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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 1,459 records · Page 81
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Recovery of active recombinant EGFP from the excrement of transgenic mice: A possible source of recombinant protein

Transgenic animals provide attractive systems for the production of valuable recombinant proteins. Previous studies indicate that milk is a suitable source of secreted recombinant proteins. In the current study, we examine whether excrement can be another source of recombinant proteins by using transgenic mice ubiquitously-expressing green fluorescent protein (GFP) as a model. We found that the surface of excrement from GFP-transgenic mice was fluorescent, and the supernatant after centrifugation of an excrement suspension was rich in undegraded, actively fluorescing GFP. GFP was successfully purified from stool as a fluorescent 27 kDa protein by using a common procedure. Finally, we observed that the fluorescence of digested materials began in the ileum and persisted throughout the remainder of the digestive tract. Our results demonstrate that excrement, which is produced daily regardless of the sex or age of the animal, may be another feasible source of recombinant proteins. The preparation method is simple, economical, and noninvasive.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Anti-survivin single-domain antibodies derived from an artificial library including three synthetic random regions by in vitro selection using cDNA display

Highlights: • Single-domain antibodies can be selected with an artificial DNA library synthesized chemically. • cDNA display method is useful for in vitro selection from a large single-domain antibodies library (e.g. 1013). • A Brevibacillus protein expression system is suitable for synthesis of functional single-domain antibodies. Single-domain antibodies (variable domain of the heavy chain of a heavy chain antibody; VHH) are promising reagents for therapeutics and diagnostics because of their stability, cost-effective production and material workability as a small antibody. Currently, general acquisition of a VHH using immunization of camelids is inconvenient from the standpoint of animal protection, cost and the process is time-consuming. Thus, a straightforward and efficient method for screening VHHs against a target molecule is required. In this study, we examined whether in vitro selection of a VHH against a target protein could be performed by a cDNA display method with an artificial VHH library that had the three complementarity-determining regions (CDRs) randomized by chemical synthesis. The results revealed that a particular VHH against survivin, which is a member of the inhibitor of apoptosis family, was selected with affinity in the range of 10{sup −7} to 10{sup −8} M. The in vitro selection of a VHH using cDNA display with an artificial synthesized library without animal immunization was shown to be effective for rapid and inexpensive screening of VHHs against a target protein.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Presence of calpain-5 in mitochondria

Highlights: • Calpain-5 is present in the inner and outer segments of photoreceptor cells. • Calpain-5 is present in the mitochondria of photoreceptor cells. • Calpain-5 is localized in each mitochondrial subfraction of the retina. • The molecular weight of mitochondrial calpain-5 is smaller than cytosolic one. Calpains are Ca{sup 2+}-dependent cysteine proteases that are widely distributed in animal tissues and modulate a variety of cellular processes. There are 15 members of the calpain family in mammals. In animal cells, there are three types of calpains, viz., calpain-1, calpain-2, and calpain-10 in the mitochondria. The three types of calpains have been shown to play significant roles in pathophysiological conditions, including in apoptosis- and necrosis-like cell death. One of the severe retinal diseases, autosomal dominant neovascular inflammatory vitreoretinopathy, is known to be induced by mutations of the calpain-5 gene. However, the distribution of calpain-5 in the retina has not been elucidated. Therefore, in the present study, we determined the localization of calpain-5 in the porcine retina. We detected calpain-5 in the inner segment of photoreceptor cells using immunohistochemistry. With immunoelectron microscopy, calpain-5 was localized in the mitochondria of photoreceptor cells. Western blot analyses showed that calpain-5 was present in each mitochondrial subfraction. Furthermore, we showed that the molecular weight of mitochondrial calpain-5 was slightly smaller than cytosolic one. Our results demonstrated that a novel mitochondrial calpian, calpain-5, was localized in the mitochondria of retinal photoreceptor cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Phosphocreatine attenuates endoplasmic reticulum stress-mediated hepatocellular apoptosis ameliorates insulin resistance in diabetes model

Highlights: • PCr decrease blood glucose level improve body weight. • PCr protected liver tissues against STZ/MGO caused apoptosis. • PCr attenuates hepatic endoplasmic reticulum stress markers. • PCr ameliorates insulin resistance. Diabetes mellitus (DM) associated liver damage is a major health burden. Hepatocellular-damage in DM characterized with elevated endoplasmic reticulum stress (ER) and may enhanced insulin-resistance. Phosphocreatine (PCr) a rapidly high-energy-reserve molecule of phosphates naturally occurs in liver, brain and skeletal muscle. This study aimed to investigate the protective effect of PCr on the liver-injury-associated with DM and to report the mechanism involved. Wistar rat's diabetes model was induced using streptozotocin (STZ), and the animals were treated with 20 mg/kg, or 50 mg/kg PCr injection. Blood glucose level, and body wt were recorded. Liver tissues homogenate were analyzed for liver damage markers alanine transaminase (ALT), aspartate transaminase (AST). Liver tissues proteins further evaluated for apoptosis, endoplasmic reticulum stress (ER), and insulin resistance biomarkers using western blotting. Our results revealed that PCr reduced blood glucose level, improved body wt, ameliorates liver function enzymes. Furthermore, PCr upregulates anti-apoptotic Bcl2 proteins expression, and down-regulates significantly pro-apoptotic casp3 and Bax proteins expression in vivo and invitro. Moreover, ER stress CHOP, GRP78 and ATF4 biomarkers level were significantly attenuated in PCr treated animals comparing to STZ diabetes associated liver-damage model with significant improving in insulin-resistance Akt and IRS-1. Our results revealed that treating with PCr in diabetes-associated liver injury models decreased blood glucose level and possess protective effect in-vitro and in-vivo, which could be suggested as potential therapeutic strategy for diabetes associated liver injury patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

A preliminary regional PBPK model of lung metabolism for improving species dependent descriptions of 1,3-butadiene and its metabolites

1,3-Butadiene (BD), a volatile organic chemical (VOC), is used in synthetic rubber production and other industrial processes. It is detectable at low levels in ambient air as well as in tobacco smoke and gasoline vapors. Inhalation exposures to high concentrations of BD have been associated with lung cancer in both humans and experimental animals, although differences in species sensitivity have been observed. Metabolically active lung cells such as Pulmonary Type I and Type II epithelial cells and club cells (Clara cells) 1 are potential targets of BD metabolite-induced toxicity. Metabolic capacities of these cells, their regional densities, and distributions vary throughout the respiratory tract as well as between species and cell types. Here we present a physiologically based pharmacokinetic (PBPK) model for BD that includes a regional model of lung metabolism, based on a previous model for styrene, to provide species-dependent descriptions of BD metabolism in the mouse, rat, and human. Since there are no in vivo data on BD pharmacokinetics in the human, the rat and mouse models were parameterized to the extent possible on the basis of in vitro metabolic data. Where it was necessary to use in vivo data, extrapolation from rat to mouse was performed to evaluate the level of uncertainty in the human model. A kidney compartment and description of downstream metabolism were also included in the model to allow for eventual use of available urinary and blood biomarker data in animals and humans to calibrate the model for estimation of BD exposures and internal metabolite levels. Results from simulated inhalation exposures to BD indicate that incorporation of differential lung region metabolism is important in describing species differences in pulmonary response and that these differences may have implications for risk assessments of human exposures to BD.

1,3-Butadiene↗
DOE OSTI2019

Reaction: Proteins from Chemocatalysis; It’s What’s for Dinner

Supporting the agricultural needs of a rising global population is becoming increasingly difficult. In particular, supplying the animal-based protein demand is causing significant environmental impacts, including contributing to 12% of global greenhouse gas emissions and 30% of human-induced loss of terrestrial biodiversity. And the problem is getting worse. Even conservative estimates suggest that the demand for animal-based protein will double by 2050. Aside from systemic changes to the diets of billions, alternative protein sources must be developed to mitigate these issues. From an engineering perspective, the use of livestock as a 'process' to convert grown crops to protein is wildly inefficient and results in widespread environmental damage. Technological innovation is thus required to produce food-grade protein with lower environmental impacts.

09 BIOMASS FUELS↗
DOE OSTI2018

Multivariate physiological recordings in an experimental hemorrhage model

In this paper we describe a data set of multivariate physiological measurements recorded from conscious sheep ( N = 8; 37.4 ± 1.1 kg) during hemorrhage. Hemorrhage was experimentally induced in each animal by withdrawing blood from a femoral artery at two different rates (fast: 1.25 mL/kg/min; and slow: 0.25 mL/kg/min). Data, including physiological waveforms and continuous/intermittent measurements, were transformed to digital file formats (European Data Format [EDF] for waveforms and Comma-Separated Values [CSV] for continuous and intermittent measurements) as a comprehensive data set and stored and publicly shared here (Appendix A). The data set comprises experimental information (e.g., hemorrhage rate, animal weight, event times), physiological waveforms (arterial and central venous blood pressure, electrocardiogram), time-series records of non-invasive physiological measurements (SpO 2 , tissue oximetry), intermittent arterial and venous blood gas analyses (e.g., hemoglobin, lactate, SaO 2 , SvO 2 ) and intermittent thermodilution cardiac output measurements. A detailed explanation of the hemodynamic and pulmonary changes during hemorrhage is available in a previous publication (Scully et al., 2016)

Yaghouby, Farid↗
DOE OSTI2018

The confluences of ideas leading to, and the flow of ideas emerging from, individual-based modeling of riverine fishes

In this review article, we trace the history of events leading to the development of individual-based models (IBMs) to represent aquatic organisms in rivers and streams. As a metaphor, we present this history as a series of confluences between individual scientists (tributaries) sharing ideas. We describe contributions of these models to science and management. One iconic feature of river IBMs is the linkage between flow and the physical habitat experienced by individual animals, and the first model that focused on this linkage is briefly described. We continue by reviewing the contributions of riverine IBMs to eight broad areas of scientific inquiry. The first four areas include research to understand the effects of flow regimes on fish populations, species interactions (e.g., size-mediated competition and predation), fish movement and habitat selection, and contaminant and water quality impacts on populations. Next, we review research using IBMs to guide conservation biology of imperiled taxa through population viability analysis, including research to understand river fragmentation by dams and reconnection, to understand genetic outcomes for riverine metapopulations, and to anticipate the future effects of temperature and climate change. This rich body of literature has contributed to both theoretical insights (e.g., about animal behavior and life history) and applied insights (e.g., population-level effects of flow regimes, temperature, and the effects of hydropower and other industries that share rivers with aquatic biota). Lastly, we finish by exploring promising branches that lie ahead in the braided, downstream channel that represents future river modeling research.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Greenhouse gas emissions from the enteric fermentation and manure storage of dairy and beef cattle in China during 1961–2010

Due to the expanding dairy and beef population in China and their contribution to global CH{sub 4} and N{sub 2}O budgets, a framework considering changes in feed, manure management and herd structure was established to indicate the trends of CH{sub 4} and N{sub 2}O emissions from the enteric formation and manure storage in China's beef and dairy production and the underlying driving forces during the period 1961–2010. From 1961 to 2010, annual CH{sub 4} and N{sub 2}O emissions from beef cattle in China increased from 2.18 Mt to 5.86 Mt and from 7.93 kt–29.56 kt, respectively, while those from dairy cattle increased from 0.023 to 1.09 Mt and 0.12 to 7.90 kt, respectively. These increases were attributed to the combined changes in cattle population and management practices in feeds and manure storage. Improvement in cattle genetics during the period increased the bodyweight, required dry matter intake and gross energy and thus resulted in increased enteric CH{sub 4} EFs for each category of beef and dairy cattle as well as the overall enteric EFs (i.e., Tier 1 in IPCC). However, for beef cattle, such an impact on the overall enteric EFs was largely offset by the herd structure transition from draft animal-oriented to meat animal-oriented during 1961–2010. Although the CO{sub 2}-eq of CH{sub 4} and N{sub 2}O from manure storage was less than the enteric emissions during 1961–2010 in China, it tended to increase both in beef and dairy cattle, which was mainly driven by the changes in manure management practices. - Highlights: • CH{sub 4} emissions dominated the CO{sub 2}-eq emissions from dairy and beef cattle in China. • Beef herd transition played an important role in CH{sub 4} emissions. • Changes of manure managements increased the manure EFs of CH{sub 4} and N{sub 2}O. • Manure contributed very less to the total CO{sub 2}-eq emissions but tended to grow.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Tracking the sources of polybrominated diphenyl ethers in birds: Foraging in waste management facilities results in higher DecaBDE exposure in males

Differences in feeding ecology are now recognized as major determinants of inter-individual variations in contaminant profiles of free-ranging animals, but exceedingly little attention has been devoted to the role of habitat use. Marked inter-individual variations and high levels of polybrominated diphenyl ethers (PBDEs) (e.g., DecaBDE) have previously been documented in ring-billed gulls (Larus delawarensis) breeding in a colony near Montreal (QC, Canada). However, the environmental sources of these compounds, and thus the reasons causing these large inter-individual variations remain unidentified. In the present study, we used GPS-based telemetry (±5 to 10 m precision) to track ring-billed gulls from this colony to reconstruct their movements at the landscape level. We related habitat use of individual gulls (n=76) to plasma concentrations (ng/g ww) and relative contributions (percentages) to Σ{sub 38}PBDEs of major congeners in the internationally restricted PentaBDE and current-use DecaBDE mixtures. Male gulls that visited waste management facilities (WMFs; i.e., landfills, wastewater treatment plants and related facilities; 25% of all GPS-tracked males) exhibited greater DecaBDE (concentrations and percentages) and lower PentaBDE (percentages) relative to those that did not. In contrast, no such relationships were found in females. Moreover, in males, DecaBDE (concentrations and percentages) increased with percentages of time spent in WMFs (i.e., ~5% of total foraging time), while PentaBDE (percentages) decreased. No relationships between percentages of time spent in other habitats (i.e., urban areas, agriculture fields, and St. Lawrence River) were found in either sex. These findings suggest that animals breeding in the vicinity of WMFs as well as mobile species that only use these sites for short stopovers to forage, could be at risk of enhanced DecaBDE exposure. - Highlights: • The study was conducted on breeding gulls with high levels of flame retardants. • Ring-billed gulls were GPS-tracked to associate habitat use with plasma PBDEs. • Males that visited waste management facilities had greater DecaBDE. • DecaBDE also increased with time spent in waste management facilities in males. • No relationships between habitat use and PBDEs were found in females.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms

Highlights: • Chemicals that cause mammary tumors in animals also influence breast cancer risk. • Few studies assessed exposure in biologically relevant times of breast development. • Studies of early life exposure show risk for some OCPs, air pollution and solvents. • Genetic variants may modify breast cancer risk associated with PAH exposure. Many common environmental chemicals are mammary gland carcinogens in animal studies, activate relevant hormonal pathways, or enhance mammary gland susceptibility to carcinogenesis. Breast cancer’s long latency and multifactorial etiology make evaluation of these chemicals in humans challenging.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Molecular characterization of Cryptococcus neoformans and Cryptococcus gattii from environmental sources and genetic comparison with clinical isolates in Apulia, Italy

Highlights: • Meta-analysis of data recorded during environmental surveys of Cryptococcus spp in Apulia. • Olive trees can be an alternative ecological niche for C. neoformans and C. gattii. • Correlation clinical cases with possible new environmental sources of infection. The present study investigated the environmental distribution of Cryptococcus neoformans and C. gattii species complex molecular types, mating types and sequence types in Apulia, a region of Southern Italy. A total of 2078 specimens from arboreal and animal sources were analyzed. The percentage of positive samples was similar among both arboreal and animal specimens: 4.2% vs. 5.1% for C. neoformans species complex and 0.6% vs. 1.4% for C. gattii species complex. Molecular typing identified 78 isolates as VNI (76 αA and two aA), one as AD-hybrid αADa, and 16 as VGI aB. VNI isolates presented 10 different sequence types (STs) and VGI isolates two. The most frequent STs among C. neoformans and C. gattii species complex isolates were ST23 (51%) and ST156 (90%), respectively. Comparison with molecular types and STs results obtained from 21 clinical isolates collected in Apulia showed that one C. neoformans VNI clinical isolate shared an identical sequence type of one arboreal isolate (ST61) and that one C. gattii VGI clinical isolate matched with the main ST (ST156) present in the environment. In addition, molecular type VNIV was found only among clinical isolates and was absent in the investigated environmental area. In conclusion, the present study identified which C. neoformans and C. gattii species complex genotypes are circulating in Apulia, defined their ecological niches and revealed the relationship with clinical cases. It represents a basal study for addressing future investigations and public health interventions in the region.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Relationship between serum trimethylamine N-oxide and exposure to dioxin-like pollutants

Highlights: • TMAO has been linked to cardiovascular disease risk in human studies and animal models. • TMAO was positively associated with 22 indexes of dioxin-like pollutant exposures in ACHS-II. • Associations with TMAO were significant among females (except at high BMIs) but not among males. • The dioxin TEQ: TMAO association was unaltered by adjustment for independent covariates of TMAO. Trimethylamine N-oxide (TMAO) is a diet and gut microbiota-derived metabolite that has been linked to cardiovascular disease risk in human studies and animal models. TMAO levels show wide inter and intra individual variability in humans that can likely be accounted for by multiple factors including diet, the gut microbiota, levels of the TMAO generating liver enzyme Flavin-containing monooxygenase 3 (FMO3) and kidney function. We recently found that dioxin-like (DL) environmental pollutants increased FMO3 expression to elevate circulating diet-derived TMAO in mice, suggesting that exposure to this class of pollutants might also contribute to inter-individual variability in circulating TMAO levels in humans. To begin to explore this possibility we examined the relationship between body burden of DL pollutants (reported by serum lipid concentrations) and serum TMAO levels (n = 340) in the Anniston, AL cohort, which was highly exposed to polychlorinated biphenyls (PCBs). TMAO concentrations in archived serum samples from the Anniston Community Health Survey (ACHS-II) were measured, and associations of TMAO with 28 indices of pollutant body burden, including total dioxins toxic equivalent (TEQ), were quantified. Twenty-three (22 after adjustment for multiple comparisons) of the 28 indices were significantly positively associated with TMAO. Although the design of ACHS-II does not enable quantitative assessment of the contributions of previously known determinants of TMAO variability to this relationship, limited multivariate modeling revealed that total dioxins TEQ was significantly associated with TMAO among females (except at high BMIs) but not among males. Our results from this cross-sectional study indicate that exposure to DL pollutants may contribute to elevated serum TMAO levels. Prospective longitudinal studies will be required to assess the joint relationship between DL pollutant exposures, other determinants of TMAO, and health outcomes.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Elemental mercury neurotoxicity and clinical recovery of function: A review of findings, and implications for occupational health

Highlights: • Substantial human studies, both acute and chronic, are available for evaluation. • Elemental mercury induced toxicity often displays substantial recovery. • Numerous examples fail to show full recovery from elemental mercury toxicity. • Recovery from elemental mercury toxicity is affected by age and endpoint. • Few animal studies have been directed to elemental mercury toxicity recovery. This paper assessed approximately 30 studies, mostly involving occupationally exposed subjects, concerning the extent to which those who developed elemental mercury (Hg)-induced central and/or peripheral neurotoxicities from chronic or acute exposures recover functionality and/or performance. While some recovery occurred in the vast majority of cases, the extent of such recoveries varied considerably by individual and endpoint. Factors accounting for the extensive inter-individual variation in toxicity and recovery were not specifically assessed such as age, gender, diet, environmental enrichment, chelation strategies and dose-rate. While the data indicate that psychomotor endpoints often show substantial and relatively rapid (i.e., 2–6 months) recovery and that neuropsychological endpoints display slower and less complete recovery, generalizations are difficult due to highly variable study designs, use of different endpoints measured between studies, different Hg exposures based on blood/urine concentrations and Hg dose-rates, the poor capacity for replicating findings due to the unpredictable/episodic nature of harmful exposures to elemental Hg, and the inconsistency of the initiation of studies after induced toxicities and the differing periods of follow up during recovery periods. Finally, there is strikingly limited animal model literature on the topic of recovery/reversibility of elemental Hg toxicity, a factor which significantly contributes to the overall marked uncertainties for predicting the rate and magnitude of recovery and the factors that affect it.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Exposure to perfluoroalkyl substances and associations with serum thyroid hormones in a remote population of Alaska Natives

Highlights: • Serum concentrations PFOA, PFNA, PFUnA and PFDA were positively associated with TSH in individual models. • No serum PFASs are associated with total or free T{sub 4}. • The associations between serum PFOA and PFNA and free T{sub 3,} as well as PFNA and total T3 are modified by sex. • The effect of PFAS exposure on thyroid hormone homeostasis differs between sexes. Perfluoroalkyl substances (PFASs) are known to accumulate in traditional food animals of the Arctic, and arctic indigenous peoples may be exposed via consumption of subsistence-harvested animals. PFASs are suspected of disrupting thyroid hormone homeostasis in humans. The aim of this study is to assess the relationship between serum PFASs and thyroid function in a remote population of Alaska Natives. Serum samples were collected from 85 individuals from St. Lawrence Island, Alaska. The concentrations of 13 PFASs, as well as free and total thyroxine (T{sub 4}), free and total triiodothyronine (T{sub 3}), and thyrotropin (TSH) were quantified in serum samples. The relationships between circulating concentrations of PFASs and thyroid hormones were assessed using multiple linear regression fit with generalized estimating equations. Several PFASs, including perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), were positively associated with TSH concentrations when modeled individually. PFOS and PFNA were significantly associated with free T{sub 3} and PFNA was significantly associated with total T{sub 3} in models with PFAS*sex interactive terms; these associations suggested negative associations in men and positive associations in women. PFASs were not significantly associated with concentrations of free or total T{sub 4}. Serum PFASs are associated with circulating thyroid hormone concentrations in a remote population of Alaska Natives. The effects of PFAS exposure on thyroid hormone homeostasis may differ between sexes.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Climatic factors and human population changes in Eurasia between the Last Glacial Maximum and the early Holocene

Archaeological records document a significant expansion of populations from the Last Glacial Maximum (LGM, ~23–19 ka) to the early Holocene (EH, ~9 ka) in Eurasia, which is often attributed to the influence of orbital-scale climate changes. Yet, information remains limited concerning the climatic factor(s) which were responsible for conditioning demographic patterns. Here, in this work, we present results from an improved Minimalist Terrestrial Resource Model (MTRM), forced by a transient climate simulation from the LGM to the EH. Simulated potential hunter-gatherer population densities and spatial distributions across Eurasia are supported by observed archaeological sites in Europe and China. In the low latitudes, potential population size change was predominantly controlled by precipitation and its strong influence on plant and animal resources. In the middle-high latitudes, temperature was the dominant driver in influencing potential population size change and animal resource availability. Different regional responses of potential populations to climate change across Eurasia - owing to variations in available food resources between the LGM and EH - provide a better understanding of human dispersal during the Late Pleistocene.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Determining critical overlap concentration of polyethylene oxide to support excipient safety assessment of opioid products

Intravenous administration of abuse-deterrent opioid products poses high safety risks, in part due to the presence of high molecular weight polymeric excipients. Previous in vivo studies in animal models have shown that the higher molecular weight (Mw) polymeric excipients like polyethylene oxide (PEO) were directly linked to such adverse responses as intravenous hemolysis and kidney damage. PEO polymers have been widely used in abuse-deterrent formulations (ADF) of opioid products, adding to concerns over the general safety of the opioid category due to the unknown safety risk from abuse via unintended routes. Here, the current study focused on the determination of the critical overlap concentration (c*) at various PEO molecular weights to aid in explaining differences in observed adverse responses from previous animal studies on the intravenous administration of PEO solutions. Adverse in vivo responses may be related to the viscoelastic regime of the polymer solution, which depends not only on Mw but also on concentration. Having a localized polymer concentration in the blood above the c*, i.e., the transition from the dilute to semi-dilute entangled viscoelastic regime, may influence the flow behavior and interactions of cells in the blood. The relationship of c* to this combination of physical, chemical, and rheological effects is a possible driving force behind adverse in vivo responses.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Local Hypothermia as a Radioprotector of the Rectal Wall During Prostate Stereotactic Body Radiation Therapy

Purpose: To compare the single-fraction dose-related incidence of rectal obstruction and/or bleeding in normothermic and hypothermic rectums of a rat model. Methods and Materials: A 1.9-cm length of rectum was irradiated with a single fraction in 57 Sprague-Dawley rats using a dedicated image-guided small animal irradiator and Monte Carlo–based treatment planning system. All rats had a rectal temperature control apparatus placed during irradiation and were stratified to achieve either a normothermic (37°C) or hypothermic (15°C) rectal wall temperature. Radiation was delivered to a 1-cm-diameter cylindrical volume about the cooling device and rectal wall. The radiation dose was escalated from 16 Gy up to 37 Gy to assess the dose response in each arm. The primary endpoint of this study was rectal obstruction and/or bleeding during a follow-up of 180 to 186 days. Histologic scoring was performed on all study rats. Results: Probit analysis showed a dose associated with a 50% incidence of rectal obstruction of 24.6 Gy and 40.8 Gy for normothermic and hypothermic arms, respectively. The occurrence of obstruction and/or bleeding correlated with the posttreatment histologic score for normothermic rats; however, there was no difference in histologic score between normothermic and hypothermic rats at the highest dose levels evaluated. Conclusions: A significant radioprotective effect was observed using local hypothermia during a single large dose of radiation for the functional endpoint of rectal obstruction and/or bleeding. A confirmatory study in a large animal model with anatomic and physiologic similarities to humans is suggested.

62 RADIOLOGY AND NUCLEAR MEDICINE↗