission data. We will discuss several results of our study, including comparison of measured SD signal to predicted radiance reduction based on a solar disk radiance model; nominal and outlier behavior as a function of bands, detectors, and mirror-sides; and comparison with other data sets. Our main conclusion from this study is that there is no notable correlation of detector-dependent trend with radiance level for most RSB bands.

Terra↗

Opportunistic bone density screening for the abdominal radiologist using colored CT images: a pilot retrospective study

Purpose: The purpose of the study was to develop an accurate and reproducible method for detecting low spinal bone density on abdominal CT images. Methods: For this IRB-approved HIPAA-compliant single-center retrospective study, nonenhanced CT images of the lower abdomen were obtained in 631 African-American participants. Mean attenuation of L3/L4 was associated with quantitative CT bone density (QCT) in a randomly selected training cohort (N = 511), and receiver operating characteristics analysis was used to identify the optimal mean attenuation threshold for differentiating normal from low bone density. Custom image processing software was used to generate grayscale and colored CT images of the midline spine, with green for normal and red for low bone density. Five radiologists independently assessed bone density at L3/L4 in a validation cohort (N = 120) using various methods: QCT, visual assessment of sagittal grayscale images (Grayscale), quantitative measurement of mean attenuation on a midline sagittal image (Attenuation), and visual assessment of a midline sagittal colored image (Color). Accuracy was calculated using the average QCT bone density as a reference standard. Inter-observer agreement was assessed using intraclass correlation coefficient (ICC). Results: The optimal mean attenuation threshold for differentiating normal from low bone density at L3/L4 was 145 Hounsfield Units. The average accuracy of Grayscale, Attenuation, and Color methods was 58, 87, and 91% (p < 0.001), respectively. Inter-observer agreement was poor for Grayscale (ICC: 0.20; 95% CI 0.12, 0.28) and excellent for both Attenuation (ICC: 0.85; 95% CI 0.73, 0.91) and Color methods (ICC: 0.87; 95% CI 0.83, 0.90). Conclusion: Detection of low spinal bone density using colored abdominal CT images was highly accurate and reproducible.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Beyond the Debye–Hückel limit: Toward a general theory for concentrated electrolytes

The phenomenon of underscreening in concentrated electrolyte solutions leads to a larger decay length of the charge–charge correlation than the prediction of Debye–Hückel (DH) theory and has found a resurgence of both theoretical and experimental interest in the chemical physics community. To systematically understand and investigate this phenomenon in electrolytes requires a theory of concentrated electrolytes to describe charge–charge correlations beyond the DH theory. We review the theories of electrolytes that can transition from the DH limit to concentrations where charge correlations dominate, giving rise to underscreening and the associated Kirkwood Transitions (KTs). In this perspective, we provide a conceptual approach to a theoretical formulation of electrolyte solutions that exploits the competition between molecular-informed short-range (SR) and long-range interactions. We demonstrate that all deviations from the DH limit for real electrolyte solutions can be expressed through a single function ΣQ that can be determined both theoretically and numerically. Importantly, ΣQ can be directly related to the details of SR interactions and, therefore, can be used as a tool to understand how differences in representations of interaction can influence collective effects. The precise function form of ΣQ can be inferred through a Gaussian field theory of both the number and charge densities. The resulting formulation is validated by experiment and can accurately describe the collective phenomenon of screening in concentrated bulk electrolytes. Importantly, the Gaussian field theory predictions of the screening lengths appear to be less than ∼1 nm at concentrations above KTs.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Dose–Volume Modeling of Brachial Plexus-Associated Neuropathy After Radiation Therapy for Head-and-Neck Cancer: Findings From a Prospective Screening Protocol

Purpose: Data from a prospective screening protocol administered for patients previously irradiated for head-and-neck cancer was analyzed to identify dosimetric predictors of brachial plexus-associated neuropathy. Methods and Materials: Three hundred fifty-two patients who had previously completed radiation therapy for squamous cell carcinoma of the head and neck were prospectively screened from August 2007 to April 2013 using a standardized self-administered instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from radiation therapy was 40 months (range, 6-111 months). A total of 177 patients (50%) underwent neck dissection. Two hundred twenty-one patients (63%) received concurrent chemotherapy. Results: Fifty-one patients (14%) reported brachial plexus-related neuropathic symptoms with the most common being ipsilateral pain (50%), numbness/tingling (40%), and motor weakness and/or muscle atrophy (25%). The 3- and 5-year estimates of freedom from brachial plexus-associated neuropathy were 86% and 81%, respectively. Clinical/pathological N3 disease (P<.001) and maximum radiation dose to the ipsilateral brachial plexus (P=.01) were significantly associated with neuropathic symptoms. Cox regression analysis revealed significant dose–volume effects for brachial plexus-associated neuropathy. The volume of the ipsilateral brachial plexus receiving >70 Gy (V70) predicted for symptoms, with the incidence increasing with V70 >10% (P<.001). A correlation was also observed for the volume receiving >74 Gy (V74) among patients treated without neck dissection, with a cutoff of 4% predictive of symptoms (P=.038). Conclusions: Dose–volume guidelines were developed for radiation planning that may limit brachial plexus-related neuropathies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Mining a human transcriptome database for chemical modulators of NRF2

Nuclear factor erythroid-2 related factor 2 (NRF2) encoded by the NFE2L2 gene is a transcription factor critical for protecting cells from chemically-induced oxidative stress. We developed computational procedures to identify chemical modulators of NRF2 in a large database of human microarray data. A gene expression biomarker was built from statistically-filtered gene lists derived from microarray experiments in primary human hepatocytes and cancer cell lines exposed to NRF2-activating chemicals (oltipraz, sulforaphane, CDDOIm) or in which the NRF2 suppressor Keap1 was knocked down by siRNA. Directionally consistent biomarker genes were further filtered for those dependent on NRF2 using a microarray dataset from cells after NFE2L2 siRNA knockdown. The resulting 143-gene biomarker was evaluated as a predictive tool using the correlation-based Running Fisher algorithm. Using 59 gene expression comparisons from chemically-treated cells with known NRF2 activating potential, the biomarker gave a balanced accuracy of 93%. The biomarker was comprised of many well-known NRF2 target genes (AKR1B10, AKR1C1, NQO1, TXNRD1, SRXN1, GCLC, GCLM), 69% of which were found to be bound directly by NRF2 using ChIP-Seq. NRF2 activity was assessed across ~9840 microarray comparisons from ~1460 studies examining the effects of ~2260 chemicals in human cell lines. A total of 260 and 43 chemicals were found to activate or suppress NRF2, respectively, most of which have not been previously reported to modulate NRF2 activity. Using a NRF2-responsive reporter gene in HepG2 cells, we confirmed the activity of a set of chemicals predicted using the biomarker. The biomarker will be useful for future gene expression screening studies of environmentally-relevant chemicals.

59 BASIC BIOLOGICAL SCIENCES↗

Alternate Protocol for Detecting Biological Contamination on Sensitive Hardware

The purpose of this project is to develop a sterile water based rapid bioburden test. Contamination engineers use two tests to assess the level of biological contamination on hardware: the rapid five minute bioburden test, which is a molecular screening for Adenosine triphosphate (ATP), a molecule found in all cells on the hardware, and a slower colony growth test, which is used to give a more accurate representation of the amount of microbes on the hardware. However, the rapid bioburden test has limited application because it leaves a residue that can be detrimental to sensitive hardware. This can cause project delays while waiting for the results from the three day colony growth test. We address this problem by adapting the commercial germicide based ATP system to a sterile water based system. The test works by reacting ATP with D-Luciferin and Luciferase protein to yield light. The light is then detected by a luminometer that outputs a Relative Light Unit (RLU) amount depending on how much ATP is present. To analyze the effectiveness of the new test, we developed a correlation between amounts of ATP and the RLU produced using the germicide based system. From these experiments, we've generated a consistent relationship between the two in the form of a power curve. From there, we developed a correlation curve between the amount of colonies and the RLU they produced. Initial tests of the new protocol have shown that the water based system isn't as sensitive as the germicide based test.

planetary protection↗

Effects of Functional Groups in Redox-Active Organic Molecules: A High-Throughput Screening Approach

Nonaqueous redox flow batteries have attracted recent attention with their potential for high electrochemical storage capacity, with organic electrolytes serving as solvents with a wide electrochemical stability window. Organic molecules can also serve as electroactive species, where molecules with low reduction potentials or high oxidation potentials can provide substantial chemical energy. To identify promising electrolytes in a vast chemical space, high-throughput screening (HTS) of candidate molecules plays an important role, where HTS is used to calculate properties of thousands of molecules and identify a few organic molecules worthy of further attention in battery research. Here, in this work, we present reduction and oxidation potentials obtained from HTS of 4178 molecules. The molecules are composed of base groups of five- or six-membered rings with one or two functional groups attached, with the set of possible functional groups including both electron-withdrawing and electron-donating groups. In addition to observing the trends in potentials that result from differences in organic base groups and functional groups, we analyze the effects of molecular characteristics such as multiple bonds, Hammett parameters, and functional group position. In conclusion, this work provides useful guidance in determining how the identities of the base groups and functional groups are correlated with desirable reduction and oxidation potentials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Circular RNA hsa-circ-0010729 regulates vascular endothelial cell proliferation and apoptosis by targeting the miR-186/HIF-1α axis

Circular RNAs (circRNAs) are a group of non-protein-coding RNAs generated from back splicing. Emerging evidence has demonstrated its vital regulation on angiogenesis. However, the underlying mechanism responsible for circRNAs effects on vascular endothelial cells is still unclear. In the present study, we screened the expression profiles and investigated the physiological role of circRNAs in hypoxia-induced human umbilical vein endothelial cells (HUVECs). Using circRNA microarray analysis, we identified 36 circRNAs that were significantly dysregulated including 14 down-regulated circRNAs and 22 up-regulated with 2-fold change (P < 0.05). From the over-expressed circRNAs, hsa-circ-0010729 was selected as candidate circRNA and which was validated to be significantly up-regulated using RT-PCR. In loss-of-function experiments of HUVECs, hsa-circ-0010729 knockdown suppressed the proliferation and migration ability and enhanced apoptosis. Bioinformatic prediction and luciferase assay revealed that hsa-circ-0010729 and hypoxia inducible factor 1 alpha (HIF-1α) were targeted by miR-186. Validation experiments verified that hsa-circ-0010729 was co-expressed with HIF-1α, being negatively correlated with miR-186. Moreover, rescue experiments demonstrated that miR-186 inhibitor could reverse the role of hsa-circ-0010729 knockdown on HUVECs progression. Overall, the present study identifies the crucial regulation of hsa-circ-0010729 on vascular endothelial cell proliferation and apoptosis via targeting miR-186/HIF-1α axis. - Highlights: • Circular RNA expression profile identifies hsa-circ-0010729 is up-regulated in hypoxia-induced HUVECs. • Hsa-circ-0010729 knockdown suppresses the proliferation and migration ability, and enhanced the apoptosis. • Hsa-circ-0010729 acts as an endogenous sponge of miR-186. • HIF-1α is targeted by miR-186. • Hsa-circ-0010729 regulates vascular endothelial cells proliferation and apoptosis via targeting miR-186/HIF-1α axis.

60 APPLIED LIFE SCIENCES↗

Nanometer-scale electrical potential imaging on absorber of CdSeTe solar cells

Here, we report on nm-scale electrical potential imaging throughout As-doped and Cu-doped CdSeTe absorbers using Kelvin probe force microscopy (KPFM). The potential imaging was conducted both laterally and vertically on beveled films using ion milling at small glancing angle. KPFM images electrical potential on the beveled surface and assesses defect charging in the subsurface region within a screening length from the beveled surface. We found that the grain boundaries were positively charged and that there were significant potential fluctuations in both grain boundary versus grain interior and intragrain. We further found that these potential fluctuations decreased significantly toward the front interface. Time of flight secondary ion mass spectrometry imaging shows that Se content increased toward the front interface, consistent with Se passivation of defects. The potential fluctuation was induced by defect charging, and the results elucidate different details of the defect configurations and grain structures of the films with different CdCl 2 treatment temperatures in the As-doped CdSeTe. The defect configurations in the region near the front interface can be a main factor contributing to the device performance difference. Our potential imaging provides insights about the defects throughout the absorber films, and shows that the potential fluctuation has a direct correlation to the V oc deficit.

14 SOLAR ENERGY↗

Dysregulation of Macrophage Activation Profiles by Engineered Nanoparticles

Although the potential human health impacts from exposure to engineered nanoparticles (ENPs) are uncertain, past epidemiological studies have established correlations between exposure to ambient air pollution particulates and the incidence of pneumonia and lung infections. Using amorphous silica and superparamagnetic iron oxide (SPIO) as model high production volume ENPs, we examined how macrophage activation by bacterial lipopolysaccharide (LPS) or the lung pathogen Streptococcus pneumoniae is altered by ENP pretreatment. Neither silica nor SPIO treatment elicited direct cytotoxic or pro-inflammatory effects in bone marrow-derived macrophages. However, pretreatment of macrophages with SPIO caused extensive reprogramming of nearly 500 genes regulated in response to LPS challenge, hallmarked by exaggerated activation of oxidative stress response pathways and suppressed activation of both pro- and anti-inflammatory pathways. Silica pretreatment altered regulation of only 67 genes, but there was strong correlation with gene sets affected by SPIO. Macrophages exposed to SPIO displayed a phenotype suggesting an impaired ability to transition from an M1 to M2-like activation state, characterized by suppressed IL-10 induction, enhanced TNFα production, and diminished phagocytic activity toward S. pneumoniae. Studies in macrophages deficient in scavenger receptor A (SR-A) showed SR-A participates in cell uptake of both the ENPs and S. pneumonia and co-regulates the anti-inflammatory IL-10 pathway. Thus, mechanisms for dysregulation of innate immunity exist by virtue that common receptor recognition pathways are used by some ENPs and pathogenic bacteria, although the extent of transcriptional reprogramming of macrophage function depends on the physicochemical properties of the ENP after internalization. Our results also illustrate that biological effects of ENPs may be indirectly manifested only after challenging normal cell function. Finally, nanotoxicology screening strategies should therefore consider how exposure to these materials alters susceptibility to other environmental exposures.

Kodali, Vamsi↗

Hypofractionated Whole-Breast Radiation Therapy: Does Breast Size Matter?

Purpose: To evaluate the effects of breast size on dose-volume histogram parameters and clinical toxicity in whole-breast hypofractionated radiation therapy using intensity modulated radiation therapy (IMRT). Materials and Methods: In this retrospective study, all patients undergoing breast-conserving therapy between 2005 and 2009 were screened, and qualifying consecutive patients were included in 1 of 2 cohorts: large-breasted patients (chest wall separation >25 cm or planning target volume [PTV] >1500 cm{sub 3}) (n=97) and small-breasted patients (chest wall separation <25 cm and PTV <1500 cm{sub 3}) (n=32). All patients were treated prone or supine with hypofractionated IMRT to the whole breast (42.4 Gy in 16 fractions) followed by a boost dose (9.6 Gy in 4 fractions). Dosimetric and clinical toxicity data were collected and analyzed using the R statistical package (version 2.12). Results: The mean PTV V95 (percentage of volume receiving >= 95% of prescribed dose) was 90.18% and the mean V105 percentage of volume receiving >= 105% of prescribed dose was 3.55% with no dose greater than 107%. PTV dose was independent of breast size, whereas heart dose and maximum point dose to skin correlated with increasing breast size. Lung dose was markedly decreased in prone compared with supine treatments. Radiation Therapy Oncology Group grade 0, 1, and 2 skin toxicities were noted acutely in 6%, 69%, and 25% of patients, respectively, and at later follow-up (>3 months) in 43%, 57%, and 0% of patients, respectively. Large breast size contributed to increased acute grade 2 toxicity (28% vs 12%, P=.008). Conclusions: Adequate PTV coverage with acceptable hot spots and excellent sparing of organs at risk was achieved by use of IMRT regardless of treatment position and breast size. Although increasing breast size leads to increased heart dose and maximum skin dose, heart dose remained within our institutional constraints and the incidence of overall skin toxicity was comparable to that reported in the literature. Taken together, these data suggest that hypofractionated radiation therapy using IMRT is a viable and appropriate therapeutic modality in large-breasted patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗