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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 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Wearable radio-frequency sensing of respiratory rate, respiratory volume, and heart rate

Abstract Many health diagnostic systems demand noninvasive sensing of respiratory rate, respiratory volume, and heart rate with high user comfort. Previous methods often require multiple sensors, including skin-touch electrodes, tension belts, or nearby off-the-body readers, and hence are uncomfortable or inconvenient. This paper presents an over-clothing wearable radio-frequency sensor study, conducted on 20 healthy participants (14 females) performing voluntary breathing exercises in various postures. Two prototype sensors were placed on the participants, one close to the heart and the other below the xiphoid process to couple to the motion from heart, lungs and diaphragm, by the near-field coherent sensing principle. We can achieve a satisfactory correlation of our sensor with the reference devices for the three vital signs: heart rate ( r = 0.95), respiratory rate ( r = 0.93) and respiratory volume ( r = 0.84). We also detected voluntary breath-hold periods with an accuracy of 96%. Further, the participants performed a breathing exercise by contracting abdomen inwards while holding breath, leading to paradoxical outward thorax motion under the isovolumetric condition, which was detected with an accuracy of 83%.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Elevated nocturnal respiratory rates in the mitochondria of CAM plants: current knowledge and unanswered questions

Abstract Crassulacean acid metabolism (CAM) is a metabolic adaptation that has evolved convergently in 38 plant families to aid survival in water-limited niches. Whilst primarily considered a photosynthetic adaptation, CAM also has substantial consequences for nocturnal respiratory metabolism. Here, we outline the history, current state and future of nocturnal respiration research in CAM plants, with a particular focus on the energetics of nocturnal respiratory oxygen consumption. Throughout the 20th century, research interest in nocturnal respiration occurred alongside initial discoveries of CAM, although the energetic and mechanistic implications of nocturnal oxygen consumption and links to the operation of the CAM cycle were not fully understood. Recent flux balance analysis (FBA) models have provided new insights into the role that mitochondria play in the CAM cycle. Several FBA models have predicted that CAM requires elevated nocturnal respiratory rates, compared to C3 species, to power vacuolar malic acid accumulation. We provide physiological data, from the genus Clusia, to corroborate these modelling predictions, thereby reinforcing the importance of elevated nocturnal respiratory rates for CAM. Finally, we outline five unanswered questions pertaining to nocturnal respiration which must be addressed if we are to fully understand and utilize CAM plants in a hotter, drier world.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

TU-H-CAMPUS-TeP2-01: A Comparison of Noninvasive Techniques to Assess Radiation-Induced Lung Damage in Mice

Purpose: To evaluate the use of post-irradiation changes in respiratory rate and CBCT-based morphology as predictors of survival in mice. Methods: C57L/J mice underwent whole-thorax irradiation with a Co-60 beam to four different doses [0Gy (n=3), 9Gy (n=5), 11Gy (n=7), and 13Gy (n=5)] in order to induce varying levels of pneumonitis. Respiratory rate measurements, breath-hold CBCTs, and free-breathing CBCTs were acquired pre-irradiation and at six time points between two and seven months post-irradiation. For respiratory rate measurements, we developed a novel computer-vision-based technique. We recorded mice sleeping in standard laboratory cages with a 30 fps, 1080p webcam (Logitech C920). We calculated respiratory rate using corner detection and optical flow to track cyclical motion in the fur in the recorded video. Breath-hold and free-breathing CBCTs were acquired on the X-RAD225Cx system. For breathhold imaging, the mice were intubated and their breath was held at full-inhale for 20 seconds. Healthy lung tissue was delineated in the scans using auto-threshold contouring (0–0.7 g/cm{sup 3}). The volume of healthy lung was measured in each of the scans. Next, lung density was measured in a 6-mm{sup 2} ROI in a fixed anatomic location in each of the scans. Results: Day-to-day variability in respiratory rate with our technique was 13%. All metrics except for breath-hold lung volume were correlated with survival: lung density on free-breathing (r=−0.7482,p<0.01) and breath-hold images (r=−0.5864,p<0.01), free-breathing lung volume (r=0.7179,p<0.01), and respiratory rate (r= 0.6953,p<0.01). Lung density on free-breathing scans was correlated with respiratory rate (r=0.7142,p<0.01) and lung density on breath-hold scans (r=0.5543,p<0.01). One significant practical hurdle in the CBCT measurements was that at least one lobe of the lung was collapsed in 36% of free-breathing scans and 45% of breath-hold scans. Conclusion: Lung density and lung volume on free-breathing CBCTs and respiratory rate outperform breath-hold CBCT measurements as indicators for survival from radiation-induced pneumonitis. This work was partially funded by Elekta.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Antibiotics induce mitonuclear protein imbalance but fail to inhibit respiration and nutrient activation in pancreatic β-cells

Chloramphenicol and several other antibiotics targeting bacterial ribosomes inhibit mitochondrial protein translation. Inhibition of mitochondrial protein synthesis leads to mitonuclear protein imbalance and reduced respiratory rates as confirmed here in HeLa and PC12 cells. Unexpectedly, respiration in INS-1E insulinoma cells and primary human islets was unaltered in the presence of chloramphenicol. Resting respiratory rates and glucose stimulated acceleration of respiration were also not lowered when a range of antibiotics including, thiamphenicol, streptomycin, gentamycin and doxycycline known to interfere with bacterial protein synthesis were tested. However, chloramphenicol efficiently reduced mitochondrial protein synthesis in INS-1E cells, lowering expression of the mtDNA encoded COX1 subunit of the respiratory chain but not the nuclear encoded ATP-synthase subunit ATP5A. Despite a marked reduction of the essential respiratory chain subunit COX1, normal respiratory rates were maintained in INS-1E cells. ATP-synthase dependent respiration was even elevated in chloramphenicol treated INS-1E cells. Consistent with these findings, glucose-dependent calcium signaling reflecting metabolism-secretion coupling in beta-cells, was augmented. We conclude that antibiotics targeting mitochondria are able to cause mitonuclear protein imbalance in insulin secreting cells. We hypothesize that in contrast to other cell types, compensatory mechanisms are sufficiently strong to maintain normal respiratory rates and surprisingly even result in augmented ATP-synthase dependent respiration and calcium signaling following glucose stimulation. The result suggests that in insulin secreting cells only lowering COX1 below a threshold level may result in a measurable impairment of respiration. When focusing on mitochondrial function, care should be taken when including antibiotics targeting translation for long-term cell culture as depending on the sensitivity of the cell type analyzed, respiration, mitonuclear protein imbalance or down-stream signaling may be altered. - Highlights: • Chloramphenicol inhibits mitochondrial translation and respiration in HeLa and PC12. • Respiration is normal in chloramphenicol treated INS-1E cells and human islets. • Chloramphenicol inhibits mitochondrial translation in insulin secreting INS-1E cells. • Antibiotics induce a mitochondrial unfolded protein response in INS-1E and PC12. • Chloramphenicol slightly promotes metabolism-secretion coupling in INS-1E cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Effects of cold stress on metabolic regulation in the overwintering larvae of the Chinese white pine beetle, Dendroctonus armandi

Abstract The Chinese white pine beetle, Dendroctonus armandi Tsai & Li (Coleoptera: Curculionidae, Scolytinae), is considered the most destructive forest pest in the Qinling and Bashan Mountains of China. In recent years, winter temperature has dropped in these regions, and extremely low temperatures are hard to survive for insects. Cold hardiness becomes a crucial strategy because temperature change often leads to fluctuations in insect abundance, and the metabolism rate is a key index of resistance to cold in overwintering insects. Therefore, we investigated the relationship between the change in respiratory rate and the activity of metabolism‐related mitochondrial enzymes in D. armandi larvae under cold conditions. We found that the respiratory rate decreased, and it was matched with the activity of glutamate dehydrogenase, aconitase, and lipase during overwintering. Among the various test times under cold conditions, the respiratory rate also decreased with decreasing temperature and increased under very low temperatures. At all cold stress periods, glutamate dehydrogenase and lipase showed increased activity at higher temperatures and decreased activity under lower temperatures, but the activity of NAD‐malic enzyme, NADP‐malic enzyme, mitochondrial isocitrate dehydrogenase, and aconitase were contrary. Under all low temperatures, the activity of enzymes – except for NADP‐malic enzyme, glutamate dehydrogenase, and lipase – increased in short‐term cold stress and decreased in long‐term cold stress at 4, 0, −4, −6, −8, and −10 °C. However, at −2 °C, the activity of enzymes showed a decreasing trend in short‐term treatments and an increasing trend in long‐term treatments, except for mitochondrial isocitrate dehydrogenase. The results not only improve our understanding of the metabolic mechanism of cold adaptation in D. armandi , but also provide an important experimental basis for further study and biological pest control.

Fu, Danyang↗
DOE OSTI2018

Association between human and animal thermal comfort indices and physiological heat stress indicators in dairy calves

Warm summer episodes have a significant effect on the overall health and well-being of young cattle; however, it is not known which temperature measure should be used for estimating heat stress in dairy calves. In this study, generalized linear mixed-effects models were used to estimate the relationships between thermal comfort indices and animal-based heat stress indicators in sixteen Holstein bull calves that were housed in individual calf hutches. Data were collected under continental weather characteristics over a 5-day period: day 1 (lower-temperature day), days 2 and 3 (heat stress days), and a 2-day post-stress period. Relative humidity, ambient temperature, the heat index, the humidex and five different temperature–humidity indices (THI) were used as thermal indices. Physiological variables monitored included respiratory rate, rectal temperature, ear skin temperature and heart rate. The heat index and the humidex measuring human thermal comfort were more closely associated with physiological measures than were the ambient temperature or the THIs (in case of heat index: R{sup 2} = 0.87 for respiratory rate, R{sup 2} = 0.63 for rectal temperature, R{sup 2} = 0.70 for ear skin temperature, and R{sup 2} = 0.78 for heart rate, respectively; in case of humidex: R{sup 2} = 0.85 for respiratory rate, R{sup 2} = 0.60 for rectal temperature, R{sup 2} = 0.68 for ear skin temperature, and R{sup 2} = 0.75 for heart rate, respectively). Based on our results, parameters of human outdoor comfort seem better to estimate heat stress in dairy calves in a continental region than those of THIs or ambient temperature.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed the dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late RILD are also due to different pathologies. As such, new radiation techniques reducing irradiated volume might change the dose-limiting toxicity of the radiation therapy treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Geometric validation of self-gating k-space-sorted 4D-MRI vs 4D-CT using a respiratory motion phantom

Purpose: MRI is increasingly being used for radiotherapy planning, simulation, and in-treatment-room motion monitoring. To provide more detailed temporal and spatial MR data for these tasks, we have recently developed a novel self-gated (SG) MRI technique with advantage of k-space phase sorting, high isotropic spatial resolution, and high temporal resolution. The current work describes the validation of this 4D-MRI technique using a MRI- and CT-compatible respiratory motion phantom and comparison to 4D-CT. Methods: The 4D-MRI sequence is based on a spoiled gradient echo-based 3D projection reconstruction sequence with self-gating for 4D-MRI at 3 T. Respiratory phase is resolved by using SG k-space lines as the motion surrogate. 4D-MRI images are reconstructed into ten temporal bins with spatial resolution 1.56 × 1.56 × 1.56 mm{sup 3}. A MRI-CT compatible phantom was designed to validate the performance of the 4D-MRI sequence and 4D-CT imaging. A spherical target (diameter 23 mm, volume 6.37 ml) filled with high-concentration gadolinium (Gd) gel is embedded into a plastic box (35 × 40 × 63 mm{sup 3}) and stabilized with low-concentration Gd gel. The phantom, driven by an air pump, is able to produce human-type breathing patterns between 4 and 30 respiratory cycles/min. 4D-CT of the phantom has been acquired in cine mode, and reconstructed into ten phases with slice thickness 1.25 mm. The 4D images sets were imported into a treatment planning software for target contouring. The geometrical accuracy of the 4D MRI and CT images has been quantified using target volume, flattening, and eccentricity. The target motion was measured by tracking the centroids of the spheres in each individual phase. Motion ground-truth was obtained from input signals and real-time video recordings. Results: The dynamic phantom has been operated in four respiratory rate (RR) settings, 6, 10, 15, and 20/min, and was scanned with 4D-MRI and 4D-CT. 4D-CT images have target-stretching, partial-missing, and other motion artifacts in various phases, whereas the 4D-MRI images are visually free of those artifacts. Volume percentage difference for the 6.37 ml target ranged from 5.3% ± 4.3% to 10.3% ± 5.9% for 4D-CT, and 1.47 ± 0.52 to 2.12 ± 1.60 for 4D-MRI. With an increase of respiratory rate, the target volumetric and geometric deviations increase for 4D-CT images while remaining stable for the 4D-MRI images. Target motion amplitude errors at different RRs were measured with a range of 0.66–1.25 mm for 4D-CT and 0.2–0.42 mm for 4D-MRI. The results of Mann–Whitney tests indicated that 4D-MRI significantly outperforms 4D-CT in phase-based target volumetric (p = 0.027) and geometric (p < 0.001) measures. Both modalities achieve equivalent accuracy in measuring motion amplitude (p = 0.828). Conclusions: The k-space self-gated 4D-MRI technique provides a robust method for accurately imaging phase-based target motion and geometry. Compared to 4D-CT, the current 4D-MRI technique demonstrates superior spatiotemporal resolution, and robust resistance to motion artifacts caused by fast target motion and irregular breathing patterns. The technique can be used extensively in abdominal targeting, motion gating, and toward implementing MRI-based adaptive radiotherapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Direct and indirect effects of climatic variations on the interannual variability in net ecosystem exchange across terrestrial ecosystems

Our study indicates that climatic variables not only directly affect the interannual variability (IAV) in net ecosystem exchange of CO 2 (NEE) but also indirectly drive it by changing the physiological parameters. Identifying these direct and indirect paths can reveal the underlying mechanisms of carbon (C) dynamics. In this study, we applied a path analysis using flux data from 65 sites to quantify the direct and indirect climatic effects on IAV in NEE and to evaluate the potential relationships among the climatic variables and physiological parameters that represent physiology and phenology of ecosystems. We found that the maximum photosynthetic rate was the most important factor for the IAV in gross primary productivity (GPP), which was mainly induced by the variation in vapour pressure deficit. For ecosystem respiration (RE), the most important drivers were GPP and the reference respiratory rate. The biome type regulated the direct and indirect paths, with distinctive differences between forests and non-forests, evergreen needleleaf forests and deciduous broadleaf forests, and between grasslands and croplands. Different paths were also found among wet, moist and dry ecosystems. However, the climatic variables can only partly explain the IAV in physiological parameters, suggesting that the latter may also result from other biotic and disturbance factors. In addition, the climatic variables related to NEE were not necessarily the same as those related to GPP and RE, indicating the emerging difficulty encountered when studying the IAV in NEE. Overall, our results highlight the contribution of certain physiological parameters to the IAV in C fluxes and the importance of biome type and multi-year water conditions, which should receive more attention in future experimental and modelling research.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

Respiration Signal Pattern Analysis for Doppler Radar Sensor with Passive Node and Its Application in Occupancy Sensing of a Stationary Subject

Doppler radar node occupancy sensors are promising for applications in smart buildings due to their simple circuits and price advantage compared to quadrature radar sensors. However, single-channel sensitivity limitations may result in low sensitivity and misinterpreted motion rates if the detected subject is at or close to “null” points. We designed and tested a novel method to eliminate such limits, demonstrating that passive nodes can be used to detect a sedentary person regardless of position. This method is based on characteristics of chest motion due to respiration, found via both simulations and experiments based on a sinusoidal model and a more realistic model of cardiorespiratory motion. In addition, respiratory rate variability is considered to distinguish a true human presence from a mechanical target. Sensor node data were collected simultaneously with an infrared camera system, which provided a respiration signal reference, to test the algorithm with 19 human subjects and a mechanical target. The results indicate that a human presence was detected with 100% accuracy and successfully differentiated from a mechanical target in a controlled environment. The developed method can greatly improve the occupancy detection accuracy of single-channel radar-based occupancy sensors and facilitate their adoption in smart building applications.

Song, Chenyan↗
DOE OSTI2019

The Safety and Efficacy of Oxycodone Versus Fentanyl in Percutaneous Microwave Ablation of a Liver Tumour Abutting the Capsule

Purpose: The present study compared the safety and efficacy of oxycodone with those of fentanyl under non-intubated general anaesthesia in percutaneous microwave ablation (MWA) of a liver tumour abutting the capsule. Materials and Methods: Thirty-eight patients underwent MWA of liver cancers abutting the capsule. Patients received 0.1 mg/kg oxycodone (O group) or 1 μg/kg fentanyl (F group) prior to the start of ablation. Both groups received continuous infusions of propofol for non-intubated general anaesthesia during ablation. The primary outcomes were the pain scores (11-point numeric rating scale, NRS) within 24 h after MWA. Vital signs, body movement during ablation, and opioid side effects after ablation were recorded. The need for additional analgesics was recorded 24 h after MWA. Results: The pain NRS scores were lower in the O group than in the F group at 0.5 (P = 0.035), 3 (P = 0.002), and 6 h (P = 0.001) after MWA, and fewer patients required additional analgesics in the O group (6 of 20 vs. 13 of 18, P = 0.022) within 24 h. The average 24-h dose of dezocine was 5.5 ± 4.1 mg in the F group and 2.1 ± 3.3 mg in the O group (P = 0.008). A significant reduction in the respiratory rate (P = 0.020) and more body movements were observed in the F group (P = 0.027) during ablation with non-intubated general anaesthesia. No differences in post-operative nausea and vomiting (PONV) were observed between the two groups, but dizziness occurred significantly more often in the O group (P = 0.033). No significant differences in other vital signs were observed before, during, and after the procedure. Conclusions: Oxycodone provides better analgesia and reduces post-operative opioid consumption without significant respiratory or hemodynamic instability.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

TH-EF-207A-05: Feasibility of Applying SMEIR Method On Small Animal 4D Cone Beam CT Imaging

Purpose: Small animal cone beam CT imaging has been widely used in preclinical research. Due to the higher respiratory rate and heat beats of small animals, motion blurring is inevitable and needs to be corrected in the reconstruction. Simultaneous motion estimation and image reconstruction (SMEIR) method, which uses projection images of all phases, proved to be effective in motion model estimation and able to reconstruct motion-compensated images. We demonstrate the application of SMEIR for small animal 4D cone beam CT imaging by computer simulations on a digital rat model. Methods: The small animal CBCT imaging system was simulated with the source-to-detector distance of 300 mm and the source-to-object distance of 200 mm. A sequence of rat phantom were generated with 0.4 mm{sup 3} voxel size. The respiratory cycle was taken as 1.0 second and the motions were simulated with a diaphragm motion of 2.4mm and an anterior-posterior expansion of 1.6 mm. The projection images were calculated using a ray-tracing method, and 4D-CBCT were reconstructed using SMEIR and FDK methods. The SMEIR method iterates over two alternating steps: 1) motion-compensated iterative image reconstruction by using projections from all respiration phases and 2) motion model estimation from projections directly through a 2D-3D deformable registration of the image obtained in the first step to projection images of other phases. Results: The images reconstructed using SMEIR method reproduced the features in the original phantom. Projections from the same phase were also reconstructed using FDK method. Compared with the FDK results, the images from SMEIR method substantially improve the image quality with minimum artifacts. Conclusion: We demonstrate that it is viable to apply SMEIR method to reconstruct small animal 4D-CBCT images.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Humanin promotes mitochondrial biogenesis in pancreatic MIN6 β-cells

Highlights: • Humanin stimulated the expressions of PGC-1α, NRF1 and TFAM. • Humanin increased Mitochondrial mass, mtDNA/nDNA, and cytochrome B expression. • The effects of Humanin on mitochondrial biogenesis were mediated by AMPK. • Humanin led to a functional gain of the mitochondria. Mitochondrial dysfunction is associated with β-cell failure and insulin resistance in diabetes. Humanin is an endogenous cytoprotective peptide. In the current study, we aimed to define the effects of Humanin on mitochondrial biogenesis in pancreatic β-cells. Our findings demonstrated that Humanin treatment significantly increased the expression of PGC-1α and its downstream target genes NRF1 and TFAM in MIN6 β-cells. Notably, Humanin treatment significantly promoted mitochondrial biogenesis by increasing mitochondrial mass, elevating mtDNA/nDNA ratio, and stimulating the expression of cytochrome B, which were suppressed by the specific AMPK inhibitor compound C. Indeed, Humanin treatment caused the phosphorylation of AMPK, which was involved in the induction of PGC-1α, NRF1, and TFAM by Humanin. Importantly, our findings indicate that Humanin treatment led to a possible functional gain of the mitochondria by increasing ATP levels and respiratory rate. Our findings provided a new insight into the molecular mechanisms of action by which Humanin improves pancreatic β-cell function via enhanced mitochondrial mass and performance.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Ropivacaine impairs mitochondrial biogenesis by reducing PGC-1α

Highlights: • Ropivacaine inhibits the expressions of PGC-1α, NRF-1, and TFAM in M17 cells. • Ropivacaine impairs mitochondrial biogenesis and causes mitochondrial malfunction. • Ropivacaine-induced reduction of PGC-1α requires the inactivation of CREB. • PGC-1α rescues Ropivacaine-caused impairment of mitochondrial biogenesis. Ropivacaine is one of the commonly used local anesthetics in medical and dental care. However, preclinical and observational studies indicate that ropivacaine could have substantial side effects including neurotoxicity, which has raised concern regarding the safety of this drug. In the present study, we investigated the effects of clinically relevant doses of ropivacaine on mitochondrial biogenesis and function in neuronal cells. Our data indicate that exposure to ropivacaine leads to reduced expression of the major mitochondrial regulator PGC-1α and its downstream transcription factors NRF1 and TFAM. Ropivacaine treatment induces impairment of mitochondrial biogenesis by reducing mitochondrial mass, the ratio of mtDNA to nDNA (mtDNA/nDNA), cytochrome C oxidase activity, and COX-1 expression. Additionally, treatment with ropivacaine causes “loss of mitochondrial function” by impairing the mitochondrial respiratory rate and ATP production. Mechanistically, the reduction of PGC-1α caused by ropivacaine exposure requires inactivation of CREB, while re-introduction of PGC-1α completely rescues ropivacaine-induced mitochondrial abnormalities. In summary, our results provide supporting evidence that mitochondrial impairment is a key event in ropivacaine-mediated neurotoxicity, and the reduction of PGC-1α and its downstream signals are likely the molecular mechanism behind its cellular toxicity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Hardware-in-Loop Modules for Testing Automated Ventilator Controllers

Automated ventilator controllers have the potential to simplify oxygen and carbon dioxide management for trauma. In the pre-hospital or military medicine environment, trauma care can be required for prolonged periods by personnel with limited ventilator management training. As such, there is a need for closed-loop control systems that can adapt ventilator management to a complex, ever-changing medical environment. Here, we present a novel hardware-in-loop test platform for the independent troubleshooting and evaluation of oxygen and carbon dioxide automated ventilator management capabilities. The oxygen management system provides an analogue blood oxygen signal that is responsive to the fraction of inspired oxygen and the peak inspiratory pressure ventilator settings. A tested oxygenation controller successfully reached the target oxygen saturation within 5 min. The carbon dioxide removal system integrates with commercial ventilator technology and mimics carbon dioxide generation, lung compliance, and airway resistance while providing an end-tidal carbon dioxide level that is responsive to changes in the tidal volume and respiratory rate settings. A test mechanical ventilator controller was able to regulate EtCO2 regardless of the starting value within 10 min. This highlights the system’s functionality and provides proof-of-concept demonstrations for how the hardware-in-loop test platforms can be used for evaluating closed-loop controller technologies.

Berard, David (ORCID:0000000322863846)↗
DOE OSTI2015

Responses of two understory herbs, Maianthemum canadense and Eurybia macrophylla , to experimental forest warming: Early emergence is the key to enhanced reproductive output

Understory herbs might be the most sensitive plant form to global warming in deciduous forests, yet they have been little studied in the context of climate change. A field experiment set up in Minnesota, United States simulated global warming in a forest setting and provided the opportunity to study the responses of Maianthemum canadense and Eurybia macrophylla in their natural environment in interaction with other components of the ecosystem. Effects of +1.7° and +3.4°C treatments on growth, reproduction, phenology, and gas exchange were evaluated along with treatment effects on light, water, and nutrient availability, potential drivers of herb responses. Overall, growth and gas exchanges of these two species were modestly affected by warming. They emerged up to 16 ( E. macrophylla ) to 17 d ( M. canadense ) earlier in the heated plots than in control plots, supporting early-season carbon gain under high light conditions before canopy closure. This additional carbon gain in spring likely supported reproduction. Eurybia macrophylla only flowered in the heated plots, and both species had some aspect of reproduction that was highest in the +1.7°C treatment. The reduced reproductive effort in the +3.4°C plots was likely due to reduced soil water availability, counteracting positive effects of warming. In conclusion, global warming might improve fitness of herbaceous species in deciduous forests, mainly by advancing their spring emergence. However, other impacts of global warming such as drier soils in the summer might partly reduce the carbon gain associated with early emergence.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein

Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Acrolein (100–275 ppm, 10–30 min) caused upper airway epithelial sloughing, bradypnea and oral gasping, hypothermia, cardiac depression and mortality. Male wild-type mice (WT, C57BL/6; 5–52 weeks) were significantly more sensitive to high-level acrolein than age-matched, female WT mice. Both male and female TRPA1-null mice were more sensitive to acrolein-induced mortality than age- and sex-matched WT mice. Acrolein exposure increased lung weight:body weight ratios and lung albumin and decreased plasma albumin to a greater extent in TRPA1-null than in WT mice. Lung and plasma protein-acrolein adducts were not increased in acrolein-exposed TRPA1-null mice compared with WT mice. To assess TRPA1-dependent protective mechanisms, respiratory parameters were monitored by telemetry. TRPA1-null mice had a slower onset of breathing rate suppression (‘respiratory braking’) than WT mice suggesting TRPA1 mediates this protective response. Surprisingly, WT male mice treated either with a TRPA1 antagonist (HC030031; 200 mg/kg) alone or with combined TRPA1 (100 mg/kg) and TRPV1 (capsazepine, 10 mg/kg) antagonists at 30 min post-acrolein exposure (i.e., “real world” delay in treatment) were significantly protected from acrolein-induced mortality. These data show TRPA1 protects against high-level acrolein-induced toxicity in a sex-dependent manner. Post-exposure TRPA1 antagonism also protected against acrolein-induced mortality attesting to a complex role of TRPA1 in cardiopulmonary injury. - Highlights: • TRPA1 protects mice against toxicity and mortality of inhaled high-level acrolein. • TRPA1 protection against inhaled high-level acrolein is sex-dependent in mice. • Age (5–52 weeks old) was not a determinant of acrolein-induced mortality in mice. • TRPA1 antagonist is protective after inhaled high-level acrolein in male mice.

60 APPLIED LIFE SCIENCES↗