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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 1,117 records · Page 62
All sourcesNASA NTRSDOE OSTI
DOE OSTI2013

Endovascular Broad-Neck Aneurysm Creation in a Porcine Model Using a Vascular Plug

Ruptured cerebral arterial aneurysms require prompt treatment by either surgical clipping or endovascular coiling. Training for these sophisticated endovascular procedures is essential and ideally performed in animals before their use in humans. Simulators and established animal models have shown drawbacks with respect to degree of reality, size of the animal model and aneurysm, or time and effort needed for aneurysm creation. We therefore aimed to establish a realistic and readily available aneurysm model. Five anticoagulated domestic pigs underwent endovascular intervention through right femoral access. A total of 12 broad-neck aneurysms were created in the carotid, subclavian, and renal arteries using the Amplatzer vascular plug. With dedicated vessel selection, cubic, tubular, and side-branch aneurysms could be created. Three of the 12 implanted occluders, two of them implanted over a side branch of the main vessel, did not induce complete vessel occlusion. However, all aneurysms remained free of intraluminal thrombus formation and were available for embolization training during a surveillance period of 6 h. Two aneurysms underwent successful exemplary treatment: one was stent-assisted, and one was performed with conventional endovascular coil embolization. The new porcine aneurysm model proved to be a straightforward approach that offers a wide range of training and scientific applications that might help further improve endovascular coil embolization therapy in patients with cerebral aneurysms.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Robotically Assisted Sonic Therapy (RAST) for Noninvasive Hepatic Ablation in a Porcine Model: Mitigation of Body Wall Damage with a Modified Pulse Sequence

Purpose: Robotically assisted sonic therapy (RAST) is a nonthermal, noninvasive ablation method based on histotripsy. Prior animal studies have demonstrated the ability to create hepatic ablation zones at the focal point of an ultrasound therapy transducer; however, these treatments resulted in thermal damage to the body wall within the path of ultrasound energy delivery. The purpose of this study was to evaluate the efficacy and safety of a pulse sequence intended to mitigate prefocal body wall injury. Materials and Methods: Healthy swine (n = 6) underwent hepatic RAST (VortxRx software version 1.0.1.3, HistoSonics, Ann Arbor MI) in the right hepatic lobe. A 3.0 cm spherical ablation zone was prescribed for each. Following treatment, animals underwent MRI which was utilized for ablation zone measurement, evaluation of prefocal injury, and assessment of complications. Each animal was euthanized, underwent necropsy, and the tissue was processed for histopathologic analysis of the ablation zone and any other sites concerning for injury. Results: No prefocal injury was identified by MRI or necropsy in the body wall or tissues overlying the liver. Ablation zones demonstrated uniform cell destruction, were nearly spherical (sphericity index = 0.988), and corresponded closely to the prescribed size (3.0 × 3.1 × 3.4 cm, p = 0.70, 0.36, and 0.01, respectively). Ablation zones were associated with portal vein (n = 3, one occlusive) and hepatic vein thrombosis (n = 4, one occlusive); however, bile ducts remained patent within ablation zones (n = 2). Conclusions: Hepatic RAST performed with a modified ultrasound pulse sequence in a porcine model can mitigate prefocal body wall injuries while maintaining treatment efficacy. Further study of hepatic RAST appears warranted, particularly in tumor models.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis

Matrix metalloproteinases (MMPs) are zinc (Zn{sup 2+}) and calcium (Ca{sup 2+}) dependant endopeptidases, capable of degradation of numerous components of the extracellular matrix. Cadmium (Cd{sup 2+}) is a well known environmental contaminant which could impair the activity of MMPs. In this sense, this study was conducted to evaluate if Cd{sup 2+} intake inhibits these endopeptidases activities at the rat prostate and testicles and if it directly inhibits the activity of MMP2 and MMP9 at gelatinolytic assays when present in the incubation buffer. To investigate this hypothesis, Wistar rats (5 weeks old), were given tap water (untreated, n = 9), or 15 ppm CdCl{sub 2} diluted in drinking water, during 10 weeks (n = 9) and 20 weeks (n = 9). The animals were euthanized and their ventral prostate, dorsal prostate, and testicles were removed. These tissue samples were processed for protein extraction and subjected to gelatin zymography evaluation. Additionally, we performed an experiment of gelatin zymography in which 5 μM or 2 mM cadmium chloride (CdCl{sub 2}) was directly dissolved at the incubation buffer, using the prostatic tissue samples from untreated animals that exhibited the highest MMP2 and MMP9 activities in the previous experiment. We have found that CdCl{sub 2} intake in the drinking water led to the inhibition of 35% and 30% of MMP2 and MMP9 (p < 0.05) at the ventral prostate and testis, respectively, in Cd{sup 2+} treated animals when compared to controls. Moreover, the activities of the referred enzymes were 80% and 100% inhibited by 5 μM and 2 mM of CdCl{sub 2}, respectively, even in the presence of 10 mM of CaCl{sub 2} within the incubation buffer solution. These important findings demonstrate that environmental cadmium contamination may deregulate the natural balance in the extracellular matrix turnover, through MMPs downregulation, which could contribute to the toxic effects observed in prostatic and testicular tissue after its exposure. - Highlights: • Wistar rats were given tap water or 15 ppm CdCl{sub 2} diluted in drinking water. • Ventral prostate, dorsal prostate, and testicles were tested for MMPs activity. • CdCl{sub 2} was also directly dissolved at the incubation buffer in another experiment. • Cadmium inhibited the activity of MMP2 and MMP9 in both experiments. • Cadmium contamination may deregulate the natural balance in the ECM turnover.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

A chemically defined culture medium containing Rho kinase inhibitor Y-27632 for the fabrication of stratified squamous epithelial cell grafts

With the development of a culture method for stratified squamous epithelial cells, tissue-engineered epithelial cell sheets have been successfully applied as clinical cell grafts. However, the implementation of these cell sheets without the use of any animal-derived materials is highly desirable. In this study, Rho-associated protein kinase inhibitor Y-27632 was used to develop a chemically defined culture medium for the fabrication of stratified epithelial cell grafts consisting of human epidermal and oral keratinocytes, and the proliferation activity, cell morphology, and gene expressions of the keratinocytes were analyzed. The results of a colorimetric assay indicated that Y-27632 significantly promoted the proliferation of the keratinocytes in culture media both with and without fetal bovine serum (FBS), although there were no indications of Y-27632 efficacy on cell morphology and stratification of the keratinocytes in culture medium without any animal-derived materials. The results of quantitative RT-PCR revealed that gene expressions correlated with cell adhesion, cell–cell junction, proliferation markers, and stem/progenitor markers in cultured keratinocytes were not strongly affected by the addition of Y-27632 to the culture medium. Moreover, gene expressions of differentiation markers in stratified keratinocytes cultured in medium without FBS were nearly identical to those of keratinocytes co-cultured with 3T3 feeder cells. Interestingly, the expressions of differentiation markers in cultured stratified keratinocytes were suppressed by FBS, whereas they were reconstructed by either co-culture of a 3T3 feeder layer or addition of Y-27632 into the culture medium containing FBS. These findings indicate that Y-27632 is a useful supplement for the development of a chemically defined culture medium for fabrication of stratified epithelial cell grafts for clinical applications for the purpose of developing the culture medium with a lower risk of pathogen transmission that might arise from animal-derived materials. - Highlights: • Y-27632 promotes the proliferation of human keratinocytes. • Human keratinocytes with Y-27632 can stratify similarly to traditional method. • Y-27632 is useful for culture medium of human keratinocyte in clinical setting.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

A thematic review of life cycle assessment (LCA) applied to pig production

Commercial livestock production is known to have significant impacts on the environment. Pig production is a complex system which involves the production of animal feed, transportation, animal rearing and waste management. One tool for assessing the environmental performance of such complex systems is life cycle assessment (LCA). LCA has been applied to pig production considerably to date. This paper provides a chronological review of state-of-the-art pig production LCAs under three themes: feed production; entire-system livestock rearing; and waste management. The study considers how LCA applications have addressed technological improvements in animal husbandry, and highlights methodological limitations, particularly related to cross-study comparisons. Recent research demonstrates crude protein reduction in feed and anaerobic treatment of pig excreta resulting in bioenergy production are the key targets for environmental performance improvements related to pig production. - Highlights: • An extensive review of LCA applied to pig production is provided chronologically over the past decade. • Individual studies have been categorised into feed, whole-system pig production and waste management themes. • We consider how LCAs have addressed state-of-the-art pig husbandry. • We offer a discussion on key findings, limitations and future research.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2019

Oxytocin modulates the expression of norepinephrine transporter, β3-adrenoceptors and muscarinic M2 receptors in the hearts of socially isolated rats

Social stress produces behavioral alterations, and autonomic and cardiac dysfunction in animals. In addition to the well-known roles of oxytocin on birth and maternal bonding, recent evidence shows that this neuropeptide possesses cardio-protective properties. However less is known about its role in the regulation of the autonomic nervous system. The direct influence of oxytocin on the cardiac catecholamine synthesizing enzyme, transport beta-adrenoceptors and muscarinic receptors in animals exposed to chronic social isolation stress has not yet been studied. In this study, we examined the influence of peripheral chronic oxytocin treatment on anxiety-related behavior, the morphology and content of epinephrine and norepinephrine, mRNA and protein levels of tyrosine hydroxylase (TH), norepinephrine transporter (NET) and receptors 3 (β3-AR) and muscarinic 2 (M2 MR) in the right and left cardiac atrium and ventricle of chronically socially isolated male rats. Our results show that oxytocin treatment exhibits an anxiolytic effect, decreases the heart/body weight ratio and prevents the hypertrophy of cardiomyocytes in the wall of the left ventricle of stressed rats. Epinephrine and TH protein levels were unchanged after prolonged oxytocin treatment. Peripheral oxytocin administration led to the enhancement of gene expression of β3-AR in both atria, NET protein in the left ventricle and gene expression of M2 MR in the right atrium and the left ventricle of chronically socially isolated rats. The study provides evidence that oxytocin treatment in chronically socially isolated animals enhances norepinephrine uptake and expression of cardio-inhibitory receptors in cardiac tissues, which could have a beneficial effect on the cardiovascular system under the increased activity of the sympathoneural system. © 2018 Elsevier Inc.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered rhTPP1 to treat CLN2.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Nerve cell-mimicking liposomes as biosensor for botulinum neurotoxin complete physiological activity

Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding. Following triggered membrane translocation of the toxin's Light Chain, the endopeptidase activity can be quantitatively monitored employing a FRET-based reporter assay within the functionalized liposomes. We were able to detect BoNT/B physiological activity at picomolar concentrations in short time, opening the possibility for future replacement of animal experimentation in pharmaceutical BoNT testing. - Highlights: • A cell-free in vitro system was used to measure BoNT/B physiological function. • The system relies on nerve-cell mimicking liposomes as a novel detection system. • A FRET-based reporter assay is used as final readout of the test system. • BoNT/B physiological activity was detected at picogram quantities in short time. • The method opens the possibility to replace animal experimentation in BoNT testing.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes. Significantly higher percentages of apoptotic (AC3+) Kupffer cells were also found in acute and AIDS stages. However, productively infected cells were not detected in liver of 41/42 animals examined, despite abundant infected cells in gut and lymph nodes of all animals. Increased rates of Kupffer cell proliferation resulting in an increase in Kupffer cells without productive infection indicate SIV infection affects Kupffer cells, but the liver does not appear to be a major site of productive viral replication. - Highlights: • Kupffer cells increase in the liver of SIV-infected macaques. • Increased proliferation and apoptosis of Kupffer cells occurs in SIV infection. • Productively infected cells are rarely detected in the liver. • The liver is not a major site for SIV replication.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

DNA cleavage enzymes for treatment of persistent viral infections: Recent advances and the pathway forward

Treatment for most persistent viral infections consists of palliative drug options rather than curative approaches. This is often because long-lasting viral DNA in infected cells is not affected by current antivirals, providing a source for viral persistence and reactivation. Targeting latent viral DNA itself could therefore provide a basis for novel curative strategies. DNA cleavage enzymes can be used to induce targeted mutagenesis of specific genes, including those of exogenous viruses. Although initial in vitro and even in vivo studies have been carried out using DNA cleavage enzymes targeting various viruses, many questions still remain concerning the feasibility of these strategies as they transition into preclinical research. Here, we review the most recent findings on DNA cleavage enzymes for human viral infections, consider the most relevant animal models for several human viral infections, and address issues regarding safety and enzyme delivery. Results from well-designed in vivo studies will ideally provide answers to the most urgent remaining questions, and allow continued progress toward clinical application. - Highlights: • Recent in vitro and in vivo results for DNA cleavage enzymes targeting persistent viral infections. • Analysis of the best animal models for testing enzymes for HBV, HSV, HIV and HPV. • Challenges facing in vivo delivery of therapeutic enzymes for persistent viral infections. • Safety issues to be addressed with proper animal studies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A novel in vivo mouse intervertebral disc degeneration model induced by compressive suture

Intervertebral disc degeneration (IDD) is the root cause of many musculoskeletal disorders of the spine. However, the etiology of IDD is complex and still not well understood. Animal models of IDD would be useful in deciphering the underlying mechanisms. But the existing animal models have their limitations. Therefore, to establish a novel mouse model that can simulate the human IDD process in vivo, we proposed to carefully circumcise the 2 mm-wide tail skin and then compressively sutured the defect with a simple end-to-end suture to exert excessive pressure on the disc. After 1-week, 2-week, and 4-week compression, the mice were sacrificed and the intervertebral discs were harvested for tissue analysis. The radiological, morphological, and molecular modifications of intervertebral discs were measured to characterize this model. Radiologically, the water content of the intervertebral disc decreased significantly after 2-week compression. Morphologically, the nucleus pulposus showed a decrease in volume and the number of notochordal cells. The compressive suture also broke the balance between anabolic and catabolic enzymes in nucleus pulposus, which led to the remodeling of the extracellular matrix in nucleus pulposus as the content of aggrecan and collagen II decreased. The compressive suture could induce intervertebral discs degeneration in a more reasonable way, which was solely influenced by mechanical loading, as the mice caudal vertebrae still moved freely after the operation. This kind of animal model could be adapted as a reliable in vivo mouse IDD model for the research regarding the etiology and treatments of IDD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-QI-19: Evaluation of a Clinical 1.5T MRI for Prostate Cancer MRS Imaging Using a In Vivo Tumor Model

Purpose: Magnetic resonance spectroscopic (MRS) imaging may provide important bio-markers to distinguish normal/cancerous prostate tissue. While MRS imaging requires a high uniform magnetic field, the ability of a clinical 1.5T MRI to achieve a comparable MRS signal is of interest for radiation treatment planning/assessment. This study is to evaluate the MRS imaging of a 1.5T clinical MRI for prostate cancers by comparing with a small animal 7T MRS scanner. Methods: A tumor model was developed by implanting LNCaP tumor cells in nude mice prostates. Tumor was monitored 3 weeks after implantation using MRI, and MRS imaging was performed on the tumor area when the tumor reached around 1cm in diameter. The 1.5T GE clinical MR scanner and the 7T Bruker small animal MR scanner were used for each mouse. MR spectrums acquired with these scanners were analyzed and compared. The signals of Choline and Citrate were considered. Results: The prostate tumor MR spectrum under the 1.5T clinical MRI showed a similar spectrum pattern to that acquired using the 7T animal MRI. The Choline signal (3.2ppm) is clear and there is no clear peak for Citrate (2.6ppm). However, the signal magnitude for Choline is not dominant compared to the background signal under 1.5T MRI. Typical cancerous prostate tissue MR spectrum with an increased Choline signal and a reduced Citrate signal was observed. In addition, signal variation is noticeable between repeated spectrum scans. The average of these scans showed a comparable and consistent spectrum to those under 7T MRI. Conclusion: The clinical 1.5T MRI is able to acquire a MR spectrum for prostate cancer comparable to those acquired using a dedicated 7T MRS scanner. However, to achieve a consistent and reliable spectrum, multiple repeated scans were necessary to get a statistical result and reduce the noise-induced artifact. This work was supported in part by the National Cancer Institute Grant R21 CA131979 and R01CA172638.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Multisource inverse-geometry CT. Part I. System concept and development

Purpose: This paper presents an overview of multisource inverse-geometry computed tomography (IGCT) as well as the development of a gantry-based research prototype system. The development of the distributed x-ray source is covered in a companion paper [V. B. Neculaes et al., “Multisource inverse-geometry CT. Part II. X-ray source design and prototype,” Med. Phys. 43, 4617–4627 (2016)]. While progress updates of this development have been presented at conferences and in journal papers, this paper is the first comprehensive overview of the multisource inverse-geometry CT concept and prototype. The authors also provide a review of all previous IGCT related publications. Methods: The authors designed and implemented a gantry-based 32-source IGCT scanner with 22 cm field-of-view, 16 cm z-coverage, 1 s rotation time, 1.09 × 1.024 mm detector cell size, as low as 0.4 × 0.8 mm focal spot size and 80–140 kVp x-ray source voltage. The system is built using commercially available CT components and a custom made distributed x-ray source. The authors developed dedicated controls, calibrations, and reconstruction algorithms and evaluated the system performance using phantoms and small animals. Results: The authors performed IGCT system experiments and demonstrated tube current up to 125 mA with up to 32 focal spots. The authors measured a spatial resolution of 13 lp/cm at 5% cutoff. The scatter-to-primary ratio is estimated 62% for a 32 cm water phantom at 140 kVp. The authors scanned several phantoms and small animals. The initial images have relatively high noise due to the low x-ray flux levels but minimal artifacts. Conclusions: IGCT has unique benefits in terms of dose-efficiency and cone-beam artifacts, but comes with challenges in terms of scattered radiation and x-ray flux limits. To the authors’ knowledge, their prototype is the first gantry-based IGCT scanner. The authors summarized the design and implementation of the scanner and the authors presented results with phantoms and small animals.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Quantifying drivers of wild pig movement across multiple spatial and temporal scales

The movement behavior of an animal is determined by extrinsic and intrinsic factors that operate at multiple spatio-temporal scales, yet much of our knowledge of animal movement comes from studies that examine only one or two scales concurrently. Understanding the drivers of animal movement across multiple scales is crucial for understanding the fundamentals of movement ecology, predicting changes in distribution, describing disease dynamics, and identifying efficient methods of wildlife conservation and management. We obtained over 400,000 GPS locations of wild pigs from 13 different studies spanning six states in southern U.S.A., and quantified movement rates and home range size within a single analytical framework. We used a generalized additive mixed model framework to quantify the effects of five broad predictor categories on movement: individual-level attributes, geographic factors, landscape attributes, meteorological conditions, and temporal variables. We examined effects of predictors across three temporal scales: daily, monthly, and using all data during the study period. We considered both local environmental factors such as daily weather data and distance to various resources on the landscape, as well as factors acting at a broader spatial scale such as ecoregion and season. We found meteorological variables (temperature and pressure), landscape features (distance to water sources), a broad-scale geographic factor (ecoregion), and individual-level characteristics (sex-age class), drove wild pig movement across all scales, but both the magnitude and shape of covariate relationships to movement differed across temporal scales. The analytical framework we present can be used to assess movement patterns arising from multiple data sources for a range of species while accounting for spatio-temporal correlations. Our analyses show the magnitude by which reaction norms can change based on the temporal scale of response data, illustrating the importance of appropriately defining temporal scales of both the movement response and covariates depending on the intended implications of research (e.g., predicting effects of movement due to climate change versus planning local-scale management). We argue that consideration of multiple spatial scales within the same framework (rather than comparing across separate studies post-hoc) gives a more accurate quantification of cross-scale spatial effects by appropriately accounting for error correlation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Genomic Diversity of Escherichia Isolates from Diverse Habitats

Our understanding of the Escherichia genus is heavily biased toward pathogenic or commensal isolates from human or animal hosts. Recent studies have recovered Escherichia isolates that persist, and even grow, outside these hosts. Although the environmental isolates are typically phylogenetically distinct, they are highly related to and phenotypically indistinguishable from their human counterparts, including for the coliform test. To gain insights into the genomic diversity of Escherichia isolates from diverse habitats, including freshwater, soil, animal, and human sources, we carried out comparative DNA-DNA hybridizations using a multi-genome E. coli DNA microarray. The microarray was validated based on hybridizations with selected strains whose genome sequences were available and used to assess the frequency of microarray false positive and negative signals. Our results showed that human fecal isolates share two sets of genes (n>90) that are rarely found among environmental isolates, including genes presumably important for evading host immune mechanisms (e.g., a multi-drug transporter for acids and antimicrobials) and adhering to epithelial cells (e.g., hemolysin E and fimbrial-like adhesin protein). These results imply that environmental isolates are characterized by decreased ability to colonize host cells relative to human isolates. Our study also provides gene markers that can distinguish human isolates from those of warm-blooded animal and environmental origins, and thus can be used to more reliably assess fecal contamination in natural ecosystems.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Improving the Cost-Effectiveness of Algal CO2 Utilization by Synergistic Integration With Power Plant and Wastewater Treatment Operations

Creating an economic demand for carbon utilization products will require lowering the overall cost of the products to compete within the current market. Photosynthetic uptake of carbon dioxide is an emerging pathway for product development in the animal feed market that globally amounts to over 400 Billion USD and is expected to continue growing. This project aims to continue the development of a process that utilizes carbon dioxide while increasing the cost competitiveness of algae as an animal feed product. The overall goal of the project is to demonstrate an engineering-scale open raceway pond algae cultivation system (180 m2) including integration of technologies that utilize coal-fired power plant CO2 and wastewater nutrient inputs. The system is designed to maximize the cost-effectiveness and environmental benefits of algal biomass production for commodity animal feed.

20 FOSSIL-FUELED POWER PLANTS↗
DOE OSTI2017

Final report for project "Effects of Low-Dose Irradiation on NFkB Signaling Networks and Mitochondria"

Low dose ionizing radiation effects are difficult to study in human population because of the numerous confounding factors such as genetic and lifestyle differences. Research in mammalian model systems and in vitro is generally used in order to overcome this difficulty. In this program project three projects have joined together to investigate effects of low doses of ionizing radiation. These are doses at and below 10 cGy of low linear energy transfer ionizing radiation such as X-ray and gamma rays. This project was focused on cellular signaling associated with nuclear factor kappa B (NFkB) and mitochondria - subcellular organelles critical for cell aging and aging-like changes induced by ionizing radiation. In addition to cells in culture this project utilized animal tissues accumulated in a radiation biology tissue archive housed at Northwestern University (http://janus.northwestern.edu/janus2/index.php). Major trust of Project 1 was to gather all of the DoE sponsored irradiated animal (mouse, rat and dog) data and tissues under one roof and investigate mitochondrial DNA changes and micro RNA changes in these samples. Through comparison of different samples we were trying to delineate mitochondrial DNA quantity alterations and micro RNA expression differences associated with different doses and dose rates of radiation. Historic animal irradiation experiments sponsored by DoE were done in several national laboratories and universities between 1950’s and 1990’s; while these experiments were closed data and tissues were released to Project 1. Project 2 used cells in culture to investigate effects that low doses or radiation have on NFκB and its target genes manganese superoxide dismutase (MnSOD) and genes involved in cell cycle: Cyclins (B1 and D1) and cyclin dependent kinases (CDKs). Project 3 used cells in culture such as “normal” human cells (breast epithelial cell line MCF10A cells and skin keratinocyte cells HK18) and mouse embryo fibroblast (mef) cells to focus on role of NFkB protein and several other proteins such as survivin (BIRC5) in radiation dependent regulation of tumor necrosis factor alpha (TNFα) and its downstream signaling.

59 BASIC BIOLOGICAL SCIENCES↗