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At least 1,171 records · Page 65

Microbial Responses to Radiation at the Single-Cell Level

Exploring the biological effects of deep space radiation is crucial for developing protective protocols for humans traveling beyond Earth’s magnetosphere. Saccharomyces cerevisiae, or budding yeast, is an ideal model organism to study the effects of radiation on eukaryotes as it shares several pathways with humans, including DNA repair mechanisms. Here, we used time-lapse imaging of colony growth on agar plates to monitor the effects of radiation exposure on individual yeast cells and their progeny.

Paola J. Maldonado Martinez↗

Temperature-At-Depth Maps For the Conterminous US and Geothermal Resource Estimates

A third generation geothermal resource assessment has recently been completed for the conterminous US based on a revised heat flow map using over 35,000 data sites. Improvements include: nearly doubling the number of data points used in the analysis, more detailed thermal conductivity models for temperature-at-depth and heat flow calculations, and addition of a significant number of calibration wells as checks on the bottom hole temperature (BHT) correction. The results increase the accuracy of temperature-at-depth models for the conterminous US. These temperature models are the key input required for evaluating the non-conventional geothermal resources on a regional to sub-regional basis. The new resource assessment was prepared according to a proposed global protocol for estimating Enhanced/ Engineered Geothermal Systems (EGS) resource potential. A comparison of the new assessment approach with previous studies is provided, along with a discussion of the differences associated with the revised approach.

15 GEOTHERMAL ENERGY↗

Open Source Intelligence for Cybersecurity Events via Twitter Data

Open-Source Intelligence (OSINT) is largely regarded as a necessary component for cybersecurity intelligence gathering to secure network systems. With the advancement of artificial intelligence (AI) and increasing usage of social media, like Twitter, we have a unique opportunity to obtain and aggregate information from social media. In this study, we propose an AI-based scheme capable of automatically pulling information from Twitter, filtering out security-irrelevant tweets, performing natural language analysis to correlate the tweets about each cybersecurity event (e.g., a malware campaign), and validating the information. This scheme has many applications, such as providing a means for security operators to gain insight into ongoing events and helping them prioritize vulnerabilities to deal with. To give examples of the possible uses, we present three case studies demonstrating the event discovery and investigation processes. We also examine the potential of OSINT for identifying the network protocols associated with specific events, which can aid in the mitigation procedures by informing operators if the vulnerability is exploitable given their system’s network configurations.

Dale, Dakota↗

Ultrasonic Studies of Composites Undergoing Thermal and Fatigue Loading

New composite materials possess attractive properties for use in advanced aircraft. A necessary requirement for their introduction into aeronautic use is an accurate understanding of their long term aging processes so that proper design criteria can be established. In order to understand those properties, these composites must be exposed to thermal and load cycles that are characteristic of flight conditions. Additionally, airline companies will require nondestructive evaluation (NDE) methods that can be used in the field to assess the condition of these new materials as they age. As part of an effort to obtain the required information about new composites for aviation use, we are performing ultrasonic measurements both in the NDE laboratory and in the materials testing laboratory at NASA. The materials testing laboratory is equipped with environmental chambers mounted on load frames so that composite samples can be exposed to thermal and loading cycles representative of flight protocols. Applying both temperature and load simultaneously will help to highlight temperature and load interactions during the aging of these composite materials. This study reports on our initial ultrasonic attenuation results from thermoset and thermoplastic composite samples. Ultrasonic attenuation measurements have been used reliably to assess the effects of material degradation. For example, recently, researchers have shown that by using frequencies of ultrasound on the order of 24 MHz, they could obtain adequate contrast in the evaluation of thermal degradation in these composites. This paper will present data that shows results at a lower frequency range. In addition, we report results on the frequency dependence of attenuation as the slope of attenuation with respect to frequency, beta = delta alpha (f) / delta f. The slope of attenuation is an attractive parameter since it is quantitative, yet does not require interface corrections like conventional quantitative attenuation measurements. This is a consequence of the assumption that interface correction terms are frequently independent. Uncertainty in those corrections terms compromises the value of conventional quantitative attenuation data.

Madaras, Eric I.↗

Design and evaluation of a cyber‐physical testbed for improving attack resilience of power systems

Abstract A power system is a complex cyber‐physical system whose security is critical to its function. A major challenge is to model, analyse and visualise the communication backbone of the power systems concerning cyber threats. To achieve this, the design and evaluation of a cyber‐physical power system (CPPS) testbed called Resilient Energy Systems Lab (RESLab) are presented to capture realistic cyber, physical, and protection system features. RESLab is architected to be a fundamental platform for studying and improving the resilience of complex CPPS to cyber threats. The cyber network is emulated using Common Open Research Emulator (CORE), which acts as a gateway for the physical and protection devices to communicate. The physical grid is simulated in the dynamic time frame using Power World Dynamic Studio (PWDS). The protection components are modelled with both PWDS and physical devices including the SEL Real‐Time Automation Controller (RTAC). Distributed Network Protocol 3 (DNP3) is used to monitor and control the grid. Then, the design is exemplified and the tools are validated. This work presents four case studies on cyberattack and defence using RESLab, where we demonstrate false data and command injection using Man‐in‐the‐Middle and Denial of Service attacks and validate them on a large‐scale synthetic electric grid.

Sahu, Abhijeet↗

Metal leaching from Lithium-ion and Nickel-metal hydride batteries and photovoltaic modules in simulated landfill leachates and municipal solid waste materials

Photovoltaic (PV) modules and batteries can either be recycled or disposed of in landfills at end-of-life (EoL). This work focuses on disposal since the benefit of recycling PV modules and batteries is well established. This study characterizes the potential toxicity due to metals leaching from selected PV modules and batteries through both the Toxicity Characteristic Leaching Procedure (TCLP) and in-house batch leaching protocols to probe the impact on metallic ion mobility as a function of the different types of e-waste entering the waste stream, the magnitude of device damage when placed into the waste stream, and the simulated municipal solid waste (SMSW) composition. Our results showed that one PV module and three battery types in this study should be classified as hazardous waste within the U.S. However, for some of the other e-wastes, metals of concern including Cr, Cu, Hg, Ni, Pb, and Zn leached during the batch tests but not in the TCLP regulatory method. For most of the waste types, the amounts of metals that leached in the TCLP test and batch tests were much lower than the total extractable amounts, demonstrating the potential for additional unaccounted for amounts of metals to leach. Our results demonstrate that the TCLP regulatory method might fail at predicting potential leaching and at capturing the complexity of e-waste leaching in landfill conditions. It confirms that additional work is needed urgently to develop appropriate EoL procedures for MSW with PV and battery e-waste.

42 ENGINEERING↗

Practical reconstruction protocol for quantitative {sup 90}Y bremsstrahlung SPECT/CT

Purpose: To develop a practical background compensation (BC) technique to improve quantitative {sup 90}Y-bremsstrahlung single-photon emission computed tomography (SPECT)/computed tomography (CT) using a commercially available imaging system. Methods: All images were acquired using medium-energy collimation in six energy windows (EWs), ranging from 70 to 410 keV. The EWs were determined based on the signal-to-background ratio in planar images of an acrylic phantom of different thicknesses (2–16 cm) positioned below a {sup 90}Y source and set at different distances (15–35 cm) from a gamma camera. The authors adapted the widely used EW-based scatter-correction technique by modeling the BC as scaled images. The BC EW was determined empirically in SPECT/CT studies using an IEC phantom based on the sphere activity recovery and residual activity in the cold lung insert. The scaling factor was calculated from 20 clinical planar {sup 90}Y images. Reconstruction parameters were optimized in the same SPECT images for improved image quantification and contrast. A count-to-activity calibration factor was calculated from 30 clinical {sup 90}Y images. Results: The authors found that the most appropriate imaging EW range was 90–125 keV. BC was modeled as 0.53× images in the EW of 310–410 keV. The background-compensated clinical images had higher image contrast than uncompensated images. The maximum deviation of their SPECT calibration in clinical studies was lowest (<10%) for SPECT with attenuation correction (AC) and SPECT with AC + BC. Using the proposed SPECT-with-AC + BC reconstruction protocol, the authors found that the recovery coefficient of a 37-mm sphere (in a 10-mm volume of interest) increased from 39% to 90% and that the residual activity in the lung insert decreased from 44% to 14% over that of SPECT images with AC alone. Conclusions: The proposed EW-based BC model was developed for {sup 90}Y bremsstrahlung imaging. SPECT with AC + BC gave improved lesion detectability and activity quantification compared to SPECT with AC only. The proposed methodology can readily be used to tailor {sup 90}Y SPECT/CT acquisition and reconstruction protocols with different SPECT/CT systems for quantification and improved image quality in clinical settings.

61 RADIATION PROTECTION AND DOSIMETRY↗

A Real-Time Testbed for Smart Inverter Cyber Security Studies

Distributed energy resources (DER) have become a popular solution to modern-day issues surrounding the efficiency and reliability of power generation, as well as climate change concerns. Energy centers are shifting towards incorporating smart inverters with embedded functionalities such as high voltage ride through (HVRT), low voltage ride through (LVRT), active and reactive power compensation. However, the integration of smart inverters leave DER systems highly vulnerable to cybersecurity threats. The distributed network protocol 3 (DNP3) is a common method of communication between grid-tied hardware. Despite its popularity, the level of security leaves all hardware connected to the grid at risk of severe cyber-attacks. Thus, it is important to study any potential cybersecurity threats towards grid-tied smart inverters to mitigate cybersecurity vulnerabilities and refine existing cyber-security protections. This report describes the proposed testbed design to study cybersecurity threats to smart inverters. The testbed utilizes a real-time simulation case in RSCAD that includes a grid-tied wind turbine (WT) topology featuring two back-to-back two-level voltage source converters (BTB,2L-VSCs) and a permanent magnet synchronous machine (PMSM). The simulated case runs within the NovaCor real time digital simulator (RTDS). This report focuses on the design and implementation of a single module of the GTNETx2 card as a distributed network protocol and the configuration of an IEEE 1518 DNP database file that includes input and output variables mapped to different connection points in the grid that transmit and receive discrete, analog, and binary signals on command. This allows realistic emulation of the communication between the smart inverter and the grid for cybersecurity studies.

97 MATHEMATICS AND COMPUTING↗

Establishing the Framework for e-VTOL Flight Mission Scenario Development for Urban Air Mobility Research using Cognitive Task Analysis

This paper focuses on applying specific protocol aspects of Cognitive Task Analysis (CTA) methods to formulate non-routine flight mission use-case scenarios in support of a potential research study at the National Aeronautics and Space Administration (NASA) Langley Research Center under the Air Traffic Management – eXploration (ATM-X) Urban Air Mobility (UAM) sub-project. The objective of use-case scenarios is to provide a hypothetical situation to elicit expert knowledge and feedback in a specific subject matter area. Use-case scenarios in the field of aviation, including UAM, can help to support the safe integration of these vehicles into the National Airspace System (NAS) through the examination of airspace procedures during non-routine events. Inherent in this type of research is the need to study in-flight non-routine scenarios that the UAM vehicle could encounter. Situations categorized as non-routine events are any events that occur outside of the original flight plan such as a mechanical malfunction or other in-flight emergency requiring special procedures, which can include diversions to a specified, or non-specified, emergency landing area. In specific instances, some non-routine events could be considered as “routine” during in-flight operations, such as the need to perform a go-around due to a balked landing. As the rate of technological expansion surrounding UAM grows rapidly in modern aviation, so does the need for research that focuses on the safe integration of these vehicles including research with a focus on the methods and development of airspace operational procedures. Research rooted in CTA methods provides a framework for developing use-case scenarios appropriate for environments where mental demands are substantial. Substantial mental demands exist while operating in the NAS for pilots, airline dispatchers, and air traffic controllers among many others. With the focus on UAM in mind, it is critical to frame a baseline use-case scenario using information as it pertains to current-day airspace operations. According to Dr. Robert R. Hoffman’s “Protocols for Cognitive Task Analysis,” one of the first steps to applying CTA methods to research is the concept of “bootstrapping” in which the researcher(s) familiarize themselves with the domain that is being studied. To formulate the non-routine flight mission use-case scenarios for the purpose of this potential NASA ATM-X UAM research study, and to inform the baseline use-case scenario, the practice of bootstrapping was utilized to acquire knowledge of current-day airspace procedures.

Heidi S Glaudel↗

ISOS-3 Inter-Laboratory Collaboration Focused on the Stability of a Variety of Organic Photovoltaic Devices

Seven distinct sets (n {>=} 12) of state of the art organic photovoltaic devices were prepared by leading research laboratories in a collaboration planned at the Third International Summit on Organic Photovoltaic Stability (ISOS-3). All devices were shipped to RISO DTU and characterized simultaneously up to 1830 h in accordance with established ISOS-3 protocols under three distinct illumination conditions: accelerated full sun simulation; low level indoor fluorescent lighting; and dark storage with daily measurement under full sun simulation. Three nominally identical devices were used in each experiment both to provide an assessment of the homogeneity of the samples and to distribute samples for a variety of post soaking analytical measurements at six distinct laboratories enabling comparison at various stages in the degradation of the devices. Over 100 devices with more than 300 cells were used in the study. We present here design and fabrication details for the seven device sets, benefits and challenges associated with the unprecedented size of the collaboration, characterization protocols, and results both on individual device stability and uniformity of device sets, in the three illumination conditions.

14 SOLAR ENERGY↗

Batch crystallization of rhodopsin for structural dynamics using an X-ray free-electron laser

A new batch preparation method is presented for high-density micrometre-sized crystals of the G protein-coupled receptor rhodopsin for use in time-resolved serial femtosecond crystallography at an X-ray free-electron laser using a liquid jet. Rhodopsin is a membrane protein from the G protein-coupled receptor family. Together with its ligand retinal, it forms the visual pigment responsible for night vision. In order to perform ultrafast dynamics studies, a time-resolved serial femtosecond crystallography method is required owing to the nonreversible activation of rhodopsin. In such an approach, microcrystals in suspension are delivered into the X-ray pulses of an X-ray free-electron laser (XFEL) after a precise photoactivation delay. Here, a millilitre batch production of high-density microcrystals was developed by four methodical conversion steps starting from known vapour-diffusion crystallization protocols: (i) screening the low-salt crystallization conditions preferred for serial crystallography by vapour diffusion, (ii) optimization of batch crystallization, (iii) testing the crystal size and quality using second-harmonic generation (SHG) imaging and X-ray powder diffraction and (iv) production of millilitres of rhodopsin crystal suspension in batches for serial crystallography tests; these crystals diffracted at an XFEL at the Linac Coherent Light Source using a liquid-jet setup.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Single-Cell Analysis of Yeast (Saccharomyces cerevisiae) Using Hydrogel Encapsulation

Space radiation poses a major health risk to astronauts. To fulfill NASA’s mission of exploration beyond Earth, the biological effects of Galactic Cosmic Radiation and gamma radiation must be investigated to elucidate cellular damage mechanisms and inform countermeasure protocols to safely bring humans beyond Earth’s magnetosphere. Budding yeast (Saccharomyces cerevisiae) are commonly used in experiments as a model organism for studying the effects of radiation on eukaryotes. Radiobiology of yeast at the single cell level is poorly understood, yet crucial for informing models to aid in the design and interpretation of experiments. We are using a novel method of microencapsulation in hydrogel particles (PicoShells) to enable analysis of the distribution of radiation-induced damage among yeast cells at the single-cell level, in high throughput. Here we describe the development of methods for culturing, visualization, and quantification of encapsulated yeast. The encapsulated yeast are cultured in Yeast extract-Peptone-Dextrose (YPD) medium, fixed in formaldehyde or ethanol, and stained with DAPI or propidium iodide, then visualized using microscopy or enumerated using flow cytometry, with the aim of developing a protocol to enumerate the distribution of viable cells in each PicoShell. This will allow us to quantify how different forms of radiation can generate different distributions of damage across a population of cells, ultimately providing insight into the biological effects of space-relevant ionizing radiation.

yeast↗

The Challenge for Arms Control Verification in the Post-New START World

Nuclear weapon arms control treaty verification is a key aspect of any agreement between signatories to establish that the terms and conditions spelled out in the treaty are being met. Historically, arms control negotiations have focused more on the rules and protocols for reducing the numbers of warheads and delivery systems - sometimes resorting to complex and arcane procedures for counting forces - in an attempt to address perceived or real imbalances in a nation's strategic posture that could lead to instability. Verification procedures are generally defined in arms control treaties and supporting documents and tend to focus on technical means and measures designed to ensure that a country is following the terms of the treaty and that it is not liable to engage in deception or outright cheating in an attempt to circumvent the spirit and the letter of the agreement. As the Obama Administration implements the articles, terms, and conditions of the recently ratified and entered-into-force New START treaty, there are already efforts within and outside of government to move well below the specified New START levels of 1550 warheads, 700 deployed strategic delivery vehicles, and 800 deployed and nondeployed strategic launchers (Inter-Continental Ballistic Missile (ICBM) silos, Submarine-Launched Ballistic Missile (SLBM) tubes on submarines, and bombers). A number of articles and opinion pieces have appeared that advocate for significantly deeper cuts in the U.S. nuclear stockpile, with some suggesting that unilateral reductions on the part of the U.S. would help coax Russia and others to follow our lead. Papers and studies prepared for the U.S. Department of Defense and at the U.S. Air War College have also been published, suggesting that nuclear forces totaling no more than about 300 warheads would be sufficient to meet U.S. national security and deterrence needs. (Davis 2011, Schaub and Forsyth 2010) Recent articles by James M. Acton and others suggest that the prospects for maintaining U.S. security and minimizing the chances of nuclear war, while deliberately reducing stockpiles to a few hundred weapons, is possible but not without risk. While the question of the appropriate level of cuts to U.S. nuclear forces is being actively debated, a key issue continues to be whether verification procedures are strong enough to ensure that both the U.S. and Russia are fulfilling their obligations under the current New Start treaty and any future arms reduction treaties. A recent opinion piece by Henry Kissinger and Brent Scowcroft (2012) raised a number of issues with respect to governing a policy to enhance strategic stability, including: in deciding on force levels and lower numbers, verification is crucial. Particularly important is a determination of what level of uncertainty threatens the calculation of stability. At present, that level is well within the capabilities of the existing verification systems. We must be certain that projected levels maintain - and when possible, reinforce - that confidence. The strengths and weaknesses of the New START verification regime should inform and give rise to stronger regimes for future arms control agreements. These future arms control agreements will likely need to include other nuclear weapons states and so any verification regime will need to be acceptable to all parties. Currently, China is considered the most challenging party to include in any future arms control agreement and China's willingness to enter into verification regimes such as those implemented in New START may only be possible when it feels it has reached nuclear parity with the U.S. and Russia. Similarly, in keeping with its goals of reaching peer status with the U.S. and Russia, Frieman (2004) suggests that China would be more willing to accept internationally accepted and applied verification regimes rather than bilateral ones. The current verification protocols specified in the New START treaty are considered as the baseline case and are contrasted with possible alternative verification protocols that could be effective in a post-New START era of significant reductions in U.S. and other countries nuclear stockpiles. Of particular concern is the possibility of deception and breakout when declared and observed numbers of weapons are below the level considered to pose an existential threat to the U.S. In a regime of very low stockpile numbers, 'traditional' verification protocols as currently embodied in the New START treaty might prove less than adequate. I introduce and discuss a number of issues that need to be considered in future verification protocols, many of which do not have immediate solutions and so require further study. I also discuss alternatives and enhancements to traditional verification protocols, for example, confidence building measures such as burden sharing against the common threat of weapon of mass destruction (WMD) terrorism, joint research and development.

45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEF↗

Sampling Soil for Characterization and Site Description

The sampling scheme for soil characterization within the GLOBE program is uniquely different from the sampling methods of the other protocols. The strategy is based on an understanding of the 5 soil forming factors (parent material, climate, biota, topography, and time) at each study site, and how each of these interact to produce a soil profile with unique characteristics and unique input and control into the atmospheric, biological, and hydrological systems. Soil profile characteristics, as opposed to soil moisture and temperature, vegetative growth, and atmospheric and hydrologic conditions, change very slowly, depending on the parameter being measured, ranging from seasonally to many thousands of years. Thus, soil information, including profile description and lab analysis, is collected only one time for each profile at a site. These data serve two purposes: 1) to supplement existing spatial information about soil profile characteristics across the landscape at local, regional, and global scales, and 2) to provide specific information within a given area about the basic substrate to which elements within the other protocols are linked. Because of the intimate link between soil properties and these other environmental elements, the static soil properties at a given site are needed to accurately interpret and understand the continually changing dynamics of soil moisture and temperature, vegetation growth and phenology, atmospheric conditions, and chemistry and turbidity in surface waters. Both the spatial and specific soil information can be used for modeling purposes to assess and make predictions about global change.

Levine, Elissa↗

Intrafraction Bladder Motion in Radiation Therapy Estimated From Pretreatment and Posttreatment Volumetric Imaging

Purpose: The use of image guidance protocols using soft tissue anatomy identification before treatment can reduce interfractional variation. This makes intrafraction clinical target volume (CTV) to planning target volume (PTV) changes more important, including those resulting from intrafraction bladder filling and motion. The purpose of this study was to investigate the required intrafraction margins for soft tissue image guidance from pretreatment and posttreatment volumetric imaging. Methods and Materials: Fifty patients with muscle-invasive bladder cancer (T2-T4) underwent an adaptive radiation therapy protocol using daily pretreatment cone beam computed tomography (CBCT) with weekly posttreatment CBCT. A total of 235 pairs of pretreatment and posttreatment CBCT images were retrospectively contoured by a single radiation oncologist (CBCT-CTV). The maximum bladder displacement was measured according to the patient's bony pelvis movement during treatment, intrafraction bladder filling, and bladder centroid motion. Results: The mean time between pretreatment and posttreatment CBCT was 13 minutes, 52 seconds (range, 7 min 52 sec to 30 min 56 sec). Taking into account patient motion, bladder centroid motion, and bladder filling, the required margins to cover intrafraction changes from pretreatment to posttreatment in the superior, inferior, right, left, anterior, and posterior were 1.25 cm (range, 1.19-1.50 cm), 0.67 cm (range, 0.58-1.12 cm), 0.74 cm (range, 0.59-0.94 cm), 0.73 cm (range, 0.51-1.00 cm), 1.20 cm (range, 0.85-1.32 cm), and 0.86 cm (range, 0.73-0.99), respectively. Small bladders on pretreatment imaging had relatively the largest increase in pretreatment to posttreatment volume. Conclusion: Intrafraction motion of the bladder based on pretreatment and posttreatment bladder imaging can be significant particularly in the anterior and superior directions. Patient motion, bladder centroid motion, and bladder filling all contribute to changes between pretreatment and posttreatment imaging. Asymmetric expansion of CTV to PTV should be considered. Care is required in using image-guided radiation therapy protocols that reduce CTV to PTV margins based only on daily pretreatment soft tissue position.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Heat pump concepts for nZEB Technology developments, design tools and testing of heat pump systems for nZEB in the USA: Country report IEA HPT Annex 40 Task 2, Task 3 and Task 4 of the USA

The IEA HPT Annex 40 "Heat pump concepts for Nearly Zero Energy Buildings" deals with the application of heat pumps as a core component of the HVAC system for Nearly or Net Zero energy buildings (nZEB). This report covers Task 2 on the system comparison and optimisation and Task 3 dedicated to the development of adapted technologies for nZEB and field monitoring results of heat pump systems in nZEB. In the US team three institutions are involved and have worked on the following projects: The Oak Ridge National Laboratory (ORNL) will summarize development activities through the field demonstration stage for several integrated heat pump (IHP) systems electric ground-source (GS-IHP) and air-source (AS-IHP) versions and an engine driven AS-IHP version. The first commercial GS-IHP product was just introduced to the market in December 2012. This work is a contribution to Task 3 of the Annex. The University of Maryland will contribute a software development project to Task 2 of the Annex. The software ThermCom evaluates occupied space thermal comfort conditions accounting for all radiative and convective heat transfer effects as well as local air properties. The National Institute of Standards and Technology (NIST) is working on a field study effort on the NIST Net Zero Energy Residential Test Facility (NZERTF). This residential building was constructed on the NIST campus and officially opened in summer 2013. During the first year, between July 2013 and June 2014, baseline performance of the NZERTF was monitored under a simulated occupancy protocol. The house was equipped with an air-to-air heat pump which included a dedicated dehumidification operating mode. Outdoor conditions, internal loads and modes of heat pump operation were monitored. Field study results with respect to heat pump operation will be reported and recommendations on heat pump optimization for a net zero energy building will be provided. This work is a contribution to Task 3 of the Annex.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Specialized physiological studies in support of manned space flight

The areas of physiological research reported include: (1) evaluation of the single-breath method for determining cardiac output, (2) optimum protocol for the assessment of cardio-pulmonary competence, (3) body fluids and electrolytes under conditions of single and combined stress, (4) re-evaluation of the open-circuit method for measuring metabolic rate with regard to the alleged metabolic production of gaseous nitrogen, and (5) the use of the forced-oscillation method to determine total respiratory conductance in healthy subjects and pulmonary patients.

Luft, U. C.↗

Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina

Purpose: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (L)-4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. Methods: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. Results: Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor-to-normal boron concentration ratio of 2. Conclusions: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.

60 APPLIED LIFE SCIENCES↗