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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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All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Advanced solvent based methods for molecular characterization of soil organic matter by high-resolution mass spectrometry

Soil organic matter (SOM) a complex, heterogeneous mixture of above and belowground plant litter and animal and microbial residues at various degrees of decomposition, is a key reservoir for carbon (C) and nutrient biogeochemical cycling in soil based ecosystems. A limited understanding of the molecular composition of SOM limits the ability to routinely decipher chemical processes within soil and predict accurately how terrestrial carbon fluxes will response to changing climatic conditions and land use. To elucidate the molecular-level structure of SOM, we selectively extracted a broad range of intact SOM compounds by a combination of different organic solvents from soils with a wide range of C content. Our use of Electrospray ionization (ESI) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and a suite of solvents with varying polarity significantly expands the inventory of the types of organic molecules present in soils. Specifically, we found that hexane is selective for lipid-like compounds with very low O:C ratios; water was selective for carbohydrates with high O:C ratios; acetonitrile preferentially extracts lignin, condensed structures, and tannin poly phenolic compounds with O:C > 0.5; methanol has higher selectivity towards compounds characterized with low O:C < 0.5; and hexane, MeOH, ACN and water solvents increase the number and types of organic molecules extracted from soil for a broader range of chemically diverse soil types. Our study of SOM molecules by ESI-FTICR MS revealed new insight into the molecular-level complexity of organics contained in soils.

Environmental Molecular Sciences Laboratory↗
DOE OSTI2011

Fiscalini Farms Biomass Energy Project

In this final report describes and documents research that was conducted by the Ecological Engineering Research Program (EERP) at the University of the Pacific (Stockton, CA) under subcontract to Fiscalini Farms LP for work under the Assistance Agreement DE-EE0001895 'Measurement and Evaluation of a Dairy Anaerobic Digestion/Power Generation System' from the United States Department of Energy, National Energy Technology Laboratory. Fiscalini Farms is operating a 710 kW biomass-energy power plant that uses bio-methane, generated from plant biomass, cheese whey, and cattle manure via mesophilic anaerobic digestion, to produce electricity using an internal combustion engine. The primary objectives of the project were to document baseline conditions for the anaerobic digester and the combined heat and power (CHP) system used for the dairy-based biomass-energy production. The baseline condition of the plant was evaluated in the context of regulatory and economic constraints. In this final report, the operation of the plant between start-up in 2009 and operation in 2010 are documented and an interpretation of the technical data is provided. An economic analysis of the biomass energy system was previously completed (Appendix A) and the results from that study are discussed briefly in this report. Results from the start-up and first year of operation indicate that mesophilic anaerobic digestion of agricultural biomass, combined with an internal combustion engine, is a reliable source of alternative electrical production. A major advantage of biomass energy facilities located on dairy farms appears to be their inherent stability and ability to produce a consistent, 24 hour supply of electricity. However, technical analysis indicated that the Fiscalini Farms system was operating below capacity and that economic sustainability would be improved by increasing loading of feedstocks to the digester. Additional operational modifications, such as increased utilization of waste heat and better documentation of potential of carbon credits, would also improve the economic outlook. Analysis of baseline operational conditions indicated that a reduction in methane emissions and other greenhouse gas savings resulted from implementation of the project. The project results indicate that using anaerobic digestion to produce bio-methane from agricultural biomass is a promising source of electricity, but that significant challenges need to be addressed before dairy-based biomass energy production can be fully integrated into an alternative energy economy. The biomass energy facility was found to be operating undercapacity. Economic analysis indicated a positive economic sustainability, even at the reduced power production levels demonstrated during the baseline period. However, increasing methane generation capacity (via the importation of biomass codigestate) will be critical for increasing electricity output and improving the long-term economic sustainability of the operation. Dairy-based biomass energy plants are operating under strict environmental regulations applicable to both power-production and confined animal facilities and novel approached are being applied to maintain minimal environmental impacts. The use of selective catalytic reduction (SCR) for nitrous oxide control and a biological hydrogen sulfide control system were tested at this facility. Results from this study suggest that biomass energy systems can be compliant with reasonable scientifically based air and water pollution control regulations. The most significant challenge for the development of biomass energy as a viable component of power production on a regional scale is likely to be the availability of energy-rich organic feedstocks. Additionally, there needs to be further development of regional expertise in digester and power plant operations. At the Fiscalini facility, power production was limited by the availability of biomass for methane generation, not the designed system capacity. During the baseline study period, feedstocks included manure, sudan grass silage, and refused-feed. The ability of the dairy to produce silage in excess of on-site feed requirements limited power production. The availability of biomass energy crops and alternative feedstocks, such as agricultural and food wastes, will be a major determinant to the economic and environmental sustainability of biomass based electricity production.

03 NATURAL GAS↗
DOE OSTI2012

AVESTAR Center for Operational Excellence of Electricity Generation Plants

To address industry challenges in attaining operational excellence for electricity generation plants, the U.S. Department of Energy’s (DOE) National Energy Technology Laboratory (NETL) has launched a world-class facility for Advanced Virtual Energy Simulation Training and Research (AVESTARTM). This presentation will highlight the AVESTARTM Center simulators, facilities, and comprehensive training, education, and research programs focused on the operation and control of high-efficiency, near-zero-emission electricity generation plants. The AVESTAR Center brings together state-of-the-art, real-time, high-fidelity dynamic simulators with full-scope operator training systems (OTSs) and 3D virtual immersive training systems (ITSs) into an integrated energy plant and control room environment. AVESTAR’s initial offering combines--for the first time--a “gasification with CO2 capture” process simulator with a “combined-cycle” power simulator together in a single OTS/ITS solution for an integrated gasification combined cycle (IGCC) power plant with carbon dioxide (CO2) capture. IGCC systems are an attractive technology option for power generation, especially when capturing and storing CO2 is necessary to satisfy emission targets. The AVESTAR training program offers a variety of courses that merge classroom learning, simulator-based OTS learning in a control-room operations environment, and immersive learning in the interactive 3D virtual plant environment or ITS. All of the courses introduce trainees to base-load plant operation, control, startups, and shutdowns. Advanced courses require participants to become familiar with coordinated control, fuel switching, power-demand load shedding, and load following, as well as to problem solve equipment and process malfunctions. Designed to ensure work force development, training is offered for control room and plant field operators, as well as engineers and managers. Such comprehensive simulator-based instruction allows for realistic training without compromising worker, equipment, and environmental safety. It also better prepares operators and engineers to manage the plant closer to economic constraints while minimizing or avoiding the impact of any potentially harmful, wasteful, or inefficient events. The AVESTAR Center is also used to augment graduate and undergraduate engineering education in the areas of process simulation, dynamics, control, and safety. Students and researchers gain hands-on simulator-based training experience and learn how the commercial-scale power plants respond dynamically to changes in manipulated inputs, such as coal feed flow rate and power demand. Students also analyze how the regulatory control system impacts power plant performance and stability. In addition, students practice start-up, shutdown, and malfunction scenarios. The 3D virtual ITSs are used for plant familiarization, walk-through, equipment animations, and safety scenarios. To further leverage the AVESTAR facilities and simulators, NETL and its university partners are pursuing an innovative and collaborative R&D program. In the area of process control, AVESTAR researchers are developing enhanced strategies for regulatory control and coordinated plant-wide control, including gasifier and gas turbine lead, as well as advanced process control using model predictive control (MPC) techniques. Other AVESTAR R&D focus areas include high-fidelity equipment modeling using partial differential equations, dynamic reduced order modeling, optimal sensor placement, 3D virtual plant simulation, and modern grid. NETL and its partners plan to continue building the AVESTAR portfolio of dynamic simulators, immersive training systems, and advanced research capabilities to satisfy industry’s growing need for training and experience with the operation and control of clean energy plants. Future dynamic simulators under development include natural gas combined cycle (NGCC) and supercritical pulverized coal (SCPC) plants with post-combustion CO2 capture. These dynamic simulators are targeted for use in establishing a Virtual Carbon Capture Center (VCCC), similar in concept to the DOE’s National Carbon Capture Center for slipstream testing. The VCCC will enable developers of CO2 capture technologies to integrate, test, and optimize the operation of their dynamic capture models within the context of baseline power plant dynamic models. The objective is to provide hands-on, simulator-based “learn-by-operating” test platforms to accelerate the scale-up and deployment of CO2 capture technologies. Future AVESTAR plans also include pursuing R&D on the dynamics, operation, and control of integrated electricity generation and storage systems for the modern grid era. Special emphasis will be given to combining load-following energy plants with renewable and distributed generating supplies and fast-ramping energy storage systems to provide near constant baseload power.

97 MATHEMATICS AND COMPUTING↗
NASA NTRS2001

Changes in gene expression and signal transduction in microgravity

Studies from space flights over the past three decades have demonstrated that basic physiological changes occur in humans during space flight. These changes include cephalic fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known and until recently, the general approach was to investigate general systemic changes, not basic cellular responses to microgravity. This laboratory has recently studied gene growth and activation of normal osteoblasts (MC3T3-El) during spaceflight. Osteoblast cells were grown on glass coverslips and loaded in the Biorack plunger boxes. The osteoblasts were launched in a serum deprived state, activated in microgravity and collected in microgravity. The osteoblasts were examined for changes in gene expression and signal transduction. Approximately one day after growth activation significant changes were observed in gene expression in 0-G flight samples. Immediate early growth genes/growth factors cox-2, c-myc, bcl2, TGF beta1, bFGF and PCNA showed a significant diminished mRNA induction in microgravity FCS activated cells when compared to ground and 1-G flight controls. Cox-1 was not detected in any of the samples. There were no significant differences in the expression of reference gene mRNA between the ground, 0-G and 1-G samples. The data suggest that quiescent osteoblasts are slower to enter the cell cycle in microgravity and that the lack of gravity itself may be a significant factor in bone loss in spaceflight. Preliminary data from our STS 76 flight experiment support our hypothesis that a basic biological response occurs at the tissue, cellular, and molecular level in 0-G. Here we examine ground-based and space flown data to help us understand the mechanism of bone loss in microgravity.

manned↗
DOE OSTI2013

A Systematic Evaluation of Traditional and Non-Traditional Data Streams for Integrated Global Biosurveillance (Final Report)

Living in a closely connected and highly mobile world presents many new mechanisms for rapid disease spread and in recent years, global disease surveillance has become a high priority. In addition, much like the contribution of non-traditional medicine to curing diseases, non-traditional data streams are being considered of value in disease surveillance. Los Alamos National Laboratory (LANL) was tasked by the Defense Threat Reduction Agency (DTRA)-Joint Science and Technology Office (JSTO) to determine the relevance of data streams for an integrated global biosurveillance system through the use of defined metrics and methodologies. The long-term, broad objective of this project was to provide information and analysis that can be leveraged from existing and developing national and international disease surveillance systems and methodologies, to create a global disease monitoring system, ultimately providing decision makers with timely information to prepare for and mitigate the spread of disease. Specifically, this project evaluated data streams that are currently being used in surveillance systems and data streams that had the potential for being used in surveillance to enable early disease detection. LANL’s focus was on infectious disease surveillance and the term “biosurveillance” will be used to refer to this scope hereafter. Data stream evaluation was conducted using two different methods: Multi criteria decision analysis (MCDA) using a tool called Logical Decisions ® that assigns utility scores to data streams based on weighted metrics and assigned values specific to data stream categories; and a Surveillance Window concept developed at LANL that assigns a window or windows of time specific to a disease within which information coming from various data streams can be determined to have utility. A cross method analysis was performed between the surveillance window based evaluation and the MCDA-based evaluation to identify data stream categories that showed high utility for both methods. In addition, algorithms that can integrate useful data streams to facilitate early disease detection were also examined. This project provided an understanding of data streams relevant to early warning, early detection and monitoring of disease outbreaks. The report describes the results of LANL’s evaluation of 16 data stream categories using the two methods, and recommendations for next steps. The project evolved significantly over its course, and significant improvements in our approaches were made compared to the initial proposed processes. A key outcome of this effort was that LANL was able to bring together several diverse entities involved in disease surveillance and lay the foundation for new collaborations that straddled military and civilian health surveillance. The robust evaluation framework developed by LANL has generated significant interest and there is interest in adopting this framework for various applications both within disease surveillance as well as other public health initiatives. Finally, LANL developed the Biosurveillance Resource Directory (BRD), a relational database that underwent pilot testing by members of the human, plant and animal disease surveillance community. The BRD is intended to be a global resource to facilitate rapid information access.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1999

Is skeletal muscle ready for long-term spaceflight and return to gravity?

It is now clear that prevention of muscle debilitation during spaceflight will require a broader approach than simple exercise aimed at strengthening of the muscle fibers. The levels of several hormones and receptors are altered by unloading and must be returned to homeostasis. Pharmacotherapy and gene transfer strategies to raise the relative level of structural proteins may minimize the problems faced by astronauts in readapting to Earth-gravity. Up to now, we have only minimally exploited microgravity for advancing our understanding of muscle biology. A research laboratory in the space station with a centrifuge facility (gravity control) is essential for conducting basic research in this field. Microgravity has proven an excellent tool for noninvasively perturbing the synthesis of muscle proteins in the search for molecular signals and gene regulatory factors influencing differentiation, growth, maintenance and atrophy of muscle. Understanding the relation between blood flow and interstitial edema and between workload and subsequent structural failure are but two important problems that require serious attention. The roles of hormones and growth factors in regulating gene expression and their microgravity-induced altered production are other urgent issues to pursue. These types of studies will yield information that advances basic knowledge of muscle biology and offers insights into countermeasure design. This knowledge is likely to assist rehabilitation of diseased or injured muscles in humans on Earth, especially individuals in the more vulnerable aging population and persons participating in strenuous sports. Will the skeletal muscle system be prepared for the increased exposure to microgravity and the return to gravity loading without injury when space station is operational? The answer depends in large part on continued access to space and funding of ground-based models and flight experiments. The previous two decades of spaceflight research have described the effects of microgravity on multiple systems. The next generation of experiments promises to be even more exciting as we are challenged to define the cellular and molecular mechanisms of microgravity-induced changes.

manned↗
DOE OSTI2011

A physiologically based pharmacokinetic model for atrazine and its main metabolites in the adult male C57BL/6 mouse

Atrazine (ATR) is a chlorotriazine herbicide that is widely used and relatively persistent in the environment. In laboratory rodents, excessive exposure to ATR is detrimental to the reproductive, immune, and nervous systems. To better understand the toxicokinetics of ATR and to fill the need for a mouse model, a physiologically based pharmacokinetic (PBPK) model for ATR and its main chlorotriazine metabolites (Cl-TRIs) desethyl atrazine (DE), desisopropyl atrazine (DIP), and didealkyl atrazine (DACT) was developed for the adult male C57BL/6 mouse. Taking advantage of all relevant and recently made available mouse-specific data, a flow-limited PBPK model was constructed. The ATR and DACT sub-models included blood, brain, liver, kidney, richly and slowly perfused tissue compartments, as well as plasma protein binding and red blood cell binding, whereas the DE and DIP sub-models were constructed as simple five-compartment models. The model adequately simulated plasma levels of ATR and Cl-TRIs and urinary dosimetry of Cl-TRIs at four single oral dose levels (250, 125, 25, and 5 mg/kg). Additionally, the model adequately described the dose dependency of brain and liver ATR and DACT concentrations. Cumulative urinary DACT amounts were accurately predicted across a wide dose range, suggesting the model's potential use for extrapolation to human exposures by performing reverse dosimetry. The model was validated using previously reported data for plasma ATR and DACT in mice and rats. Overall, besides being the first mouse PBPK model for ATR and its Cl-TRIs, this model, by analogy, provides insights into tissue dosimetry for rats. The model could be used in tissue dosimetry prediction and as an aid in the exposure assessment to this widely used herbicide.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-684: Analysis of Cherenkov Excitation in Tissue and the Feasibility of Cherenkov Excited Photodynamic Therapy

Purpose: The irradiation of photodynamic agents with radiotherapy beams has been demonstrated to enhance tumor killing in various studies, and one proposed mechanism is the optical fluence of Cherenkov emission activating the photosensitizer. This mechanism is explored in Monte Carlo simulations of fluence as well as laboratory measurements of fluence and radical oxygen species. Methods: Simulations were completed using GAMOS/GEANT4 with a 6 MV photon beam in tissue. The effects of blood vessel diameter, blood oxygen saturation, and beam size were examined, recording spectral fluence. Experiments were carried out in solutions of photosensitizer and phantoms. Results: Cherenkov produced by a 100×100um{sup 2} 6 MV beam resulted in fluence of less than 1 nJ/cm{sup 2}/Gy per 1 nm wavelength. At this microscopic level, differences in absorption of blood and water in the tissue affected the fluence spectrum, but variation in blood oxygenation had little effect. Light in tissue resulting from larger (10mm ×10mm) 6 MV beams had greater fluence due to light transport and elastic scattering of optical photons, but this transport process also resulted in higher absorption shifts. Therefore, the spectrum produced by a microscopic beam was weighted more heavily in UV/blue wavelengths than the spectrum at the macroscopic level. At the macroscopic level, the total fluence available for absorption by Verteporfin (BPD) in tissue approached uJ/cm{sup 2} for a high radiation dose, indicating that photodynamic activation seems unlikely. Tissue phantom confirmation of these light levels supported this observation, and photosensitization measurements with a radical oxygen species reporter are ongoing. Conclusion: Simulations demonstrated that fluence produced by Cherenkov in tissue by 6 MV photon beams at typical radiotherapy doses appears insufficient to activate photosensitizers to the level required for threshold effects, yet this disagrees with published biological experiments. Experimental validation in tissue phantoms and cell studies are ongoing to clarify this discrepancy. Funding from NIH grant R01CA109558.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1995

Non-invasive assessment of otolith formation during development of the Japanese red-bellied newt, Cynops pyrrhogaster

Pre-mated adult female newts and embryos have been flown on the International Microgravity Laboratory-2 (IML-2) Space Shuttle flight in 1994 (Wiederhold et al., 1992b). With the specimens available from this flight, the calcification of otoliths, ulna, radius and backbone of the flown larvae and adult newts were analyzed. The experiments presented here studied the development of the otoliths on the ground. Otoliths of living newts, from embryo to adult, were observed in situ with the application of a new X-ray and bio-imaging analyzer system. For the establishment of this method, newts at different developmental stages were used. An imaging plate temporarily stores the X-ray energy pattern at the bio-imaging analyzer. A latent image on the imaging plate was transformed into a digital time series signal with an image reader. Acquired digital information was computed with the image processor. The processed information was recorded on film with an image recorder, in order to visualize it on an enlargement computed radiograph. To analyze development of the otoliths, photo-stimulated luminescence level was detected by an image analyzer, using transmitted X-ray photons. A single clump of otoconia could first be seen at stage 33. Stage-36 embryos first have distinguishable otoliths, with the utricle in front and saccule behind. Our results show that this X-ray method detects the otoliths equally as well as sectioning. In the newt, the mandibular/maxillary bone formed before the spine. It is suspected that for the newt embryo, living in water, feeding becomes necessary prior to support of the body.

NASA Discipline Neuroscience↗
NASA NTRS1993

Amphibian fertilization and development in microgravity

During the year before launch, female frogs will be tested every 3 months for the quantity and quality of eggs produced. Two weeks or more prior to launch, male and female frogs will be transported to the John F. Kennedy Space Center (KSC). During the few weeks before launch, groups will be periodically tested for egg quality to assure that the frogs have adapted to the KSC laboratory environment. About 27 hours before launch, four females will be placed in a damp foam-lined box, called the Adult Frog Box (AFB), through which 100 cc/min of air wil be circulated. The AFB will be lowered into the Spacelab and loaded into the Frog Environmental Unit (FEU) during the final pre-launch preparations. A sperm suspension, for use in flight to fertilize the eggs, will also be prepared and loaded during the pre-launch period. The sperm suspension, together with a kit of syringes containing Human Chorionic Gonadotropin (HCG), will be stored in a refrigerator aboard the shuttle until needed in flight. On the first day of flight, the AFB will be transferred from the FEU to the General Purpose Work Station (GPWS), which is a type of glove box specially designed to allow the crew to use chemicals and biological materials during the flight without contaminating the shuttle/Spacelab environment. Inside the GPWS the four adult frogs will be injected with the HCG hormone and returned to the FEU. Approximately 16 hours after injection, ovulation should have taken place and 15 to 20 eggs from each frog will be placed on each of two egg baskets and covered with sperm for 10 minutes. The egg baskets are inserted into acrylic egg chambers and 50 ml of 'pond water' (20 percent strength Modified Ringers solution (is added. One of the chambers from each frog will be placed on a centrifuge within the FEU and rotated to simulate normal terrestrial gravity (1 g). The remaining chambers are incubated under microgravity conditions within the FEU. Forty minutes after fertilization, the four chambers exposed to 1 g will be removed and observed within the GPWS using a dissecting microscope and camera system. On the basis of egg rotation and egg appearance, the 'best' and 'second best' frogs will be selected to contribute additional eggs. Using the two best frogs, 22 egg chambers will be loaded with eggs and fertilized. Eleven chambers wil be incubated at microgravity and eleven will be incubated on the centrifuge. At various times during the flight, chambers will be removed from the FEU and transferred to the GPWS where a formaldehyde-based fixative will be injected in order to preserve important developmental stages for in depth study following the flight. Five of the 22 chambers plus the eight fertilization test chambers will be returned to Earth with live tadpoles. The swimming behavior of these free swimming tadpoles will be examined within several hours of landing and some will be fixed for a detailed analysis of their inner ear, the otolity, the animals 'balance system.' Lychakov and Vinikov reported an increase in otolith size in tadpoles that developed (but were not fertilized) in space. Live tadpoles from the SL-J flight will be raised through metamorphsis for studies of maturation including an analysis of the effects of space flight on their ability to produce normal progency. Following the flight, the fixed embryos will be serially sectioned and stained using procedures that were developed for this experiment. The embroys fixed at the 2-4 cell stage will be examined for the distribution of cytoplasmic contents, including the various classes of yolk platelets, and the location and shape of the cleavage furrows. The gastrulae will be assessed for the normality of the complex cellular rearrangements that constitute blastopore formation and involution, i.e., the differentiation of the embryo into its specialized body parts. Using a new procedure, the gastrulae will be bleached which will enable the initial sperm entry point (SEP) to be located. The correlation between the SEP and the dorsal lip of the blastopore will be determined. Under normal terrestrial conditions it was shown that the SEP typically is located on the side of the egg opposite the future dorsal side of the embryo. The neurulae will be examined for the normality and completeness of the neural plate and archenteron expansion. The tadpole stages will be used to study the allometry and morphology of the various organ systems.

Souza, Kenneth A.↗
DOE OSTI2014

Early biomarkers of doxorubicin-induced heart injury in a mouse model

Cardiac troponins, which are used as myocardial injury markers, are released in plasma only after tissue damage has occurred. Therefore, there is a need for identification of biomarkers of earlier events in cardiac injury to limit the extent of damage. To accomplish this, expression profiling of 1179 unique microRNAs (miRNAs) was performed in a chronic cardiotoxicity mouse model developed in our laboratory. Male B6C3F{sub 1} mice were injected intravenously with 3 mg/kg doxorubicin (DOX; an anti-cancer drug), or saline once a week for 2, 3, 4, 6, and 8 weeks, resulting in cumulative DOX doses of 6, 9, 12, 18, and 24 mg/kg, respectively. Mice were euthanized a week after the last dose. Cardiac injury was evidenced in mice exposed to 18 mg/kg and higher cumulative DOX dose whereas examination of hearts by light microscopy revealed cardiac lesions at 24 mg/kg DOX. Also, 24 miRNAs were differentially expressed in mouse hearts, with the expression of 1, 1, 2, 8, and 21 miRNAs altered at 6, 9, 12, 18, and 24 mg/kg DOX, respectively. A pro-apoptotic miR-34a was the only miRNA that was up-regulated at all cumulative DOX doses and showed a significant dose-related response. Up-regulation of miR-34a at 6 mg/kg DOX may suggest apoptosis as an early molecular change in the hearts of DOX-treated mice. At 12 mg/kg DOX, up-regulation of miR-34a was associated with down-regulation of hypertrophy-related miR-150; changes observed before cardiac injury. These findings may lead to the development of biomarkers of earlier events in DOX-induced cardiotoxicity that occur before the release of cardiac troponins. - Highlights: • Upregulation of miR-34a before doxorubicin-induced cardiac tissue injury • Apoptosis might be an early event in mouse heart during doxorubicin treatment. • Expression of miR-150 declined before doxorubicin-induced cardiac tissue injury.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Large-scale proteome analysis of abscisic acid and ABSCISIC ACID INSENSITIVE3-dependent proteins related to desiccation tolerance in Physcomitrella patens

Desiccation tolerance is an ancestral feature of land plants and is still retained in non-vascular plants such as bryophytes and some vascular plants. However, except for seeds and spores, this trait is absent in vegetative tissues of vascular plants. Although many studies have focused on understanding the molecular basis underlying desiccation tolerance using transcriptome and proteome approaches, the critical molecular differences between desiccation tolerant plants and non-desiccation plants are still not clear. The moss Physcomitrella patens cannot survive rapid desiccation under laboratory conditions, but if cells of the protonemata are treated by the phytohormone abscisic acid (ABA) prior to desiccation, it can survive 24 h exposure to desiccation and regrow after rehydration. The desiccation tolerance induced by ABA (AiDT) is specific to this hormone, but also depends on a plant transcription factor ABSCISIC ACID INSENSITIVE3 (ABI3). Here we report the comparative proteomic analysis of AiDT between wild type and ABI3 deleted mutant (Δabi3) of P. patens using iTRAQ (Isobaric Tags for Relative and Absolute Quantification). From a total of 1980 unique proteins that we identified, only 16 proteins are significantly altered in Δabi3 compared to wild type after desiccation following ABA treatment. Among this group, three of the four proteins that were severely affected in Δabi3 tissue were Arabidopsis orthologous genes, which were expressed in maturing seeds under the regulation of ABI3. These included a Group 1 late embryogenesis abundant (LEA) protein, a short-chain dehydrogenase, and a desiccation-related protein. Our results suggest that at least three of these proteins expressed in desiccation tolerant cells of both Arabidopsis and the moss are very likely to play important roles in acquisition of desiccation tolerance in land plants. Furthermore, our results suggest that the regulatory machinery of ABA- and ABI3-mediated gene expression for desiccation tolerance might have evolved in ancestral land plants before the separation of bryophytes and vascular plants. - Highlights: • Large-scale proteomics highlighted proteins related to plant desiccation tolerance. • The proteins were regulated by both the phytohormone ABA and ABI3. • The proteins accumulated in desiccation tolerant cells of both Arabidopsis and moss. • Evolutionary origin of regulatory machinery for desiccation tolerance is proposed.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

New Coaxial Transseptal Needle for Creation of Atrial Septal Defects in Adult Sheep

Objectives: To introduce a new transseptal (TS) needle assembled in our laboratory-the coaxial TS (CTS) needle-and describe our experience with it in creating experimental atrial septal defects (ASD) in adult sheep.BackgroundWith commercially available TS needles, we were not able to consistently perform TS puncture at the fossa ovalis in adult sheep.Material and MethodsTen adult sheep with a mean weight of 63.5 kg were used. The CTS needle consists of four components: a 9F Teflon catheter, a 14-gauge blunt curved-tip metal cannula, a 4F tapered catheter, and a 20-gauge open needle. A transjugular 5F pigtail catheter was used to display the septal anatomy by angiocardiography and was left in place to mark the level of the fossa ovalis. The septum was then probed by a transfemoral 5F curved-tip end-hole catheter. The CTS needle was aligned with the tip of the transjugular catheter, and the TS puncture was performed under fluoroscopic guidance. After documenting a left atrial position, a balloon angioplasty catheter was used for creation of the ASD. Results: A small patent foramen ovale was discovered by septal probing in one sheep. All sheep underwent successful TS punctures without complications. The ASD size ranged from 13 to 15 mm. In eight sheep, the ASD was in fossa ovalis. In the first two sheep where the needle was not well aligned with the marking catheter, the ASD was in the septum secundum. No damage to the atrial or other heart structures was found at necropsy. Conclusion: The CTS needle is a suitable needle for TS puncture and ASD creation in adult sheep. Proper alignment of the CTS needle with a catheter marking the fossa ovalis is essential for successful puncture.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS2001

Risk analysis: divergent models and convergent interpretations

Material presented at a NASA-sponsored workshop on risk models for exposure conditions relevant to prolonged space flight are described in this paper. Analyses used mortality data from experiments conducted at Argonne National Laboratory on the long-term effects of external whole-body irradiation on B6CF1 mice by 60Co gamma rays and fission neutrons delivered as a single exposure or protracted over either 24 or 60 once-weekly exposures. The maximum dose considered was restricted to 1 Gy for neutrons and 10 Gy for gamma rays. Proportional hazard models were used to investigate the shape of the dose response at these lower doses for deaths caused by solid-tissue tumors and tumors of either connective or epithelial tissue origin. For protracted exposures, a significant mortality effect was detected at a neutron dose of 14 cGy and a gamma-ray dose of 3 Gy. For single exposures, radiation-induced mortality for neutrons also occurred within the range of 10-20 cGy, but dropped to 86 cGy for gamma rays. Plots of risk relative to control estimated for each observed dose gave a visual impression of nonlinearity for both neutrons and gamma rays. At least for solid-tissue tumors, male and female mortality was nearly identical for gamma-ray exposures, but mortality risks for females were higher than for males for neutron exposures. As expected, protracting the gamma-ray dose reduced mortality risks. Although curvature consistent with that observed visually could be detected by a model parameterized to detect curvature, a relative risk term containing only a simple term for total dose was usually sufficient to describe the dose response. Although detectable mortality for the three pathology end points considered typically occurred at the same level of dose, the highest risks were almost always associated with deaths caused by tumors of epithelial tissue origin.

Non-NASA Center↗
NASA NTRS2000

Effects of spaceflight and simulated weightlessness on longitudinal bone growth

Indirect measurements have suggested that spaceflight impairs bone elongation in rats. To test this possibility, our laboratory measured, by the fluorochrome labeling technique, bone elongation that occurred during a spaceflight experiment. The longitudinal growth rate (LGR) in the tibia of rats in spaceflight experiments (Physiological Space Experiments 1, 3, and 4 and Physiological-Anatomical Rodent Experiment 3) and in two models of skeletal unloading (hind-limb elevation and unilateral sciatic neurotomy) were calculated. The effects of an 11 day spaceflight on gene expression of cartilage matrix proteins in rat growth plates were also determined by northern analysis and are reported for the first time in this study. Measurements of longitudinal growth indicate that skeletal unloading generally did not affect LGR, regardless of age, strain, gender, duration of unloading, or method of unloading. There was, however, one exception with 34% suppression in LGR detected in slow-growing, ovariectomized rats skeletally unloaded for 8 days by hind-limb elevation. This detection of reduced LGR by hind-limb elevation is consistent with changes in steady-state mRNA levels for type II collagen (-33%) and for aggrecan (-53%) that were detected in rats unloaded by an 11 day spaceflight. The changes detected in gene expression raise concern that spaceflight may result in changes in the composition of extracellular matrix, which could have a negative impact on conversion of growth-plate cartilage into normal cancellous bone by endochondral ossification.

manned↗
DOE OSTI2021

Ad-apoptin inhibits glycolysis, migration and invasion in lung cancer cells targeting AMPK/mTOR signaling pathway

Ad-apoptin is a recombinant oncolytic adenovirus constructed by our laboratory that can express apoptin. It can selectively kill tumor cells without damaging normal cells. This study investigated the effects of Ad-apoptin on glycolysis, migration and invasion of non-small cell lung cancer. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, respectively. Glycolysis was investigated by glucose consumption, lactic acid production and glycolytic key enzyme protein levels. Migration and invasion were evaluated via wound healing, transwell assays and epithelial-mesenchymal transition (EMT) protein levels. The interaction between apoptin and AMPK was detected by Co-IP. A nude mice tumor model was established to investigate the anti-cancer role of Ad-apoptin in vivo. The results showed that Ad-apoptin inhibits cell viability and induces apoptosis of A549 and NCI–H23 cells. Ad-apoptin can reduce the glucose uptake and lactic production in lung cancer cells, and reduce the expression of related glycolysis-limiting enzymes. At the same time, Ad-apoptin inhibited the migration and invasion of lung cancer. Immunoprecipitation showed that apoptin and AMPK could interact directly. Moreover, knockdown of AMPK significantly attenuated the inhibitory effect of Ad-apoptin on glycolysis, migration and invasion of A549 and NCI–H23 cells. Ad-apoptin can inhibit the growth of tumors in nude mice. Compared with the control group, Ad-apoptin had a significant inhibitory effect on AMPK knockdown tumors. The immunohistochemical results of tumor tissues were consistent with those in vitro. Collectively, Ad-apoptin targets AMPK and inhibits glycolysis, migration and invasion of lung cancer cells through the AMPK/mTOR signaling pathway. This suggests that Ad-apoptin may have therapeutic potential for lung cancer by targeting AMPK activation.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1995

Role of calcium in growth inhibition induced by a novel cell surface sialoglycopeptide

Our laboratory has purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) from intact bovine cerebral cortex cells. Evidence presented here demonstrates that sensitivity to CeReS-18-induced growth inhibition in BALB-c 3T3 cells is influenced by calcium, such that a decrease in the calcium concentration in the growth medium results in an increase in sensitivity to CeReS-18. Calcium did not alter CeReS-18 binding to its cell surface receptor and CeReS-18 does not bind calcium directly. Addition of calcium, but not magnesium, to CeReS-18-inhibited 3T3 cells results in reentry into the cell cycle. A greater than 3-hour exposure to increased calcium is required for escape from CeReS-18-induced growth inhibition. The calcium ionophore ionomycin could partially mimic the effect of increasing extracellular calcium, but thapsigargin was ineffective in inducing escape from growth inhibition. Increasing extracellular calcium 10-fold resulted in an approximately 7-fold increase in total cell-associated 45Ca+2, while free intracellular calcium only increased approximately 30%. However, addition of CeReS-18 did not affect total cell-associated calcium or the increase in total cell-associated calcium observed with an increase in extracellular calcium. Serum addition induced mobilization of intracellular calcium and influx across the plasma membrane in 3T3 cells, and pretreatment of 3T3 cells with CeReS-18 appeared to inhibit these calcium mobilization events. These results suggest that a calcium-sensitive step exists in the recovery from CeReS-18-induced growth inhibition. CeReS-18 may inhibit cell proliferation through a novel mechanism involving altering the intracellular calcium mobilization/regulation necessary for cell cycle progression.

Non-NASA Center↗
NASA NTRS2002

Pathology effects at radiation doses below those causing increased mortality

Mortality data from experiments conducted at the Argonne National Laboratory (ANL) on the long-term effects of external whole-body irradiation on B6CF(1) mice were used to investigate radiation-induced effects at intermediate doses of (60)Co gamma rays or fission-spectrum neutrons either delivered as a single exposure or protracted over 60 once-weekly exposures. Kaplan-Meier analyses were used to identify the lowest dose in the ANL data (within radiation quality, pattern of exposure, and sex) at which radiation-induced mortality caused by primary tumors could be detected (approximately 1-2 Gy for gamma rays and 10-15 cGy for neutrons). Doses at and below these levels were then examined for radiation-induced shifts in the spectrum of pathology detected at death. To do this, specific pathology events were pooled into larger assemblages based on whether they were cancer, cardiovascular disease or non-neoplastic diseases detected within the lungs and pleura, liver and biliary tract, reproductive organs, or urinary tract. Cancer and cardiovascular disease were further subdivided into categories based on whether they caused death, contributed to death, or were simply observed at death. Counts of how often events falling within each of these combined pathology categories occurred within a mouse were then used as predictor variables in logistic regression to determine whether irradiated mice could be distinguished from control mice. Increased pathology burdens were detected in irradiated mice at doses lower than those causing detectable shifts in mortality-22 cGy for gamma rays and 2 cGy for neutrons. These findings suggest that (1) models based on mortality data alone may underestimate radiation effects, (2) radiation may have adverse health consequences (i.e. elevated health risks) even when mortality risks are not detected, and (3) radiation-induced pathologies other than cancer do occur, and they involve multiple organ systems.

Non-NASA Center↗