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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3

SU-F-T-670: From the OR to the Radiobiology Lab: The Journey of a Small X-Ray Source

Purpose: Irradiation of small animal tumor models within laboratories is vital to radiobiological experiments. Often the animals are not able to be brought back into the lab after being taken out for irradiation. Cell biology laboratories benefit from irradiation capability available around the clock without regard to patient load in an associated radiotherapy clinic. Commercial systems are available, but bulky and expensive. Methods: An intraoperative kV irradiation system (IntraBeam™) designed to deliver spherical dose distributions to surgical cavities has been repurposed for the irradiation of cell plates and small laboratory animals. An applicator has been altered to allow for simple, open fields. Special collimators are being developed. BEAMnrc Monte Carlo simulations with the “NRC swept BEAM” source model have been performed to characterize the dose distributions, to develop optimal collimators and as basis for dose prescription. Measurements with radiochromic film and with an ionization chamber were performed to characterize the beam and to validate the simulations. Results: Using its highest setting (50 kV and 40 µA) the x-ray unit is capable of delivering dose rates over 1 Gy/min homogeneously to standard cell plates even without an optimized collimator. Smaller areas (tumors in animals) can be irradiated with significantly higher dose rates (> 20 Gy/min) depending on distance of the source to the tumor. The HVL was found to be 0.21 mm Al which means the shielding requirements for the device are easily achievable in the lab. Conclusion: A mobile irradiation facility is feasible. It will allow easier access to radiation for radiobiology experiments. The modified system is versatile in that for cell plates homogenous irradiations can be achieved through distance from the source, while for high dose rate small field irradiations the source can be brought in close proximity to the target.

60 APPLIED LIFE SCIENCES↗

Prototype Laboratory Concept

The prototype laboratory concept was developed to simplify the laboratory design process, and should be considered for use as a new laboratory design methodology. Many developing countries lack adequate public and animal health laboratories and typically do not have the economic means and the design and construction expertise to build a laboratory on their own. These countries rely on international sponsors to provide the funds necessary to design and construct a laboratory. However, these international sponsors are often located far away, making travel back and forth difficult, which leads to an increase in overall costs and delays for the project. The prototype laboratory concept and design methodology were developed to streamline the design process, saving time and money, while also minimizing the number of errors that typically arise using a traditional design process by providing well considered design decisions in advance of the project. By solving numerous detailed design issues early, this methodology will allow the time, attention and energies of the design team to be focused on addressing the specific needs of the end users, the unique design challenges related to a given site and scientific program, and the biosafety and biosecurity risks associated with the scientific activities planned to be conducted in the facility. While the concept could be expanded to cover other types of laboratories to date, it has primarily focused on supporting the implementation of good laboratory design best practices for infectious disease diagnostic and research laboratories for both the human and animal health sectors. This report presents the laboratory design concept and details associated with the modular layouts. It builds on the work previously provided in the interim prototype laboratory concept report delivered to the Cooperative Biological Engagement Program (CBEP) at the Defense Threat Reduction Agency (DTRA) in 2014. This report includes a number of revised and additional module layouts, more detailed information regarding laboratory finishes and equipment, engineering service information, electrical and lighting layouts, plumbing service information and two mechanical service options for each prototype module. Additionally, this report also includes a description of a cost estimating tool that will accompany this report and allow funding agencies to generate an approximate cost for the construction of a laboratory that utilizes the prototype laboratory concept modules. This report is intended to serve a complete document and includes all relevant information from the 2014 prototype laboratory concept report.

42 ENGINEERING↗

Optimization of Diode Laser System to Treat Benign Prostate Hyperplasia Final Report CRADA No. TSB-1154-95

Benign prostate hyperplasia (BPH) is a pervasive condition of enlargement of the male prostate gland which leads to several urinary difficulties ranging from hesitancy to incontinence to kidney dysfunction in severe cases. Currently the most common therapy is transurethral resection of the prostate (TURP) utilizing an electrosurgical device. Although TURP is largely successful, new BPH therapy methods are desired to reduce the cost and recovery time, improve the success rate, and reduce side effects. Recently, lasers have been introduced for this purpose. Indigo Medical Inc. is currently engaged in the development, testing, and preparation for sales of a new diode laser based BPH therapy system. The development is based on laboratory experiments, animal studies, and a limited FDA-approved clinical trial in the US and in other countries. The addition of sophisticated numerical modeling, of the sort that has been highly developed at Lawrence Livermore National Laboratory, can greatly aid in the design of the system and treatment protocol. The benefits to DOE include the maintenance and advancement of numerical modeling expertise in radiation-matter interactions of the sort essential for the stockpile stewardship, inertial confinement fusion, and advanced manufacturing, and the push on advanced scientific computational methods, ultimately in areas such as 3-D transport.

42 ENGINEERING↗

Plasma Retention and Systemic Kinetics of 90 Sr Intramuscularly Injected in Female Nonhuman Primates

Thirteen female Rhesus macaques were intramuscularly injected with 90 Sr(NO 3 ) 2 diluted in sodium citrate solution. The biokinetic data from these animals were compared against the predictions of the NCRP 156 wound models combined with the ICRP systemic models. We observed observed that the activities measured in plasma of these nonhuman primates (NHPs) were consistently lower than those predicted by the default human biokinetic models. The urinary excretion from the NHPs at times immediately after injection was much greater than that in humans. The fecal excretion rates were found to be in relatively better agreement with humans. Similarly, the activities retained in the skeleton of the NHPs were lower than that in humans. These differences were attributed to the higher calcium diet of the NHPs (0.03 to 0.12 g/d/kg body weight) compared to that of humans. These observations were consistent with the early animal and human studies that showed the effect of calcium on strontium metabolism, specifically urinary excretion. Strontium is preferentially filtered at a much higher rate in kidneys than calcium because it is less completely bound to protein than is calcium. Furthermore, these differences, along with large inter-animal variability, should be considered when estimating the behavior of Sr in humans from the metabolic data in animals or vice-versa.

61 RADIATION PROTECTION AND DOSIMETRY↗

X-Rays Compton Detectors For Biomedical Application

Collimators are usually needed to image sources emitting X-rays that cannot be focused. Alternately, one may employ a Compton Camera (CC) and measure the direction of the incident X-ray by letting it interact with a thin solid, liquid or gaseous material (Tracker) and determine the scattering angle. With respect to collimated cameras, CCs allow higher gamma-ray efficiency in spite of lighter geometry, and may feature comparable spatial resolution. CCs are better when the X-ray energy is high and small setups are required. We review current applications of CCs to Gamma Ray Astronomy and Biomedical systems stressing advantages and drawbacks. As an example, we focus on a particular CC we are developing, which is designed to image small animals administered with marked pharmaceuticals, and assess the bio-distribution and targeting capability of these latter. This camera has to address some requirements: relatively high activity of the imaged objects; detection of gamma-rays of different energies that may range from 140 keV (Tc99m) to 511 keV; presence of gamma and beta radiation with energies up to 2 MeV in case of 188Re. The camera consists of a thin position-sensitive Silicon Drift Detector as Tracker, and a further downstream position-sensitive system employing scintillating crystals and a multi-anode photo-multiplier (Calorimeter). The choice of crystal, pixel size, and detector geometry has been driven by measurements and simulations with the tracking code GEANT4. Spatial resolution, efficiency and scope are discussed.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Thiazolidinediones abrogate cervical cancer growth

Peroxisome proliferator-activated receptor gamma (PPAR γ) is activated by thiazolidinedione drugs (TZDs) and can promote anti-cancer properties. We used three TZDs (pioglitazone, rosiglitazone, and ciglitazone) to target cervical cancer cell lines and a nude mouse animal model. Each agent increased activation of PPAR γ, as judged by a luciferase reporter gene assay in three HPV-associated cell lines (CaSki, SiHa, and HeLa cells) while decreasing cellular proliferation in a dose-dependent manner. They also promoted Oil Red O accumulation in treated cell lines and upregulated the lipid differentiation marker adipsin. Interestingly, xenograft HeLa tumors in nude mice treated with 100 mg/kg/day pioglitazone exhibited decreased growth compared to control mice or mice treated with standard cervical chemotherapy. In conclusion, TZDs slow tumor cell growth in vitro and in vivo with decreases in cell proliferation and increases in PPAR γ and adipsin. These agents may be interesting treatments or treatment adjuncts for HPV-associated cancers or perhaps even precancerous conditions. - Highlights: • Thiazolidinediones decreases cervical cancer proliferation. • Pioglitazone increases cervical cancer differentiation. • Pioglitazone decreases tumor growth in mice. • Pioglitazone may be a useful treatment adjunct.

60 APPLIED LIFE SCIENCES↗

Lymphangiography and Post-lymphangiographic Multidetector CT for Preclinical Lymphatic Interventions in a Rabbit Model

Purpose: To describe the feasibility of lymphangiography and the visibility of the lymphatic system using post-lymphangiographic multidetector CT (MDCT) for preclinical lymphatic interventions in a rabbit model. Materials and Methods: Lymphangiography via the popliteal lymph node or vessel after surgical exposure was performed, using six healthy female Japanese White rabbits. Lipiodol was manually injected for lymphangiography. Post-lymphangiographic MDCT examinations were performed in all rabbits. The dataset images were subjected to image processing analysis utilizing the three-dimensional maximum intensity projection technique. Three reviewers evaluated the degree of depiction of the lymphatic system using a four-point visual score (1, poor; 2, fair; 3, good; 4, excellent). The distance between the body surface and cisterna chyli was measured on post-lymphangiographic MDCT axial image. Results: Lymphangiography was successfully performed in all rabbits. The popliteal lymph node was detectable in 90%. The visualization of lymphatic system via the popliteal node was achieved in 89%. Mean visual scores of > 3.0 were realized by the right femoral lymphatic vessel, left femoral lymphatic vessel, left iliac lymphatic vessel, left lumbar lymphatic trunks and cisterna chyli, whereas mean visual scores of < 3.0 were yielded by the right iliac lymphatic vessel, right lumbar lymphatic trunks and thoracic duct. The distance between the body surface and cisterna chyli on post-lymphangiographic MDCT axial images was 4.33 ± 0.14 cm. Conclusion: Lymphangiography is feasible, and the visibility of the lymphatic system on post-lymphangiographic MDCT in a rabbit model provides enough information for interventional radiologists to perform preclinical lymphatic interventions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Evaluation of photon irradiation treatment upon calcium content of ribs of Wistar rats using micro-XRF

Therapeutic doses of radiation have been shown to have deleterious consequences on bone health. Among the treatment strategies used for breast cancer treatment, the most used are radiotherapy and chemotherapy. Radiotherapy may be given to destroy the cancer cells using high-dose x-rays. Protocols vary considerably, but generally whole body irradiation totals from 10 to 15 Gy, whereas local therapy totals from 40 to 70 Gy. In clinical practice, the quantitative evaluation of bone tissue relies on measurements of bone mineral density values, which are closely associated with the risk of osteoporotic fracture. Improved survivorship rates of cancer patients receiving radiotherapy increase the importance of understanding the mechanisms and long-term effects of radiation-induced bone loss. In this work, we investigated the variation on calcium distribution in ribs of female Wistar rats (Rattus norvegicus) submitted to photon irradiation with a single dose of 20 Gy. The determination of the calcium distribution was performed using synchrotron radiation microfluorescence (SR-{mu}XRF) at the X-ray Fluorescence beamline at Brazilian Synchrotron Light Laboratory (LNLS). Animals were irradiated using the linear accelerator Varian registered (CLINAC 2100) at the University Centre for Cancer Control of the State University of Rio de Janeiro (CUCC/UERJ). The total dose delivered was 20 Gy. The animals were about three months old and weighting about 200g. They were distributed into two groups (seven per group): control (did not receive any treatment) and irradiated (submitted to irradiation procedure) groups. Results showed that calcium content decreased within the dorsal ribs of rats submitted to radiotherapy in comparison to the control group.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Behavior of Americium in Simulated Wounds in Nonhuman Primates

An americium solution injected intramuscularly into several nonhuman primates (NHPs) was found to behave differently than predicted by the wound models described in the NCRP Report 156. This was because the injection was made along with a citrate solution, which is known to be more soluble than chlorides, oxides, or nitrates on which the NCRP Report was based. We developed a multi-exponential wound model specific to the injected americium solution based on the retention in the intramuscular sites. The model was coupled with the americium systemic model to interpret the urinary excretion data and assess the intake, and it was determined that the models were adequate to predict early urinary excretion in most cases but unable to predict late urinary excretion. This was attributed to the differences in the systemic handling of americium between humans and nonhuman primates. Furthermore, information on the type of wounds, solubility, particle size, mass, chemical form, etc., should always be considered when performing wound dosimetry.

61 RADIATION PROTECTION AND DOSIMETRY↗

Radiobiology, Omics and Microdosimetry of Systemic and Targeted Radiotherapeutics Workshop

The Radiobiology, Omics and Microdosimetry of Systemic and Targeted Radiotherapeutics Workshop fostered engagement across disciplines on critical topics that impact the development of targeted radionuclide therapies, bringing together scientific and medical professionals actively involved in radiotherapeutic design, optimization testing, patient treatment, and clinical trials along with basic science researchers, whose novel techniques have the potential to further our understanding of targeted radionuclide therapy. Discussion of the applications of radiotherapeutics to pediatric and adult, brain, prostate and blood cancers, and metastatic disease allowed scientific research to be presented in the context of real-world medical applications and provided an important backdrop to the basic research performed in computers, laboratories, and animal facilities. The workshop format, presentations, and panel discussions were designed to consider a holistic approach to the development of systemic and targeted radiotherapies, integrating radiobiology and microdosimetry, biological assessments on the microscale, and physiologically relevant models of tumor and tissue microenvironments. Important needs highlighted in the workshop include better models to assess the biological effects of radionuclide therapy, novel strategies to target radiotherapeutics to disease sites with high specificity, and new dosimetry techniques that address the importance of tumor microenvironments.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

classLog: Logistic regression for the classification of genetic sequences

Introduction Sequencing and phylogenetic classification have become a common task in human and animal diagnostic laboratories. It is routine to sequence pathogens to identify genetic variations of diagnostic significance and to use these data in realtime genomic contact tracing and surveillance. Under this paradigm, unprecedented volumes of data are generated that require rapid analysis to provide meaningful inference. Methods We present a machine learning logistic regression pipeline that can assign classifications to genetic sequence data. The pipeline implements an intuitive and customizable approach to developing a trained prediction model that runs in linear time complexity, generating accurate output rapidly, even with incomplete data. Our approach was benchmarked against porcine respiratory and reproductive syndrome virus (PRRSv) and swine H1 influenza A virus (IAV) datasets. Trained classifiers were tested against sequences and simulated datasets that artificially degraded sequence quality at 0, 10, 20, 30, and 40%. Results When applied to a poor-quality sequence data, the classifier achieved between >85% to 95% accuracy for the PRRSv and the swine H1 IAV HA dataset and this increased to near perfect accuracy when using the full dataset. The model also identifies amino acid positions used to determine genetic clade identity through a feature selection ranking within the model. These positions can be mapped onto a maximum-likelihood phylogenetic tree, allowing for the inference of clade defining mutations. Discussion Our approach is implemented as a python package with code available at https://github.com/flu-crew/classLog .

Zeller, Michael A.↗

Operation and Maintenance of the National Radiobiology Archives

The National Radiobiology Archives (NRA) are an archival program, started in 1989, to collect, organize and maintain data, laboratory notebooks, and animal tissue specimens from government (Department of Energy and its predecessor agencies) sponsored radiobiology life-span animal studies. These unique records, histopathology slides and paraffin embedded tissue blocks are maintained in a central facility and are available for further research study. The materials include electronic and paper records for each of more than 6,000 life-span-observations on dogs as well as details of major studies involving nearly 30,000 mice. Although these studies were performed over many years and at different laboratories with differing data management systems, the NRA has translated them into a standardized set of relational database tables. These can be distributed to interested individuals on written request. Specific Aims are: (1) To Maintain the Archive of Written Records from the Animal Experiments - The USTUR continued to maintain the NRA archives which consist of approximately 175 storage boxes containing laboratory notebooks, animal exposure records, animal pathologic records, and radiographs. These were stored in a 6,000 square foot leased facility in Richland, WA. Additionally, through a collaboration with Pacific Northwest National Laboratory's (PNNL) Low Dose Program, many of these records were scanned into digital files. These totaled 34 GB of data, which are saved in 2,407 separate PDF files that are organized by box number and animal identification number. (2) To Maintain the Archive of Animal Tissues at Washington State University - The USTUR continued to house the NRA dog tissue collection in the leased facility. The NRA tissue collection consisted of pathology slides and tissue blocks. Approximately 25% of the laboratory facility was dedicated to the storage of the NRA materials. (3) To Organize the Datasets of These Animals in the Context of Other Datasets so That They Can be Used by the Scientific Community at Large - As was reported in the FY2009 NRA progress report, Dr. Chuck Watson (NRA Database Consultant) completed his service as the US representative on the European Radiobiological Archives (ERA) Advisory Board during FY2009. Unfortunately, due to the lack of financial support during FY2010, the NRA was not able to make further contributions to the ERA's efforts.

59 BASIC BIOLOGICAL SCIENCES↗

No-touch measurements of vital signs in small conscious animals

Measuring the heartbeat and respiration of small conscious animals is important for assessing their health and behavior, but present techniques such as electrocardiogram (ECG), ultrasound, and auscultation rely on close skin contact with the animal. These methods can also require surface preparation, cause discomfort or stress to animals, and even require anesthetic administration, especially for birds, reptiles, and fish. Here, we show that radio frequency near-field coherent sensing (NCS) can provide a new solution to animal vital sign monitoring while ensuring minimal pain and distress. We first benchmarked NCS with synchronous ECG on an anesthetized rat. NCS was then applied to monitor a conscious hamster from outside its cage, and was further extended to a parakeet, Russian tortoise, and betta fish in a noninvasive manner. Our system can revolutionize vital sign monitoring of small conscious animals in their laboratory living quarters or natural habitats.

47 OTHER INSTRUMENTATION↗

Biosafety and biosecurity in veterinary laboratories

Here, with recent outbreaks of MERS-Cov, Anthrax, Nipah, and Highly Pathogenic Avian Influenza, much emphasis has been placed on rapid identification of infectious agents globally. As a result, laboratories are building capacity, conducting more advanced and sophisticated research, increasing laboratory staff, and establishing collections of dangerous pathogens in an attempt to reduce the impact of infectious disease outbreaks and characterize disease causing agents. With this expansion, the global laboratory community has started to focus on laboratory biosafety and biosecurity to prevent the accidental and/or intent ional release o f these agents. Laboratory biosafety and biosecurity systems are used around the world to help mit igate the risks posed by dangerous pathogens in the laboratory. Veterinary laboratories carry unique responsibilities to workers and communities to safely and securely handle disease causing microorganisms. Many microorganisms studied in veterinary laboratories not only infect animals, but also have the potential to infect humans. This paper will discuss the fundamentals of laboratory biosafety and biosecurity.

59 BASIC BIOLOGICAL SCIENCES↗

Past and Future Work on Radiobiology Mega-Studies: A Case Study At Argonne National Laboratory

Between 1952 and 1992, more than 200 large radiobiology studies were conducted in research institutes throughout Europe, North America, and Japan to determine the effects of external irradiation and internal emitters on the lifespan and tissue toxicity development in animals. At Argonne National Laboratory, 22 external beam studies were conducted on nearly 700 beagle dogs and 50,000 mice between 1969 and 1992. These studies helped to characterize the effects of neutron and gamma irradiation on lifespan, tumorigenesis, and mutagenesis across a range of doses and dosing patterns. The records and tissues collected at Argonne during that time period have been carefully preserved and redisseminated. Using these archived data, ongoing statistical work has been done and continues to characterize quality of radiation, dose, dose rate, tissue, and gender-specific differences in the radiation responses of exposed animals. The ongoing application of newly-developed molecular biology techniques to the archived tissues has revealed gene-specific mutation rates following exposure to ionizing irradiation. The original and ongoing work with this tissue archive is presented here as a case study of a more general trend in the radiobiology megastudies. These experiments helped form the modern understanding of radiation responses in animals and continue to inform development of new radiation models. Recent archival efforts have facilitated open access to the data and materials produced by these studies, and so a unique opportunity exists to expand this continued research.

59 BASIC BIOLOGICAL SCIENCES↗

Large Game Distribution Camera Study at Los Alamos National Laboratory

The unique habitats at the Laboratory support a diverse community of wildlife. The habitat types that include Pinon Juniper, Ponderosa Pine, and Mixed-conifer forests each provide different resources important for a variety of species. Wildlife monitoring for large game animals can be challenging because they avoid interactions with humans, and prefer undeveloped areas. This study was conducted to analyze the distribution of predators and other game animals seasonally across the Laboratory. This research informs decisions regarding wildlife management recommendations for conservation and protection. This study utilized game cameras to remotely monitor wildlife. As camera technology has advanced, game cameras have become adequate for documenting individuals, and are commonly used in wildlife studies on predation, abundance, occupancy, diversity, and endangered species detection. Twenty cameras were placed across the LANL landscape using a modified systematic sampling design. They were deployed in February 2018 and retrieved in January 2019, thus each camera sampled for one full year. All images were reviewed and the species, number, age, and sex of all animals in the photo were recorded. Here we present data for the most abundant species encountered: deer, elk, coyote, bear, bobcat, mountain lion, and fox respectively. The data were summarized by species and season. Future work will include occupancy modelling for each species. This will allow the development of heat maps showing species distributions across the Laboratory.

59 BASIC BIOLOGICAL SCIENCES↗

Large Game Distribution Camera Study at Los Alamos National Laboratory [Poster]

The unique habitats at the Laboratory support a diverse community of wildlife. The habitat types that include Pinon Juniper, Ponderosa Pine, and Mixed-conifer forests each provide different resources important for a variety of species. Wildlife monitoring for large game animals can be challenging because they avoid interactions with humans, and prefer undeveloped areas. This study was conducted to analyze the distribution of predators and other game animals seasonally across the Laboratory. The data gathered will be used to make recommendations regarding wildlife management for conservation and protection. Utilizing game cameras to remotely monitor wildlife was determined to be the most effective, noninvasive method to gather the necessary data. As camera technology has advanced, game cameras have become adequate for documenting individuals, and are commonly used in wildlife studies on predation, abundance, occupancy, diversity, and endangered species detection. Twenty cameras were placed across the LANL landscape using a modified systematic sampling design. They were deployed in February 2018 and retrieved in January 2019, thus each camera sampled for one full year. All images were reviewed and the species, number, age, and sex of all animals in the photo were recorded. Here we present data for the most abundant species encountered: deer, elk, coyote, bear, bobcat, mountain lion, and fox respectively. The data were summarized by species and season. Future work will include occupancy modelling for each species. This will allow the development of heat maps showing species distributions across the Laboratory.

54 ENVIRONMENTAL SCIENCES↗