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At least 109 records · Page 6

Regulatory Mechanism of Muscle Disuse Atrophy in Adult Rats

During the last phase of NAG 2-386 we completed three studies. The effects of 14 days of weightlessness; the vastus medialis (VM) from flight rats in COSMOS 2044 was compared with the VM from tail suspended rats and other controls. The type I and II fibers in the mixed fiber portion of the VM were significantly reduced in flight rats and capillary densities paralleled the fiber density changes. The results of this project compared favorably with those in the extensor digitorum longus following seven days of flight in SL 3. The cardiovascular projects focused on the blood pressure changes in head down tilted rats (HDT) and non-head down tilted (N-HDT) rats. Blood pressures (MAP, SP and DP) were significantly elevated through seven days of HDT and rapidly returned to control levels within one day after removal from the HDT position. The N-HDT showed some slight rise in blood pressure but these were not as great and they were not as rapid. The HDT rats were characterized as exhibiting transient hypertension. These results led to some of the microvascular and vascular graduate student projects of Dr. Bernhard Stepke. Also our results refute or, at least, do not agree with previous reports from other laboratories. Each animal, in our blood pressure projects, served as its own control thereby providing more accurate results. Also, our experiments focused on recovery studies which can, in and of themselves, provide guidelines for flight experiments concerned with blood pressure changes. Another experiment was conducted to examine the role of testicular atrophy in whole body suspended (WBS) and tail suspended (TS) rats. We worked in conjunction with Dr. D.R. Deaver's laboratory at Pennsylvania State University and Dr. R. P. Amann at Colorado State University. In the TS rats the testes are retracted into the abdominal cavity, unless a ligature is placed to maintain them in the external scrotal sac. The cryptorchid condition in TS rats results in atrophy of the testes and lowered levels of spermatid formation. Hormonal changes due to testes atrophy must be considered in future experiments where related effects may modify muscle, bone or other tissue changes. Also, some new assessments of past results (published by many researchers) may warrant revised interpretations. The blood pressure studies and the testicular function results were presented and reviewed during an invited lecture at the University of Bordeaux II during the Animals in Space Symposium in March 1993. In summary, each of these three projects complied with the objectives of the proposal and serve to demonstrate the utility of animal models in preparations and interpretations of space flight results. All funding has been expended in accordance with the approved budget.

Source record↗

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 ↗

Investigations of rhesus monkey video-task performance: evidence for enrichment

We have developed the Language Research Center's Computerized Test System (LRC-CTS) for psychological research. Basically, the LRC-CTS is a battery of software tasks--computerized versions of many of the classic testing paradigms of cognitive and comparative psychology--and the hardware required to administer them. An XT- or 386-compatible computer is connected to a color monitor, onto which computer-generated stimuli are presented. Sound feedback is delivered through an external speaker/amplifier, and a joystick is used as an input device. The animals reach through the mesh of their home cages to manipulate the joystick, which causes isomorphic movements of a cursor on the screen thereby allowing animals to respond according to the varied demands of the tasks. Correct responses are rewarded with a fruit-flavored chow pellet. Using this technology, we have trained and tested rhesus monkeys, a variety of apes, human adults, and normally developing or mentally retarded human children. Other labs using the LRC-CTS are beginning to report encouraging results with other monkey species as well. From this research, a number of interesting and important psychological findings have resulted. In the present paper, however, evidence will be reviewed which suggests that the LRC-CTS is an effective means of providing environmental enrichment to singly housed rhesus monkeys.

Non-NASA Center↗

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.↗

Animal studies on Spacelab-3

The flight of two squirrel monkeys and 24 rates on Spacelab-3 was the first mission to provide hand-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity-dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space-adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferon production by spleen cells, defective release of growth hormone by somatotrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythopoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

Schatte, C.↗

Animal studies on Spacelab-3

Two squirrel monkeys and 24 rats were flown on Spacelab-3 to provide hands-on maintenance of animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity-dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space-adaptation syndrome. Among parameters measured in the rats, most notable is the dramatic loss of muscle mass and increased fragility of long bones. Other rat findings include suppressed interferon production by spleen cells, defective release of growth hormone by somatrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythropoietin.

Schatte, C.↗

Animal studies on Spacelab-3

The flight of two squirrel monkeys and 24 rats on Spacelab-3 was the first mission to provide hands-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferom production by spleen cells, defective release of growth hormone by somatrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythropoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

Schatte, C.↗

Plant and animal accommodation for Space Station Laboratory

An extended study has been conducted with the goals of defining and analyzing relevant parameters and significant tradeoffs for the accommodation of nonhuman research aboard the NASA Space Station, as well as conducting tradeoff analyses for orbital reconfiguring or reoutfitting of the laboratory facility and developing laboratory designs and program plans. The two items exerting the greatest influence on nonhuman life sciences research were identified as the centrifuge and the specimen environmental control and life support system; both should be installed on the ground rather than in orbit.

Olson, Richard L.↗

Atlas 2 Animation

The Atmospheric Laboratory for Applications and Science-2 (ATLAS-2), was designed to collect data on the relationship between the sun's energy output and Earth's middle atmosphere and how these factors affect the ozone layer. The ATLAS-2 flew on the Space Shuttle Discovery's mission SST-56, launched on April 8, 1993. The videotape consists of an animated tour of the instruments that were included as part of the mission. The first half of the tape shows the various instruments, pointing to each in turn and identifying each by the associated initialisms. The instruments identified were: the Atmospheric Trace Molecule Spectroscopy (ATMOS), Millimeter Wave Atmospheric Sounder (MAS), Shuttle Solar Backscatter Ultraviolet/A (SSBUV/A) spectrometer, Solar Spectrum Measurement (SOLSPEC) instrument, Solar Ultraviolet Irradiance Monitor (SUSIM), Active Cavity Radiometer (ACR) and Solar Constant (SOLCON).) The second half of the animation shows the same tour without the pointing or the identification of the instruments.

Source record↗

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↗