Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “RESPIRATION”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Unraveling the effects of management and climate on carbon fluxes of U.S. croplands using the USDA Long-Term Agroecosystem (LTAR) network

Understanding the carbon fluxes and dynamics from a broad range of agricultural systems has the potential to improve our ability to increase carbon sequestration while maintaining crop yields. Short-term, single-location studies have limited applicability, but long-term data from a network of many locations can provide a broader understanding across gradients of climate and management choices. Here we examine eddy covariance measured carbon dioxide (CO 2 ) fluxes from cropland sites across the United States Department of Agriculture's Long-Term Agroecosystem Research (LTAR) network. The dataset was collected between 2001 and 2020, spanning 13 sites for a total of 182 site-years. Average seasonal patterns of net ecosystem CO 2 exchange (NEE), gross primary productivity (GPP), and ecosystem respiration (R eco ) were determined, and subsequent regression analysis on these “flux climatologies” was used to identify relationships to mean annual temperature (MAT), mean annual precipitation (MAP), cropping systems, and management practices. At rainfed sites, carbon fluxes were better correlated with MAP (r2 ≤ 0.5) than MAT (r2 ≤ 0.22). Net carbon balance was different among cropping systems (p < 0.001), with the greatest net carbon uptake occurring in sugarcane (Saccharum spp. hybrids) and the least in soybean (Glycine max) fields. Crop type had a greater effect on carbon balance than irrigation management at a Nebraska site. Across cropping systems, grain crops often had higher GPP and were more likely to have net uptake when compared to legume crops. This multi-site analysis highlights the potential of the LTAR network to further carbon flux research using eddy covariance measurements.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer

Targeting mitochondrial biogenesis has become a potential therapeutic strategy in cancer due to their unique metabolic dependencies. In this study, we show that levofloxacin, a FDA-approved antibiotic, is an attractive candidate for breast cancer treatment. This is achieved by the inhibition of proliferation and induction of apoptosis in a panel of breast cancer cell lines while sparing normal breast cells. It also acts synergistically with conventional chemo drug in two independent in vivo breast xenograft mouse models. Importantly, levofloxacin inhibits mitochondrial biogenesis as shown by the decreased level of mitochondrial respiration, membrane potential and ATP. In addition, the anti-proliferative and pro-apoptotic effects of levofloxacin are reversed by acetyl-L-Carnitine (ALCAR, a mitochondrial fuel), confirming that levofloxacin's action in breast cancer cells is through inhibition of mitochondrial biogenesis. A consequence of mitochondrial biogenesis inhibition by levofloxacin in breast cancer cells is the deactivation of PI3K/Akt/mTOR and MAPK/ERK pathways. We further demonstrate that breast cancer cells have increased mitochondrial biogenesis than normal breast cells, and this explains their different sensitivity to levofloxacin. Our work suggest that levofloxacin is a useful addition to breast cancer treatment. Our work also establish the essential role of mitochondrial biogenesis on the activation of PI3K/Akt/mTOR and MAPK/ERK pathways in breast cancer cells. - Highlights: • Levofloxacin targets a panel of breast cancer cell lines in vitro and in vivo. • Levofloxacin acts synergistically with 5-Fluorouracil in breast cancer. • Levofloxacin targets breast cancer cells via inhibiting mitochondrial biogenesis. • Breast cancer cells have increased mitochondrial biogenesis than normal cells. • Mitochondrial biogenesis inhibition lead to deactivation of PI3K/Akt/mTOR pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

PKM2 Thr454 phosphorylation increases its nuclear translocation and promotes xenograft tumor growth in A549 human lung cancer cells

Pyruvate kinase M2 (PKM2) is a key enzyme of glycolysis which is highly expressed in many tumor cells, and plays an important role in the Warburg effect. In previous study, we found PIM2 phosphorylates PKM2 at Thr454 residue (Yu, etl 2013). However, the functions of PKM2 Thr454 modification in cancer cells still remain unclear. Here we find PKM2 translocates into the nucleus after Thr454 phosphorylation. Replacement of wild type PKM2 with a mutant (T454A) enhances mitochondrial respiration, decreases pentose phosphate pathway, and enhances chemosensitivity in A549 cells. In addition, the mutant (T454A) PKM2 reduces xenograft tumor growth in nude mice. These findings demonstrate that PKM2 T454 phosphorylation is a potential therapeutic target in lung cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Optineurin E50K triggers BDNF deficiency-mediated mitochondrial dysfunction in retinal photoreceptor cell line

Highlights: • E50K mutation triggers BDNF deficiency in RGC-5 cells. • BDNF deficiency results in mitochondrial bioenergetic dysfunction in RGC-5 cells. • BDNF deficiency induces mitophagosome formation in RGC-5 cells. Optineurin (OPTN) mutations are linked to glaucoma pathology and E50K mutation shows massive cell death in photoreceptor cells and retinal ganglion cells. However, little is known about E50K-mediated mitochondrial dysfunction in photoreceptor cell degeneration. We here show that overexpression of E50K expression triggered BDNF deficiency, leading to Bax activation in RGC-5 cells. BDNF deficiency induced mitochondrial dysfunction by decreasing mitochondrial maximal respiration and reducing intracellular ATP level in RGC-5 cells. However, BDNF deficiency did not alter mitochondrial dynamics. Also, BDNF deficiency resulted in LC3-mediated mitophagosome formation in RGC-5 cells. These results strongly suggest that E50K-mediated BDNF deficiency plays a critical role in compromised mitochondrial function in glaucomatous photoreceptor cell degeneration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Direct measurement and characterization of active photosynthesis zones inside biofuel producing and wastewater remediating microalgal biofilms

Abstract: Microalgal biofilm based technologies are of keen interest due to their high biomass concentrations and ability to utilize renewable resources, such as light and CO2. While photoautotrophic biofilms have long been used for wastewater remediation applications, biofuel production represents a relatively new and under-represented focus area. However, the direct measurement and characterization of fundamental parameters required for physiological analyses are challenging due to biofilm heterogeneity. This study evaluated oxygenic photosynthesis and biofuel precursor molecule production using a novel rotating algal biofilm reactor (RABR) operated at field- and laboratory-scales for wastewater remediation and biofuel production, respectively. Clear differences in oxygenic-photosynthesis, respiration and biofuel-precursor capacities were observed between the two systems and different conditions based on light and nitrogen availability. Nitrogen depletion was not found to have the same effect on lipid accumulation compared to prior planktonic studies. Physiological characterizations of these microalgal biofilms identify potential areas for future process optimization.

Biofilm↗
DOE OSTI2020

A dynamic thermal algal growth model for pilot-scale open-channel raceways

Here this study describes the makeup of and results from a simulation consisting of a lumped thermal model integrated with a dynamic algae growth model to simulate the microalgae productivity of an open-channel raceway cultivation system. The thermal model considers the dynamic effects of weather, light absorption, convective heat transfer, radiation heat transfer, conductive heat transfer, thermal capacitance, and water control strategies. The dynamic algae growth model solves a set of ordinary differential equations consisting of growth functions dependent on incident radiation, temperature, nutrient availability, basal metabolism, and losses due to dark- and photo-respiration. Relative errors in the predicted ash-free dry weight of Nannochloropsis oceanica are 12.5%, -6.1%, and 4.4% for three separate replicates of cultivation cycles (~4.2 m 2 ) performed at AzCATI during the ATP 3 Unified Field Studies in Fall, Spring, and Summer. This research demonstrates that thermal modeling is an essential contributor to the validation of microalgae growth models.

09 BIOMASS FUELS↗
DOE OSTI2014

Prospective Evaluation of Dual-Energy Imaging in Patients Undergoing Image Guided Radiation Therapy for Lung Cancer: Initial Clinical Results

Purpose: A prospective feasibility study was conducted to investigate the utility of dual-energy (DE) imaging compared to conventional x-ray imaging for patients undergoing kV-based image guided radiation therapy (IGRT) for lung cancer. Methods and Materials: An institutional review board-approved feasibility study enrolled patients with lung cancer undergoing IGRT and was initiated in September 2011. During daily setup, 2 sequential respiration-gated x-ray images were obtained using an on-board imager. Imaging was composed of 1 standard x-ray image at 120 kVp (1 mAs) and a second image obtained at 60 kVp (4 mAs). Weighted logarithmic subtraction of the 2 images was performed offline to create a soft tissue-selective DE image. Conventional and DE images were evaluated by measuring relative contrast and contrast-to-noise ratios (CNR) and also by comparing spatial localization, using both approaches. Imaging dose was assessed using a calibrated ion chamber. Results: To date, 10 patients with stage IA to IIIA lung cancer were enrolled and 57 DE images were analyzed. DE subtraction resulted in complete suppression of overlying bone in all 57 DE images, with an average improvement in relative contrast of 4.7 ± 3.3 over that of 120 kVp x-ray images (P<.0002). The improvement in relative contrast with DE imaging was seen for both smaller (gross tumor volume [GTV] ≤5 cc) and larger tumors (GTV >5 cc), with average relative contrast improvement ratios of 3.4 ± 4.1 and 5.4 ± 3.6, respectively. Moreover, the GTV was reliably localized in 95% of the DE images versus 74% of the single energy (SE images, (P=.004). Mean skin dose per DE image set was 0.44 ± 0.03 mGy versus 0.43 ± 0.03 mGy, using conventional kV imaging parameters. Conclusions: Initial results of this feasibility study suggest that DE thoracic imaging may enhance tumor localization in lung cancer patients receiving kV-based IGRT without increasing imaging dose.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Determination of Internal Target Volume for Radiation Treatment Planning of Esophageal Cancer by Using 4-Dimensional Computed Tomography (4DCT)

Purpose: To determine an efficient strategy for the generation of the internal target volume (ITV) for radiation treatment planning for esophageal cancer using 4-dimensional computed tomography (4DCT). Methods and Materials: 4DCT sets acquired for 20 patients with esophageal carcinoma were analyzed. Each of the 4DCT sets was binned into 10 respiratory phases. For each patient, the gross tumor volume (GTV) was delineated on the 4DCT set at each phase. Various strategies to derive ITV were explored, including the volume from the maximum intensity projection (MIP; ITV{sub M}IP), unions of the GTVs from selected multiple phases ITV2 (0% and 50% phases), ITV3 (ITV2 plus 80%), and ITV4 (ITV3 plus 60%), as well as the volumes expanded from ITV2 and ITV3 with a uniform margin. These ITVs were compared to ITV10 (the union of the GTVs for all 10 phases) and the differences were measured with the overlap ratio (OR) and relative volume ratio (RVR) relative to ITV10 (ITVx/ITV10). Results: For all patients studied, the average GTV from a single phase was 84.9% of ITV10. The average ORs were 91.2%, 91.3%, 94.5%, and 96.4% for ITV{sub M}IP, ITV2, ITV3, and ITV4, respectively. Low ORs were associated with irregular breathing patterns. ITV3s plus 1 mm uniform margins (ITV3+1) led to an average OR of 98.1% and an average RVR of 106.4%. Conclusions: The ITV generated directly from MIP underestimates the range of the respiration motion for esophageal cancer. The ITV generated from 3 phases (ITV3) may be used for regular breathers, whereas the ITV generated from 4 phases (ITV4) or ITV3 plus a 1-mm uniform margin may be applied for irregular breathers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Six Degrees-of-Freedom Prostate and Lung Tumor Motion Measurements Using Kilovoltage Intrafraction Monitoring

Purpose: Tumor positional uncertainty has been identified as a major issue that deteriorates the efficacy of radiation therapy. Tumor rotational movement, which is not well understood, can result in significant geometric and dosimetric inaccuracies. The objective of this study was to measure 6 degrees-of-freedom (6 DoF) prostate and lung tumor motion, focusing on the more novel rotation, using kilovoltage intrafraction monitoring (KIM). Methods and Materials: Continuous kilovoltage (kV) projections of tumors with gold fiducial markers were acquired during radiation therapy for 267 fractions from 10 prostate cancer patients and immediately before or after radiation therapy for 50 fractions from 3 lung cancer patients. The 6 DoF motion measurements were determined from the individual 3-dimensional (3D) marker positions, after using methods to reject spurious and smooth noisy data, using an iterative closest point algorithm. Results: There were large variations in the magnitude of the tumor rotation among different fractions and patients. Various rotational patterns were observed. The average prostate rotation angles around the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) axes were 1.0 ± 5.0°, 0.6 ± 3.3°, and 0.3 ± 2.0°, respectively. For 35% of the time, the prostate rotated more than 5° about the LR axis, indicating the need for intrafractional adaptation during radiation delivery. For lung patients, the average LR, SI, and AP rotation angles were 0.8 ± 4.2°, −0.8 ± 4.5°, and 1.7 ± 3.1°, respectively. For about 30% of the time, the lung tumors rotated more than 5° around the SI axis. Respiration-induced rotation was detected in 2 of the 3 lung patients. Conclusions: The prostate and lung tumors were found to undergo rotations of more than 5° for about a third of the time. The lung tumor data represent the first 6 DoF tumor motion measured by kV images. The 6 DoF KIM method can enable rotational and translational adaptive radiation therapy and potentially reduce treatment margins.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Modeling Pancreatic Tumor Motion Using 4-Dimensional Computed Tomography and Surrogate Markers

Purpose: To assess intrafractional positional variations of pancreatic tumors using 4-dimensional computed tomography (4D-CT), their impact on gross tumor volume (GTV) coverage, the reliability of biliary stent, fiducial seeds, and the real-time position management (RPM) external marker as tumor surrogates for setup of respiratory gated treatment, and to build a correlative model of tumor motion. Methods and Materials: We analyzed the respiration-correlated 4D-CT images acquired during simulation of 36 patients with either a biliary stent (n=16) or implanted fiducials (n=20) who were treated with RPM respiratory gated intensity modulated radiation therapy for locally advanced pancreatic cancer. Respiratory displacement relative to end-exhalation was measured for the GTV, the biliary stent, or fiducial seeds, and the RPM marker. The results were compared between the full respiratory cycle and the gating interval. Linear mixed model was used to assess the correlation of GTV motion with the potential surrogate markers. Results: The average ± SD GTV excursions were 0.3 ± 0.2 cm in the left-right direction, 0.6 ± 0.3 cm in the anterior-posterior direction, and 1.3 ± 0.7 cm in the superior-inferior direction. Gating around end-exhalation reduced GTV motion by 46% to 60%. D95% was at least the prescribed 56 Gy in 76% of patients. GTV displacement was associated with the RPM marker, the biliary stent, and the fiducial seeds. The correlation was better with fiducial seeds and with biliary stent. Conclusions: Respiratory gating reduced the margin necessary for radiation therapy for pancreatic tumors. GTV motion was well correlated with biliary stent or fiducial seed displacements, validating their use as surrogates for daily assessment of GTV position during treatment. A patient-specific internal target volume based on 4D-CT is recommended both for gated and not-gated treatment; otherwise, our model can be used to predict the degree of GTV motion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Intrafraction Variability and Deformation Quantification in the Breast

Purpose: To evaluate intrafraction variability and deformation of the lumpectomy cavity (LC), breast, and nearby organs. Methods and Materials: Sixteen left-sided postlumpectomy and 1 bilateral breast cancer cases underwent free-breathing CT (FBCT) and 10-phase 4-dimensional CT (4DCT). Deformable image registration was used for deformation analysis and contour propagation of breast, heart, lungs, and LC between end-exhale and end-inhale 4DCT phases. Respiration-induced motion was calculated via centroid analysis. Two planning target volumes (PTVs) were compared: PTV{sub FBCT} from the FBCT volume with an isotropic 10 mm expansion (5 mm excursion and 5 mm setup error) and PTV{sub 4DCT} generated from the union of 4DCT contours with isotropic 5 mm margin for setup error. Volume and geometry were evaluated via percent difference and bounding box analysis, respectively. Deformation correlations between breast/cavity, breast/lung, and breast/heart were evaluated. Associations were tested between cavity deformation and proximity to chest wall and breast surface. Results: Population-based 3-dimensional vector excursions were 2.5 ± 1.0 mm (range, 0.8-3.8 mm) for the cavity and 2.0 ± 0.8 mm (range, 0.7-3.0 mm) for the ipsilateral breast. Cavity excursion was predominantly in the anterior and superior directions (1.0 ± 0.8 mm and −1.8 ± 1.2 mm, respectively). Similarly, for all cases, LCs and ipsilateral breasts yielded median deformation values in the superior direction. For 14 of 17 patients, the LCs and breast interquartile ranges tended toward the anterior direction. The PTV{sub FBCT} was 51.5% ± 10.8% larger (P<.01) than PTV{sub 4DCT}. Bounding box analysis revealed that PTV{sub FBCT} was 9.8 ± 1.2 (lateral), 9.0 ± 2.2 (anterior–posterior), and 3.9 ± 1.8 (superior–inferior) mm larger than PTV{sub 4DCT}. Significant associations between breast and cavity deformation were found for 6 of 9 axes. No dependency was found between cavity deformation and proximity to chest wall or breast surface. Conclusions: Lumpectomy cavity and breast deformation and motion demonstrated large variability. A PTV{sub 4DCT} approach showed value in patient-specific margins, particularly if robust interfraction setup analysis can be performed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Quantification of Intrafraction and Interfraction Tumor Motion Amplitude and Prediction Error for Different Liver Tumor Trajectories in Cyberknife Synchrony Tracking

To research the fiducial-based, real-time tracking intrafraction (during the fraction [intra-]) and interfraction (between fractions [inter-]) tumor respiration amplitude, motion trajectory, and prediction error and quantify their relationships for different types of motion trajectories during Cyberknife-based stereotactic ablation radiotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Assessment of Lung Tumour Motion and Volume Size Dependencies Using Various Evaluation Measures

The purpose of the study was to assess internal target volume changes through the breathing cycle and associated tumour motion for lung patients and to establish possible correlations between different parameters. Respiration-induced volume changes with breathing cycle and the associated tumour motion were analyzed for 11 patients. Selected phases were the maximum and average intensity projections and the 10 phases of equal duration and separation obtained through the respiratory cycle. Tumour centre of mass (COM) motion planes were generated using least square fitting, and their angles and orientations were then compared between the cases studied. Trajectories that are composed by the points of COM location in different phases were identified, and their interrelation was assessed through different similarity measures. The results were used to determine if there is any correlation between parameters chosen and if the margins conventionally used for the planning target volume creation successfully encompassed lung tumour motion and volume change. The results show that the extent of tumour motion was related to its volume and location. The tumour displacement was predominantly left and inferior. Planar fitting to COM motion data through respiratory phases demonstrated some correlation in best fit motion plane positions between different data sets. In the plane fit comparison, for each patient, the lower root mean square error values showed that a good planar fit can be achieved for the COM motion path. The evaluation of the inhale and exhale trajectories may allow, for certain tumour locations and size, contouring on only inhalation or exhalation phases, knowing that tumour motion will be adequately covered on the other phases. Taking all the data into account and knowing the tumour size and location, a good estimate can be made of the motion plane position in the three-dimensional space and the required dosimetric margins.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Clinical benefits of new immobilization system for hypofractionated radiotherapy of intrahepatic hepatocellular carcinoma by helical tomotherapy

Objective: A comprehensive clinical evaluation was conducted, assessing the Body Pro-Lok immobilization and positioning system to facilitate hypofractionated radiotherapy of intrahepatic hepatocellular carcinoma (HCC), using helical tomotherapy to improve treatment precision. Methods: Clinical applications of the Body Pro-Lok system were investigated (as above) in terms of interfractional and intrafractional setup errors and compressive abdominal breath control. To assess interfractional setup errors, a total of 42 patients who were given 5 to 20 fractions of helical tomotherapy for intrahepatic HCC were analyzed. Overall, 15 patients were immobilized using simple vacuum cushion (group A), and the Body Pro-Lok system was used in 27 patients (group B), performing megavoltage computed tomography (MVCT) scans 196 times and 435 times, respectively. Pretreatment MVCT scans were registered to the planning kilovoltage computed tomography (KVCT) for error determination, and group comparisons were made. To establish intrafractional setup errors, 17 patients with intrahepatic HCC were selected at random for immobilization by Body Pro-Lok system, undergoing MVCT scans after helical tomotherapy every week. A total of 46 MVCT re-scans were analyzed for this purpose. In researching breath control, 12 patients, randomly selected, were immobilized by Body Pro-Lok system and subjected to 2-phase 4-dimensional CT (4DCT) scans, with compressive abdominal control or in freely breathing states, respectively. Respiratory-induced liver motion was then compared. Results: Mean interfractional setup errors were as follows: (1) group A: X, 2.97 ± 2.47 mm; Y, 4.85 ± 4.04 mm; and Z, 3.77 ± 3.21 mm; pitch, 0.66 ± 0.62°; roll, 1.09 ± 1.06°; and yaw, 0.85 ± 0.82°; and (2) group B: X, 2.23 ± 1.79 mm; Y, 4.10 ± 3.36 mm; and Z, 1.67 ± 1.91 mm; pitch, 0.45 ± 0.38°; roll, 0.77 ± 0.63°; and yaw, 0.52 ± 0.49°. Between-group differences were statistically significant in 6 directions (p < 0.05). Mean intrafractional setup errors with use of the Body Pro-Lok system were as follows: X, 0.41 ± 0.46 mm; Y, 0.86 ± 0.80 mm; Z, 0.33 ± 0.44 mm; and roll, 0.12 ± 0.19°. Mean liver-induced respiratory motion determinations were as follows: (1) abdominal compression: X, 2.33 ± 1.22 mm; Y, 5.11 ± 2.05 mm; Z, 2.13 ± 1.05 mm; and 3D vector, 6.22 ± 1.94 mm; and (2) free breathing: X, 3.48 ± 1.14 mm; Y, 9.83 ± 3.00 mm; Z, 3.38 ± 1.59 mm; and 3D vector, 11.07 ± 3.16 mm. Between-group differences were statistically different in 4 directions (p < 0.05). Conclusions: The Body Pro-Lok system is capable of improving interfractional and intrafractional setup accuracy and minimizing tumor movement owing to respirations in patients with intrahepatic HCC during hypofractionated helical tomotherapy.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2018

Soil moisture drives microbial controls on carbon decomposition in two subtropical forests

Knowledge of microbial mechanisms is critical to understand Earth's biogeochemical cycle under climate and environmental changes. However, large uncertainties remain in model simulations and predictions due to the lack of explicit parameterization of microbial data and few applications beyond the laboratory. In addition, most experimental and modeling studies of warming-induced changes in soil carbon (C) focus on temperature sensitivity, neglecting concomitant effects of changes in soil moisture. Soil microbes are sensitive to moisture, and their responses can dramatically impact soil biogeochemical cycles. Here we represent microbial and enzymatic functions in response to changes in moisture in the Microbial-ENzyme Decomposition (MEND) model. Through modeling with long-term field observations from subtropical forests, we demonstrate that parameterization with microbial data in addition to respiration fluxes greatly increases confidence in model simulations. We further employ the calibrated model to simulate the responses of soil organic C (SOC) under multiple environmental change scenarios. The model shows significant increases in SOC in response to decreasing soil moisture and only minor changes in SOC in response to increasing soil temperature. Increasing litter inputs also cause a significant increase in SOC in the pine forest, whereas an insignificant negative effect is simulated in the broadleaf forest. We also demonstrate the co-metabolism mechanism for the priming effects, i.e., more labile inputs to soil could stimulate microbial and enzymatic growth and activity. Furthermore our study provides strong evidence of microbial control over soil C decomposition and suggests the future trajectory of soil C may be more responsive to changes in soil moisture than temperature, particularly in tropical and subtropical environments.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Revising the dynamic energy budget theory with a new reserve mobilization rule and three example applications to bacterial growth

Dynamic energy budget (DEB) theory has been applied to model a wide range of organisms, including microbes. In the standard DEB model, biomass is partitioned into reserve and structural compartments, where reserve biomass is mobilized in a pseudolinear manner (while the reserve biomass density, defined as the ratio between reserve and structural biomass, decays linearly) to drive maintenance and the growth of structural biomass (and extracellular enzyme production if it is considered). However, the linear dynamics of the reserve biomass density makes the standard DEB model incapable of explaining the slowdown of microbial growth at high reserve density that is caused by macromolecular crowding effect which reduces biochemical reaction rates (a typical situation occurs when microbes are experiencing severe moisture stress) and is inconsistent with the observation that intracellular enzymatic reactions generally follow non-linear kinetics. By partitioning biomass into reserve, kinetic, and structural compartments, we show here that the Equilibrium Chemistry Approximation (ECA) kinetics can be used to represent enzymatically catalyzed reserve biomass mobilization that can then drive the kinetic and structural biomass synthesis. This revised DEB model better represents the tradeoff in ribosome allocation for structural growth and internal enzyme production, is structurally compatible with metabolic models of cell individuals, and includes the standard DEB model and the popular compromise model as special cases for representing population growth. We then applied the revised DEB model to interpret components of bacterial respiration, their dependence on substrate availability, and emergent microbial carbon use efficiency dynamics for an exponentially growing population. We found that the revised DEB model enables a better understanding of bacterial substrates use (carbon in our examples) than that can be derived from a few other models in the literature. In particular, the revised DEB model explains why carbon use efficiency may first increase, then plateau, and finally decrease with growth rate (and substrate uptake rate), as a function of proteomics. Additionally, the revised DEB model explains why the kinetic biomass compartment needs to be divided to reasonably incorporate proteomic control of microbial growth.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated, with no adverse events. • Overall, human fibrinogen concentrate demonstrated a good safety profile. • This data adds to the safety information available to date on this hemostatic agent.

60 APPLIED LIFE SCIENCES↗